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oai:figshare.com:article/34053246 2026-10-02T04:32:51Z category_393 portal_316 item_type_3 month_year_10_2026

Table 1_Mapping the complement-targeted landscape in igA nephropathy: a systematic review with structured descriptive synthesis.docx Xin-Yu Li (1378743) Chang-Ying Zhong (25161090) Li-Nan Zhang (10841076) Yang Liu (4829) Foetal Development and Medicine complement inhibitors eGFR slope IgA nephropathy iptacopan proteinuria systematic review Background<p>Complement activation is a key driver of disease progression in IgA nephropathy (IgAN). While previous syntheses were limited to phase II evidence, pivotal phase III data—including the 24-month results of the APPLAUSE-IgAN trial—have recently emerged, necessitating an updated appraisal of complement-targeted therapies.</p>Methods<p>We conducted a systematic literature search in PubMed, Web of Science, Embase, and Cochrane up to April 24, 2026, for randomized controlled trials of complement inhibitors in adults with biopsy-proven IgA nephropathy. Due to marked mechanistic heterogeneity across agents targeting distinct complement nodes, a quantitative meta-analysis was not performed. Instead, we performed a structured descriptive synthesis, a predefined, domain-based comparative method, focusing on efficacy signals, safety profiles, and methodological disparities across trials.</p>Results<p>Four RCTs comprising 584 patients were included, representing factor B and C5 inhibition. The phase III iptacopan trial demonstrated robust proteinuria reduction, eGFR slope attenuation, and a decreased risk of kidney failure, but a higher serious-infection rate and confirmed pneumococcal infections highlighted that alternative-pathway inhibition attenuates rather than abolishes encapsulated-bacteria risk. Phase II trials of ravulizumab, iptacopan, and cemdisiran provided early efficacy signals with no encapsulated-bacterial events reported, though small size and short follow-up limit safety inference. All trials required prophylactic vaccination, and infection-risk obligations differed by target—terminal-pathway inhibitors carrying the strictest REMS requirements. Methodological heterogeneity—particularly regarding biopsy timing and fibrosis exclusion—emerged as a major barrier to cross-trial comparisons. Beyond these RCTs, a dynamic pipeline of ASO, siRNA, and small-molecule inhibitors continues to evolve.</p>Conclusion<p>Complement inhibitors show promising but heterogeneous signals across individual trials; however, marked differences in molecular targets, trial design, and eligibility preclude any inference of a uniform class effect. Infection risk mitigation differs by complement target—terminal-pathway inhibitors carry the highest encapsulated-bacterial burden and strictest regulatory constraints, whereas alternative-pathway inhibitors preserve partial vaccine-mediated defence but still require comprehensive vaccination and surveillance. These observations are hypothesis-generating and underscore the need for mechanism-specific phase III programmes with hard renal endpoints and individual patient-level meta-analyses to advance precision complement therapeutics in IgAN.</p>Systematic Review Registration<p>https://www.crd.york.ac.uk/PROSPERO/view/CRD420261385690</p> 2026-10-02T04:32:51Z Dataset Dataset 10.3389/fmed.2026.1933632.s001 https://figshare.com/articles/dataset/Table_1_Mapping_the_complement-targeted_landscape_in_igA_nephropathy_a_systematic_review_with_structured_descriptive_synthesis_docx/34053246 CC BY 4.0