Caplacizumab may induce faster resolution of a thrombotic thrombocytopenic purpura episode

1. Caplacizumab reduced time to normalization of platelets by 39% or about 2 days as compared to placebo.

2. There was an increased risk of mild to moderate bleeding in the caplacizumab group as compared to placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Thrombotic thrombocytopenic purpura (TTP) is a potentially deadly microangiopathy, which causes showering of microthrombi throughout the body resulting in renal failure, hemolytic anemia, thrombocytopenia, and mental status changes. Rapid diagnosis allows prompt treatment with plasma exchange, which removes autoantibodies and the large von Willebrand factor multimers that bind platelets. A medication that could prevent binding of platelets to the large von Willebrand factor multimers would help reduce the burden of microthrombi and thus reduce mortality and microthrombotic sequelae. Caplacizumab is an anti-von Willebrand factor immunoglobulin that prevents binding with platelets and this RCT evaluated its potential for treating acquired TTP.

Caplacizumab administration reduced time to response by 39% as compared to placebo.

There were more mild to moderate bleeding related adverse events in the caplacizumab group than placebo. Other adverse events were distributed similarly across both groups. No patients died in the caplacizumab group as compared to two deaths in the placebo group. Strengths of this study is that it is a randomized trial. Limitations of this study include heavy involvement of pharmaceutical company Ablynx, who designed and conducted the study and analyzed all data.

Click to read the study in NEJM

Relevant Reading: Management of thrombotic thrombocytopenic purpura: current perspectives

In-Depth [randomized controlled trial]: This phase 2, international, randomized, single-blind, parallel-group trial was conducted from October 2010 to January 2014. This study was designed, conducted, and analyzed by Ablynx, the pharmaceutical sponsor. The study population included adults with an acute episode of acquired TTP with platelets <100,000 per cubic millimetre, without active bleeding and requiring plasma exchange. They were assigned 1:1 to caplacizumab or placebo. All patients received standard of care treatment which included daily plasma exchange and immunosuppressive therapy. The primary end point was time to response, defined as confirmed normalization of the platelet count to >150,000 per cubic millimetre. Authors also monitored for relapses and adverse events.

Seventy-five patients were recruited to the study and underwent randomization: 36 to caplacizumab and 39 to placebo. The median time to response in patients who had never undergone plasma-exchange prior to enrollment was 3.0 days (95% [CI], 2.7-3.9) in the treatment group and 4.9 days (95% [CI], 3.2-6.6) in the placebo group. In patients who undergone plasma-exchange before enrollment the median time to response was 2.4 days (95% [CI], 1.9-3.0) in the caplacizumab group and 4.3 days (95% [CI], 2.9-5.7) in the placebo group. This translated to 39% reduction in median time to response in the caplacizumab group as compared to placebo (Event rate ratio 2.20, 95% [CI], 1.28-3.78; p=0.005). Bleeding-related adverse events were higher in the caplacizumab group as compared to placebo (54%, vs. 38%, respectively). Most of these events were described as mild to moderate.

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