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Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program.

ABSTRACT: Cold agglutinin disease (CAD) causes predominantly extravascular hemolysis and anemia via complement activation. Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s. We aimed to evaluate the safety and efficacy of long-term maintenance treatment with sutimlimab in patients with CAD. Seven CAD patients treated with sutimlimab as part of a phase 1B study were transitioned to a named patient program. After a loading dose, patients received biweekly (once every 2 weeks) infusions of sutimlimab at various doses. When a patient's laboratory data showed signs of breakthrough hemolysis, the dose of sutimlimab was increased. Three patients started with a dose of 45 mg/kg, another 3 with 60 mg/kg, and 1 with a fixed dose of 5.5 g every other week. All CAD patients responded to re-treatment, and sutimlimab increased hemoglobin from a median initial level of 7.7 g/dL to a median peak of 12.5 g/dL (P = .016). Patients maintained near normal hemoglobin levels except for a few breakthrough events that were related to underdosing and which resolved after the appropriate dose increase. Four of the patients included were eventually treated with a biweekly 5.5 g fixed-dose regimen of sutimlimab. None of them had any breakthrough hemolysis. All patients remained transfusion free while receiving sutimlimab. There were no treatment-related serious adverse events. Overlapping treatment with erythropoietin, rituximab, or ibrutinib in individual patients was safe and did not cause untoward drug interactions. Long-term maintenance treatment with sutimlimab was safe, effectively inhibited hemolysis, and significantly increased hemoglobin levels in re-exposed, previously transfusion-dependent CAD patients.

SUBMITTER: Gelbenegger G

PROVIDER: S-EPMC7094024 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program.

Gelbenegger Georg G Schoergenhofer Christian C Derhaschnig Ulla U Buchtele Nina N Sillaber Christian C Fillitz Michael M Schenk Thomas M TM D'Sa Shirley S Cartwright Ronwyn R Gilbert James C JC Jilma Bernd B Jaeger Ulrich U

Blood advances 20200301 6

Cold agglutinin disease (CAD) causes predominantly extravascular hemolysis and anemia via complement activation. Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s. We aimed to evaluate the safety and efficacy of long-term maintenance treatment with sutimlimab in patients with CAD. Seven CAD patients treated with sutimlimab as part of a phase 1B study were transitioned to a named patient program. After a loading dose, patients received bi ...[more]

PMID: 32176765

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Project description:BackgroundScholarly Concentrations programs in U.S. medical schools aim to instill passion for critical thinking and promote careers in academic medicine. The rise of these programs has seen variable goals, structure, and outcomes. Transformation of these programs internationally is in its infancy.MethodsWe describe implementation of the Johns Hopkins School of Medicine Scholarly Concentrations program, offering Basic Science, Clinical Science, Medical Ethics/Healing Arts, History of Medicine, and Public Health/Community Service, at Bezmiâlem Vakif University in Istanbul, Turkey. Over six modules in the preclinical years, students develop a faculty-mentored experience which encourages the acquisition of attitudes and skills for self-directed, lifelong learning and scholarship. This culminates in abstract and project presentation. We report program characteristics (context and logistics) and outcomes (student engagement and experiences).ResultsThe Scholarly Concentrations program at Bezmiâlem began in 2014, with nearly two completed cohorts of students. In comparison to Johns Hopkins, students at Bezmiâlem begin at an earlier age (thus do not have as much prior research experience) and are subsequently evaluated for residency in terms of test scores rather than scholarship and publications, but have a similar level of intellectual curiosity and desire to take ownership of their project. Eighty-two percent of Bezmiâlem students stated the project they pursued was either their own idea or was an idea they formed after meeting with their mentor. Students at Bezmialem were more likely to choose Clinical Science projects (p = 0.009). Only 5% of Bezmiâlem students in end-of-course survey felt dissatisfied with the level of ownership they experienced with their project, a frequency similar to that seen by Johns Hopkins students (2%).ConclusionsScholarly Concentrations programs play an important role in U.S. medical schools, and these programs can be successfully implemented internationally. The Scholarly Concentrations program at Johns Hopkins has been transformed to a program at Bezmiâlem in Istanbul, the first program outside North America or the European Union. When designing these programs, one must consider the context, logistics, student engagement, and outcomes. While long-term outcomes are needed, this can serve as a model for implementation elsewhere.

Dataset Information

Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program.

Publications

Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program.

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