Sutimlimab increases Hb levels, prevents hemolysis in cold agglutinin disease: NEJM
Delhi: Selective upstream inhibition of activity in the classic complement pathway rapidly reduced fatigue, increased hemoglobin levels, and halted hemolysis in patients with cold agglutinin disease who received sutimlimab, finds a recent study. Sutimlimab prevents chronic hemolysis, markedly increases hemoglobin levels and improves quality of life in cold agglutinin disease. The study has been published in the New England journal of Medicine.
Cold agglutinin disease is a rare autoimmune hemolytic anemia. It is characterized by hemolysis that is caused by activation of the classic complement pathway. Sutimlimab is a humanized monoclonal antibody that selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathway.
Alexander Röth and colleagues aimed to assess the efficacy and safety of intravenous sutimlimab in patients with cold agglutinin disease and a recent history of transfusion by conducting a 26-week multicenter, open-label, single-group study.
The composite primary end point was a normalization of the hemoglobin level to 12 g or more per deciliter or an increase in the hemoglobin level of 2 g or more per deciliter from baseline, without red-cell transfusion or medications prohibited by the protocol.
The researchers enrolled total of 24 patients who received at least one dose of sutimlimab. Out of which 13 patients (54%) met the criteria for the composite primary end point.
Key findings of the study include:
- The least-squares mean increase in hemoglobin level was 2.6 g per deciliter at the time of treatment assessment (weeks 23, 25, and 26).
- A mean hemoglobin level of more than 11 g per deciliter was maintained in patients from week 3 through the end of the study period.
- The mean bilirubin levels normalized by week 3.
- A total of 17 patients (71%) did not receive a transfusion from week 5 through week 26.
- Clinically meaningful reductions in fatigue were observed by week 1 and were maintained throughout the study.
- Activity in the classic complement pathway was rapidly inhibited, as assessed by a functional assay.
- Increased hemoglobin levels, reduced bilirubin levels, and reduced fatigue coincided with inhibition of the classic complement pathway.
- At least one adverse event occurred during the treatment period in 22 patients (92%).
- Seven patients (29%) had at least one serious adverse event, none of which were determined by the investigators to be related to sutimlimab.
- No meningococcal infections occurred.
"In patients with cold agglutinin disease who received sutimlimab, selective upstream inhibition of activity in the classic complement pathway rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue," wrote the authors.
The study titled, "Sutimlimab in Cold Agglutinin Disease," is published in the New England Journal of Medicine.