Details

Autor(en) / Beteiligte

• Inês, Luís Sousa

Titel

I25 Which is the optimal primary endpoint for lupus clinical trials?

Ist Teil von

• Lupus science & medicine, 2024-03, Vol.11 (Suppl 1), p.A4-A4

Ort / Verlag

London: Lupus Foundation of America

Erscheinungsjahr

2024

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Systemic lupus erythematosus (SLE) causes a wide range of immune-mediated manifestations in most organ-systems. The presentation of SLE is highly heterogeneous in terms of affected systems, type, and severity of disease features, both between- and within- patients over disease course (SLE disease activity). This complexity hinders the development of Clinical Outcome Assessments (COA) for SLE. Lupus clinical trials evaluate the efficacy of drugs that directly reduce or control disease activity through a mode-of-action that modifies immune processes. Clinical expertise is required to identify and quantify appropriately the treatment-related changes in SLE disease activity. Therefore, a Clinician-Reported Outcome Measure (ClinRO) is required as COA for primary assessment of efficacy in SLE clinical trials. Importantly, the primary endpoint in clinical trials should be patient-focused, that is, must be associated with meaningful impact in the main health aspects of importance to patients that are affected by SLE disease activity. Notably, there is an indirect association between how the patients fell and function and SLE disease activity. The primary endpoint for SLE clinical trials should be a precisely defined variable that is cumulatively able to: (1) capture a direct effect of the study drug in changing the SLE disease activity (with a ClinRO); (2) associate with a meaningful (indirect) impact in the patients’ main health aspects; (3) be statistically analised to address the research question of drug efficacy in the context of use.However, the primary endpoints currently used in SLE clinical trials have well recognized limitations that may have hampered the demonstration of efficacy of many promising drugs in SLE clinical trials. These endpoints are defined as a dichotomous response variable obtained through composite responder indexes, namely the SLE Responder Index (SRI) and the British Isles Lupus Assessment Group (BILAG) Composite Lupus Assessment (BICLA), both aggregating the BILAG, the SLE Disease Activity Index (SLEDAI), and the Physician Global Assessment (PGA). Therefore, novel COA are needed to provide an optimal primary endpoint for lupus clinical trials.The Treatment Response Measure for SLE (TRM-SLE) consortium is in the early phases of a project to develop and validate a novel COA for use in SLE clinical trials. The SLE Disease Activity Score (SLE-DAS) is a novel, easy to use (http://sle-das.eu/), validated ClinRO COA instrument, with high accuracy and sensitivity to change in SLE disease activity. New evidence with validation of thresholds in the context of clinical trials support the interpretation of the SLE-DAS scores into categories of SLE disease activity and treatment targets. These SLE-DAS score categories are concordant with a wide range of health aspects impacted by SLE assessed in Patient-Reported Outcomes (PRO). Importantly, differences in the SLE-DAS scores are sensitive to clinically meaningful and interpretable changes within patients over time in SLE disease activity and reflect an expected impact on patients’ health experiences. There is promising evidence that SLE-DAS is a fit-for-purpose COA and may provide an optimised primary endpoint for lupus clinical trials.