scholarly journals Anti-TNF-α Therapy Suppresses Proinflammatory Activities of Mucosal Neutrophils in Inflammatory Bowel Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Cui Zhang ◽  
Weigang Shu ◽  
Guangxi Zhou ◽  
Jian Lin ◽  
Feifei Chu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Critical Role ◽  
Mucosal Healing ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Inflammatory Bowel

Neutrophils have been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and anti-TNF-α mAb (i.e., infliximab) therapy is demonstrated to be effective in the induction of clinical remission and mucosal healing in these patients. However, how anti-TNF-α mAb regulates the functions of neutrophils is still unknown. Herein, we found that anti-TNF-α therapy significantly downregulated infiltration of neutrophils in inflamed mucosa of IBD patients. Importantly, anti-TNF-α mAb could inhibit neutrophils to produce proinflammatory mediators, such as ROS, calprotectin, IL-8, IL-6, and TNF-α. These data indicate that TNF-α plays a critical role in the induction of mucosal inflammatory response, and that blockade of TNF-α modulates intestinal homeostasis through balancing immune responses of neutrophils.

scholarly journals P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S355-S355
Author(s):  
M I Calvo Moya ◽  
I Omella Usieto ◽  
M I Vera Mendoza ◽  
V Matallana Royo ◽  
I Gonzalez Partida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Mucosal Healing ◽  
Surveillance Colonoscopy ◽  
Previously Treated ◽  
Inflammatory Bowel

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was defined by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was defined by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

scholarly journals Relationship between Serum Adalimumab Levels and Clinical Outcome in the Treatment of Inflammatory Bowel Disease

2019 ◽  
Vol 37 (6) ◽  
pp. 444-450 ◽  
Author(s):  
Joaquín Hinojosa ◽  
Fernando Muñoz ◽  
Gregorio Juan Martínez-Romero
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Outcome ◽  
Maintenance Therapy ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Meta Analysis ◽  
Serum Levels ◽  
Mucosal Healing ◽  
Endoscopic Remission ◽  
Inflammatory Bowel

Background: Adalimumab (ADA) is an anti-tumor necrosis factor agent that has been shown to be effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. The relationship between the ADA trough levels and clinical efficacy has been demonstrated, but there is variability in the definition of the most suitable range for its clinical applicability. Summary: A review of published studies during the last 5 years on ADA serum levels and its relationship with the clinical outcome was performed. The studies selected included 7 observational studies, a systematic review, a meta-analysis and a post hoc analysis of a clinical trial. The reported ADA levels that discriminate patients in clinical remission from those with active disease range from 4.5 to 8 µg/mL. This therapeutic range varies when considering endoscopic remission (7.5 to >13.9 µg/mL). Although the sample of patients with ulcerative colitis is small, a tendency to reach higher levels of ADA is observed in both clinical and endoscopic remission. Key Messages: The optimal therapeutic cut-off point of serum ADA levels ranges from 4.5–5 to 12 µg/mL, where ADA levels are associated with an adequate clinical monitoring of the disease during maintenance therapy. These ranges vary according to the target, suggesting levels of 4.8 µg/mL as the cut-off for clinical remission and levels ≥7.5 µg/mL for mucosal healing/endoscopic response. Controlled prospective studies are required to determine the optimal therapeutic interval of ADA serum levels both as induction and as maintenance therapy.

scholarly journals THE SAFETY, TOLERABILITY, AND EFFECTIVENESS OF BIOLOGICS/SMALL MOLECULE THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND CIRRHOSIS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S45-S46
Author(s):  
Muyi Li ◽  
Sameer Khan ◽  
Deborah Proctor ◽  
Jill Gaidos ◽  
Badr Al-Bawardy
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Small Molecules ◽  
Small Molecule ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Infusion Reaction ◽  
Mucosal Healing ◽  
Biologic Agents ◽  
Inflammatory Bowel

