Biological Therapy In Crohn's Disease Research Articles

Real-World Effectiveness of Vedolizumab vs Anti-TNF in Biologic-naïve Crohn's Disease Patients: A 2-year Propensity-score-adjusted Analysis from the VEDOIBD-Study.

The aim of this observational, real-world evidence, modified intention-to-treat (mITT) study based on prospectively collected data from the VEDOIBD registry was to compare the effectiveness of vedolizumab (VEDO) vs antitumor necrosis factor (anti-TNF) in biologic-naïve Crohn's disease (CD) patients. Between 2017 and 2020, 557 CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany. Per study protocol, the analysis excluded biologic-experienced patients and those with a missing Harvey-Bradshaw Index score, resulting in a final sample of 327 biologic-naïve CD patients. Clinical remission was measured using the Harvey-Bradshaw Index at the end of induction therapy and after 1 and 2 years. Switching to a different therapy was considered an outcome failure. Propensity score adjustment with inverse probability of treatment weighting was used to correct for confounding. The effectiveness of both VEDO (n = 86) and anti-TNF (n = 241) was remarkably high for induction treatment, but VEDO performed significantly less well than anti-TNF (clinical remission: 56.3% vs 73.9%, P < .05). In contrast, clinical remission after 2 years was significantly better for VEDO compared with anti-TNF (74.2% vs 44.7%; P < .05; odds ratio, 0.45; 95% CI, 0.22-0.94). Remarkably, only 17% of patients switched from VEDO to another biologic vs 44% who received anti-TNF. The results of this prospective, 2-year, real-world evidence study suggest that the choice of VEDO led to higher remission rates after 2 years compared with anti-TNF. This could support the role of VEDO as a first-line biologic therapy in CD.

The effectiveness of ustekinumab and vedolizumab as third-line biologic therapy in patients with Crohn's disease.

The effectiveness of Ustekinumab (UST) and Vedolizumab (VDZ) in patients with Crohn's disease (CD) as third-line biologic therapies is unclear. We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ among highly-refractory patients with CD. Data of consecutive patients with CD treated with UST and VDZ as third-line biologic therapy until December 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). 143 patients (UST: n=113; VDZ: n=30) were included. At the end of induction, the rates of clinical response (CR) were 61.9% for UST and 60.0% for VDZ (p=1.00), with steroid-free clinical remission (SFCR) achieved in 38.1% of patients in the UST group and 43.3% of patients in the VDZ group (p=0.75). After 52 weeks of observation, the rates of CR were 65.9% for UST and 71.4% for VDZ (p=0.77), while the rates of SFCR were 51.8% for UST and 57.1% for VDZ (p=0.78). At multiple Cox proportional hazard regression model, age (HR 0.98; p=0.04) and need for systemic steroids at baseline (HR 3.29; p=0.003) were found to be independent predictors of treatment discontinuation. Both VDZ and UST showed high effectiveness as third-line biologic therapy in CD, without significant differences between them.

Biological therapy prior to repeat ileocolic resection in Crohn's disease can reduce the postoperative complication rate.

The aim of this study was to assess the effect of preoperative biologic therapy on the surgical outcome of Crohn's disease (CD) patients undergoing repeat ileocolic resection. This was a retrospective analysis of all CD patients who underwent repeat ileocolic resection at Cleveland Clinic Florida between January 2011 and April 2021. Patients were divided into two groups: treatment biologic therapy prior to surgery and controls. Sixty-five patients (31males, median age 54 [range 23-82] years) were included in the study. Twenty nine (44.6%) were treated with biologic therapy prior to repeat ileocolic resection. No demographic differences were found between the biologic therapy and control groups. In addition, no differences were found in mean time from index ileocolic resection (p = 0.9), indication for surgery (p = 0.11), and preoperative albumin (p = 0.69). The majority of patients (57; 87.7%) were operated on laparoscopically, and mean overall operation time was 225 (SD 49.27) min. Overall, the postoperative complication rate was 43.1% (28 patients) and median length of stay was 5 (range 2-21) days. Postoperative complications were more common in the control group, compared to the biologic therapy group (55.6 vs 27.5%; p = 0.04). Conversion rate (35.7 vs 20.7%; p = 0.24), operation time (223 vs 219min; p = 0.75), length of stay (5.2 vs 5.9days; p = 0.4), and readmission (16.6 vs 11.1%; p = 0.72) were similar between the two groups. Multivariate analysis of risk factors for postoperative complications showed that biologic treatment was correlated with a lower risk (HR -0.28, CI 95% -0.5596 to -0.01898, p = 0.03). Patients treated with biologic therapy for CD who underwent repeat ileocolic resection had fewer postoperative complications.

