ArticleBlood advances2023
Complement gene variant effect on relapse of complement-mediated thrombotic microangiopathy after eculizumab cessation.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Efficacy of eculizumab discontinuation in atypical hemolytic uremic syndrome: a systematic review and meta-analysis.Blood advances · 2025Pooled it
- IPNA clinical practice recommendations for the management of aHUS and secondary TMA in children.Pediatric nephrology (Berlin, Germany) · 2026Article
- Complement Inhibition in the Clinic: Are We Doing Enough to Protect Patients From Infection?European journal of immunology · 2026Review
- A review of genetic and epigenetic biomarkers involved in the occurrence of atypical hemolytic uremic syndrome and its therapeutic strategies.Molecular biology reports · 2026Review
- Complement Dysregulation in Kidney Diseases: Mechanisms, Biomarkers, and Emerging Targeted Therapies.International journal of molecular sciences · 2026Review
- Article
- Case Report: Complement-mediated thrombotic microangiopathy masquerading as a pancreatic mass.Frontiers in medicine · 2026Article
- Excellent Response to Eculizumab in a Patient With Complement-Mediated Thrombotic Microangiopathy and a Novel Plasminogen Gene Variant.Case reports in hematology · 2026Article
- Complement-targeted therapies for C3 glomerulopathy and atypical hemolytic uremic syndrome: a time-limited rapid systematic review with narrative synthesis.Frontiers in medicine · 2026Review
- Which Factors Influence Decisions to Withdraw from Eculizumab: A Qualitative Study of Patients Diagnosed with aHUS.The patient · 2026Article
- Long-term outcome and management of complement-mediated thrombotic microangiopathy/aHUS.Hematology. American Society of Hematology. Education Program · 2025Review
- Effectiveness and safety of ravulizumab for Japanese patients with atypical hemolytic uremic syndrome switched from eculizumab: an analysis of a post-marketing surveillance.Clinical and experimental nephrology · 2025Article
- The Patient-Reported Outcomes Measurement Information System perspective of adults with long-standing atypical hemolytic uremic syndrome.Research and practice in thrombosis and haemostasis · 2025Article
- Clinical Outcomes and Treatment Strategies of Adult Transplant-Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High-Risk Criteria.American journal of hematology · 2025Article
- A Case of Atypical Hemolytic Uremic Syndrome With a Complement Factor I Mutation Triggered by a Femoral Neck Fracture.Nephrology (Carlton, Vic.) · 2025Article
- Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy.Transplantation · 2025Article
- Complement-mediated HUS revisited: evolving insights into pathophysiology, diagnosis, and treatment.Frontiers in immunology · 2025Review
- Atypical presentation of H1N1-induced thrombotic microangiopathy with CD46 gene mutation .Clinical nephrology. Case studies · 2025Article
- Atypical Hemolytic Uremic Syndrome Following Influenza B: A Case Report.HCA healthcare journal of medicine · 2024Article
- Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eculizumab is effective for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy had been suggested, discontinuation does not universally lead to relapse. Comprehensive data evaluating risk factors for recurrence following discontinuation are limited. Our aim was to systematically review available literature assessing the role of complement genetic variants in this setting. Reports on CM-TMA and eculizumab withdrawal published before 1 January 2021, were included. Key reasons for patient exclusion were no follow-up after drug withdrawal and patients lacking complement genetic testing. Two-hundred eighty patients from 40 publications were included. Median age was 28 years, and 25 patients had a known history of renal transplant. Complement genetic variants were identified in 60%, most commonly in CFH (n = 59) and MCP/CD46 (n = 38). Of patients with a complement gene variant, 51.3% had ≥1 likely pathogenic/pathogenic variant whereas the remaining had variants of uncertain significance (VUS). Overall relapse rate after therapy discontinuation was 29.6%. Relapse rate was highest among patients with CFH variants and MCP/CD46 variants in canonical splice regions. VUS (P < .001) and likely pathogenic/pathogenic variants (P < .001) were associated with increased relapse. Presence of a renal allograft (P = .009); decreasing age (P = .029); and detection of variants in CFH (P < .001), MCP/CD46 (P < .001), or C3 (P < .001) were all independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.