Abstract Introduction Biologic agents and small molecules have been shown to be effective and relatively safe in the treatment of inflammatory bowel disease (IBD). However, data is lacking regarding the use of these agents in patients with IBD and concomitant cirrhosis. The aim of this study is to examine the safety, tolerability and effectiveness of biologics and small molecules in patients with IBD and concomitant cirrhosis. Methods This is a retrospective study of adult patients diagnosed with both IBD and cirrhosis (by liver biopsy or Fibroscan) treated with biologic agents or small molecule agents between 2012 and 2020 within the Yale-New Haven Hospital system. We included patients on tofacitinib or any of the following biologic agents: infliximab, adalimumab, certolizumab pegol, golimumab, vedolizumab, ustekinumab. Primary outcomes were rates of adverse events (infection, infusion reaction, IBD-related hospitalization) and mortality. Secondary outcomes were clinical remission (defined by the physician global assessment) and mucosal healing (Mayo endoscopic score of 0 or 1 for ulcerative colitis (UC) and absence of erosion/ulcerations in Crohn’s disease (CD)). Results A total of 18 patients (72% CD, 28% UC) with median age of 50 (26–73) years were included (Table 1). Decompensated cirrhosis was present in 33.3% of the population prior to initiation of biologic/small molecule therapy. The most common etiology of cirrhosis was primary sclerosing cholangitis at 38.9%. IBD therapy included: infliximab/adalimumab (44.5%), vedolizumab (27.7%), and ustekinumab (22.2%) and tofacitinib (5.6%). A total of 4 patients (22.2%) were on concomitant corticosteroid therapy and 3 on combination therapy with thiopurines (Table 2). Adverse events occurred in 27.7% (n=5; 1 infusion reaction and 4 infections). The 4 patients with infections included: 2 on infliximab/adalimumab, 1 on ustekinumab, 1 on vedolizumab. Two of these patients were on concomitant thiopurines and 1 on corticosteroid. Biologic therapy was stopped in 3 patients, 2 for non-response and 1 for an infusion reaction. Mortality rate was 11% and all were liver-related. Clinical remission was achieved in 66.7% and mucosal healing was noted in 72.7% (8/11). Conclusions In this cohort of patients with IBD and cirrhosis, biologic/small molecule therapies were effective for IBD. Approximately a quarter of patients experienced adverse events that were mainly due to infections. Larger studies are needed to elucidate the relative safety of different biologic agents and small molecules in IBD patients with cirrhosis.

scholarly journals Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort

2019 ◽  
Vol 13 (9) ◽  
pp. 1111-1120 ◽  
Author(s):  
N Plevris ◽  
C S Chuah ◽  
R M Allen ◽  
I D Arnott ◽  
P N Brennan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Inflammatory Bowel

Abstract Background & Aims Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn’s disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. Methods This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn’s disease with objective evidence of active inflammation at baseline (Harvey–Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan–Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. Results Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn’s disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26–52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn’s disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. Conclusions Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn’s disease.

scholarly journals P139 CORRELATION OF CLINICAL REMISSION WITH MUCOSAL HEALING IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

2018 ◽  
Vol 24 (suppl_1) ◽  
pp. S50-S50
Author(s):  
Denise Young ◽  
Megha Mehta ◽  
Nori Minich ◽  
Judy Splawski ◽  
Thomas J Sferra ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel

Vedolizumab Drug Level Correlation With Clinical Remission, Biomarker Normalization, and Mucosal Healing in Inflammatory Bowel Disease

2018 ◽  
Vol 25 (3) ◽  
pp. 580-586 ◽  
Author(s):  
Badr Al-Bawardy ◽  
Guilherme Piovezani Ramos ◽  
Maria Alice V Willrich ◽  
Sarah M Jenkins ◽  
Sang Hyoung Park ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Drug Level ◽  
Mucosal Healing ◽  
Inflammatory Bowel

scholarly journals Efficacy and Safety of Vedolizumab for Pediatrics With Inflammatory Bowel Disease: a Systematic Review

2021 ◽  
Author(s):  
Shengbo Fang ◽  
Yanqing Song ◽  
Chunyan Zhang ◽  
Libo Wang
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Children And Adolescents ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Efficacy And Safety ◽  
Remission Rates ◽  
Inflammatory Bowel ◽  
Quality Evidence

Abstract Background: Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD). Methods: PubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to November 21 2020. Results: 7 studies, comprising 238 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (19/67) at 14 weeks, 32% (17/53) at 22 weeks, and 25% (1/4) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 52% (32/61) at 14 weeks, 53% (24/45) at 22 weeks, and 60% (6/10) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events.Conclusions: According to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks. Long-term benefit profile data and high quality evidence are still needed.

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