Adaptive steroid tapering impedes corticosteroid-free remissions compared to forced tapering in clinical trials of ulcerative colitis.

INTRODUCTION: It is unclear if steroid tapering protocols can impact clinical trial outcomes in ulcerative colitis (UC), particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals and adaptive steroid tapering utilizes investigator discretion as determined by the patient's response. METHODS: In this post-hoc analysis from six clinical trials of UC (VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE and ULTRA2), responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for treat-through versus re-randomization designs and multivariate regression was performed to account for other potential confounding variables. The primary outcome was corticosteroid-free clinical remission (CR) at one-year and secondary outcomes were CR and endoscopic improvement. RESULTS: There was a total of 861 patients who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid tapering regimens were less likely to achieve corticosteroid-free CR at one year (odds ratio [OR] 0.66 [95% CI 0.48-0.92], p=0.015) but had increased odds for achieving CR at one year (OR 1.9 [95% CI 1.43-2.52], p<0.001). The steroid tapering regimen was not associated with achievement of endoscopic improvement at one year. CONCLUSIONS: Among patients with UC on corticosteroids in clinical trials, patients using adaptive steroid weaning regimens were less likely to achieve corticosteroid-free CR at one year but more likely to achieve CR at one year. Consideration should be given to implementing mandatory fixed steroid weaning protocols in future clinical trials of UC.

Subcutaneous Infliximab (CT-P13) as Maintenance Therapy for Inflammatory Bowel Disease: 2 Randomized Phase 3 Trials.

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. We aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. Co-primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease.

BACKGROUND: Ozanimod showed efficacy and safety in the phase 2 STEPSTONE study conducted in patients with moderately to severely active Crohn's disease. AIMS: This analysis assessed the effects of ozanimod on circulating lymphocytes in Crohn's disease. METHODS: Patients received ozanimod 0.92 mg for 12 weeks. Lymphocyte subtypes were evaluated using multicolor flow analysis on blood samples collected before treatment and on Week 12. Absolute lymphocyte count changes were analyzed by Wilcoxon signed rank tests. Disease activity changes and efficacy outcomes were evaluated at Week 12, and associations with lymphocyte subtype levels were assessed using Spearman's correlation and logistic regression. RESULTS: Reductions in median total T, Th, and cytotoxic T cells occurred at Week 12 (45.4%-76.8%), with reductions in most subtypes of 47.5% to 91.3% (P < 0.001). CD8+ terminally differentiated effector memory cells were largely unaffected (median change, - 19%; P = 0.44). Reductions in median total B cells occurred at Week 12 (76.7%), with reductions in subtypes of 71.4% to 81.7% (P < 0.001). Natural killer and monocyte cell counts were unchanged. Greater baseline levels and changes in nonswitched memory B cells were significantly associated with clinical, endoscopic, and histologic efficacy (P < 0.05, all comparisons). CONCLUSIONS: Ozanimod reduced circulating levels of all B-cell and most T-cell subsets but not monocytes or natural killer cells. Key subsets relevant to immune surveillance were not reduced, supporting the low risk of infection and malignancy with ozanimod in chronic inflammatory diseases. Levels of nonswitched memory B cells were associated with efficacy, providing a potential marker for ozanimod response. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02531113, EudraCT: 2015-002025-19.

Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancer.

Neutrophil (PMN) tissue accumulation is an established feature of ulcerative colitis (UC) lesions and colorectal cancer (CRC). To assess the PMN phenotypic and functional diversification during the transition from inflammatory ulceration to CRC we analyzed the transcriptomic landscape of blood and tissue PMNs. Transcriptional programs effectively separated PMNs based on their proximity to peripheral blood, inflamed colon, and tumors. In silico pathway overrepresentation analysis, protein-network mapping, gene signature identification, and gene-ontology scoring revealed unique enrichment of angiogenic and vasculature development pathways in tumor-associated neutrophils (TANs). Functional studies utilizing ex vivo cultures, colitis-induced murine CRC, and patient-derived xenograft models demonstrated a critical role for TANs in promoting tumor vascularization. Spp1 (OPN) and Mmp14 (MT1-MMP) were identified by unbiased -omics and mechanistic studies to be highly induced in TANs, acting to critically regulate endothelial cell chemotaxis and branching. TCGA data set and clinical specimens confirmed enrichment of SPP1 and MMP14 in high-grade CRC but not in patients with UC. Pharmacological inhibition of TAN trafficking or MMP14 activity effectively reduced tumor vascular density, leading to CRC regression. Our findings demonstrate a niche-directed PMN functional specialization and identify TAN contributions to tumor vascularization, delineating what we believe to be a new therapeutic framework for CRC treatment focused on TAN angiogenic properties.

