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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
New guidelines for management of gout (February 2017)
Several professional organizations have recently published guidelines for the management of gout, including the European League Against Rheumatism (EULAR) , an international task force , and the American College of Physicians (ACP) . The ACP guidelines depart from recommendations of the American College of Rheumatology (ACR), EULAR, the international task force, and others by suggesting a treat-to-avoid-symptoms approach (ie, monitoring the adequacy of urate-lowering drug dosing based on the frequency and severity of acute attacks) rather than a treat-to-target approach based on serum urate levels. We concur with the ACR, EULAR, and international guidelines groups, based upon the available clinical evidence and an understanding of the pathophysiology of gout, and we continue to recommend monitoring serum urate levels and using such data to make treatment choices and titrate dosing. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Recommendations of major groups'.)
ORTHOPEDICS, SPINE, AND SOFT TISSUE RHEUMATIC DISORDERS
Intradiscal glucocorticoid injection and chronic low back pain with active discopathy (June 2017)
Chronic back pain exacerbations are sometimes related to inflammation of an intervertebral disc ("active discopathy"), which can be detected on magnetic resonance imaging (MRI) scan. In a randomized trial of 135 patients with chronic low back pain and active discopathy comparing a single injection of prednisolone and contrast with contrast alone, pain reduction at one month was greater in the prednisolone group (55 versus 33 percent) . The groups did not differ in pain intensity at 12 months or in secondary outcomes at one or 12 months. In general, we do not suggest intradiscal glucocorticoid injections for patients with chronic low back pain. More research is needed to confirm its effectiveness and potential risks in the subgroup of patients that were studied. (See "Subacute and chronic low back pain: Nonsurgical interventional treatment", section on 'Intradiscal injection'.)
Spinal manipulative therapy for acute low back pain (June 2017)
Spinal manipulative therapy (SMT) has been used for acute low back pain, but the literature has shown inconsistent results. In a recent systematic review and meta-analysis of 26 randomized controlled trials, 15 showed moderate-quality evidence of improvement in pain and 12 showed moderate-quality evidence of improvement in function . The magnitude of clinical benefit was modest, and there were no serious adverse effects. Prior reviews have reported less consistent benefit. We offer SMT to patients based on their individual preferences and access to this intervention. (See "Treatment of acute low back pain", section on 'Spinal manipulation'.)
Updated ACP guideline on management of low back pain (April 2017)
The American College of Physicians (ACP) recently published an updated guideline for the management of acute, subacute, and chronic low back pain . Notable changes from their previous guideline include emphasis of nonpharmacologic therapy as an initial management approach and preference for nonsteroidal anti-inflammatory drugs (NSAIDs) for first-line pharmacotherapy over acetaminophen. Our recommendations are generally consistent with the updated ACP guideline. (See "Treatment of acute low back pain" and "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)
Inpatient versus home-based physical therapy after total knee arthroplasty (March 2017)
Inpatient rehabilitation programs are widely used after total knee arthroplasty (TKA); however, there are limited data as to whether clinical outcomes are superior when compared with lower cost home-based physical therapy (PT) programs. In a trial with 165 adults who had undergone a TKA for osteoarthritis, patients were randomly assigned to either 10 days of inpatient rehabilitation followed by eight weeks of monitored home-based PT or to the monitored home-based program alone . At 26 weeks, all outcomes were similar between groups, including the six-minute walk test and measures of pain, function, and quality of life. Although more data are needed, this study suggests that inpatient rehabilitation is not superior to home-based PT for patients undergoing unilateral, uncomplicated TKA. (See "Total knee arthroplasty", section on 'Postoperative management'.)
Role of pharmaceutical-grade chondroitin for knee osteoarthritis (June 2017)
The use of chondroitin for the treatment of knee osteoarthritis (OA) has been controversial due to conflicting data, with more favorable results associated with higher doses and higher-grade formulations. In an industry-sponsored randomized trial of 604 patients with symptomatic knee OA, pharmaceutical-grade chondroitin (800 mg) was statistically superior to placebo and similar to celecoxib in reducing pain and improving function . An important limitation of the study is the uncertain clinical relevance of the modest improvements in pain and functional scores. Also, the number of patients who achieved a clinically important improvement in pain was not different among the three groups. These issues limit the strength of the findings. (See "Management of knee osteoarthritis", section on 'Glucosamine and chondroitin'.)
