For patients with rheumatoid arthritis (RA) who did not respond to adalimumab, switching to baricitinib provided disease control without increasing adverse events, according to study results published in the Annals of the Rheumatic Diseases.
Researchers evaluated the efficacy and safety of baricitinib for patients with RA who were rescued to baricitinib during the RA-BEAM trial or switched to baricitinib for the long-term extension RA-BEYOND trial. The RA-BEAM trial was a 52-week, double-blind, placebo-controlled, phase 3 study where patients with active RA were randomly assigned to an oral baricitinib 4-mg, once-daily cohort; a subcutaneous adalimumab 40-mg, biweekly cohort; or a placebo cohort.
At 16 weeks, patients who did not respond to adalimumab could opt to switch and receive oral baricitinib 4 mg once daily with hopes of a rescue treatment. At 24 weeks, the placebo cohort was switched, without their knowledge, to oral baricitinib 4 mg once daily. The RA-BEYOND trial is a 7-year, long-term extension, phase 3 study open to RA-BEAM participants who switched from adalimumab therapy to baricitinib and participants who continued to receive baricitinib treatment. Efficacy was defined as a high proportion of patients achieving low disease activity and remission and positive changes in baseline measurements. Safety analysis included infections, gastrointestinal disorders, discontinuations, and serious adverse events. Data were collected on physical function, pain, erythrocyte sedimentation rate, and serum high-sensitivity C-reactive protein.
In the RA-BEAM trial, 7% of patients treated with baricitinib (n=487) and 12% of patients treated with adalimumab (n=330) were rescued to open-label baricitinib. Then, 78% of patients treated with baricitinib and 72% of patients treated with adalimumab entered the RA-BEYOND trial. Patients who remained on baricitinib or switched to baricitinib experienced significant improvements at week 12 in disease activity score using the 28-joint count with erythrocyte sedimentation rate, Clinical Disease Activity Index, Simplified Disease Activity Index, pain assessment, and physical function (P ≤.001 for all).
For patients who switched to baricitinib, significant decreases were found in C-reactive protein and erythrocyte sedimentation rate by 12 weeks (P ≤.001 for both). Both patients who switched to baricitinib and patients who continued on baricitinib maintained disease control during the RA-BEYOND trial. By week 24, significant improvements were found for the mean disease activity score using the 28-joint count with erythrocyte sedimentation rate, Clinical Disease Activity Index, and Simplified Disease Activity Index in the cohort of patients who switched to baricitinib from adalimumab at the start of the RA-BEYOND trial (P ≤.001 for all). Also by week 24, in the RA-BEYOND trial, both cohorts had similar outcomes for pain and physical function. Serious adverse events, adverse events leading to discontinuation, and exposure-adjusted incidence rate for infections were higher in patients who continued baricitinib during the RA-BEAM trial, while exposure-adjusted incidence rate for treatment-emergent adverse events and serious infections were similar between the 2 cohorts in the RA-BEYOND trial.
Limitations of this study include the potential subjective responses after switching to open-label baricitinib, and that switching to baricitinib was not randomized.
The researchers concluded “[s]witching from adalimumab to baricitinib (without adalimumab washout) was associated with improvements in disease control, physical function and pain during the initial 12 weeks postswitch, without an increase in [treatment-emergent adverse events], serious adverse events, or infections.”
These studies were sponsored by Eli Lilly and Company and Incyte Corporation, and several other authors reported multiple associations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.
Tanaka Y, Fautrel B, Keystone EC, et al. Clinical outcomes in patients switched from adalimumab to baricitinib due to non-response and/or study design: phase III data in patients with rheumatoid arthritis [published online April 30, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214529