近日，美国西奈山伊坎医学院Bruce E. Sands及其课题组的最新研究提出了Ustekinumab可诱导维持治疗溃疡性结肠炎。相关论文2019年9月26日发表于《新英格兰医学杂志》。

Ustekinumab是一种白介素-12和23的p40亚单位拮抗剂，其诱导维持治疗溃疡性结肠炎的疗效尚不清楚。研究组共招募了961名患者，将其随机分配，其中320名静脉注射Ustekinumab 130mg，322名按每6mg/kg体重的剂量注射Ustekinumab，319名接受安慰剂治疗。治疗8周后，对Ustekinumab诱导有反应的患者再次随机分组进行维持治疗，其中172名患者每12周注射Ustekinumab 90mg，176名每8周注射Ustekinumab 90mg，175名注射安慰剂。

治疗8周后，Ustekinumab 130mg组和Ustekinumab 6mg/kg组中分别有15.6%和15.5%的患者获得临床缓解，均显著高于安慰剂组（5.3%）。继续治疗44周后，接受每12周或每8周注射一次Ustekinumab进行维持治疗的患者中有38.4%获得临床缓解，显著高于安慰剂组（24.0%）。Ustekinumab组的严重不良事件发生率与安慰剂组相比差别不大。经过52周的治疗，Ustekinumab组中共发生2例死亡和7例癌症，安慰剂组没有死亡和患癌事件发生。

综上，Ustekinumab诱导和维持治疗中重度溃疡性结肠炎在病情缓解方面优于安慰剂。

附：英文原文

Title: Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis

Author: Bruce E. Sands, William J. Sandborn, Remo Panaccione, Christopher D. O’Brien, Hongyan Zhang, Jewel Johanns, Omoniyi J. Adedokun, Katherine Li, Laurent Peyrin-Biroulet, Gert Van Assche, Silvio Danese, Stephan Targan, Maria T. Abreu, Tadakazu Hisamatsu, Philippe Szapary, Colleen Marano

Issue&Volume: Vol 381 No 13

Abstract: 

BACKGROUND
The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.

METHODS
We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range–based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components).

RESULTS
The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P=0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.

CONCLUSIONS
Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis.

DOI: 10.1056/NEJMoa1900750

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1900750