Dataset Information
Long-term efficacy and safety of continued complement C1s inhibition with sutimlimab in cold agglutinin disease: CADENZA study Part B.
Ontology highlight
ABSTRACT: 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.
SUBMITTER: Roth A
PROVIDER: S-EPMC11293518 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
Publications
Long-term efficacy and safety of continued complement C1s inhibition with sutimlimab in cold agglutinin disease: CADENZA study Part B.
EClinicalMedicine 20240718
<h4>Background</h4>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.<h4>Methods</h4>The CADENZA study (NCT03347422) started in March 2018 (Part A) and comp ...[more]