Lerman Melissa A, Lewen Michael D, Kempen John H, Mills Monte D
Division of Rheumatology, The Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania.
New England Eye Center, Tufts Medical Center, Boston, Massachusetts.
Am J Ophthalmol. 2015 Jul;160(1):193-200.e1. doi: 10.1016/j.ajo.2015.04.016. Epub 2015 Apr 17.
To evaluate reactivation of pediatric uveitis during/following treatment with tumor necrosis factor alpha inhibition (anti-TNFα).
Retrospective cohort study.
We assessed the incidence of uveitis reactivation in children ≤18 years who had achieved uveitis quiescence under anti-TNFα. Survival analysis was used to calculate reactivation rates while still on (primary outcome), and following discontinuation of (secondary outcome), anti-TNFα. Potential predictive factors were assessed.
Among 50 children observed to develop quiescence of uveitis under anti-TNFα, 39 met criteria to be "at risk" of the primary (19 for the secondary) outcome. 60% were female, ∼half had juvenile idiopathic arthritis, and most were treated with infliximab. Overall, the estimated proportion relapsing within 12 months was 27.8% (95% confidence interval [CI]: 15.9%-45.8%); the estimated probability of reactivation was higher following (63.8% [95% CI: 38.9%-87.7%]) vs before (21.6% [95% CI: 10.8%-40.2%]) anti-TNFα discontinuation. Among those who discontinued anti-TNFα, the likelihood of reactivation was higher for those treated with adalimumab vs infliximab (hazard ratio [HR] 13.4, P = .01, 95% CI: 2.2-82.5) and those with older age at uveitis onset (HR 1.3, P = .09, 95% CI: 1.0-1.7). The duration of suppression, on medication, did not significantly affect the likelihood of reactivation when quiescence was maintained for ≥1.5 years.
Approximately 75% of children remaining on anti-TNFα following achievement of uveitis quiescence remain quiescent at 1 year. However, most reactivate following anti-TNFα discontinuation. These results suggest that infliximab more often is followed by remission, off medication, than adalimumab. The data do not suggest that maintenance of suppression for more than 1.5 years decreases the reactivation risk.
评估肿瘤坏死因子α抑制治疗(抗TNFα)期间及之后儿童葡萄膜炎的复发情况。
回顾性队列研究。
我们评估了年龄≤18岁且在抗TNFα治疗下葡萄膜炎已缓解的儿童中葡萄膜炎复发的发生率。采用生存分析计算在继续使用抗TNFα(主要结局)以及停用抗TNFα后(次要结局)的复发率。评估了潜在的预测因素。
在50名经观察在抗TNFα治疗下葡萄膜炎达到缓解的儿童中,39名符合主要结局(19名符合次要结局)“有风险”的标准。60%为女性,约一半患有幼年特发性关节炎,大多数接受英夫利昔单抗治疗。总体而言,估计12个月内复发的比例为27.8%(95%置信区间[CI]:15.9%-45.8%);停用抗TNFα后(63.8%[95%CI:38.9%-87.7%])的复发概率高于停用前(21.6%[95%CI:10.8%-40.2%])。在停用抗TNFα的患者中,接受阿达木单抗治疗的患者比接受英夫利昔单抗治疗的患者复发可能性更高(风险比[HR]13.4,P = 0.01,95%CI:2.2-82.5),葡萄膜炎发病时年龄较大的患者复发可能性也更高(HR 1.3,P = 0.09,95%CI:1.0-1.7)。当缓解状态维持≥1.5年时,用药期间的抑制持续时间对复发可能性没有显著影响。
葡萄膜炎缓解后继续使用抗TNFα治疗的儿童中,约75%在1年时仍保持缓解状态。然而,大多数患者在停用抗TNFα后复发。这些结果表明,与阿达木单抗相比,英夫利昔单抗停药后更常出现缓解。数据并不表明抑制状态维持超过1.5年会降低复发风险。