Safety, Pharmacokinetics, and Efficacy Study of Porcine and Rabbit Antithymocyte Globulin in the Treatment of Patients With Severe Aplastic Anemia: A Multicenter, Prospective, Randomized, Open‐Label Clinical Trial

ABSTRACT Severe aplastic anemia (SAA) is a T lymphocyte‐mediated bone marrow failure disorder. Only porcine ATG (p‐ATG) and rabbit ATG (r‐ATG) are available in mainland China, with the optimal first‐line regimen undetermined. This study compared their pharmacokinetics, efficacy, and safety. Ninety‐three SAA patients ineligible for transplantation or lacking a suitable donor (p‐ATG, n = 55; r‐ATG, n = 38) who were receiving immunosuppressive therapy were prospectively enrolled between 2020 and 2024. The primary endpoint was dynamic changes in lymphocyte subsets. Both ATGs peaked on treatment Day 5; r‐ATG cleared significantly faster, with comparable peak active concentrations. The p‐ATG group showed a stable early neutrophil increase, whereas the r‐ATG group had an initial decline, with comparable recovery at 1 month. The r‐ATG group exhibited prolonger lymphopenia, lower CD3 + /CD4 + T cells, reduced Treg cells, and higher CD19 + B‐cell proportions. IL‐10 was significantly elevated on day 2 after ATG administration. At 6 months, the CRR was 18.87% with p‐ATG and 18.92% with r‐ATG; ORR was 69.81% with p‐ATG and 56.76% with r‐ATG. Two‐year ORR and overall survival were similar, with no significant differences in infection or serum sickness. P‐ATG and r‐ATG have distinct pharmacokinetic and immunomodulatory but comparable efficacy and safety profiles, supporting interchangeable use in clinical practice.