Review
Pharmacology & Pharmacy
Donald C. Moore, Justin R. Arnall
Summary: Sutimlimab, a first-in-class complement C1s inhibitor, is an effective therapeutic option for the management of CAD-associated hemolysis. It rapidly improves hemoglobin levels and symptoms. However, safety concerns include infusion-related reactions and the risk of infections.
ANNALS OF PHARMACOTHERAPY
(2023)
Article
Immunology
Ken T. Simmons, Joanne Chan, Sami Hussain, Eileen L. Rose, Kate Markham, Tony S. Byun, Sandip Panicker, Graham C. Parry, Michael Storek
Summary: The objective of this study was to characterize the complement-inhibiting activity of SAR445088, a monoclonal antibody specific for the active form of C1s. The results demonstrated that SAR445088 is a potent, selective inhibitor of the classical pathway of complement. In addition, it was found that SAR445088 has potential therapeutic effects in treating classical pathway-driven diseases.
CLINICAL IMMUNOLOGY
(2023)
Article
Hematology
Catherine M. Broome
Summary: Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia characterized by the presence of IgM antibodies that recognize the 'I' antigen on red blood cell membranes. Sutimlimab, a drug that inhibits classical complement pathway activation, has shown rapid and sustained effects on hemoglobin levels, hemolytic markers, and fatigue in CAD patients.
EXPERT REVIEW OF HEMATOLOGY
(2023)
Article
Immunology
Sigbjorn Berentsen, Wilma Barcellini, Shirley D'Sa, Bernd Jilma
Summary: Sutimlimab, the first complement inhibitor to be extensively studied in cold agglutinin disease, has shown high response rates with low toxicity. The drug appears highly useful in severely anemic patients and in those in whom chemoimmunotherapy is contraindicated or has failed. The choice of therapy in cold agglutinin disease should be individualized.
Article
Hematology
Alexander Roeth, Sigbjorn Berentsen, Wilma Barcellini, Shirley D'Sa, Bernd Jilma, Marc Michel, Ilene C. Weitz, Masaki Yamaguchi, Jun-ichi Nishimura, Josephine M. Vos, Michael Storek, Nancy Wong, Parija Patel, Xiaoyu Jiang, Deepthi S. Vagge, Marek Wardecki, Frank Shafer, Michelle Lee, Catherine M. Broome
Summary: Sutimlimab, a humanized monoclonal antibody, shows potential as an important advancement in the treatment of cold agglutinin disease (CAD) by selectively inhibiting the classical complement pathway and rapidly halting hemolysis.
Article
Pharmacology & Pharmacy
Thomas Frank, Andreas Kovar, Ashley Strougo, Chandravathi Vage, Nathan Teuscher, Nancy Wong
Summary: Sutimlimab, a humanized monoclonal antibody, is approved for the treatment of hemolytic anemia in adults with cold agglutinin disease. This study aimed to support dose selection for phase 3 studies and establish the relationship between sutimlimab exposure and clinical outcome. After analysis, a pharmacokinetic-pharmacodynamic model was developed to relate the Hb-elevating effect of sutimlimab to plasma exposure. Simulations showed that the approved dosing provided adequate sutimlimab exposure to maximize the effects on Hb, bilirubin, and total complement component C4 levels.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Hematology
Alexander Roeth, Wilma Barcellini, Shirley D'Sa, Yoshitaka Miyakawa, Catherine M. Broome, Marc Michel, David J. Kuter, Bernd Jilma, Tor Henrik Anderson Tvedt, Ilene C. Weitz, Ronnie Yoo, Deepthi Jayawardene, Deepthi S. Vagge, Katarina Kralova, Frank Shafer, Marek Wardecki, Michelle Lee, Sigbjorn Berentsen
Summary: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. Sutimlimab showed sustained improvement in hemolysis, anemia, and quality of life during a 2-year treatment period. However, disease activity reoccurred after cessation of sutimlimab treatment.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Alexander Roeth, Wilma Barcellini, Tor Henrik Anderson Tvedt, Yoshitaka Miyakawa, David J. Kuter, Jun Su, Xiaoyu Jiang, William Hobbs, Jaime Morales Arias, Frank Shafer, Ilene C. Weitz
Summary: This study evaluated the efficacy and safety of Sutimlimab in patients with cold agglutinin disease (CAD) through patient-reported outcomes. The results demonstrate that Sutimlimab treatment can significantly improve fatigue symptoms and quality of life in CAD patients.
ANNALS OF HEMATOLOGY
(2022)
Review
Hematology
Sigbjorn Berentsen
Summary: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia and a bone marrow clonal lymphoproliferative disorder. Hemolysis in CAD is complement-dependent and mediated by the classical activation pathway. Sutimlimab, a humanized monoclonal IgG4 antibody, is the most extensively investigated complement inhibitor for the treatment of CAD. It has been proven to be highly efficacious with low toxicity in clinical trials and is approved for CAD treatment in multiple countries.
Review
Hematology
Sigbjorn Berentsen
Summary: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by complement-dependent hemolysis. Sutimlimab, a humanized monoclonal IgG4 antibody that inhibits complement protein C1s, has been proven to be a highly effective and low-toxic treatment for CAD. However, it does not improve cold-induced circulatory symptoms. Individual assessment and consideration for inclusion in clinical trials should guide the choice of therapy for CAD.
Article
Hematology
Alexander Roeth, Catherine M. Broome, Wilma Barcellini, Bernd Jilma, Quentin A. Hill, David Cella, Tor Henrik Anderson Tvedt, Masaki Yamaguchi, Michelle Lee, Frank Shafer, Marek Wardecki, Xiaoyu Jiang, Parija Patel, Florence Joly, Ilene C. Weitz
Summary: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia that leads to fatigue and reduced quality of life. In the Phase 3 CADENZA trial, treatment with the complement inhibitor sutimlimab showed rapid improvement in hemolysis, increased hemoglobin levels, and alleviated fatigue in CAD patients. Patient-reported outcomes also demonstrated significant benefits from sutimlimab treatment.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Ram Gelman, Fadi Kharouf, Yuval Ishay, Alexander Gural
Summary: Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are two distinct immune-mediated hematologic disorders, and while no clear association exists between them, complement activation is known to occur in both cases.
ACTA HAEMATOLOGICA
(2021)
Review
Biotechnology & Applied Microbiology
Georg Gelbenegger, Sigbjorn Berentsen, Bernd Jilma
Summary: Cold agglutinin disease (CAD) is a difficult-to-treat autoimmune hemolytic anemia and B cell lymphoproliferative disorder. This review summarizes clinical and experimental antibody-based treatments for CAD and discusses potential future treatments for CAD.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Review
Hematology
Sigbjorn Berentsen, Geir E. Tjonnfjord
Summary: Cold agglutinin disease can be treated through targeted therapies focusing on clonal B-cell lymphoproliferation and complement-mediated hemolysis. Bendamustine plus rituximab combination and sutimlimab have shown success in treating the disease. Bendamustine-rituximab is effective but slow-acting, while sutimlimab is highly efficacious and acts rapidly with low toxicity.
TRANSFUSION MEDICINE REVIEWS
(2022)
Article
Education, Scientific Disciplines
Jenny McDade Despotovic, Taylor Olmsted Kim
Summary: Cold reactive autoimmune hemolytic anemia is a rare condition caused by the production of autoantibodies against endogenous red blood cells. Treatment mainly focuses on reducing antibody production to manage the disease.
HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM
(2022)
