Caplacizumab Effective, Safe in Treating Immune TTP

Cases of immune thrombotic thrombocytopenic purpura (iTTP) that are refractory to plasma exchange, treated through readministration, and do not include previous plasma exchange treatment could be treated with caplacizumab safely and effectively, according to a study published in Frontiers in Medicine. No major adverse events were reported when patients took the medicine.

A severe deficiency of ADAMTS13 is used to indicate a diagnosis of iTTP. Treatment usually involves plasma exchange and immunosuppression to replenish ADAMTS13 in patients with TTP. Caplacizumab has also been approved as a treatment for iTTP following trials that found it can speed up platelet recovery and reduce recurrence. The present study aimed to test the safety and efficacy of caplacizumab in a real-world setting using a multicenter design.

Red blood cells circulating in the blood vessels | Image credit: Design Cells - stock.adobe.com

Data from adults 18 years and older with iTTP diagnosed between 2011 and 2022 were collected. Clinical presentation and the measurement of ADAMTS13 in plasma was used to diagnose iTTP, and levels of ADAMTS13 were used to determine how long caplacizumab would be given until ADAMTS13 activity was raised to 10% or higher.

Eleven hematology departments in Greece and the United Kingdom were included in the study, and patient records were recorded retrospectively. The participating centers mostly treated patients with iTTP using steroids and daily plasma exchange. The control group, which consisted primarily of patients who were refractory or who had relapsed or patients who had severe presentation, received rituximab. Relapse was defined as deterioration after 30 days in remission.

Seventy patients were included in this study—47 patients in the control group and 23 in the caplacizumab group—and their median (IQR) age was 45 (19-85) years. All but 2 patients received plasma exchange, all patients received corticosteroids, and most also received rituximab. Patients in the caplacizumab group more frequently used rituximab as first-line treatment compared with the control group (68% vs 32%).

Patients were given caplacizumab a median 7 (1-43) days after diagnosis, for a median of 32 (6-47) doses. Sixty-fice percent of patients used caplacizumab for their first episode of iTTP. All but 4 patients intended to use caplacizumab as their first treatment, with the 4 only using the medication after being unresponsive to plasma exchange. Seventy percent of cases were given caplacizumab within 72 hours of their diagnosis, with 2 cases having iTTP occurring after COVID-19 infection. Plasma exchange sessions occurred a median of 12 (8-23) times in the caplacizumab group vs 14 (6-32) times in the control group.

All patients had early platelet normalization a median of 5 (3-7) days after administration of caplacizumab, and ADAMTS13 levels became detectable (25%-52%) by the end of treatment in all patients receiving caplacizumab. The timing of caplacizumab initiation, whether within 72 hours of diagnosis or after, did not have a significant different in platelet recovery or plasma exchange duration. Two of the 23 patients who received caplacizumab relapsed within 13 and 18 months of their first dose compared with 29 of the 47 patients who were in the control group. After restarting caplacizumab, both patients had platelet count normalize within 10 and 4 days. Only 1 death occurred in the caplacizumab group compared with 4 in the control group.

Administration of caplacizumab did not lead to major bleeding events or a grade 3 complication. Twnety-one percent of patients who received caplacizumab reported minor bleeding events vs 15% of the control group.

The researchers concluded that caplacizumab was safe and effective in treating patients with iTTP. Rapid platelet recovery and low relapse rates were associated with caplacizumab, even as overall therapeutic plasma exchange duration did not differ.

Reference

Gavriilaki E, Nikolousis E, Koravou EE, et al. Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data. Front Med. Published online October 11, 2023. doi:10.3389/fmed.2023.1226114