Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis

• Main Authors: Paul Emery, Yoshiya Tanaka, Tracy Cardillo, Douglas Schlichting, Terence Rooney, Scott Beattie, Cameron Helt, Josef S. Smolen
• Format: Article
• Language: English
• Published: BMC 2020-05-01
• Series: Arthritis Research & Therapy
• Subjects: Rheumatoid arthritis; DMARDs (biologics); JAK inhibitors; Drug interruption
• Online Access: http://link.springer.com/article/10.1186/s13075-020-02199-8

Abstract Background In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery. To characterize temporary interruptions of baricitinib and placebo-matched tablets in phase 3 studies of patients with moderate-to-severe rheumatoid arthritis (RA) and describe their impact on efficacy and safety. Methods During 4 baricitinib phase 3 studies, investigators documented timing, reason, and duration of investigator-initiated temporary interruptions of study drug. In 2 studies, patients recorded RA symptoms in daily diaries for 12 weeks. Post hoc analyses investigated changes in symptom scores during interruptions and resumption of treatment. Interruptions were evaluated for reoccurrence of adverse events or laboratory abnormalities after retreatment. Results Across the placebo-controlled studies, interruptions occurred in larger proportions of baricitinib- (2 mg, 18%; 4 mg, 18%) vs placebo-treated (9%) patients in only one study (bDMARD-inadequate responder patients, RA-BEACON). In the active comparator-controlled studies, the lowest rates of interruption were in the baricitinib monotherapy arm (9%) of RA-BEGIN (vs methotrexate monotherapy or combination therapy), and proportions were similar for baricitinib (10%) and adalimumab (9%) in RA-BEAM. Adverse events were the most common reason for interruption, but their reoccurrence after drug restart was infrequent. Most interruptions lasted ≤ 2 weeks. Daily diaries indicated modest symptom increases during interruption with return to pre-interruption levels or better after resumption. Interruptions had no impact on long-term efficacy outcomes. Conclusions Consistent with its pharmacologic properties, brief interruptions of baricitinib during phase 3 studies were associated with minor increases in RA symptoms that resolved following retreatment. This analysis provides useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA. Trial registration ClinicalTrials.gov; NCT01710358 , NCT01711359 , NCT01721057 , NCT01721044