Short interruptions in the treatment of rheumatoid arthritis (RA) with baricitinib are associated with small increases in RA symptoms, but these symptoms generally resolve after retreatment, according to study results published in Arthritis Research & Therapy.
Researchers analyzed the effects of temporary treatment interruptions of barcitinib using data from 4 phase 3 clinical trials that included patients with RA who were treated with either placebo or baricitinib alone or in combination with another RA therapy. In 1 trial, patients with active RA were randomly assigned to either placebo (n=228) or once-daily baricitinib 2 mg (n=229) or 4 mg (n= 227). A similar trial included in the analysis evaluated patients randomly assigned to either placebo (n= 176) or baricitinib 2 mg (n=174) or 4 mg (n=177).
In another trial, patients received either once-daily placebo (n= 488), once-daily baricitinib 4mg (n= 487), or subcutaneous adalimumab every 2 weeks (n= 330). The fourth trial included patients with RA who were randomly assigned to either oral methotrexate every week (n=210), once-daily baricitinib 4 mg (n=159), or once-daily baricitinib 4 mg plus methotrexate every week (n=215).
Changes in efficacy and symptom scores were assessed during therapy interruptions and resumptions. In addition, the investigators examined the effect of treatment interruptions on safety, specifically the reoccurrence of either post-retreatment adverse events or laboratory value abnormalities.
Across all studies, 84% of interrupted treatment regimens were able to restart treatment with either baricitinib or placebo. In 1 placebo-controlled study, interruptions occurred more frequently with baricitinib 2 mg (17.8%) and 4 mg (18.1%) compared with placebo (8.5%). In 2 of the placebo-controlled trials, a similar percentage of patients in both placebo groups experienced treatment interruptions (11.1% and 12.7%). The percentage of patients with baricitinib interruptions in these studies was 10.3% and 15.0% for baricitinib 4 mg. The most common reason for interruptions was the occurrence of adverse events.
The majority of treatment interruptions lasted ≤2 weeks. According to daily diaries kept by patients in 2 of the studies, modest increases in RA symptoms (morning joint stiffness, tiredness, and joint pain) occurred during interruption of baricitinib or placebo in a majority of patients, but these symptoms resolved after resumption of therapy. Long-term efficacy outcomes were not affected by therapy interruptions.
With regard to safety, the same adverse event that caused the treatment interruption in 361 cases reoccurred after retreatment at a rate of 9%, leading to either another temporary interruption (38%) or permanent discontinuation (13%). The researchers also recorded 37 temporary treatment interruptions caused by abnormal laboratory results; 4 of these cases had a reoccurrence of laboratory value abnormalities after retreatment, which led to no additional temporary interruptions in treatment but 1 permanent discontinuation.
A limitation of this study was the lack of assessment for the duration of time between the onset of abnormal laboratory values after interruption to normalization after resumption of therapy.
The researchers who performed this analysis suggested these findings “should serve to provide useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA.”
Disclosure: All 4 clinical trials in this study were designed and funded by Eli Lilly and Company. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Emery P, Tanaka Y, Cardillo T, et al. Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis. Arthritis Res Ther. 2020;22(1):115.