University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
University of Leeds, Leeds, UK.
Arthritis Rheumatol. 2017 Jul;69(7):1440-1450. doi: 10.1002/art.40093. Epub 2017 Jun 5.
To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS).
We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness.
All 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group).
The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.
研究抗 B 细胞治疗药物利妥昔单抗是否能改善原发性干燥综合征（pSS）患者的疲劳和口干症状。
我们进行了一项多中心、随机、双盲、安慰剂对照、平行组试验，并进行了卫生经济学分析。2011 年 8 月至 2014 年 1 月，从英国 25 家风湿病诊所招募了抗 Ro 阳性、原发性 SS、有症状性疲劳和口干的患者。患者经中央随机分配，分别接受静脉（IV）安慰剂（250 ml 生理盐水）或 IV 利妥昔单抗（250 ml 生理盐水中 1000 mg），在第 0、2、24 和 26 周进行 2 个疗程，预输注和输注药物均包括皮质类固醇。主要终点是在 48 周时，通过视觉模拟量表（VAS）评估，疲劳或口干症状改善 30%的患者比例。其他结局指标包括唾液和泪液流量、生活质量、欧洲抗风湿病联盟（EULAR）干燥综合征患者报告指数和 EULAR 干燥综合征疾病活动指数评分、眼部和总体干燥症状、疼痛、全球评估疾病活动度和成本效益。
所有随机接受安慰剂（n=66）或利妥昔单抗（n=67）治疗的 133 名患者均纳入主要分析。在完成数据的患者中，56 名安慰剂治疗患者中有 21 名和 61 名利妥昔单抗治疗患者中有 24 名达到了主要终点。在对缺失结果进行多次插补后，安慰剂组和利妥昔单抗组的缓解率分别为 36.8%和 39.8%（调整后的优势比 1.13[95%置信区间 0.50，2.55]）。除未刺激唾液流外，任何结局指标均无显著改善。利妥昔单抗和安慰剂的每位患者平均（±标准差）费用分别为 10752 英镑（±264.75 英镑）和 2672 英镑（±241.71 英镑）。利妥昔单抗组总的不良事件（AE）报告略多，但严重 AE 无差异（每组 10 例）。
本研究结果表明，在该患者人群中，利妥昔单抗既无临床疗效，也无成本效益。
