Disclosures: Steven R Feldman, MD, PhD Grant/Research/Clinical Trial Support: Galderma [Psoriasis (Clobetasol, calcitriol)]; National Biological Corporation [Psoriasis (Phototherapy equipment)]. Speaker's Bureau: Janssen [Psoriasis (Ustekinumab, infliximab, golimumab)]; Celgene [Psoriasis (Apremilast)]; Novartis [Psoriasis (Secukinumab)]. Consultant/Advisory Boards: Galderma [Psoriasis (Clobetasol, calcitriol)]; GSK/Stiefel [Psoriasis (Acitretin)]; Leo Pharma [Psoriasis (Betamethason, calcipotriene)]; Celgene [Psoriasis (Apremilast)]; Pfizer [Psoriasis (Tofacitinib)]; Abbvie [Psoriasis (Adalimumab)]; Amgen [Psoriasis (Etanercept)]; Janssen [Psoriasis (Ustekinumab, infliximab, golimumab)]; Lilly [Psoriasis (Ixekizumab)]; Novartis [Psoriasis (Secukinumab)]. Robert P Dellavalle, MD, PhD, MSPH Nothing to disclose. Kristina Callis Duffin, MD Grant/Research/Clinical Trial Support: Amgen [Psoriasis (Etanercept, brodalumab)]; Pfizer [Psoriasis (tofacitinib)]; Bristol-Myers Squibb [Psoriasis (abatacept)]; Eli Lilly [Psoriasis (ixekizumab)]; AbbVie [Psoriasis (Adalimumab)]; Janssen [Psoriasis (Ustekinumab, guselkumab, infliximab); Novartis [psoriasis (secukinumab)]; Celgene [psoriasis (apremilast)]; Steifel; Xenoport [psoriasis (calcipotriene)]. Consultant/Advisory Boards: Amgen [Psoriasis (Etanercept, brodalumab)]; Pfizer [Psoriasis (tofacitinib)]; Bristol-Myers Squibb [Psoriasis (abatacept)]; Eli Lilly [Psoriasis (ixekizumab)]; AbbVie [Psoriasis (Adalimumab)]; Janssen [Psoriasis (Ustekinumab, guselkumab, infliximab); Novartis [psoriasis (secukinumab)]; Celgene [psoriasis (apremilast)]; Steifel; Xenoport [psoriasis (calcipotriene)]. Abena O Ofori, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Psoriasis is a common chronic skin disorder typically characterized by erythematous papules and plaques with a silver scale, although other presentations occur. Most cases are not severe enough to affect general health and are treated in the outpatient setting. Rare life-threatening presentations can occur that require intensive inpatient management.
This topic reviews the treatment of psoriatic skin disease. The epidemiology, clinical manifestations, and diagnosis of psoriatic skin disease are discussed in detail separately, as are psoriatic arthritis and the management of psoriasis in pregnant women and special populations. (See "Epidemiology, clinical manifestations, and diagnosis of psoriasis" and "Treatment of psoriatic arthritis" and "Pathogenesis of psoriatic arthritis" and "Clinical manifestations and diagnosis of psoriatic arthritis" and "Management of psoriasis in pregnancy" and "Treatment selection for moderate to severe plaque psoriasis in special populations".)
APPROACH — Psoriasis is a chronic disease that can have a significant effect on quality of life. Therefore, management of psoriasis involves addressing both psychosocial and physical aspects of the disease.
Numerous topical and systemic therapies are available for the treatment of the cutaneous manifestations of psoriasis. Treatment modalities are chosen on the basis of disease severity, relevant comorbidities, patient preference (including cost and convenience), efficacy, and evaluation of individual patient response . Although medication safety plays an important role in treatment selection, this must be balanced by the risk of undertreatment of psoriasis, leading to inadequate clinical improvement and patient dissatisfaction .
Psychosocial aspects — Psoriasis can be a frustrating disease for the patient and the provider. The clinician needs to be empathetic and spend adequate time with the patient. It may be helpful for the clinician to touch the patient when appropriate to communicate physically that the skin disorder is neither repulsive nor contagious.
Clinicians should lay out reasonable aims of treatment, making it clear to the patient that the primary goal of treatment is control of the disease. Although treatment can yield almost complete clearance of visible psoriasis in some patients, there is no cure for psoriasis.
Educating the patient about psoriasis is important and referral to an organization such as the National Psoriasis Foundation (www.psoriasis.org) is often helpful.
Psoriasis may affect patients' perceptions of themselves and this can potentially initiate or exacerbate psychological disorders such as depression [3,4]. Patients with limited skin disease may still have significant psychosocial disability . Some patients with psoriasis may benefit from counseling and/or treatment with psychoactive medications.
Choice of therapy — For most patients, the initial decision point around therapy will be between topical and systemic therapy. However, even patients on systemic therapy will likely continue to need some topical agents. Topical therapy may provide symptomatic relief, minimize required doses of systemic medications, and may even be psychologically cathartic for some patients.
For purposes of treatment planning, patients may be grouped into mild-to-moderate and moderate-to-severe disease categories. Limited, or mild-to-moderate, skin disease can often be managed with topical agents, while patients with moderate-to-severe disease may need systemic therapy. The location of the disease and the presence of psoriatic arthritis also affect the choice of therapy. Psoriasis of the hand, foot, or face can be debilitating functionally or socially and may deserve a more aggressive treatment approach. The treatment of psoriatic arthritis is discussed separately. (See "Treatment of psoriatic arthritis".)
Moderate-to-severe psoriasis is typically defined as involvement of more than 5 to 10 percent of the body surface area (the entire palmar surface, including fingers, of one hand is approximately 1 percent of the body surface area ) or involvement of the face, palm or sole, or disease that is otherwise disabling. Patients with more than 5 to 10 percent body surface area affected are generally candidates for systemic therapy, since application of topical agents to a large area is not usually practical or acceptable for most patients. Attempts to treat extensive disease with topical agents are often met with failure, can add cost, and lead to frustration in the patient-clinician relationship.
There is ample evidence of efficacy of the newer systemic therapies ("biologics"); however, cost is a major consideration with these agents. Established therapies such as methotrexate and phototherapy continue to play a role in the management of moderate to severe plaque psoriasis. (See 'Biologic agents' below.)
The management of patients with extensive or recalcitrant disease is a challenge even for experienced dermatologists. However, the availability of biologic medications has reduced the challenge considerably.
The concept that many patients with psoriasis in the United States do not receive sufficient treatment to control the disease is suggested by an analysis of surveys performed by the National Psoriasis Foundation between 2003 and 2011 . Among the 5604 survey respondents with psoriasis, 52 percent expressed dissatisfaction with their treatment. Many patients received no treatment, including 37 to 49 percent of respondents with mild psoriasis, 24 to 36 percent of respondents with moderate psoriasis, and 9 to 30 percent of respondents with severe psoriasis. Further studies will be useful for clarifying the reasons for these observations and for determining the value of interventions to increase the accessibility of treatment.
Widespread pustular disease requires aggressive treatment, which may include hospitalization. Therapeutic approaches to generalized pustular psoriasis and psoriatic arthritis are discussed separately. (See "Pustular psoriasis: Management" and "Treatment of psoriatic arthritis".)
Mild-to-moderate disease — Limited plaque psoriasis responds well to topical corticosteroids and emollients. Alternatives include vitamin D analogs, such as calcipotriene and calcitriol, tar, and topical retinoids (tazarotene). For facial or intertriginous areas, topical tacrolimus or pimecrolimus may be used as alternatives or as corticosteroid sparing agents, though improvement may not be as rapid. Localized phototherapy is another option for recalcitrant disease.
Combinations of potent topical corticosteroids (table 1) and either calcipotriene, calcitriol, tazarotene, or UVB phototherapy are commonly prescribed by dermatologists. Calcipotriene in combination with Class I topical corticosteroids is highly effective for short-term control. Calcipotriene alone can then be used continuously and the combination with potent corticosteroids used intermittently (on weekends) for maintenance. A combination product containing calcipotriene and betamethasone dipropionate is available for this use. With proper adherence, considerable improvement with topical therapies may be seen in as little as one week, though several weeks may be required to demonstrate full benefits.
Because adherence to topical treatment can be a major hurdle, keeping the treatment regimen simple and using treatment vehicles that the patient finds acceptable is often beneficial.
Severe disease — Severe psoriasis requires phototherapy or systemic therapies such as retinoids, methotrexate, cyclosporine, or biologic immune modifying agents. Biologic agents used in the treatment of psoriasis include the anti-TNF agents adalimumab, etanercept, and infliximab and the anti-IL-12/23 antibody ustekinumab. Improvement usually occurs within weeks. Patients with severe psoriasis generally require care by a dermatologist.
Intertriginous psoriasis — Intertriginous (inverse) psoriasis should be treated with class VI and VII low potency corticosteroids (table 1) due to an increased risk of corticosteroid-induced cutaneous atrophy in the intertriginous areas. Topical calcipotriene or calcitriol and the topical calcineurin inhibitors tacrolimus or pimecrolimus are additional first-line treatments [7,8]. These agents may be used alone or in combination with topical corticosteroids as corticosteroid sparing agents for long term maintenance therapy. Calcipotriene, tacrolimus, and pimecrolimus are more expensive options than topical corticosteroids. Some concerns have been raised about the safety of the calcineurin inhibitors (see 'Calcineurin inhibitors' below and "Epidemiology, clinical manifestations, and diagnosis of psoriasis", section on 'Inverse psoriasis').
Scalp psoriasis — The presence of hair on the scalp can make topical treatment of psoriasis challenging because patients may find certain products messy or difficult to apply. Recognizing the patient's preference for a drug vehicle may help to improve adherence to therapy. For many patients, lotion, solution, gel, foam, or spray vehicles are preferable to thicker creams or ointments.
Topical corticosteroids are the primary topical agents used for psoriasis on the scalp . Support for the use of these agents is evident in a systematic review of randomized trials that found that very potent or potent topical corticosteroids are more effective treatments for scalp psoriasis than topical vitamin D analogs . Combining a corticosteroid and vitamin D analog may offer additional benefit; in the systematic review, combination treatment with a potent topical corticosteroid and a vitamin D analog appeared slightly more effective than potent topical corticosteroid monotherapy. However, in clinical practice, complicating the treatment regimen with more than one topical product may reduce the likelihood of consistent adherence to the treatment regimen. Thus, we usually prescribe a topical corticosteroid alone as initial therapy. A commercially available betamethasone dipropionate-calcipotriene combination product is available, but is more expensive than most topical corticosteroid preparations.
Other topical therapies used for psoriasis (eg, tazarotene, coal tar shampoo, anthralin) and intralesional corticosteroid injections also may be beneficial for scalp involvement, though data on efficacy specifically in scalp disease are limited . Salicylic acid can be a helpful adjunctive treatment because of its keratolytic effect. Phototherapy (eg, excimer laser) and systemic agents are additional treatment options for patients who cannot achieve sufficient improvement with topical agents .
Guttate psoriasis — The management of guttate psoriasis is reviewed separately. (See "Guttate psoriasis", section on 'Treatment'.)
Generalized pustular psoriasis — The management of generalized pustular psoriasis is reviewed separately. (See "Pustular psoriasis: Management".)
Localized pustular psoriasis — Localized pustular psoriasis (palms and soles) is difficult to treat. Approaches include potent topical corticosteroids and topical bath PUVA. Data are limited on the use of systemic retinoids for localized pustular psoriasis. However, these drugs appear to be particularly effective in the treatment of pustular psoriasis, and we consider them first line therapy. Acitretin is the retinoid that is used most often for this indication. Acitretin is a potent teratogen and should not be used in women who might become pregnant. Pregnancy is contraindicated for three years following acitretin therapy. (See 'Retinoids' below.)
Nail psoriasis — Although nail involvement alone is uncommon, many patients with psoriasis have disease that involves the nails. Psoriasis pathology resides in the nail matrix, nail bed, and hyponychium. (See "Epidemiology, clinical manifestations, and diagnosis of psoriasis", section on 'Nail psoriasis'.)
Physical maneuvers to improve nail appearance or comfort may be helpful for some patients. Patients can thin their nails by scraping them with a file or shaving them down with the edge of a glass slide. Thick toenails that are painful or interfere with footwear can be removed by a podiatrist.
Despite advances in the treatment of cutaneous disease, the treatment of psoriasis of the nails remains difficult. There is relatively little high-quality evidence to guide the choice of therapies for nail disease [11-13].
Topical therapies are sometimes tried; however, delivering topical treatment is difficult because of the physical barrier of the nail plate. If improvement in nail appearance occurs, it can be expected to be slow, as 8 to 12 months are needed to generate a new, healthy nail.
There is no standardized regimen for the treatment of nail psoriasis with topical agents . For distal nail onycholysis (separation of the nail from the nail bed), we suggest starting with a class I or II topical corticosteroid (table 1), such as clobetasol 0.05% solution, combined with calcipotriene 0.005% solution dripped into the nail bed and hyponychium twice daily. For patients with nail pitting and other superficial nail defects, the pathologic process is occurring under the proximal nail fold. We typically use a high potency topical corticosteroid (class I or II) and a topical vitamin D analog applied once or twice daily under an occlusive dressing. The use of a combination product containing both a corticosteroid and a vitamin D analog may simplify treatment . Cutaneous atrophy is a potential adverse effect of the long-term use of potent topical corticosteroids.
