Enthesitis and Dactylitis Resolution with Risankizumab for Active Psoriatic Arthritis: Integrated Analysis of the Randomized KEEPsAKE 1 and 2 Trials

Abstract

Introduction: The presence (vs absence) of enthesitis/dactylitis is associated with greater psoriatic arthritis (PsA) activity and reduced health-related quality of life. Risankizumab, an interleukin 23 antagonist, demonstrated superior treatment efficacy over placebo in patients with PsA, including enthesitis/dactylitis. Herein, we report the efficacy of risankizumab on complete resolution of enthesitis and/or dactylitis and improvements in patient-reported outcomes in patients with PsA.

Methods: This integrated post hoc analysis of data from KEEPsAKE 1 and KEEPsAKE 2 included patients with baseline enthesitis (Leeds Enthesitis Index > 0) and/or dactylitis (Leeds Dactylitis Index > 0). Efficacy outcomes at weeks 24 and 52 included proportion of patients achieving enthesitis and/or dactylitis resolution and minimal clinically important differences (MCID) in pain, Health Assessment Questionnaire-Disability Index, and Functional Assessment of Chronic Illness Therapy-Fatigue.

Results: Of 1407 patients, approximately 63%, 28%, and 20% had baseline enthesitis, dactylitis, and both enthesitis/dactylitis, respectively. At week 24, higher response rates were observed for risankizumab vs placebo for resolution of enthesitis, dactylitis, and both enthesitis/dactylitis (differences of 13.9%, 16.9%, and 13.3%, respectively; p < 0.05). By week 52, risankizumab treatment resulted in complete resolution of enthesitis, dactylitis, and both enthesitis and dactylitis in 55.0%, 76.1%, and 52.3% of patients; similar resolution rates occurred among patients who switched from placebo to risankizumab. Among risankizumab-treated patients who achieved resolution of enthesitis and/or dactylitis, MCIDs were also attained in patient-reported pain, disability, and fatigue at week 24 (all p < 0.05; except fatigue in patients with resolution of both enthesitis/dactylitis); responses were sustained through week 52.

Conclusions: Higher proportions of risankizumab-treated (vs placebo-treated) patients achieved enthesitis and/or dactylitis resolution and meaningful improvements in patient-reported outcomes at week 24 and generally sustained responses at week 52. Thus, risankizumab may result in sustained alleviation of PsA-related pathognomonic musculoskeletal lesions of enthesitis/dactylitis.

Gov identifiers: NCT03675308, and NCT03671148.

Keywords: Biologic; Dactylitis; Enthesitis; Interleukin 23; Psoriasis; Psoriatic arthritis; Risankizumab.

Fig. 1

Proportion of patients achieving resolution of enthesitis (randomized to RZB, n = 444; PBO, n = 448) (a), dactylitis (RZB, n = 188; PBO, n = 204) (b), and both enthesitis/dactylitis (RZB, n = 128; PBO, n = 147) (c). Missing data were imputed using nonresponder imputation incorporating multiple imputation to handle missing data resulting from COVID-19 in the double-blind period and nonresponder imputation (as observed) in the open-label extension period. *p < 0.05; **p < 0.01; ***p < 0.001 vs PBO. CI confidence interval, PBO placebo, RZB risankizumab

Fig. 2

Mean change in LEI among patients with baseline enthesitis (a) and in LDI among patients with baseline dactylitis (b). Mixed-effect model repeated measurement analysis was used for the double-blind period; as-observed data were used for the open-label extension period. *p < 0.05; ***p < 0.001 vs PBO. CI confidence interval, LDI Leeds Dactylitis Index, LEI Leeds Enthesitis Index, LS least squares, PBO placebo, RZB risankizumab

Fig. 3

Proportion of patients who achieved MCID in PROs among those who achieved resolution of enthesitis (a), dactylitis (b), and both enthesitis/dactylitis (c). MCID cutoffs are ≥ 10-mm decrease on a 100-mm visual analog scale (pain),  ≥ 0.35-unit decrease (HAQ-DI), and ≥ 4-point increase (FACIT-Fatigue). Missing data were imputed using nonresponder imputation incorporating multiple imputation to handle missing data resulting from COVID-19 in the double-blind period and nonresponder imputation (as observed) in the open-label extension period. *p < 0.05; **p < 0.01; ***p < 0.001 vs PBO. CI confidence interval, FACIT-Fatigue Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire-Disability Index, MCID minimally clinical important difference, PBO placebo, PRO patient-reported outcome, RZB risankizumab