Trends in Corticosteroid Use During the Era of Biologic Therapy: A Population-Based Analysis.

Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear. We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time. The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1-4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1-2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC. Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.

80 Hospitalization and Surgery Risk in Crohn's Disease in the Biological Era - Results From the Dutch Population-Based IBD-SL Cohort

Background Many patients with Crohn's disease (CD) require hospital admission or surgery for CD-related complications or refractory inflammatory disease. As from biological availability, more aggressive treatment strategies (e.g. early use of immunomodulators and biologicals, and combination therapy) are advised for patients with expected poor prognosis to improve long-term outcome. Its effect on disease outcome is yet unknown, mostly due to lack of data before and after biological availability from the same source population. Therefore, we aimed to compare disease outcome of CD patients diagnosed in the prebiological era to CD patients diagnosed in the biological era in a population-based cohort. MethodsSince 1991, incident IBD cases in the South-Limburg (SL) area are included in our populationbased IBD-SL cohort, with over 93% completeness. All CD patients were divided in two time cohorts. The pre-biological cohort comprised patients diagnosed between 1991 and 1998, followed until 1999 (registration of biological therapy for CD). The biological cohort comprised patients diagnosed between 1999 and July 2011, followed until 2014. Disease outcome, in terms of hospitalization and surgery risk, was analyzed with a Kaplan-Meier survival curve, and hazard ratios (HR) were calculated using a Cox regression model. Results In total, 342 patients in the pre-biological and 820 patients in the biological era were included, with a mean follow-up of 4.0 (SD 2.5) and 6.4 (SD 3.6) years, respectively. At diagnosis, patients in the biological era were less often hospitalized (21.1% vs. 36.8%, HR

The influence of anti-TNF therapy on CD31 and VEGF expression in colonic mucosa of Crohn's disease patients in relation to mucosal healing.

Immune-mediated angiogenesis may play an important role in the pathogenesis of inflammatory lesions in Crohn's disease (CD). The study aimed to assess the influence of anti-tumour necrosis factor (anti-TNF) therapy on the angiogenesis in relation to microscopic and endoscopic healing in CD patients. Colonic tissue samples from 17 CD patients were taken during colonoscopy before and after anti-TNF therapy. Endoscopic and microscopic severities were estimated using validated scores. Immunohistochemical expression of CD31 and vascular endothelial growth factor (VEGF) were assessed in parallel. The expression of CD31 and VEGF decreased significantly after the anti-TNF therapy in parallel to endoscopic improvement; however, the microscopic activity did not change significantly. There was a correlation between the change in CD31 and VEGF expression (p = 0.01; r = 0.6), as well as endoscopic healing (p = 0.04; r = 0.4). CD31 immunoexpression correlated with the number of poly- and mononuclear cells in the infiltrates in the mucosal lamina propria before the therapy (p = 0.02; r = 0.5). We suggest that modulation of vascular proliferation can be a novel option to increase the efficacy of biological therapy in CD.

Modificação do tratamento com infliximab na doença de Crohn: experiência de um centro

IntroductionTreatment of Crohn disease in pediatric patients must ensure not only symptom control but also remission, allowing normal growth and development. Infliximab has been shown to be effective in controlling disease in children and adolescents unresponsive to first-line treatment, although 30 to 55% of failure occurs, requiring therapeutic adjustments. Recent pediatric studies have shown that the efficacy of reducing the range from 8 to 6/7 weeks, increasing the dose to 10mg/kg dose or shortening the interval up to 4 weeks is similar. Objective and methodsRetrospective descriptive study of pediatric patients who were diagnosed with Crohn Disease and had infliximab treatment in last five years, with evaluation of treatment failure situations. ResultsWe included 16 patients (10 males, 6 females) treated with infliximab induction regimen, followed by 5mg/kg every 8 weeks. In most patients, treatment was initiated 10 months after diagnosis. In 50% there was clinical and/or analytical relapse, on average after 10 cycles of treatment (median 6.5), leading to an adjustment of the therapeutic regimen: 6 shortened the interval to 6/7 weeks, 1 shortened the interval to 4 weeks and 1 increased the dose to 10mg/kg. Of the 6 patients with 5mg/kg dose and interval of 6/7 weeks, all had initial favorable response but 4 required an increase of the dose to 10mg/kg, 2 of them are in remission. The disease remission with infliximab was 81.2%. DiscussionTreatment with infliximab was effective in controlling Crohn disease and in reducing the need of steroids, but dose adjustments were necessary, often occurring in the first year of treatment. Clinical changes determined the need of dose or interval increases or reductions. The predictable need to adjust treatment after a few months of treatment justifies that the choice of biologic therapy in Crohn disease has to be carefully considered after failure of other options.

