medwireNews: Brief interruptions are common among people receiving baricitinib for rheumatoid arthritis (RA) and are associated with minor increases in symptoms that resolve following retreatment without impacting long-term efficacy, phase 3 trial data show.
Paul Emery (Leeds Musculoskeletal Biomedical Research Centre, UK) and colleagues analyzed the results of four placebo- and active-controlled studies among patients with active RA who were naïve to conventional synthetic (cs)DMARDs (RA-BEGIN) or had an inadequate response to previous treatment with methotrexate (RA-BEAM), csDMARDs (RA-BUILD), or biologic DMARDs (RA-BEACON) to characterize the impact of temporary baricitinib interruptions on symptoms and efficacy.
Click here for a guide to the phase 3 trials of baricitinib in RA patients
During the course of the four studies, which included a total of 3104 patients, there were 640 interruptions of baricitinib or matching placebo, of which 84% were temporary.
In RA-BEGIN, 9.4% participants who received baricitinib 4 mg had needed at least one interruption by week 52, compared with 22.3% of those who received baricitinib 4 mg plus methotrexate and 14.8% of those who received methotrexate alone.
For RA-BEAM the proportions were 10.3%, 11.1%, and 8.5% with baricitinib 4 mg, placebo, and adalimumab, respectively, at week 24.
As with RA-BEAM, the baricitinib 4 mg and placebo groups in RA-BUILD had similar interruption rates at week 24 (15.0% and 12.7%, respectively). This study also included a baricitinib 2 mg treatment group, which showed a slightly lower rate of 9.2%.
Conversely, in RA-BEACON individuals who received baricitinib 4 mg and baricitinib 2 mg had similar interruption rates at week 24 (18.1 and 17.8%, respectively) whereas the rate among those who received placebo was lower (8.5%).
The researchers report in Arthritis Research & Therapy that the time from the first dose of study treatment to interruption of baricitinib or placebo was generally around 40–70 days on average, with the exception of the RA-BEGIN trial where interruptions occurred after an average of 121–147 days.
Regardless of when the interruptions began, most lasted for approximately 2 weeks and did not appear to impact efficacy outcomes such as ACR20 and ACR50 response rates and DAS28-CRP scores, the investigators note.
Emery and team found that adverse events (AEs), typically mild respiratory infections, were the most common reason for interruption. Few (9%) AEs that led to an interruption resulted in another interruption or permanent discontinuation.
Two of the studies (RA-BEAM and RA-BUILD) required patients to keep a daily diary of symptoms. These diaries showed that the severity of morning joint stiffness, worst joint pain, and worst tiredness all increased during baricitinib or placebo interruptions but returned to pre-interruption levels or lower following treatment reinitiation.
Emery et al conclude: “Consistent with its pharmacologic properties, temporary interruption of baricitinib during phase 3 studies was not followed by significant reactivation of disease and baricitinib was rarely interrupted again after an initial interruption.”
They add: “The present study should serve to provide useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA.”
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