Locking the Door to Leukocytes: Use of Integrin Inhibitors for the Treatment of Crohn's Disease

2010 ◽  
Vol 2 ◽  
pp. CMT.S4013
Author(s):  
Gerald W. Dryden
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Current Knowledge ◽  
Daily Basis ◽  
Biologic Therapies ◽  
Tnf Α ◽  
Treatment Paradigm ◽  
Inflammatory Bowel ◽  
Clinical Advances ◽  
Necrosis Factor

Inflammatory Bowel Disease (IBD) treatments are rapidly evolving. Current knowledge of the immunopathology responsible for IBD grows on a daily basis. These scientific discoveries are quickly being translated into clinical advances for improved treatment of IBD patients. The breakthrough in biologic therapy occurred with the introduction of infliximab for the treatment of Crohn's disease. Since then, research applying biologic therapies for IBD has expanded dramatically. Even though significant therapeutic gains have occurred with the expanded use of biologic therapies directed against tumor necrosis factor (TNF)-α, some patients still remain underserved by this type of treatment. Clinicians need to be familiar with alternative biological therapeutics to so that patients will have an opportunity to benefit from this effective class of medications. This review will highlight the advances made in integrin inhibitor therapy, and discuss the application of this therapy to an IBD treatment paradigm.

scholarly journals Fulminant Herpes Simplex Hepatitis Secondary to Adalimumab in Crohn’s Disease: A Case Report

2019 ◽  
Vol 12 ◽  
pp. 117954761985897 ◽  
Author(s):  
Kanika Goel ◽  
Mark Bunker ◽  
Anna Balog ◽  
Jan F Silverman
Keyword(s):  
Crohn’S Disease ◽  
Case Report ◽  
Herpes Simplex ◽  
Crohn's Disease ◽  
Rare Case ◽  
Treatment Modalities ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Simplex Virus ◽  
Necrosis Factor

Herpes simplex virus (HSV) hepatitis is an uncommon cause of fulminant hepatic failure, seen mostly in immunocompromised patients. Conventional treatment modalities for inflammatory bowel disease (IBD), such as steroids and azathioprine, have been known to cause HSV hepatitis. However, the reported incidence of HSV hepatitis in IBD patients undergoing tumor necrosis factor (TNF)-α inhibitor therapy is very rare. In this case report, we describe a rare case of fulminant HSV hepatitis that developed in a patient with Crohn’s disease after treatment with the TNF-α inhibitor, adalimumab.

Pathogenic aspects and therapeutic avenues of intestinal fibrosis in Crohn's disease

2015 ◽  
Vol 129 (12) ◽  
pp. 1107-1113 ◽  
Author(s):  
Francesca Zorzi ◽  
Emma Calabrese ◽  
Giovanni Monteleone
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Current Knowledge ◽  
Experimental Models ◽  
Human Beings ◽  
Intestinal Fibrosis ◽  
Bowel Diseases ◽  
Ecm Extracellular Matrix ◽  
Inflammatory Bowel ◽  
Related Proteins

In Crohn's disease, one of the two major forms of inflammatory bowel diseases in human beings, persistent and chronic inflammation promotes fibrotic processes thereby facilitating formation of strictures, the most common indication for surgical intervention in this disorder. The pathogenesis of Crohn's disease-associated fibrosis is not fully understood, but variants of genes involved in the recognition of microbial components/products [e.g. CARD15 (caspase-activating recruitment domain 15) and ATG16L1 (autophagy-related 16-like 1)] are associated with this phenotype, and experimental evidence suggests that intestinal fibrosis results from an altered balance between deposition of ECM (extracellular matrix) and degradation of ECM by proteases. Studies have also contributed to identify the main phenotypic and functional alterations of cells involved in the fibrogenic process, as well as molecules that stimulate such cells to produce elevated amounts of collagen and other ECM-related proteins. In the present review, we assess the current knowledge about cellular and molecular mediators of intestinal fibrosis and describe results of recent studies aimed at testing the preventive/therapeutic effect of compounds in experimental models of intestinal fibrosis.

scholarly journals Food and Drug Administration guidances on biosimilars: an update for the gastroenterologist

2018 ◽  
Vol 11 ◽  
pp. 175628481879960 ◽  
Author(s):  
Michael Epstein
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
The United States ◽  
Biologic Therapies ◽  
Tnf Α ◽  
The Us ◽  
Guidance Documents ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

The management of inflammatory bowel disease (IBD), a significant cause of morbidity in the United States (US), has been revolutionized over the last two decades by the introduction of biologic therapies. These include antitumor necrosis factor α (TNF-α) agents. Since 2016, five biosimilar TNF-α inhibitors have been approved by the US Food and Drug Administration (FDA) for use in the treatment of IBD. The FDA has published a series of guidance documents related to the evaluation, licensing, and approval of biosimilars. The aim of this review is to provide an overview of these FDA guidances and the issues associated with biosimilars in the US.

