Effectiveness, safety, and methotrexate dose-tapering pattern over two years of treatment with adalimumab and ≥12 mg/week methotrexate for early rheumatoid arthritis: Results of the HAWK postmarketing surveillance study in Japan

<b>Objectives:</b> To investigate the long-term effectiveness, safety, and methotrexate (MTX) dose-tapering patterns in patients with rheumatoid arthritis (RA) receiving adalimumab plus high-dose MTX. <b>Methods:</b> In this prospective, postmarketing study (2012–2017), conducted at 128 sites in Japan, biologic-naïve patients with RA (duration ≤2 years) previously treated with MTX for ≥3 months, initiated treatment with adalimumab and MTX (≥12 mg/week). Effectiveness by Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), safety, and MTX dose-tapering were assessed from baseline to 104 weeks. <b>Results:</b> In the effectiveness analysis set (<i>n</i> = 292), DAS28-CRP remission (&lt;2.6) was achieved in 92.3% (<i>n</i> = 120/130) of patients at week 104. The proportions of patients receiving MTX dose &lt;10 mg/week increased to 32.3% (<i>n</i> = 50/155) and ≥12 mg/week reduced to 52.9% (<i>n</i> = 82/155) by week 104. Per univariate regression analysis, MTX dose tapering was associated with longer adalimumab drug survival. Of 70 patients with joint X-rays available, 59 (84.3%) achieved Δ modified total Sharp score ≤1.0 at 104 weeks. In the safety analysis set (<i>n</i> = 300), 143 adverse drug reactions were reported in 92 patients (30.7%, non-serious; 24.7%, serious 8.7%). <b>Conclusion:</b> The long-term effectiveness and safety of adalimumab with high-dose MTX was confirmed in biologic-naïve patients with early RA in a real-world setting in Japan. <b>Clinical Trial Registration:</b> This study is registered at ClinicalTrials.gov (identifier: NCT01736189; retrospectively registered 29 November 2012, due to administrative reasons).

<b>研究目的:</b> 探讨接受阿达木单抗（adalimumab）联合高剂量甲氨蝶呤（methotrexate, MTX）治疗的类风湿关节炎（rheumatoid arthritis, RA）患者的长期疗效、安全性以及甲氨蝶呤剂量递减模式。<b>研究方法:</b> 本项前瞻性上市后研究于2012年至2017年在日本128家研究中心开展，纳入既往接受甲氨蝶呤治疗≥3个月、病程≤2年且未使用过生物制剂的类风湿关节炎患者，予以阿达木单抗联合甲氨蝶呤（每周剂量≥12mg）起始治疗。于基线至第104周期间，评估基于C反应蛋白的28关节疾病活动度评分（Disease Activity Score in 28 joints using C-reactive protein, DAS28-CRP）的疗效、安全性以及甲氨蝶呤剂量递减情况。<b>研究结果:</b> 在疗效分析集（n=292）中，至第104周时，92.3%（130例中的120例）的患者达到DAS28-CRP缓解（评分<2.6）。至第104周时，接受甲氨蝶呤剂量<10mg/周的患者比例升至32.3%（155例中的50例），而接受剂量≥12mg/周的患者比例降至52.9%（155例中的82例）。单变量回归分析显示，甲氨蝶呤剂量递减与阿达木单抗药物留存时间更长存在相关性。在70例具备关节X线影像资料的患者中，59例（84.3%）在第104周时的改良总Sharp评分变化量（Δ modified total Sharp score）≤1.0。在安全性分析集（n=300）中，92例患者共报告143例次药品不良反应，其中非严重不良反应占30.7%，严重不良反应占8.7%（原文括号内表述为"30.7%, non-serious; 24.7%, serious 8.7%"，存在排版疏漏）。<b>研究结论:</b> 本研究证实，在日本真实世界研究场景下，未使用过生物制剂的早期类风湿关节炎患者接受阿达木单抗联合高剂量甲氨蝶呤治疗的长期疗效与安全性均得到验证。<b>临床试验注册:</b> 本研究已在ClinicalTrials.gov注册（注册编号：NCT01736189；因行政原因于2012年11月29日完成回溯注册）。