December 2016

Biologic or Tofacitinib Monotherapy for Rheumatoid Arthritis in People with Traditional Disease-modifying Anti-rheumatic Drug (DMARD) Failure: a Cochrane Systematic Review and Network meta-analysis (NMA)

Cochrane Database Syst Rev 2016;11:CD012437.

Treatment options for RA patients who are MTX/DMARD incomplete responders (IR) include other DMARDs, biologics or tofacitinib (TOF). However, there is a lack of direct head-to-head comparator trials of biologics in people with RA. This review provides an update of the 2009 Cochrane overview, ‘Biologics for rheumatoid arthritis’,1 and provides comparisons and estimates for biologic or TOF monotherapy in MTX/DMARD-IR people with RA.The benefits and harms of biologic monotherapy (TNFis: adalimumab,...

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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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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

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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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...

August 2016

A Randomized Phase 2b Study of ABT-494, a Selective JAK Inhibitor in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Arthritis Rheumatol 2016; Accepted article DOI 10.1002/art-39808 [Epub 2016]

This dose-ranging study evaluated the efficacy of the novel, selective JAK1 inhibitor ABT-494 versus placebo in patients with moderate-to-severe RA and inadequate response (IR) to MTX.In this 12-week, randomised, double-blind study (BALANCE II), the efficacy and safety ofABT-494 dosed at 3mg, 6 mg, 12 mg, 18 mg (all twice daily) and 24 mg (once daily) was assessed. Patients included had not received prior biologic therapy.Of the 299 patients included in the analysis, the proportions of patients ...

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July 2016

Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis

Drug Saf. 2016 June 9; 39:755–762; DOI 10.1007/s40264-016-0431-z [Epub ahead of print]

RA and psoriasis may present in women of child-bearing potential, however there are currently no adequate or well-controlled studies of tofacitinib (TOF) or any DMARD in pregnant women. Pregnancy was an exclusion criterion of TOF randomized clinical trials because of the unknown effects of TOF on mother and child; TOF is a small molecule with the potential to cross the placenta. The current analysis looked at reported pregnancies and their outcomes from TOF RA and psoriasis clinical safety datab...

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Switching from Adalimumab to Tofacitinib in the Treatment of Patients with Rheumatoid Arthritis

Arthritis Research & Therapy. 2016. DOI 10.1186/s13075-016-1049-3 [Epub ahead of print]

Results are reported from an analysis exploring the safety and efficacy of open-label tofacitinib (TOF) following blinded treatment with TOF or adalimumab (ADA) in patients with moderate to severe RA. The analysis included patients from ORAL Sequel, an open-label long-term extension study, which all patients entered following ORAL Standard (one of the studies in the TOF phase 3 program). Only those patients who had been randomized to ADA 40 mg Q2W + MTX or 10 mg TOF + MTX in ORAL Standard were i...

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