For severe or recalcitrant nail disease, intralesional therapy with corticosteroids is a reasonable next option.
Systemic therapy may be more effective than topical therapy. A randomized trial of infliximab in patients with moderate to severe psoriasis (82 percent of whom had nail psoriasis) found marked improvements in nail pathology compared with baseline and with placebo . Treatment with other biologic agents, including adalimumab, etanercept, ustekinumab, golimumab, secukinumab, and certolizumab pegol have also led to improvement in nail psoriasis [17-23].
Oral retinoids, oral methotrexate, and oral cyclosporine have been utilized in the treatment of nail psoriasis with some success [24,25]. A study of low-dose acitretin (0.2-0.3 mg/kg) given to 36 patients with isolated nail psoriasis for six months led to complete or almost complete clearance in 25 percent, moderate improvement in 25 percent, mild improvement in 33 percent, and no improvement in 11 percent . At a six month follow-up visit after the end of treatment, recurrence of nail psoriasis was noted. However, patients who improved with acitretin had less severe nail findings than at the start of treatment. (See 'Retinoids' below.)
Photochemotherapy (PUVA) and pulsed dye laser therapy  have also been used for the treatment of nail psoriasis. Evidence for the efficacy of PUVA is limited to reports from small, uncontrolled studies [27,28].
In choosing among treatments, serious consideration must be given to the risks of systemic therapy and photochemotherapy.
Erythrodermic psoriasis — There is no high quality evidence to support specific recommendations for the management of erythrodermic psoriasis. Based upon data from open-label or retrospective studies and case reports, a panel of experts suggested that patients with severe, unstable disease should be treated with cyclosporine or infliximab due to the rapid onset and high efficacy of these agents . Patients with less acute disease can be treated with acitretin or methotrexate as first-line agents. The panel advised against the use of systemic glucocorticoids due to the perceived potential for these drugs to induce a flare of psoriasis upon withdrawal of therapy. (See 'Systemic therapies' below.)
Data are limited on the efficacy of biologic agents other than infliximab for the treatment of erythrodermic psoriasis. Etanercept was effective in an open-label study of 10 patients , and case reports have documented successful treatment with adalimumab and ustekinumab [31,32].
In general, patients with erythrodermic psoriasis should be cared for by a dermatologist and may require hospitalization and/or combinations of systemic treatments. Topical therapies, such as mid-potency topical corticosteroids, emollients, wet dressings, and oatmeal baths can be used in concordance with systemic treatment to manage symptoms . Long-term maintenance therapy for psoriasis is required.
Children — The immediate and long-term adverse effects of therapies for psoriasis are of particular concern in the pediatric population. Many agents used in the treatment of adult psoriasis have also been used for children. However, high quality studies on the efficacy and safety of therapies for psoriasis in children are limited. Guidelines for the treatment of children based upon the available evidence have been published .
Special populations — The treatment of psoriasis in pregnant women and patients with hepatitis B, hepatitis C, human immunodeficiency virus infection, latent tuberculosis, or malignancy is reviewed separately. (See "Treatment selection for moderate to severe plaque psoriasis in special populations" and "Management of psoriasis in pregnancy".)
Referral — Referral to a dermatologist should be considered in the following settings:
●Confirmation of the diagnosis is needed.
●The response to treatment is inadequate as measured by the clinician, patient, or both.
●There is significant impact on quality of life.
●The primary care clinician is not familiar with the treatment modality recommended such as PUVA, phototherapy, or immunosuppressive medications.
●The patient has widespread severe disease.
●In cases of psoriatic arthritis, referral and/or collaboration with a rheumatologist is indicated. (See "Treatment of psoriatic arthritis".)
TOPICAL THERAPIES — Patient adherence may be the largest barrier to treatment success with topical therapies; early patient follow-up (within a week of initiating treatment) may improve adherence. Published guidelines for the treatment of psoriasis with topical therapies are available .
Emollients — Hydration and emollients are valuable and inexpensive adjuncts to psoriasis treatment. Keeping psoriatic skin soft and moist minimizes the symptoms of itching and tenderness. Additionally, maintaining proper skin hydration can help prevent irritation and thus the potential for subsequent Koebnerization (development of new psoriatic lesions at sites of trauma).
The most effective are ointments such as petroleum jelly or thick creams, especially when applied immediately after a hydrating bath or shower.
Corticosteroids — Topical corticosteroids remain the mainstay of topical psoriasis treatment despite the development of newer agents . The mechanism of action of corticosteroids in psoriasis is not fully understood. Corticosteroids exert antiinflammatory, antiproliferative, and immunosuppressive actions by affecting gene transcription.
The inherent potency of a topical corticosteroid is frequently reported using a I to VII scale based on vasoconstrictive assays (table 1). Although ointments are sometimes thought to be inherently more effective because of their occlusive properties, this is not uniformly correct. In practice, the efficacy/potency of a topical corticosteroid is dependent on many factors including skin type, plaque thickness, and, perhaps most importantly, compliance.
To minimize adverse effects and maximize compliance, the site of application needs to be considered in choosing the appropriately potent corticosteroid:
●On the scalp or in the external ear canal, potent corticosteroids in a solution or foam vehicle (eg, fluocinonide 0.05% or clobetasol propionate 0.05%) are frequently indicated. Clobetasol 0.05% shampoo or spray can also be used for scalp involvement.
●On the face and intertriginous areas, a low potency cream (eg, hydrocortisone 1%) is often sufficient.
The typical regimen consists of twice daily application of topical corticosteroids. Most patients will show a rapid decrease in inflammation with such therapy, but complete normalization of skin or lasting remission is unpredictable.
Topical corticosteroids generally can be continued as long as the patient has thick active lesions. Skin atrophy from topical corticosteroids usually is not a problem unless the medication is continuously applied after the skin has returned to normal thickness. Once clinical improvement occurs, the frequency of application should be reduced . For patients in whom lesions recur quickly, topical corticosteroids can be applied intermittently (such as on weekends only) to maintain improvement. The addition of non-corticosteroid topical treatments can also facilitate the avoidance of long-term daily topical corticosteroids. (See 'Mild-to-moderate disease' above.)
The risks of cutaneous and systemic side effects associated with chronic topical corticosteroid use are increased with high potency formulations. Data support limiting the continuous application of Class I topical corticosteroids to two to four weeks; thus, close clinician supervision should be employed if longer treatment durations are required (table 1) . Data are less clear regarding treatment durations for less potent topical corticosteroids. Side effects of topical corticosteroids, including the potential for suppression of the hypothalamic axis, are discussed separately. (See "Pharmacologic use of glucocorticoids" and "General principles of dermatologic therapy and topical corticosteroid use".)
The cost of topical corticosteroids varies widely. The price of a 60 gram tube of a potent corticosteroid brand name product can be hundreds of dollars. There are generic preparations in each potency class that have reduced the cost somewhat, though generic prices in the United States are rising . Examples of available generics include, in order of increasing potency, hydrocortisone 1%, triamcinolone 0.1%, fluocinonide 0.05%, betamethasone dipropionate 0.05%, and clobetasol 0.05%.
Different formulations have been developed in an effort to enhance the delivery of topical corticosteroids. Betamethasone valerate in a foam had superior efficacy for scalp psoriasis and was preferred by patients when compared with betamethasone valerate lotion . The foam becomes a liquid on contact with skin and is also well tolerated by patients with trunk and extremity psoriasis . A clobetasol propionate spray is also available; like foams, sprays are easy to apply to large areas . The main advantage of these newer preparations is likely greater patient acceptance, which may translate into greater adherence; the main disadvantage is cost.
Topical vitamin D analogs — Topical vitamin D analogs for the treatment of psoriasis include calcipotriene (calcipotriol), calcitriol, and tacalcitol. Although topical vitamin D analogs are effective as monotherapy for some patients, a systematic review found that combination therapy with a topical corticosteroid is more effective than either treatment alone .
Until 2009, calcipotriene was the only topical vitamin D analog available in the United States. Calcipotriene is obtainable as a cream, solution, ointment, or foam, or as a combination ointment or suspension with betamethasone dipropionate. Topical calcitriol ointment has been prescribed in Europe for years, and is now available in the United States. When compared with calcipotriene, calcitriol appears to induce less irritation in sensitive areas of the skin (eg, skin folds) .
Calcipotriene — Calcipotriene (calcipotriol) is an established therapy in psoriasis. The precise mechanism is not clear, but a major effect is the hypoproliferative effect on keratinocytes . An immune modulating effect has been postulated for calcipotriene, but has not been shown to be significant in psoriasis to date .
In a systematic review of randomized controlled trials, calcipotriene was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5% . Only potent topical corticosteroids appeared to have comparable efficacy at eight weeks. Skin irritation is the main adverse event associated with calcipotriene.
Combined use of calcipotriene and superpotent corticosteroids has demonstrated increased clinical response and tolerance in clinical trials compared with either agent used alone [45-47]. One regimen employed daily use of both calcipotriene ointment and halobetasol ointment for two weeks, followed by weekend use of the halobetasol ointment and weekday use of calcipotriene . This regimen produced six-month remission maintenance in 76 percent compared with 40 percent with weekend halobetasol alone. A similar regimen with calcipotriene ointment and clobetasol propionate foam also appears to be effective .
In addition, a randomized trial found that a preparation that combines calcipotriene with betamethasone dipropionate (0.064%) was effective with once daily usage, and more effective than once daily therapy with either betamethasone or calcipotriene ; this combination preparation typically costs more than $400 for a 60 g tube. Patients who use topical corticosteroids in combination with calcipotriene must be monitored for adverse effects as with corticosteroid monotherapy. (See 'Corticosteroids' above.)
Thus, topical calcipotriene may be used as an alternative or adjunct to topical corticosteroid therapy. It is applied twice daily when used as monotherapy. No controlled trials guide how best to use topical corticosteroids in conjunction with calcipotriene. Once daily use of each may be adequate. Acidic products can inactivate topical calcipotriene, and some topical corticosteroids may be acidic. A reasonable approach to combination therapy is to have patients apply topical calcipotriene and topical corticosteroids each once daily at different times of day.
Other than skin irritation, side effects of topical calcipotriene are usually minimal; the risk of hypercalcemia is low when the drug is used appropriately . However, topical calcipotriene is more expensive than many generic potent corticosteroids.
Calcitriol — The mechanism of action of calcitriol is thought to be similar to that of calcipotriene and involves the drug's ability to inhibit keratinocyte proliferation and stimulate keratinocyte differentiation . In addition, calcitriol inhibits T-cell proliferation and other inflammatory mediators . In two randomized trials with a total of 839 patients with mild to moderate plaque psoriasis, calcitriol 3 mcg/g ointment was more effective than vehicle . At the end of the study periods (up to eight weeks), 39.6 and 32.7 percent of the calcitriol groups versus 21.2 and 12 percent of the vehicle groups exhibited at least marked global improvement.
In a systematic review, calcipotriene and calcitriol were equally effective . However, on sensitive areas of the skin, calcitriol appears to be less irritating than calcipotriene. An intraindividual randomized trial of 75 patients compared treatment with calcitriol 3 mcg/g ointment to calcipotriene 50 mcg/g ointment for mild to moderate psoriasis on facial, hairline, retroauricular, and flexural areas . Perilesional erythema, perilesional edema, and stinging or burning sensations were significantly lower in the areas treated with calcitriol. A 52-week open-label study of the safety of calcitriol ointment did not reveal an adverse effect on calcium homeostasis .
Similar to calcipotriene, calcitriol ointment is more expensive than many generic potent topical corticosteroids. The drug is applied twice daily.
Tar — The use of tar is a time-honored modality for treating psoriasis, although newer (and less messy) treatment options have reduced its popularity. The precise mechanism of action of tar is not known; it has an apparent antiproliferative effect.
Tar can be helpful as an adjunct to topical corticosteroids. There are no commercially available corticosteroid/tar combinations. Tar products are available without a prescription in the form of shampoos, creams, lotions, ointments, and oils. Newer products include a solution and a foam. Some patients may prefer the less messy formulations.
Tar can also be compounded into creams and ointments. A commonly used compound is 2% or 3% crude coal tar in triamcinolone cream 0.1% applied twice daily to individual plaques. An alternative is 4 to 10% LCD (liquor carbonis detergens, a tar distillate) in triamcinolone cream or ointment, used similarly. A preparation of 1% tar in a fatty-acid based lotion may be superior to conventional 5% tar products  and appears to have efficacy similar to that of calcipotriene .
Topical tar preparations, including shampoos, creams, and other preparations, can be used once daily. Patients should be warned that tar products have the potential to stain hair, skin, and clothing. It may help to use them at night and wear inexpensive night clothes (eg, old pajamas) as they tend to be messy. Patients may also find the odor of tar products unpleasant.
