U.S. Food and Drug Administration (FDA) has approved the 2-mg dose of OLUMIANT®(baricitinib), a once-daily oral medication for the treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) who showed inadequate response to one or more tumor necrosis factor (TNF) antagonists. OLUMIANT may be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs).
Baricitinib is a Janus kinase (JAK) inhibitor that works by modulating the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of signal transducers and activators of transcription (STAT).
The OLUMIANT clinical trial program included the RA-BEACON study, a randomized, double-blind, placebo-controlled study in which patients were randomly assigned to receive OLUMIANT 2 mg, baricitinib 4 mg or placebo, in addition to conventional DMARDs that they were currently using. The study included 527 patients who had an inadequate response or intolerance to one or more TNF inhibitor therapies.
The efficacy and safety of OLUMIANT 2 mg once daily were assessed in two confirmatory phase 3 trials. These trials were randomized, double-blind, multicenter studies in patients with active rheumatoid arthritis. Patients over 18 years of age were eligible if at least 6 tender and 6 swollen joints were present at baseline.
The two studies (Studies III and IV) evaluated OLUMIANT 2 mg and baricitinib 4 mg. Study III was a 24-week trial in 684 patients with moderately to severely active rheumatoid arthritis who had an inadequate response or intolerance to conventional DMARDs (cDMARDs).
Patients received OLUMIANT 2 mg or 4 mg once daily or placebo added to existing background cDMARD treatment. From Week 16, nonresponding patients could be rescued to receive baricitinib 4 mg once daily. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12.
Study IV was a 24-week trial in 527 patients with moderately to severely active rheumatoid arthritis who had an inadequate response or intolerance to 1 or more TNF inhibitor therapies with or without other biologic DMARDs (TNFi-IR). Patients received OLUMIANT 2 mg or baricitinib 4 mg once daily or placebo added to background cDMARD treatment. From Week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12.
Results showed Olumiant-treated patients had higher rates of ACR response and Disease Activity Score (DAS28-CRP) <2.6 vs placebo-treated patients. In Study III, the percentage of patients achieving ACR20 response was 66% vs 39% at week 12, and 61% vs 42% at week 24, respectively. More patients in the Olumiant group achieved DAS28-CRP <2.6 vs placebo at week 12 (26% vs 9%) and week 24 (31% vs 11%).
In Study IV, the rates of ACR20 response were 49% vs 27% at week 12, and 45% vs 27% at week 24, respectively. More patients in the Olumiant group achieved DAS-28 CRP <2.6 vs placebo at week 12 (11% vs 4%) and week 24 (11% vs 6%).
OLUMIANT is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants (eg, azathioprine, cyclosporine).
Reported infections include:
• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before initiating OLUMIANT and during therapy.
• Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
RA is a chronic, painful and progressive form of arthritis. It is estimated that about two-thirds of established RA patients will not reach clinical remission with their first TNF inhibitor therapy, and a significant percentage will not maintain efficacy as time goes on.