December 2016

Sarilumab and Non-biologic Disease-Modifying Antirheumatic Drugs in Patients with Active RA and Inadequate Response or Intolerance to TNF Inhibitors

Arthritis Rheumatol 2016. DOI:10.1002/art.39944.

In this Phase 3 study (TARGET) of TNF-IR patients, sarilumab plus csDMARD(s) demonstrated clinical efficacy and improvements in physical function versus placebo plus csDMARD(s).Patients (N=546) were randomised 1:1:1 to sarilumab 150 mg, 200 mg Q2W or placebo (all plus csDMARD[s]). Two co-primary endpoints versus placebo were investigated: ACR20 response rate at Week 24, and HAQ-DI change from baseline at Week 12.As well as improvements in ACR20 responses (33.7% vs 55.8 and 60.9%, for placebo, sa...

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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 2016. DOI 10.1136/annrheumdis-2016-210310

In this Phase 3 superiority study (MONARCH) of patients with active RA who should not continue treatment with MTX because of intolerance or inadequate response, sarilumab monotherapy demonstrated superior efficacy to adalimumab (ADA) monotherapy. Patients receiving sarilumab versus ADA also reported greater improvement in health status, including a trend towards greater improvement in fatigue.In this randomised, multicentre study, patients received sarilumab 200 mg Q2W plus placebo (n=184) or AD...

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Peficitinib, a JAK Inhibitor, in the Treatment of Moderate-to-severe Rheumatoid Arthritis in Methotrexate-inadequate Responders

Arthritis & Rheum 2016; ePub ahead of print

This Phase 2b study of peficitinib (ASP015K), an orally administered once-daily JAK inhibitor, plus MTX, demonstrated efficacy across multiple secondary endpoints with higher peficitinib doses. Peficitinib in combination with MTX was well tolerated with a safety profile that was consistent with previous studies.A high placebo response rate was seen in both Latin and North America, when patient data were stratified. This high placebo rate is problematic for the accurate interpretation of peficit...

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Efficacy of VX-509 (decernotinib) in Combination with a Disease-modifying Antirheumatic Drug in Patients with Rheumatoid Arthritis: Clinical and MRI Findings

Ann Rheum Dis 2016;75:1979–83

This Phase 2b study of VX-509 (decernotinib), a selective JAK3 inhibitor, showed that VX-509 in combination with stable DMARD therapy was effective for improving synovitis and osteitis as assessed by MRI in patients who had an inadequate response to DMARD therapy.Patients were randomised to treatment groups receiving either placebo, VX-509 100 mg, 200 mg or300 mg for 12 weeks. Minimum inclusion criteria included Grade ≥2 clinical synovitis in either the wrist or two metacarpophalangeal joints. A...

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Baricitinib, Methotrexate, or Combination in Patients with Rheumatoid Arthritis and no or Limited Prior Disease-Modifying Antirheumatic Drug Treatment

Arthritis Rheumatol 2016. DOI 10.1002/art.39953. Accepted article

In this 52-week study of patients receiving initial therapy for RA, baricitinib alone or in combination with MTX demonstrated superior efficacy compared with MTX alone.Patients naïve to csDMARD (no or <3 doses of MTX) or bDMARD were randomised 4:3:4 (N=588) toMTX QW, baricitinib 4 mg QD or baricitinib 4 mg QD + MTX QW. The primary endpoint assessment was noninferiority of baricitinib monotherapy to MTX based on ACR20 response at Week 24.Not only was the primary endpoint met, baricitinib monother...

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October 2016

Tocilizumab as Monotherapy or Combination Therapy for Treating Active Rheumatoid Arthritis: a Meta-analysis of efficacy and Safety Reported in Randomized Controlled Trials

Arthritis Res Ther 2016; 18:211. DOI 10.1186/s13075-016-1108-9

This is the first meta-analysis comparing efficacy and safety of TCZ monotherapy (TCZMONO) versus TCZ + csDMARD (TCZCOMBI) in patients with RA. The findings show that similar efficacy can be expected with TCZ monotherapy in patients with intolerance to csDMARDs compared with inadequate responders to csDMARDs who switch to TCZ add-on therapy.A total of 6679 patients from 13 studies were included, receiving: 1298, TCZMONO; 3077, TCZCOMBI; 2204, csDMARDs. Meta-analyses were performed for the follow...

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Sarilumab plus Methotrexate Improves Patient-reported Outcomes in Patients with Active Rheumatoid Arthritis and Inadequate Responses to Methotrexate: Results of a Phase III Trial

Arthritis Res Ther 2016; 18:198. DOI.10.1186/s13075-016-9

Evidence is presented that treatment with sarilumab improves patient-reported outcomes (PROs). These improvements complement the clinical efficacy previously reported for sarilumab.Data were analysed from the 52-week Phase 3 MOBILITY randomised controlled trial in adult patients with active RA and previous inadequate response to MTX. Patients received subcutaneous placebo or sarilumab 150 mg or 200 mg every 2 weeks in combination with MTX, for 52 weeks.PROs assessed were: Patient Global Assessme...

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Tofacitinib in Combination with Conventional DMARDs in Patients with Active Rheumatoid Arthritis: PROs from a Phase 3 Randomised Controlled Trial

Arthritis Care Res 2016; Accepted article. DOI 10.1002/acr.23004

Further evidence is presented that treatment with tofacitinib improves patient-reported outcomes (PROs), in addition to improving underlying disease activity.Data were analysed from the Phase 3 ORAL Sync 12-month randomised controlled trial in adult patients with active RA and previous inadequate response to ≥1 conventional or biologic DMARD(s). Patients received (4:4:1:1) TOF 5mg or 10mg BID or Placebo advanced to 5 mg or10 mg BID plus conventional DMARD(s).PROs assessed at Month 3 were: Patien...

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RAPID3 and ACR/EULAR Provisional Definitions as Predictors of Radiographic Outcome in a Rheumatoid Arthritis Clinical Trial with Tocilizumab

Arthritis Care Res 2016; Accepted article. DOI 10.1002/acr.23008.

The findings reported represent the first validation of RAPID3 (Routine Assessment of Patient Index Data 3) remission ± SJC ≤1 as an alternative to the established SDAI or Boolean remission definitions, which can be time consuming and costly to measure. RAPID3 is a pooled index of the patient-reported measures: function, pain and Patient Global estimate of status.Data were analysed from the TociLIzumab Safety and THE Prevention of Structural Joint Damage (LITHE) study, a 2-year double-blind Phas...

September 2016

Treating Experimental Arthritis with the Innate Immune Inhibitor Interleukin-37 Reduces Joint and Systemic Inflammation

Rheumatology (Oxford) 2016; DOI 10.1093/rheumatology/kew325

IL-37, a member of the IL-1 family, has recently been characterised as a fundamental inhibitor of innate inflammation. This study examines the effects of recombinant IL-37 on joint inflammation and pathology in a mouse model of arthritis, and also explores its potential in the treatment of human joint inflammation.In this mouse model of experimental arthritis, short-term, low-dose treatment with IL-37 suppressed joint and systemic inflammation. Wild-type mice received three intraperitoneal doses...

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