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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.
ORTHOPEDICS, SPINE, AND SOFT TISSUE RHEUMATIC DISORDERS
Gabapentinoids not effective for chronic low back pain (September 2017)
A meta-analysis evaluating gabapentinoids (gabapentin or pregabalin) for the treatment of chronic low back pain included eight randomized trials, which were evaluated as three groups . Gabapentin, compared with placebo, resulted in a minimal and nonsignificant improvement in pain, and gabapentin increased the risk of side effects (primarily dizziness, fatigue, mentation difficulties). Pregabalin as primary therapy was less effective than other analgesics. In the largest study of pregabalin as adjuvant therapy, no additive benefit was found, although the adjuvant studies were too heterogeneous to pool. We suggest not treating patients for chronic low back pain with gabapentinoids. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment", section on 'Antiepileptic medications'.)
Mindfulness-based stress reduction for low back pain (August 2017)
Mindfulness-based stress reduction (MBSR) has been used for the management of low back pain. In a recent systematic review and meta-analysis of seven randomized controlled trials involving 864 patients with low back pain (most with subacute or chronic low back pain), MBSR was associated with modest short-term improvements in pain intensity and physical functioning compared with usual care . We offer MBSR as a nonpharmacologic intervention for patients with subacute or chronic low back pain. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment", section on 'Mind-body interventions'.)
Perioperative medication management in rheumatic disease patients undergoing total hip or knee replacement (July 2017)
An expert panel of rheumatologists and orthopedic surgeons has developed guidelines for the perioperative management of various immunosuppressive medications in patients undergoing total hip or knee arthroplasty . In patients with rheumatic diseases, decisions must balance the potential risks of infection related to immunosuppressive medications with the risk of worsened disease control when medications are withheld. Important recommendations include that nonbiologic disease-modifying antirheumatic drugs (DMARDs) may be continued through the perioperative period, whereas biologic DMARDs should be withheld as close to one dosing cycle as scheduling permits prior to elective hip or knee replacement surgery. (See "Preoperative evaluation and perioperative management of patients with rheumatic diseases", section on 'Medication management'.)
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'.)
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'.)
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'.)
Tofacitinib plus methotrexate for rheumatoid arthritis (September 2017)
The orally administered Janus kinase (JAK) inhibitor, tofacitinib, has not previously been compared with combination therapy in patients with active rheumatoid arthritis (RA) despite initial therapy with methotrexate (MTX). In a three-arm noninferiority trial involving over 1100 such patients, the response to tofacitinib monotherapy was inferior to that of either MTX plus tofacitinib or MTX plus subcutaneous adalimumab (a tumor necrosis factor inhibitor) . Rates of discontinuation and safety were similar in the three groups. These results favoring combination therapy are similar to those in trials comparing other biologic agents used as monotherapy or as a component of combination therapy in this setting. (See "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'Tofacitinib'.)
Cost-effectiveness of nonbiologic triple therapy in rheumatoid arthritis (September 2017)
In patients with active rheumatoid arthritis (RA) despite initial therapy with methotrexate (MTX), the addition of sulfasalazine and hydroxychloroquine (ie, conventional triple therapy) has shown similar efficacy to MTX plus a biologic agent (eg, a tumor necrosis factor inhibitor), including in patients with high levels of disease activity or adverse prognostic features. However, this approach remains relatively underutilized. In a cost-effectiveness analysis, the use of triple therapy was found to be highly cost-effective compared with MTX plus a biologic agent, providing comparable or near-comparable clinical benefit, depending upon the trial . These findings support our recommended treatment approach for this group of patients. (See "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy", section on 'Choice of therapy'.)
SCLERODERMA AND OTHER SYSTEMIC RHEUMATIC DISEASES
Treatment outcomes in early diffuse cutaneous systemic sclerosis (July 2017)
There are limited data on the effectiveness of immunosuppressive therapies for early (within three years of onset) diffuse cutaneous systemic sclerosis (dcSSc). A large observational study of over 300 patients with early dcSSc compared the efficacy of methotrexate, mycophenolate mofetil, cyclophosphamide, and no immunosuppression and found a modest improvement in clinician-assessed skin thickening across all groups at 12 months, with the least improvement in the no immunosuppression group . The presence of lung or cardiac involvement at baseline was associated with decreased survival at 24 months. Thus, most treatments for dcSSc demonstrate only a modest benefit, and better therapies are needed. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Diffuse skin sclerosis'.)
Updated EULAR recommendations on management of systemic sclerosis (July 2017)
The European League Against Rheumatism (EULAR) has published updated recommendations for the treatment of systemic sclerosis to incorporate new data on existing therapies as well as include newer therapeutic options [14,15]. Compared with the previous recommendations, the treatment of Raynaud phenomenon and pulmonary arterial hypertension have undergone the most revision. A discussion on the role of hematopoietic stem cell transplant for selected patients with rapidly progressive disease has also been added. Our management approach is generally consistent with these guidelines. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'General principles of management'.)
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'.)
Safety of arthrocentesis and joint injection in patients on direct oral anticoagulants (October 2017)
Until recently, the safety of joint aspiration or injection in patients on anticoagulation was based on studies with warfarin, which reported only a small risk of increased bleeding. The first study to provide data on the risk of bleeding in patients on direct oral anticoagulants (DOACs) undergoing joint aspiration or injection is a retrospective review of 1050 consecutive procedures from Mayo Clinic over a six-year period . There were no bleeding complications during the median follow-up period of five days. Of the 1050 procedures, 22 percent were performed in patients receiving a DOAC plus aspirin, and 1 percent were performed in patients on a DOAC plus clopidogrel. These findings support the safety of arthrocentesis and joint injection in patients receiving uninterrupted DOACs and/or antiplatelet therapy. (See "Joint aspiration or injection in adults: Technique and indications", section on 'Approach to the patient on anticoagulants'.)
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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