Should we consider caplacizumab as routine treatment for acute thrombotic thrombocytopenic purpura? An expert perspective on the pros and cons.

INTRODUCTION: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disorder. Caplacizumab has been the latest drug incorporated into the initial treatment of acute episodes, allowing for faster platelet recovery and a decrease in refractoriness, exacerbation, thromboembolic events, and mortality. However, caplacizumab is also associated with a bleeding risk and higher treatment costs, which prevent many centers from using it universally. AREAS COVERED: Studies that included iTTP and/or caplacizumab to date were selected for this review using PubMed and MEDLINE platforms. We describe outcomes in the pre-caplacizumab era and after it, highlighting the benefits and risks of its use early in frontline, and also pointing out special situations that require careful management. EXPERT OPINION: It is clear that the availability of caplacizumab has significantly and favorably impacted the management of iTTP patients. Whether this improvement is cost-effective still remains uncertain, and data on long-term sequelae and different healthcare systems will help to clarify this point. In addition, evidence of the bleeding/thrombotic risk of iTTP patients under this drug needs to be better addressed in future studies.

Spanish registry of thrombotic thrombocytopenic purpura (REPTT): Data evidence and new developments.

Immuno Thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially fatal disorder characterized by systemic microvascular thrombosis because of a severe deficiency of ADAMTS13. It is difficult to generate knowledge about TTP because of its low incidence and the lack of clinical trials. Most of the evidence on diagnosis, treatment, and prognosis has been generated from real-world data registries. In 2004, the Spanish Apheresis Group (GEA) implemented the Spanish registry of TTP (REPTT) with 438 patients suffering 684 acute episodes in 53 hospitals up to January 2022. REPTT has studied several aspects of TTP in Spain. The iTTP incidence in Spain our country is 2.67 (95 % CI 1.90-3.45) and the prevalence is 21.44 (95 % CI % 19.10-23.73) patients per million inhabitants. The refractoriness incidence is 4.8 % and exacerbation incidence was 8.4 %, with a median of follow-up of 131.5 months (IQR: 14-178 months). In a 2018 review, the mortality in the first episode due to TTP was 7.8 %. We have also found that de novo episodes require fewer PEX procedures than relapses. Since June 2023, REPTT will involve Spain and Portugal, with a recommended sampling protocol and new variables to improve the neurological, vascular and quality of life evaluation of these patients. The main strength of this project will be the involvement of a combined population of more than 57 million inhabitants, which implies an annual incidence of close to 180 acute episodes per year. This will allow us to provide better answers to questions like treatment efficacy, associated morbidity and mortality, and the possible neurocognitive and cardiac sequelae.

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX.