medwireNews: Patients with psoriatic arthritis (PsA) undergoing stable treatment with tofacitinib plus methotrexate may be able to withdraw methotrexate without having an adverse impact on disease activity, suggests a substudy of the OPAL Balance trial.
“OPAL Balance was an open-label, long-term extension study of tofacitinib in patients with psoriatic arthritis who participated in the OPAL Broaden and OPAL Beyond phase 3 studies,” explain Dona Fleishaker (Pfizer Inc, Groton, Connecticut, USA) and colleagues.
The methotrexate withdrawal substudy included 179 patients from OPAL Balance who had received tofacitinib treatment for 2 years or more, at a stable dose of 5 mg twice daily for at least 3 months, alongside methotrexate 7.5–20.0 mg/week for at least 4 weeks. Participants were randomly assigned to continue with methotrexate or switch to placebo alongside continued treatment with the Janus kinase inhibitor at a dose of 5 mg twice daily.
Fleishaker and team report in The Lancet Rheumatology that changes in PsA disease activity score from baseline to the 6-month follow-up were not significantly different among patients in the methotrexate and placebo groups, with least squares mean (LSM) increases of 0.14 and 0.23 points, respectively. Similarly, LSM increases in HAQ-DI were a corresponding 0.02 and 0.04 points, a nonsignificant difference.
In all, 46% and 48% of patients in the methotrexate and placebo arms, respectively, experienced adverse events (AEs) over 1 year of follow-up. The corresponding rates of serious AEs were 3% and 4%, and there were no deaths in the study. The researchers say that AE profiles were similar in the two treatment groups, with the exception of a greater proportion of patients with elevated liver enzymes in the methotrexate arm.
“Overall, tofacitinib safety in this substudy was consistent with previously reported findings,” say the investigators.
Writing in an accompanying comment, Roy Fleischmann (University of Texas Southwestern Medical Center, Dallas, USA) says that while the OPAL Balance substudy results are “interesting and clinically important,” the study had a number of limitations and therefore “can only be viewed as hypothesis-generating rather than conclusive.”
For instance, he points out that the recommended methotrexate dose for PsA is 25 mg/week, but the maximum dose used in the study was 20 mg/week (average 15 mg/week), and therefore “there is a possibility that many of the patients who maintained their response with tofacitinib monotherapy did so because they were treated with a suboptimal, ineffective dose of methotrexate before inclusion.”
He says that the study could not establish the efficacy of tofacitinib versus optimal-dose methotrexate monotherapy, nor that of either tofacitinib or optimal-dose methotrexate monotherapy compared with combination therapy.
“To answer these questions, a powered, three-arm, head-to-head, trial would have to be done,” he recommends.
And Fleischmann concludes: “[O]ne might suspect that, as shown in rheumatoid arthritis, many patients will do well with tofacitinib monotherapy, but not quite as many as will do well with combination therapy.”
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Lancet Rheumatol 2020; doi:10.1016/S2665-9913(20)30339-8
Lancet Rheumatol 2020; doi:10.1016/S2665-9913(20)30395-7