For shampoos, the emphasis should be on making sure the product reaches the scalp. Tar shampoo should be left in place for 5 to 10 minutes before rinsing it out.
Tazarotene — Tazarotene is a topical retinoid that was safe and effective in two randomized, vehicle-controlled trials that included 1303 patients with psoriasis . The 0.1% cream was somewhat more effective than 0.05% cream, but with a slightly higher rate of local side effects. Another study found that once daily administration of tazarotene gel, 0.05% or 0.1%, compared favorably with the twice daily administration of topical fluocinonide 0.05% . Absorption of tazarotene was minimal over the 12-week course of the study, suggesting that systemic toxicity is unlikely during long-term therapy. A small uncontrolled study of short contact tazarotene found that a 20 minute application followed by washing appeared to be less irritating than traditional use, and seemed to have similar efficacy . Irritation limits use of tazarotene by itself; the irritation is reduced by concomitant treatment with a topical corticosteroid .
Calcineurin inhibitors — Topical tacrolimus 0.1% and pimecrolimus 1% are effective in the treatment of psoriasis [60-63]. Facial and intertriginous areas may be well suited to these treatments, which can allow patients to avoid chronic topical corticosteroid use:
●An eight-week randomized trial in 167 patients ages 16 and older found that twice daily treatment to intertriginous and facial lesions with tacrolimus 0.1% ointment resulted in more patients achieving clearance of lesions or excellent improvement compared with placebo (65 versus 32 percent) .
●An eight-week randomized trial in 57 adults with moderate to severe inverse psoriasis found that twice daily treatment with pimecrolimus 1% cream resulted in more patients clearing or almost clearing lesions compared with placebo (71 versus 21 percent) .
Topical tacrolimus and pimecrolimus are generally well tolerated when used to treat facial and intertriginous psoriasis [64,65]. However, corticosteroid therapy may be more effective, at least compared with pimecrolimus. This was suggested in a four-week randomized trial in 80 patients with intertriginous psoriasis that compared various therapies applied once daily . Betamethasone valerate 0.1% was more effective than pimecrolimus 1%.
In 2005, the US Food and Drug Administration (FDA) issued an alert about a possible link between topical tacrolimus and pimecrolimus and cases of lymphoma and skin cancer in children and adults , and in 2006 placed a "black box" warning on the prescribing information for these medications . No definite causal relationship has been established; however, the FDA recommended that these agents only be used as second line agents for atopic dermatitis. Subsequent studies have not, however, found evidence of an increased risk of lymphoma [69,70]. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical calcineurin inhibitors'.)
Anthralin — Topical anthralin (also known as dithranol) is an effective treatment for psoriasis that has been utilized since the early 20th century [71-73]. The mechanism of action of anthralin in psoriasis is not well understood, but may involve antiinflammatory effects and normalization of keratinocyte differentiation .
Skin irritation is an expected side effect of anthralin that can limit the use of this therapy. This side effect and the ability of anthralin to cause permanent red-brown stains on clothing and temporary staining of skin have contributed to a decline in the use of anthralin therapy.
In order to minimize irritation, anthralin treatment is usually prescribed as a short-contact regimen that is titrated according to patient tolerance. For example, treatment may begin with concentrations as low as 0.1% or 0.25% applied for 10 to 20 minutes per day, with weekly step-wise increases in duration to reach a total contact time up to one hour . Then, weekly, serial increases in the concentration of anthralin can be performed (eg, 0.5, 1, and 2%) based upon patient tolerance and lesion response.
In the United States, anthralin is commercially marketed only as a 1% or 1.2% cream or a 1% shampoo. Thus, in the outpatient setting in the United States, the initial treatment regimen often consists of 1% or 1.2% anthralin applied for 5 to 10 minutes per day. Subsequently, the application time is titrated up to 20 to 30 minutes as tolerated.
Application to surrounding unaffected skin should be avoided to minimize irritation. For patients with well-defined plaques, petrolatum or zinc oxide may be applied to the surrounding skin as a protectant prior to application. After the desired contact period has elapsed, anthralin should be washed off the treated area .
Benefit from anthralin therapy is often evident within the first few weeks of therapy. When administered by patients in the outpatient setting, anthralin is less effective than topical vitamin D or potent topical corticosteroid therapy [40,75,76].
ULTRAVIOLET LIGHT — Ultraviolet (UV) irradiation has long been recognized as beneficial for the control of psoriatic skin lesions. As an example, patients often notice improvement in skin lesions during the summer months. UV radiation may act via antiproliferative effects (slowing keratinization) and anti-inflammatory effects (inducing apoptosis of pathogenic T-cells in psoriatic plaques). In choosing UV therapy, consideration must be given to the potential for UV radiation to accelerate photodamage and increase the risk of cutaneous malignancy.
Phototherapy and photochemotherapy require the supervision of a dermatologist trained in these treatment modalities. The American Academy of Dermatology has provided guidelines for the treatment of psoriasis with ultraviolet light . Despite high efficacy and safety, the use of office-based phototherapy has declined in the United States because of administrative issues and the development of new systemic medications .
Modalities — Therapeutic doses of ultraviolet light can be administered in several ways:
●Ultraviolet B (UVB) radiation (290 to 320 nm) is used in patients with extensive disease, alone or in combination with topical tar. The mechanism of action of UVB is likely through its immunomodulatory effects . Patients receive near-erythema-inducing doses of UVB at least three times weekly until remission is achieved, after which a maintenance regimen is usually recommended to prolong the remission.
●Narrow band UVB (311 nm) is an alternative to standard (broadband- 290 to 320 nm) UVB in the treatment of psoriasis. Suberythemogenic doses of narrow band UVB are more effective than broadband UVB in clearing plaque psoriasis . Apoptosis of T cells is also more common with 311 nm than with broadband UVB.
●Photochemotherapy (PUVA) involves treatment with either oral or bath psoralen followed by ultraviolet A (UVA) radiation (320 to 400 nm) under strict medical supervision. UVA penetrates deeper into the dermis than UVB and does not have the latter's potential for burning the skin. A number of possible mechanisms have been postulated to explain PUVA's effects . With oral PUVA, patients ingest the photosensitizing drug, 8-methoxypsoralen, followed within two hours by exposure to UVA; this sequence is performed three times weekly in increasing doses until remission, then twice or once weekly as a maintenance dose. With bath PUVA, the psoralen capsules are dissolved in water, and affected skin (hands, feet, or total body) is soaked for 15 to 30 minutes prior to UVA exposure. There are few data on the comparative efficacy of oral and bath PUVA for psoriasis. A small open randomized trial of 74 patients with moderate to severe psoriasis did not find a significant difference in efficacy between the two treatments . Additional studies are necessary to confirm this finding.
Some patients take psoralen prior to coming into the office or clinic for PUVA. Increased photosensitivity is typically present starting one hour after an oral dose and resolves after eight hours. Pre and post treatment photoprotection (eg, hat, sunscreen, sun protective goggles) are critical in preventing serious burn injury to the skin and eyes from being outside. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)
Pretreatment emollients have long been thought to improve results with UVB. However, while thin oils do not impede UV penetration, emollient creams can actually inhibit the penetration of the UV and should not be applied before treatment . Gentle removal of plaques by bathing does help prior to UV exposure.
Uncertainty remains about the comparative efficacy of UVB phototherapy and PUVA photochemotherapy for plaque psoriasis. Randomized trials comparing the efficacy of narrowband UVB to PUVA have yielded inconsistent findings . The convenience of not needing to administer a psoralen prior to treatment is a favorable feature of UVB phototherapy.
Home phototherapy — An alternative to office-based phototherapy is the use of a home ultraviolet B (UVB) phototherapy unit prescribed by the treating clinician . This option may be preferred by patients who are not in close proximity to an office-based phototherapy center, whose schedules do not permit frequent office visits, or for whom the costs of in-office treatment exceed those of a home phototherapy unit. Home units cost about $3000, but may prove cost-effective in the long term, particularly when compared with biologic therapies. Insurance coverage of these units varies.
For some dermatologists, uncertainty regarding the safety of home units has led to a reluctance to prescribe them. Some have expressed concern for the potential for improper or excessive usage of these devices . In contrast, a randomized trial of 196 subjects found that narrowband UVB administered via home units was as safe and effective as office-based treatments . Home phototherapy units that are equipped with electronic controls that allow only a prescribed number of treatments are available and may help to mitigate clinician concerns.
Commercial tanning beds can improve psoriasis and are occasionally used for patients without access to medical phototherapy [87,88]. However, data are limited on this mode of treatment, and clinicians and patients should be cognizant that there is significant variability in the UV output of tanning beds .
Excimer laser — Another development in ultraviolet therapy for psoriasis involves use of a high energy 308 nm excimer laser. The laser allows treatment of only involved skin; thus, considerably higher doses of UVB can be administered to psoriatic plaques at a given treatment compared with traditional phototherapy. Uncontrolled trials suggest that laser therapy results in faster responses than conventional phototherapy [90,91]. As an example, one study of excimer laser therapy involved 124 patients with stable mild to moderate plaque psoriasis, of whom 80 completed the entire protocol . Treatments were scheduled twice weekly. After 10 or fewer treatments, 84 and 50 percent of patients achieved the outcomes of 75 percent or better and 90 percent or better clearing of plaques, respectively. This number of treatments was far fewer than that typically required of phototherapy (25 or more). Side effects of laser therapy included erythema and blistering; these were generally well tolerated, and no patient discontinued therapy because of adverse effects.
A common sequela of excimer laser therapy is the induction of UV-induced hyperpigmentation (tanning) in treated areas, which can be cosmetically distressing for some patients. Hyperpigmentation resolves after the discontinuation of treatment.
Like 311 nm UVB, the excimer laser represents a therapeutic advance toward specific wavelength therapies for psoriasis. While both the excimer laser and narrow band UVB are approved for use in psoriasis, inconsistencies in third party coverage for these treatments limit their utilization.
Cancer risk — A concern with PUVA is an increased risk of nonmelanoma skin cancer and melanoma. Ongoing monitoring is indicated in patients who have received prolonged courses of PUVA. In general, phototherapy is contraindicated in patients with a history of melanoma or extensive nonmelanoma skin cancer. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Skin cancer'.)
Folate deficiency — Folate deficiency has been associated with health disorders such as neural tube defects in fetuses of affected pregnant women, anemia, and hyperhomocysteinemia (a risk factor for cardiovascular disease). In an in vitro study, exposure of plasma to UVA led to a 30 to 50 percent decrease in the serum folate level within 60 minutes . However, folate deficiency secondary to UVA exposure has not been proven to occur in vivo. In a small randomized trial of healthy subjects, no difference in serum folate levels was identified between subjects irradiated with UVA for six sessions and untreated subjects . In addition, an observational study of 35 psoriasis patients found that narrow band UVB had no effect on serum folate levels after 18 treatment sessions .
Saltwater baths — As discussed above, exposure to natural sunlight has been observed to improve psoriasis. Bathing in sea water in combination with sun exposure (climatotherapy) has also been used as a therapy for psoriasis, as has the use of salt water baths with artificial UV exposure (balneophototherapy).
A large, open, randomized trial found that treatment with UVB after a saltwater bath had greater efficacy than UVB after a tap-water bath, and similar efficacy to bath PUVA . Although the raters of disease severity were intended to be blinded, treatment assignment was known to the raters in nearly 60 percent of cases. Additionally, less than half the patients were considered to have met the study's prespecified criteria for having been eligible and treated per protocol. In per-protocol analyses, no difference was found between saltwater and tap-water baths, and bath PUVA was superior to UVB after a saltwater bath.
Additional studies are required to demonstrate that combining saltwater baths with phototherapy is superior to tap-water baths plus phototherapy or to phototherapy alone.
SYSTEMIC THERAPIES — A variety of systemic medications are used for the treatment of psoriasis [96-98], particularly for patients with more than 10 percent body surface area involvement or less extensive, but debilitating disease. In 2008 and 2009, the American Academy of Dermatology published guidelines for the management of psoriasis with systemic therapies [96,97].
Options for systemic therapy include immunosuppressive or immunomodulatory drugs such as methotrexate, cyclosporine, and biologic agents. Systemic retinoids, which improve psoriasis through effects on epidermal proliferation and differentiation as well as immunomodulation, are also used for the treatment of this condition .
The efficacies of the various systemic treatments for psoriasis were compared in a 2013 systematic review of randomized trials. Indirect comparisons of the proportion of patients in placebo-controlled trials who achieved at least 75 percent improvement in the Psoriasis Area and Severity Index (PASI) score after 8 to 16 weeks of treatment showed that the efficacy of infliximab within this time period was superior to etanercept, adalimumab, ustekinumab (45 mg dose), alefacept, cyclosporine, and methotrexate . In addition, head-to-head trials included in the systematic review supported the superiority of infliximab and adalimumab over methotrexate therapy and the superiority of ustekinumab over etanercept therapy. Although knowledge of the relative efficacies of systemic treatments for psoriasis is useful, consideration of factors such as drug side effects, patient preference, drug availability, and treatment cost (eg, the high cost of biologic agents compared with conventional therapies) also play an important role in treatment selection.
