Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

ExpLOring the role of the intestinal MiCrobiome in InflammATory bowel disease-AssocIated SpONdylarthritis (LOCATION-IBD).

Background: Inflammatory Bowel Disease (IBD)-associated arthritis is a frequent and potentially debilitating complication of IBD, that can affect those with or without active intestinal disease, and is often difficult to treat. The microbiome is known to play a role in IBD development and has been shown to be associated with inflammatory arthritis without concomitant IBD, but its role in IBD-associated arthritis is still unexplored. Further, disease localization is associated with development of IBD-associated arthritis, and stool compositional profiles are predictive of disease localization, yet mucosal location-specific microbiomes have not been well characterized. To address this gap in understanding, we designed a study (LOCATION-IBD) to characterize the mucosa-associated intestinal microbiome and metabolome in IBD-associated arthritis. Methods: Adults with an established diagnosis of IBD undergoing clinical colonoscopy between May of 2021 and February of 2023 were invited to participate in this study; those interested in participation who met inclusion criteria were enrolled. Prior to enrollment, participants were stratified into those with or without IBD-associated arthritis. All participants were interviewed and had clinical and demographic data collected, and 97.8% completed clinical colonoscopy with biopsy collection. Results and conclusion: A total of 182 participants, 53 with confirmed IBD-associated arthritis, were enrolled in this study, resulting in 1151 biopsies obtained for microbiome and metabolome analysis (median 6, mean 6.3 per participant). Clinical and demographic data obtained from the study population will be analyzed with microbiome and metabolome data obtained from biopsies, with the goal of better understanding the mechanisms underpinning the host-microbiome relationship associated the development of IBD-associated arthritis.

Monitoring Patients With Inflammatory Bowel Disease at High Risk of Anal Cancer.

Anal cancer is a rare but deadly disease that disproportionately affects patients with inflammatory bowel disease (IBD). Rates of adenocarcinoma and human papillomavirus-related squamous cell carcinoma have been consistently demonstrated to be higher in patients with ulcerative colitis and Crohn's disease. Despite this increased risk, uniform screening, diagnosis, and treatment algorithms are lacking. This review describes the most recent literature surrounding anal cancer in the IBD population as well as the unique challenges inherent in diagnosing and treating this population. We conclude by proposing a new screening motif based off literature review and multidisciplinary clinical experience that aims to increase early detection of anal cancers in the IBD population.

Review of Adalimumab Biosimilar SB5 in Immune-Mediated Inflammatory Diseases.

SB5 is an approved biosimilar of adalimumab, a recombinant monoclonal anti-tumor necrosis factor (TNF) antibody. The approval of SB5 was based on the comparison with reference adalimumab in analytical studies, pharmacokinetic (PK) and immunogenicity assessments, and randomized controlled trials. Efficacy data was primarily obtained in patients with rheumatoid arthritis, and extended to include additional indications such as psoriasis, Crohn's disease, or ulcerative colitis by extrapolation. Following its approval, additional post-marketing data have been collected comparing SB5 with reference adalimumab. This review summarizes the clinical data on SB5 from randomized controlled trials and provides a comprehensive overview of the available post-approval data. In "real-world" settings, SB5 was as effective as its reference product across different indications and countries, treatment persistence was well maintained throughout studies, and no new safety concerns were identified. In both controlled and "real-world" settings, switching from reference adalimumab to SB5 was not associated with altered efficacy or clinical complications. In post-approval studies, the quality of SB5 was consistent over time, independent of the batch and process changes, and the SB5 autoinjector was preferred over other autoinjectors by both healthcare professionals and patients. Taken together, these data support the use of SB5 whenever reference adalimumab is appropriate and demonstrate that switching from reference adalimumab to SB5 is feasible.

Histologic Inflammation can Predict Future Clinical Relapse in Ulcerative Colitis Patients in Endoscopic Remission.

