Kochhar, Gursimran

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49–0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48–0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Abstract Background Crohn’s disease (CD) is a chronic progressive condition that is complicated by intestinal or colonic stricture in nearly 30% of cases within 10 years of the initial diagnosis. Endoscopic balloon dilation (EBD) is associated with a risk of perforations and recurrence rates of up to 60% at 5 years. Endoscopic stenting has been used as an alternative to EBD, but data on its safety and efficacy are limited. We conducted a systematic review and meta-analysis to assess the outcomes of endoscopic stenting in CD-related strictures. Methods A systematic and detailed search was run in January 2022 with the assistance of a medical librarian for studies reporting on outcomes of endoscopic stenting in CD-related strictures. Meta-analysis was performed using random-effects model, and results were expressed in terms of pooled proportions along with relevant 95% confidence intervals (CIs). Results Nine studies with 163 patients were included in the final analysis. Self-expanding metal stents (SEMS) including both partial and fully covered were used in 7 studies, whereas biodegradable stents were used in 2 studies. Pooled rate of clinical success and technical success was 60.9% (95% CI, 51.6-69.5; I2 = 13%) and 93% (95% CI, 87.3-96.3; I2 = 0%), respectively. Repeat stenting was needed in 9.6% of patients (95% CI, 5.3-16.7; I2 = 0%), whereas pooled rate of spontaneous stent migration was 43.9% (95% CI, 11.4-82.7; I2 = 88%). Pooled incidence of overall adverse events, proximal stent migration, perforation, and abdominal pain were 15.7%, 6.4%, 2.7%, and 17.9%, respectively. Mean follow-up period ranged from 3 months to 69 months. Discussion Endoscopic stenting in CD-related strictures is a safe technique that can be performed with technical ease, albeit with a limited clinical success. Postprocedure abdominal pain and proximal stent migration are some of the common adverse events reported.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40–60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0–1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0–1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4–6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

AbstractIntroductionThere are concerns regarding the effectiveness and safety of SARS‐CoV‐2 vaccine in inflammatory Bowel Disease (IBD) patients. This systematic review and meta‐analysis comprehensively summarises the available literature regarding the safety and effectiveness of SARS‐CoV‐2 vaccine in IBD.MethodsThree independent reviewers performed a comprehensive review of all original articles describing the response of SARS‐CoV‐2 vaccines in patients with IBD. Primary outcomes were (1) pooled seroconversion rate SARS‐CoV‐2 vaccination in IBD patients (2) comparison of breakthrough COVID‐19 infection rate SARS‐CoV‐2 vaccination in IBD patients with control cohort and (3) pooled adverse event rate of SARS‐CoV‐2 vaccine. All outcomes were evaluated for one and two doses of SARS‐CoV‐2 vaccine. Meta‐regression was performed. Probability of publication bias was assessed using funnel plots and with Egger’s test.ResultsTwenty‐one studies yielded a pooled seroconversion rate of 73.7% and 96.8% in IBD patients after one and two doses of SARS‐CoV‐2 vaccine respectively. Sub‐group analysis revealed non‐statistically significant differences between different immunosuppressive regimens for seroconversion. Meta‐regression revealed that the vaccine type and study location independently influenced seroconversion rates. There was no statistically significant difference in breakthrough infection in IBD patients as compared to control after vaccination.ConclusionIn summary, the systematic review and meta‐analysis suggest that SARS‐CoV‐2 vaccine is safe and effective in IBD patients.

