美国罗切斯特大学医学中心Christopher T Ritchlin研究小组研究了Bimekizumab治疗活动期银屑病关节炎患者的疗效。该研究于2020年2月8日发表于国际一流学术期刊《柳叶刀》杂志上。
将其随机分为5组，其中42名接受安慰剂，41名接受16mg的bimekizumab，41名接受160mg的bimekizumab，41名先接受160mg的bimekizumab，后加量至320mg；41名接受320mg的bimekizumab。每4周注射一次，持续12周。12周后，安慰剂组和16mg bimekizumab组再随机接受160mg或320mg bimekizumab进行治疗，所有患者均治疗48周。
在第12周时，与安慰剂组相比，16mg bimekizumab组、160mg bimekizumab组和160mg bimekizumab加载剂量组的患者关节炎改善超过50%（ACR50）的比例显著增加。安慰剂组中不良事件发生率为57%，bimekizumab组164名患者中不良事件的发生率为41%。这些不良反应多为轻中度。共有9例患者出现严重不良事件，其中bimekizumab组有8例。没有死亡或炎症性肠病发生。
Title: Bimekizumab in patients with active psoriatic arthritis: results from a 48-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2b trial
Author: Christopher T Ritchlin, Arthur Kavanaugh, Joseph F Merola, Georg Schett, Jose U Scher, Richard B Warren, Alice B Gottlieb, Deepak Assudani, Kathy Bedford-Rice, Jason Coarse, Barbara Ink, Iain B McInnes
Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis.
BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525.
Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio [OR] 4·2 [95% CI 1·1–15·2]; p=0·032), 160 mg bimekizumab (8·1 [2·3–28·7]; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 [2·7–34·3]; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported.
Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis.