Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases.

BACKGROUND: Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn's disease (CD) are emerging. OBJECTIVE: To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. METHODS: A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. RESULTS: The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non-structuring, non-penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. CONCLUSION: Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.

Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study.

OBJECTIVE: To investigate duration of remission, including risk factors for relapse and response to retreatment with infliximab (IFX), in patients with Crohn's disease (CD) and ulcerative colitis (UC) who had discontinued IFX while in clinical remission. METHODS: Observational, single-center, retrospective study of all patients with a primary response to IFX who discontinued IFX therapy while in steroid-free remission. Relapse was defined as reintroduction of treatment with a biologic, systemic steroid or surgery. RESULTS: Of 219, 53 (24%) CD patients, and 28 of 97 (30%) UC patients discontinued IFX while in clinical steroid-free remission. The proportion of patients in remission declined steadily with 61% of CD patients, and 75% of UC patients being in remission after 1 year. Half the patients maintained remission after median 2 years (680 days (412-948)) and 3.5 years (1334 days (995-1673)), respectively; p = 0.057. Twelve percent with CD and 40% with UC were in remission at the end of follow-up after 10 and 4.5 years, respectively. Longer disease duration was associated with relapse in univariate analysis in CD, OR 1.1 (1.0-1.1), p = 0.022. Of 25, 24 CD patients (96%), and 5 of 7 UC patients (71%) experienced complete clinical remission when retreated with IFX after relapse. CONCLUSION: While the short-term prognosis seems favorable, the majority of patients who discontinue IFX while in remission relapse over time. The response to retreatment with IFX at relapse seems favorable in this subpopulation.

Outcomes and Long-Term Effects of COVID-19 in Patients with Inflammatory Bowel Diseases - A Danish Prospective Population-Based Cohort Study with Individual-Level Data.

BACKGROUND AND AIMS: The health consequences of coronavirus disease 2019 [COVID-19] among patients with ulcerative colitis [UC] and Crohn's disease [CD] remain largely unknown. We aimed to investigate the outcomes and long-term effects of COVID-19 in patients with UC or CD. METHODS: We conducted a prospective, population-based study covering all Danish patients with CD or UC and confirmed COVID-19 between January 28, 2020 and April 1, 2021, through medical records and questionnaires. RESULTS: All 319 patients with UC and 197 patients with CD who developed COVID-19 in Denmark were included in this study and compared with the Danish background population with COVID-19 [N = 230 087]. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N = 46 [14.4%], relative risk [RR] = 2.49 [95% confidence interval, CI, 1.91-3.26]) and CD (N = 24 [12.2%], RR = 2.11 [95% CI 1.45-3.07]) as compared with the background population (N = 13 306 [5.8%]). A similar pattern was observed for admission to intensive care (UC: N = 8 [2.51%], RR = 27.88 [95% CI 13.88-56.00]; CD: N = 3 [1.52%], RR = 16.92 [95% CI 5.46-52.46]). After a median of 5.1 months (interquartile range [IQR] 4.5-7.9), 58 [42.3%] and 39 [45.9%] patients with UC and CD, respectively, reported persisting symptoms which were independently associated with discontinuation of immunosuppressive therapies during COVID-19 (odds ratio [OR] = 1.50 [95% CI 1.07-10.22], p = 0.01) and severe COVID-19 (OR = 2.76 [95% CI 1.05-3.90], p = 0.04), but not with age or presence of comorbidities. CONCLUSION: In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent, affecting 43.7% of COVID-19-infected patients. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era.

Discontinuation of Infliximab Therapy in Patients with Crohn's Disease.

BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn's disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn's disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse. RESULTS: This study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported. CONCLUSIONS: Discontinuation of infliximab for patients with Crohn's disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)

Prevalence and Outcomes of COVID-19 Among Patients With Inflammatory Bowel Disease-A Danish Prospective Population-based Cohort Study.

BACKGROUND AND AIMS: As no population-based study has investigated the susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases [IBD], we aimed to investigate this topic in a population-based setting. METHODS: Two cohorts were investigated. First, a nationwide cohort of all IBD patients diagnosed with COVID-19 was prospectively followed to investigate the disease courses of both diseases. Second, within a population-based cohort of 2.6 million Danish citizens, we identified all individuals tested for SARS-CoV-2 to determine the occurrence of COVID-19 among patients with and without IBD and other immune-mediated inflammatory diseases [IMIDs]. RESULTS: Between January 28, 2020 and June 2, 2020, a total of 76 IBD patients with COVID-19 were identified in the national cohort and prospectively followed for 35 days (interquartile range [IQR]: 25-51). A large proportion [n = 19: 25%] required a COVID-19-related hospitalisation for 7 days [IQR: 2-8.5] which was associated with being 65 years or older (odds ratio [OR] = 23].80, 95% confidence interval [CI] 6.32-89.63, p <0.01) and presence of any non-IMID comorbidity [OR = 8.12, 95% CI 2.55-25.87, p <0.01], but not use of immunomodulators [p = 0.52] or biologic therapies [p = 0.14]. In the population-based study, 8476 of 231 601 [3.7%] residents tested positive for SARS-CoV-2; however, the occurrence was significantly lower among patients with IBD [62 of the 2486 patients = 2.5%, p <0.01] and other IMIDs [531 of 16 492 patients = 3.2%, p <0.01] as compared with patients without IMIDs. CONCLUSIONS: Patients with IMIDs, including IBD, had a significantly lower susceptibility to COVID-19 than patients without IMIDs, and neither immunosuppressive therapies nor IBD activity were associated with the disease course of COVID-19.

Association Between the Clinical, Biochemical, and Endoscopic Activity of Inflammatory Bowel Diseases and Severity and Long-term Outcomes of Coronavirus Disease 2019-A Population-based Study.

This brief report investigated the impact of clinical, biochemical, and endoscopic activity of IBD on the severity and long-term outcomes of COVID-19 in a prospective population-based cohort. The study did not identify any association between IBD activity and COVID-19 outcomes.