According to recent study findings, some patients with psoriatic arthritis who are stable on tofacitinib with background methotrexate may be able to discontinue methotrexate without clinically meaningful changes in disease activity and safety.
The study findings suggested the feasibility of discontinuing methotrexate in patients who had received tofacitinib in combination with methotrexate.
Philip Mease, MD, and a team of investigators evaluated the efficacy and safety of tofacitinib 5 mg twice daily monotherapy after methotrexate withdrawal. The team conducted a 12-month, randomized, double-blind, placebo-controlled, methotrexate withdrawal sub-study from OPAL Balance. OPAL Balance was an open-label study of tofacitinib in patients with psoriatic arthritis who participated in the OPAL Broaden and OPAL Beyond phase 3 studies. The sub-study included patients who completed tofacitinib treatment for at least 24 months and were receiving methotrexate (7.5-20 mg/week).
Participants were blindly randomized and received open-label tofacitinib 5 mg twice daily with either placebo (tofacitinib 5 mg twice daily plus placebo group) or continued methotrexate (tofacitinib 5 mg twice daily plus methotrexate group).
Primary endpoints were changes from sub-study baseline in psoriatic arthritis disease activity score (PASDAS) and health assessment questionnaire-disability index (HAQ-DI) at 6 months in all randomized patients with at least 1 sub-study drug dose.
Overall, 90 patients received tofacitinib 5 mg twice daily plus placebo and 89 patients were assigned to tofacitinib plus methotrexate. At 6 months, least squares mean (LSM) changes in PASDAS were .23 for tofacitinib 5 mg twice daily plus placebo and .14 for tofacitinib 5 mg twice daily plus methotrexate (treatment difference: LSM, .9; [95% CI, -.13 to .31]). Changes in HAQ-DI were .04 for the placebo group and .02 for the methotrexate group (treatment difference, .03; [95% CI, -.05 to .1]).
Between both groups, rates of adverse events, discontinuations because of adverse events, adverse events of special interest, and laboratory changes were generally similar. Liver enzyme elevations were more common in the methotrexate cohort than the placebo group. Worsening symptoms were reported in 1% of the 90 patients in the tofacitinib 5 mg twice daily plus placebo group.
This was the first study to assess tofacitinib as monotherapy for the treatment of psoriatic arthritis. There were no clinically meaningful differences in efficacy observed between the open-label tofacitinib 5 mg twice daily as monotherapy after masked methotrexate withdrawal versus tofacitinib 5 mg twice daily with masked continued methotrexate.
“The results of this sub-study provide further characterization of the efficacy of tofacitinib in patients with psoriatic arthritis, and suggest that some patients receiving tofacitinib 5 mg twice daily with background methotrexate who are in a stable disease state might be able to discontinue methotrexate to receive tofacitinib monotherapy, without an adverse effect on their overall disease activity or health-related quality of life,” the study authors concluded.
The study, “Tofacitinib as monotherapy following methotrexate withdrawal in patients with psoriatic arthritis previously treated with open-label tofacitinib plus methotrexate: a randomised, placebo-controlled substudy of OPAL Balance,” was published online in The Lancet Rheumatology.