Post-traumatic stress disorder symptoms are frequent among inflammatory bowel disease patients of South Asian descent-A case-control study.

BACKGROUND: Post-traumatic stress (PTS) is the psycho-physiological response to a traumatic or life-threatening event and is implicated in inflammatory bowel disease (IBD). IBD-PTS is present in up to 30% of white, non-Hispanic patients. The rates of IBD in Asian populations are expanding, making the exploration of IBD-PTS in this population imperative. METHODS: Adult patients of South/Southeast (S/SE) Asian decent with IBD for more than 6 months were recruited online via social media and patient-support groups. Participants completed the post-traumatic stress disorder (PTSD) Checklist-5 (PCL-5), the United States National Institutes of Health's Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) -43 profile and demographics. S/SE Asian participants were age and sex matched (1:2) with randomly selected white, non-Hispanic controls. Statistical analyses evaluated differences in IBD-PTS symptoms between groups, the relationship between disease severity and health-related quality of life (HRQoL) and predictors of IBD-PTS severity. RESULTS: Forty-seven per cent of the 51 S/SE Asian participants met the diagnostic cut-off for PTSD on the PCL-5 compared to 13.6% of 110 IBD controls. The mean global score on the PCL-5 was three times higher in S/SE Asians. Patients of S/SE Asian decent were over five times more likely to have PTSD due to their IBD experiences than controls, nearly doubling when controlling for disease activity. More severe IBD-PTS was present in S/SE Asian patients with active disease and those with extraintestinal manifestations. Higher global levels of IBD-PTS were associated with poorer HRQoL in S/SE Asians where increased hyperarousal from IBD-PTS predicted more sleep disturbance. CONCLUSIONS: S/SE Asian patients are five times more likely to experience IBD-PTS than their white, non-Hispanic counterparts. Several cultural factors lead to IBD-PTS in S/SE Asian patients that must be considered by IBD providers. Preventing, screening for and treating IBD-PTS in this population appears warranted.

Evolution of Symptoms After Ustekinumab Induction Therapy in Patients With Crohn's Disease.

BACKGROUND & AIMS: Ustekinumab is an effective treatment of Crohn's disease (CD). Of interest to patients is knowing how soon symptoms may improve. We analyzed ustekinumab response dynamics from the ustekinumab CD trials. METHODS: Patients with CD received intravenous induction with ustekinumab ∼6 mg/kg (n = 458) or placebo (n = 457). Week 8 ustekinumab responders received subcutaneous ustekinumab 90 mg as the first maintenance dose or as an extended induction dose for nonresponders. Patient-reported symptom changes (stool frequency, abdominal pain, general well-being) within the first 14 days and clinical outcomes through week 44 were evaluated using the CD Activity Index. RESULTS: After ustekinumab infusion, stool frequency improvement was significantly (P < .05) greater than placebo on day 1 and for all patient-reported symptoms by day 10. In patients with no history of biologic failure or intolerance, cumulative clinical remission rates increased from 23.0% at week 3 to 55.5% at week 16 after the subcutaneous dose at week 8. Corresponding cumulative rates for patients with a history of biologic failure or intolerance increased from 12.9% to 24.1%. Neither change from baseline in CD Activity Index score nor week 8 ustekinumab pharmacokinetics were associated with week 16 response. Among all patients who received subcutaneous ustekinumab 90 mg q8w, up to 66.7% were in clinical response at week 44. CONCLUSIONS: Ustekinumab induction provided symptom relief by day 1 post-infusion. Following ustekinumab infusion and a subcutaneous 90 mg injection, clinical outcomes continued to increase through week 16 and up to week 44. Regardless of week 8 clinical status or ustekinumab pharmacokinetics, patients should receive additional treatment at week 8. CLINICALTRIALS: gov numbers, NCT01369329, NCT01369342, and NCT01369355.

