Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

Significant Differences in IBD Care and Education across Europe: Results of the Pan-European VIPER Survey.

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study.

BACKGROUND: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. METHODS: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. RESULTS: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively. CONCLUSION: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

P004 Steroid-Free Remission in Patients With Ulcerative Colitis Receiving Tofacitinib in Real Clinical Practice.

BACKGROUND: Tofacitinib is a selective immunosuppressant, the first representative of the inhibitors of the janus kinase family, which has high selectivity against other kinases of the human genome. According to the results of the study, tofacitinib inhibits JAK-1, JAK-2, and in high concentrations - JAK-3 and tyrosine kinase-2. The drug is registered in Russia for the treatment of patients with ulcerative colitis. According to the OCTAVE Sustain study, steroid-free remission in patients with ulcerative colitis receiving tofacitinib at a dose of 10 and 20 mg per day is 27.7% and 27.6%, respectively. OBJECTIVE: To identify the frequency of steroid-free remission in patients with ulcerative colitis receiving tofacitinib in real clinical practice. METHODS: In the Department of Inflammatory Bowel Diseases of the Moscow Clinical Scientific and Practical Center named after A. S. Loginov, 58 patients with ulcerative colitis (UC) who received tofacitinib were observed. The effectiveness of therapy was evaluated (the value of the Mayo index less than 2, ESR, CRP, hemoglobin, fecal calprotectin (FCP) and the need for the appointment of glucocorticosteroids (GCS). The follow-up period was 12 months from the start of tofacitinib therapy. RESULTS: During the follow-up period, out of 58 (100%) UC patients treated with tofacitinib, 9 (15.5%) patients did not respond to therapy. A prolonged induction course at a dose of 20 mg of tofacitinib was required in 14 (24.1%) patients who had previously received anti-TNF-α drugs. All patients at the time of initiation received GCS at an average therapeutic dose of 40 mg. After the induction course, corticosteroids were discontinued in 49 (100%) patients who responded to treatment. All patients achieved remission within 12 months of therapy (Meyo < 2). Repeated administration of corticosteroids for exacerbation or "eluding" of the response to tofacitinib was required in 11 of 49 (22.4%) patients. CONCLUSION: Steroid-free remission in patients with ulcerative colitis, receiving tofacitinib for 12 months, in real clinical practice is 77.6%.

P006 The Relationship of Histological Remission With the Duration of the Anamnesis Ulcerative Colitis.

BACKGROUND: The objectives of the treatment of patients with ulcerative colitis (UC) in accordance with the STRIDE-I provision, involves endoscopic healing of the colon mucosa. Histological remission is associated with endoscopic healing, which can be a predictor of long-term results. Biological and cellular therapy is most effective in the early stages of the disease. OBJECTIVE: To assess the depth of histological remission with the duration of UC. METHODS: The biopsy material of 75 patients with total or left-sided UC of moderate severity and severe severity aged from 22 to 56 years (average age 31 ± 2.5 years), who were divided into groups depending on the therapy, was studied. The first group of patients with UC aged 22 to 51 years (Me-32) (n = 29) received anti-inflammatory therapy using mesenchymal stromal cell culture (MSCs) 2 million/kg; the second group of patients with UC (n = 27) aged 24 to 56 years (Me-38) received vedolizumab (VDB) according to the recommended scheme, the third group of patients with UC (n = 19) aged 27 to 52 years (Me-31) received MSCs+VDB. The achievement of histological remission was assessed by the score of Geboes (SG). RESULTS: In 1st group, patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 14 (48.3%) patients, less than 5 years - 5 (17.2%) (95% CI 1.256 - 19.293; x2-7.635; p = 0.006). In the 2nd group of patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 15 (55.5%) patients, less than 5 years - 4 (14.9%) (95% CI 1.262 - 20.615; x2-7.026; p = 0.009). In the 3rd group of patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 4 (21.1%) patients, less than 5 years - 7 (36.8%) (95% CI 1.080 - 138.995; x2-4.968; p = 0.026). CONCLUSION: A statistically significant majority of patients who achieved histological remission, regardless of the therapy, had a disease duration of less than 5 years.

P007 The Frequency of Anxiety and Depression in Patients With Inflammatory Bowel Diseases in the Moscow Clinical Scientific Center.

BACKGROUND: Anxiety and depression occur in a significant number of patients with inflammatory bowel diseases (IBD). The prevalence of anxiety and / or depression is 13-44.4% in patients with IBD compared to 4.4% among the world population. OBJECTIVE: To identify the frequency of anxiety and depression in patients with inflammatory bowel diseases in the Moscow Clinical Scientific Center named after A. S. Loginov. METHODS: A questionnaire was conducted on the Hospital Anxiety and Depression Scale (HADS) questionnaire for 370 patients with moderate to severe UC during the period of exacerbation of the disease. RESULTS: Of the 370 patients with UC, 283 (76.48%) had clinical and subclinical signs of anxiety and depression. Subclinical depression was noted in 76 (26.8%), clinically pronounced depression - 11 (3.4%), signs of anxiety had higher indicators-subclinical anxiety was found in 172 (60.8%) of the surveyed patients, pronounced clinical anxiety - in 24 (8.4%) patients with UC. Statistically significant correlations of average strength between the indicators of adherence according to the Morisky - Green questionnaire with scores on the HADS scale, both for anxiety and depression (p < 0.001, r - 0.6299) were revealed Among patients with anxiety and depression, the ratio of patients with high adherence to therapy (HAT) and low adherence to therapy (LAT) was 204 (55,1%) 79 (21,4%), accordingly. When comparing the degree of adherence depending on the presence of anxiety and depression, we found that HAT was associated with anxiety and depression in patients with UC (OR = 0.024; 95% CI 0.003-0.186; p < 0.001). CONCLUSION: The prevalence of anxiety and/or depression is 77% in patients with IBD during an exacerbation in the Moscow Clinical Scientific Center named after A. S. Loginov.