A 35-year-old woman has autoimmune haemolytic anaemia (AIHA). Direct Coombs test is strongly positive with warm IgG antibodies, Hb 6.2 g/dL, reticulocyte count 12%, elevated indirect bilirubin, and spherocytes on blood film. She fails prednisolone 1 mg/kg/day after 4 weeks. The CARDINAL trial evaluated which agent for warm AIHA and showed clinically meaningful durable responses?
- A Rituximab (anti-CD20) — long-established second-line standard without formal RCT data
- B Eculizumab — anti-C5 complement inhibitor for cold AIHA and warm AIHA refractory cases
- C Fostamatinib — spleen tyrosine kinase (SYK) inhibitor evaluated in CARDINAL showing durable haemoglobin response in steroid-refractory warm AIHA ✓
- D Sutimlimab — anti-C1s antibody specifically studied in warm antibody AIHA in CARDINAL
Explanation
The CARDINAL trial (Blood 2020; NEJM 2021 update) evaluated fostamatinib, an oral SYK inhibitor, in adults with warm AIHA who had failed ≥ 1 prior therapy. SYK inhibition reduces macrophage-mediated phagocytosis of IgG-opsonised red blood cells in the spleen. CARDINAL showed 26–30% durable haemoglobin response rate (Hb ≥ 10 g/dL and ≥ 2 g/dL increase from baseline), earning FDA breakthrough therapy designation. Sutimlimab (anti-C1s) targets cold agglutinin disease (CADENZA/CARDINAL = different trials). Rituximab is the most widely used second-line but lacks Phase III RCT evidence in AIHA.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.