Lupus Research Alliance

Objectives To evaluate longitudinal changes in health-related quality of life (HRQoL) over two years in patients with systemic lupus erythematosus (SLE) and identify determinants of HRQoL trajectories.Methods This prospective cohort enrolled 1,005 SLE patients fulfilling the ACR criteria.HRQoL was assessed using the Short Form-36 (SF-36) questionnaire at baseline, 12, and 24 months.Disease activity and organ damage were measured by the SLE Disease Activity Index-2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index, respectively.Temporal changes in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were analyzed using generalized estimating equations adjusted for demographic and clinical factors.Results Among 915 women (91.0%), the median age was 35.2 years (IQR 28.1-45.3).Both PCS and MCS scores improved significantly over 24 months (beta = 0.73, 95% CI 0.48-0.98;p < 0.001 for PCS; beta = 0.85, 95% CI 0.57-1.13;p < 0.001 for MCS).Age >= 50 years correlated with lower PCS (beta = -4.2,p < 0.001) but higher MCS scores (beta = 2.1, p = 0.032).Male sex predicted greater MCS improvement (beta = 2.3, p = 0.003) without significant PCS effect.Higher SLEDAI-2K scores were associated with reduced PCS (beta = -0.94,p < 0.001) and MCS (beta = -0.52,p < 0.001) scores.Increasing SLICC damage index independently predicted lower PCS (beta = -1.2,p < 0.001) and MCS (beta = -0.8,p = 0.009) scores.Different organ damage domains exerted distinct effects on HRQoL: musculoskeletal damage had the greatest negative impact on PCS (beta = -3.8,p < 0.001), followed by cardiovascular damage (beta = -2.9,p = 0.001), whereas neuropsychiatric damage had minimal influence (beta = -0.6,p = 0.43).In contrast, organ-specific damage domains did not differentially affect MCS trajectories after accounting for total damage burden.Conclusions HRQoL in SLE patients tends to improve over time, but disease activity, cumulative organ damage, age, and sex significantly shape its trajectory.The novel observation that physical-but not mental-health is differentially affected by specific organ damage domains highlights the importance of domain-based assessment and targeted rehabilitation strategies to optimize long-term outcomes in SLE.

The Lupus Research Alliance formed the Lupus Accelerating Breakthroughs Consortium (Lupus ABC) in 2023 as a public-private partnership with investigators, pharmaceutical companies, the Food and Drug Administration, National Institutes of Health, patient-focused non-profits and professional societies with the goals of developing initiatives to accelerate lupus drug development in a precompetitive setting, and ensuring that perspectives of people with lived experience of lupus are included into the drug development process. Patient-reported outcome (PRO) measures are a top area of focus for the Lupus ABC. To support future work in the area of PROs, a public meeting was held on 16–17 October 2024 with the objectives of (1) assessing the current state of PROs used in lupus clinical trials, (2) developing a roadmap to advance the use of PROs in lupus clinical trials and (3) identifying and setting priorities for efforts to be pursued by a Lupus ABC PRO Working Group. After a series of presentations, small groups addressed what PRO domains to measure, the questionnaire burden for trial participants, how PROs should be selected for trials and what efforts are needed to advance use of PROs in lupus clinical trials.Meeting participants concluded that although PROs are being collected in most lupus clinical trials, they may be underused as primary or secondary/exploratory endpoints. A strong desire to change the focus in trials from disease activity and signs to include PROs, as a way of highlighting patients’ voices, was noted. The group concluded that the specific steps needed are to identify PRO measures appropriate for the target populations of interest, incorporate PROs into endpoints for regulatory decision-making, ensure PRO data are publicly available and accessible to researchers and involve people living with lupus in selection of PRO domains, measures and trial design. For these actions, collaborations among industry, researchers, regulators, payors and patients are needed.

