目的:当开始英夫利昔单抗治疗克罗恩病时,与硫嘌呤联合治疗是有利的;然而,最佳的6-硫鸟嘌呤核苷酸(TGN)水平以及诱导后硫嘌呤持续多长时间尚不确定。我们旨在比较克罗恩病患者诱导后和维持期间联合治疗与英夫利昔单抗单药治疗的结局,并检查TGN水平是否与结局相关。
方法:回顾性分析英夫利昔单抗联合或不联合硫嘌呤诱导的克罗恩患者。分析了对随后6个月维持学期的诱导反应和临床结果。TGN水平≥235pmol/8×108红细胞被认为是治疗性的。
结果:在89例患者中,联合治疗对诱导的反应高于单药治疗(74vs47%,P=0.04)。这种益处仅在治疗性TGN患者中可见(比值比3.72,置信区间1.07-13.0,P=0.04)。与单药治疗相比,诱导期间的联合治疗导致随后需要治疗升级或治疗失败的时间延长了三倍(29vs9个月,P=0.01),多变量分析具有治疗性和亚治疗性TGNs独立预测因子。在370个学期中,联合治疗和单药治疗之间的结果没有差异(P=0.42),当组合学期按治疗性TGN与亚治疗性TGN进行分层时(P=0.56)。仅在第一学期,与亚治疗TGN相比,治疗性TGN的缓解率明显更高(76%vs33%,P=0.02)。
结论:用优化的噻嘌呤联合治疗在诱导反应方面优于英夫利昔单抗单药治疗,响应的持久性,和诱导后的前6个月的临床结果。此后,联合治疗没有产生临床优势,支持在个案基础上考虑硫嘌呤的戒断。
OBJECTIVE: Combining therapy with a thiopurine is favored when commencing infliximab in Crohn\'s disease; however, the optimal 6-thioguanine nucleotide (TGN) level and how long to continue thiopurines after induction are uncertain. We aimed to compare outcomes after induction and during maintenance in combination therapy versus infliximab monotherapy in Crohn\'s and to examine whether TGN levels were associated with outcomes.
METHODS: Crohn\'s patients induced with infliximab with or without concomitant thiopurines were retrospectively identified. Response to induction and clinical outcomes in subsequent 6-month maintenance semesters were analyzed. A TGN level ≥235 pmol/8 × 108 red blood cells was considered therapeutic.
RESULTS: In 89 patients, response to induction was higher in combination therapy than monotherapy (74 vs 47%, P = 0.04). This benefit was only seen in patients with a therapeutic TGN (odds ratio 3.72, confidence interval 1.07-13.0, P = 0.04). Combination therapy during induction yielded a three times longer time to subsequent need for treatment escalation or treatment failure compared with monotherapy (29 vs 9 months, P = 0.01), with both therapeutic and subtherapeutic TGNs independent predictors on multivariate analysis. Among 370 semesters, there was no difference in outcomes between combination therapy and monotherapy (P = 0.42), nor when combination semesters were stratified by therapeutic versus subtherapeutic TGN (P = 0.56). In semester 1 only, a significantly higher remission rate was observed with therapeutic compared with subtherapeutic TGN (76% vs 33%, P = 0.02).
CONCLUSIONS: Combination therapy dosed with an optimized thiopurine was superior to infliximab monotherapy for induction of response, durability of response, and clinical outcomes in the first 6 months following induction. Thereafter, combination therapy yielded no clinical advantage, supporting consideration of thiopurine withdrawal on a case-by-case basis.