The Impact of Anti-Tumor Necrosis Factor Alpha Therapy on Postoperative Complications in Pediatric Crohn's Disease

2019 ◽  
Vol 30 (01) ◽  
pp. 027-032
Author(s):  
Vojtech Dotlacil ◽  
Jiri Bronsky ◽  
Ondrej Hradsky ◽  
Barbora Frybova ◽  
Stepan Coufal ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Postoperative Complications ◽  
Tumor Necrosis Factor ◽  
Crohn's Disease ◽  
Abdominal Surgery ◽  
Tumor Necrosis ◽  
Tnf Α ◽  
Significant Difference ◽  
The Impact ◽  
Necrosis Factor

Abstract Introduction The incidence of Crohn's disease (CD) within the pediatric population is increasing worldwide. Despite a growing number of these patients receiving anti-tumor necrosis factor α therapy (anti-TNF-α), one-third of them still require surgery. There is limited data as to whether anti-TNF-α influences postoperative complications. We evaluated postoperative complications in patients who were or were not exposed to anti-TNF-α therapy in our institutional cohort. Materials and Methods A retrospective review of CD patients who underwent abdominal surgery between September 2013 and September 2018 was performed. The patients were divided into two groups based on whether they were treated with anti-TNF-α within 90 days before surgery. Thirty-day postoperative complications were assessed using Clavien–Dindo classification (D-C); this examination included surgical site infections (SSIs), stoma complications, intra-abdominal septic complications, non-SSIs, bleeding, ileus, readmission rate, and return to the operating room. Mann–Whitney U-test, Fisher's exact test, and multivariate logistic regression analyses were used for statistical analysis. Results Sixty-five patients (41 males) with a median age of 16 years (range: 7–19) at the time of operation were identified. The most common surgery was ileocecal resection in 49 (75%) patients. Forty-three (66.2%) patients were treated with anti-TNF-α preoperatively. Seven patients (11%) experienced postoperative complications. There was no statistically significant difference in postoperative complication in patients who did or did not receive anti-TNF-α before surgery (D-C minor 2.3% vs. 4.6%, p = 1; D-C major 7% vs. 9.1%, p = 1). Conclusion The use of anti-TNF-α in pediatric CD patients within the 90 days prior to their abdominal surgery was not associated with an increased risk of 30-day postoperative complications.

25 years of anti-TNF treatment for inflammatory bowel disease: lessons from the past and a look to the future

Gut ◽  
2021 ◽  
pp. gutjnl-2019-320022
Author(s):  
Geert R D'Haens ◽  
Sander van Deventer
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Development ◽  
Good Time ◽  
The Past ◽  
Clinical Observations ◽  
Open Questions ◽  
Inflammatory Bowel ◽  
Maintenance Schedules ◽  
Necrosis Factor

Anti-tumour necrosis factor (TNF) antibodies have been widely used for approximately 25 years now. The first clinical observations in patients with refractory Crohn’s disease rapidly responding to infliximab prompted accelerated clinical development and approval for this indication. However, many questions remained unanswered when this treatment came to market related to maintenance schedules, pharmacokinetics, toxicity and positioning. Many of these open questions were addressed by investigators and sponsors during more than two decades of clinical use. The authors were among the first to use infliximab in Crohn’s disease and felt that now is a good time to look back and draw lessons from the remarkable anti-TNF story. Even today, new insights continue to appear. But more importantly, what was learnt in the past 25 years has created a platform for future development of even stronger and safer therapies. We should not forget to learn from the past.

Comparison of Two Different Techniques to Assess Adalimumab Trough Levels in Patients with Crohn’s Disease

2015 ◽  
Vol 24 (4) ◽  
pp. 451-456 ◽  
Author(s):  
Giorgia Bodini ◽  
Vincenzo Savarino ◽  
Edoardo G. Giannini ◽  
Manuele Furnari ◽  
Elisa Marabotto ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Tumor Necrosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mobility Shift ◽  
Loss Of Response ◽  
Inflammatory Bowel ◽  
Mobility Shift Assay ◽  
Trough Levels ◽  
Necrosis Factor

