Effect of tofacitinib on dactylitis and patient-reported outcomes in patients with active psoriatic arthritis: post-hoc analysis of phase III studies

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post-hoc analysis of two phase III studies in patients with PsA treated with tofacitinib assessed dactylitis by location, and the impact on patient-reported outcomes (PROs).

Methods: Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo. Endpoints included change from baseline in Dactylitis Severity Score (DSS), proportions of patients with dactylitis, Psoriatic Arthritis Disease Activity Score (PASDAS), and PROs (Health Assessment Questionnaire-Disability Index [HAQ-DI]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]; Short Form-36 Health Survey [SF-36] Physical Component Summary [PCS], Mental Component Summary [MCS], and physical functioning [PF]; arthritis pain; and Work Limitations Questionnaire [WLQ]). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs were evaluated by multivariate linear regression.

Results: The analysis included 373/337 patients with baseline DSS > 0/DSS = 0. Regardless of location, DSS improvements in patients with DSS > 0 were greater from month 1 with tofacitinib (10 mg BID) versus placebo. For patients with DSS > 0/DSS = 0, both doses of tofacitinib led to mean dactylitis presence ≤ 15%/< 2% for all digits at month 6, and PASDAS (by dactylitis location) was lower versus placebo at month 3. Dactylitis location was not significantly associated with change from baseline in PROs.

Conclusion: Tofacitinib resulted in sustained improvements in dactylitis irrespective of location, with minimal emergence of new dactylitis. Trial registration NCT01877668; NCT01882439.

Keywords: Dactylitis; Patient-reported outcomes; Psoriatic arthritis; Spondyloarthritis; Tofacitinib.

Conflict of interest statement

A-M Orbai has received grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead Sciences, Horizon, Janssen, and Novartis; and is a consultant for Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB. PJ Mease has received grant/research support from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, Sun, and UCB; is a consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, Sun, and UCB; and has been on speakers’ bureaus for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, and UCB. PS Helliwell has received consulting fees from Eli Lilly; and has received fees for educational services from AbbVie, Janssen, Novartis, and Pfizer Inc. O FitzGerald has received grant/research support from AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer Inc, and UCB; has received consulting fees from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and Pfizer Inc; and has been on speakers’ bureaus for AbbVie, Janssen, and Pfizer Inc. DL Fleishaker, R Mundayat, and P Young are employees and shareholders of Pfizer Inc.

© 2022. The Author(s).

Figures

Fig. 1

Change from baseline in DSS and dactylitic digits count (patients with baseline DSS > 0). Data for a DSS and b dactylitis digit count were stratified by dactylitis location and pooled from OPAL Broaden and OPAL Beyond. *Comparisons where the 95% CI for tofacitinib does not overlap with the 95% CI for placebo. Dactylitis was defined as swelling of an entire digit; DSS ranged from 0 to 60 (60 = highest dactylitis severity) [20]. BID twice daily, CI confidence interval, DSS Dactylitis Severity Score, N total number of patients with DSS > 0 at baseline, n number of patients applicable for each category

Fig. 2

Proportion of patients with dactylitis stratified by location (patients with baseline DSS > 0). Data for a right hand fingers, b left hand fingers, c right foot toes, and d left foot toes were pooled from OPAL Broaden and OPAL Beyond. *Comparisons where the 95% CI for tofacitinib does not overlap with the 95% CI for placebo. Dactylitis was defined as swelling of an entire digit; DSS ranged from 0 to 60 (60 = highest dactylitis severity) [20]. BID twice daily, CI confidence interval, DSS Dactylitis Severity Score, N total number of patients with DSS > 0 at baseline, n number of patients applicable for each category

Fig. 3

PASDAS by dactylitis location in patients with DSS > 0 or DSS = 0 at baseline. Data for patients with a DSS > 0 and b DSS = 0 at baseline were pooled from OPAL Broaden and OPAL Beyond. *Comparisons where the 95% CI for tofacitinib does not overlap with the 95% CI for placebo. Dactylitis was defined as swelling of an entire digit; DSS ranged from 0 to 60 (60 = highest dactylitis severity) [20]. BID twice daily, CI confidence interval, DSS Dactylitis Severity Score, N total number of patients, PASDAS Psoriatic Arthritis Disease Activity Score

Fig. 4

Change from baseline in HAQ-DI scores and response rates. Change from baseline data in a HAQ-DI score and b HAQ-DI response rate† by dactylitis location in patients with DSS > 0 at baseline; and c HAQ-DI score and d HAQ-DI response rate†, in patients with DSS = 0 at baseline were pooled from OPAL Broaden and OPAL Beyond. *Comparisons where the 95% CI for tofacitinib does not overlap with the 95% CI for placebo. †Defined as ≥ 0.35-point decrease from baseline in HAQ-DI score. Dactylitis was defined as swelling of an entire digit; DSS ranged from 0 to 60 (60 = highest dactylitis severity) [20]. BID twice daily, CI confidence interval, DSS Dactylitis Severity Score, HAQ-DI Health Assessment Questionnaire-Disability Index, N total number of patients, n number of patients applicable for each category