Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, OR, USA.
Department of Dermatology, New York Medical College at Metropolitan Hospital, New York, NY, USA.
Lancet. 2018 Jun 2;391(10136):2213-2224. doi: 10.1016/S0140-6736(18)30952-8. Epub 2018 Jun 1.
Guselkumab, a human monoclonal antibody that binds to the p19 subunit of interleukin 23, has been approved for the treatment of moderate-to-severe psoriasis. Psoriatic arthritis is a common comorbidity of psoriasis with an umet need for novel treatments. We assessed the efficacy and safety of guselkumab in patients with active psoriatic arthritis.
We did a randomised, double-blind, placebo-controlled, phase 2a trial at 34 rheumatology and dermatology practices in Canada, Germany, Poland, Romania, Russia, Spain, and the USA. Eligible participants were aged 18 years or older with active psoriatic arthritis and plaque psoriasis affecting at least 3% of their body surface area, with three or more of 66 tender joints and three or more of 68 swollen joints, who had an inadequate response or intolerance to standard treatments. We randomly assigned patients (2:1) via a central interactive web-response system using computer-generated permuted blocks with a block size of six, stratified by previous anti-tumour necrosis factor-α use, to receive subcutaneous guselkumab 100 mg or placebo at week 0, week 4, and every 8 weeks thereafter for 24 weeks. Patients, investigators, and site staff were masked to treatment assignment until final database lock at week 56. At week 16, patients with less than 5% improvement in swollen and tender joint counts were eligible for early escape to ustekinumab. At week 24, the remaining placebo-treated patients crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 and guselkumab-treated patients received a placebo injection at week 24, followed by guselkumab injections at weeks 28, 36, and 44. The primary endpoint was the proportion of patients with at least 20% improvement at week 24 in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria (ACR20) in the modified intention-to-treat population (ie, all randomly assigned patients who received at least one dose of study treatment). Safety analyses included patients according to the study drug received. This study is registered with ClinicalTrials.gov, number NCT02319759.
Between March 27, 2015, and Jan 17, 2017, we randomly assigned 149 patients to treatment: 100 to guselkumab and 49 to placebo. 17 (35%) of 49 patients in the placebo group and ten (10%) of 100 patients in the guselkumab group were eligible for early escape to ustekinumab at week 16. 29 (59%) of 49 patients in the placebo group crossed over and received guselkumab at week 24. Three (6%) of 49 patients in the placebo group, one (3%) of 29 patients who crossed over from placebo to guselkumab, and six (6%) of 100 patients in the guselkumab group discontinued study treatment before week 44. 58 (58%) of 100 patients in the guselkumab group and nine (18%) of 49 patients in the placebo group achieved an ACR20 response at week 24 (percentage difference 39·7% [95% CI 25·3-54·1]; p<0·0001). Between week 0 and week 24, 36 (36%) of 100 guselkumab-treated patients and 16 (33%) of 49 placebo-treated patients had at least one adverse event. The most frequent adverse event was infection in both groups (16 [16%] of 100 patients in the guselkumab group vs ten [20%] of 49 patients in the placebo group). The prevalence of adverse events between week 0 and week 56 in guselkumab-treated patients (51 [40%] of 129) indicated no disproportional increase with longer guselkumab exposure. No deaths occurred.
Guselkumab, a novel anti-interleukin 23p19 antibody, significantly improved signs and symptoms of active psoriatic arthritis and was well tolerated during 44 weeks of treatment. The results of this study support further development of guselkumab as a novel and comprehensive treatment in psoriatic arthritis.
Janssen Research & Development.
Guselkumab 是一种与人白细胞介素 23p19 亚单位结合的单克隆抗体，已被批准用于治疗中度至重度银屑病。银屑病关节炎是银屑病的常见合并症，需要新的治疗方法。我们评估了 Guselkumab 在活动性银屑病关节炎患者中的疗效和安全性。
我们在加拿大、德国、波兰、罗马尼亚、俄罗斯、西班牙和美国的 34 个风湿病和皮肤科诊所进行了一项随机、双盲、安慰剂对照、2a 期试验。符合条件的参与者年龄在 18 岁或以上，患有活动性银屑病关节炎和斑块状银屑病，影响其身体表面积的至少 3%，有 66 个压痛关节中的 3 个或更多，68 个肿胀关节中的 3 个或更多，对标准治疗反应不足或不耐受。我们通过中央互动网络响应系统，使用计算机生成的、大小为 6 的置换块，按先前使用抗肿瘤坏死因子-α的情况，将患者（2:1）随机分配接受 Guselkumab 100mg 或安慰剂，在第 0 周、第 4 周和此后每 8 周一次，共 24 周。在第 56 周最终数据库锁定之前，患者、研究者和现场工作人员对治疗分配保持盲态。在第 16 周，肿胀和压痛关节计数改善不足 5%的患者有资格早期改用乌司奴单抗。在第 24 周，其余接受安慰剂治疗的患者交叉接受 Guselkumab 100mg，在第 24、28、36 和 44 周，接受 Guselkumab 治疗的患者在第 24 周接受安慰剂注射，然后在第 28、36 和 44 周接受 Guselkumab 注射。主要终点是在改良意向治疗人群（即，接受至少一剂研究治疗的所有随机分配患者）中，第 24 周时根据美国风湿病学会标准（ACR20）评估的银屑病关节炎体征和症状改善至少 20%的患者比例。安全性分析包括根据研究药物接受治疗的患者。本研究在 ClinicalTrials.gov 注册，编号为 NCT02319759。
在 2015 年 3 月 27 日至 2017 年 1 月 17 日期间，我们随机分配了 149 名患者接受治疗：100 名接受 Guselkumab 治疗，49 名接受安慰剂治疗。49 名安慰剂组中的 17 名（35%）和 100 名 Guselkumab 组中的 10 名（10%）患者在第 16 周有资格早期改用乌司奴单抗。49 名安慰剂组中的 29 名（59%）患者在第 24 周交叉接受 Guselkumab 治疗。49 名安慰剂组中的 3 名（6%）患者、从安慰剂交叉至 Guselkumab 的 29 名患者中的 1 名（3%）患者和 Guselkumab 组中的 6 名（6%）患者在第 44 周前停止了研究治疗。Guselkumab 组中有 58 名（58%）患者和安慰剂组中有 9 名（18%）患者在第 24 周达到 ACR20 反应（差异百分比为 39.7%[95%CI 25.3-54.1]；p<0.0001）。在第 0 周至第 24 周期间，Guselkumab 治疗组中有 36 名（36%）患者和安慰剂组中有 16 名（33%）患者发生至少一次不良事件。两组中最常见的不良事件均为感染（Guselkumab 组 100 名患者中有 16 名[16%]，安慰剂组 49 名患者中有 10 名[20%]）。在 Guselkumab 治疗患者中，从第 0 周到第 56 周的不良事件发生率（129 名中的 51 名[40%]）表明，随着 Guselkumab 暴露时间的延长，不良事件没有不成比例的增加。没有死亡发生。
Guselkumab，一种新型抗白细胞介素 23p19 抗体，显著改善了活动性银屑病关节炎的体征和症状，在 44 周的治疗期间耐受性良好。这项研究的结果支持进一步开发 Guselkumab 作为银屑病关节炎的一种新型综合治疗方法。
杨森研究与开发公司。