Background & Aims:  Loss of response to anti-tumor necrosis factor (TNF) drugs in patients with inflammatory bowel disease is likely due to low drug serum levels, and dosing anti-TNF drug concentrations may improve patients’ outcome. However, there are limited data on the diagnostic accuracy and utility of currently available assays for measuring anti-TNF levels. In this study, our aim was to compare serum adalimumab concentrations with two different techniques. Methods: We assessed serum adalimumab concentrations in 23 patients with Crohn’s disease during a 96-week follow-up period. Adalimumab trough levels were assessed using a sandwich principle-based enzyme-linked immunosorbent assay (ELISA) and a homogeneous mobility shift assay (HMSA). Results: At week 48, adalimumab trough levels were significantly lower in patients who experienced relapse compared to patients in remission, using both ELISA and HMSA methods: 4.8 mcg/mL (2.4-7.2 mcg/mL) vs. 7.5 mcg/mL (6.6-8.4 mcg/mL) (P=0.01) and 6.5 mcg/mL (3-10 mcg/mL) vs. 11.6 mcg/mL (7-16.2 mcg/ml) (P=0.004), respectively. Similar results were obtained at week 96: 5.9 mcg/mL (3.3-8.5 mcg/mL) vs. 12.8 mcg/mL (9.4-16.2 mcg/mL) (P=0.001) and 4.1 mcg/mL (1.6-6.6 mcg/mL) vs. 7.5 mcg/mL (5.7-9.3 mcg/mL) (P=0.009), respectively. There was a significant correlation between ELISA and HMSA adalimumab trough levels at both 48 (r = 0.691, P=0.0003) and 96 week (r = 0.822, P=0.0001). Conclusions: ELISA and HMSA assays are accurate methods to assess adalimumab trough levels in patients with Crohn’s disease and those who experience loss of response. The preferential use of one of the two techniques should be based on local availability and physicians’ experience.Abbreviations: ADA: Adalimumab; AA: Anti-drug antibodies; anti-TNF: Anti-tumor necrosis factor; CD: Crohn’s disease; ELISA: Enzyme-linked immunosorbent assay; HBI: Harvey-Bradshaw Index; HMSA: Homogeneous mobility shift assay; IBD: Inflammatory bowel diseases; LOR: Loss of response.

New Therapy for Orolaryngeal Manifestations of Crohn's Disease

2003 ◽  
Vol 112 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Francesco Ottaviani ◽  
Antonio Schindler ◽  
Mara Petrone ◽  
Pasquale Capaccio ◽  
Gabriele Bianchi Porro
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Damage ◽  
Chimeric Antibody ◽  
Cell Mediated Immunity ◽  
Tissue Destruction ◽  
Relative Safety ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Entire Gastrointestinal Tract

Crohn's disease is a chronic inflammation that may involve the entire gastrointestinal tract, from the mouth to the anus. The most widely accepted etiologic theory involves an immunologic aberration leading to local tissue destruction. Cell-mediated immunity with increased tumor necrosis factor (TNF) production may play a role in mucosal damage. Oral and laryngeal involvement are rare manifestations of Crohn's disease that are usually treated successfully by steroids. We here report a rare case of extra-intestinal Crohn's disease resistant to steroid therapy, which was successfully treated with infliximab, a chimeric antibody directed against TNF-α that is the only registered agent for the treatment of Crohn's disease. The relative safety, efficacy, and efficiency of infliximab make it an alternative treatment of which otolaryngologists should be aware.

scholarly journals A Case of Adalimumab-Induced Pneumonitis in a 45-Year-Old Man with Crohn’s Disease

2011 ◽  
Vol 18 (5) ◽  
pp. 262-264 ◽  
Author(s):  
James D Reid ◽  
Brian Bressler ◽  
John English
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Lung Injury ◽  
Tumour Necrosis ◽  
Human Monoclonal Antibody ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
Factor Alpha ◽  
Necrosis Factor

Adalimumab is a human monoclonal antibody against tumour necrosis factor-alpha that has been associated with acute lung toxicity, mainly in patients with rheumatoid arthritis. Descriptions of similar patterns of lung injury in patients treated with adalimumab for inflammatory bowel disease are emerging in the literature. A case involving a 45-year-old man with Crohn’s disease who developed a nonbronchiolitis inflammatory nodular pattern of lung injury after starting adalimumab is reported.

scholarly journals Case Report: Refractory Chronic Spontaneous Urticaria Treated With Omalizumab in an Adolescent With Crohn’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Simona Barni ◽  
Mattia Giovannini ◽  
Giulia Liccioli ◽  
Lucrezia Sarti ◽  
Anna Gissi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Case Reports ◽  
Chronic Spontaneous Urticaria ◽  
Tumor Necrosis Factors ◽  
T Helper 2 ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Moment

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is often associated with autoimmune or autoinflammatory conditions. Omalizumab is recommended in the treatment of refractory CSU in patients over 12 years of age who do not respond to four standard doses of antihistamines. Omalizumab blocks the mast cells’ degranulation, thus interrupting the resulting inflammatory cascade driven by T-helper 2 (Th2) cytokines. The efficacy of omalizumab in controlling CSU and possible associated diseases has been studied in few patients so far. In particular, some case reports describe adults with CSU and concomitant inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) or ulcerative colitis (UC). Although the treatment of CD with anti-tumor necrosis factors-α (TNF-α) seems to be effective in controlling CSU, no cases of the utility of omalizumab in patients with both conditions have been described so far. At the moment, there is no evidence that the pathogenetic mechanisms underlying CD are linked to the same pathways that are inhibited by omalizumab for the treatment of CSU. We present the first pediatric case of refractory CSU and CD in which omalizumab led to CSU remission, even if the follow-up period was limited. In conclusion, our experience shows how CSU could be associated with CD and successfully treated with the monoclonal anti-IgE antibody in a patient on immunosuppressive therapy. However, more data is needed from a larger population.

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