Real-World Data with the Use of Caplacizumab in the Treatment of Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

INTRODUCTION For more than two decades, the treatment of aTTPconsisted of therapeutic plasma exchange (TPE) and immunosuppressive agents. The addition of caplacizumab, a nano-antibody that binds to the A1 domain of the von Willebrand factor, inhibiting platelet aggregation, has been shown to reduce the time to resolution of thrombocytopenia, the rate of recurrence and the aTTP-related death. Real-world evidence of the effectiveness of caplacizumab is limited yet. The objective of our study was to assess the results of the introduction of caplacizumab in our internal protocol and to compare those results with the patients treated before the drug was available. METHODS A single-center retrospective observational study that evaluates the clinical characteristics and response to treatment of 18 consecutively diagnosed aTTP patients between May/14 to May/20. All patients received initial treatment with TPE and prednisone (PDN) 1 mg/Kg; the control group did not receive any other initial therapy, whereas nine patients received caplacizumab in addition to PEX and PDN once ADAMTS-13 deficiency was confirmed. Complete response (CR) was defined as the second of two consecutive days with platelets ≥150x109/L, refractoriness as the lack of platelet increase despite optimal therapy after 7 days, exacerbation as the decrease in platelet count during the first 30 days of discontinuation of TPE, and relapse as a new episode of aTTP beyond 30 days after the last TPE. All results are given as median (interquartile range). Statistical analysis was conducted using STATA/IC software. RESULTS The clinical characteristics at diagnosis of patients treated with or without caplacizumab were similar, except for a lower percentage of males and lower neurological involvement in the caplacizumab group (Table 1). Caplacizumab was started at a median of 3 days after diagnosis following ADAMTS-13 deficiency determination, and was administered during a median of 39 days (IQR 33-39). Adverse events related to caplacizumab were mild: 1 patient presented mild metrorrhagia, 1 developed pain and erythema at the puncture area and 1 suffered an urticarial dermatitis, the last case leading to the suspension of the drug since levels of ADAMTS-13 were recovered. The caplacizumab group achieved CR after a median of 4 days (IQR 3-4) vs. 6 days (IQR 5-14) in the control group (p = 0.016). Likewise, the number of TPE was lower with caplacizumab (Figure 1), with a median of 10 TPE (IQR 9-11) vs. 19 (IQR 16-23) (p = 0.001). Hospitalization time was also shorter in the caplacizumab group with a median of 12 days (IQR 12-14) vs. 26 (IQR 20-27) (p = 0.002). Finally the time of hospitalization into the intensive care unit was shorter in the caplacizumab group with a median of 3 days (IQR 2-4) vs. 4 (IQR 3-13) (p=0.1). In the caplacizumab group (median follow-up of 6.8 months), there were no refractory cases. There was 1 exacerbation before initiation of caplacizumab and 1 relapse. Both cases were treated with rituximab. In contrast, in the control group (median follow-up of 51.8 months), we observed 4 refractory cases (1 aTTP-related death), 3 exacerbations and 1 relapse; rituximab was necessary in 8 patients and a 3rd line with vincristine was administered in 4 cases. CONCLUSIONS The observed benefits of caplacizumab in our series are in line with the ones identified in randomized clinical trials. Caplacizumab can be used in combination with other therapies to attain a faster response and reduce aTTP-related complications. Disclosures Bosch: Hoffmann-La Roche: Research Funding.