Use of Biologics for the Treatment of Inflammatory Conditions of the Pouch: A Systematic Review.

BACKGROUND: Patients with medically-refractory ulcerative colitis or advanced neoplasia are often offered an ileal-pouch-anal anastomosis to restore bowel continuity. However, up to 50% of patients can suffer from inflammatory conditions of the pouch, some of which require biological therapy to treat. The aim of this study was to determine the efficacy of each biological agent for the treatment of inflammatory conditions of the pouch. MATERIALS AND METHODS: A comprehensive literature search was performed in the major databases from inception through February 11, 2020, for studies assessing the efficacy of biologics in chronic antibiotic-refractory pouchitis (CARP) and Crohn's disease (CD) of the pouch. Both prospective and retrospective studies were included. The primary outcomes of interest were complete and partial responses were defined within each study. χ 2 test was used to compare variables. RESULTS: Thirty-four studies were included in the systematic review and meta-analysis. Sixteen studies (N=247) evaluated the use of infliximab (IFX), showing complete response in 50.7% and partial response in 28.1% for CARP, and complete response in 66.7% and partial response in 20% for CD of the pouch. Seven studies (n=107) assessed the efficacy of adalimumab. For CARP, 33.3% of patients had a complete response, and 38.1% had a partial response, whereas for CD of the pouch, 47.7% experienced a complete response, and 24.6% had a partial response. Three studies (n=78) reported outcomes with the use of ustekinumab, showing 50% complete response and 3.8% partial response for CARP. For the CD of the pouch, 5.8% had a complete response and 78.8% had a partial response. Seven studies (n=151) reported the efficacy of vedolizumab, showing 28.4% complete response and 43.2% partial response in patients with CARP, whereas 63% of patients experienced partial response in CD of the pouch. IFX had higher rates of complete response in CARP compared with adalimumab ( P =0.04) and compared with vedolizumab ( P =0.005), but not compared with ustekinumab ( P =0.95). There were no new safety signals reported in any of the studies. CONCLUSIONS: Biologics are safe and efficacious in the treatment of chronic, refractory inflammatory conditions of the pouch. IFX seems to be more efficacious than adalimumab and vedolizumab for CARP. Further prospective, head-to-head evaluations are needed to compare biological therapies in the treatment of CARP and CD of the pouch.

Efficacy and safety of biologic therapy in microscopic colitis: systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis (MC). METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on biologic use (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) for induction and maintenance of remission in MC. We assessed clinical remission and response rates and all reported adverse events (AEs). RESULTS: A total of 376 studies were screened yielding 13 articles (including four abstracts) with a combined information on 78 patients for efficacy and safety outcomes. Most studies were case series. Vedolizumab was used in five studies, adalimumab in three, and a combination of infliximab and adalimumab in five studies. The rates of remission were 66.08% (95% CI, 36.79-95.37%; I2 , 71%) at weeks 3-6 and 54.20% (95% CI, 39.39-69.01%; I2 , 0%) at weeks 12-16. Clinical response rates were 100% (95% CI, 88.04-100%; I2 , 0%) at weeks 3-6 and 67.20% (95% CI, 47.72-86.69%; I2 , 52%) at weeks 12-16. Most frequent AE was medication discontinuation with a pooled incidence of 16.1% (95% CI, 5.9-37.5%). No deaths attributable to biologic use were reported. The overall quality of evidence was very low due to the high risk of biases. CONCLUSION: Low-quality evidence supports the short-term efficacy of biologics in budesonide refractory MC. While our findings represent the most comprehensive evaluation of biologic therapy in severe MC, further research including randomized clinical trials is needed to better define the role of specific agents and long-term therapy.

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis.

BACKGROUND: The objective of our systematic review and meta-analysis was to evaluate the effectiveness and safety of tofacitinib in the treatment of moderate-severe ulcerative colitis (UC). METHODS: We searched Medline, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on tofacitinib use in UC. Primary outcome assessed was remission. Secondary outcomes included clinical response, steroid free remission, and adverse events (AEs). RESULTS: A total of 26 studies were included. The rates of remission were 29.81% [95% confidence interval (CI): 22.37%-37.25%, I2 : 90%] at week 8, 32.27% (95% CI: 27.67%-36.88%, I2 : 42%) at 6 months and 38.03% (95% CI: 33.59%-42.48%, I2 : 0%) at 1-year. Clinical response rates were 59.41% (95% CI: 55.03%-63.94%, I2 : 61%) at week 8, 48.99% (95% CI: 36.92%-61.06%, I2 : 91%) at 6 months and 50.87% (95% CI: 42.16%-59.58%, I2 : 67%) at 1-year. Odds ratio of clinical response at week 8 in biologic naive versus biologic experienced patients was 1.59 (95% CI: 0.54-4.63). Pooled incidence rate for serious infections, major adverse cardiovascular events, and nonmelanotic squamous cell malignancies across all doses was 4.41 per 100-patient years (PYs) (95% CI: 2.32-8.38 per 100-PY, I2 : 78%), 0.91 per 100-PY (95% CI: 0.43-1.93 per 100-PY, I2 : 37%) and 0.91 per 100-PY (95% CI: 0.61-1.34 per 100-PY, I2 : 0%), respectively. Higher dose was associated with an increased frequency of AEs. CONCLUSIONS: While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation. Rate of clinical response after tofacitinb induction was similar in biologic naive and biologic experienced patients.

