To compare the efficacy, serum drug concentrations, immunogenicity, and safety of FKB327 with the adalimumab reference product (RP) in combination with methotrexate in patients with moderate-to-severe, active rheumatoid arthritis (RA). Patients were randomized 1:1 in a double-blind study (NCT02260791), received 40 mg of FKB327 or RP by subcutaneous injection every other week for 24 weeks (Period I), then re-randomized 2:1, remaining on the same study drug or switching to the other up to week 54 in an open-label extension (Period II, NCT02405780). Efficacy was evaluated using American College of Rheumatology (ACR20) response rate difference at week 24 with equivalence margins of ± 13% and − 12% to + 15% using 95% and 90% confidence intervals (CIs), respectively. Efficacy, serum drug concentrations, immunogenicity, and safety were compared at week 54. A total of 730 patients were randomized in Period I (n = 367 FKB327, n = 363 RP), and 645 transitioned to Period II (n = 216 FKB327–FKB327, n = 108 FKB327–RP, n = 108 RP–FKB327, n = 213 RP–RP). At week 24, ACR20 response rates were 74.1% with FKB327 versus 75.7% with RP. 95% and 90% CI of the response rate difference were − 7.9 to 4.7% and − 7.3 to 3.6%, respectively, meeting predefined equivalence margins. The ACR20 response rate remained over 70% of patients to week 54 with all treatment sequences. In Period I, mean trough serum drug concentrations were slightly higher for patients receiving FKB327 than those receiving RP. Mean concentrations were stable over time and reflected steady state in Period II. The proportions of patients with samples positive for neutralizing antidrug antibodies (ADAs) were comparable (57.7% with FKB327 vs. 55.5% with RP) at week 24, and no consistent difference in ADA were seen between continuous and switched treatments in Period II. Efficacy was slightly reduced in the small proportion of patients with high ADA titers in all treatment groups. No clinically significant differences were observed in the incidence of commonly reported treatment-emergent adverse events between the treatments across Periods I and II. FKB327 was equivalent to RP in clinical efficacy and demonstrated comparable safety and immunogenicity in patients with moderate-to-severe RA. No effect of switching between FKB327 and RP was observed. ClinicalTrials.gov, NCT02260791, Registered 29 July 2014. ClinicalTrials.gov, NCT02405780, Registered 17 July 2015.

中文翻译：

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阿达木单抗生物仿制药FKB327与参考产品的比较：一项随机，III期，双盲研究及其开放标签扩展的结果

为了比较FKB327与阿达木单抗参考产品（RP）联合甲氨蝶呤在中度至重度活动性类风湿关节炎（RA）患者中的疗效，血清药物浓度，免疫原性和安全性。患者在双盲研究（NCT02260791）中以1：1随机分组，每隔一周皮下注射40毫克FKB327或RP，持续24周（期间I），然后以2：1重新随机分组，继续进行同一研究药物或在开放标签扩展中的第54周之前切换至其他药物（Period II，NCT02405780）。使用美国风湿病学会（ACR20）在第24周时的反应率差异评估疗效，当量裕度分别为±13％和-12％至+ 15％，分别使用95％和90％的置信区间（CI）。功效，血清药物浓度，免疫原性，在第54周时对安全性和安全性进行了比较。总共730例患者在I期中随机分组（n = 367 FKB327，n = 363 RP），并且有645例患者过渡到II期（n = 216 FKB327–FKB327，n = 108 FKB327–RP ，n = 108 RP–FKB327，n = 213 RP–RP）。在第24周时，FKB327对ACR20的应答率为74.1％，而对RP为75.7％。响应率差异的95％和90％CI分别为-7.9至4.7％和-7.3至3.6％，满足了预定的当量裕度。到第54周为止，所有治疗顺序的ACR20反应率仍超过70％。在第一阶段，接受FKB327的患者的平均谷液血清药物浓度略高于接受RP的患者。平均浓度随时间推移是稳定的，并且在时期II中反映出稳定状态。在第24周，中和抗药抗体（ADAs）阳性的患者比例相当（FKB327为57.7％，RP为55.5％），并且在第二阶段的连续治疗和转换治疗之间，ADA均未见一致的差异。在所有治疗组中，小比例的ADA滴度高的患者的疗效略有降低。在第I和第II期，各治疗之间通常报道的治疗紧急不良事件的发生率未观察到临床上的显着差异。FKB327的临床疗效与RP相当，并且在中度至重度RA患者中显示出可比的安全性和免疫原性。没有观察到在FKB327和RP之间切换的效果。ClinicalTrials.gov，NCT02260791，于2014年7月29日注册。ClinicalTrials.gov，NCT02405780，