Positive results have been reported from a pivotal phase 3 study of baricitinib (Eli Lilly/Incyte Corporation), a once-daily oral medication under regulatory review for the treatment of patients with moderate-to-severe rheumatoid arthritis (RA). The study met its primary endpoint of an improved ACR20 response for baricitinib compared with placebo at week 12.
Baricitinib is a once-daily oral selective Janus kinase 1 (JAK1) and JAK2 inhibitor currently in late-stage clinical studies for inflammatory and autoimmune diseases. There are four known JAK enzymes: JAK1, JAK2, JAK3, and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of several inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of inflammatory conditions. Baricitinib demonstrated approximately 100-fold greater potency of inhibition against JAK1 and JAK2 than against JAK3 in kinase assays.
The RA-BEACON trial enrolled 527 patients who had failed treatment with at least one tumor necrosis factor (TNF) inhibitor, and included 199 patients who also had received treatment with one or more non–anti-TNF biologic agents. The patients received baricitinib (2 mg or 4 mg) or placebo daily, in addition to their existing background therapies, for 24 weeks.
The study’s primary endpoint, ACR20, represents at least a 20% improvement across selected measures of disease activity. The ACR20 response rates were 55% for baricitinib 4 mg, 49% for baricitinib 2 mg, and 27% for placebo (P < 0.001 for each baricitinib dose versus placebo). A significant improvement in the ACR20 response rate with baricitinib versus placebo was observed as early as one week (P < 0.01). ACR50 and ACR70 response rates were also significantly higher for baricitinib compared with placebo at week 12 (P < 0.01). Further, a significantly greater proportion of patients treated with baricitinib achieved a DAS28-CRP score––a measure of RA disease activity––of less than 2.6 (indicating disease remission) at week 12 compared with patients receiving placebo.
Through 24 weeks of treatment, the rate of treatment-emergent adverse events (AEs) was higher for baricitinib 4 mg (77%) and baricitinib 2 mg (71%) than for placebo (64%). Discontinuation rates due to AEs were 6%, 4%, and 4%, respectively. The most common AEs associated with baricitinib included headache, upper respiratory tract infections, and nasopharyngitis. The rates of serious AEs were 10% for baricitinib 4 mg, 4% for baricitinib 2 mg, and 7% for placebo. One death (from stroke) was reported in the baricitinib 4 mg group.
The study was published in the New England Journal of Medicine.
Source: Eli Lilly; March 31, 2016.