title: Efficacy and safety of rituximab in Japanese patients with acquired thrombotic thrombocytopenic purpura refractory to conventional therapy.
abstract: Thrombotic thrombocytopenic purpura (TTP), while rare, is a potentially life-threatening disorder. Plasma exchange (PE) is considered the primary treatment for TTP. In Western countries, rituximab, an anti-CD20 antibody, is recommended with PE for the treatment of refractory/relapsed TTP, and as up-front therapy in newly diagnosed TTP with neurological/cardiac pathology. The present open-label, single-arm, multicenter study evaluated the efficacy and safety of rituximab in Japanese patients with refractory/relapsed TTP. Patients received rituximab 375 mg/m(2) intravenously, once weekly for a total of four treatments, with PE and steroids. Of six evaluable patients in the full analysis set, two met the primary efficacy endpoint (platelet count >150 × 10(9)/L at week 4), yielding a 33.3 % response rate (95 % confidence interval: 4.3-77.7). While the lower confidence limit of the primary efficacy endpoint failed to reach the pre-specified threshold of 30 %, clinically significant recovery of platelet count with discontinuation of PE, increase of ADAMTS13 activity, disappearance of ADAMTS13 inhibitor, and improvement of TTP-associated clinical manifestations were observed after rituximab therapy in all patients. No safety concerns were identified in this study; therefore, rituximab is considered a useful treatment option in Japanese TTP patients who are refractory to conventional therapy. Trial registration JMA-IIA00160.
authors.affiliation: Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyamamachi, Irumagun, Saitama, 350-0495, Japan. miyakawa@saitama-med.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyakawa
authors.affiliation: Department of Hematology, Kokura Memorial Hospital, Fukuoka, Japan.|Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imada
authors.affiliation: Department of Hematology and Oncology, Hiroshima University, Hiroshima, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
authors.affiliation: Department of General Medicine, Nara Medical University, Nara, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Department of Preventive Medicine and Public Health, Biostatistics Unit at the Clinical and Translational Research Center, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Hematology/Oncology, Kurashiki Central Hospital, Okayama, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000071120:ADAMTS13 Protein / Q000378:metabolism; D044466:Asian People; D006801:Humans; D010951:Plasma Exchange; D010976:Platelet Count; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy*; D012008:Recurrence; D000069283:Rituximab / Q000627:therapeutic use*; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000069283:Rituximab; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Rituximab; Thrombotic thrombocytopenic purpura