We aimed to describe the real-world effectiveness of tofacitinib in ulcerative colitis (UC). We analysed a retrospective, multi-centre cohort from six centres in the USA. UC patients started on tofacitinib (10 mg BID) for active disease were included. Primary outcome was clinical response (>50% reduction in symptoms) at Week 8 as determined by physician global assessment. Secondary outcomes included clinical remission (no symptoms) at Week 8, clinical response/remission at Week 16 and endoscopic healing (defined as Mayo endoscopic score ≤1 or absence of erosions/ulcerations) within 6 months of initiating tofacitinib. Descriptive statistics and Fisher exact tests were performed. Logistic regression assessed predictors of Week 8 response. A multi-variable model was created using backward elimination. A total of 123 UC patients were included with a median age of 38 years (IQR 27–46) and 5 years disease duration (IQR 2–9). 56.1% were men and 60.2% had pancolitis. 28.5% were bio-naïve while 40.7% had been exposed to both anti-tumour necrosis factor (anti-TNF) biologics and vedolizumab (VDZ). Ninety-six patients completed 8 weeks of tofacitinib. 60.8% had clinical response and 13.5% clinical remission at Week 8. At Week 16 (total n = 74), 55.4% had clinical response and 48.6% clinical remission. 64.9% (total n = 57) had endoscopic healing. A larger proportion of bio-naïve patients achieved clinical response with no difference between those exposed to both anti-TNF and VDZ or either alone (Table 1). Patients with prior exposure to 2 biologic classes (anti-TNF and VDZ) had lower rates of endoscopic healing compared with bio-naïve and 1 biologic class exposure (Table 1). Bio-naïve status and higher albumin were associated with greater chance of Week 8 response while pancolitis, baseline endoscopic Mayo score 3, concomitant steroids at start of tofacitinib, and male gender were associated with lower chance of response (Table 2). In multi-variable analysis, bio-naïve status (aOR 5.50, 95% CI 1.71–17.65), concomitant steroids (aOR 0.25, 95% CI 0.07–0.83), and male gender (aHR 0.25, 95% CI 0.08–0.83) were associated with Week 8 response. Tofacitinib is effective at inducing clinical response in a real-world clinical setting. Prior exposure to biologics is associated with reduced chance of clinical response and endoscopic healing. Table 1. Tofacitinib response rates by prior biologic exposure. (*p = 0.007, **p < 0.001, *** p < 0.001. Patients who discontinued tofacitinib before Week 8 or 16 were considered non-responders.) Table 1. Tofacitinib response rates by prior biologic exposure. (*p = 0.007, **p < 0.001, *** p < 0.001. Patients who discontinued tofacitinib before Week 8 or 16 were considered non-responders.) Table 2. Baseline variables significantly associated with tofacitinib clinical response at Week 8 OR: odds ratio; CI: confidence interval. Table 2. Baseline variables significantly associated with tofacitinib clinical response at Week 8 OR: odds ratio; CI: confidence interval.
Introduction: Patients with inflammatory bowel disease (IBD) are at risk of malnutrition given factors including protein enteropathy, impaired nutrient absorption, and increased metabolic demand during disease flares. The prevalence of malnutrition among outpatients with IBD is between 20-50%. Malnourished patients can develop sarcopenia, which is associated with increased need for surgery and postoperative complications. The primary aim of this study is to assess the feasibility of implementing malnutrition screening in IBD patients in GI clinics at a tertiary care center. Here we present preliminary findings and exploratory analysis from the proposed intervention. Methods: Patients in GI clinic at a tertiary care center between August and December 2022 with a diagnosis of ulcerative colitis (UC) or Crohn’s Disease (CD) were included. Patients were screened using the mMUST survey which includes BMI < 18.5, 5% weight loss within the past 6 months, and IBD flare with poor intake lasting > 5 days within 6 months. A point was assigned for the presence of each variable. Patients with mMUST > 1 were sent to a dietician for assessment including Body Impedance Analysis (BIA), hand grip strength, and nutritional history. Data was extracted via chart review. Exploratory analysis involved t-tests for comparison between numerical values and Fischer’s exact tests for categorical comparisons. Spearman’s correlation matrix was used due to small sample size. Results: Of 1629 eligible patients, 921 underwent mMUST screening. Of 40 patients with mMUST > 1, 19 patients completed dietician evaluation. Characteristics of these patients are displayed in Table 1. More patients with BMI ≤ 25 had muscle depletion (P = 0.003). Patients with BMI ≤ 25 had lower BIA fat mass and BIA percent body fat compared to those with BMI > 25 (P < 0.001). There were significant (P < 0.05) positive correlations between BIA body fat mass and BMI (P = 0.96) as well as hand grip and BIA skeletal muscle mass (P = 0.75). Conclusion: 56.5% of IBD patients were screened for malnutrition during the study, suggesting that standardized malnutrition screening is feasible. 81.25% of patients who completed the dietician evaluation had a BMI ≤ 25, which could indicate a role for education about malnutrition in overweight patients. Potential barriers to implementation identified include provider documentation, patient buy-in, and verbiage used by schedulers. Continued study with interventions to improve uptake is warranted. Table 1. - Characteristics of nineteen patients who completed mMUST screening as well as dietician evaluation. Units in number of patients per category unless otherwise denoted Total Patients BMI ≤ 25 BMI > 25 Crohn's Disease 13 9 4 Ulcerative Colitis 6 4 2 Mean Disease Duration (years) 13.47 ± 13.23 16.54 ± 14.79 6.83 ± 5.27 Current biologic or small molecule use 16 10 6 Steroid Use within 3 months 13 8 5 Disease flare within 3 months 17 11 6 History of surgery due to IBD 10 8 2 mMUST > 1 7 5 2 Daily nutritional intake < 75% needs 6 4 2
