J. Smolen et al.
Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR’s most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
Kevin D. Deane, MD, PhD
Stopping Tumor Necrosis Factor Inhibitor Therapy in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial
Ghiti Moghadam M, Vonkeman HE, Ten Klooster PM, et al; Dutch National POET Collaboration
Arthritis Rheumatol. 2016;68:1810-1817
In this study, Ghiti Moghadam and colleagues from The Netherlands used a pragmatic trial design to investigate rates of rheumatoid arthritis (RA) flare after cessation of anti-tumor necrosis factor (anti-TNF) therapy. They analyzed 817 patients, all of whom had a Disease Activity Score in 28 joints (DAS28) < 3.2 for 6 months before inclusion.
Individuals with RA were randomized in a 2:1 ratio to stop or continue anti-TNF therapy (531 and 286 patients, respectively). The primary outcome was flare of disease, as determined by a DAS28 ≥ 3.2 over 12 months of follow-up or an increase in score ≥ 0.6.
At 12 months, the anti-TNF discontinuation group had more flares (approximately 51% vs 18%; P < .001) and a higher mean DAS28 (P < .001). Of the 195 patients who restarted anti-TNF therapy, around 85% regained a DAS28 < 3.2 after 6 months. Besides stopping anti-TNF therapy, predictors of time to a flare were a higher baseline DAS28 and disease duration > 10 years at the time of study entry. In terms of safety, there was one death due to an infection in the continuation group, and 34 hospitalizations in the discontinuation group compared with seven in the continuation group (P = .012)
Increasing numbers of studies have been investigating the possibility that individuals with RA can decrease therapy and yet continue to have excellent disease control. These studies were reviewed in an outstanding article by Schett and colleagues that was published in the May 2016 edition of the Annals of Rheumatic Diseases. Results have been variable, although there has been substantial heterogeneity across the studies.
From Medscape Prof Jonathan Kay Professor of medicine at the University of Massachusetts Medical School.
Tocilizumab, an interleukin (IL)-6 receptor inhibitor in giant cell arteritis. This study was an efficacy and safety study looking at tocilizumab in patients with documented giant cell arteritis to see whether tocilizumab improved the remission of patients after tapering from glucocorticoid therapy. The patients were studied for 52 weeks, and patients who were at least 50 years of age who had giant cell arteritis confirmed by temporal artery biopsy or cross-sectional imaging with elevation of acute-phase reactants that was attributable to giant cell arteritis were randomly assigned 1:1:2:1 into four groups.
The first group was treated with a short course of prednisone over 26 weeks, which was tapered, and they were given a weekly subcutaneous placebo. The second group received a long course of prednisone tapered over 52 weeks, again, with a weekly subcutaneous placebo. The third group received weekly subcutaneous tocilizumab at the usual dose of 162 mg and a 26-week short-course prednisone taper. The fourth group received an every-other-week dose of tocilizumab subcutaneously at 162 mg and a short-course prednisone taper over 26 weeks. The randomization allowed twice as many patients to be entered into the weekly subcutaneous tocilizumab arm as into the other three arms.
Lesinurad (Zurampic) was approved earlier this year as adjunctive therapy to other urate-lowering therapies (ULT). It is a selective uric acid reabsorption inhibitor (URAT-1 inhibitor) designed to treat gout, and be used in combination with other xanthine oxidase inhibitors.The results of the CLEAR 1 trial were pivotal in the FDA review of this drug and have been reported in the August issue of Arthritis & Rheumatology.
This was a 12-month, randomized, phase-III trial of lesinurad (200-mg or 400-mg qd) added to standard doses of allopurinol in gout patients with a serum urate (sUA) above <6.0 mg/dL and ≥2 gout flares in the prior year. Primary endpoint was achieving sUA <6.0 mg/dL at month 6.
Gout patients (N=603) were predominantly male, a mean gout duration 11.8±9.4 years, and mean baseline sUA 6.94.
Lesinurad at 200-mg and 400-mg doses, added to allopurinol, significantly increased proportions of subjects achieving the sUA target. At month 6, 54.2% of lesinurad 200 mg/d, 59.2% of lesinurad 400 mg/d, and 27.9% of allopurinol patients achieved the goal.
Surprisingly, lesinurad was not significantly superior in secondary endpoints: rates of gout flares and complete tophus resolution. The safety profile showed the drug to be generally well-tolerated; but, there was a higher incidences of predominantly-reversible serum creatinine elevation in those on lesinurad.
Lesinurad may prove to be a useful option for patients inadequately controlled on allopurinol, or those who cannot increase their allopurinol dose above 300 mg per day to reduce sUA levels to target.
An Interview With Emilio Martín-Mola
Received: 17.03.16 Accepted: 19.07.16
Citation: EMJ. 2016;1:76-84.
On January 14th 2016, SB4 (Benepali®) received marketing authorisation application approval from the European Commission (EC). It is the first biosimilar to etanercept available in Europe as well as the first subcutaneous anti-tumour necrosis factor biosimilar. Benepali® was approved for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic spondyloarthritis), and plaque psoriasis.
SB4 adds to the available biologic armamentarium of biosimilars in rheumatology, which also includes two infliximab biosimilars; one under the brand names Remsima® and Inflectra®, and the other under the brand name Flixabi®. Unlike infliximab biosimilar, which is a chimeric monoclonal antibody, SB4 is a fusion protein.
We aimed to review the current European Medicines Agency (EMA) requirements for the approval of biosimilars and how these products can integrate into daily clinical practice in rheumatology.
To that effect, we recently discussed with Dr Emilio Martín-Mola about the European framework for approval of biosimilars and the controversies that may surround this new category of medicinal products. We discussed how the advent of biosimilars in rheumatology has the potential to truly be a game-changer for both physicians and patients