Methotrexate — The folic acid antagonist methotrexate has been used successfully in the treatment of psoriasis for over 30 years. It is also effective for the treatment of psoriatic arthritis and psoriatic nail disease. Initial thoughts on the mechanism of action centered around the antiproliferative effects of methotrexate on DNA synthesis in epidermal cells; subsequent evidence supports the concept that it is the immunosuppressive effects of methotrexate on activated T-cells that controls psoriasis .
Methotrexate appears to be less effective than at least some of the biologic agents (see 'Biologic agents' below). In one trial, 271 patients with moderate to severe plaque psoriasis were randomized to receive methotrexate, adalimumab, or placebo . After 16 weeks, the proportion of patients achieving a 75 percent improvement in symptoms with methotrexate was more than that with placebo but less than with adalimumab (36, 19, and 80 percent respectively).
Methotrexate is usually administered in an intermittent low-dose regimen such as once weekly. Similar regimens are in use in patients with rheumatoid arthritis. Administration can be oral, intravenous, intramuscular, or subcutaneous; the usual dose range is between 7.5 mg and 25 mg per week. Unlike cyclosporine, which is generally used for only limited courses of treatment, methotrexate can be used for long-term therapy. (See "Use of methotrexate in the treatment of rheumatoid arthritis" and 'Systemic calcineurin inhibitors' below.)
Folic acid, 1 mg daily, protects against some of the common side effects seen with low-dose methotrexate such as stomatitis . Folate does not appear to protect against pulmonary toxicity, and it is uncertain whether it protects against hepatic toxicity; monitoring for bone marrow suppression and hepatotoxicity are necessary during therapy. Concurrent use of other medications that interfere with folic acid metabolism, such as sulfa antibiotics, can increase the toxicity of methotrexate. (See "Major side effects of low-dose methotrexate".)
Hepatotoxicity and liver biopsy — In the past, the American Academy of Dermatology (AAD) recommended that all patients with psoriasis undergo liver biopsy to evaluate for hepatotoxicity after every 1 to 1.5 g of cumulative methotrexate . In 2009, the AAD and the National Psoriasis Foundation updated this recommendation with monitoring guidelines that are dependent upon the presence or absence of risk factors for hepatotoxicity [96,104].
●History of more than moderate alcohol consumption
●Persistent abnormal liver chemistry studies
●History of liver disease, such as chronic hepatitis B or C
●Family history of inherited liver disease (eg, hemochromatosis)
●History of significant exposure to hepatotoxic drugs (other than methotrexate) or chemicals
●Absence of folate supplementation during methotrexate therapy
Patients without risk factors for hepatotoxicity should have liver chemistries drawn every one to three months. If five out of nine serum AST levels are elevated over the course of 12 months, or if the serum albumin level is decreased in the context of normal nutritional status and well-controlled psoriasis, a liver biopsy should be performed.
Liver biopsy should also be considered after a cumulative dose of 3.5 to 4 g of methotrexate has been administered. Once patients have reached this dose, options include proceeding with a liver biopsy, continuing to monitor without a liver biopsy, or discontinuing methotrexate therapy.
In patients with risk factors for hepatotoxicity for whom the decision is made to proceed with methotrexate, liver biopsies are considered earlier in the course of therapy. Since a fair number of patients will discontinue therapy within the first two to six months, it is reasonable to perform the biopsy after this time period. For patients who continue methotrexate, liver biopsies should be considered after every 1 to 1.5 g of cumulative methotrexate. Once patients have reached this dose, options include proceeding with a liver biopsy, discontinuing methotrexate, or consulting with a hepatologist for further evaluation.
Retinoids — Systemic retinoids (derivatives of vitamin A) are utilized for patients with severe psoriasis, including pustular and erythrodermic forms, and in patients with HIV-associated psoriasis. The retinoid of choice in psoriasis is acitretin. In a pilot study, 6 of 11 patients with psoriasis and HIV infection achieved good to excellent results with acitretin therapy, with four achieving complete clearing of their skin disease . The usual dose range of acitretin is 25 mg every other day to 50 mg daily.
Monitoring for hypertriglyceridemia and hepatotoxicity are required with retinoid therapy. Common side effects include cheilitis and alopecia. Acitretin is teratogenic; it is only indicated in men and in women of non-reproductive potential. Pregnancy is contraindicated for three years after discontinuing the drug .
Systemic calcineurin inhibitors — The T-cell suppressor cyclosporine is effective in patients with severe psoriasis [109,110]. Usual doses are in the range of 3 to 5 mg/kg per day orally. Improvement is generally observed within four weeks.
The use of cyclosporine in psoriasis is based upon multiple studies supporting its status as a highly and rapidly effective treatment [96,111-113]. As an example, a placebo-controlled randomized trial found that after eight weeks of treatment with 3, 5, or 7.5 mg/kg of cyclosporine per day, 36, 65, and 80 percent of patients, respectively, were rated as clear or almost clear of psoriasis . All three regimens were superior to placebo, and patients who received the 5 mg dose were least likely to require dose alterations due to side effects or lack of efficacy.
A few randomized trials have compared the efficacy of cyclosporine and methotrexate, utilizing varying treatment regimens and providing different results. Although a 16-week randomized trial in 88 patients failed to find a significant difference in the effects of cyclosporine (3 to 5 mg/kg per day) and methotrexate (15 to 22.5 mg per week) on moderate to severe plaque psoriasis , a subsequent 12-week randomized trial of 84 patients with moderate to severe plaque psoriasis found results that indicated superiority of cyclosporine (3 to 5 mg/kg per day) over methotrexate (7.5 to 15 mg per week) . A smaller trial of patients with severe psoriasis found superior efficacy of methotrexate over cyclosporine (3 to 4 mg/kg per day), but utilized much higher doses of methotrexate than are typically prescribed in clinical practice (0.5 mg/kg per week) .
Close monitoring is required since renal toxicity and hypertension are common and often limit the long-term use of cyclosporine in patients with psoriasis. (See "Cyclosporine and tacrolimus nephrotoxicity".)
An investigational oral calcineurin inhibitor, ISA247, was efficacious in randomized trials in patients with moderate to severe plaque psoriasis, and may have less nephrotoxicity than cyclosporine .
Biologic agents — Biologic agents are important treatment options for moderate to severe plaque type psoriasis [118-120]. The available biologics for psoriasis have excellent short-term and long-term efficacy and favorable tolerability. Biologic therapies available for the treatment of psoriasis include etanercept, infliximab, adalimumab, and ustekinumab. The FDA approved secukinumab, an additional biologic agent, in January 2015.
Network meta-analyses evaluating etanercept, infliximab, adalimumab, and ustekinumab support the designation of infliximab as the most effective of these biologic agents for psoriasis [121-123]. As an example, in the first network meta-analysis of randomized trials for biologic therapy designed to adjust for inter-trial variability in reference arm responses, infliximab was associated with the highest likelihood for achieving 75 percent improvement in Psoriasis Area and Severity Index (PASI 75) scores . In addition, ustekinumab (45 or 90 mg dose) and adalimumab yielded significantly higher PASI 75 rates than etanercept (25 or 50 mg dose). Of note, the network meta-analysis was based upon PASI 75 rates achieved after 8 to 16 weeks of therapy. Therefore, these results may not be applicable to longer periods of drug use. A subsequent systematic review and meta-analysis that included the newer biologic agent secukinumab and evaluated randomized trials with treatment durations of at least 24 weeks found evidence to support infliximab, secukinumab, and ustekinumab as the most effective long-term therapies . In a head-to-head trial, a 16-week course of secukinumab was more effective than ustekinumab. (See 'Secukinumab' below.)
Alefacept, another biologic agent, is no longer marketed. Itolizumab, a biologic agent marketed in India, is not available in the United States.
There is a concern that all TNF-alpha inhibitors have the potential to activate latent infections such as tuberculosis, and increased rates of infection have been seen in patients with rheumatoid arthritis treated with etanercept, infliximab, and adalimumab. In addition, risk for herpes zoster may be increased in patients receiving biologic therapy in combination with methotrexate .
Data from a large observational study of 12,095 patients receiving or eligible to receive biologic therapy (PSOLAR) provides some reassurance regarding the use of biologic therapy for psoriasis . Compared with treatment with non-biologic agents, biologic therapy did not appear to be a significant predictor of death, major adverse cardiovascular events (MACE), or malignancy.
Potential side-effects of TNF-alpha inhibitors are reviewed in greater detail separately. (See "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections" and "Tumor necrosis factor-alpha inhibitors and mycobacterial infections" and "Tumor necrosis factor-alpha inhibitors: Risk of malignancy" and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)
Etanercept — The TNF-alpha inhibitor etanercept is of benefit in psoriasis [127-130]. It is approved by the FDA for psoriatic arthritis and for adults with chronic moderate to severe plaque psoriasis. Standard dosing for etanercept for adults is subcutaneous injection of 50 mg twice weekly for the initial three months of therapy, followed by a 50 mg injection once weekly for maintenance therapy.
A randomized trial of etanercept in 652 adult patients with active but stable plaque psoriasis involving at least 10 percent of the body surface area found three doses of subcutaneous etanercept (25 mg weekly, 25 mg twice weekly, 50 mg twice weekly) significantly superior to placebo . After 12 weeks, there was at least a 75 percent improvement in a psoriasis area and severity index (PASI) score in 14, 34, 49, and 4 percent, respectively. After 24 weeks, such an improvement was seen in 25, 44, and 59 percent, respectively (no patients received placebo for more than 12 weeks). Etanercept was well tolerated with adverse events and infections occurring at similar rates in all four groups.
A 12-week randomized trial found similar benefits with subcutaneous etanercept 50 mg twice weekly, and that, compared with placebo, patients receiving etanercept had significant improvements in measures of fatigue and depression . Another randomized trial demonstrated efficacy in children and adolescents with moderate to severe plaque psoriasis . The long-term safety of etanercept for psoriasis is supported by a 96-week study of etanercept 50 mg twice weekly .
The formation of anti-etanercept antibodies has been reported to occur in 0 to 18 percent of patients treated with the drug for psoriasis . However, in contrast to antibodies against infliximab and adalimumab in patients treated for psoriasis with those agents, the formation of anti-etanercept antibodies does not appear to reduce treatment efficacy .
Infliximab — The TNF-alpha inhibitor infliximab is of benefit in patients with moderate to severe plaque psoriasis and appears to generally be well tolerated [135-138]. In addition, the findings of a systematic review suggest that the onset of action of infliximab is faster than other commercially available biologic agents . Standard dosing for infliximab for adults is intravenous infusion of 5 mg/kg at weeks 0, 2, and 6, followed by every eight weeks thereafter.
Infliximab was efficacious for psoriasis in a multicenter randomized trial in 249 patients with severe plaque psoriasis. Compared with placebo, more patients treated with infliximab 3 mg/kg or 5 mg/kg (given intravenously at weeks zero, two, and six) achieved at least a 75 percent improvement in the PASI score at week 10 (6 percent versus 72 and 88 percent, respectively) . The duration of response appeared to be longer with the higher dose. More patients treated with infliximab had serious adverse events (12 versus 0), including four cases that the authors felt were reasonably related to treatment: squamous cell carcinoma, cholecystitis, diverticulitis, and pyelonephritis with sepsis.
The efficacy of infliximab (5 mg/kg given at weeks 0, 2, 6, 14, and 22) was compared with methotrexate (15 to 20 mg per week) in a 26-week open-label randomized trial in patients with moderate to severe psoriasis (RESTORE1 trial) . At week 16, patients who did not achieve at least 50 percent improvement were able to switch to the alternative therapy. The trial found that patients treated with infliximab (n = 653) exhibited greater improvement (78 versus 42 percent achieved 75 percent improvement in the PASI score by week 16) and were much less likely than patients in the methotrexate group (n = 215) to require switching to the alternative therapy (1 versus 29 percent) . In addition, patients who were transitioned from methotrexate to infliximab fared better than those who switched to methotrexate from infliximab; 73 versus 11 percent achieved 75 percent improvement in the PASI score.
Maintenance therapy with infliximab also appears to be effective [138,141,142]. A randomized trial using the dosing schedule above with infliximab 5 mg/kg through six weeks, but then adding maintenance dosing of infliximab 5 mg/kg every eight weeks through 46 weeks found that 61 percent of patients had at least a 75 percent improvement in the PASI score at week 50 . Infliximab was generally well tolerated. The use of maintenance therapy was further supported by a 50-week randomized trial; patients treated with continuous therapy (3 or 5 mg/kg infusion every eight weeks after induction therapy at zero, two, and six weeks) maintained the response to treatment better than patients who received intermittent "as needed" therapy (3 or 5 mg/kg infusions separated by at least four weeks when PASI improvement fell below 75 percent) .
