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

Area of Science:

• Nephrology
• Rheumatology
• Clinical Pharmacology

Background:

• Lupus nephritis (LN) management relies on evidence from randomized clinical trials (RCTs).
• Assessing the generalizability and identifying evidence gaps in current LN pharmacological therapy research is crucial.

Purpose of the Study:

• To conduct a scoping review of RCTs on pharmacological therapies for initial lupus nephritis management.
• To analyze study design, participant populations, and outcome definitions to evaluate generalizability and identify research gaps.

Main Methods:

• Systematic evaluation of RCTs for initial LN therapy (2000-2024).
• Extracted data on study design, participant criteria, outcomes, and clinical characteristics.
• Classified interventions into guideline-recommended (e.g., cyclophosphamide, mycophenolic acid analogues) and other regimens.
• Assessed study robustness using the Fragility Index (FI).

Main Results:

• 124 intervention arms from 61 RCTs involving 7058 participants were analyzed.
• Guideline-recommended therapies (MPAA, NIH-CYC, triple-drug) comprised 63.7% of interventions.
• Multinational studies were common for triple-drug therapies but rare for NIH-CYC and tacrolimus.
• Limited follow-up (≥24 months) in most RCTs (14.8%).
• Under-representation of Black/other races and specific global regions was noted.
• Serious adverse events and patient-reported outcomes were infrequently reported.
• Outcome definitions and assessment intervals for response were variable.
• Low robustness (FI 1-3) was observed for RCTs of double-drug guideline-recommended therapies.

Conclusions:

• There is a need for broader inclusion of under-represented populations in LN clinical trials.
• Homogenization of study design and outcome reporting is essential for improved generalizability.
• Further research is warranted to explore novel interventions and treatment comparisons in areas with limited evidence.