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.

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.