Responsiveness of patient-reported outcomes by disease trajectory in SLE.

Abstract

Objectives: SLE is a heterogeneous autoimmune disease with persistent symptoms that profoundly impair quality of life yet are often under-recognized by clinician-assessed instruments. Patient-reported outcomes (PROs) are increasingly incorporated in clinical trials to capture treatment benefit from the patient perspective. However, the responsiveness of PRO instruments and their alignment with clinician-assessed disease activity across distinct SLE trajectories remain incompletely defined. We evaluated the longitudinal responsiveness and convergent validity of PRO measures across predefined disease trajectory classes.

Methods: Secondary analysis of pooled patient-level data from two phase III randomized clinical trials of belimumab in adults with active SLE (n = 1908), stratified into four previously derived trajectory classes defined by baseline disease activity and treatment response. PROs included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), 36-Item Short Form Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), EuroQol 5-Dimension 3-level (EQ-5D-3L) and EuroQol Visual Analogue Scale (EQ-VAS). Responsiveness was quantified using standardized response means (SRMs). Convergent validity was evaluated using repeated-measures correlations between within-person changes in PROs and clinician-assessed disease activity measures (SLEDAI-2K, BILAG and Physician's Global Assessment [PGA]), with sensitivity analyses performed to assess the robustness of findings.

Results: FACIT-F and SF-36 PCS generally demonstrated the greatest responsiveness, while EQ-5D-3L showed smaller changes and less consistent responsiveness across classes and timepoints. FACIT-F demonstrated early responsiveness, whereas SF-36 PCS showed sustained responsiveness over later follow-up. PRO changes were most consistently associated with PGA. Sensitivity analyses showed broadly similar patterns.

Conclusion: FACIT-F and SF-36 PCS demonstrated the greatest responsiveness and alignment with clinician-assessed disease activity. EQ-5D-3L showed less consistent responsiveness, suggesting domain-specific PROs may better capture treatment benefit in SLE trials and health technology assessments.