Abstract Background and study aims Endoscopic mucosal resection (EMR) of laterally spreading tumors (LSTs) > 20 mm in size can be challenging. Piecemeal EMR of these lesions results in high rates of adenoma recurrence at first surveillance colonoscopy (SC1). Snare tip soft coagulation (STSC) of post resection margins is a safe and effective technique to prevent adenoma recurrence. We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of this technique. Patients and methods Multiple databases were searched through April 2021 for studies that reported on outcomes of post EMR STSC for LSTs > 20 mm in size. Meta-analysis was performed to determine pooled odds of adenoma recurrence as well as pooled proportion of adverse events including intraprocedural and delayed bleeding as well as intraprocedural perforation events. Results Six studies including two randomized controlled trials (RCT) and four cohort studies with 2122 patients were included in the final analysis. Overall pooled odds of adenoma recurrence at SC1 with post EMR STSC compared to no STSC was 0.27 (95 % 0.18–0.42; I2 = 0 %), P < 0.001. Pooled rate of adenoma recurrence at SC1 in post EMR STSC cohort was 6 %. Rates of intraprocedural bleeding, delayed bleeding and intraprocedural perforation were 10.3 %, 6.5 % and 2 % respectively. Conclusions Our results show that thermal ablation of resection margins with STSC in LSTs > 20 mm is a safe and effective technique in reducing the incidence of adenoma recurrence.

SummaryBackgroundAccurate estimates for the risk of COVID‐19 in IBD, and an understanding of the impact of COVID‐19 on IBD course and the risk of incident post‐infectious IBD are needed.AimsTo estimate the risk of COVID‐19 in IBD and study its impact on IBD course and the risk of incident post‐infectious IBD.MethodsA retrospective propensity score matched cohort study utilising multi‐institutional research network TriNetX. COVID‐19 patients with and without IBD were identified to quantify the risk of COVID‐19 in patients with IBD, COVID‐19 outcomes in patients with IBD and the impact of COVID‐19 on IBD disease course. The risk of incident post‐infectious IBD in COVID‐19 patients was compared to the population not infected with COVID‐19 during a similar time period.ResultsIncidence rate ratio for COVID‐19 was lower in IBD patients compared to the non‐IBD population (0.79, 95% CI: 0.72‐0.86). COVID‐19‐infected patients with IBD were at increased risk for requiring hospitalisation compared to non‐IBD population (RR: 1.17, 95% CI: 1.02‐1.34) with no differences in need for mechanical ventilation or mortality. Patients with IBD on steroids were at an increased risk for critical care need (RR: 2.22, 95% CI: 1.29‐3.82). Up to 7% of patients with IBD infected with COVID‐19 suffered an IBD flare 3‐months post‐infection. Risk for incident IBD post‐COVID was lower than that seen in the non‐COVID population (RR: 0.64, 95% CI: 0.54‐0.65).ConclusionWe observed no increase in risk for COVID‐19 amongst patients with IBD or risk for de novo IBD after COVID‐19 infection. We confirmed prior observations regarding the impact of steroid use on COVID‐19 severity in patients with IBD.

Abstract Background Oral contraceptive pill (OCP) use in the general population is associated with a failure rate as low as 0.3% with perfect use but as high as 9% with typical use. Women with Crohn’s disease (CD) may have malabsorption in the setting of small bowel disease or resection, which could affect absorption of OCPs. Our aim was to determine the incidence of pregnancy in women with CD on OCPs. Methods This is a retrospective study assessing the incidence rate of OCP failure in females between 18 and 45 years of age seen at the Mayo Clinic with a diagnosis of CD and provided a prescription for OCPs, between 2016 and 2020. Failure was defined as clear documentation of becoming pregnant while using OCPs or having an active prescription of OCP at the time of conception. Results A total of 818 female patients with CD between 18 and 45 years of age with a prescription for an OCP were included in our study. Sixty-six patients (8%) conceived in this cohort. Of the 66 patients who became pregnant, 57 stopped the OCP before conceiving, 5 were excluded due to lack of data, and 4 women had active oral contraceptive prescriptions when they became pregnant (pregnancy rate of 0.5%). Conclusions In female patients with CD who are using OCPs for contraception, we found a low rate of pregnancy (0.5%) similar to the rate of pregnancy with perfect use of OCPs in the general population. OCPs are an effective method of birth control in women with CD.