Matsubara Tsukasa, Inoue Hiroshi, Nakajima Toshihiro, Tanimura Kazuhide, Sagawa Akira, Sato Yukio, Osano Kei, Nagano Shuji, Ueki Yukitaka, Hanyu Tadamasa, Hashizume Koichi, Amano Norihito, Tanaka Yoshiya, Takeuchi Tsutomu
Department of Orthopedics, Matsubara Mayflower Hospital, Hyogo, Japan.
Department of Orthopaedic Surgery, Inoue Hospital, Gunma, Japan.
RMD Open. 2018 Dec 4;4(2):e000813. doi: 10.1136/rmdopen-2018-000813. eCollection 2018.
To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX.
In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups.
Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic non-progression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations.
Compared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.
评估阿巴西普联合甲氨蝶呤（MTX）对比安慰剂联合MTX，用于生物制剂初治、抗瓜氨酸化蛋白抗体（ACPA）阳性的日本活动性类风湿关节炎（RA）及早期侵蚀患者的疗效和安全性。
在这项IV期、多中心、双盲研究（NCT01758198）中，患者按1:1随机分组，接受静脉注射阿巴西普（约10mg/kg）或安慰剂，加用MTX（≥6mg/周）。主要疗效指标是比较阿巴西普联合MTX组与安慰剂联合MTX组在第16周时美国风湿病学会20（ACR20）反应率，以及在第24周时范德海伊德改良总Sharp评分（vdH-mTSS）较基线的平均变化。
总体上，分别有203例和202例患者接受了阿巴西普联合MTX和安慰剂联合MTX治疗。在第16周时，阿巴西普组的ACR20反应率（75.4%）高于安慰剂组（27.7%；p<0.001）。在第24周时，阿巴西普组vdH-mTSS较基线的平均变化为0.84，安慰剂组为1.26（p=0.017）。影像学无进展率（vdH-mTSS变化≤最小可检测变化（2.4））在阿巴西普组和安慰剂组分别为88.1%和75.4%。在第16周时，疾病活动评分28（C反应蛋白）（DAS28（CRP））较基线的调整后平均变化显示，阿巴西普组较安慰剂组在数值上有更大幅度的降低。至第52周时，阿巴西普组达到DAS28（CRP）、简化疾病活动指数和临床疾病活动指数缓解的患者比例高于安慰剂组。阿巴西普的安全性与既往观察结果一致。
与单用MTX相比，阿巴西普联合MTX改善了ACPA阳性、日本RA、早期侵蚀且对MTX反应不佳患者的临床症状，并抑制了结构损伤进展。