Anti-Adhesion Molecule Strategies for Crohn Disease

The last few years have been highlighted by further knowledge and optimism regarding the use of biologic therapy in Crohn disease. The introduction of anti-tumor necrosis factor (TNF) therapy into clinical practice in the form of the murine chimeric monoclonal antibody infliximab, and more recently the fully human monoclonal antibody adalimumab, has significantly advanced treatment for Crohn disease. Despite the introduction of the anti-TNF agents, 20-40% of patients will fail to respond to initial induction therapy, and of the initial responders only 60-70% will have a sustained response at 1 year. Therefore, there remains a significant unmet need in the treatment of patients with Crohn disease. A novel approach in suppressing inflammation is to intervene in the mechanisms responsible for the migration of leukocytes into inflamed tissue. One such method is by selective adhesion molecule inhibition. Several agents based on this strategy have been evaluated in the treatment of inflammatory bowel disease. It is expected that these agents will offer an alternative to the anti-TNF agent class in patients with moderate to severe Crohn disease.

Medical therapy of Crohn disease

This review will outline the current management of Crohn disease and highlight the knowledge gained from published studies and abstracts in the year 2003. The year 2003 was highlighted by further knowledge on the use of biologic therapy in Crohn disease. Important lessons were learned from the expanding clinical experience with infliximab. Several other studies of agents targeting tumor necrosis factor-alpha revealed mixed and sometimes disappointing results. However, this was balanced by encouraging results of several studies of biologic agents that inhibit lymphocyte trafficking. Other studies evaluated a variety of small molecules, including tacrolimus, leflutamide, and mycophenolate. Finally, controversy was raised with published studies looking at the efficacy and safety of 6-thiogunaine. There appears to be an expanding array of treatment options that will become available to clinicians for the treatment of Crohn disease. New treatment paradigms have emerged for managing mild to moderate disease. Small molecules may provide alternatives for immunomodulation other than the purine antimetabolites and methotrexate. Increased understanding of the pathophysiologic mechanisms of Crohn disease has allowed the development of novel therapeutics directed at specific molecular targets. However, as the treatment options expand, questions regarding optimal combination treatment strategies will need to be answered.

Therapy of ulcerative colitis

The past year has brought forth several controversies regarding the treatment of ulcerative colitis along with several potentially important clinical advances. The aim of this review is to provide the practicing gastroenterologist with a summation of these recent developments, with particular emphasis on advances that have already moved toward acceptance into clinical practice. Controversies remain regarding the optimal formulations and doses of aminosalicylates. At the same time, the potential for chemoprotective effects in patients using maintenance therapy with mesalamine derivatives has been expanded. In addition, advances in biologic therapy for Crohn disease are beginning to be formally evaluated in ulcerative colitis, although the benefits of anti-tumor necrosis factor therapy in this condition remain to be established. Biologic therapies are beginning to be explored as adjunctive therapy for steroid-refractory ulcerative colitis, where trials of calcineurin inhibitors are also advancing clinical practice for this poor prognostic subgroup of patients. Finally, after surgery for ulcerative colitis, the treatment and prevention of pouchitis has become the one established indication for probiotic therapy. Despite some inroads into the medical therapy of ulcerative colitis, controversies remain regarding the optimal dosing and delivery systems of the most fundamental therapies, and how to optimize therapy for severe ulcerative colitis. Clinical research will continue to investigate new biologic agents that inhibit tumor necrosis factor and other pro-inflammatory cytokines, and ongoing trials with leukocyte apheresis are currently under way.