Frontline use of rituximab may prevent ADAMTS13 inhibitor boosting during caplacizumab treatment in patients with iTTP: post hoc analysis of a phase 2/3 study in Japan

Kazunori Imada; Yoshitaka Miyakawa; Satoshi Ichikawa; Hitoji Uchiyama; Yasunori Ueda; Yasuhiro Hashimoto; Masashi Nishimi; Masako Tsukamoto; Sayaka Tahara; Masanori Matsumoto

doi:10.1186/s12959-024-00642-3

Frontline use of rituximab may prevent ADAMTS13 inhibitor boosting during caplacizumab treatment in patients with iTTP: post hoc analysis of a phase 2/3 study in Japan

Thromb J. 2024 Aug 2;22(1):72. doi: 10.1186/s12959-024-00642-3.

Authors

Affiliations

¹ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
² Department of Hematology, Saitama Medical University Hospital, Saitama, Japan.
³ Department of Hematology, Tohoku University Hospital, Sendai, Japan.
⁴ Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
⁵ Department of Hematology Oncology, Kurashiki Central Hospital, Kurashiki, Japan.
⁶ Sanofi K.K, Tokyo, Japan.
⁷ Department of Hematology and Blood Transfusion Medicine, Nara Medical University Hospital, 840 Shijyo-Cho, Kashihara, Nara, 634-8522, Japan. mmatsumo@naramed-u.ac.jp.

Abstract

Background: A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population.

Methods: A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed.

Results: Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9-24.8), 18.5 (5.9-31.8), and 47.5 (18.5-60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0-101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event.

Conclusions: In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting.

Trial registration: NCT04074187.

Keywords: ADAMTS13 activity; ADAMTS13 inhibitors; Caplacizumab; Immune-mediated thrombotic thrombocytopenic purpura; TTP.

Associated data

ClinicalTrials.gov/NCT04074187