Rituximab prolongs the time to relapse in patients with immune thrombotic thrombocytopenic purpura: analysis of off-labe
- PDF / 1,001,610 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 2 Downloads / 205 Views
ORIGINAL ARTICLE
Rituximab prolongs the time to relapse in patients with immune thrombotic thrombocytopenic purpura: analysis of off‑label use in Japan Masayuki Kubo1 · Kazuya Sakai1 · Yumi Yoshii1 · Masaki Hayakawa1 · Masanori Matsumoto1 Received: 1 July 2020 / Revised: 6 August 2020 / Accepted: 17 August 2020 © Japanese Society of Hematology 2020
Abstract Immune thrombotic thrombocytopenic purpura (iTTP) is caused by ADAMTS13 deficiency due to anti-ADAMTS13 autoantibodies. Rituximab, an anti-CD20 monoclonal antibody, is often used to suppress these autoantibodies. This retrospective study, conducted in an iTTP cohort in Japan, evaluated the long-term efficacy of rituximab as off-label treatment for refractory or relapsed cases. A total of 252 iTTP patients with severe ADAMTS13 deficiency ( 95% of all TTP cases [8]. In about 90% of cases, TTP is fatal if therapeutic plasma exchange (TPE) is not performed [1]. However, TPE dramatically improves the survival rate of patients with iTTP to 80–85% [9, 10]. TPE can supplement ADAMTS13 and eliminate both anti-ADAMTS13 autoantibodies and unusually large VWF multimers, which are the most active form of VWF [11]. Corticosteroids are often used in combination with TPE to suppress the production of anti-ADAMTS13 autoantibodies. However, some patients are resistant to conventional treatment, including TPE and corticosteroids, or relapse soon after they are administered [12]. Rituximab, an antiCD20 chimeric monoclonal antibody, is effective in refractory or relapsed patients with iTTP [13–15]. Platelet counts increased in over 80% of refractory TTP patients after the
13
Vol.:(0123456789)
addition of rituximab to TPE and corticosteroids [16]. A second use of rituximab is to administer it in combination with conventional treatments as a first-line treatment for iTTP [17]. iTTP is associated with a high rate of relapse, with as many as 40% of patients experiencing at least one recurrence between 7 and 10 years after initial onset [12]. A meta-analysis showed that rituximab use in the acute phase may reduce the relapse rate [18]. However, some studies indicated that rituximab administration resulted in no difference in the relapse rate during long-term observation [14, 19]. The third use of rituximab that is now being discussed is to administer it as prophylaxis in asymptomatic patients with severe ADAMTS13 deficiency [16, 20]. Some groups reported that ADAMTS13 deficiency during remission is a risk factor for relapse [21, 22]. A French group found that prophylactic rituximab administration during remission significantly reduced the number of relapses [23]. In Japan, the first successful use of rituximab for refractory TTP that was resistant to repeated TPE, high-dose corticosteroids, and splenectomy was reported in 2005 [24]. Since then, rituximab has been used off-label in many cases. The efficacy and safety of rituximab in refractory iTTP patients were confirmed in phase II clinical trial in Japan [25], and it was approved for refractory or relapsed cases of iTTP by Jap
Data Loading...
