Leissinger C, Josephson C D, Granger S, Konkle B A, Kruse-Jarres R, Ragni M V, Journeycake J M, Valentino L, Key N S, Gill J C, McCrae K R, Neufeld E J, Manno C, Raffini L, Saxena K, Torres M, Marder V, Bennett C M, Assmann S F
Suzanne Granger, MS, New England Research Institutes, Inc., 480 Pleasant St., Watertown, MA 02472, USA, Tel.: +1 617 972 3319, Fax: +1 617 926 8246, E-mail:
Thromb Haemost. 2014 Sep 2;112(3):445-58. doi: 10.1160/TH14-01-0078. Epub 2014 Jun 12.
The development of antibodies against infused factor VIII (FVIII) in patients with haemophilia A is a serious complication leading to poorly controlled bleeding and increased morbidity. No treatment has been proven to reduce high titre antibodies in patients who fail immune tolerance induction or are not candidates for it. The Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (RICH) study was a phase II trial to assess whether rituximab can reduce anamnestic FVIII antibody (inhibitor) titres. Male subjects with severe congenital haemophilia A and an inhibitor titre ≥5 Bethesda Units/ml (BU) following a FVIII challenge infusion received rituximab 375 mg/m² weekly for weeks 1 through 4. Post-rituximab inhibitor titres were measured monthly from week 6 through week 22 to assess treatment response. Of 16 subjects who received at least one dose of rituximab, three (18.8%) met the criteria for a major response, defined as a fall in inhibitor titre to <5 BU, persisting after FVIII re-challenge. One subject had a minor response, defined as a fall in inhibitor titre to <5 BU, increasing to 5-10 BU after FVIII re-challenge, but <50% of the original peak inhibitor titre. Rituximab is useful in lowering inhibitor levels in patients, but its effect as a solo treatment strategy is modest. Future studies are indicated to determine the role of rituximab as an adjunctive therapy in immune tolerisation strategies.
在甲型血友病患者中，针对输入的凝血因子VIII（FVIII）产生抗体是一种严重的并发症，会导致出血控制不佳和发病率增加。对于免疫耐受诱导失败或不适合进行免疫耐受诱导的患者，尚无经证实可降低其高滴度抗体的治疗方法。利妥昔单抗治疗先天性甲型血友病抑制物（RICH）研究是一项II期试验，旨在评估利妥昔单抗是否能降低回忆性FVIII抗体（抑制物）滴度。在接受FVIII激发输注后，抑制物滴度≥5 Bethesda单位/毫升（BU）的重度先天性甲型血友病男性受试者，在第1至4周每周接受375毫克/平方米的利妥昔单抗治疗。从第6周开始至第22周，每月测量利妥昔单抗治疗后的抑制物滴度，以评估治疗反应。在16名接受至少一剂利妥昔单抗治疗的受试者中，三名（18.8%）达到主要反应标准，主要反应定义为抑制物滴度降至<5 BU，在FVIII再次激发后持续存在。一名受试者有轻微反应，定义为抑制物滴度降至<5 BU，在FVIII再次激发后升至5 - 10 BU，但低于原始峰值抑制物滴度的50%。利妥昔单抗有助于降低患者的抑制物水平，但其作为单一治疗策略的效果一般。未来的研究旨在确定利妥昔单抗在免疫耐受策略中作为辅助治疗的作用。
