The Food and Drug Administration (FDA) has approved Olumiant (baricitinib; Eli Lilly and Incyte Corporation) for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to ≥1 tumor-necrosis factor (TNF) antagonists. It 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 approval was supported by a clinical program that included dose-ranging trials (Study I and II) and confirmatory Phase 3 trials (Study III and IV). In Study I (N=301), the observed ACR response was similar for baricitinib 1mg and 2mg daily and for baricitinib 4mg and 8mg daily; the highest response was seen in the 8mg arm. In Study II (N=145), no clear trend of dose response was seen and response rates were comparable for 1mg and 4mg and 2mg and 8mg.
Study III (N=684) and Study IV (N=527) were 24-week, randomized, double-blind, multicenter studies in patients with active RA aged ≥18 years who had ≥6 tender and 6 swollen joints at baseline. Both studies evaluated the safety and efficacy of Olumiant 2mg and 4mg once daily vs placebo added to existing background conventional DMARD treatment. The primary endpoint was the proportion of patients who achieved an ACR20 response at week 12.
Study III specifically enrolled adults with RA who had inadequate response or intolerance to conventional DMARDs whereas Study IV enrolled those who had inadequate response or intolerance to ≥1 TNF inhibitor therapies with or without biologic DMARDs.
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 were 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 carries a Boxed Warning regarding serious infections, malignancy, and thrombosis. It is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants (eg, azathioprine, cyclosporine). The most common adverse reactions include upper respiratory tract infections, nausea, herpes simplex, and herpes zoster.
Olumiant is supplied as 2mg tablets in 30-count bottles. It is expected to be available by the end of the second quarter of 2018 at a price that is 60% less than the leading TNF inhibitor, according to a press release issued by Lilly and Incyte.
For more information call (800) 545-5979 or visit Lilly.com.