Sutimlimab provides clinically meaningful improvements in patient‐reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo‐controlled, Phase 3 <scp>CADENZA</scp> study

<jats:title>Abstract</jats:title><jats:p>Cold agglutinin disease (CAD) is a rare chronic autoimmune haemolytic anaemia, driven mainly by classical complement pathway activation, leading to profound fatigue and poor quality of life. In the Phase 3 CADENZA trial, sutimlimab—a C1s complement inhibitor—rapidly halted haemolysis, increased haemoglobin levels and improved fatigue versus placebo in patients with CAD without a recent history of transfusion. Patient‐reported outcomes (PROs) included Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐Fatigue), 12‐Item Short Form Health Survey (SF‐12), EuroQol visual analogue scale (EQ‐VAS), Patient Global Impression of Change (PGIC) and Patient Global Impression of (fatigue) Severity (PGIS). Sutimlimab resulted in significant rapid and meaningful improvements versus placebo in PROs. From Week 1, the FACIT‐Fatigue mean score increased >5 points above baseline (considered a clinically important change [CIC]). Least‐squares (LS) mean change in FACIT‐Fatigue score from baseline to treatment assessment timepoint was 10.8 vs. 1.9 points (sutimlimab vs. placebo; <jats:italic>p</jats:italic> < 0.001). Improvements in physical (PCS) and mental (MCS) component scores of the SF‐12 were also considered CICs (LS mean changes from baseline to Week 26: PCS 5.54 vs. 1.57 [<jats:italic>p</jats:italic> = 0.064]; MCS 5.65 vs. –0.48 [<jats:italic>p</jats:italic> = 0.065]). These findings demonstrate that in addition to improving haematologic parameters, sutimlimab treatment demonstrates significant patient‐reported benefits. Study registered at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</jats:ext-link>: NCT03347422.</jats:p>