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

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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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

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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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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Risk for Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologics

Arthritis Rheumatol. 2016 May 17. DOI 10.1002/art.39761 [Epub ahead of print]

Historically, patients with RA have suffered with upper tract gastrointestinal perforation (GIPs), associated with NSAID use. More recently, the IL-6 receptor antagonist tocilizumab (TCZ) has been associated with lower tract GIPs. Janus kinase (JAK) inhibitors, including tofacitinib (TOF), with some downstream effects on IL-6 signalling, also have potential for an increased risk of GIPs.There is limited real-world evidence and almost no comparative evidence on the risk for GIP associated with TC...

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Two-year Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis in Clinical Practice

Reumatol Clin. 2016; May 10 doi: 10.1016/j.reuma.2016.03.014 [Epub ahead of print]

The efficacy and safety of tocilizumab has been studied in several randomized clinical trials (RCTs) but due to the strict inclusion and exclusion criteria of RCTs, real-life observational studies are needed to supplement the findings from these trials. This small longitudinal, open-label study from an outpatient clinic in Spain evaluated the effectiveness, survival rate and reasons for treatment discontinuations in 85 patients treated with tocilizumab over a 24-month period. The study also ass...