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.

Efficacy and Safety of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease.

BACKGROUND AND AIMS: Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1 developed as treatment for inflammatory bowel disease. METHODS: Six phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trials compared efficacy and safety of ontamalimab [25 mg and 75 mg once every 4 weeks] with placebo in patients with moderate-to-severe ulcerative colitis or Crohn's disease [two induction studies and one re-randomised maintenance study per condition]. This clinical trial programme was discontinued in 2020 for reasons unrelated to drug safety/efficacy; Crohn's disease studies are described in the supplementary materials. RESULTS: The induction [12-week] and maintenance [52-week] studies included 659 and 366 randomised patients, respectively. More patients who received ontamalimab induction than placebo achieved the primary endpoint of clinical remission at week 12 [25 mg, 18.5% vs 15.8% (p = 0.617), 27.0% vs 12.5% (p = 0.027); 75 mg, 29.8% vs 15.8% (p = 0.018), 29.5% vs 12.5% (p = 0.014)]; significantly more patients who received ontamalimab maintenance therapy than placebo achieved week 52 clinical remission [25 mg, 53.5% vs 8.2%, p < 0.001; 75 mg, 40.2% vs 12.8%, p < 0.001]. Endoscopic improvement was generally significantly different vs placebo [induction: 25 mg, 27.8% vs 21.1 (p = 0.253), 35.1% vs 12.5% (p = 0.001); 75 mg, 41.1% vs 21.1 (p = 0.002), 33.9% vs 12.5% (p = 0.003); maintenance: 25 mg, 56.3% vs 9.6% (p < 0.001); 75 mg, 48.8% vs 15.1% (p < 0.001)]. Adverse event rates were similar between ontamalimab and placebo groups. CONCLUSIONS: Ontamalimab 75 mg was effective with no safety concerns as induction and maintenance therapy for patients with moderate-to-severe ulcerative colitis.

The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.

This study shows that the disease severity index (DSI) for inflammatory bowel disease (IBD) is a valid and reliable instrument encapsulating the disease phenotype, disease activity, and impact of the disease on the patient; and it accurately predicts for incident disease complications.

Persistent perineal sinus following proctocolectomy in the inflammatory bowel disease patient.

Prolonged perineal wound healing following proctocolectomy in patients with inflammatory bowel disease (IBD) is a frustrating result for the medical team and patients who were hoping for improved quality of life. Prolonged healing, which lasts more than 6 months following proctocolectomy, is termed persistent perineal sinus (PPS) and typically necessitates further surgical management. Healing of the PPS is difficult due to the resulting "dead space" following proctocolectomy, necessitating the need to fill the void with viable tissue in an area with anatomic constraints. Here we provide a narrative review and comprehensively address the incidence, pathogenesis, and clinical and operative management of a PPS in patients with IBD following proctocolectomy. Operative methods discussed include surgical debridement, flap closure of the perineum, omental flap closure, and gracilis muscle transposition. It is necessary to further investigate and establish a gold standard of care for these patients.

Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.

BACKGROUND AND AIMS: This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-TNF therapy in patients with UC or CD. METHODS: TREM-1 whole blood gene expression was analysed by RNA sequencing [RNA-seq] in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD]. RESULTS: TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p=0.48], endoscopic remission [p=0.53], clinical response [p=0.58] or clinical remission [p=0.79] at Week 8, or clinical response [p=0.60] at Week 52. However, an association was observed with endoscopic response [p=0.01], endoscopic remission [p=0.048], and clinical remission [p=0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p=0.56], endoscopic remission [p=0.33], clinical response [p=0.07], clinical remission [p=0.65] at Week 12, or endoscopic response [p=0.61], endoscopic remission [p=0.51], clinical response [p=0.62] or clinical remission [p=0.97] at Week 56. CONCLUSIONS: Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with IBD.

Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.

BACKGROUND AND AIMS: Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial. METHODS: A vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety. RESULTS: There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean ±â€…SD: -86.2 ±â€…92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 ±â€…4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 ±â€…1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-γ [46-52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation. CONCLUSIONS: Neuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life.

The importance of predicting patient responses to monoclonal antibodies for Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a chronic immune-mediated inflammatory bowel disease that results in relapsing and remitting symptoms but progressive transmural bowel damage leading to significant morbidity. CD results from dysregulation of the immune system related to genetic and environmental factors. While the use of monoclonal antibodies targeting cytokines and adhesion molecules has been shown to improve outcomes in CD patients, their widespread use has been limited due to high costs as well as variable access. Here, we summarize the factors that have been shown to correlate with responsiveness to biologic agents for use in practice. AREAS COVERED: We summarize the current literature regarding factors that have been shown to influence patient response to various biologic agents including: patient-related factors (e.g. age, gender, weight smoking history); disease-specific factors (e.g. disease duration, location/extension, behavior/phenotype, severity); genetic markers; transcription factors, and the gut microbiome. Finally, we review the utility of prediction models and present data supporting the use of recently developed decision support tools. EXPERT OPINION: Clinical decision support tools developed by machine learning are currently available for the selection of biologic agents in CD patients. We expect these models to become an integral tool for clinicians in the treatment of CD in the coming years.

A randomised, double-blind, placebo-controlled study of the LAG-3-depleting monoclonal antibody GSK2831781 in patients with active ulcerative colitis.

BACKGROUND: Selective depletion of T cells expressing LAG-3, an immune checkpoint receptor that is upregulated on activated T cells, has been investigated in pre-clinical models as a potential therapeutic approach in inflammatory and autoimmune diseases where activated T cells are implicated. AIMS: GSK2831781, a depleting monoclonal antibody that specifically binds LAG-3 proteins, may deplete activated LAG-3+ cells in ulcerative colitis (UC). METHODS: Patients with moderate to severe UC were randomised to GSK2831781 or placebo. Safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of GSK2831781 were evaluated. RESULTS: One hundred four participants across all dose levels were randomised prior to an interim analysis indicating efficacy futility criteria had been met. Efficacy results focus on the double-blind induction phase of the study (GSK2831781 450 mg intravenously [IV], N = 48; placebo, N = 27). Median change from baseline (95% credible interval [CrI]) in complete Mayo score was similar between groups (GSK2831781 450 mg IV: -1.4 [-2.2, -0.7]; placebo: -1.4 [-2.4, -0.5]). Response rates for endoscopic improvement favoured placebo. Clinical remission rates were similar between groups. In the 450-mg IV group, 14 (29%) participants had an adverse event of UC versus 1 (4%) with placebo. LAG-3+ cells were depleted to 51% of baseline in blood; however, there was no reduction in LAG-3+ cells in the colonic mucosa. Transcriptomic analysis of colon biopsies showed no difference between groups. CONCLUSION: Despite evidence of target cell depletion in blood, GSK2831781 failed to reduce inflammation in the colonic mucosa suggesting no pharmacological effect. The study was terminated early (NCT03893565).

The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease.

INTRODUCTION: Janus Kinase inhibitors (JAKi) are a new class of oral therapies for the treatment of moderate-severe ulcerative colitis with additional potential for the treatment of moderate-severe Crohn's disease. In contrast to biologic therapies JAKi provide the opportunity for non-immunogenic once or twice daily oral therapies. AREAS COVERED: Janus Kinase inhibitors for the treatment of ulcerative colitis and Crohn's disease based on mechanism of action, pharmacokinetics, clinical trial and real-world data regarding safety and efficacy; focusing on regulatory approvals in the U.S. and Europe. EXPERT OPINION: Janus Kinase inhibitors are considered among the 'advanced therapies' for IBD and are approved for the treatment of moderate to severe ulcerative colitis in adults with pending approvals for Crohn's disease in the U.S. JAKi offer non-immunogenic, oral options for patient not responding to other conventional agents but, have been 'restricted' by the FDA to patients with inadequate response to TNF blockers. JAKi offer rapidly acting oral alternatives to biologic agents for moderate-severe ulcerative colitis where the risks of cardiovascular and thrombotic events noted in rheumatoid arthritis have not been observed in IBD clinical trials. Nevertheless, monitoring of infections (primarily herpes zoster) and risk factors for cardiovascular and thrombotic complications is appropriate.

