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Updated: Jul 14, 2026
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Long-term efficacy and safety of continued complement C1s inhibition with sutimlimab in cold agglutinin disease:
Alexander Röth1, Sigbjørn Berentsen2, Wilma Barcellini3
1Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Insights
Sutimlimab offers sustained treatment for cold agglutinin disease (CAD), improving anemia and fatigue. However, discontinuing sutimlimab leads to the recurrence of CAD symptoms.
Area of Science:
- Hematology
- Immunology
- Pharmacology
Background:
- Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia driven by the classical complement pathway (CP).
- Sutimlimab is a targeted therapy inhibiting the CP by targeting complement C1s, thereby reducing hemolysis and anemia.
- Previous studies demonstrated sutimlimab's efficacy in reducing hemolysis, anemia, and fatigue in CAD patients.
Purpose of the Study:
- To evaluate the long-term efficacy and safety of sutimlimab in treating cold agglutinin disease.
- To assess the sustained effects of sutimlimab treatment over an extended period.
- To investigate the impact of treatment discontinuation on disease activity.
Main Methods:
- The CADENZA study included Part A (placebo-controlled) and Part B (open-label extension).
- Patients received sutimlimab for up to 1 year, with efficacy and safety assessed throughout.
- A 9-week washout period was included post-treatment to observe disease recurrence.
Main Results:
- Sustained improvements in hemoglobin, bilirubin levels, and quality of life (FACIT-Fatigue) were observed in patients receiving sutimlimab.
- Treatment with sutimlimab led to sustained reduction in hemolysis and anemia.
- Upon discontinuation and after a 9-week washout, complement pathway activity resumed, and hemolytic markers returned to baseline levels, indicating disease recurrence.
Conclusions:
- Sutimlimab demonstrates sustained efficacy and a favorable safety profile for the long-term treatment of cold agglutinin disease.
- The study highlights the importance of continuous treatment as disease activity reoccurs upon discontinuation of sutimlimab.
- Sutimlimab effectively manages CAD symptoms by inhibiting the classical complement pathway.
Background:
Cold agglutinin disease (CAD) is a rare autoimmune haemolytic anaemia mediated by the classical complement pathway (CP). Sutimlimab selectively targets complement C1s inhibiting classical CP activation. In CADENZA Part A (26-weeks), a placebo-controlled study in patients without recent transfusion history, sutimlimab reduced haemolysis, anaemia, and fatigue, and was generally well tolerated.
Methods:
The CADENZA study (NCT03347422) started in March 2018 (Part A) and completed in December 2021 (Part B). All patients in Part B were eligible to receive sutimlimab for up to 1 year after the last patient completed Part A. Efficacy and safety was assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout.
Findings:
In total, 32/39 patients completed Part B; median treatment duration: 99 weeks. Similar sustained improvements in haemolysis, anaemia, and quality of life were observed in patients switching to sutimlimab and those continuing sutimlimab. Mean LV values for the combined group (ie, placebo-to-sutimlimab group and sutimlimab-to-sutimlimab group) improved from baseline for haemoglobin (≥11.0 g/dL on-treatment vs 9.3 g/dL at baseline), bilirubin (≤20.0 μmol/L on-treatment vs 35.0 μmol/L at baseline), and FACIT-Fatigue scores. Following a 9-week washout, inhibition of CP activity was reversed, and haemolytic markers approached baseline levels. Overall, sutimlimab was generally well tolerated throughout the study. No patients developed systemic lupus erythematosus or meningococcal infections. During the 9-week washout, most adverse events could be attributed to recurrence of underlying CAD.
Interpretation:
The CADENZA Part B results support the sustained efficacy and safety of sutimlimab for treatment of CAD; however, upon discontinuation disease activity reoccurs.
Funding:
Sanofi.
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