Lifetime risk of revision after total hip or knee replacement (June 2017)
Determining the best timing for total hip or knee replacement surgery for end-stage arthritis is challenging in younger patients because the replacement can fail over time. A population-based study evaluated the lifetime risk of revision surgery in adults aged 50 or older using data from a registry with over 63,000 total hip replacements and 54,000 total knee replacements . The lifetime risk of revision surgery for either total hip or knee replacement in patients older than 70 years was about 5 percent, with no difference between men and women. The risk increased with decreasing age and was highest for men in their early 50s. For men aged 50 to 54, the lifetime risk of revision for total hip and knee replacement was 30 and 35 percent, respectively. These data suggest that there may be some benefit to delaying surgery, particularly among younger men. (See "Total hip arthroplasty", section on 'Indications' and "Total knee arthroplasty", section on 'Indications'.)
Lack of benefit of intraarticular glucocorticoid injections for knee osteoarthritis (May 2017)
Although limited evidence suggests that intraarticular glucocorticoid injections for knee osteoarthritis (OA) may result in short-term pain relief, data for longer-term outcomes are less favorable. A randomized trial including 140 patients with symptomatic knee OA and ultrasound features of synovitis found that pain reduction was no different comparing injections of 40 mg triamcinolone acetonide with placebo every 12 weeks for two years . Furthermore, two years of triamcinolone injections resulted in greater cartilage volume loss. These findings do not support intraarticular glucocorticoid injections in patients with symptomatic knee OA and are consistent with our practice. In addition, we discourage the use of serial injections (eg, every three months) due to progressive cartilage damage in knee OA patients. (See "Management of moderate to severe knee osteoarthritis", section on 'Intraarticular glucocorticoid injection'.)
Internet-delivered therapy for chronic knee pain (February 2017)
Nonpharmacologic interventions are known to be effective in the treatment of chronic knee pain and osteoarthritis (OA), but implementation of such therapies is often limited. In a trial of 148 adults with chronic knee pain and disability, patients were randomized to either a novel internet-based intervention or a control group . Both groups had access to internet-based educational material, but the intervention group also received interactive online training in pain-coping skills as well as videoconferencing sessions with a physiotherapist for home exercise. At three months, the intervention group reported improved pain and function compared with the control group, which was sustained for at least six months. More data are needed to evaluate internet-based strategies as a practical way to deliver care for OA patients. (See "Management of moderate to severe knee osteoarthritis", section on 'Psychological interventions'.)
Outcomes in children with ANCA-associated vasculitides (July 2017)
The combination of glucocorticoids and cyclophosphamide or other remittive agents (eg, methotrexate, rituximab) has greatly improved patient outcomes for systemic vasculitis. One study of early outcomes in 105 children with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) reported a remission rate of 42 percent, an improvement rate of 92 percent, and no fatalities at 12 months . This compares with the nearly universal mortality due to one form of AAV, granulomatosis with polyangiitis, prior to the regimens now in use. However, more than half of the cohort had evidence of organ damage at 12 months despite high improvement rates and aggressive treatment. (See "Vasculitis in children: Management overview", section on 'Outcomes'.)
Adalimumab for uveitis in juvenile idiopathic arthritis (May 2017)
Adalimumab, a human anti-tumor necrosis factor (TNF) alpha monoclonal antibody that is effective in adults with uveitis, has now been shown to be effective for treatment-resistant, juvenile idiopathic arthritis (JIA)-associated uveitis. In the randomized SYCAMORE trial involving 90 children, the addition of adalimumab to ongoing therapy with methotrexate and topical glucocorticoids with our without systemic glucocorticoids reduced intraocular inflammation and lowered the rate of treatment failure compared with placebo . Serious adverse events were infrequent in both groups but occurred more commonly with adalimumab. Although more data are needed on long-term outcomes and safety, these results add support to the use of adalimumab in children with JIA-associated uveitis that fails to respond to glucocorticoids and methotrexate. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Treatment'.)
Methotrexate for moderate oligoarticular juvenile idiopathic arthritis (February 2017)
Methotrexate is used as part of initial therapy in oligoarticular juvenile idiopathic arthritis (JIA) for those with severe disease activity and poor prognostic risk factors, but it is not clear if it should be used in patients with moderate disease. In a randomized, open-label trial of over 200 children with moderate oligoarticular JIA, the addition of oral methotrexate to glucocorticoid injections did not improve the proportion of children who achieved inactive disease or clinical remission at 12 months, although it did increase the time to flare (by approximately four months) . Further study is needed to determine if methotrexate should be used for the initial therapy of children with moderate-risk JIA, including whether oral methotrexate is as effective as subcutaneous administration in this setting. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Initial therapy'.)
