دورية أكاديمية
Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study.
| العنوان: | Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study. |
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| المؤلفون: | Laber DA; Department of Satellite and Community Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Patel PC; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Logothetis CN; Divisions of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri, USA., Patel AK; Department of Satellite and Community Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Jaglal M; Department of Satellite and Community Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Haider M; Department of Satellite and Community Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Visweshwar N; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Rajasekaran-Rathnakumar G; Department of Satellite and Community Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Eatrides J; Department of Satellite and Community Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA. |
| المصدر: | European journal of haematology [Eur J Haematol] 2024 Mar; Vol. 112 (3), pp. 450-457. Date of Electronic Publication: 2023 Nov 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Country of Publication: England NLM ID: 8703985 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0609 (Electronic) Linking ISSN: 09024441 NLM ISO Abbreviation: Eur J Haematol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2005->: Oxford : Blackwell Original Publication: Copenhagen : Munksgaard, c1987- |
| مواضيع طبية MeSH: | Thrombotic Microangiopathies*/diagnosis , Thrombotic Microangiopathies*/drug therapy , Thrombotic Microangiopathies*/etiology , Atypical Hemolytic Uremic Syndrome*/drug therapy , Atypical Hemolytic Uremic Syndrome*/genetics , Complement Inactivator Proteins*, Humans ; Middle Aged ; Retrospective Studies ; Complement System Proteins |
| مستخلص: | Background: Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy. Methods: We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. Results: We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 10 9 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up. Conclusions: Our study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our study adds practical, real-world experience to the literature, but future research remains imperative. (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
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| معلومات مُعتمدة: | P30 CA076292 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: atypical hemolytic uremic syndrome; eculizumab; ravulizumab; thrombotic microangiopathy |
| المشرفين على المادة: | 0 (anticomplement) 9007-36-7 (Complement System Proteins) 0 (Complement Inactivator Proteins) |
| تواريخ الأحداث: | Date Created: 20231120 Date Completed: 20240219 Latest Revision: 20240829 |
| رمز التحديث: | 20240830 |
| مُعرف محوري في PubMed: | PMC11351077 |
| DOI: | 10.1111/ejh.14136 |
| PMID: | 37984551 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1600-0609 |
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| DOI: | 10.1111/ejh.14136 |