In addition to experiencing better maintenance of response, there are some data that suggest that patients who receive continuous maintenance therapy with infliximab may be less likely to experience serious infusion-related reactions than patients who receive intermittent maintenance therapy. In trials comparing the two modes of maintenance therapy, slightly higher rates of infusion-related reactions have been observed among recipients of intermittent maintenance therapy [141,142]. A 128-week randomized trial (RESTORE2 trial) designed to compare the long-term efficacy of continuous maintenance therapy (5 mg/kg of infliximab every eight weeks after induction) and intermittent maintenance therapy (reinduction with up to four 5 mg/kg infusions of infliximab over 14 weeks if more than a 50 percent reduction in PASI improvement occurred) was terminated early (at week 124) due to an observation of a higher proportion of serious infusion-related reactions in the intermittent therapy group (8 of 219 [4 percent] versus 1 of 222 patients [<1 percent]) . The reason for this observation was unclear. Whether other regimens of intermittent maintenance therapy would be less likely to yield infusion reactions remains to be seen.
Studies in psoriasis, inflammatory bowel disease, and rheumatoid arthritis have suggested that the production of antibodies to infliximab may contribute to the loss of response to infliximab in some patients with these diseases [134,143-145]. Anti-infliximab antibodies have been reported to occur in 5 to 44 percent of patients who receive infliximab for psoriasis [134,146]. (See "Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases", section on 'Anti-drug antibodies'.)
Adalimumab — Adalimumab, a humanized monoclonal antibody with activity against TNF-alpha, was originally used for patients with rheumatoid arthritis and is also effective for psoriatic arthritis (see "Treatment of psoriatic arthritis"). Adalimumab is approved by the FDA for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. Standard dosing for adalimumab for adults is an initial subcutaneous injection of 80 mg of adalimumab followed by 40 mg given every other week, beginning one week after the initial dose.
Examples of studies supporting the efficacy of adalimumab include:
●A randomized trial in 147 patients with moderate to severe plaque psoriasis compared adalimumab by subcutaneous injection 40 mg every other week, 40 mg weekly, and placebo . After 12 weeks, more patients treated with adalimumab every other week or weekly achieved at least a 75 percent improvement in the PASI score (53 and 80 percent, respectively), versus 4 percent with placebo. In an open label extension of the study, improvements were sustained for 60 weeks.
●A randomized trial in 490 patients with moderate to severe psoriasis who had achieved a 75 percent improvement in the PASI score after 32 weeks of adalimumab found that continuing adalimumab resulted in a higher percentage of patients maintaining their response at 52 weeks (95 versus 72 percent) .
●A randomized trial found that adalimumab was more effective than placebo for the treatment of moderate to severe chronic plaque psoriasis involving the hands or feet . After 16 weeks, disease was cleared or almost cleared in 15 out of 49 patients in the adalimumab group (31 percent) compared with 1 out of 23 patients in the placebo group (4 percent).
Adalimumab may be an effective alternative for patients who fail to respond to etanercept [150-152]. In a multicenter, open-label study, patients who did not improve with 50 mg of etanercept twice weekly (n = 50) or who worsened following a dose reduction of etanercept to 50 mg once weekly (n = 35) were treated with 40 mg of adalimumab every other week . After 12 weeks, psoriasis was cleared or almost cleared in 34 percent (95% CI 20-48) of patients who had failed etanercept and 31 percent (95% CI 15-48) of patients who had disease recurrence on the lower dose of etanercept. Treatment success rates approached 50 percent when adalimumab (40 mg weekly or every other week) was given for an additional 12 weeks.
Formation of antibodies against adalimumab is reported to occur in 6 to 50 percent of patients treated with adalimumab for psoriasis and may reduce the response to therapy [134,146,153]. (See "Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases", section on 'Anti-drug antibodies'.)
Ustekinumab — Ustekinumab is a human monoclonal antibody that targets IL-12 and IL-23. In September 2009, ustekinumab was approved by the US Food and Drug Administration for the treatment of adult patients with moderate to severe psoriasis who are candidates for phototherapy or systemic therapy. Dosing of ustekinumab is weight-based. Standard dosing for ustekinumab for adults ≤100 kg is 45 mg given at weeks 0, 4, and every 12 weeks thereafter. A 90 mg dose given in the same regimen is recommended for adults who weigh more than 100 kg.
●A randomized trial in 766 patients with moderate to severe plaque psoriasis found that more patients treated with ustekinumab 45 mg or 90 mg achieved at least a 75 percent improvement in the PASI score at week 12 than those treated with placebo (67 and 66 versus 3 percent) . Ustekinumab was administered monthly by subcutaneous injection for the first two doses and then every 12 weeks. Responders who were kept on therapy generally maintained improvements in psoriasis out to at least 76 weeks. Serious adverse events were seen at similar rates in the ustekinumab and placebo arms.
●A second similarly designed trial in 1230 patients with moderate to severe plaque psoriasis also found that more patients treated with ustekinumab 45 mg or 90 mg achieved at least a 75 percent improvement in the PASI score at week 12 than those treated with placebo (67 and 76 versus 4 percent) . Patients who achieved a partial response at week 28 were randomly assigned to continue every 12 week dosing or escalate to every 8 week dosing. More frequent dosing did not enhance response rates at one year in patients receiving 45 mg, but did enhance 75 percent improvement rates in those receiving 90 mg (69 versus 33 percent with continued 12 week dosing). Serious adverse events were again seen at similar rates in the ustekinumab and placebo arms.
The efficacy of ustekinumab appears to persist over time. Follow-up data from one of the phase III randomized trials above  demonstrated maintenance of a high level of drug efficacy over the course of three years . In addition, treatment appears to be well tolerated [161,162].
A randomized trial reported superior efficacy of ustekinumab over etanercept for the treatment of psoriasis . In this trial, 903 patients with moderate to severe psoriasis received 90 mg of ustekinumab at weeks 0 and 4, 45 mg of ustekinumab at weeks 0 and 4, or 50 mg of etanercept twice weekly. After 12 weeks, 75 percent improvement in the PASI score was observed in 73.8, 67.5, and 56.8 percent of patients in the 90 mg ustekinumab, 45 mg ustekinumab, and etanercept groups, respectively. In addition, some patients who did not respond to etanercept benefited from treatment with ustekinumab. Twelve weeks after crossover to 90 mg of ustekinumab (administered at weeks 16 and 20), 48.9 percent achieved 75 percent improvement in the PASI score. The incidence of serious adverse effects was similar between treatment groups.
Data are limited on the best methods for transitioning patients from other therapies to ustekinumab. In a randomized trial (TRANSIT trial) performed in 490 patients with moderate to severe plaque psoriasis who had insufficient responses to methotrexate, measures of the efficacy and safety of ustekinumab after 12 weeks were similar among patients who immediately discontinued methotrexate at the start of ustekinumab therapy and patients who gradually withdrew methotrexate during the first four weeks after starting ustekinumab . Standard doses of ustekinumab were given; patients weighing 100 kg or less and patients weighing more than 100 kg were assigned to 45 and 90 mg doses, respectively. The findings of this study suggest that tapering of methotrexate during the transition to ustekinumab treatment may not be necessary. While there are not extensive data on the use of ustekinumab with methotrexate in patients with psoriasis, ustekinumab is FDA approved as a treatment with or without concomitant methotrexate in patients with psoriatic arthritis. (See "Treatment of psoriatic arthritis".)
Because of its immunomodulatory mechanism of action, there is concern that ustekinumab may increase the risk for infections and malignancy. However, five-year safety data showed no dose-related or cumulative sign of increased risk of severe infection or malignancy . Uncommon drug-related adverse effects, such as reversible posterior leukoencephalopathy syndrome and a lymphomatoid drug eruption have occurred in two separate patients [165,166]. (See "Reversible posterior leukoencephalopathy syndrome".)
Although randomized trials have demonstrated efficacy of ustekinumab for psoriatic arthritis, concern has been raised about whether psoriatic arthritis may worsen in certain patients during ustekinumab therapy. A case series documents four patients with psoriasis in whom psoriatic arthritis flared during ustekinumab therapy . (See "Treatment of psoriatic arthritis".)
Reports of major adverse cardiovascular events (MACE) during phase II and III studies for ustekinumab and briakinumab, another anti-IL-12/23 agent, led to the performance of a meta-analysis of placebo-controlled randomized trials evaluating the relationship between anti-IL-12/23 therapy and major adverse cardiovascular events in patients with chronic plaque psoriasis . The meta-analysis found that more major adverse cardiovascular events were reported in patients who received active treatment with ustekinumab or briakinumab than in those who received placebo (10 out of 3179 patients versus 0 out of 1474 patients). Although the difference in events was not statistically significant, the trial lengths were short (12 to 20 weeks), and the meta-analysis may have been underpowered to detect a significant difference.
A review of pooled data from phase II and phase III trials with up to five years follow-up did not reveal an increased risk for major adverse cardiovascular events . In addition, analysis of data from a large observational study of patients receiving or eligible to receive systemic therapy for psoriasis (PSOLAR) did not find an association between ustekinumab therapy and major adverse cardiovascular events .
Anti-ustekinumab antibodies have been reported to occur in 4 to 6 percent of patients treated with ustekinumab for psoriasis; however, an effect of anti-ustekinumab antibody formation on treatment efficacy remains to be confirmed .
Secukinumab — In January 2015, the FDA approved secukinumab, an anti-IL-17A monoclonal antibody, for the treatment of moderate to severe psoriasis. Two 52-week phase III placebo-controlled trials (ERASURE trial and FIXTURE trial) support the efficacy of secukinumab for moderate to severe plaque psoriasis . In both trials, secukinumab was given as a 300 mg or 150 mg dose once weekly for five weeks, then once every four weeks. In the ERASURE trial (n = 738) a 75 percent reduction in Psoriasis Area and Severity Index (PASI) score at week 12 was achieved by 82 percent of patients in the 300 mg secukinumab group and 72 percent of patients in the 150 mg secukinumab group, compared with only 5 percent of patients in the placebo group. The FIXTURE trial (n = 1306), which incorporated similar doses of secukinumab, found that secukinumab was superior to both etanercept (50 mg twice weekly for 12 weeks, then once weekly) and placebo. After 12 weeks, a 75 percent reduction in PASI score was detected in 77 percent of patients in the 300 mg secukinumab group, 67 percent of patients in the 150 mg secukinumab group, 44 percent of patients in the etanercept group, and 5 percent of patients in the placebo group. Placebo-controlled randomized trials evaluating the efficacy of secukinumab administered with an autoinjector or prefilled syringe on moderate to severe psoriasis also support the drug's efficacy [170,171].
Secukinumab has demonstrated greater efficacy for moderate to severe plaque psoriasis than ustekinumab with a similar degree of safety. In a prospective trial (CLEAR trial), 676 adults with moderate to severe plaque psoriasis were randomly assigned to secukinumab (300 mg given at baseline, week 1, week 2, and week 3, then every 4 weeks) and ustekinumab (45 mg or 90 mg given at baseline, week 4, and then every 12 weeks) . After 16 weeks, 90 percent improvement in PASI score occurred in 79 percent of patients in the secukinumab group compared with 58 percent of patients in the ustekinumab group. The rates of adverse effects were similar in the two groups.
Alefacept — The recombinant protein alefacept was effective for the treatment of psoriasis [173-175]. However, in late 2011, production and distribution of alefacept was discontinued by the drug manufacturer . The discontinuation of production was neither due to new safety concerns nor a mandatory recall. Alefacept was generally considered to be less effective for psoriasis than other biologic therapies.
Other — Itolizumab, a monoclonal antibody against the T-cell costimulator CD6, is a biologic agent that is available for the treatment of psoriasis in India. Itolizumab is not available in the United States.
The findings of a phase III trial support the superiority of itolizumab compared with placebo for the treatment of moderate to severe plaque psoriasis . However, response rates in the phase III trial were lower than those reported in phase III trials of infliximab, adalimumab, and ustekinumab therapy [138,148,156,157]. The efficacy of itolizumab has not been directly compared with other biologic agents.
Other immunosuppressive agents — Other immunosuppressive agents are sometimes used in selected cases of severe psoriasis . These drugs include hydroxyurea, 6-thioguanine, and azathioprine, which have a place in the treatment of psoriasis when other systemic modalities cannot be used, and tacrolimus, which is similar to cyclosporine and requires larger studies before it can be considered an accepted alternative . Daclizumab, which is used for prevention of renal transplant rejection, and the cancer chemotherapeutic drug paclitaxel are also under investigation for use in severe psoriasis [178,179].
Apremilast — Apremilast, a phosphodiesterase 4 inhibitor, is a new oral agent for the treatment of moderate severe plaque psoriasis [180-183]. Phosphodiesterase 4 inhibition reduces production of multiple cytokines involved in the pathogenesis of psoriasis. Apremilast is costly, priced closer to biologics than to methotrexate.
In September 2014, the US Food and Drug Administration (FDA) approved apremilast for the treatment of moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy. The approval was supported by the findings of two 16-week multicenter randomized trials in which a total 1257 adults with moderate to severe psoriasis were randomly assigned to receive 30 mg of apremilast twice daily or placebo . In the first trial, 33 percent of 562 patients treated with apremilast achieved 75 percent improvement in the Psoriasis Area and Severity Index (PASI-75), compared with only 5 percent of 282 patients in the placebo group. Results of the second trial were similar; 29 percent of 274 adults treated with apremilast achieved PASI-75, compared with 6 percent of 137 patients in the placebo group. Although apremilast represents an alternative systemic agent for the treatment of psoriasis, reported treatment success rates with apremilast are lower than those frequently reported for cyclosporine, anti-TNF biologic agents, and ustekinumab .
