Tofacitinib Met Clinical Response Endpoints in Patients With Psoriatic Arthritis

Most patients with psoriatic arthritis (PsA) receiving tofacitinib reported a shorter timeline to clinically meaningful responses compared with placebo according to a study published in Arthritis Research and Therapy.¹

“The long-term success of a particular treatment for PsA may be predictable as early as 3 months following treatment initiation, emphasizing the importance of the timely assessment and adjustment of the disease management approach, if necessary, to optimize patient outcomes by reducing disease activity,” investigators concluded.

Two phase 3 randomized, double-blind, placebo-controlled studies, OPAL Broaden (n = 422) and OPAL Beyond (n = 394) were used in this analysis. Patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks (OPAL Broaden), or placebo (switching to tofacitinib 5 or 10 BID at the 3-month mark). Eligible patients were aged 18 or older and had a PsA diagnosis for 6 months or more. A predetermined Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Psoriatic Arthritis Disease Activity Score (PASDAS), and minimal disease activity (MDA) composite (meeting at least 5 of the 7 criteria) evaluated the baseline to initial response time.

Of the 816 total participants, within the OPAL Broaden study, the median time to HAQ-DI score response was 29 days in the tofacitinib 5 BID group, 53 days in the tofacitinib 10 mg BID group, and 30 days in the adalimumab group, compared with 162 and 112 days for those receiving placebo or switching between groups. The HAQ-DI score was defined as ≥ 0.35-point improvement from baseline. Across both studies, the time to 25th percentile to HAQ-DE was similar between the tofacitinib groups and adalimumab-treated cohorts (15-16 days) and shorter compared with those who received placebo for 3 months and then switched to tofacitinib 10 mg BID (29-30 days).

Regarding FACIT-F total scores, tofacitinib 5 mg BID scores were shorter (approximately 31 days) when compared with other groups (84-92 days) in both studies.

In OPAL Broaden, the MDA and 6-9 months PASDAS (defined as a post-baseline score of ≤ 3.2 and > 1.6-point improvement from baseline) were shorter in those receiving tofacitinib or adalimumab.

The study was limited by the time-to-response timeframes of the original studies as both studies were not designed to compare time-to-response outcomes. A finite number of visits may have created uneven Kaplan–Meier curves that may have created results that were more difficult to interpret. As placebos were only available to the 3-month mark, the value of time-to-event analysis was limited. Additionally, comparisons between adalimumab and tofacitinib were not possible between both groups.

“Numerical similarity was observed between tofacitinib and adalimumab in OPAL Broaden,” investigators concluded. “Our findings provide an estimate for physicians of when a clinically meaningful response can be expected with tofacitinib. Considering the limitations noted above, the results of this analysis should be considered exploratory and, therefore, future research is needed for confirmation.”

Reference:

Gladman DD, Coates LC, Wu J, et al. Time to response for clinical and patient-reported outcomes in patients with psoriatic arthritis treated with tofacitinib, adalimumab, or placebo. Arthritis Res Ther. 2022;24(1):40. Published 2022 Feb 9. doi:10.1186/s13075-022-02721-0