托珠单抗皮下注射联合改善病情抗风湿药物治疗类风湿关节炎的两年疗效和安全性：包括递增至每周给药方案。
Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis.
机构信息
From the Altoona Center for Clinical Research, Duncansville, Pennsylvania; University of Nevada School of Medicine, Las Vegas, Nevada; Clinical Research Center of Reading, Reading, Pennsylvania; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Genentech, South San Francisco, California, USA; Universidad Autónoma de Chihuahua, Chihuahua; Centro de Investigacion en Enfermedades Reumaticas, Mexicali, Baja California, Mexico; Hospital Virgen Macarena, Servicio de Reumatología, Sevilla, Spain; Universidade Federal do Paraná, Curitiba, Brazil; Roche Pharmaceuticals, Welwyn Garden City, London, UK; St. Joseph's Health Centre, Western University, London, Ontario, Canada.
F. Navarro-Sarabia received consulting fees and speakers bureau fees from Roche Pharmaceuticals. S.C. Radominski received research grants from Roche Pharmaceuticals. J.T. Merrill received consulting fees from Roche Pharmaceuticals and Genentech. J. Pei is an employee of Genentech. C. Nasmyth-Miller is an employee of Roche Pharmaceuticals. A. Kivitz, MD, Altoona Center for Clinical Research; E. Olech, MD, University of Nevada School of Medicine; M.A. Borofsky, MD, Clinical Research Center of Reading; B. Zazueta, MD, Centro de Investigacion en Enfermedades Reumaticas; F. Navarro-Sarabia, MD, Hospital Virgen Macarena, Servicio de Reumatología; S.C. Radominski, MD, Universidade Federal do Paraná; J.T. Merrill, MD, Oklahoma Medical Research Foundation; C. Pacheco-Tena, MD, Universidad Autónoma de Chihuahua; J. Pei, BS, Genentech; C. Nasmyth-Miller, DPhil, Roche Pharmaceuticals; J.E. Pope, MD, St. Joseph's Health Centre, Western University.
出版信息
J Rheumatol. 2018 Apr;45(4):456-464. doi: 10.3899/jrheum.161539. Epub 2017 Dec 15.
OBJECTIVE
To evaluate the longterm efficacy and safety of subcutaneous tocilizumab (TCZ-SC) every 2 weeks (q2w) over 2 years in patients with rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARD).
METHODS
Patients (n = 656) were randomized 2:1 to TCZ-SC 162 mg q2w or placebo-SC q2w plus DMARD. After a 24-week double-blind period, patients (n = 457) were rerandomized to open-label TCZ-SC q2w by means of prefilled syringe or autoinjector. Escape therapy with weekly TCZ-SC was available for patients with inadequate efficacy from Week 12. Maintenance of response and safety to 2 years was assessed. Analyses used nonresponder imputation.
RESULTS
The American College of Rheumatology (ACR) 20 response after TCZ-SC was maintained beyond Week 24 and was > 70% at each timepoint. ACR50/70, 28-joint Disease Activity Score remission, and ≥ 0.30 decrease from baseline in the Health Assessment Questionnaire-Disability Index response rates were also maintained after Week 24 in the TCZ-SC arm (≥ 50%, > 25%,> 32% and > 56%, respectively). Following escape for inadequate efficacy, many patients achieved ACR20 at the end of the study, 35% after escape from TCZ-SC, and 63% from placebo. The rates of serious adverse events [(11.20/100 patient-years (PY)] including serious infections (3.25/100 PY) were stable through Week 96. No association between anti-TCZ antibody development and loss of efficacy or adverse events was observed.
CONCLUSION
Efficacy and safety of TCZ-SC q2w was maintained up to 2 years and remained comparable with previously published data for intravenous TCZ. Dose escalation to weekly TCZ-SC was associated with ACR responses in prior nonresponders and was well tolerated.
目的
评估皮下注射托珠单抗（TCZ-SC）每 2 周（q2w）治疗对改善疾病修饰抗风湿药物（DMARD）应答不足的类风湿关节炎患者的长期疗效和安全性。
方法
将 656 例患者随机分为 2:1 接受 TCZ-SC 162mg/q2w 或安慰剂-SC q2w 联合 DMARD 治疗。24 周双盲期后，457 例患者（n=457）采用预充式注射器或自动注射器接受开放标签 TCZ-SC q2w 治疗。从第 12 周开始，对于疗效不足的患者可采用每周 TCZ-SC 进行解救治疗。评估 2 年时的应答维持和安全性。分析采用非应答者推断法。
结果
TCZ-SC 治疗后，美国风湿病学会（ACR）20 应答在第 24 周后仍得以维持，且各时间点应答率均>70%。ACR50/70、28 关节疾病活动度评分缓解和健康评估问卷残疾指数（HAQ-DI）自基线的≥0.30 降幅的应答率在 TCZ-SC 治疗组也在第 24 周后得以维持（分别为≥50%、>25%、>32%和>56%）。在因疗效不足进行解救治疗后，许多患者在研究结束时达到了 ACR20，其中 35%来自 TCZ-SC 解救，63%来自安慰剂解救。严重不良事件（AE）发生率（11.20/100 患者年[PY]），包括严重感染（3.25/100 PY），在第 96 周时保持稳定。未观察到抗 TCZ 抗体的产生与疗效丧失或不良事件之间存在关联。
结论
TCZ-SC q2w 的疗效和安全性可维持 2 年，与先前发表的 TCZ 静脉制剂数据相当。对先前无应答者进行 TCZ-SC 剂量递增至每周治疗与 ACR 应答相关，且耐受性良好。
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