Background: In ulcerative colitis (UC), endoscopic improvement, defined as a Mayo Endoscopic Score (MES) of 0 or 1, is a target of treatment. The aim of our study was to evaluate the risk of clinical relapse between patients with an MES of 0 or 1 and determine if histologic activity using the Robarts Histopathologic Index (RHI) was predictive of clinical relapse. Methods: UC patients with an MES score of 0 or 1, no prior colectomy, and at least 1 year of outpatient follow-up after colonoscopy were included. Demographic, clinical characteristics, and clinical relapse were retrospectively collected. Biopsy specimens were read by a gastrointestinal pathologist. Primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and/or colectomy. Results: Four hundred and forty-five UC patients were identified. Ninety-five percent of patients with MES 0 were in histologic remission by the RHI whereas only 35% of patients with MES 1 were in histologic remission. Twenty-six percent of patients experienced a clinical relapse; patients with MES 1 or RHI > 3 were significantly more likely to relapse (P < .01) compared to patients with MES 0 or RHI ≤ 3. When patients were stratified into 4 groups (MES 0, RHI ≤ 3; MES 0, RHI > 3; MES 1, RHI ≤ 3; MES 1, RHI > 3) and adjusted for age and sex, RHI > 3 was predictive of relapse (P = .008). Conclusions: UC patients with endoscopic improvement have a high rate of clinical relapse over time. Histologic activity is a predictor of clinical relapse.

Assessing Progression of Biologic Therapies Based on Smoking Status in Patients With Crohn's Disease.

BACKGROUND: Active smoking is a well-established risk factor for developing Crohn's disease (CD) and negatively impacts overall disease progression. Patients who start or continue smoking after CD diagnosis are at risk for poor outcomes, higher therapeutic requirements, and have higher rates of relapse. However, it remains unclear if the exposure to smoking leads to increased sequencing through treatment therapies, especially biologics. METHODS: The Study of Prospective Adult Research Cohort with IBD (SPARC IBD) registry has been collecting patient-reported outcomes data in real-time, as well as laboratory, endoscopic, and pathologic samples from 17 tertiary referral centers since 2016. In this study, we conducted a retrospective review of the SPARC clinical registry collected between December 2016 and January 2021 from 1 participating site, the University of Maryland School of Medicine's Inflammatory Bowel Disease Program. A total of 619 patients were enrolled in the SPARC IBD database. Four hundred twenty-five patients with CD were included for initial review of completeness of data; of these, 144 patients were excluded due to missing data on smoking status and/or biologic treatment, resulting in a final cohort of 281 patients. We collected and analyzed baseline demographic and clinical characteristics. The final cohort was categorized into 3 exposure groups: current, former, and never smokers. Our outcome of interest was number biologics used, categorized into 3 groups: 0, 1, or ≥2 biologics. RESULTS: One hundred seventy-two never smokers, 70 former smokers, and 39 current smokers were identified. Current, former, and never smokers had no statistically significant differences in number of biologics used (ie, biologic sequencing). However, statistically significant independent risk factors for increased sequencing of biologics were identified. These risk factors included female sex, ileocolonic disease location, younger age at diagnosis, and prolonged disease duration; none of these factors remained significant in adjusted analyses. CONCLUSION: To date, this is the first study assessing the association of smoking and sequencing of biologics. Although current or former smokers were not found to sequence through more biologics when compared with never smokers, smoking is a well-established risk factor for poor health outcomes, and efforts should be made to counsel patients to quit. Further, additional research must be done to stratify risk to patients based on amount of tobacco exposure.

Current, former, and nonsmokers were found to have similar rates of biologic sequencing in patients with Crohn's disease. This was true even when controlling for multiple potential confounders.

Efficacy of biologic and small molecule agents as second-line therapy after exposure to TNF inhibitors in patients with ulcerative colitis: A propensity-matched cohort study.

