Nguyen Nghia, Zhang Bing, Holubar Stefan D, Pardi Darrell S, Singh Siddharth
Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
Cochrane Database Syst Rev. 2019 May 28;5(5):CD001176. doi: 10.1002/14651858.CD001176.pub4.
Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC).
The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis.
We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings.
Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion.
Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome.
Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear.Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence).Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain.
At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence).
AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.
在因慢性溃疡性结肠炎（UC）行回肠储袋肛管吻合术（IPAA）的患者中，约50%会发生储袋炎。
主要目的是确定药物治疗预防或治疗急性或慢性储袋炎的疗效和安全性。
我们检索了从数据库建立至2018年7月25日的MEDLINE、Embase和CENTRAL。我们还检索了参考文献、试验注册库和会议论文集。
纳入针对因UC行IPAA的成人预防或治疗急性或慢性储袋炎的随机对照试验。
两名作者独立筛选研究的合格性、提取数据并评估偏倚风险。使用GRADE评估证据的确定性。主要结局是急性或慢性储袋炎患者的临床改善或缓解，或IPAA后无储袋炎发作的参与者比例。不良事件（AE）是次要结局。我们计算了每个二分结局的风险比（RR）和相应的95%置信区间（CI）。
纳入15项研究（547名参与者）。4项研究评估急性储袋炎的治疗。5项研究评估慢性储袋炎的治疗。6项研究评估储袋炎的预防。3项研究偏倚风险低。3项研究偏倚风险高，其他研究情况不明。
所有环丙沙星组参与者（7/7）在2周时达到缓解，而甲硝唑组参与者为33%（3/9）（RR 2.68，95%CI 1.13至6.35，极低确定性证据）。环丙沙星组参与者无AE（0/7），而甲硝唑组参与者为33%（3/9）（RR 0.18，95%CI 0.01至2.98；极低确定性证据）。AE包括呕吐、味觉障碍或短暂性周围神经病变。甲硝唑组43%（6/14）的参与者在6周时达到缓解，而布地奈德灌肠组为50%（6/12）（RR 0.86，95%CI 0.37至1.96，极低确定性证据）。甲硝唑组50%（7/14）的参与者在6周时临床改善，而布地奈德灌肠组为58%（7/12）（RR 0.86，95%CI 0.42至1.74，极低确定性证据）。甲硝唑组57%（8/14）的参与者发生AE，而布地奈德灌肠组为25%（3/12）（RR 2.29，95%CI 0.78至6.73，极低确定性证据）。AE包括厌食、恶心、头痛、乏力、金属味、呕吐、感觉异常和抑郁。利福昔明组25%（2/8）的参与者在4周时达到缓解，而安慰剂组为0%（0/10）（RR 6.11，95%CI 0.33至111.71，极低确定性证据）。利福昔明组38%（3/8）的参与者在4周时临床改善，而安慰剂组为30%（3/10）（RR 1.25，95%CI 0.34至4.60，极低确定性证据）。利福昔明组75%（6/8）的参与者发生AE，而安慰剂组为50%（5/10）（RR 1.50，95%CI 0.72至3.14，极低确定性证据）。AE包括腹泻、肠胃气胀、恶心、直肠疼痛、呕吐、口渴、念珠菌感染、上呼吸道感染、肝酶升高和丛集性头痛。鼠李糖乳杆菌GG组10%（1/10）的参与者在12周时临床改善，而安慰剂组为0%（0/10）（RR 3.00，95%CI 0.14至65.90，极低确定性证据）。
德西蒙配方组85%（34/40）的参与者在9至12个月时维持缓解，而安慰剂组为3%（1/36）（RR 20.24，95%CI 4.28至95.81，2项研究；低确定性证据）。德西蒙配方组2%（1/40）的参与者发生AE，而安慰剂组为0%（0/36）（RR 2.43，95%CI 0.11至55.89；低确定性证据）。AE包括腹部绞痛、呕吐和腹泻。阿达木单抗组50%（3/6）的患者在4周时临床改善，而安慰剂组为43%（3/7）（RR 1.17，95%CI 0.36至3.76，低确定性证据）。谷氨酰胺组60%（6/10）的参与者在3周时维持缓解，而丁酸盐组为33%（3/
