Golimumab for moderate to severe ulcerative colitis
Anne S Strik1, Sophie E Berends2, Ron A Mathôt2
1a Department of Gastroenterology and Hepatology , Academic Medical Center , Amsterdam , The Netherlands.
Expert Review of Gastroenterology & Hepatology
|March 10, 2017
Summary
Golimumab (GLM) helps maintain remission in ulcerative colitis (UC) but some patients lose response. Therapeutic drug monitoring may optimize GLM dosing for better outcomes.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Golimumab (GLM) is an anti-tumor necrosis factor (TNF) biologic approved for moderate to severe ulcerative colitis (UC).
- GLM has demonstrated maintained clinical remission rates up to 50% in UC patients.
- However, approximately 50% of patients do not respond to induction therapy, and up to 40% of responders lose efficacy over time.
Purpose of the Study:
- To explore the association between golimumab serum concentrations and clinical outcomes in UC patients.
- To discuss the potential role of therapeutic drug monitoring (TDM) in optimizing GLM therapy.
- To evaluate strategies for managing loss of response to GLM.
Main Methods:
- Review of clinical data and pharmacokinetic studies related to golimumab in UC.
- Analysis of factors associated with response and loss of response to GLM.
- Discussion of TDM principles and their application to GLM therapy.
Main Results:
- Higher golimumab serum concentrations are associated with improved clinical outcomes and remission.
- Loss of response to GLM is frequently linked to low serum GLM concentrations, indicating insufficient drug exposure.
- Therapeutic drug monitoring may help identify patients with suboptimal exposure and guide dose adjustments.
Conclusions:
- Optimizing golimumab exposure through TDM may improve clinical outcomes and success rates in UC patients.
- Further research is needed to define the therapeutic window for GLM.
- TDM offers a potential strategy to manage non-response and loss of response to golimumab in UC.
Related Concept Videos
01:29Drugs for Treatment of Ulcerative Colitis in IBD
578
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
578
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
618
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
618
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
584
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
584
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
670
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
670
01:29Inflammatory Bowel Disease IV: Pharmacological Management
874
Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
Pharmacologic...
874
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
1.3K
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
1.3K