From the Faculty of Translational Health Sciences (C.A.B.), University of Bristol (J.I., K.B., R.K.), and the Bristol Haematology and Oncology Centre (C.A.B.) and the Research Design Service (R.G.), University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, the Centre for Trials Research, Cardiff University (J.P., I.T.), and the Department of Haematology, Cardiff and Vale University Health Board (R.R.), Cardiff, Leeds Teaching Hospitals NHS Trust, Leeds (Q.H.), Glasgow Royal Infirmary, Glasgow (C.B.), the Department of Immunology and Inflammation, Imperial College London, London (N.C.), East Kent Hospitals University NHS Foundation Trust, Canterbury (G.E.), and Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne (K.T.) - all in the United Kingdom.
N Engl J Med. 2021 Sep 2;385(10):885-895. doi: 10.1056/NEJMoa2100596.
Immune thrombocytopenia is a rare autoimmune disorder with associated bleeding risk and fatigue. Recommended first-line treatment for immune thrombocytopenia is high-dose glucocorticoids, but side effects, variable responses, and high relapse rates are serious drawbacks.
In this multicenter, open-label, randomized, controlled trial conducted in the United Kingdom, we assigned adult patients with immune thrombocytopenia, in a 1:1 ratio, to first-line treatment with a glucocorticoid only (standard care) or combined glucocorticoid and mycophenolate mofetil. The primary efficacy outcome was treatment failure, defined as a platelet count of less than 30×10 per liter and initiation of a second-line treatment, assessed in a time-to-event analysis. Secondary outcomes were response rates, side effects, occurrence of bleeding, patient-reported quality-of-life measures, and serious adverse events.
A total of 120 patients with immune thrombocytopenia underwent randomization (52.4% male; mean age, 54 years [range 17 to 87]; mean platelet level, 7×10 per liter) and were followed for up to 2 years after beginning trial treatment. The mycophenolate mofetil group had fewer treatment failures than the glucocorticoid-only group (22% [13 of 59 patients] vs. 44% [27 of 61 patients]; hazard ratio, 0.41; range, 0.21 to 0.80; P = 0.008) and greater response (91.5% of patients having platelet counts greater than 100×10 per liter vs. 63.9%; P<0.001). We found no evidence of a difference between the groups in the occurrence of bleeding, rescue treatments, or treatment side effects, including infection. However, patients in the mycophenolate mofetil group reported worse quality-of-life outcomes regarding physical function and fatigue than those in the glucocorticoid-only group.
The addition of mycophenolate mofetil to a glucocorticoid for first-line treatment of immune thrombocytopenia resulted in greater response and a lower risk of refractory or relapsed immune thrombocytopenia, but with somewhat decreased quality of life. (Funded by the U.K. National Institute for Health Research; FLIGHT ClinicalTrials.gov number, NCT03156452; EudraCT number, 2017-001171-23.).
免疫性血小板减少症是一种罕见的自身免疫性疾病，伴有出血风险和疲劳。免疫性血小板减少症的一线推荐治疗方法是大剂量糖皮质激素，但副作用、反应差异和高复发率是严重的缺点。
在英国进行的这项多中心、开放性、随机、对照试验中，我们将患有免疫性血小板减少症的成年患者按照 1:1 的比例随机分配，一线治疗采用糖皮质激素单药（标准治疗）或糖皮质激素联合霉酚酸酯。主要疗效终点是治疗失败，定义为血小板计数<30×10/L 并开始二线治疗，采用时间事件分析进行评估。次要终点是反应率、副作用、出血发生情况、患者报告的生活质量测量和严重不良事件。
共有 120 名免疫性血小板减少症患者接受了随机分组（52.4%为男性；平均年龄 54 岁[范围 17 至 87]；平均血小板水平 7×10/L），并在开始试验治疗后长达 2 年进行随访。霉酚酸酯组的治疗失败率低于糖皮质激素单药组（22%[59 例患者中的 13 例] vs. 44%[61 例患者中的 27 例]；风险比为 0.41；范围为 0.21 至 0.80；P=0.008），反应率更高（血小板计数>100×10/L 的患者为 91.5% vs. 63.9%；P<0.001）。我们没有发现两组在出血、抢救治疗或治疗副作用（包括感染）方面存在差异。然而，与糖皮质激素单药组相比，霉酚酸酯组患者在身体功能和疲劳方面的生活质量评分较差。
在糖皮质激素一线治疗免疫性血小板减少症时，加用霉酚酸酯可提高反应率，并降低难治性或复发性免疫性血小板减少症的风险，但生活质量略有下降。（由英国国家卫生研究院资助；FLIGHT ClinicalTrials.gov 编号，NCT03156452；EudraCT 编号，2017-001171-23。）
