Caplacizumab, a humanized nanobody, blocks the interaction between von Willebrand factor and platelets. While early administration of caplacizumab in patients with the rare disease immune thrombotic thrombocytopenic purpura (iTTP) does not prevent the requirement for immunosuppression to treat disease, the drug shortens the duration of plasma exchange (PEX) without the addition of major safety concerns. María Eva Mingot-Castellano, MD, PhD, a hematologist at the Hospital Universitario Virgen del Rocío in Spain, and colleagues recently published their analysis of data from the Spanish Registry of Thrombotic Thrombocytopenic Purpura in Blood. Their investigation included 113 iTTP episodes in 108 patients, 75 of whom were treated with caplacizumab.
The researchers found no difference between caplacizumab-treated and non-treated episodes in the time to achieve ADAMTS13 activity of at least 20% after PEX end (14.5 vs. 13.0 median days, p=0.653). When they focused their analysis on the 36 episodes where caplacizumab was initiated less than three days after iTTP diagnosis, they found that the time to ADAMTS13 restoration from PEX end was higher than in those episodes where caplacizumab was initiated more than three days after iTTP diagnosis (20.0 vs. 11.0 days, p=0.003), and higher than in non-caplacizumab-treated episodes (p=0.033). The investigators noted one limitation of the study was that the registry did not contain inhibitor titers, so they were unable to compare baseline levels among the different treatment groups.
Current guidelines from the International Society on Thrombosis and Haemostasis state that patients with iTTP experiencing an acute event (first event or relapse) should be treated with caplacizumab. “The most interesting point of our work,” Dr. Mingot-Castellano said, “is that we don’t have to be afraid of caplacizumab delaying recovery.” She explained that hematologists often initiate treatment with caplacizumab out of concern that patients will relapse. Always severe, such relapses result in the death of 90% of patients. Moreover, she said that the moment patients receive caplacizumab, their symptoms stop, and those who receive early treatment with caplacizumab have reduced need for PEX. Dr. Mingot-Castellano explained that while historically there is a correlation between PEX and ADAMTS13 recovery in patients with iTTP, the correlation is lost upon treatment with caplacizumab. She thus suggested that hematologists be open to administering caplacizumab without PEX.
Patients treated with caplacizumab still require treatment with rituximab, however. “Rituximab needs some time to block the production of antibodies,” Dr. Mingot-Castellano said. “It manages the future.”
Dr. Mingot-Castellano explained that caplacizumab is an expensive anti-platelet drug and its use can be difficult to justify, given that patients with iTTP do not present with severe bleeding. “Here in Europe, caplacizumab is commonly used,” she said. “In North America, not so much.” In the U.S., the debate centers on the balance between the high cost of the drug and desire to reduce PEX and hospitalization. “At the end of the day, in every country, this situation should be reviewed because cost-effectiveness isn’t the same in every country,” she said.
The current study relies on real-world evidence. “It’s quite complicated to do a randomized study in these patients,” Dr. Mingot-Castellano said. Absent clinical trial data, rare disease studies often rely on real-world evidence from registries, and Dr. Mingot-Castellano looks to registries to answer additional questions of importance for patients with iTTP. For example, these patients have a higher incidence of strokes, raising questions as to whether the strokes are the result of patients having high plasma levels of the von Willebrand factor multimers for a long time, or if caplacizumab treatment could help mitigate future risk of stroke for these patients. Dr. Mingot-Castellano encourages hospitals to standardize the way they follow patients with iTTP and enter the data in the registries. If done properly, the registries will continue to provide valuable insight into how to care for these one-in-a-million patients.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Mingot-Castellano ME, García-Candel F, Nieto JM, et al. ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy. The Spanish registry [published online ahead of print, 2024 Jan 18]. Blood. doi: 10.1182/blood.2023022725.
