Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.
Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
J Crohns Colitis. 2021 Apr 6;15(4):575-582. doi: 10.1093/ecco-jcc/jjaa188.
In paediatric patients with Crohn's disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months.
Using Danish registries, we identified patients with Crohn's disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015.
We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32-0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45-0.97] in patients receiving combination therapy.
The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.
在患有克罗恩病的儿科患者中，联合治疗（英夫利昔单抗联合免疫调节剂[硫嘌呤或甲氨蝶呤]）的作用存在争议，且相关数据较少。我们研究了与单独使用英夫利昔单抗相比，在 24 个月内，英夫利昔单抗联合免疫调节剂是否降低了手术或切换抗肿瘤坏死因子[TNF]α 药物类型的治疗失败风险。
我们使用丹麦登记处，确定了在首次英夫利昔单抗治疗时年龄≤20 岁的克罗恩病患者，并检索了他们的合并用药数据。我们使用 Cox 回归模型，于 2003 年 1 月 1 日至 2015 年 12 月 31 日，观察手术或切换抗肿瘤 TNFα 药物类型的情况。
我们纳入了 581 名患者。联合治疗组 2 年的手术累计百分比为 8.5%，而单独使用英夫利昔单抗组为 14.5%。与单独使用英夫利昔单抗相比，接受联合治疗的患者在 2 年内手术的调整后风险比[HR]为 0.53（95%置信区间[CI] 0.32-0.88）。当我们观察抗肿瘤 TNFα 药物的转换时，纳入了 536 名患者。在 2 年内，联合治疗组中有 18.3%的患者发生转换，单独使用英夫利昔单抗组有 24.8%的患者发生转换，接受联合治疗的患者调整后 HR 为 0.66（95%CI 0.45-0.97）。
与单独使用英夫利昔单抗相比，接受联合治疗的儿科和青少年患者的肠内手术和转换为另一种抗肿瘤 TNFα 药物的风险 HR 降低。这些结果表明英夫利昔单抗联合免疫调节剂治疗具有益处，但需要在具有额外临床信息的数据中加以证实。
