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

Abstract

Objective.To assess the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) up to 128 weeks in a phase IIb study (NCT01185353).Methods.After a 24-week blinded period, eligible patients entered an initial 52-week open-label extension (OLE); patients receiving 8 mg once daily (QD) continued with that dose and all others received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at investigator discretion when ≥ 6 tender and ≥ 6 swollen joints were present. Patients completing the first OLE were eligible to enter a second 52-week OLE and receive 4 mg QD regardless of previous dose.Results.In the 4-mg (n = 108) and 8-mg (n = 93) groups, treatment-emergent adverse events (AE) occurred in 63% and 67%, serious AE in 16% and 13%, infections in 35% and 40%, and serious infections in 5% and 3% of patients, respectively. Exposure-adjusted incidence rates for AE for all baricitinib groups in the second OLE were similar to or lower than rates observed in the first OLE. No opportunistic infections, tuberculosis cases, or lymphomas were observed through 128 weeks; 1 death occurred during the first OLE. Among all patients in both OLE, the proportions who achieved disease improvement at Week 24 were similar or increased at weeks 76 and 128.Conclusion.In a phase IIb study in RA, the safety and tolerability profile of baricitinib, up to 128 weeks, remained consistent with earlier observations, without unexpected late signals. Clinical improvements seen in the 24-week blinded period were maintained during the OLE.

Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: A 52-week, randomized, single-blind, extension study

“…In our extension study, all improvements in RA observed following the initial 12 weeks of active treatment were maintained (or further improved) during the next 52-week period (Figure 2). This pattern is similar to the results at weeks 24, 76, and 128 from a trial of baricitinib in a multinational population with active RA despite MTX therapy [11]. In addition, maintenance of efficacy with baricitinib up to 24 weeks has also been observed in patients with RA and an inadequate response to biologic DMARDs [8] or conventional synthetic DMARDs [7], and up to 52 weeks in DMARD-naïve patients [10].…”

“…The safety findings of this extension period were generally consistent with the initial 12-week treatment period [5], and with other international baricitinib studies with shortterm and long-term treatment [8,9,11]. Overall, baricitinib was well tolerated, and the nature of TEAEs and the incidence and nature of SAEs were similar between the 4 mg and 8 mg groups.…”

“…In a multinational Phase 2b study with patients who had active RA despite methotrexate (MTX) therapy, a greater proportion of patients receiving baricitinib achieved an American College of Rheumatology 20% (ACR20) response after 12 weeks, compared with placebo [9]. Importantly, the clinical efficacy observed at weeks 12 and 24 of this study, including ACR responses and disease activity, was maintained or improved in patients during the extension period of the study for up to 128 weeks, with acceptable safety and tolerability [11,12].…”

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

“…Adverse event rates were similar in the combined 4/8-mg baricitinib group and the placebo group. In the open-label extension of the study, clinical improvements observed with baricitinib were maintained through 128 weeks and safety signals were consistent with those seen in the first 12 weeks of treatment 10,11 .…”

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

“…Baricitinib is a JAK2 and JAK1 inhibitor, and multiple phase 3 clinical trials have shown its efficacy in RA. [68][69][70][71][72][73] Treatment-naïve patients with active RA showed significant responses to baricitinib both as monotherapy and in combination with methotrexate.…”