PV140 / #234Poster Topic:AS17 - MiscellaneousBackground/PurposeLupus is a systemic autoimmune disease characterized by complicated etiopathogenesis, heterogeneous clinical manifestations and a range of immunological abnormalities that affects millions of people worldwide. At present, therapy for lupus is mostly empiric and involves largely nonspecific anti-inflammatory and immunosuppressive agents. The Lupus Research Alliance (LRA), the world’s largest private funder of lupus research, has invested over US$270M in more than 600 individual research programs since 1999. Recently, the LRA successfully completed its previous 5-year research strategic plan, resulting in the establishment of robust research governing bodies, a tripling of the number of grant programs, and the establishment of critical translational and clinical research infrastructure to include a Public-Private Partnership with the FDA, Lupus ABC, a lupus registry, biorepository, and data exchange platform, Lupus Nexus, and has significantly increased the number of clinical studies the organization supports through the clinical affiliate, Lupus Therapeutics. To build upon this success, the LRA set out to create a new 5-year Research Strategic Plan as part of an organization-wide goal to directly impact individuals living with lupus by enabling research that advances safer and accessible treatment options.MethodsMore than 30 interviews with lupus patients and US and international lupus/related fields researchers were conducted, as well as a survey of the research and clinical landscape and a detailed analysis of the clinical trial landscape usingclinicaltrials.govand other sources. Additionally, an in-depth evaluation of LRA’s research portfolio and broader funding landscape analyses were performed to inform the evolution of LRA’s grant programs and ensure they continue to synergize with external research funding. A planning committee of academic and industry experts, and patients advised the development of the strategy by analyzing the data and engaging in discussions about emerging gaps and opportunities.ResultsWith recent developments in understanding lupus pathogenesis and heterogeneity, impactful technological advancements, and the emergence of engineered cell therapy as a novel treatment paradigm for lupus, the LRA is uniquely positioned to address critical gaps and opportunities to accelerate precision medicine for people living with lupus. The clinical trial landscape analysis highlighted that while the number of lupus clinical trials has increased, there is a high failure rate for primary outcomes, demonstrating the need for better trial design and population characterization, as well as mechanistic understanding of therapies entering trials and for diagnostics/prognostics to stratify patients and quantify outcomes. Importantly, the analysis showed that the LRA clinical affiliate, Lupus Therapeutics, participated in ~25-30% of all lupus trials. The new strategic plan was built on its unique capabilities and the LRA’s robust infrastructure and research programs and includesthree5-year research goals, each with corresponding objectives and intended patient impact: 1) Improve understanding of patient heterogeneity as a basis for individual therapeutic choices; 2) Increase the number of molecular stratification, prognostic/diagnostic tools, and biomarkers; 3) Accelerate development of treatments that reprogram the immune system. The new Plan calls for the LRA to become an effective driver of clinical development, for substantive changes to LRA’s funding portfolio to focus on the new priorities, and the establishment of new partnerships and patient-centric research initiatives.ConclusionsBy implementing this plan, the LRA envisions a future where patients are promptly diagnosed, clinically and molecularly profiled, and offered safer and more effective personalized treatments and possible cures.

To develop evidenced recommendations to allow the global systemic lupus erythematosus (SLE) advocacy community to effectively advocate for change and improve care for patients with SLE. A Global Working Group consisting of representatives from patient advocacy groups, professional organisations, and the SLE healthcare community defined key areas of unmet need in patients with SLE. Targeted principles for each area of unmet need guided a literature review to investigate the current global situation, pre-existing advocacy efforts, and best practices from other therapy areas. The results from this literature review allowed the Working Group to develop recommendations to improve care for patients with SLE. Barriers faced by patients with SLE can stem from poor recognition of symptoms, which leads to delays in accurate diagnosis, cycling between different healthcare professionals, and inconsistencies in receiving optimal care. Patient access to approved treatments for SLE also remains limited. This Patient Charter, co-developed with a group of internationally recognised clinicians and patient advocates, sets out the minimum standard of care people living with SLE should expect and receive under 4 principles with distinct recommendations for change. The intention is to improve health outcomes by uniting and empowering patients, caregivers, patient groups, and healthcare professionals to advocate for reforms to healthcare practices for people living with SLE.

To assess outcomes related to Lupus Therapeutics' Patient Advocates for Lupus Studies (LT-PALS), a peer-to-peer lupus clinical trial (LCT) education program designed to improve representation of diverse groups in LCTs. Patients with lupus and clinical trial participation experience were trained as peer educators (PALs) providing trial-agnostic education to trial-naive patients with lupus. We used a two-arm, randomized pretest/posttest study design to evaluate outcomes related to LCT participation: knowledge, attitudes, self-efficacy, and intentions to participate in an LCT. Five academic medical centers piloted the program. The intervention group (IG) individually received peer-to-peer education sessions with trained PALs, primarily via telephone; the control group (CG) received a 3-week waiting period. We conducted within/between-group t-tests and multiple linear regressions with posttest scores as dependent variables and participation in LT-PALS as the exposure variable. The sample (n=136) included 64 IG and 72 CG participants, with 67.7% identifying as Black. At posttest, IG participants had higher knowledge (P < 0.01) scores than the CG participants. Regression models controlling for participant characteristics showed higher IG posttest scores for knowledge (P < 0.001) and intentions (P < 0.05). From pretest to 3-month follow-up, IG self-efficacy scores increased (P < 0.01). About half (46.9%) of IG participants reported engagement with an LCT at 1-year follow-up. Black and Hispanic participants rated higher overall program satisfaction compared with White (P < 0.01) and non-Hispanic (P < 0.05) participants. Findings demonstrated feasibility of LT-PALS and showed promise in increasing engagement from groups underrepresented in LCTs.