Citations

INTRODUCTION: Many patients with chronic pouchitis and Crohn's-like disease of the pouch (CLDP) are treated with biologics; however, the comparative effectiveness of advanced therapies in this population has not been systematically evaluated. We sought to compare the effectiveness of antitumor necrosis factor α (anti-TNF) therapies and ustekinumab in patients with chronic inflammatory conditions of the pouch. METHODS: We conducted a prospective, multicenter, cohort study. We included patients with chronic pouchitis and CLDP initiating treatment with anti-TNF therapies or ustekinumab. The primary outcome was clinical remission at 6 months after induction. We also evaluated clinical remission at 6 months among patients with chronic pouchitis and CLDP separately. RESULTS: Among 132 patients, 106 (80%) had a diagnosis of CLDP and 82 (62%) initiated therapy with ustekinumab. A significantly higher proportion of patients with CLDP treated with ustekinumab were in clinical remission at 6 months as compared with patients treated with anti-TNF therapy (62% vs 40%, P = 0.027); however, there was no significant difference among patients with chronic pouchitis ( P = 0.946). There was no independent statistical significance in the odds of remission at 6 months among patients with CLDP among patients receiving ustekinumab compared with anti-TNF therapy (adjusted odds ratio 1.91, 95% confidence interval 0.69–5.30) after adjusting for presence of a fistula, number of preoperative advanced therapies, and number of advanced therapies after IPAA. DISCUSSION: These data suggest the potential benefit of ustekinumab in patients with CLDP and should prompt future novel effectiveness evaluations in this population.

Abstract Background Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. Methods We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. Results We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn’s disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). Conclusions SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

Lay Summary In this prospective, multicenter observational study of highly refractory patients with Crohn’s disease of the pouch, risankizumab achieved the primary outcome of clinical remission in 50% and the more stringent secondary outcome of antibiotic- and steroid-free remission in 30.8% at 12 weeks.

AbstractBackgroundMany patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)‐like symptoms. Although these symptoms cause significant reductions in quality of life, evidence‐based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS‐like symptoms in IBD patients with quiescent disease.MethodsWe performed a single‐center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 μg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS‐like symptoms in IBD patients.Key ResultsA total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0–82.0) 63.3 per 1000 person‐years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g.Conclusions & InferencesMood disorder and Crohn's disease were positively associated with IBS‐like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS‐like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS‐like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

AbstractChildren with very early onset inflammatory bowel disease (VEO‐IBD) may respond differently to coronavirus disease 2019 (COVID‐19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO‐IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO‐IBD experience robust humoral immune response to COVID‐19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO‐IBD respond well and safely to SARS‐CoV‐2 vaccination.

SummaryBackgroundUpadacitinib is an oral, selective Janus kinase inhibitor.AimTo assess the efficacy and safety of upadacitinib in patients with moderate‐to‐severe ulcerative colitis following 16‐week extended induction therapy, and 52‐week maintenance therapy in patients achieving clinical response after 16‐week extended induction therapyMethodsPatients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re‐randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52‐week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout.ResultsOverall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib.ConclusionsPatients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy.Clinical trial registration: NCT02819635; NCT03653026

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Abstract Background Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) are limited. Methods We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn’s disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. Results Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. Conclusions In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population.