Long, Millie D.

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.

Abstract Background Inflammatory bowel disease (IBD)–associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. Methods A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. Results A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. Conclusions This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

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.

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.

Abstract: Background and Aims The BNT162b2 and mRNA-1273 COVID-19 vaccines are efficacious in patients with inflammatory bowel disease; but there is a lack of data examining if holding immunosuppressive therapy around vaccination improves immune response. We studied the effect of holding IBD medications around the time of vaccination on antibody response and breakthrough COVID-19 infection. Methods Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID is a prospective cohort of individuals with IBD receiving COVID-19 vaccination. Quantitative measurement of anti-receptor binding domain IgG antibodies to SARS-CoV-2 was performed 8 weeks after completing a vaccination series. Results A total of 1854 patients were included; 59% were on anti-tumour necrosis factor [TNF] [10% of these on combination therapy], 11% on vedolizumab, and 14% on ustekinumab; 11% of participants held therapy before or after vaccine administration for at least 2 weeks. Antibody levels were similar in participants continuing versus holding anti-TNF monotherapy before or after the second vaccine [BNT162b2: 10 μg/mL vs 8.9 μg/mL; mRNA-1273: 17.5 μg/mL vs 14.5 μg/mL]. Comparable results were seen in those on combination therapy. Antibody titres in those on ustekinumab or vedolizumab were higher compared with anti-TNF users, but there was no significant difference if the drug was held or continued [BNT162b2: 22.5 μg/mL vs 23 μg/mL; mRNA-1273: 88 μg/mL vs 51 μg/mL]. Holding therapy was not associated with decreased rate of COVID-19 infection compared with those not holding therapy [BNT162b2: 28% vs 29%; mRNA-1273: 19% vs 31%]. Conclusion We recommend continuing IBD medications while receiving mRNA COVID-19 vaccination without interruption.

Objective Perianal Crohn’s disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B ( CFB ). Design Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. Results Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB , in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. Conclusion pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.