medwireNews: The final analysis of the OPAL Balance long-term extension (LTE) study suggests that the Janus kinase (JAK) inhibitor tofacitinib has a consistent safety profile for up to 48 months in patients with psoriatic arthritis (PsA).
The phase 3 study included 686 people with active PsA (average age 49 years, 54% women) from 124 centers in 16 countries who had previously taken part in OPAL Broaden or OPAL Beyond. Participants were treated with open-label tofacitinib 5 mg twice daily in OPAL Balance, with a dose increase to 10 mg twice daily permitted in cases of inadequate symptom control.
In all, 66% of participants completed the study, a proportion of whom had switched to the 12-month methotrexate substudy after a minimum of 24 months in OPAL Beyond. The average duration of tofacitinib treatment was 795 days for those who remained in the LTE study and 879 days for those who switched to the methotrexate substudy; the maximum follow-up for any participant was 48 months.
Dona Fleishaker (Pfizer Inc, Groton, Connecticut, USA) and co-investigators report in The Lancet Rheumatology that 84% of all patients treated with tofacitinib experienced adverse events (AEs) during the study period, while 17% experienced serious AEs and 11% discontinued the JAK inhibitor due to an AE.
The team says that rates of AEs of special interest “were consistent with those reported in the interim analysis, suggesting that risk of these adverse events did not increase over time.”
Incidence rates per 100 person–years were 1.0 for serious infections, 0.4 for opportunistic infections, 1.7 for herpes zoster, 0.7 for malignancies excluding nonmelanoma skin cancer (NMSC), 0.9 for NMSC, 0.2 for major adverse cardiovascular events, 0.1 for pulmonary embolism, and 0.4 for arterial thromboembolism. There were no reports of deep vein thrombosis.
Fleishaker and colleagues report that “changes in laboratory parameters in this analysis were as expected with tofacitinib treatment,” and “efficacy was maintained” during OPAL Balance.
This analysis “represent[s] the longest time period of any tofacitinib clinical study for active psoriatic arthritis to date,” and supports long-term use of the JAK inhibitor, say the researchers.
They report that the efficacy of the 10 mg dose of tofacitinib was generally “less pronounced” than that of the 5 mg dose, but note that this finding was based on an exploratory analysis and “the study was not designed to compare doses.”
Nevertheless, the author of an accompanying comment, Vibeke Strand (Stanford University, Palo Alto, California, USA), points out that similar findings were seen in the OPAL Beyond trial, “in which the 10 mg dose did not result in substantially better outcomes than 5 mg twice daily.”
“Together, these data should therefore give us confidence in using tofacitinib at the approved 5 mg twice daily dose for treatment of psoriatic arthritis,” she concludes.
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Lancet Rheumatol 2021; 3: e270–283
Lancet Rheumatol 2021; 3: e239–240