Collins P W, Mathias M, Hanley J, Keeling D, Keenan R, Laffan M, Perry D, Liesner R
School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UK.
J Thromb Haemost. 2009 May;7(5):787-94. doi: 10.1111/j.1538-7836.2009.03332.x. Epub 2009 Mar 5.
SUMMARY BACKGROUND AND OBJECTIVES: he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab in up to 57% of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias of reporting good outcomes and relatively short follow up, a consecutive cohort of all patients treated in the UK with prolonged follow up was analyzed.
A national survey of all Comprehensive Care Haemophilia Center in the UK.
A total of 15 patients were reported of whom six (40%) achieved a negative inhibitor titer by Bethesda assay. Durable responses were unusual, observed in only 14% of cases. Clinically significant responses with either a negative inhibitor or an inhibitor titer < 5 BU mL(-1) and no spontaneous bleeding with FVIII replacement were observed in seven (47%) cases. Concomitant use of FVIII appeared to be important. Of the 12 patients treated with rituximab and FVIII, six (50%) achieved a negative inhibitor titer and seven (58%) had a clinically beneficial response. None of the three patients treated without FVIII responded.
These data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon.
摘要背景与目的：对于重度甲型血友病且对标准免疫耐受有抵抗的VIII因子（FVIII）抑制物患者的管理具有挑战性。近期有病例报告称，作为挽救性免疫耐受方案的一部分，利妥昔单抗在高达57%的患者中成功使用。由于病例报告和小样本系列研究容易出现报告良好结果和随访相对较短的潜在偏差，因此对英国所有接受治疗且随访时间延长的患者连续队列进行了分析。
对英国所有综合护理血友病中心进行全国性调查。
共报告了15例患者，其中6例（40%）通过贝塞斯达试验实现抑制物滴度阴性。持久反应并不常见，仅在14%的病例中观察到。7例（47%）病例观察到具有临床意义的反应，即抑制物阴性或抑制物滴度<5 BU/mL（-1）且使用FVIII替代治疗无自发出血。同时使用FVIII似乎很重要。在接受利妥昔单抗和FVIII治疗的12例患者中，6例（50%）实现抑制物滴度阴性，7例（58%）有临床有益反应。未接受FVIII治疗的3例患者均无反应。
这些数据表明，利妥昔单抗联合FVIII的使用对于对标准免疫耐受有抵抗的抑制物患者可能是一种有用的治疗方法，尽管持续根除抑制物并不常见。
