Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery

Tvedt, Tor Henrik Anderson; Steien, Egil; Øvrebø, Bente; Haaverstad, Rune; Hobbs, William E.; Wardęcki, Marek; Tjønnfjord, Geir E.; Berentsen, Sigbjørn

doi:10.1002/ajh.26409

Cited by 10 publications

(9 citation statements)

References 11 publications

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“…Low temperature activates CAs and the classical complement cascade resulting in haemagglutination, lysis, increased blood viscosity, microvascular thrombosis and organ failure which can be fatal [22]. In both CAD and CAS, the IgM bound to antigens on the surface of RBCs causes complications involving two mechanisms [22,33]: (i) activation of the classical complement pathway (by binding of the C1 complex) and phagocytosis of erythrocytes opsonized with complement protein C3b results in predominantly extravascular RBC destruction and modest intravascular haemolysis, and (ii) agglutination of erythrocytes in acral body parts reduces microcirculation, causes vasospasm and acrocyanosis.…”

Section: Discussionmentioning

confidence: 99%

“…The most recent studies reported a rapid and sustained effect in patients with chronic CAHA treated with sutimlimab, a selective complement C1s inhibitor [62,[65][66][67][68]. In a patient with CAD, sutimlimab sufficiently blocked exacerbation of haemolysis during surgery and postoperatively [33]. The new drugs, unfortunately, are still expensive and not always available.…”

Section: Discussionmentioning

confidence: 99%

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Perioperative Challenges in Orthogeriatric Patients with Cold Agglutinin Haemolytic Anaemia: Case Report and Management Algorithm

2022

Ann Case Report

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Most published reports on cold agglutinin (CA) haemolytic anaemia (CAHA), a rare condition with significant perioperative management challenges, are from patients who have undergone cardiothoracic surgery with hypothermia. Here, we report a hip fracture patient with CAHA, and review the perioperative management. This is the second published case report regarding CAHA in an orthopaedic patient. An 86 year old female with a 4-year history of recurrent episodes of CAHA and multiple comorbidities (atrial fibrillation, hypertension, strokes, secondary epilepsy, vascular dementia, and type 2 diabetes mellitus complicated by diabetic retinopathy, osteoporosis, urinary incontinence, recurrent urinary tract infections, and multinodular goitre) was admitted because of a hip fracture. She was commenced on prednisolone a month prior the hip fracture. On admission, her haemoglobin was 69 g/L, lactate dehydrogenase 494 U/L, haptoglobin <0.1 g/L and the blood film showed red blood cell agglutination at room temperature, which dissociated at 37 o C. She required transfusion of 5 units of packed red blood cells during her admission. Her management included intensive temperature monitoring, use of body thermal blanket, warming intravenous and irrigation fluids and medications before administration. Surgery was performed under general anesthesia on the 4th admission day. She received unfractionated heparin for venous thromboembolism prophylaxis, antibiotics for wound infection prophylaxis, continued prednisolone, and started anti-osteoporotic medications. The patient was discharged to another hospital for rehabilitation on the 7th postoperative day. Perioperative examination and treatment of orthogeriatric patients with CAHA is challenging. The pathophysiology of CAHA is shortly revied and a management algorithm is presented.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Perioperative Challenges in Orthogeriatric Patients with Cold Agglutinin Haemolytic Anaemia: Case Report and Management Algorithm

2022

Ann Case Report

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“…Acute exacerbations of CAD are often triggered by cold exposure, febrile infection, major trauma, or major surgery ( 61 , 139 , 140 ). In these situations, it is reasonable to treat the cause of exacerbation when relevant, transfuse the patient if required and, in many cases, wait several weeks for improvement of the hemolytic anemia.…”

Section: How To Select Therapy In Cadmentioning

confidence: 99%

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

2023

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Autoimmune hemolytic anemia (AIHA) is defined by increased erythrocyte turnover mediated by autoimmune mechanisms. While corticosteroids remain first-line therapy in most cases of warm-antibody AIHA, cold agglutinin disease is treated by targeting the underlying clonal B-cell proliferation or the classical complement activation pathway. Several new established or investigational drugs and treatment regimens have appeared during the last 1-2 decades, resulting in an improvement of therapy options but also raising challenges on how to select the best treatment in individual patients. In severe warm-antibody AIHA, there is evidence for the upfront addition of rituximab to prednisolone in the first line. Novel agents targeting B-cells, extravascular hemolysis, or removing IgG will offer further options in the acute and relapsed/refractory settings. In cold agglutinin disease, the development of complement inhibitors and B-cell targeting agents makes it possible to individualize therapy, based on the disease profile and patient characteristics. For most AIHAs, the optimal treatment remains to be found, and there is still a need for more evidence-based therapies. Therefore, prospective clinical trials should be encouraged.

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“…Sutimlimab also prevented complement enhancement and exacerbation of CAD in a patient undergoing cardiac surgery described in a case report. 54 …”

Section: Efficacy Of Sutimlimab: Clinical Trialsmentioning

confidence: 99%

Sutimlimab for the Treatment of Cold Agglutinin Disease

Berentsen

2023

HemaSphere

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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. Patients also frequently suffer from fatigue and cold-induced circulatory symptoms. Although not all patients need treatment, the symptom burden has previously been underestimated. Effective therapies target the clonal lymphoproliferation or the complement activation. Sutimlimab, a humanized monoclonal IgG4 antibody that binds and inactivates complement protein C1s, is the most extensively investigated complement inhibitor for the treatment of CAD. This review addresses the preclinical studies of sutimlimab and the studies of pharmacokinetics and pharmacodynamics. We then describe and discuss the prospective clinical trials that established sutimlimab as a rapidly acting, highly efficacious, and low-toxic therapeutic agent. This complement inhibitor does not improve the cold-induced circulatory symptoms, which are not complement-mediated. Sutimlimab is approved for the treatment of CAD in the US, Japan, and the European Union. A tentative therapeutic algorithm is presented. The choice of therapy for CAD should be based on an individual assessment, and patients requiring therapy should be considered for inclusion in clinical trials.

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Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery

Cited by 10 publications

References 11 publications

Perioperative Challenges in Orthogeriatric Patients with Cold Agglutinin Haemolytic Anaemia: Case Report and Management Algorithm

Perioperative Challenges in Orthogeriatric Patients with Cold Agglutinin Haemolytic Anaemia: Case Report and Management Algorithm

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

Sutimlimab for the Treatment of Cold Agglutinin Disease

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