The use of a 30 mg twice daily dose of apremilast is further supported by a phase II randomized trial of 352 adults with moderate to severe plaque psoriasis that found lower efficacy with reduced doses. Among patients treated with 30 mg twice daily, 20 mg twice daily, 10 mg twice daily, and placebo, PASI-75 was achieved by 41, 29, 11, and 6 percent of patients, respectively .
Apremilast is associated with a short-term risk of diarrhea, especially when treatment is started, occurring in roughly 15 to 20 percent of patients. Tolerability of apremilast is improved by slowly ramping up the dose when treatment is initiated. The recommended dose titration schedule for adults is as follows:
●Day 1: 10 mg in morning
●Day 2: 10 mg in morning and 10 mg in evening
●Day 3: 10 mg in morning and 20 mg in evening
●Day 4: 20 mg in morning and 20 mg in evening
●Day 5: 20 mg in morning and 30 mg in evening
●Day 6 and thereafter: 30 mg twice daily
In adult patients with severe renal impairment the recommended final dose is 30 mg once daily. At the start of therapy, only the morning dose of the above titration schedule is given.
Examples of other reported side effects of apremilast include nausea, upper respiratory infection, headache, and weight loss. Periodic monitoring of weight is recommended . Advising patients, their caregivers, and families to be alert for worsening depression, suicidal thoughts, or other mood changes during treatment also is suggested based upon the possibility of a slight increase in risk for depression .
Fumaric acid esters — Fumaric acid esters (fumarates) have been used to treat psoriasis in Northern Europe . In a randomized trial of 60 patients with moderate to severe psoriasis, reductions in disease severity after treatment with fumaric acid esters were similar to those observed with methotrexate therapy . Additional trials of fumarates are being performed.
Lymphopenia is an occasional side effect of treatment with fumaric acid esters. In 2013, two cases of progressive multifocal leukoencephalopathy (PML) were reported in patients who continued to receive long-term fumaric acid ester therapy despite the development of severe lymphopenia [187,188]. These patients did not have other known causes of immunodeficiency.
TONSILLECTOMY — An association between psoriasis (especially guttate psoriasis) and streptococcal infection has contributed to investigations of the role of tonsillectomy for the treatment of psoriasis. (See "Guttate psoriasis", section on 'Pathogenesis'.)
A systematic review that evaluated data on tonsillectomy for guttate or plaque psoriasis from controlled and observational studies (including case reports and case series) found that the majority of reported patients experienced improvement in psoriasis after tonsillectomy (290 of 410 patients) . Lengthening of psoriasis remissions and improvement in response to treatments for psoriasis were also documented. However, data were insufficient to recommend the routine use of tonsillectomy for psoriasis because most of the patient data were derived from case reports and case series and publication bias may have contributed to the favorable results. Further study is necessary to confirm the effects of tonsillectomy on psoriasis.
Given the limitations of the available data, tonsillectomy should be reserved for select patients with recalcitrant psoriasis that clearly exhibits exacerbations related to episodes of tonsillitis . Tonsillectomy is not a benign procedure; infection, hemorrhage, laryngospasm, bronchospasm, temporomandibular joint dysfunction, vocal changes, and rarely airway compromise are potential adverse effects . Relapse after tonsillectomy is also possible.
FUTURE THERAPIES — There are multiple therapies under development for the treatment of psoriasis. These therapies are designed to mediate psoriasis through a variety of mechanisms.
●Therapies targeting the Th17 pathway – Interleukins in the Th17 pathway play a pivotal role in the pathogenesis of psoriasis and have become targets for drug development. Drugs such as briakinumab [190-193], ixekizumab [194-196], and brodalumab [197,198] have been developed to target this pathway.
Phase III placebo-controlled randomized trials have supported the efficacy of briakinumab, a monoclonal antibody targeting IL-12/23, in moderate to severe plaque psoriasis, and the drug has exhibited efficacy superior to that of etanercept and methotrexate [190-193]. However, concerns have been raised regarding a potential relationship between briakinumab treatment and major cardiovascular adverse events (see 'Ustekinumab' above) . Marketing plans for briakinumab have been suspended, and it remains uncertain whether the drug will become available for clinical use.
Phase II trials have demonstrated efficacy of an anti-IL-17 monoclonal antibody (ixekizumab) , an anti-IL-17 receptor monoclonal antibody (brodalumab) . Examples of other drugs under investigation for psoriasis include guselkumab (a human monoclonal antibody directed against IL-23) [199,200] as well as tildrakizumab and BI 655066 (human monoclonal antibodies directed against the p19 subunit of IL-23) [201,202].
●Anti-TNF therapy – A phase II trial supports the efficacy of a humanized anti-TNF monoclonal antibody Fab fragment linked to polyethylene glycol (certolizumab pegol) in moderate to severe plaque psoriasis .
●Small molecules – Other potential therapies include various small molecules that target the interruption of cellular signaling; such signaling is critical to propagation of the inflammatory response. Examples of small molecules that are being studied for the treatment of psoriasis include molecules that block janus kinases (JAK) [204-207], lipids , and a protein kinase C inhibitor .
Oral tofacitinib, a small molecule JAK inhibitor approved and marketed for the treatment of rheumatoid arthritis, has demonstrated efficacy for moderate to severe plaque psoriasis in randomized trials [205,206,210,211]. In a phase III trial that randomly assigned 1106 adults with moderate to severe plaque psoriasis to treatment with tofacitinib 10 mg twice daily, tofacitinib 5 mg twice daily, etanercept (50 mg twice weekly), or placebo, tofacitinib 10 mg twice daily was superior to placebo and non-inferior to etanercept for achieving 75 percent improvement in PASI score . By week 12, 64, 40, 59, and 6 percent of patients treated with tofacitinib 10 mg twice daily, tofacitinib 5 mg twice daily, etanercept, and placebo achieved this endpoint, respectively. Additional phase III trials comparing tofacitinib 10 mg twice daily, tofacitinib 5 mg twice daily, and placebo for chronic plaque psoriasis also have demonstrated efficacy of tofacitinib therapy . The best results are achieved with 10 mg twice-daily dosing.
The onset of effect of tofacitinib can be fairly rapid, with responses evident by week four. Treatment is generally well tolerated. Tofacitinib may increase risk for infection. Elevations of cholesterol and creatinine phosphokinase levels also may occur during therapy [210,211].
Targeting of the sphingosine 1-phosphate receptor 1 (S1PR1), a receptor involved in the movement of lymphocytes from secondary lymphoid tissues into the circulation, may be an additional effective method to treat psoriasis. Ponesimod, a selective modulator of S1PR1 also studied for the treatment of multiple sclerosis, induces internalization of S1PR1, thereby inhibiting sphingosine 1-phosphate (S1P)-induced egress of lymphocytes. In a phase II randomized trial that evaluated ponesimod in 326 patients with moderate to severe chronic plaque psoriasis, patients treated with ponesimod were significantly more likely than patients treated with placebo to achieve a 75 percent reduction in PASI score after 16 weeks .
In small, uncontrolled studies, treatment with a glucagon-like peptide 1 (GLP-1) analog (exenatide or liraglutide) seemed to promote modest improvement in psoriasis in patients with both psoriasis and type 2 diabetes [213,214]. However, a placebo-controlled randomized trial (n = 20) found liraglutide ineffective for plaque psoriasis .
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient information: Psoriasis (The Basics)")
●Beyond the Basics topics (see "Patient information: Psoriasis (Beyond the Basics)")
The National Psoriasis Foundation is a nonprofit organization that provides useful information to patients with psoriasis and their clinicians. Membership includes access to a newsletter that provides information on current areas of research and new treatments. Brochures on various forms of psoriasis treatment (topical, phototherapy, systemic agents) and specific fact sheets on each biologic treatment are available from the Foundation and its website.
National Psoriasis Foundation
6600 SW 92nd Ave., Suite 300
Portland, OR 97223-7195
SUMMARY AND RECOMMENDATIONS — Numerous topical and systemic therapies are available for the treatment of psoriasis. Treatment modalities are chosen on the basis of disease severity, relevant comorbidities, patient preference (including cost and convenience), efficacy, and evaluation of individual patient response. (See 'Approach' above.)
Alternatives include tar, topical retinoids (tazarotene), topical vitamin D, and anthralin. For facial or intertriginous areas, topical tacrolimus or pimecrolimus may be used as alternatives or as corticosteroid sparing agents. Improvement can be anticipated within one or two months. Combination regimens may be required, including localized phototherapy. Patient adherence may be the largest barrier to treatment success with topical therapies; early follow-up (one week after starting treatment) may improve compliance. (See 'Topical therapies' above and 'Ultraviolet light' above.)
The topical therapies discussed above are generally also required as adjuvant therapy and for symptomatic relief (see 'Topical therapies' above). In patients with contraindications to phototherapy or who have failed phototherapy, we suggest treatment with a systemic agent (Grade 2B).
Financial considerations or time constraints may also make systemic therapy preferable to phototherapy for some patients. Systemic agents include retinoids, methotrexate, cyclosporine, apremilast, and biologic immune modifying agents such as adalimumab, etanercept, infliximab, ustekinumab, and secukinumab. Treatment of psoriatic arthritis is discussed in detail separately. (See "Treatment of psoriatic arthritis".)
Improvement should be observed within weeks. Patients with moderate to severe psoriasis on systemic treatment will generally require care by a dermatologist. (See 'Severe disease' above.)
For patients receiving methotrexate for the management of psoriasis, the decision to perform a liver biopsy should be individualized based upon a patient's risk factors, liver chemistry results, and cumulative methotrexate dose, in accord with updated guidelines from the American Academy of Dermatology (AAD). (See 'Hepatotoxicity and liver biopsy' above.)
- Menter A, Griffiths CE. Current and future management of psoriasis. Lancet 2007; 370:272.
- Armstrong AW, Robertson AD, Wu J, et al. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from the National Psoriasis Foundation surveys, 2003-2011. JAMA Dermatol 2013; 149:1180.
- Esposito M, Saraceno R, Giunta A, et al. An Italian study on psoriasis and depression. Dermatology 2006; 212:123.
- Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 2010; 146:891.
- Perrott SB, Murray AH, Lowe J, Mathieson CM. The psychosocial impact of psoriasis: physical severity, quality of life, and stigmatization. Physiol Behav 2000; 70:567.
- Thomas CL, Finlay AY. The 'handprint' approximates to 1% of the total body surface area whereas the 'palm minus the fingers' does not. Br J Dermatol 2007; 157:1080.
- Kalb RE, Bagel J, Korman NJ, et al. Treatment of intertriginous psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2009; 60:120.
- American Academy of Dermatology Work Group, Menter A, Korman NJ, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011; 65:137.
- Chan CS, Van Voorhees AS, Lebwohl MG, et al. Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2009; 60:962.
- Mason AR, Mason JM, Cork MJ, et al. Topical treatments for chronic plaque psoriasis of the scalp: a systematic review. Br J Dermatol 2013; 169:519.
- Crowley JJ, Weinberg JM, Wu JJ, et al. Treatment of nail psoriasis: best practice recommendations from the Medical Board of the National Psoriasis Foundation. JAMA Dermatol 2015; 151:87.
- de Vries AC, Bogaards NA, Hooft L, et al. Interventions for nail psoriasis. Cochrane Database Syst Rev 2013; 1:CD007633.
- Armstrong AW, Tuong W, Love TJ, et al. Treatments for nail psoriasis: a systematic review by the GRAPPA Nail Psoriasis Work Group. J Rheumatol 2014; 41:2306.
- Jiaravuthisan MM, Sasseville D, Vender RB, et al. Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy. J Am Acad Dermatol 2007; 57:1.
- Rigopoulos D, Gregoriou S, Daniel Iii CR, et al. Treatment of nail psoriasis with a two-compound formulation of calcipotriol plus betamethasone dipropionate ointment. Dermatology 2009; 218:338.
- Rich P, Griffiths CE, Reich K, et al. Baseline nail disease in patients with moderate to severe psoriasis and response to treatment with infliximab during 1 year. J Am Acad Dermatol 2008; 58:224.
- Van den Bosch F, Manger B, Goupille P, et al. Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions. Ann Rheum Dis 2010; 69:394.
- Luger TA, Barker J, Lambert J, et al. Sustained improvement in joint pain and nail symptoms with etanercept therapy in patients with moderate-to-severe psoriasis. J Eur Acad Dermatol Venereol 2009; 23:896.
- Kavanaugh A, McInnes I, Mease P, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009; 60:976.
- Ortonne JP, Paul C, Berardesca E, et al. A 24-week randomized clinical trial investigating the efficacy and safety of two doses of etanercept in nail psoriasis. Br J Dermatol 2013; 168:1080.
