Abstract：
OBJECTIVE: Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. We evaluated the efficacy of ustekinumab for these patients.
METHODS: We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI.
RESULTS: We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7-10) to 7 (IQR, 4-9) at week 16 (P = .007) and 4 (IQR, 1.75-7.25) at week 48 (P < .001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2-4) to 2 (IQR, 1-3) at week 16 (P = .009) and 1 (IQR, 0-2.25) at week 48 (P = .001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4-6) to 4 (IQR, 3-6) at week 16 (P = .032) and 3 (IQR, 1.75-4.25) at week 48 (P = .001).
CONCLUSIONS: Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).
METHODS: We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI.
RESULTS: We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7-10) to 7 (IQR, 4-9) at week 16 (P = .007) and 4 (IQR, 1.75-7.25) at week 48 (P < .001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2-4) to 2 (IQR, 1-3) at week 16 (P = .009) and 1 (IQR, 0-2.25) at week 48 (P = .001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4-6) to 4 (IQR, 3-6) at week 16 (P = .032) and 3 (IQR, 1.75-4.25) at week 48 (P = .001).
CONCLUSIONS: Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).
摘要：
目的：17%的溃疡性结肠炎患者接受直肠结肠切除术并进行囊袋手术会发展为慢性囊炎。我们评估了ustekinumab对这些患者的疗效。
方法：我们对慢性囊炎患者进行了一项前瞻性研究，这些患者在基线时接受了ustekinumab静脉注射（~6mg/kg），之后每8周接受一次90mgustekinumab皮下注射。在基线时评估改良囊炎疾病活动指数(mPDAI),第16周和第48周。主要终点是在第16周时达到无类固醇缓解（mPDAI<5且减少≥2分）的患者比例。次要终点包括在第48周达到缓解的患者比例，在第16周和第48周达到缓解（mPDAI降低≥2分）的患者比例，以及mPDAI的变化。
结果：我们招募了22名患者（59%为男性，中位年龄42.2岁)。缓解在第16周时为27.3%，在第48周时为36.4%。在第16周和第48周，反应均为54.5％。中位数（IQR）mPDAI从第16周的8（7-10）降至7（4-9）（p=0.007），第48周的4（1.75-7.25）（p<0.001）。临床mPDAI子评分在第16周从3.5(2-4)降至2(1-3)(p=0.009),在第48周从1(0-2.25)(p=0.001)。在第16周（p=0.032）和第3周（1.75-4.25）时（p=0.001），内镜mPDAI子评分从5.5（4-6）降至4（3-6）。
结论：Ustekinumab在一半慢性囊炎患者中有效。因此，Ustekinumab应定位在慢性囊炎的治疗算法中。（ClinicalTrials.gov编号NCT04089345）。
方法：我们对慢性囊炎患者进行了一项前瞻性研究，这些患者在基线时接受了ustekinumab静脉注射（~6mg/kg），之后每8周接受一次90mgustekinumab皮下注射。在基线时评估改良囊炎疾病活动指数(mPDAI),第16周和第48周。主要终点是在第16周时达到无类固醇缓解（mPDAI<5且减少≥2分）的患者比例。次要终点包括在第48周达到缓解的患者比例，在第16周和第48周达到缓解（mPDAI降低≥2分）的患者比例，以及mPDAI的变化。
结果：我们招募了22名患者（59%为男性，中位年龄42.2岁)。缓解在第16周时为27.3%，在第48周时为36.4%。在第16周和第48周，反应均为54.5％。中位数（IQR）mPDAI从第16周的8（7-10）降至7（4-9）（p=0.007），第48周的4（1.75-7.25）（p<0.001）。临床mPDAI子评分在第16周从3.5(2-4)降至2(1-3)(p=0.009),在第48周从1(0-2.25)(p=0.001)。在第16周（p=0.032）和第3周（1.75-4.25）时（p=0.001），内镜mPDAI子评分从5.5（4-6）降至4（3-6）。
结论：Ustekinumab在一半慢性囊炎患者中有效。因此，Ustekinumab应定位在慢性囊炎的治疗算法中。（ClinicalTrials.gov编号NCT04089345）。
