Responsiveness of Patient-Reported Outcomes by Disease Trajectory in Systemic Lupus Erythematosus

Objectives Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease with heterogeneous manifestations that cause substantial morbidity and premature mortality. Beyond organ damage, patients experience persistent symptoms such as fatigue, pain, and functional limitation, which profoundly impair quality of life and are often under-recognized by physician-assessed indices.[1] Patient-reported outcomes (PROs) are essential for capturing treatment benefit, yet their responsiveness and alignment with clinical activity across disease trajectories remain incompletely defined.

Methods We pooled patient-level data from 4 phase III belimumab trials in adults with active SLE (n=1065). Patients were stratified into 4 previously defined disease trajectory classes according to baseline disease activity (high vs moderate) and treatment response (responder vs non-responder). [2] PROs included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), 36-Item Short Form physical (PCS) and mental (MCS) component summaries, EuroQol 5-Dimension (EQ-5D), and EuroQoL Visual Analog Scale (EQ-VAS). Responsiveness was assessed with standardized response means (SRMs) across timepoints and classes. Correlations with SLEDAI-2K, BILAG, and Physician’s Global Assessment (PGA) were examined using Spearman’s coefficients and compared with Steiger’s Z (α=0.05). Sensitivity analyses were performed using complete-case datasets at each timepoint.

Results FACIT-F and SF-36 PCS were the most responsive PROs and showed the strongest correlations with clinical indices (Table 1). FACIT-F was most responsive early (up to week 20), particularly among non-responders and moderately active responders, while SF-36 PCS was most responsive later (weeks 20-52), especially among responders. EQ-5D consistently demonstrated the lowest responsiveness (peak SRM 0.54) and weakest correlations. PGA correlated most strongly with PRO changes; SLEDAI-2K correlations were weak and inconsistent. Data completeness declined modestly from 95% at baseline to 82% at week 52. Analyses restricted to patients with complete 52-week follow-up yielded results consistent with the main findings, with FACIT-F and SF-36 PCS remaining the most responsive instruments and EQ-5D showing minimal change detection.

Conclusion This is the first study to longitudinally evaluate PRO performance by disease trajectory in SLE using pooled patient-level data from belimumab trials. We show that PRO performance is dynamic, trajectory-dependent, and domain-specific. FACIT-F and SF-36 PCS consistently outperformed EQ-5D in capturing clinically meaningful change and aligning with physician assessments. The consistently poor responsiveness of EQ-5D underscore limitations of generic preference-based measures in SLE. These findings emphasize the importance of selecting sensitive, patient-centered instruments in clinical trials, routine care, and health technology assessments. Failure to do so risks underestimating the true value of therapies in a complex, symptom-driven disease such as SLE.

References [1.] Cornet A. Autoimmun Rev 2025;24:103838. [2.] Parodis I. Rheumatology (Oxford) 2025;64:2697-2705.