Teodora P. Staeva

Despite advances in lupus biomarker research, clinical translation has remained limited, leading to delayed diagnosis, imprecise disease monitoring and trial-and-error treatment approaches. This roadmap, developed by the Lupus Research Alliance’s Biomarker Roadmap Committee with input from patients and experts, identifies key priorities for translating research into clinical benefit. Three major clinical unmet needs are highlighted: improving diagnostic accuracy of SLE and neuropsychiatric SLE, developing sensitive longitudinal markers for disease activity (including LN), and predicting disease progression and treatment response. We review the current state of biomarker development across these domains and highlight barriers that hinder clinical validation, assay development and clinical adoption. We propose focused strategies to overcome these challenges, emphasizing analytically validated assays, diverse longitudinal cohorts, alignment with meaningful clinical outcomes and consortium-based efforts. The roadmap outlines a path to transform lupus diagnosis, monitoring and precision medicine, enabling research advances to improve patient care.

Introduction: SLE remains a disease of high unmet medical need. Protean manifestations and the lack of clear understanding of aetiology, pathogenesis and disease subgroups make it difficult to develop and employ targeted therapeutic approaches. Community-wide access to a longitudinal, highly curated patient dataset with linked biospecimens and cellular/molecular data is critical to enable advances and is now provided by Lupus Nexus (LNx). In this study, we describe the development of this unique resource with exemplary patient engagement. Methods and analysis: LNx, developed with guidance from over 100 partners, includes a prospective, longitudinal observational study, the Lupus Landmark Study (LLS), that will enrol up to 3500 adults living with lupus into four cohorts and will follow them over 5 years. The registry data comprises medical information, clinician-reported and patient-reported outcomes while the biorepository includes whole blood, urine, saliva, stool and tissue which are available to the research community for a broad range of analyses. Importantly, since all raw data from the biospecimen analyses will be deposited in LNx, it will amass a deep and comprehensive dataset over time. As of 25 March 2026, there are 705 enrolled participants (13.3% new onset, 27.4% extrarenal flare, 23.3% active lupus nephritis and 35% prevalent cases, with 37.6% black, 38% white and 12.6% Asian/Pacific Islander patients). Over 15 400 unique samples have been collected and specific analyses are underway. All data and samples from LNx are available via its Data Repository Exchange and Analytics platforM ( DREAM ). Importantly, a dedicated patient portal within DREAM enables participants to view their study data, connect with others and learn about the research emerging from projects using LNx. Trial registration number: NCT05934149 .

Cutaneous lupus erythematosus (CLE) is an autoimmune skin condition associated with a considerable treatment burden and diminished quality of life. The absence of a consensus outcome measure to evaluate therapeutic response has posed a challenge to CLE drug development. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in response to this need, incorporating morphological components including erythema, scale, dyspigmentation and scarring, to reflect disease activity and damage. Numerous studies have demonstrated the utility of CLASI in capturing relevant aspects of disease from clinician- and patient-based perspectives; however, no regulatory precedent for use of clinical trial data employing CLASI to evaluate treatment response in CLE exists. Thus, the Lupus Accelerating Breakthroughs Consortium commissioned a working group of members from industry, academia, the US Food and Drug Administration (FDA) and CLE patient advocates to address the potential knowledge gaps with CLASI through evidence-based research. Upon reviewing and submitting these data to the FDA, the working group reached alignment that CLASI is a suitable outcome measure for CLE clinical trials, enabling a clearer regulatory path for clinical drug development. The group recognizes the need for additional information to assess what degree of change in CLASI captures clinically meaningful improvement.