Baricitinib improved symptoms of RA in the RA-BUILD trial, a Phase 3 study of baricitinib in patients with moderately to severely active RA, refractory to or intolerant to csDMARDs. As well as providing a short-term (24 weeks) benefit, there appeared to be joint damage benefit, considered a marker of long-term disability.RA-BUILD was a 24-week randomised, double-blind, placebo-controlled parallel-group study. Patients were randomised 1:1:1 to receive once-daily doses of placebo (n=228) or barici...

January 2017

Results from the AMBITION study (Actemra versus Methotrexate double-Blind Investigate Trial In mONotherapy), showed the continuing efficacy and safety of tocilizumab up to 264 weeks.AMBITION was a 24-week randomised controlled trial in patients with active RA who were either MTX-naïve or MTX-free for 6 months prior to study entry. Patients received TCZ 8 mg/kg IV Q4W or oral MTX weekly (7.5 mg dose escalating to 20 mg). For those patients who then entered the long-term extension (LTE) study (N=1...

December 2016

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...
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...
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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October 2016

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...
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

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 ...
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...

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...