Sarilumab, an anti-IL-6 receptor antibody for treatment of rheumatoid arthritis (April 2017)
Emerging data indicate that sarilumab, an investigational human monoclonal antibody directed against the membrane-bound and soluble interleukin (IL)-6 receptor, is effective for the treatment of rheumatoid arthritis (RA). In a trial of 546 patients with RA who had an inadequate response or intolerance to tumor necrosis factor (TNF) inhibitors, sarilumab improved clinical response rates and physical function compared with placebo when given together with conventional disease-modifying antirheumatic drugs . In a separate trial of 369 patients with active RA who had failed or did not tolerate methotrexate, sarilumab was superior to the TNF inhibitor, adalimumab, as monotherapy . Sarilumab has similar safety and tolerability to the humanized anti-IL-6 receptor monoclonal antibody, tocilizumab, which is commercially available for the treatment of RA and other disorders. (See "Cytokine networks in rheumatic diseases: Implications for therapy", section on 'Anti-interleukin-6 receptor antibodies'.)
Sirukumab, an anti-IL-6 antibody for the treatment of rheumatoid arthritis (April 2017)
Sirukumab is a human anti-interleukin (IL)-6 monoclonal antibody under development for the treatment of rheumatoid arthritis (RA). In a randomized trial involving almost 900 patients with active RA refractory or intolerant to at least one tumor necrosis factor (TNF) inhibitor, sirukumab was more likely than placebo to result in a clinical response . Notably, two or more biologic agents, including non-TNF drugs, had previously been administered in the majority of patients, and most patients were receiving continued therapy with a conventional disease-modifying antirheumatic drug, usually methotrexate. Adverse reactions were similar between groups, other than injection-site erythema, which was more common with sirukumab. Further studies are ongoing with several antibodies that target IL-6 directly; it remains to be seen if this offers a strategic advantage over targeting of the receptor. (See "Cytokine networks in rheumatic diseases: Implications for therapy", section on 'Anti-interleukin-6 antibodies'.)
Baricitinib, an oral JAK-1/JAK-2 inhibitor for the treatment of rheumatoid arthritis (March 2017)
A series of recent randomized trials have documented the efficacy and relative safety of baricitinib, a small molecule, orally administered, Janus kinase (JAK)-1 and JAK-2 inhibitor, as a treatment for rheumatoid arthritis (RA). These include a trial involving almost 600 patients with active RA who were naïve (or had minimal exposure) to both conventional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and biologic DMARDs, in which baricitinib was superior to methotrexate as monotherapy ; a trial involving almost 700 patients with inadequate responses to prior DMARD therapy, in which responses were greater with the addition of baricitinib compared with placebo ; and a trial involving over 1300 patients with active RA and an inadequate response to methotrexate (MTX), in which the addition of baricitinib was more effective than adalimumab and placebo . Baricitinib was associated with minor increases in serum creatinine and LDL cholesterol and small reductions in blood neutrophil counts. Baricitinib has been approved in Europe for use either alone or in combination with MTX and is undergoing regulatory review in the United States. (See "Cytokine networks in rheumatic diseases: Implications for therapy", section on 'Baricitinib'.)
Adalimumab versus certolizumab pegol in rheumatoid arthritis with inadequate methotrexate response (March 2017)
The relative efficacy of the five available tumor necrosis factor (TNF) inhibitors has not been well studied in patients with rheumatoid arthritis (RA). Now, a randomized trial involving over 900 patients with active RA and an inadequate response to methotrexate (MTX) alone has directly compared the combination of MTX with either of two TNF inhibitors (adalimumab and certolizumab pegol) and found neither combination superior to the other . There was no difference between the groups in the proportion of patients achieving a clinical response at week 12, the number with low disease activity at week 104, other major clinical outcome measures, or adverse effects. We continue to suggest choosing a TNF inhibitor based on factors such as patient preferences regarding route of administration and frequency of treatment, comorbidities, and local regulatory and coverage constraints. (See "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy", section on 'MTX plus TNF inhibitor'.)
