ORAL Sequel demonstrates consistent long-term safety, efficacy profiles of tofacitinib
medwireNews: The Janus kinase (JAK) inhibitor tofacitinib has demonstrated a consistent safety profile and sustained efficacy in rheumatoid arthritis (RA) patients over a maximum follow-up of 9.5 years, report the ORAL Sequel investigators.
The phase III open-label extension study included 4481 individuals who previously participated in a phase I, II, or III trial of tofacitinib and were given the JAK inhibitor at a dose of 5 mg or 10 mg twice daily.
During 9.5 years of follow-up and a total 16,291 patient–years of tofacitinib exposure, 90.1% of patients experienced adverse events (AEs), the majority of which were mild or moderate in severity, and 25.0% discontinued treatment due to AEs. The most commonly occurring AEs were infections and infestations, musculoskeletal and connective tissue conditions, and gastrointestinal disorders.
Lisy Wang (Pfizer Inc, Groton, Connecticut, USA) and co-investigators say incidence rates (IRs) for serious adverse events, serious infections, major adverse cardiovascular events, deep vein thrombosis, malignancies, and pulmonary embolism in ORAL Sequel “were similar to those observed in pooled data from phase 1, 2, 3, and [long-term extension] studies, and comparable to those seen with TNFi [tumor necrosis factor inhibitors] and other biologic DMARDs.”
They also report that IRs for mortality were comparable among patients receiving the 5 mg or 10 mg twice-daily dose of tofacitinib, at 0.4 and 0.2 per 100 patient–years, respectively, and that the safety profile of tofacitinib was “generally similar” regardless of whether it was initiated as monotherapy or in combination with conventional DMARDs.
In the efficacy analysis, the researchers demonstrated that ACR20, 50 and 70 response rates were “maintained over time,” with no differences in rates between patients given the two doses.
Indeed, at the beginning of the ORAL Sequel study, 70.7% of participants in the 5 mg group and 73.6% of those in the 10 mg group achieved an ACR20 response, and the rates were 78.5% and 82.6% at the maximum follow-up times of 8 and 6 years, respectively.
Wang and colleagues also found that other measures of efficacy, including improvements in HAQ-DI score and rates of remission according to DAS28-ESR, CDAI, and SDAI scores, remained consistent over time.
The ORAL Sequel results were reported in Arthritis Research & Therapy.
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