BACKGROUND Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. METHODS This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080. FINDINGS Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. INTERPRETATION Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. FUNDING Novartis Pharma.

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Secukinumab与adalimumab治疗活动性银屑病关节炎（EXCEED）：一项双盲，平行分组，随机，活性对照的3b期临床试验。

背景技术银屑病关节炎的头对头试验有助于指导临床决策。EXCEED研究评估了苏金单抗和阿达木单抗作为一线生物学单一疗法在活动性银屑病关节炎患者中的疗效和安全性，治疗期为52周，其风湿性关节炎的主要终点为美国风湿病学会（ACR）20。方法这项平行组，双盲，主动控制，3b期，多中心（在26个国家/地区的168个试验）试验纳入了至少18岁的活动性银屑病关节炎患者。通过互动反应技术将符合条件的患者随机分配（1：1），以接受苏金单抗或阿达木单抗。患者，研究人员，现场人员和进行评估的人员（独立研究药物管理人员除外）被掩盖了研究任务。在基线，第1、2、3和4周，皮下注射300 mg苏金单抗，然后每4周注射一次，直到第48周作为预装注射器。从基线到第50周，每2周服用一次Adalimumab，剂量为每0·4 mL柠檬酸盐皮下注射40 mg。主要结局是在52周时ACR反应标准（ACR20）改善至少20％的患者比例。根据患者被随机分配的治疗方法对其进行分析。安全性分析包括报告的所有安全性数据，包括直到第52周就诊的每位接受至少一种研究药物剂量的患者。该试验已在ClinicalTrials.gov上注册，编号NCT02745080。结果在2017年4月3日至2018年8月23日之间，我们随机分配853名患者接受苏金单抗（n = 426）或阿达木单抗（n = 427）。853名患者中有709名（83％）在研究的第52周完成了治疗，其中691名（81％）在第50周接受了最后的研究治疗。secukinumab组的426名患者中有61名（14％）在第52周之前停止治疗，而在101周之前停止治疗阿达木单抗组的427名患者中有24％（24％）。未达到苏金单抗相对于阿达木单抗在52周时ACR20反应优越性的主要终点。苏金单抗组中有67％的患者在52周时获得了ACR20应答，而阿达木单抗组中的这一比例为62％（OR 1·30，95％CI 0·98-1·72； p = 0·0719）。苏金单抗和阿达木单抗的安全性与以前的报道一致。secukinumab组的426名患者中有7名（2％），阿达木单抗组的427名患者中有6名（1％）有严重感染。据报道，苏金单抗组中有1例死于结肠癌，研究者认为该死亡与研究药物无关。解释在52周时，在ACR20反应的主要终点中，Secukinumab对阿达木单抗的优越性未达到统计学显着性。但是，与Adalimumab相比，苏金单抗的治疗保留率更高。这项研究提供了具有不同作用机制的两种生物制剂的比较数据，这可能有助于指导银屑病关节炎患者管理中的临床决策。资金诺华制药。与阿达木单抗相比，苏金单抗的治疗保留率更高。这项研究提供了具有不同作用机制的两种生物制剂的比较数据，这可能有助于指导银屑病关节炎患者管理中的临床决策。资金诺华制药。与阿达木单抗相比，苏金单抗的治疗保留率更高。这项研究提供了具有不同作用机制的两种生物制剂的比较数据，这可能有助于指导银屑病关节炎患者管理中的临床决策。资金诺华制药。