Faculty Bibliography

: Chronic proctitis refers to persistent or relapsing inflammation of the rectum, which results from a wide range of etiologies with various pathogenic mechanisms. The patients may share similar clinical presentations. Ulcerative proctitis, chronic radiation proctitis or proctopathy, and diversion proctitis are the 3 most common forms of chronic proctitis. Although the diagnosis of these disease entities may be straightforward in the most instances based on the clinical history, endoscopic, and histologic features, differential diagnosis may sometimes become problematic, especially when their etiologies and the disease processes overlap. The treatment for the 3 forms of chronic proctitis is different, which may shed some lights on their pathogenetic pathway. This article provides an overview of the latest data on the clinical features, etiologies, diagnosis, and management of ulcerative proctitis, chronic radiation proctopathy, and diversion proctitis.

BACKGROUND: Infliximab is used to treat moderate to severe Crohn's disease (CD), but its efficacy varies. Although cigarette smoking worsens CD, its impact on the infliximab response is unknown. We conducted a systematic review and meta-analysis of clinical trials to determine the effect of smoking on the induction response to infliximab. METHODS: A systematic search was performed of MEDLINE, EMBASE, CINAHL, the Cochrane central register of controlled trials, the Cochrane IBD Group Specialized Trials Register for publications, and abstracts from major conferences from January 1996 to December 2010. Random effects meta-analysis using the Mantel-Haenszel method was conducted. Heterogeneity across studies was assessed using the Q statistic, the I2 statistic, and tau2. RESULTS: We identified 12 articles; four were excluded due to use of non-validated scoring systems.The remaining eight included a total of 1658 patients, with 649 active smokers. Luminal response was assessed by the Crohn's Disease Activity Index in four studies (three of which included fistula response) and the Harvey-Bradshaw index in two (both including fistula response), and two studies examined only the fistula response. The relative risk for response to infliximab among smokers was 0.99 (95% CI 0.88-1.11) (tau2 = 0.0143). Analyses of the five studies examining both inflammatory and fistulizing CD were similar to the analysis of all eight studies. The pooled relative risk was 0.92 (95% CI 0.80-1.06) (tau2 = 0.0154). CONCLUSION: Though smoking worsens CD, this meta-analysis does not show a negative effect of smoking on initial response to infliximab. This must be viewed in the proper context, as long-term maintenance of response may yet be influenced by smoking status.

OBJECTIVE: To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Seventy-nine US and Canadian centers. SUBJECTS: Patients aged >/= 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week. METHODS: Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8. RESULTS: Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred. CONCLUSION: Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).

BACKGROUND & AIMS: Tofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through gamma-chain-containing cytokines (interleukins 2, 4, 7, 9, 15, and 21). We performed a phase 2 trial to measure its efficacy in patients with moderate-to-severe active Crohn's disease. METHODS: Patients (N = 139; age, >/=18 y) with moderate-to-severe active Crohn's disease were assigned randomly to groups given 1 mg (n = 36), 5 mg (n = 34), or 15 mg (n = 35) tofacitinib or placebo (n = 34), twice daily for 4 weeks, at 48 centers in 12 countries. The primary end point was the proportion of clinical responders at week 4 (decrease from baseline in the Crohn's Disease Activity Index score of >/=70 points [Response-70]). Secondary end points included clinical remission (Crohn's Disease Activity Index score of <150 points) at week 4. RESULTS: A clinical response was observed in 36% (P = .467), 58% (P = .466), and 46% (P >/= .999) of patients given the 1-, 5-, and 15-mg doses of tofacitinib, compared with 47% of patients given placebo. Clinical remission was observed in 31% (P = .417), 24% (P = .776), and 14% (P = .540) of patients given the 1-, 5-, and 15-mg doses of tofacitinib, compared with 21% of patients given placebo. The 15-mg dose of tofacitinib reduced levels of C-reactive protein and fecal calprotectin from baseline. Adverse and serious adverse events were similar among groups. Dose-dependent increases in low- and high-density lipoprotein cholesterol were observed in patients given the 5- or 15-mg doses of tofacitinib. CONCLUSIONS: There were no significant differences in the percentage of patients with moderate-to-severe active Crohn's disease who achieved clinical responses (Response-70) or clinical remission after 4 weeks' administration of tofacitinib (1, 5, or 15 mg) or placebo twice daily. However, a large percentage of patients given placebo achieved Response-70 or remission. Reductions in C-reactive protein and fecal calprotectin levels among patients given the 15-mg dose of tofacitinib indicate its biologic activity. ClinicalTrials.gov number: NCT00615199.