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Objective: Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment., Methods: Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID)., Results: In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab., Conclusions: SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders., Competing Interests: Competing interests: RR-B and MK are employees of QualityMetric, which received consulting fees from GSK for this analysis. W-HC, SA, CH and AH are employees of GSK and hold stocks and shares in the company. KG is a former employee of GSK and holds stocks and shares in the company., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Interpretation thresholds for patient-reported outcome (PRO) scores are of crucial importance, particularly when interpreting treatment benefit. This study was designed to determine the within-patient meaningful improvement (WPMI) thresholds for the Short-Form 36 Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and the novel Rheumatoid Arthritis Symptoms and Impact Questionnaire (RASIQ) among patients with rheumatoid arthritis (RA)., Methods: In this post-hoc analysis, anchor-based and supportive distribution-based methods were used to derive WPMI based on blinded data from all treatment arms in two Phase 2 RA trials with otilimab. Patient's Global Assessment of Disease Activity (PtGA) was the general anchor for all SF-36v2 scales. SF-36 Patient's Global Impression of Status (PGIS), PtGA, and VT03 (an SF-36v2 item) were used as anchors for FACIT-Fatigue. SF-36 PGIS, PtGA, and Patient's Assessment of Arthritis Pain (PAIN) were anchors for RASIQ. Mean change was calculated for the anchor category associated with minimal meaningful improvement from baseline to Week 24 for SF-36v2 and FACIT-Fatigue, and to Week 12 for RASIQ. Sensitivity and specificity were used to evaluate the accuracy of estimated WPMI values., Results: For the SF-36v2 physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health domains, anchor-based estimates of WPMI based on 0-100 scores were 24.5, 24.5, 25.4, 13.6, 21.5, 20.5, 16.9, and 14.3, respectively. Anchor-based WPMI estimates were 9.7 for the Physical Component Summary score and 7.6 for the Mental Component Summary score (using norm-based T-score metric). For FACIT-Fatigue (range 0-52), WPMI estimates ranged from 9.7 to 11.3 points. For RASIQ (range 0-100), anchor-based WPMI was determined as a change between -32.7 and -21.7 points for the Joint Pain scale, -26.7 to -23.7 for the Joint Stiffness scale, and -21.1 to -17.4 for the Impact scale., Conclusions: This study derived WPMI thresholds for SF-36v2, FACIT-Fatigue, and RASIQ among patients with RA, using multiple anchors. Derivation of WPMI thresholds for these PRO instruments will enable their broader use in evaluating and interpreting treatment benefit in future RA studies., (© 2024. The Author(s).)

This study reports health-related quality of life (HRQL) among newly-diagnosed immunoglobulin light-chain (AL) patients (n = 914) treated with a bortezomib-based regimen and its association with response depth and survival. Haematologic response/HRQL were assessed over 24 months in an ongoing, prospective study. HRQL change was calculated across haematologic/cardiac response levels. The relationship between baseline HRQL and survival was evaluated by the Cox proportional-hazard model (PH). Shared-random-effects models (SREMs) estimated time-to-death conditional on current HRQL/longitudinal HRQL trajectory. At 3 months, there was consistent decline in 5/8 HRQL domains across all haematologic response levels. By 12 months, 3/5 declining domains improved among complete response (CR) patients. In contrast, the mean change in less-than-CR patients did not indicate improvement. Under the Cox PH, having a baseline HRQL score five points higher than the sample mean was associated with 20% lower mortality risk. SREMs indicated a five-point greater HRQL score at the event time correlated with an approximately 30% decrease in mortality risk. For each one-point increase in HRQL score trajectory slope, mortality risk decreased by approximately 88%. Only CR patients had HRQL improvement, while partial response patients had less decline but no meaningful improvements. These data show the importance of HRQL serial assessments of AL patients and its importance as an end-point., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)