Therapeutic plasma exchange (TPE) with corticosteroids, along with frontline rituximab and caplacizumab, may lead to significant improvements in care for patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), according to an article published in Transfusion and Apheresis Science. The authors wrote that this new treatment paradigm should become the standard of care as it may lead to improved mortality in this patient population.1
Adrien Picod, MD, and Paul Coppo, MD, PhD, both of the Hôpitaux de Paris in France, noted that this combination therapy may reduce the number of TPE sessions patients must undergo, thereby leading to fewer treatment-related complications. In addition, they theorized this treatment may yield significant cost savings by keeping many patients out of the hospital.
iTTP is a rare and severe disease marked by a severe deficiency in ADAMTS13, which is the von Willebrand factor-cleaving protease. Historically, patients with iTTP have relied solely on TPE for treatment; the authors noted TPE is still the only way to deliver large amounts of ADAMTS13 without risking fluid overload. However, advances in the treatment landscape for iTTP may change the optimal treatment for this patients.
Clinical Advances With Caplacizumab
In January 2019, researchers published data in the New England Journal of Medicine from a double blind, controlled trial (HERCULES; ClinicalTrials.gov Identifier: NCT02553317) with 145 patients with iTTP who received caplacizumab (10 mg intravenous loading bolus followed by 10 mg daily subcutaneously), a humanized, bivalent anti-von Willebrand factor nanobody, during plasma exchange. The study showed that treatment with caplacizumab was associated with faster normalization of platelet counts and lower incidence of a composite of TTP-related death, TTP recurrence, or a thromboembolic event compared with placebo (12% vs 49%; P <.001).2
Based on these findings, the US Food and Drug Administration approved caplacizumab in combination with plasma exchange and immunosuppressive therapy. The efficacy of caplacizumab was established based on achieving a platelet count of at least 150,000/µL followed by cessation of daily plasma exchange within 5 days. The HERCULES study showed that the time to platelet count response was significantly better in patients treated with caplacizumab compared with those receiving placebo (2.69 days vs 2.88 days; P =.01). The most common adverse reactions in patients treated with this agent were epistaxis, headache, and gingival bleeding.