Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study.
Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study.
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DOI：
10.1016/s2468-1253(17)30252-2
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
Denson LA
中科院分区：
文献类型：
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作者：
Hyams JS;Davis S;Mack DR;Boyle B;Griffiths AM;LeLeiko NS;Sauer CG;Keljo DJ;Markowitz J;Baker SS;Rosh J;Baldassano RN;Patel A;Pfefferkorn M;Otley A;Heyman M;Noe J;Oliva-Hemker M;Rufo P;Strople J;Ziring D;Guthery SL;Sudel B;Benkov K;Wali P;Moulton D;Evans J;Kappelman MD;Marquis A;Sylvester FA;Collins MH;Venkateswaran S;Dubinsky M;Tangpricha V;Spada KL;Britt A;Saul B;Gotman N;Wang J;Serrano J;Kugathasan S;Walters T;Denson LA
既往回顾性小儿溃疡性结肠炎（UC）研究描述疾病进展和确定治疗反应预测因子的能力有限。多中心队列研究旨在确定与初次诊断后标准化治疗结果相关的特征。我们在美国和加拿大的29个中心完成了一项前瞻性多中心初始队列研究，研究对象为新诊断为UC的4-17岁儿童患者，这些患者接受了根据儿童UC活动指数（PUCAI）指导的美沙拉嗪或皮质类固醇（CS）初始标准化治疗。该分析的关键结局是第12周无CS缓解（定义为PUCAI<10且仅服用美沙拉嗪），以及最初接受静脉（IV）CS治疗的患者治疗升级至抗TNF α、免疫调节剂或结肠切除术。采用符合方案的方法，通过多变量逻辑回归确定独立的预测因素。在clinicaltrials.gov注册：NCT 01536535 428名儿童开始使用美沙拉嗪（n=136）、口服CS（n=144）或IV CS（n=148），初始平均值±标准差PUCAI分别为31±13、50±14和67±14（p<0.001）。到第12周，仅服用美沙拉嗪的无CS缓解率为48%（64/132），口服CS为33%（47/141），IV CS为21%（30/143）（p<0.001）。分别有7%（9/132）、15%（21/141）和36%（52/143）的患者需要治疗升级（p<0.001）; 8例患者最初均接受IV CS治疗，后接受结肠切除术。第12周无CS缓解的预测因子为基线PUCAI <35（比值比（OR）2.4，95% CI 1.4-4.2; p=0.002），年龄< 12岁的患者基线白蛋白升高1 g/dL（4.1，1.9-8.6; p=0.0003），第4周缓解（6.3，3.8-10.4; p<0.0001）。在最初接受IV CS治疗的患者中，到第12周治疗递增的预测因素包括基线总马约评分≥11（2.6，0.9-7.2; p=0.068），直肠活检嗜酸性粒细胞计数≤32/高倍视野（4.6，1.6-12.8; p=0.004），直肠活检表面绒毛状变化（3.1，1.1-8.6; p=0.034），第4周未达到缓解（30.2，6.4-144.2; p<0.0001）。我们的研究结果为评估新诊断UC儿童对标准化初始治疗的反应提供了指导，并确定了治疗反应和失败的预测因素。这些数据表明，额外的治疗干预可能是必要的，以改善早期结果，特别是在那些严重的疾病，需要静脉注射皮质类固醇。
Previous retrospective pediatric ulcerative colitis (UC) studies had limited ability to describe disease progression and identify predictors of treatment response. The PROTECT multicentre inception cohort aimed to identify characteristics associated with outcomes following standardized therapy after initial diagnosis. We completed a prospective multicentre inception cohort study at 29 centres in the USA and Canada of paediatric patients aged 4–17 years newly diagnosed with UC who received initial standardized treatment with mesalamine or corticosteroids (CS) guided by the Pediatric UC Activity Index (PUCAI). The key outcomes for this analysis were week 12 CS-free remission, defined as PUCAI<10 and taking only mesalamine, and treatment escalation to anti-TNFα, immunomodulators or colectomy among those initially treated with intravenous (IV) CS. Independent predictors were identified through multivariable logistic regression using a per-protocol approach. Registered with clinicaltrials.gov: NCT01536535 428 children initiated mesalamine (n=136), oral CS (n=144), or IV CS (n=148) with initial mean ± standard deviation PUCAI of 31±13, 50±14, and 67±14, respectively (p<0.001). By week 12, CS-free remission taking mesalamine only was achieved by 48% (64/132) initiating with mesalamine, 33% (47/141) with oral CS, and 21% (30/143) with IV CS (p<0.001). Treatment escalation was required in 7% (9/132), 15% (21/141), and 36% (52/143), respectively (p<0.001); 8 patients, all initially treated with IV CS, received colectomy. Predictors of week 12 CS-free remission were baseline PUCAI <35 (odds ratio (OR) 2.4, 95% CI 1.4–4.2; p=0.002), higher baseline albumin by 1 g/dL increments among age < 12 years (4.1, 1.9–8.6; p=0.0003), and week 4 remission (6.3, 3.8–10.4; p<0.0001). Predictors of treatment escalation by week 12 in those initially treated with IV CS included baseline total Mayo score ≥11 (2.6, 0.9–7.2; p=0.068), rectal biopsy eosinophil count ≤32/high power field (4.6, 1.6–12.8; p=0.004), rectal biopsy surface villiform changes (3.1, 1.1–8.6; p=0.034) and not achieving week 4 remission (30.2, 6.4–144.2; p<0.0001). Our findings provide guidelines to assess response of children newly diagnosed with UC to standardized initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions may be warranted to improve early outcomes, especially in those presenting with severe disease and requiring intravenous corticosteroids.