BACKGROUND: There is limited real-world data on comparative effectiveness of different biologic or small molecule agents as second-line therapies in patients with ulcerative colitis (UC) with prior exposure to a tumour necrosis factor inhibitor (TNFi). METHODS: We conducted a retrospective cohort study using TriNetX, a multi-institutional database to assess the efficacy of tofacitinib, vedolizumab and ustekinumab in patients with ulcerative colitis (UC) with prior exposure to a TNFi. Failure of medical therapy was defined as a composite outcome of intravenous steroids or colectomy within 2 years. One-to-one propensity score matching was performed for demographics, disease extent, mean haemoglobin, C-reactive protein, albumin and calprotectin, prior IBD medications and steroid use between cohorts. RESULTS: Among 2141 patients with UC and prior exposure to TNFi, 348 (16.2%), 716 (33.4%) and 1077 (50.3%) were switched to tofacitinib, ustekinumab and vedolizumab, respectively. After propensity-score matching, there was no difference in the composite outcome (aOR: 0.77, 95% CI: 0.55-1.07) but higher risk of colectomy (aOR: 2.69, 95% CI: 1.31-5.50) in the tofacitinib cohort than the vedolizumab cohort. There was no difference in the risk of composite outcome (aOR: 1.29, 95% CI: 0.89-1.86) but higher risk of colectomy (aOR: 2.63, 95% CI: 1.24-5.58) in the tofacitinib cohort than the ustekinumab cohort. The vedolizumab cohort had a higher risk of composite outcome (aOR: 1.67, 95% CI: 1.29-2.16) than the ustekinumab cohort. CONCLUSION: Ustekinumab might be the preferred second-line therapy over tofacitinib and vedolizumab in patients with UC that were previously exposed to a TNFi.

Impact of Holding Immunosuppressive Therapy in Patients with Inflammatory Bowel Disease Around mRNA COVID-19 Vaccine Administration on Humoral Immune Response and Development of COVID-19 Infection.

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.

Management of Inflammatory Bowel Disease Using E-health Technologies: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Technological advances have provided innovative, adaptive, and responsive models of care for inflammatory bowel diseases [IBD]. We conducted a systematic review to compare e-health interventions with standard care in management of IBD. METHODS: We searched electronic databases for randomised, controlled trials [RCT] comparing e-health interventions with standard care for patients with IBD. Effect measures were standardised mean difference [SMD], odds ratio [OR], or rate ratio [RR], calculated using the inverse variance or Mantel-Haenszel statistical method and random-effects models. Version 2 of the Cochrane tool was used to assess the risk of bias. The certainty of evidence was appraised with the GRADE framework. RESULTS: Fourteen RCTs [n = 3111; 1754 e-health and 1357 controls] were identified. The difference in disease activity scores (SMD 0.09, 95% confidence interval [CI]: -0.09-0.28) and clinical remission (odds ratio [OR] 1.12, 95% CI: 0.78-1.61) between e-health interventions and standard care were not statistically significant. Higher quality of life [QoL] [SMD 0.20, 95% CI: 0.05-0.35) and IBD knowledge [SMD 0.23, 95% CI: 0.10-0.36] scores were noted in the e-health group, and self-efficacy levels [SMD -0.09, 95% CI: -0.22-0.05] were comparable. E-health patients had fewer office [RR 0.85, 95% CI: 0.78-0.93] and emergency [RR 0.70, 95% CI: 0.51- 0.95] visits, with no statistically significant difference in endoscopic procedures, total health care encounters, corticosteroid use, and IBD related hospitalisation or surgery. The trials were judged to be at high risk of bias or to have some concerns for disease remission. The certainty of evidence was moderate or low. CONCLUSION: E-health technologies may have a role in value-based care in IBD.

Clinical Evaluation of Risankizumab in the Treatment of Adults with Moderately to Severely Active Crohn's Disease: Patient Selection and Reported Outcomes.

This article will review risankizumab, a monoclonal antibody targeting interleukin 23 (IL-23) for the treatment of moderate-to-severe Crohn's disease. The article will detail the mechanism of action and dosing strategies. Efficacy in induction and maintenances will be reviewed from available clinical trials as well as an evaluation of safety of the medication for use in Crohn's disease and other immune mediated diseases. Finally, a discussion of when to use this medication for treatment in Crohn's disease as well as how to monitor patients after medication initiation will be discussed.

