Roblin X, Boschetti G, Williet N, Nancey S, Marotte H, Berger A, Phelip J M, Peyrin-Biroulet L, Colombel J F, Del Tedesco E, Paul S, Flourie B
Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France.
Department of Gastroenterology, Hospices Civils de Lyon, INSERM U1111, Lyon, France.
Aliment Pharmacol Ther. 2017 Jul;46(2):142-149. doi: 10.1111/apt.14106. Epub 2017 Apr 27.
Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD).
To identify the AZA optimal dose that is required for efficacy when receiving combination therapy.
Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25 mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy.
Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1 year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45 μg/mL, P=.9) and in group AZA down (3.95 vs 3.60 μg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15 μg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN <105 pmoles/8.10 RBC was associated with an unfavourable evolution of IFX pharmacokinetics.
Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.
在炎症性肠病（IBD）中，英夫利昔单抗（IFX）联合硫唑嘌呤（AZA）比IFX单药治疗更有效。
确定联合治疗时达到疗效所需的AZA最佳剂量。
将联合治疗处于持续缓解期的IBD患者随机分为三组，进行为期1年的开放标签前瞻性试验：AZA维持组（2 - 2.5mg/kg/天，n = 28）、AZA减量组（剂量减半至1 - 1.25mg/kg/天，n = 27）和AZA停药组（n = 26）。主要终点为失败，定义为临床复发和/或IBD治疗发生任何变化。
纳入81例患者。AZA维持组、AZA减量组和AZA停药组分别有5例（17.9%）、3例（11.1%）和8例（30.8%）患者在1年时出现失败（三组间P = 0.1）。AZA维持组入组时IFX的中位谷浓度与随访结束时测得的浓度相近（3.65对3.45μg/mL，P = 0.9），AZA减量组也是如此（3.95对3.60μg/mL，P = 0.5），而AZA停药组这些浓度从4.25μg/mL降至2.15μg/mL（P = 0.02）。AZA维持组、AZA减量组和AZA停药组分别有4例（14.3%）、4例（14.8%）和11例（42.3%）患者出现IFX药代动力学不良演变。6 - TGN<105pmoles/8×10⁶红细胞的阈值与IFX药代动力学不良演变相关。
在联合治疗下，AZA减量而非停药似乎与全剂量持续使用AZA一样有效。
