Long-term sutimlimab improves quality of life for patients with cold agglutinin disease: CARDINAL 2-year follow-up

Abstract

Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia with a substantial burden on patient's quality of life. CARDINAL was a 2-part, open-label, single-arm, multicenter phase 3 study evaluating the C1s inhibitor, sutimlimab, for treatment of CAD. Part A consisted of the pivotal study phase, with the part B extension phase assessing long-term safety and durability of response including patient-reported outcomes, which is the focus of this report. Altogether, 22 patients continued from part A to part B, majority female (68.2%) with a median age of 71.5 years (range, 55-85). Throughout treatment, score improvement on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale exceeded a predefined, group-level clinically important change of ≥5 points vs baseline, with a mean (standard error [SE]) change of 11.7 (3.7) points at week 135. The 12-Item Short Form Health Survey physical and mental component scores remained above baseline, with week 123 mean change (SE) exceeding clinically important changes of 3.9 for physical and 2.8 for mental component scores at 4.7 (2.8) and 3.8 (5.7) points, respectively. EuroQol Visual Analogue Scale, scoring patients' self-rated health, also remained above baseline with a change of 17.1 (5.6) points at week 135. Patient Global Impression of (fatigue) Severity improved vs baseline, corroborating FACIT-Fatigue scores. Patient Global Impression of Change indicated a reduction in perceived disease burden. Data from CARDINAL part B support sustained alleviation of CAD disease burden after long-term treatment with sutimlimab over 2 years, returning toward baseline upon treatment cessation. This trial was registered at www.clinicaltrials.gov as #NCT03347396.

Graphical abstract

Figure 1.

Mean (SE) change from baseline in FACIT-Fatigue score throughout pivotal (part A) and 2-year extension (part B) phases of CARDINAL, and at the ET/SFU follow-up visit, 9 weeks after cessation of sutimlimab treatment. BL, baseline.

Figure 2.

Change from baseline in SF-12 physical and mental component scores. Mean (SE) change from baseline in Short Form Health Survey (SF-12) PCS (A) and MCS (B) throughout the 2-year extension (part B) phase of CARDINAL. Note: SF-12 data not presented at week 135 owing to low patient numbers. BL, baseline.

Figure 3.

Mean (SE) change from baseline in EQ-VAS scores throughout the 2-year extension (part B) phase of CARDINAL, and at the ET/SFU follow-up visit, 9 weeks after cessation of sutimlimab treatment. BL, baseline.

Figure 4.

Change from baseline in PGIS and PGIC questionnaires at week 135 and ET/SFU of CARDINAL. (A) Proportion of responders (%) reporting no, mild, moderate, severe or very severe fatigue at baseline, week 135 and ET/SFU. (B) Proportion of responders (%) reporting degrees of improvement from baseline, from very much improved to very much worse, at week 135 and ET/SFU.