Ustekinumab is effective for perianal fistulising Crohn's disease: a real-world experience and systematic review with meta-analysis.

BACKGROUND: Perianal Crohn's disease (pCD) is a debilitating complication affecting up to 30% of Crohn's disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied. AIM: To determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review. METHODS: A retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab. RESULTS: At 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response. CONCLUSION: Ustekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.

The Utility of EndoFLIP for Measuring Gastrojejunal Anastomosis Diameter and Distensibility in Patients Experiencing Weight Regain Post Roux-en-Y Gastric Bypass.

A dilated gastrojejunal anastomosis (GJA) diameter is an independent predictor of weight regain following Roux-en-Y gastric bypass (RYGB). Despite this, there is no standardized method for GJA diameter measurement. We performed a retrospective analysis to compare endoscopic visual estimation and endoluminal functional impedance planimetry (EndoFLIP) for measuring GJA diameter in patients with weight regain post-RYGB. Visual estimation was found to overestimate GJA diameter by a mean of 4.2mm ± 4.6mm when compared with EndoFLIP. Furthermore, we identified symptomatic patients with normal GJA diameter but increased distensibility, which may represent a previously unrecognized subgroup. Our findings suggest the potential utility of EndoFLIP in the evaluation of post-RYGB weight regain and support the need for prospective studies to investigate the relationship between GJA distensibility and weight regain.

Transoral outlet reduction: could additional sutures cause more harm?

BACKGROUND: The double purse-string pattern (DPSP) of transoral outlet reduction (TORe) should conceivably result in a more robust scaffolding for the gastrojejunal anastomosis (GJA). However, there is a paucity of literature pertaining to post-TORe stenosis as an adverse event. Our aim was to determine the rate of stenosis, its potential predictors, and other complications of DPSP TORe. METHODS: We performed a retrospective analysis of a prospectively maintained database of 129 consecutive patients who underwent DPSP TORe between December 2015 and August 2019. RESULTS: The adverse event rate of TORe was 17.1 % (n = 22), with a 13.3 % (n = 17) rate of stenosis. Stenosis was not significantly associated with any baseline characteristics. GJA diameter pre- and post-TORe, the difference between these values, and procedure duration were not predictive of stenosis. Of patients who developed stenosis, 10 (58.8 %) responded to endoscopic balloon dilation and 7 (41.2 %) required stent placement. CONCLUSION: As the DPSP technique is a challenging procedure, with high complication rate and limited benefit, it should not be used for TORe.

Endobariatrics and Metabolic Endoscopy: Can We Solve the Obesity Epidemic with Our Scope?

PURPOSE OF REVIEW: Obesity is a chronic relapsing disease that results in cardiovascular disease, diabetes mellitus, and non-alcoholic fatty liver disease. Currently, surgery represents the most effective treatment. However, the advent of minimally invasive endoscopic bariatric therapy (EBT) has shifted the treatment paradigm to less invasive, cost-effective procedures with minimal complications and recovery time that are preferred by patients. In this review, we will describe current and future EBTs, focusing on outcomes and safety. RECENT FINDINGS: The endoscope has provided an incisionless portal into the gastrointestinal tract for placement of space-occupying devices and intraluminal procedures. EBTs are no longer solely manipulating anatomic alterations; instead, they aim to improve metabolic parameters such as glycated hemoglobin, low-density lipoprotein, cholesterol, and hepatic indices by targeting the mucosal layer of the gastrointestinal tract. The endoscope has succeeded in facilitating clinically meaningful weight loss and improvement of metabolic parameters. Future, solutions to the obesity epidemic will likely entail genetic testing, evaluation of the microbiome, and delivery of personalized therapy, utilizing combination endoscopic modalities that change the anatomy and physiology of individual patients, with new targets such as the abnormal metabolic signal.