Alina Volkova1, Valentina Batorova3, Maria Ovseneva5, Kirill Peskov1
1M&S Decisions LLC, 2Marchuk Institute of Numerical Mathematics of the Russian Academy of Sciences, 3Sirius University of Science and Technology, 4BIOCAD, 5Research Center of Model-Informed Drug Development, I.M. Sechenov First Moscow State Medical University
Introduction: The development of targeted therapies for autoimmune diseases has enhanced treatment efficacy while reducing the need for general immunosuppressive drugs. However, the development of such drugs is complicated due to the high heterogeneity of the mechanisms underlying autoimmune diseases. For systemic lupus erythematosus (SLE), only two targeted therapies—anifrolumab and belimumab—have been approved. The development and comparison of the effectiveness of SLE therapies is further complicated by using various composite indices to assess patient status. This study aims to evaluate the efficacy of targeted therapies for SLE and its major manifestations (lupus nephritis, cutaneous lupus) by developing a meta-regression model of disease status assessment indexes, accounting for drug dose, dosing regimen, and the demographic and clinical characteristics of the patient population. Methods: A systematic review of randomized controlled clinical trials on targeted therapies for SLE, lupus nephritis, and cutaneous lupus erythematosus was conducted following the international PRISMA guideline [1]. Data on the time profiles of clinical endpoints, demographic and clinical characteristics, and dosing regimens were digitized and collected into a database. Quantitative assessment of the average treatment effect at the final observation point was performed for the identified studies using a random effects meta-analytic model. Exploratory data analysis and meta-analysis were conducted in R Statistics. Results: The systematic literature review identified 43 clinical trials (129 arms, 17,672 patients), including 4 trials focused on lupus nephritis and 1 on cutaneous lupus. In total, data were obtained for 22 different therapies and 26 clinical endpoints, with the most frequently encountered being SLE response index (SRI)-4 (in 30 trials), British Isles Lupus Assessment Group-based Combined Lupus Assessment (BICLA) (in 16 trials), SRI-6 (in 15 trials), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (in 11 trials), Physician’s Global Assessment (PGA) (in 11 trials), and SRI-5 (in 10 trials). Anifrolumab showed improvements in all key outcomes except for PGA and complete renal response (CRR). The efficacy of belimumab compared to the control group was confirmed across clinical endpoints, including SRI-4/5/6/7 and CRR, with belimumab demonstrating superior efficacy over anifrolumab in treating lupus nephritis in terms of CRR. Among drugs in clinical development, significant clinical improvements were observed with obinutuzumab (based on CRR), dapilolizumab and epratuzumab (BICLA), deucravacitinib (BICLA, SRI-4), litifilimab, iberdomide, and atacicept (SRI-4), ustekinumab (SRI-5/6, SLEDAI-2K), tabalumab, telitacicept, and sifalimumab (SRI-4/5/6/7). Conclusions: Thus, this meta-analysis highlights the importance of selecting clinical endpoints to confirm the efficacy of targeted therapies in SLE. Future work will involve conducting model-based meta-regression analysis incorporating dose-dependent effects and synthesizing data across multiple clinical endpoints. This study was supported by the Russian Science Foundation grant 23-71-10051.
[1] Page MJ et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021 Mar 29;372:n160. doi: 10.1136/bmj.n160
Reference: PAGE 33 (2025) Abstr 11735 [www.page-meeting.org/?abstract=11735]
Poster: Clinical Applications