Surveillance for Colorectal Neoplasia in Inflammatory Bowel Disease: When to Stop.

Patients with chronic ulcerative and Crohn's colitis are at increased risk for colorectal neoplasia(CRN [dysplasia and cancer]) compared to the general population. Risk factors for CRN include extent of colitis, cumulative inflammatory burden, family history of colorectal cancer, and primary sclerosing cholangitis. Best practices to prevent CRN include control of colonic inflammation, high quality surveillance colonoscopy with or without enhanced imaging techniques, resection of visible dysplasia if possible, and colectomy in patients with unresectable dysplasia, invisible multifocal low grade dysplasia, or invisible high grade dysplasia. Cessation of dysplasia surveillance is individualized and should involve shared decision making based on factors including but not limited to chronologic age, frailty, co-morbid conditions, life expectancy, results of prior surveillance exams, and risk factors for CRN.

Prescriber Perspectives on Biosimilar Adoption and Potential Role of Clinical Pharmacology: A Workshop Summary.

The approval and adoption of biosimilar products are essential to contain increasing healthcare costs and provide more affordable choices for patients. Despite steady progress in the number of the US Food and Drug Administration (FDA) biosimilar approvals over the years, biosimilar adoption in the United States has been slow and gradual, largely driven by payers rather than clinicians. In order to better understand the barriers to biosimilar adoption in the clinic, the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) and the FDA jointly hosted a virtual workshop on April 13, 2022, titled "Biosimilars: A Decade of Experience and Future Directions - Strategies for Improving Biosimilar Adoption and the Potential Role of Clinical Pharmacology." This summary documents the experiences of four leading academic clinicians with specialties in oncology, rheumatology, gastroenterology, and endocrinology and their perspectives on how to increase biosimilar adoption, including the role of clinical pharmacology. Besides systemic changes in pricing and reimbursement, there is a need for additional education of a broad range of providers, including advanced care practitioners, and patients themselves. Educational efforts highlighting the rigor of the studies that support the approval of biosimilars-including the clinical pharmacology studies-and the benefits of biosimilars, can play a major role in improving biosimilar acceptance.

Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

Emerging drugs for the treatment of inflammatory bowel disease.

INTRODUCTION: Anti-tumor necrosis factor (TNF)-α have been the mainstay therapy for Crohn's (CD) and ulcerative colitis (UC) for decades. With growing need for highly effective therapy, various therapeutic targets have been introduced including anti-integrins, anti-interleukin (IL) 12/23, selective anti-IL23, Janus Kinase (JAK) inhibitors, sphingosine-1-phosphate (S1P) receptor modulators, and mRNA-124 splicing agent. AREAS COVERED: The current state of available IBD therapies and those in development are reviewed, with recommendations made on positioning in clinical practice. EXPERT OPINION: Selecting and sequencing IBD therapies remains a clinical challenge. Disease phenotype, severity of symptoms, patient comorbidities, and prior drug exposure should be considered when considering therapy options. Anti-TNF remains a time-tested option that is effective in both UC and CD. The perception that newer biologics have slower onset of action is probably overestimated and providers should reconsider need for concurrent corticosteroid. JAK-inhibitors provide rapid symptom improvement in patients with moderate-severe UC. Due to safety concerns, it is recommended as a second-line therapy for UC. The goal for IBD treatment should be personalized, have rapid onset of action, induce durable clinical and endoscopic remission, and have excellent safety.

Endoscopic Balloon Dilation of Strictures: Techniques, Short- and Long-Term Outcomes, and Complications.

EBD is safe and effective for the treatment of strictures. Here we describe the technique of endoscopic balloon dilation (EBD) of strictures including preprocedure considerations, indications, contraindications, and postprocedure complications. The short- and long-term outcomes of EBD including factors associated with improved outcomes are also discussed.