Baricitinib doses can be tapered without risk of relapse in most RA patients who achieve remission or low disease activity with the targeted synthetic DMARD, a study has shown.
The first randomised controlled trial of tapering of the selective Janus kinase 1 and 2 inhibitor showed that it was feasible to move to a reduced maintenance dose of 2mg daily baricitinib after a sustained response with a 4 mg dose was achieved.
The international multicentre study was part of a trial in which 559 patients who had received baricitinib 4 mg for more than 15 months and maintained low disease activity (or remission) were blindly randomised to continue 4 mg or taper to 2 mg.
When followed up for a further 48 weeks, low disease activity was maintained in 80% of patients who were in remission at baseline with 4mg baricitinib and continued at that dose compared to 67% of those tapered to 2mg.
The corresponding rates for maintaining remission were 40% for the 4mg group and 33% for the 2mg group.
Dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks, the study showed. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% for 4 mg vs 37% for 2 mg).
Most rescued patients (67%) could regain LDA or remission after rescue to baricitinib 4 mg.
Dose reduction was associated with a lower rate of infections (30.6 per patient year of exposure for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar for both groups.
Writing in Annals of Rheumatic Diseases, the study authors said there were similar results for tapering of TNF inhibitors and their findings provided the first data from an assessment of guideline recommendations to taper DMARDs in patients who have achieved sustained disease control.
And while some patients did show increases in disease activity when the baricitinib dose was blindly tapered, “2mg proved an acceptably efficacious dose for many patients, as evidenced by the fact that fewer than 1 in 5 dose-tapered patients were rescued back to 4 mg by their treating physicians,” they noted.
Likewise, most patients who were tapered could regain their low dose activity or remission with return to 4 mg if needed, they noted.
Tapering might therefore be preferred for some patients to reduce medication burden and as a safety measure for a novel drug, they said.
“This study provides robust data to inform the use of baricitinib according to professional treatment guidelines,” they concluded.
The study was funded by Eli Lilly.