- Rich P, Bourcier M, Sofen H, et al. Ustekinumab improves nail disease in patients with moderate-to-severe psoriasis: results from PHOENIX 1. Br J Dermatol 2014; 170:398.
- Paul C, Reich K, Gottlieb AB, et al. Secukinumab improves hand, foot and nail lesions in moderate-to-severe plaque psoriasis: subanalysis of a randomized, double-blind, placebo-controlled, regimen-finding phase 2 trial. J Eur Acad Dermatol Venereol 2014; 28:1670.
- Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis 2014; 73:48.
- Tosti A, Ricotti C, Romanelli P, et al. Evaluation of the efficacy of acitretin therapy for nail psoriasis. Arch Dermatol 2009; 145:269.
- Gümüşel M, Özdemir M, Mevlitoğlu I, Bodur S. Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study. J Eur Acad Dermatol Venereol 2011; 25:1080.
- Treewittayapoom C, Singvahanont P, Chanprapaph K, Haneke E. The effect of different pulse durations in the treatment of nail psoriasis with 595-nm pulsed dye laser: a randomized, double-blind, intrapatient left-to-right study. J Am Acad Dermatol 2012; 66:807.
- Marx JL, Scher RK. Response of psoriatic nails to oral photochemotherapy. Arch Dermatol 1980; 116:1023.
- Handfield-Jones SE, Boyle J, Harman RR. Local PUVA treatment for nail psoriasis. Br J Dermatol 1987; 116:280.
- Rosenbach M, Hsu S, Korman NJ, et al. Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol 2010; 62:655.
- Esposito M, Mazzotta A, de Felice C, et al. Treatment of erythrodermic psoriasis with etanercept. Br J Dermatol 2006; 155:156.
- Richetta AG, Maiani E, Carlomagno V, et al. Treatment of erythrodermic psoriasis in HCV+ patient with adalimumab. Dermatol Ther 2009; 22 Suppl 1:S16.
- Santos-Juanes J, Coto-Segura P, Mas-Vidal A, Galache Osuna C. Ustekinumab induces rapid clearing of erythrodermic psoriasis after failure of antitumour necrosis factor therapies. Br J Dermatol 2010; 162:1144.
- de Jager ME, de Jong EM, van de Kerkhof PC, Seyger MM. Efficacy and safety of treatments for childhood psoriasis: a systematic literature review. J Am Acad Dermatol 2010; 62:1013.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009; 60:643.
- Samarasekera EJ, Sawyer L, Wonderling D, et al. Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses. Br J Dermatol 2013; 168:954.
- Reisfeld PL. How high is up? generic prices rise. Cutis 2014; 93:6.
- Franz TJ, Parsell DA, Halualani RM, et al. Betamethasone valerate foam 0.12%: a novel vehicle with enhanced delivery and efficacy. Int J Dermatol 1999; 38:628.
- Lebwohl M, Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J Am Acad Dermatol 2001; 45:487.
- Clobetasol propionate (Clobex) spray for psoriasis. Med Lett Drugs Ther 2006; 48:27.
- Mason AR, Mason J, Cork M, et al. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev 2013; 3:CD005028.
- Ortonne JP, Humbert P, Nicolas JF, et al. Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas. Br J Dermatol 2003; 148:326.
- Jensen AM, Lladó MB, Skov L, et al. Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells. Br J Dermatol 1998; 139:984.
- Vissers WH, Berends M, Muys L, et al. The effect of the combination of calcipotriol and betamethasone dipropionate versus both monotherapies on epidermal proliferation, keratinization and T-cell subsets in chronic plaque psoriasis. Exp Dermatol 2004; 13:106.
- Ashcroft DM, Po AL, Williams HC, Griffiths CE. Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis. BMJ 2000; 320:963.
- Lebwohl M, Yoles A, Lombardi K, Lou W. Calcipotriene ointment and halobetasol ointment in the long-term treatment of psoriasis: effects on the duration of improvement. J Am Acad Dermatol 1998; 39:447.
- Papp KA, Guenther L, Boyden B, et al. Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis. J Am Acad Dermatol 2003; 48:48.
- Kragballe K, van de Kerkhof PC. Consistency of data in six phase III clinical studies of a two-compound product containing calcipotriol and betamethasone dipropionate ointment for the treatment of psoriasis. J Eur Acad Dermatol Venereol 2006; 20:39.
- Koo J, Blum RR, Lebwohl M. A randomized, multicenter study of calcipotriene ointment and clobetasol propionate foam in the sequential treatment of localized plaque-type psoriasis: short- and long-term outcomes. J Am Acad Dermatol 2006; 55:637.
- Kaufmann R, Bibby AJ, Bissonnette R, et al. A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris. Dermatology 2002; 205:389.
- Bourke JF, Berth-Jones J, Hutchinson PE. Hypercalcaemia with topical calcipotriol. BMJ 1993; 306:1344.
- Rizova E, Corroller M. Topical calcitriol--studies on local tolerance and systemic safety. Br J Dermatol 2001; 144 Suppl 58:3.
- Lebwohl M, Menter A, Weiss J, et al. Calcitriol 3 microg/g ointment in the management of mild to moderate plaque type psoriasis: results from 2 placebo-controlled, multicenter, randomized double-blind, clinical studies. J Drugs Dermatol 2007; 6:428.
- Lebwohl M, Ortonne JP, Andres P, Briantais P. Calcitriol ointment 3 microg/g is safe and effective over 52 weeks for the treatment of mild to moderate plaque psoriasis. Cutis 2009; 83:205.
- Goodfield M, Kownacki S, Berth-Jones J. Double-blind, randomised, multicentre, parallel group study comparing a 1% coal tar preparation (Exorex) with a 5% coal tar preparation (Alphosyl) in chronic plaque psoriasis. J Dermatolog Treat 2004; 15:14.
- Tzaneva S, Hönigsmann H, Tanew A. Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque type psoriasis. Br J Dermatol 2003; 149:350.
- Weinstein GD, Koo JY, Krueger GG, et al. Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks. J Am Acad Dermatol 2003; 48:760.
- Lebwohl M, Ast E, Callen JP, et al. Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis. J Am Acad Dermatol 1998; 38:705.
- Veraldi S, Caputo R, Pacifico A, et al. Short contact therapy with tazarotene in psoriasis vulgaris. Dermatology 2006; 212:235.
- Gollnick H, Menter A. Combination therapy with tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis. Br J Dermatol 1999; 140 Suppl 54:18.
- Freeman AK, Linowski GJ, Brady C, et al. Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. J Am Acad Dermatol 2003; 48:564.
- Wilsmann-Theis D, Hagemann T, Dederer H, et al. Successful treatment of acrodermatitis continua suppurativa with topical tacrolimus 0.1% ointment. Br J Dermatol 2004; 150:1194.
- Mrowietz U, Wustlich S, Hoexter G, et al. An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion. Acta Derm Venereol 2003; 83:351.
- Yamamoto T, Nishioka K. Topical tacrolimus: an effective therapy for facial psoriasis. Eur J Dermatol 2003; 13:471.
- Lebwohl M, Freeman AK, Chapman MS, et al. Tacrolimus ointment is effective for facial and intertriginous psoriasis. J Am Acad Dermatol 2004; 51:723.
- Gribetz C, Ling M, Lebwohl M, et al. Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study. J Am Acad Dermatol 2004; 51:731.
- Kreuter A, Sommer A, Hyun J, et al. 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study. Arch Dermatol 2006; 142:1138.
- http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm153956.htm (Accessed on May 10, 2007).
- http://www.fda.gov/newsevents/newsroom/pressannouncements/2006/ucm108580.htm (Accessed on May 10, 2007).
- Siegfried EC, Jaworski JC, Hebert AA. Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Dermatol 2013; 14:163.
- Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors. Br J Dermatol 2011; 165:465.
- van de Kerkhof PC, van der Valk PG, Swinkels OQ, et al. A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting. Br J Dermatol 2006; 155:800.
- Jekler J, Swanbeck G. One-minute dithranol therapy in psoriasis: a placebo-controlled paired comparative study. Acta Derm Venereol 1992; 72:449.
- Oostveen AM, Beulens CA, van de Kerkhof PC, et al. The effectiveness and safety of short-contact dithranol therapy in paediatric psoriasis: a prospective comparison of regular day care and day care with telemedicine. Br J Dermatol 2014; 170:454.
- Forman SB. Miscellaneous topical agents. In: Comprehensive Dermatologic Drug Therapy, 2nd ed, Wolverton SE (Ed), Elsevier, Philadelphia 2007. p.775.
- Berth-Jones J, Chu AC, Dodd WA, et al. A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis. Br J Dermatol 1992; 127:266.
- Wall AR, Poyner TF, Menday AP. A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis. Br J Dermatol 1998; 139:1005.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol 2010; 62:114.
- Housman TS, Rohrback JM, Fleischer AB Jr, Feldman SR. Phototherapy utilization for psoriasis is declining in the United States. J Am Acad Dermatol 2002; 46:557.
- Cooper KD, Oberhelman L, Hamilton TA, et al. UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a-DR+ epidermal macrophage induction, and Langerhans cell depletion. Proc Natl Acad Sci U S A 1992; 89:8497.
- Walters IB, Burack LH, Coven TR, et al. Suberythemogenic narrow-band UVB is markedly more effective than conventional UVB in treatment of psoriasis vulgaris. J Am Acad Dermatol 1999; 40:893.
- Stern RS. Psoralen and ultraviolet a light therapy for psoriasis. N Engl J Med 2007; 357:682.
- Berneburg M, Herzinger T, Rampf J, et al. Efficacy of bath psoralen plus ultraviolet A (PUVA) vs. system PUVA in psoriasis: a prospective, open, randomized, multicentre study. Br J Dermatol 2013; 169:704.
- Lebwohl M, Martinez J, Weber P, DeLuca R. Effects of topical preparations on the erythemogenicity of UVB: implications for psoriasis phototherapy. J Am Acad Dermatol 1995; 32:469.
- Chen X, Yang M, Cheng Y, et al. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev 2013; 10:CD009481.
- Anderson KL, Feldman SR. A guide to prescribing home phototherapy for patients with psoriasis: the appropriate patient, the type of unit, the treatment regimen, and the potential obstacles. J Am Acad Dermatol 2015; 72:868.
- Koek MB, Buskens E, van Weelden H, et al. Home versus outpatient ultraviolet B phototherapy for mild to severe psoriasis: pragmatic multicentre randomised controlled non-inferiority trial (PLUTO study). BMJ 2009; 338:b1542.
- Carlin CS, Callis KP, Krueger GG. Efficacy of acitretin and commercial tanning bed therapy for psoriasis. Arch Dermatol 2003; 139:436.
- Fleischer AB Jr, Clark AR, Rapp SR, et al. Commercial tanning bed treatment is an effective psoriasis treatment: results from an uncontrolled clinical trial. J Invest Dermatol 1997; 109:170.
- Radack KP, Farhangian ME, Anderson KL, Feldman SR. A review of the use of tanning beds as a dermatological treatment. Dermatol Ther (Heidelb) 2015; 5:37.
- Feldman SR, Mellen BG, Housman TS, et al. Efficacy of the 308-nm excimer laser for treatment of psoriasis: results of a multicenter study. J Am Acad Dermatol 2002; 46:900.
- Gerber W, Arheilger B, Ha TA, et al. Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach. Br J Dermatol 2003; 149:1250.
- Branda RF, Eaton JW. Skin color and nutrient photolysis: an evolutionary hypothesis. Science 1978; 201:625.
- Gambichler T, Bader A, Sauermann K, et al. Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial. BMC Dermatol 2001; 1:8.
- Rose RF, Batchelor RJ, Turner D, Goulden V. Narrowband ultraviolet B phototherapy does not influence serum and red cell folate levels in patients with psoriasis. J Am Acad Dermatol 2009; 61:259.
- Schiener R, Brockow T, Franke A, et al. Bath PUVA and saltwater baths followed by UV-B phototherapy as treatments for psoriasis: a randomized controlled trial. Arch Dermatol 2007; 143:586.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009; 61:451.
- Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008; 58:826.
- Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol 2012; 148:95.
- Schmitt J, Rosumeck S, Thomaschewski G, et al. Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br J Dermatol 2014; 170:274.
- Gottlieb SL, Gilleaudeau P, Johnson R, et al. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med 1995; 1:442.
- Saurat JH, Stingl G, Dubertret L, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008; 158:558.
- Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994; 121:833.
- Roenigk HH Jr, Auerbach R, Maibach H, et al. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol 1998; 38:478.
- Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2009; 60:824.
- Buccheri L, Katchen BR, Karter AJ, Cohen SR. Acitretin therapy is effective for psoriasis associated with human immunodeficiency virus infection. Arch Dermatol 1997; 133:711.
- Tanew A, Guggenbichler A, Hönigsmann H, et al. Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study. J Am Acad Dermatol 1991; 25:682.
- Lebwohl M, Drake L, Menter A, et al. Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis. J Am Acad Dermatol 2001; 45:544.
- Lam J, Polifka JE, Dohil MA. Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases. J Am Acad Dermatol 2008; 59:295.
