Abstract
BackgroundIn 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.MethodsDuring 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.ResultsAcross 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.ConclusionsConsistent 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 registrationClinicalTrials.gov; NCT01710358, NCT01711359, NCT01721057, NCT01721044
Highlights
In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery
Baricitinib is an oral, selective inhibitor of Janus kinase (JAK)1 and JAK2, which belong to a family of protein tyrosine kinases that mediate signal transduction for a variety of cytokines involved in inflammatory conditions, including RA [1, 2]
For interruptions among all baricitinib-treated patients, including those who were originally randomized to placebo or active-control, but were rescued or switched to baricitinib during the studies, we provide a detailed summary of the reasons for the interruptions
Summary
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. Temporary interruption of rheumatoid arthritis (RA) therapy is common in clinical practice for various reasons including side effects, non-compliance, or necessity for surgery. Short half-life and low immunogenicity may be useful attributes for disease-modifying antirheumatic drugs (DMARDs). As a small molecule with a short half-life (approximately 12 h in RA patients) [3], baricitinib may offer advantages over injectable biologic therapies with respect to ease and speed of withdrawal and reinitiation
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