Rheumatoid Arthritis (Pediatric)

June 20, 2016

Eli Lilly and Incyte released results of two phase III trials of baricitinib compared to methotrexate or adalimumab (Humira) in patients with rheumatoid arthritis (RA). In the RA-BEGIN trial, nearly 600 patients were randomized to one of the following treatment groups: once-weekly oral methotrexate monotherapy, 4mg once-daily oral baricitinib monotherapy and 4mg once-daily oral baricitinib in combination with once-weekly oral methotrexate. At 24 weeks, 81% of patients receiving baricitinib monotherapy and 79% of patients receiving baricitinib plus methotrexate had clinically meaningful improvement in physical function compared with 70% among those receiving methotrexate alone (p<0.05). Clinically meaningful improvement was defined as an improvement in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score of 0.22. At 52 weeks, 68% of patients on baricitinib monotherapy and 72% of patients on baricitinib in combination with methotrexate saw clinically meaningful improvements in physical function compared to 57% of those treated with methotrexate alone (p<0.05). RA-BEAM was a 52-week trial of 1,305 patients who had active, moderate-to-severe RA, despite ongoing treatment with methotrexate. Patients were randomized to placebo once-daily (n=488), baricitinib 4mg once-daily (n=487) or adalimumab 40mg biweekly (n=330). All patients received background methotrexate. At week 24, patients taking placebo were crossed over to the baricitinib treatment group. At 12 weeks, 75% of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 71% of patients on adalimumab (p=0.302). Clinically meaningful improvement was defined as an improvement in HAQ-DI score of 0.22. At 24 weeks, 73% of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 64% of patients on adalimumab (p<0.05). At 52 weeks, 68% of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 58% of patients on adalimumab (p<0.01). 

April 11, 2016

Eli Lilly reported results of a phase III trial of baricitinib for moderate-to-severe rheumatoid arthritis (RA). The RA-BEACON study enrolled 527 patients who previously had failed at least one tumor necrosis factor (TNF) inhibitor, and included 199 patients who also had received prior treatment with one or more non-anti-TNF biologic agents. Patients received baricitinib 2mg or 4mg or placebo daily, in addition to their existing background therapies, for 24 weeks. The study met its primary endpoint of improved ACR 20 response for baricitinib compared with placebo at week 12. ACR 20 represents at least a 20% improvement across selected measures of disease activity. ACR 20 response rates were as follows (P≤0.001 for each baricitinib dose versus placebo): 55% for baricitinib 4mg, 49% for baricitinib 2mg and 27% for placebo. A statistically significant improvement in ACR 20 response rate with baricitinib versus placebo was observed as early as one week (P≤0.01). ACR 50 and ACR 70 response rates were also significantly higher for baricitinib compared with placebo at week 12 (P≤0.01). A significantly greater proportion of patients treated with baricitinib also achieved a DAS28-CRP scorea measure of RA disease activitybelow 2.6 (indicating disease remission) at week 12 compared with patients receiving placebo. Additionally, a greater proportion of patients treated with baricitinib versus placebo achieved score improvements of at least 0.3 on the Health Assessment Questionnaire Disability Index (HAQ-DI), a patient-reported assessment of physical function at week 12. Significant improvements in ACR response rates, DAS28-CRP and HAQ-DI that were noted with baricitinib versus placebo at week 12 were maintained through week 24. Through 24 weeks, the rate of treatment-emergent adverse events (AEs) was higher for baricitinib 4mg (77%) and baricitinib 2mg (71%) than for placebo (64%).