COVID-19 and Inflammatory Bowel Disease.

The COVID-19 pandemic caused by the SARS-CoV-2 virus represents an unprecedented global health crisis. Safe and effective vaccines were rapidly developed and deployed that reduced COVID-19-related severe disease, hospitalization, and death. Patients with inflammatory bowel disease are not at increased risk of severe disease or death from COVID-19, and data from large cohorts of patients with inflammatory bowel disease demonstrate that COVID-19 vaccination is safe and effective. Ongoing research is clarifying the long-term impact of SARS-CoV-2 infection on patients with inflammatory bowel disease, long-term immune responses to COVID-19 vaccination, and optimal timing for repeated COVID-19 vaccination doses.

Hospitalization Experiences and Post-traumatic Stress in Inflammatory Bowel Disease: Opportunities for Change.

INTRODUCTION: Medical trauma related to IBD (IBD-PTS) affects approximately 25% of patients and is associated with poor outcomes. Prior studies identify common hospitalization experiences as potentially traumatic but have not measured risk relationships for the development of IBD-PTS. We aim to investigate what aspects of hospitalizations may increase the chance of medical trauma and IBD-PTS development. METHODS: Adult patients with IBD enrolled in the IBD Partners database were recruited. Study specific questionnaires included PTSD checklist, 5th edition (PCL-5), patient experience questionnaire, and items about the patient's most stressful hospitalization and nonhospital sources of medical trauma. Established criteria for the PCL-5 identified significant IBD-PTS symptoms (re-experiencing, avoidance, mood change, hyperarousal, global diagnosis). Select disease and treatment information was obtained from the main IBD Partners dataset. Univariate and multivariate statistics evaluated the relationships between hospitalization data and IBD-PTS. RESULTS: There were 639 participants with at least 1 hospitalization for IBD included. Approximately two-thirds had Crohn's disease; most were White, non-Hispanic, female, middle-aged, and reported their IBD as being in remission. Forty percent of patients stated a hospitalization was a source of IBD-PTS. Frequent anxiety while hospitalized increased the odds of IBD-PTS 2 to 4 times; similar relationships existed for pain/pain control. Higher quality communication, information, and listening skills reduced the odds of IBD-PTS, albeit marginally. CONCLUSIONS: Patients with IBD consistently cite hospitalizations as potential sources of medical trauma. Poorly managed anxiety and pain demonstrate the greatest chance for IBD-PTS development. Gender and racial/ethnic differences emerged for these risks. Positive interactions with the medical team may help mitigate in-hospital IBD-PTS development.

This study finds IBD patients with the poorest hospital experiences and those with poor pain and anxiety control are at the highest risk of developing post-traumatic stress disorder symptoms due to medical trauma. Medical staff behavior is an important consideration.

Immune Checkpoint Inhibitor Enterocolitis vs Idiopathic Inflammatory Bowel Disease.

Immune checkpoint inhibitors have revolutionized management of advanced malignancies. However, their use is frequently complicated by immune related adverse events (irAEs), immune checkpoint inhibitor enterocolitis (IMEC) being the most common toxicity. IMEC is a distinct form of bowel inflammation that is highly reminiscent of idiopathic inflammatory bowel disorders (Crohn's disease, ulcerative colitis, and microscopic colitis). In this review, we highlight the similarities and differences in the pathophysiology, clinical presentation, evaluation, and management of these overlapping immune inflammatory bowel disorders. IMEC is an inflammatory bowel disease-like irAE that occurs as an outcome of disruption of intestinal immune surveillance and gut dysbiosis. Clinical and endoscopic presentation of both entities is strikingly similar, which often guides management. Though well established in inflammatory bowel disease, little is known about the long term outcomes of IMEC.