Thromboembolic (TE) Events in Cold Agglutinin Disease (CAD): Post-hoc Analysis PRE- and ON-sutimlimab Treatment in the Phase 3 CARDINAL and CADENZA Studies

Introduction Cold agglutinin disease (CAD), a rare chronic autoimmune hemolytic anemia mediated by classical complement pathway activation, is associated with increased risk of thromboembolic (TE) events compared with the general population. Sutimlimab inhibits complement C1s, providing a therapeutic approach for CAD. Here, we assess the TE events PRE- and ON-sutimlimab treatment from the Phase 3 CARDINAL (NCT03347396) and CADENZA (NCT03347422) studies.

Method TE event analysis included participants who had initiated sutimlimab, had a CAD diagnosis date, and had a treatment start and end date. TE events recorded during the study were medically adjudicated before inclusion. ON-sutimlimab events include all events from treatment initiation until 17 days post last dose of sutimlimab. PRE-sutimlimab and ON-sutimlimab follow-up times were matched for each patient.

Results 66 participants (24 from CARDINAL and 42 from CADENZA), were included in this analysis ([Fig. 1]). The median (min, max) follow-up time in each period was 1.8 (0.1, 3.4) years ( [Fig. 2] ). In the PRE-sutimlimab period, the TE incidence rate was 7.5 per 100 patient-years compared to 4.4 ON-sutimlimab (p=0.3056). TE events in the ON-sutimlimab period included cerebral venous sinus thrombosis (CVST) (n=1), device-related thrombosis (n=1), peripheral artery thrombosis (n=1), transient ischemic attack (TIA) (n=1), and deep vein thrombosis (n=1). CVST and peripheral artery thrombosis were reported as serious events, and all other events were reported as nonserious. Only the CVST was assessed as related to sutimlimab by the investigator; sutimlimab was temporarily interrupted due to the event. Of the participants that experienced a TE event in the ON-sutimlimab period, 4/5 had a history of TE risk factors and of those, 1 had a confirmed previous TIA.

Fig. 1  Summary of Baseline Characteristics of Patients That Met the Inclusion Criteria for the Post-hoc Analysis by Matcheda Thromboembolic (TE) Events After Treatment in the CARDINAL and CADENZA Studies

Fig. 2  Summary of Matched^a Adjudicated Thromboembolic (TE) Events for CARDINAL and CADENZA Studies

Conclusion Analysis of matched adjudicated TE events from the CARDINAL and CADENZA studies suggests a trend toward a reduced risk of TE ON-sutimlimab compared to the PRE-sutimlimab period in this medically complex CAD cohort.

Publication History

Article published online:
26 February 2024