Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Netherlands.
Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Netherlands; Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands.
Lancet Gastroenterol Hepatol. 2017 Nov;2(11):785-792. doi: 10.1016/S2468-1253(17)30248-0. Epub 2017 Aug 31.
Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life.
In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150).
Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF.
Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy.
Netherlands Organisation for Health Research and Development.
对于未对常规治疗产生应答的回肠末段克罗恩病患者，治疗方法通常会扩展到生物制剂，但手术也能提供出色的短期和长期效果。我们比较了腹腔镜回肠末段切除术和英夫利昔单抗对健康相关生活质量的影响。
在这项在荷兰和英国的 29 家教学医院和三级护理中心进行的随机对照、开放标签试验中，符合以下条件的非狭窄性、回肠末段克罗恩病成人患者，即传统疗法失败、有活动性末段回肠克罗恩病且对至少 3 个月的糖皮质激素、硫嘌呤或甲氨蝶呤常规治疗无应答，被随机分配（1:1），通过带有中心偏倚最小化的互联网随机分组模块和肛周瘘管接受腹腔镜回肠末段切除术或英夫利昔单抗治疗。合格患者的年龄为 18-80 岁，有末段回肠的活动性克罗恩病，且对至少 3 个月的糖皮质激素、硫嘌呤或甲氨蝶呤常规治疗无应答。排除有 40 cm 以上病变末段回肠或腹部脓肿的患者。主要结局是在 12 个月时采用炎症性肠病问卷（IBDQ）评估的生活质量。次要结局是采用健康调查简表（SF-36）及其身体和精神分量表测量的一般生活质量、无法参与社会生活的天数、休病假的天数、发病率（附加程序和住院）、以及体像和美容。对主要结局的分析在意向治疗人群中进行，安全性分析在符合方案人群中进行。本试验在荷兰临床试验注册中心（NTR1150）注册。
在 2008 年 5 月 2 日至 2015 年 10 月 14 日期间，73 名患者被分配接受切除术，70 名患者接受英夫利昔单抗治疗。校正基线差异后，在 12 个月时，切除术组的 IBDQ 评分平均为 178.1（95%CI 171.1-185.0），英夫利昔单抗组为 172.0（164.3-179.6）（平均差值 6.1 分，95%CI -4.2 至 16.4；p=0.25）。在 12 个月时，切除术组的 SF-36 总分平均为 112.1（95%CI 108.0-116.2），英夫利昔单抗组为 106.5（102.1-110.9）（平均差值 5.6，95%CI -0.4 至 11.6），身体成分平均分平均为 47.7（45.7-49.7），英夫利昔单抗组为 44.6（42.5-46.8；平均差值 3.1，4.2 至 6.0），精神成分平均分平均为 49.5（47.0-52.1），英夫利昔单抗组为 46.1（43.3-48.9；平均差值 3.5，-0.3 至 7.3）。切除术组休病假的平均天数为 3.4 天（SD 7.1），英夫利昔单抗组为 1.4 天（4.7）（p<0.0001），无法参与社会生活的平均天数为 1.8 天（6.3），英夫利昔单抗组为 1.1 天（4.5；p=0.20），计划住院的平均天数为 6.5 天（3.8），英夫利昔单抗组为 6.8 天（3.2；p=0.84），需要非计划住院的患者人数分别为切除术组 13 例（18%）和英夫利昔单抗组 15 例（21%）（p=0.68）。接受切除术的患者在基线时的体像量表平均得分为 16.0（95%CI 15.2-16.8），在 12 个月时为 17.8（17.1-18.4），美容量表平均得分为 17.6（16.6-18.6），在 12 个月时为 18.6（17.6-19.6）。在切除术组中，有 4 例患者的手术相关并发症按 Clavien-Dindo 分级为 IIIa 级或更高级别。在英夫利昔单抗组中，有 2 例患者发生治疗相关的严重不良事件。在中位随访 4 年（IQR 2-6）期间，英夫利昔单抗组中有 26 例（37%）患者接受了切除术，切除术组中有 19 例（26%）患者接受了抗 TNF 治疗。
对于病变末段回肠<40 cm、非狭窄性、回肠末段克罗恩病且常规治疗失败的患者，腹腔镜回肠末段切除术可能是英夫利昔单抗治疗的合理替代方案。
荷兰健康研究与发展组织。
