Comprehensive Review of Lupus Nephritis Randomized Controlled Trials Highlights Evidence Gaps and Under-represented Populations
Introduction
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that can lead to kidney failure. Recent updates to LN management guidelines recommend a combination of glucocorticoids with one of four immunosuppressive regimens. However, the evidence supporting these recommendations comes from RCTs with highly variable settings, raising concerns about their external validity.
Methods
This scoping review followed the PRISMA-ScR guidelines, evaluating RCTs published between 2000 and 2024 that assessed pharmacological interventions for initial LN therapy. The review focused on study design, selected populations, and outcome definitions to assess the generalizability of results and identify evidence gaps.
Results
The review included 124 intervention arms within 61 RCTs, involving 7058 participants. Key findings include:
- Under-representation: Black, Hispanic, and other races, as well as participants from the Middle East, North Africa, and sub-Saharan Africa, were significantly under-represented.
- Study Design Variability: Only 9 RCTs had follow-up periods of 24 months or longer, and there was significant variability in the definition of treatment response.
- Safety Reporting: Only 29 RCTs reported serious adverse events, and few included patient-reported outcomes.
Conclusions
The review highlights the need for broader inclusion of under-represented populations in LN RCTs and calls for the homogenization of study designs. It also suggests evaluating unexplored treatment comparisons and conducting research on newer interventions in clinical settings where evidence is currently lacking.
Implications for Research, Practice, or Policy
This study provides a rationale for future research to address the identified gaps, ensuring that LN treatment recommendations are applicable to a broader patient population. It emphasizes the importance of standardizing outcome definitions and including patient-reported outcomes in clinical trials to better assess the efficacy and safety of LN treatments.