皮下注射阿巴西普治疗类风湿关节炎患者的长期安全性和疗效：IIIb 期试验 5 年结果。
Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.
机构信息
From Stanford University, Palo Alto, California; Arthritis Center of Nebraska, Lincoln, Nebraska; Box Arthritis and Rheumatology of the Carolinas, Charlotte, North Carolina; Low Country Rheumatology, Charleston, South Carolina; Bristol-Myers Squibb, Princeton, New Jersey, USA; Universidad Autónoma de Chihuahua, Chihuahua; Unidad Reumatológica Las Américas S.C.P., Mérida; Köhler & Milstein Research, Mérida, Mexico; Instituto De Ginecología Y Reproducción, Lima, Peru; Organización Médica de Investigación, Buenos Aires, Argentina; Pontifical Catholic University, Porto Alegre, Brazil; University of Queensland, Brisbane, Australia; Russian Academy of Medical Sciences, Moscow, Russia; Cliniques Universitaires Saint-Luc; Université Catholique de Louvain, Brussels, Belgium; Schlosspark-Klinik University Medicine, Berlin, Germany.
M.C. Genovese, MD, Stanford University; C. Pacheco-Tena, MD, PhD, Universidad Autónoma de Chihuahua; A. Covarrubias, MD, Unidad Reumatológica Las Américas S.C.P.; G. Leon, MD, Instituto De Ginecología Y Reproducción; E. Mysler, MD, Organización Médica de Investigación; M. Keiserman, MD, Pontifical Catholic University; R.M. Valente, MD, Arthritis Center of Nebraska; P. Nash, MBBS (Hons), FRACP, University of Queensland; J.A. Simon-Campos, PhD, Köhler & Milstein Research; J. Box, MD, Box Arthritis and Rheumatology of the Carolinas; C.W. Legerton III, MD, Low Country Rheumatology; E. Nasonov, PhD, Russian Academy of Medical Sciences; P. Durez, MD, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; A. Elegbe, PhD, Bristol-Myers Squibb; R. Wong, MD, Bristol-Myers Squibb; X. Li, PhD, Bristol-Myers Squibb; S. Banerjee, MD, Bristol-Myers Squibb; R. Alten, MD, PhD, Schlosspark-Klinik University Medicine.
出版信息
J Rheumatol. 2018 Aug;45(8):1085-1092. doi: 10.3899/jrheum.170344. Epub 2018 Apr 15.
OBJECTIVE
To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).
METHODS
The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported.
RESULTS
Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study.
CONCLUSION
These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.
目的
评估皮下（SC）阿巴西普（ABA）在甲氨蝶呤（MTX）难治性类风湿关节炎（RA）患者中的 5 年安全性、耐受性和疗效。
方法
阿巴西普比较皮下与静脉注射在 MTX 应答不足的患者中的疗效（ACQUIRE）是一项 IIIb 期、随机、双盲、多国试验，比较了 RA 患者 SC 和静脉（IV）ABA 的疗效和安全性。在最初的 6 个月双盲（DB）期间，患者接受 IV 或 SC ABA，加 MTX，随后在开放标签长期扩展（LTE）期间，所有患者接受 SC ABA（125mg/周）。报告了最终 5 年的安全性、耐受性和疗效分析。
结果
在完成 DB 期的 1385 名患者中，1372 名进入 LTE，945 名（68.8%）完成了≥5 年的治疗。在 LTE 期间，有 97 名（7.1%）患者因不良事件（AE）停止治疗。AE 发生率（IR；事件/100 患者年暴露率；基于 LTE 数据，95%CI）如下：严重 AE 为 7.73（6.96-8.58）、感染为 38.60（36.24-41.12）、严重感染为 1.68（1.35-2.07）、恶性肿瘤为 1.09（0.84-1.42）、自身免疫性疾病为 1.33（1.05-1.69），且随时间稳定。免疫原性与 ABA 安全性恶化或疗效丧失之间无关联。LTE 中的疗效与 DB 期一致，并持续到研究结束。
结论
这些 5 年数据表明，SC ABA（125mg/周）具有一致的安全性和长期治疗 MTX 应答不足的 RA 患者的持久疗效。
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