Cross, Raymond K.

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.

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn’s disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the ‘real’ use of biosimilar anti-TNF-α medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-α utilization in IBD in order to support early anti-TNF-α initiation and maximize patient outcomes.

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.

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.

Abstract Background Since 2009, inflammatory bowel disease (IBD) specialists have utilized “IBD LIVE,” a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified “IBD-mimics” with consequent clinical management implications. Methods Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018–February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results Confirmed IBD cases made up 82.5% (306/371; 193 Crohn’s disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Abstract Background Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD, yet predicting who may develop them is difficult. The goal of our study was to better characterize which patients may be at highest risk of developing not only 1 EIM, but also multiple EIMs, across both diseases. Methods A retrospective study of participants enrolled in the SPARC IBD (Study of Prospective Adult Research Cohort with IBD) registry was performed, and demographic and clinical data were analyzed. A total of 1211 patients with data available on EIMs were included, and differences among variables with vs without EIMs were assessed. Results A total of 329 participants with at least 1 EIM were identified, compared with 882 participants without any EIMs. Crohn’s disease patients and women were more likely to have 2 or more EIMs (P = .005 and P ≤ .001, respectively). Participants with ocular manifestations were likeliest to have at least 2 EIMs (P ≤ .001). Even when diagnosis was controlled for, involvement of the right colon (P = .021) was predictive of IBD-associated arthritis across both diseases in a multivariate generalized linear model. Conclusions This is the first comprehensive large-cohort assessment of how EIMs relate to one another at the individual vs systems levels. Further, our analysis is the first to recognize specific locations of colon involvement associated with EIMs of IBD, regardless of IBD type. These results are important in identifying patients at risk of developing future EIMs and may help with risk stratification when choosing treatments.

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.