January 2017

Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase 2b Study in Patients with Active Rheumatoid Arthritis

Arthritis Rheumatol 2017. DOI 10.1002/art.40036.

In this analysis of the effect of baricitinib on changes in lipid profile, lipoprotein particle size and apolipoprotein content, increases in serum lipids were observed with HDL-C increases correlating with improved clinical outcomes.Eligible patients (N=301) met the inclusion criteria for the Phase 2b randomised, double-blind, placebo-controlled study.1 Patients were assigned in a 2:1:1:1:1 ratio to once-daily doses of placebo or baricitinib 1, 2, 4, or 8 mg, respectively. Those receiving 2 mg,...

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December 2016

Tofacitinib Versus Biologic Treatments in Patients with Active Rheumatoid Arthritis who have had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results from a Network Meta-Analysis

Clin Ther 2016;38:2628–40.

This network meta-analysis, performed within a Bayesian framework, concluded that tofacitinib 5 mg BID has efficacy and AE rates comparable with currently available bDMARDs over a 24-week period in patients experiencing an inadequate response to TNF therapy. A systematic literature search identified five, Phase 2 or beyond, randomised controlled trials for inclusion in the analysis. Each trial had an adult population with moderate to severe RA, with inadequate response (IR) or failed treatment w...

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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

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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August 2016

Risk for Lower Intestinal Perforations in Patients with Rheumatoid Arthritis Treated with Tocilizumab in Comparison to Treatment with Other Biologic or Conventional Synthetic DMARDs

Ann Rheum Dis 2016;0:1–7 DOI 10.1136/annrheumdis-2016-209773.

This real-life study confirms findings from the tocilizumab (TCZ) clinical development program that IL-6 inhibition with TCZ may be associated with increased risk of lower intestinal perforation (LIP). Data were analysed from the RABBIT register of patients. The primary outcome was the incidence of LIPs in patients exposed to TCZ, csDMARDs, TNFis, abatacept, or rituximab. Thirty-seven LIPs were observed in 53,972 patient years. The proportion of patients who developed a LIP was higher in patient...

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July 2016

Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan:a 12-week, randomised, double-blind, placebo-controlled phase IIb study

Ann Rheum Dis. 2016 Jun;75:1057-64. doi: 10.1136/annrheumdis-2015-208279. Epub 2015 Dec 15

Peficitinib (ASP015K) is a novel orally bioavailable JAK inhibitor in development for the treatment of RA. It inhibits JAK1, JAK2, JAK3 and Tyk2 enzyme activities and has moderate selectivity or JAK3 inhibition.Here the authors report the findings of a 12-week, randomized, double-blind, placebo-controlled phase IIb study evaluating efficacy, safety and dose response of peficitinib (25, 50, 100, or 150 mg) as once-daily oral monotherapy in Japanese patients with moderate to severe RA. The primar...

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Biologics or Tofacitinib for Rheumatoid Arthritis in Incomplete Responders to Methotrexate or Other Traditional Disease-Modifying Anti-Rheumatic Drugs: A Systematic Review and Network Meta-Analysis

Cochrane Database of Systematic Reviews 2016 Issue 5. Art. No.: CD012183 [DOI: 10.1002/14651858.CD012183].

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 head-to-head studies to show any important differences between these options in terms of benefits and harms. This review provides an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for RA.1Nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, a...

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June 2016

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

N Engl J Med 2016;375:345–56. doi: 10.1056/NEJMoa1512711

Gordon, et al. pool the results of UNCOVER-1, UNCOVER-2, and UNCOVER-3 to show that ixekizumab increases the proportion of patients achieving an sPGA score of 0/1 or PASI 75 versus placebo. Adverse events related to ixekizumab treatment included neutropenia, candidal infections, and inflammatory bowel disease.

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