Meredith Jackson

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.

Early data have shown the potential of chimeric antigen receptor (CAR) T-cell therapies to expand the therapeutic landscape in systemic lupus erythematosus (SLE). While many CAR T-cell therapy learnings can be drawn from the experience of this modality in oncology, key questions remain regarding clinical development considerations unique to lupus. To assess and discuss these issues, the Lupus Accelerating Breakthroughs Consortium, a public–private partnership, convened a multi-partner working group to collect the diverse perspectives of academics/clinicians (including rheumatologists and oncologists), industry representatives (including SLE as well as CAR T-cell clinical development experts), regulators and people living with lupus on this potentially ground-breaking therapy. The working group considered the risk/benefit considerations for eligibility criteria in lupus, early-phase dosing and dose-limiting toxicity challenges, incorporation of comparator arms in late-phase registrational trial design, SLE-specific issues in conditioning therapy and immune monitoring and the limitations of SLE pre-clinical models for studying cell therapies. The key future ‘calls to action’ for the field include the need for well-defined severity/refractoriness-based eligibility criteria, the need for long-term monitoring infrastructure and the need for educational and logistical support for rheumatologists and patients.