Acharya Nisha R, Ramanan Athimalaipet V, Coyne Alison B, Dudum Kathryn L, Rubio Elia M, Woods Sydney M, Guly Catherine M, Moraitis Elena, Petrushkin Harry J D, Armon Kate, Puvanachandra Narman, Choi Jessy T, Hawley Daniel P, Arnold Benjamin F
Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA.
Department of Paediatric Rheumatology, Bristol, UK; Translational Health Sciences, University of Bristol, Bristol, UK.
Lancet. 2025 Jan 25;405(10475):303-313. doi: 10.1016/S0140-6736(24)02468-1.
Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis.
We conducted a multicentre, double-masked, randomised, placebo-controlled trial at 20 ophthalmology and rheumatology clinics across the USA, the UK, and Australia. Patients aged at least 2 years who had controlled arthritis and uveitis for at least 1 year on adalimumab were randomly assigned in a 1:1 ratio using a web-based system to receive adalimumab or placebo, administered subcutaneously every 2 weeks until the 48-week visit or treatment failure. The primary outcome was the time to treatment failure, defined by recurrence of uveitis or arthritis; all participants were included in the primary and safety analysis. Unmasking occurred at treatment failure, and patients were offered open-label adalimumab through 48 weeks of follow-up. This trial was registered with ClinicalTrials.gov (NCT03816397).
87 patients were enrolled from March 3, 2020, to Feb 14, 2024, whereafter the prespecified interim stopping criteria were met and enrolment was stopped. One patient in each group dropped out but data were included in analyses. Six (14%) of 43 patients in the adalimumab group and 30 (68%) of 44 patients in the placebo group had treatment failure (hazard ratio 8·7, 95% CI 3·6-21·2; p<0·0001). The median time to treatment failure in the placebo group was 119 days (IQR 84-243). The median time to re-establishing sustained control of inflammation in the placebo group after restarting adalimumab was 105 days (63-196). 226 non-serious adverse events occurred in the adalimumab group (7·5 events per person-year, 95% CI 6·5-8·5), and 115 non-serious adverse events occurred in the placebo group (6·8 events per person-year, 5·6-8·1). Four serious adverse events were reported, all in the adalimumab group.
Discontinuing adalimumab led to higher rates of recurrence of uveitis, arthritis, or both in patients with previously controlled juvenile idiopathic arthritis-associated uveitis. However, all patients who had treatment failure successfully regained control of inflammation by the end of the 48-week study period after restarting adalimumab.
US National Institutes of Health (National Eye Institute).
阿达木单抗是治疗青少年特发性关节炎相关性葡萄膜炎的有效药物。关于疾病得到控制后停用阿达木单抗的效果，数据较少。我们旨在评估青少年特发性关节炎相关性葡萄膜炎患者停用治疗的疗效和安全性。
我们在美国、英国和澳大利亚的20家眼科和风湿病诊所进行了一项多中心、双盲、随机、安慰剂对照试验。年龄至少2岁、使用阿达木单抗使关节炎和葡萄膜炎得到控制至少1年的患者，通过基于网络的系统按1:1比例随机分配，接受阿达木单抗或安慰剂治疗，每2周皮下注射一次，直至第48周访视或治疗失败。主要结局是治疗失败时间，定义为葡萄膜炎或关节炎复发；所有参与者均纳入主要分析和安全性分析。治疗失败时揭盲，患者在48周随访期间接受开放标签的阿达木单抗治疗。本试验已在ClinicalTrials.gov注册（NCT03816397）。
2020年3月3日至2024年2月14日共纳入87例患者，此后达到预先设定的中期停药标准，停止入组。每组各有1例患者退出，但数据纳入分析。阿达木单抗组43例患者中有6例（14%）出现治疗失败，安慰剂组44例患者中有30例（68%）出现治疗失败（风险比8.7，95%CI 3.6 - 21.2；p<0.0001）。安慰剂组治疗失败的中位时间为119天（IQR 84 - 243）。安慰剂组重新开始使用阿达木单抗后重新建立炎症持续控制的中位时间为105天（63 - 196）。阿达木单抗组发生226例非严重不良事件（每人年7.5次事件，95%CI 6.5 - 8.5），安慰剂组发生115例非严重不良事件（每人年6.8次事件，5.6 - 8.1）。报告了4例严重不良事件，均发生在阿达木单抗组。
对于既往病情得到控制的青少年特发性关节炎相关性葡萄膜炎患者，停用阿达木单抗会导致葡萄膜炎、关节炎或两者复发率更高。然而，所有治疗失败的患者在重新开始使用阿达木单抗后，在48周研究期结束时均成功恢复了炎症控制。
美国国立卫生研究院（国家眼科研究所）。