Introduction: Approximately 20% of patients with ulcerative colitis (UC) experience an acute disease flare requiring hospitalization. Acute severe UC (ASUC) is a life-threatening condition that frequently requires intensive treatment with steroids, electrolyte and fluid supplementation, and nutritional support. Although steroids remain first line therapy, patients who fail to respond may require rescue therapy with medications such as infliximab (IFX). In patients in whom medical therapy fails, colectomy is considered. Small studies have shown that high dose tofacitinib can be an effective treatment for ASUC. We present a case of ASUC in which tofacitinib induced clinical and endoscopic remission within days following non-response to IFX. Case Description/Methods: A 33-year-old woman with UC and celiac disease, both diagnosed in September 2022, was hospitalized with an 8-week history of progressive hematochezia, rectal pain, and weight loss. The patient was biologic-naive and had received mesalamines, budesonide, and prednisone. The patient's flexible sigmoidoscopy (FS) showed Mayo 3 inflammation in the rectosigmoid colon (Figure 1a). Over the course of 7 days, the patient received IV hydrocortisone and 2 doses of IFX with minimal clinical response. FS was repeated which showed worsening ulceration despite IFX therapy (Figure 1b). Colectomy was discussed as the next treatment option but first the decision was made to initiate tofacitinib therapy at 10 mg TID. Three days afterwards, the patient had decreased hematochezia. A repeat FS showed Mayo 0 inflammation (Figure 1c). As such, colectomy was cancelled, and the patient was discharged with a steroid taper and planned transition to upadacitinib due to insurance challenges. At five month follow up, the patient remains in clinical remission on upadacitinib 30 mg daily. Discussion: This case suggests that tofacitinib is a viable rescue therapy in ASUC that does not respond to IFX. Tofacitinib therapy may be advantageous due to its rapid onset of peak serum concentration, short half-life, and decreased risk of drug loss in the setting of hypoalbuminemia and colonic protein loss. This case highlights the possible role of high-dose tofacitinib as a fast-acting and effective therapy in patients hospitalized with ASUC as a method of reducing the morbidity of colorectal surgery.Figure 1.: A: Initial flexible sigmoidoscopy revealing Mayo 3 inflammation in the rectosigmoid colon. B: Rectosigmoid colon following several days of IV hydrocortisone and 2 doses of infliximab. C: Rectosigmoid colon demonstrating mucosal healing after five days of tofacitinib therapy.
Abstract INTRODUCTION Obesity among patients with inflammatory bowel disease (IBD) is increasing with prevalence of 15-40%. Studies have shown that obesity may have poor prognostic implications on IBD treatment and outcomes. There is lack of data focused on the management of obesity in IBD patients. This study’s primary aim was to evaluate whether patients with obesity and IBD have similar rates of obesity management compared to non-IBD obese patients with and without nonalcoholic fatty liver disease (NAFLD). METHODS This is a single-center retrospective study of 400 obese (body mass index > 30 kg/m2) adult patients seen in a primary care clinic between March 2019 and August 2021. Four cohorts, each with 100 patients, were studied. The 4-level cohort analysis included patients with ulcerative colitis and obesity (UC-O), Crohn’s disease and obesity (CD-O), NAFLD and obesity (NAFLD-O), and a control group of patients with obesity only. The 3-level cohort analysis combined UC-O and CD-O and compared this cohort to the NAFLD-O and obesity-only cohorts. Obesity management data collected included: if obesity was documented (OD) in the medical record’s problem list, dietician referral, pharmacologic therapy, and bariatric surgery referral. One-way ANOVA was used to compare numeric variables and chi-squared was used for categorical variables. Logistic regression models were used for primary outcomes. RESULTS Baseline characteristics of BMI, age, gender, and race were similar among patients in the 4-level and 3-level cohort analyses (Tables 1 and 2). Across both analyses, NAFLD-O patients had the highest prevalence of OD (79% p<0.001) and 2.61 higher odds of OD than the control (p =0.003). NAFLD-O patients also had the highest prevalence of dietician referrals (69%, p=0.01). CD-O patients had the highest prevalence of pharmacologic intervention (17%, p=0.01). UC-O patients were less likely to be referred to a dietician (OR=0.55, p=0.03) while CD-O patients were more likely to have pharmacologic management (OR=3.21, p=0.02). Secondary outcomes of comparisons of IBD-specific variables between UC-O and CD-O revealed significant differences as well (Table 3). DISCUSSION This is the first study investigating differences in treatments offered for obesity in IBD. With emerging evidence that obesity likely plays a role in IBD pathogenesis, timely identification and treatment is crucial. Significant differences in management of IBD patients with obesity highlight the need for increased awareness among healthcare providers. Our findings that CD-O patients had a higher rate of corticosteroid, immunomodulator, anti-TNF, anti-interleukin use, and IBD surgery compared to UC-O patients suggests that obesity may contribute to the pathogenesis of CD more so than UC. Further studies are needed to determine which obesity therapies are most effective in the IBD population.