- Rosmarin DM, Lebwohl M, Elewski BE, et al. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2010; 62:838.
- Strober BE, Siu K, Menon K. Conventional systemic agents for psoriasis. A systematic review. J Rheumatol 2006; 33:1442.
- Ellis CN, Fradin MS, Messana JM, et al. Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. N Engl J Med 1991; 324:277.
- Faerber L, Braeutigam M, Weidinger G, et al. Cyclosporine in severe psoriasis. Results of a meta-analysis in 579 patients. Am J Clin Dermatol 2001; 2:41.
- Ho VC, Griffiths CE, Albrecht G, et al. Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study. The PISCES Study Group. Br J Dermatol 1999; 141:283.
- Heydendael VM, Spuls PI, Opmeer BC, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med 2003; 349:658.
- Flytström I, Stenberg B, Svensson A, Bergbrant IM. Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial. Br J Dermatol 2008; 158:116.
- Sandhu K, Kaur I, Kumar B, Saraswat A. Efficacy and safety of cyclosporine versus methotrexate in severe psoriasis: a study from north India. J Dermatol 2003; 30:458.
- Papp K, Bissonnette R, Rosoph L, et al. Efficacy of ISA247 in plaque psoriasis: a randomised, multicentre, double-blind, placebo-controlled phase III study. Lancet 2008; 371:1337.
- Callen JP. New psoriasis treatments based upon a deeper understanding of the pathogenesis of psoriasis vulgaris and psoriatic arthritis: a personal appraisal of their use in practice. J Am Acad Dermatol 2003; 49:351.
- Kupper TS. Immunologic targets in psoriasis. N Engl J Med 2003; 349:1987.
- Boehncke WH, Prinz J, Gottlieb AB. Biologic therapies for psoriasis. A systematic review. J Rheumatol 2006; 33:1447.
- Signorovitch JE, Betts KA, Yan YS, et al. Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response. Br J Dermatol 2015; 172:504.
- Lin VW, Ringold S, Devine EB. Comparison of Ustekinumab With Other Biological Agents for the Treatment of Moderate to Severe Plaque Psoriasis: A Bayesian Network Meta-analysis. Arch Dermatol 2012; 148:1403.
- Reich K, Burden AD, Eaton JN, Hawkins NS. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 2012; 166:179.
- Nast A, Jacobs A, Rosumeck S, Werner RN. Efficacy and Safety of Systemic Long-term Treatments for Moderate-to-Severe Psoriasis-A Systematic Review and Meta-Analysis. J Invest Dermatol 2015.
- Shalom G, Zisman D, Bitterman H, et al. Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500,000 Person-year Study. JAMA Dermatol 2015; 151:533.
- Gottlieb AB, Kalb RE, Langley RG, et al. Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies. J Drugs Dermatol 2014; 13:1441.
- Iyer S, Yamauchi P, Lowe NJ. Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy. Br J Dermatol 2002; 146:118.
- Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003; 349:2014.
- Bagel J, Lynde C, Tyring S, et al. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. J Am Acad Dermatol 2012; 67:86.
- Lebwohl MG, Kircik L, Callis Duffin K, et al. A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol 2013; 69:385.
- Tyring S, Gottlieb A, Papp K, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006; 367:29.
- Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med 2008; 358:241.
- Tyring S, Gordon KB, Poulin Y, et al. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Arch Dermatol 2007; 143:719.
- Hsu L, Snodgrass BT, Armstrong AW. Antidrug antibodies in psoriasis: a systematic review. Br J Dermatol 2014; 170:261.
- Chaudhari U, Romano P, Mulcahy LD, et al. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet 2001; 357:1842.
- Gottlieb AB, Masud S, Ramamurthi R, et al. Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris. J Am Acad Dermatol 2003; 48:68.
- Gottlieb AB, Evans R, Li S, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2004; 51:534.
- Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366:1367.
- Nast A, Sporbeck B, Rosumeck S, et al. Which antipsoriatic drug has the fastest onset of action? Systematic review on the rapidity of the onset of action. J Invest Dermatol 2013; 133:1963.
- Barker J, Hoffmann M, Wozel G, et al. Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1). Br J Dermatol 2011; 165:1109.
- Menter A, Feldman SR, Weinstein GD, et al. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol 2007; 56:31.e1.
- Reich K, Wozel G, Zheng H, et al. Efficacy and safety of infliximab as continuous or intermittent therapy in patients with moderate-to-severe plaque psoriasis: results of a randomized, long-term extension trial (RESTORE2). Br J Dermatol 2013; 168:1325.
- Hanauer SB, Wagner CL, Bala M, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease. Clin Gastroenterol Hepatol 2004; 2:542.
- Stern R, Wolfe F. Infliximab dose and clinical status: results of 2 studies in 1642 patients with rheumatoid arthritis. J Rheumatol 2004; 31:1538.
- Han PD, Cohen RD. Managing immunogenic responses to infliximab: treatment implications for patients with Crohn's disease. Drugs 2004; 64:1767.
- Bito T, Nishikawa R, Hatakeyama M, et al. Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis. Br J Dermatol 2014; 170:922.
- Gordon KB, Langley RG, Leonardi C, et al. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol 2006; 55:598.
- Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58:106.
- Leonardi C, Langley RG, Papp K, et al. Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial. Arch Dermatol 2011; 147:429.
- Bissonnette R, Bolduc C, Poulin Y, et al. Efficacy and safety of adalimumab in patients with plaque psoriasis who have shown an unsatisfactory response to etanercept. J Am Acad Dermatol 2010; 63:228.
- Van Lümig PP, Lecluse LL, Driessen RJ, et al. Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, secondary failure or intolerance to etanercept. Br J Dermatol 2010; 163:838.
- Strober BE, Poulin Y, Kerdel FA, et al. Switching to adalimumab for psoriasis patients with a suboptimal response to etanercept, methotrexate, or phototherapy: efficacy and safety results from an open-label study. J Am Acad Dermatol 2011; 64:671.
- Menting SP, van Lümig PP, de Vries AC, et al. Extent and consequences of antibody formation against adalimumab in patients with psoriasis: one-year follow-up. JAMA Dermatol 2014; 150:130.
- Menting SP, Coussens E, Pouw MF, et al. Developing a Therapeutic Range of Adalimumab Serum Concentrations in Management of Psoriasis: A Step Toward Personalized Treatment. JAMA Dermatol 2015; 151:616.
- Krueger GG, Langley RG, Leonardi C, et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007; 356:580.
- Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371:1665.
- Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371:1675.
- Lebwohl M, Yeilding N, Szapary P, et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. J Am Acad Dermatol 2010; 63:571.
- Tsai TF, Ho JC, Song M, et al. Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL). J Dermatol Sci 2011; 63:154.
- Kimball AB, Gordon KB, Fakharzadeh S, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial through up to 3 years. Br J Dermatol 2012; 166:861.
- Papp KA, Griffiths CE, Gordon K, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol 2013; 168:844.
- Langley RG, Lebwohl M, Krueger GG, et al. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol 2015; 172:1371.
- Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010; 362:118.
- Paul C, Puig L, Kragballe K, et al. Transition to ustekinumab in patients with moderate-to-severe psoriasis and inadequate response to methotrexate: a randomized clinical trial (TRANSIT). Br J Dermatol 2014; 170:425.
- Gratton D, Szapary P, Goyal K, et al. Reversible posterior leukoencephalopathy syndrome in a patient treated with ustekinumab: case report and review of the literature. Arch Dermatol 2011; 147:1197.
- Jung J, Levin EC, Jarrett R, et al. Lymphomatoid drug reaction to ustekinumab. Arch Dermatol 2011; 147:992.
- Stamell EF, Kutner A, Viola K, Cohen SR. Ustekinumab associated with flares of psoriatic arthritis. JAMA Dermatol 2013; 149:1410.
- Ryan C, Leonardi CL, Krueger JG, et al. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA 2011; 306:864.
- Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 2014; 371:326.
- Paul C, Lacour JP, Tedremets L, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2015; 29:1082.
- Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015; 172:484.
- Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol 2015.
- Roberts JL, Ortonne JP, Tan JK, et al. The safety profile and sustained remission associated with response to multiple courses of intramuscular alefacept for treatment of chronic plaque psoriasis. J Am Acad Dermatol 2010; 62:968.
- Ellis CN, Krueger GG, Alefacept Clinical Study Group. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 345:248.
- Krueger GG, Papp KA, Stough DB, et al. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol 2002; 47:821.
- http://www.psoriasis.org/page.aspx?pid=2311 (Accessed on March 18, 2012).
- Krupashankar DS, Dogra S, Kura M, et al. Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study. J Am Acad Dermatol 2014; 71:484.
- Lebwohl M. Psoriasis. Lancet 2003; 361:1197.
- Ehrlich A, Booher S, Becerra Y, et al. Micellar paclitaxel improves severe psoriasis in a prospective phase II pilot study. J Am Acad Dermatol 2004; 50:533.
- Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 2010; 159:842.
- Gottlieb AB, Strober B, Krueger JG, et al. An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr Med Res Opin 2008; 24:1529.
- Papp K, Cather JC, Rosoph L, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet 2012; 380:738.
- Papp KA, Kaufmann R, Thaçi D, et al. Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison study. J Eur Acad Dermatol Venereol 2013; 27:e376.
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206088s000lbl.pdf (Accessed on October 10, 2014).
- Harries MJ, Chalmers RJ, Griffiths CE. Fumaric acid esters for severe psoriasis: a retrospective review of 58 cases. Br J Dermatol 2005; 153:549.
- Fallah Arani S, Neumann H, Hop WC, Thio HB. Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial. Br J Dermatol 2011; 164:855.
- van Oosten BW, Killestein J, Barkhof F, et al. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N Engl J Med 2013; 368:1658.
- Ermis U, Weis J, Schulz JB. PML in a patient treated with fumaric acid. N Engl J Med 2013; 368:1657.
- Rachakonda TD, Dhillon JS, Florek AG, Armstrong AW. Effect of tonsillectomy on psoriasis: a systematic review. J Am Acad Dermatol 2015; 72:261.
- Gottlieb AB, Leonardi C, Kerdel F, et al. Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 2011; 165:652.
- Reich K, Langley RG, Papp KA, et al. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med 2011; 365:1586.
- Gordon KB, Langley RG, Gottlieb AB, et al. A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis. J Invest Dermatol 2012; 132:304.
- Strober BE, Crowley JJ, Yamauchi PS, et al. Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 2011; 165:661.
- Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 2012; 366:1190.
- Gordon KB, Leonardi CL, Lebwohl M, et al. A 52-week, open-label study of the efficacy and safety of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with chronic plaque psoriasis. J Am Acad Dermatol 2014; 71:1176.
- Saeki H, Nakagawa H, Ishii T, et al. Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis. J Eur Acad Dermatol Venereol 2015; 29:1148.
- Papp KA, Leonardi C, Menter A, et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012; 366:1181.
- Papp K, Leonardi C, Menter A, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol 2014; 71:1183.
- Sofen H, Smith S, Matheson RT, et al. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol 2014; 133:1032.
- Gordon KB, Duffin KC, Bissonnette R, et al. A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis. N Engl J Med 2015; 373:136.
- Krueger JG, Ferris LK, Menter A, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2015; 136:116.
- Kopp T, Riedl E, Bangert C, et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature 2015; 521:222.
- Reich K, Ortonne JP, Gottlieb AB, et al. Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol 2012; 167:180.
- Punwani N, Scherle P, Flores R, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol 2012; 67:658.
- Ports WC, Khan S, Lan S, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol 2013; 169:137.
- Papp KA, Menter A, Strober B, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol 2012; 167:668.
- Boy MG, Wang C, Wilkinson BE, et al. Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis. J Invest Dermatol 2009; 129:2299.
- Gudjonsson JE, Johnston A, Ellis CN. Novel systemic drugs under investigation for the treatment of psoriasis. J Am Acad Dermatol 2012; 67:139.
- Wagner J, von Matt P, Faller B, et al. Structure-activity relationship and pharmacokinetic studies of sotrastaurin (AEB071), a promising novel medicine for prevention of graft rejection and treatment of psoriasis. J Med Chem 2011; 54:6028.
- Bachelez H, van de Kerkhof PC, Strohal R, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet 2015.
- Papp KA, Menter MA, Abe M, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two, randomised, placebo-controlled, Phase 3 trials. Br J Dermatol 2015.
- Vaclavkova A, Chimenti S, Arenberger P, et al. Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet 2014; 384:2036.
- Ahern T, Tobin AM, Corrigan M, et al. Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study. J Eur Acad Dermatol Venereol 2013; 27:1440.
- Buysschaert M, Baeck M, Preumont V, et al. Improvement of psoriasis during glucagon-like peptide-1 analogue therapy in type 2 diabetes is associated with decreasing dermal γδ T-cell number: a prospective case-series study. Br J Dermatol 2014; 171:155.
- Faurschou A, Gyldenløve M, Rohde U, et al. Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on psoriasis in glucose-tolerant patients--a randomized placebo-controlled trial. J Eur Acad Dermatol Venereol 2015; 29:555.