Pharmacological interventions in IgA nephropathy: protocol for a living systematic review and network meta-analysis

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INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerular disease in adults. In recent years, there have been many significant advances in treating IgAN, with multiple successful clinical trials. We aim to determine the comparative effectiveness of available pharmaceutical interventions for treating IgAN. METHODS AND ANALYSIS: A systematic review and network meta-analysis (NMA) will be conducted to assess the comparative effectiveness and safety of various pharmacological interventions available for adults with IgAN. All randomised controlled trials (RCTs) or quasi-RCTs which have evaluated pharmacological interventions in IgAN will be included. Both published studies and those available only as conference abstracts will be considered. A systematic literature search will be conducted using Ovid MEDLINE(R) ALL, Embase, Cochrane Kidney and Transplant Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry and ClinicalTrials.gov from inception to the present. Data extraction and risk of bias assessments using Cochrane Risk of Bias 2.0 will be performed by two reviewers independently, and differences resolved through consensus. Primary outcomes assessed will be kidney function and death, and secondary outcomes will be cardiovascular disease, other adverse events and patient-reported outcomes. The NMA will be conducted using a Bayesian NMA with Markov Chain Monte Carlo simulation methods in a random-effects model framework. The certainty of the evidence will be assessed using the Confidence In Network Meta-Analysis(CINeMA) tool to manage the Grading of Recommendations, Assessment, Development and Evaluations(GRADE) assessment.After initial publication, the NMA will be maintained as a 'living model' in an open-source web application. A living 'auto-search' will be created and updated monthly to identify new evidence as it becomes available for synthesis. If new relevant studies are identified, after risk of bias assessment, data will be extracted and incorporated into the model, and findings will be updated accordingly. This will potentially provide a continuous overview of the rapidly changing therapeutic landscape of IgAN in the coming years and in future may help us to design 'living guidelines' for the management of IgAN. ETHICS AND DISSEMINATION: The findings will be published in international peer-reviewed journals. No results are being presented in this protocol. PROSPERO REGISTRATION NUMBER: CRD420251050367.

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