The aim of the study was to investigate the risk factors associated with the development of small bowel obstruction (SBO) in Crohn's disease (CD) after small bowel resection (SBR) that are not due to active/recurrent inflammation.
Cross-sectional serum vedolizumab (VDZ) levels (SVL) have been associated with disease activity in Crohn’s disease (CD) or ulcerative colitis (UC) but the role of therapeutic drug monitoring (TDM) early in the course of therapy is unknown. The aim of this study was to assess the association of serum vedolizumab (VDZ) levels (SVL) during induction and remission in CD and UC after 52 weeks (52w) of therapy. We also sought to assess predictive variables associated with SVL through the first 22w of therapy. Prospective cohort study including patients with active UC and CD starting standard therapy with VDZ. Predictive variables included demographics, pre-infusion SVL measured using a validated drug-tolerant assay at weeks 2, 6, 14 and 22 (Anser® VDZ), C-reactive protein (CRP), albumin level, feacal calprotectin (FC), Harvey–Bradshaw index (HBI) in CD and Mayo Clinical Score (MCS) in UC, Simple endoscopic score-CD (SES-CD) in CD and Mayo endoscopic score (MES) in UC. Primary outcome was deep remission at 52W, defined as HBI<5 (in CD)/MCS<3 (in UC), and SES-CD≤2 (in CD) or MES≤1 (in UC). Secondary outcome was discontinuation of VDZ due to non-response. Of the 53 patients in the study population, 28 (53%) had UC. Twenty-one (40%) achieved deep remission by week 52. These patients had higher SVL at weeks 2, 6, 14 and 22 of therapy vs. those that did not, but only the differences at Weeks 2 and 6 achieved statistical significance (Figure 1). Differences in Vedolizumab Levels at Several Time-points Between those that did and did not achieve remission by week 52 of therapy (*) Statistically significant. Nineteen (36%) patients discontinued VDZ due to non-response. Differences between those that were and were not in deep remission at week 52 are shown in Table 1. Differences between patients that did and did not achieve remission at week 52 (*) Statistically significant. Differences between patients that did and did not achieve remission at week 52 (*) Statistically significant. Patients that started VDZ on combination therapy with an immunomodulator did not have significantly higher SVL at any time-point when compared with those who did not (p > 0.05 for all). There was a positive, significant correlation between baseline albumin levels and SVL at week 6 (rho: 0.4, p = 0.003) and positive but not significant correlation and SVL at week 2 (rho: 0.2, p = 0.09). Furthermore, there was a significant negative correlation between baseline FC and SVL at week 2 (rho: −0.5, p < 0.001) and week 6 (rho: −0.33, p = 0.03). Vedolizumab levels at induction are associated with achievement of remission at 52w of therapy. While interventional studies are needed, the use of early TDM in patients on VDZ may improve outcomes.
Autoimmune gastrointestinal dysmotility (AGID) is a rare form of limited autoimmune dysautonomia caused by autoantibodies against the enteric nervous system. Our patient was a 53-year-old man with 1 year of bloating, intolerance of oral intake, and recurrent ileus. Esophageal manometry showed aperistalsis and hypotensive lower sphincter, consistent with scleroderma esophagus. However, because the patient had no other sequelae of this disease, AGID was considered. Serologic evaluation revealed ganglionic acetylcholine receptor autoantibodies. Treatment with pyridostigmine led to resolution of symptoms. Early recognition of AGID should be considered when manometry shows scleroderma esophagus in patients without other evidence of systemic sclerosis.
INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17–0.64], P < 0.001 and odds ratio per μg/mL: 1.11 [95% confidence interval: 1.05–1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.
