Background/Purpose: In patients (pts) with PsA, fatigue is a major driver of perceived impact of disease and has been identified as an important domain to be assessed in clinical trials.^1,2 The association between fatigue and other PsA domains (eg, physical function) or clinical response is not well understood. Fatigue was measured with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire in the pivotal DISCOVER-1 & -2 phase 3 studies of guselkumab (GUS) vs placebo (PBO). This post hoc analysis explores the correlation between FACIT-Fatigue and physical function and clinical response in the DISCOVER program.

Methods: This analysis used pooled data from pts (N=1120) treated with GUS or PBO. In DISCOVER-1 & -2, 381 pts with active PsA (swollen joint count [SJC] ≥3, tender joint count [TJC] ≥3, CRP ≥0.3 mg/dL) and 739 pts with active PsA (SJC ≥5, TJC ≥5, CRP ≥0.6 mg/dL) and inadequate response to standard therapies, respectively, were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at Week (W) 0, W4, then Q8W; or PBO. PBO pts switched to GUS 100 mg Q4W at W24. The FACIT-Fatigue questionnaire has 13 items that assess self-reported fatigue/tiredness over the last 7 days. Items are scored from 0 (very much fatigued) to 4 (not at all fatigued). FACIT-Fatigue response was defined as an increase of ≥4 points from baseline. Physical function was evaluated with the Health Assessment Questionnaire-Disability Index (HAQ-DI). HAQ-DI response was defined as a decrease of ≥0.35 points from baseline. Clinical response was defined as achievement of ACR 20 criteria. Relationships between FACIT-Fatigue and HAQ-DI at W8/16/24 were assessed by Pearson correlation coefficients. Mean changes in HAQ-DI scores at W8/16/24 were summarized in FACIT-Fatigue responders and nonresponders. A logistic regression model was applied to estimate odds ratios (ORs) for achievement of HAQ-DI and ACR 20 response by FACIT-Fatigue response status at each visit. A multiple linear regression model was used to evaluate the association between FACIT-Fatigue and HAQ-DI at W24 after adjusting for SJC, TJC, CRP, and pt assessment of pain.

Results: FACIT-Fatigue and HAQ-DI scores and changes from baseline were negatively correlated at W8, W16, and W24 (Table). Mean changes in HAQ-DI were −0.31, −0.43, and −0.48 at W8, W16, and W24, respectively, in FACIT-Fatigue responders and −0.06, −0.07, and −0.09, respectively, in FACIT-Fatigue nonresponders. FACIT-Fatigue responders were significantly more likely than nonresponders to achieve HAQ-DI and ACR 20 response (OR [95% CI] at W8, 2.8 [2.2-3.7] and 2.4 [1.9-3.1]; at W16, 3.6 [2.8-4.7] and 2.9 [2.3-3.7]; and at W24, 4.4 [3.4-5.7] and 3.2 [2.5-4.2], respectively; Figure). Correlations between FACIT-Fatigue and HAQ-DI remained significant after adjusting for SJC, TJC, CRP, and pt assessment of pain.

Conclusion: In pts with PsA, fatigue response is a clinically meaningful predictor of improvements in physical function and achievement of ACR 20 response, reinforcing the importance of assessing fatigue in PsA disease management.

1. Leung YY et al. J Rheumatol. 2020;96:46-9
2. Gudu T et al. Joint Bone Spine. 2016;83:439-43

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/correlations-between-reductions-in-fatigue-severity-and-improvements-in-physical-function-and-clinical-response-in-patients-with-psoriatic-arthritis-results-from-the-phase-3-discover-program/