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Low RA Disease Activity, Remission Retained After Baricitinib Reduction
Many patients with rheumatoid arthritis maintained remission or low disease activity after tapering their baricitinib dose from 4 mg to 2 mg, according to findings published in the Annals of the Rheumatic Diseases.
Researchers also found that returning to the full 4-mg dose recovered the remission or low disease activity among most who did not maintain them after tapering.
“While many patients can sustain their improved clinical state with cessation or reduction in dose, flare-ups occur in a significant number of patients,” Tsutomu Takeuchi, MD, PhD, of the Keio University School of Medicine, Tokyo, and colleagues wrote. “Reintroduction of therapy is associated with recapture of the state prior to dose reduction in most but not all patients. However, almost half of [conventional synthetic disease-modifying antirheumatic drug]-treated patients who flare following cessation of therapy do not regain their previous state of remission. The consequence of cessation or reduction in dose of [targeted synthetic] DMARDs following attainment of [low disease activity] or remission is unknown.”
The findings come from a sub-study of RA-BEYOND, an ongoing long-term extension of four phase 3 trials — RA-BEGIN, RA-BEAM, RA-BUILD and RA-BEACON — designed to determine the long-term safety and efficacy of baricitinib (Olumiant, Eli Lilly) in patients with RA. For the sub-study, Takeuchi and colleagues analyzed the effects of dose tapering among patients with RA who had achieved sustained disease control with daily 4-mg doses of baricitinib.
Patients who received daily baricitinib doses of 4 mg for at least 15 months and maintained low disease activity or remission were blindly, randomly assigned to either continue with their dosage or to reduce the treatment to 2 mg. If necessary, patients could receive a rescue return to the original 4-mg dose. The researchers evaluated dosage efficacy and safety through 48 weeks. In total, 559 participants who were randomized into the step-down sub-study were included in this 48-week analysis.
According to the researchers, low disease activity was maintained in 80% of patients who continued 4 mg, and in 67% of those who tapered to 2 mg. Among those who had previously achieved remission, 40% of those who continued with the 4-mg dose maintained that progress, compared with 33% of those whose dosages were reduced. However, dose reduction resulted in small, but statistically significant, disease activity increases at 12, 24 and 48 weeks. Drug tapering also resulted in earlier and more frequent relapse compared with maintaining the 4-mg dose (P = .001). Dose reduction was also associated with a lower rate of nonserious infections, with exposure-adjusted incidence rates per patient-years of exposure of 30.6 for 4mg and 24.9 for 2mg. The two groups demonstrated similar rates of serious adverse events and adverse events leading to discontinuation.
“These results from a large, ongoing phase-3 randomized dose-taper study indicate that in patients with RA for whom sustained clinical disease control has been induced with baricitinib 4 mg once a day, dose taper to baricitinib 2 mg results in increased disease activity for some patients,” Takeuchi and colleagues wrote. “However, most patients can either retain clinical [low disease activity]/remission following dose taper or regain it with return to 4 mg if needed. A slightly lower incidence rate of treatment-emergent [adverse events] (including infections) was observed after step-down in the dose-tapered group compared with patients who continued baricitinib 4 mg.” – by Jason Laday
Disclosures: Takeuchi reports consulting support and/or speaking fees from AbbVie GK, Asahi Kasei Medical KK, Astellas Pharma, AstraZeneca KK, Bristol-Myers KK, Celtrion, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly and Company, Janssen Pharma KK, Merck Serono, Mitsubishi Tanabe Pharma, Nipponkayaku, Novartis Pharma KK, Pfizer Japan, Takeda Pharma and UCB Japan. Please see the study for all other authors’ relevant financial disclosures.