Should all patients with immune‐mediated thrombotic thrombocytopenic purpura receive caplacizumab?

Abstract

Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life‐threatening disease that causes systemic platelet‐rich microthrombi with multiorgan damage. The historical treatment is based on therapeutic plasma exchange (TPE) and immunosuppression. Despite survival rates exceeding 85%, unfavorable outcomes including refractoriness, death, and exacerbations of the disease during treatment still calls for a better management strategy. Caplacizumab (Cablivi) appeared recently as a new treatment in iTTP. By inhibiting binding of von Willebrand factor to platelets, caplacizumab prevents platelets aggregation and the formation of microthrombi. Two pivotal randomized controlled trials have provided positive results where the use of caplacizumab is associated with faster platelet count recovery and less unfavorable outcomes. The other strength of this agent is an impressive alleviation in the burden of care, consisting in less TPE sessions and lower volumes of plasma to achieve remission, as well as substantial shortening in the length of hospitalization. However, since the recent approval of caplacizumab for the treatment of iTTP on the basis of these studies, debates remain regarding its systematic use in this indication. Should all patients be benefited from caplacizumab? Should we reserve caplacizumab only to the more severe patients? Should caplacizumab be initiated frontline or as a salvage therapy? If applicable, how should we select patients for caplacizumab? Last, is caplacizumab treatment cost‐effective? This review aims at addressing these specific questions at a time when iTTP is entering the area of targeted therapies.

The standard of care for immune thrombotic thrombocytopenic purpura today

“…This is now considered to be the standard of care for confirmed iTTP and for those with high probability of iTTP. 17,55,68,69 However, rituximab and caplacizumab may be withheld or delayed for those with intermediate to low probabilities of iTTP until a positive ADAMTS-13 result (e.g., ADAMTS-13 activity <10 IU/dl or <10% of normal) is obtained. 17,55 Caplacizumab is generally not recommended to be prescribed to a patient with a suspected iTTP but without an obtainable ADAMTS-13 test for its confirmation, citing the concern of potential bleeding complications.…”

Do patients with immune-mediated thrombotic thrombocytopenic purpura receiving caplacizumab need antithrombotic therapy?

“…Although caplacizumab seems to prevent arterial thrombotic events, current evidence does not support using caplacizumab as an anticoagulant agent in iTTP, since the rates of VTE in both caplacizumab and no-caplacizumab groups are similar [10].…”

“…Bleeding events were more frequent in patients with caplacizumab than that of controls, and most patients receiving caplacizumab did not concomitantly use antithrombotics. Since caplacizumab inhibits platelet adhesion at high-shear rates, but not at low-shear rates, there may be a lower bleeding risk when compared to other antiplatelets [10,26]. Supporting this, in the pre-caplacizumab era, TTP patients receiving aspirin and/or dipyridamole had higher rates of minor bleeding events than observed in caplacizumab-treated patients, however, although rare, major bleeding episodes seem to be more frequent in cases with caplacizumab than that of historical controls receiving antiplatelets (Table 1).…”

“…Although caplacizumab was recommended to be used in combination with PEX and corticosteroids in iTTP patients experiencing an acute episode of in the current International Society on Thrombosis and Haemostasis (ISTH) guidelines [9] it was also stated that the data informing this recommendation were of moderate certainty and caplacizumab is not yet available worldwide. Besides, the cost effectiveness of using caplacizumab in this setting is uncertain [5,10].…”

Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions

“… 15 , 53 Caplacizumab is approved for the treatment of acquired TTP 28 but the cost-effectiveness of frontline caplacizumab administration in all TTP patients remains uncertain. 54 , 55 Adverse side effects consist of hemorrhage, usually non severe.…”