Combination Therapy With Infliximab and Azathioprine Is Superior to Monotherapy With Either Agent in Ulcerative Colitis
Combination Therapy With Infliximab and Azathioprine Is Superior to Monotherapy With Either Agent in Ulcerative Colitis
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DOI：
10.1053/j.gastro.2013.10.052
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发表时间：
2014-02-01
期刊：
影响因子：
29.4
通讯作者：
Rutgeerts, Paul
中科院分区：
文献类型：
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作者：
Panaccione, Remo;Ghosh, Subrata;Rutgeerts, Paul
背景与目的：英夫利西单抗和硫唑嘌呤单独或联合治疗溃疡性结肠炎（UC）的比较疗效和安全性尚未进行评估。方法：这项随机、双盲试验评价了英夫利西单药治疗、硫唑嘌呤单药治疗或2种药物联合治疗初治的中重度UC成人患者16周的疗效和安全性。患者被随机分配在第0、2、6和14周接受英夫利西单抗5 mg/kg静脉输注+每日口服安慰剂胶囊;每日口服硫唑嘌呤2.5 mg/kg+英夫利西单抗方案安慰剂输注;或2种药物联合治疗。在第8周和第16周评价无皮质类固醇的临床缓解（主要终点，第16周）。在达到入组目标前终止研究。结果：共有239例患者纳入疗效分析。治疗组之间的基线特征相似。39.7%（31/78）接受英夫利西单抗/硫唑嘌呤治疗的患者在第16周达到无皮质类固醇缓解，而22.1%（17/77）接受英夫利西单抗治疗（P = 0.017）和23.7%（18/76）接受硫唑嘌呤治疗（P = 0.032）。62.8%（49/78）接受英夫利西单抗/硫唑嘌呤治疗的患者在第16周发生粘膜愈合，英夫利西单抗组为54.6%（42/77）（P = 0.295），硫唑嘌呤组为36.8%（28/76）（P = 0.001）。2例患者发生严重感染（1例患者接受英夫利西单抗，1例患者接受硫唑嘌呤）。结论：接受英夫利西单抗联合硫唑嘌呤治疗的未接受过抗肿瘤坏死因子-α治疗的中重度UC患者在16周时比接受任一单药治疗的患者更有可能达到无皮质类固醇缓解。联合治疗导致粘膜愈合明显优于硫唑嘌呤单药治疗。ClinicalTrials.gov编号，NCT 00537316。
BACKGROUND & AIMS: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously. METHODS: This randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-alpha antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached. RESULTS: A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine, compared with 22.1% (17 of 77) receiving infliximab alone (P = .017) and 23.7% (18 of 76) receiving azathioprine alone (P = .032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab (P = .295) and 36.8% (28 of 76) receiving azathioprine (P = .001). Serious infections occurred in 2 patients (1 patient receiving infliximab, and 1 patient receiving azathioprine). CONCLUSIONS: Antitumor necrosis factor-alpha-naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.