Lupus nephritis randomised controlled trials: evidence gaps and under-represented groups

• Published in: Lupus science & medicine Vol. 11; no. 2; p. e001331
• Main Authors: Nordmann-Gomes, Alberto, Cojuc-Konigsberg, Gabriel, Hernández-Andrade, Adriana, Navarro-Sánchez, Valeria, Ramírez-Sandoval, Juan Carlos, Rovin, Brad, Mejia-Vilet, Juan M
• Format: Journal Article
• Language: English
• Published: England Lupus Foundation of America 20.12.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Antibodies, Monoclonal, Humanized - therapeutic use; Calcineurin Inhibitors - therapeutic use; Clinical Trial; Clinical trials; Clinical Trials and Drug Discovery; Cyclophosphamide - therapeutic use; Drug Therapy, Combination; Evidence Gaps; Humans; Immunosuppressive Agents - therapeutic use; Intervention; Kidney diseases; Lupus; Lupus Nephritis; Lupus Nephritis - drug therapy; Lupus Nephritis - ethnology; Monoclonal antibodies; Mycophenolic Acid - therapeutic use; Original Research; Outcome Assessment, Health Care; Patient Reported Outcome Measures; Pediatrics; Randomized Controlled Trials as Topic; Rheumatology; Software; Systemic Lupus Erythematosus; United States > US; Systemic Lupus Erythematosus; Clinical Trial; Outcome Assessment, Health Care; Lupus Nephritis; Patient Reported Outcome Measures
• ISSN: 2053-8790; 2053-8790
• DOI: 10.1136/lupus-2024-001331

ObjectiveWe performed a scoping review of randomised clinical trials (RCTs) assessing pharmacological therapies for the initial management of lupus nephritis (LN), focusing on study design, included populations and outcome definitions, to assess the generalisability of their results and identify gaps in the evidence.MethodsRCTs evaluating pharmacological interventions for the initial therapy of LN published between 2000 and 2024 were evaluated. Extracted variables included study design, selection criteria, outcome definitions, populations recruited and clinical characteristics of participants. Each study arm was included as intervention and segregated into guideline-recommended regimens (cyclophosphamide (CYC), mycophenolic acid analogues (MPAAs), calcineurin inhibitors and belimumab) or other regimens. Data were analysed by descriptive statistics, and Fragility Index (FI) was estimated to assess robustness of studies.ResultsWe included 124 intervention arms within 61 RCT, involving 7058 participants. Seventy-nine arms (63.7%) corresponded to guideline-recommended therapies: 33 (26.6%) MPAA, 28 (22.6%) NIH-CYC and 7 (5.6%) triple-drug therapies. While 100% of triple-drug therapies RCT were multinational, only 7.1% of NIH-CYC and 0% of tacrolimus RCTs were conducted in more than one country. Only 9 (14.8%) had follow-up ≥24 months. Ten (16.4%) RCTs exclusively included participants with severe or refractory LN. Only 29 (47.5%) reported serious adverse events, and few described patient-reported outcomes. Black and other race participants were under-represented, as well as participants from Middle East, North Africa, and the sub-Saharan African region. Response was variably defined and assessed at different intervals. Robustness of RCTs evaluating double-drug guideline-recommended therapies were mostly low, with FI ranging from 1 to 3.ConclusionsConsidering new recommendations for the management of LN, we call for broader inclusion of under-represented populations and homogenisation of study design. This study provides the rationale for evaluating unexplored treatment comparisons and conducting research on newer interventions in clinical settings where evidence is currently lacking.