SYSTEMIC LUPUS ERYTHEMATOSUS AND SJOGREN'S SYNDROME
Guidelines on women's health in systemic lupus erythematosus and antiphospholipid syndrome (March 2017)
Both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) affect women of child-bearing age, and the management of these diseases in the setting of pregnancy can pose unique challenges. These include the effect of pregnancy on maternal disease, the impact of disease activity on fetal health, and the safety of medications during pregnancy and breastfeeding. The European League Against Rheumatism (EULAR) has published new recommendations for the management of women's health in patients with SLE and APS, which provide guidance for family planning, assisted reproduction, pregnancy monitoring, treatment during pregnancy, hormone replacement therapy and menopause, and malignancy screening . (See "Pregnancy in women with systemic lupus erythematosus", section on 'Pregnancy planning'.)
Trial of tocilizumab for giant cell arteritis (August 2017)
Given the adverse effects associated with prolonged glucocorticoid exposure, there has been an interest in finding an effective glucocorticoid-sparing agent for patients with giant cell arteritis (GCA). In a randomized trial of subcutaneous tocilizumab (TCZ), a humanized anti-human IL-6 receptor antibody, patients assigned to receive weekly or every-other-week TCZ injections along with a 26-week prednisone taper were more than twice as likely to achieve sustained remission compared with those assigned to placebo plus a 26- or 52-week prednisone taper (56 and 53 percent versus 14 and 18 percent, respectively) . The cumulative prednisone dose was lower in the TCZ groups, and serious adverse events (mostly infectious) were more common in the placebo groups. Longer-term follow-up data on the durability of remission and safety of TCZ are needed to help determine whether TCZ will have a role in the routine care of GCA patients. (See "Treatment of giant cell (temporal) arteritis", section on 'Tocilizumab'.)
Mepolizumab for eosinophilic granulomatosis with polyangiitis (August 2017)
Mepolizumab is a monoclonal anti-interleukin-5 antibody that is approved for use in severe eosinophilic asthma. In a multicenter trial, 136 patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) were randomly assigned to receive mepolizumab 300 mg (three times the US Food and Drug Administration-approved dose of 100 mg) or placebo subcutaneously every four weeks for 52 weeks . Mepolizumab led to significantly more accrued weeks of remission and a lower frequency of relapse than placebo. Among mepolizumab-treated subjects, 44 percent were able to taper prednisolone to ≤4 mg/day, compared with 7 percent on placebo. While not all patients respond, high-dose mepolizumab may be an additional option for selected patients with EGPA. (See "Treatment and prognosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Anti-IL-5 antibodies'.)
Intraocular fluocinolone implant for uveitis (August 2017)
An intraocular fluocinolone implant that delivers glucocorticoid into the vitreous humor continuously over several years can be used to treat refractory noninfectious uveitis, with comparable efficacy to systemic glucocorticoids and glucocorticoid-sparing immunosuppressive agents at 24 and 54 months in a randomized trial. However, long-term follow-up of trial participants now shows that visual acuity at seven years is better in patients initially allocated to receive systemic therapy . The study was limited by 30 percent loss to follow-up in both groups. We generally reserve use of the fluocinolone implant to patients whose noninfectious posterior or intermediate uveitis requires frequent local glucocorticoid injection and in whom systemic use of glucocorticoids or other immune modulators may be particularly problematic or not otherwise required. (See "Uveitis: Treatment", section on 'Intraocular glucocorticoid releasing implant'.)
Adverse events with short-term oral glucocorticoid use in adults (April 2017)
Chronic steroid use is associated with a wide spectrum of adverse effects. However, there is a paucity of clinical data on the adverse effects associated with short-term use. A retrospective cohort study and self-controlled case series assessed the risk of three adverse events (sepsis, venous thromboembolism [VTE], and fracture) in over 300,000 adults younger than 65 who received at least one short-term (<30 days) outpatient prescription for oral glucocorticoids over a three-year period . The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Within 30 days of drug initiation, there was a two- to fivefold increase in the rates of sepsis, VTE, and fracture, which then decreased over the subsequent 31 to 90 days. These findings suggest that even short courses of oral steroids are associated with adverse effects that should be considered before prescribing. (See "Major side effects of systemic glucocorticoids", section on 'Dose effects'.)
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- Kiltz U, Smolen J, Bardin T, et al. Treat-to-target (T2T) recommendations for gout. Ann Rheum Dis 2016; 76:632.
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- Buhagiar MA, Naylor JM, Harris IA, et al. Effect of Inpatient Rehabilitation vs a Monitored Home-Based Program on Mobility in Patients With Total Knee Arthroplasty: The HIHO Randomized Clinical Trial. JAMA 2017; 317:1037.
- Reginster JY, Dudler J, Blicharski T, Pavelka K. Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT). Ann Rheum Dis 2017; 76:1537.
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- Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis 2017; 76:840.
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