Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Abstract

Objective.To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX).Methods.This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events.Results.A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group.Conclusion.In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.govNCT01469013).

Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis

“…The safety and tolerability profile of baricitinib through the 104-week OLE period of this phase IIb study was generally consistent with prior observations gathered during shorter durations of exposure 3,4,5 . Few patients experienced AE leading to discontinuation, and AE rates including infection stabilized or diminished with prolonged treatment.…”

“…In a phase IIa study in patients with active RA despite treatment with disease-modifying antirheumatic drugs (DMARD), baricitinib [4, 7, or 10 mg administered once daily (QD)] improved the signs and symptoms of RA after 12 weeks of treatment compared to placebo, with no unacceptable safety findings 3 . In a phase IIb double-blind study conducted in Japanese patients, QD baricitinib was also associated with significant improvement in RA disease activity compared to placebo at the primary 12-week timepoint 4 . In a larger, phase IIb, double-blind, randomized, placebo-controlled, dose-ranging study in patients with active RA despite treatment with methotrexate (MTX) ± other conventional synthetic DMARD, significantly more patients in the…”

Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials

“…With regard to other efficacy measures in the four phase 3 studies, results obtained from Japanese subpopulations were also generally similar to those of overall study population. In all four of the phase 3 studies, the safety and tolerability profile of baricitinib in Japanese patients appeared acceptable and generally consistent with results from the prior phase 2 study of baricitinib in Japan [17], and with the overall study population data [18][19][20][21]. In study RA-BEGIN, the incidence of TEAEs during 52 weeks was 97% of the Japanese patients in the baricitinib 4-mg monotherapy group, and 92% in the baricitinib þ methotrexate group versus 83% in the methotrexate monotherapy group, compared to 71, 78 and 72%, respectively, in the overall study population.…”

“…In this study, 4-mg and 8-mg baricitinib showed earlier and/or greater improvements in most measures of disease activity than the 1-mg and 2-mg doses over 12 weeks of treatment when compared with placebo [17]. Baricitinib was well-tolerated in this study; the safety profile of 4-mg appeared to offer some advantages over the 8-mg dose, and was similar to that of the lower doses.…”

“…The efficacy and safety of baricitinib (1-mg, 2-mg, 4-mg, 8-mg) in Japanese patients with moderate-to-severe active adult-onset RA despite stable treatment with methotrexate have been assessed in a phase 2 study [17]. In this study, 4-mg and 8-mg baricitinib showed earlier and/or greater improvements in most measures of disease activity than the 1-mg and 2-mg doses over 12 weeks of treatment when compared with placebo [17].…”