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Anti-Mycobacterium paratuberculosis (MAP) therapy for Crohn's disease: an overview and update
Sailish Honap1, Emma Johnston2, Gaurav Agrawal1,3
1IBD Centre, Guy's and Saint Thomas' NHS Foundation Trust, London, UK.
Abstract:
The role of Mycobacterium avium subspecies paratuberculosis (MAP) in the pathogenesis of Crohn's disease (CD) has been strongly debated for many years. MAP is the known aetiological agent of Johne's disease, a chronic enteritis affecting livestock. At present, due to the paucity of high-quality data, anti-MAP therapy (AMT) is not featured in international guidelines as a treatment for CD. Although the much-quoted randomised trial of AMT did not show sustained benefits over placebo, questions have been raised regarding trial design, antibiotic dosing and the formulation used. There are several lines of evidence supporting the CD and MAP association with uncontrolled and controlled trials demonstrating effectiveness, including a retrospective review of cases treated at our own institution. Here, we provide an overview of the evidence supporting and refuting AMT in CD before focussing on updates of the current research in the field, including the ongoing trials with the novel RHB-104 formulation and the MAP vaccine trial. While controversial, gastroenterologists are often asked about long-term combination antibiotic therapy for CD. There has been broadcast and social media coverage surrounding this, particularly with regard to current trials. Although patients should not be deterred from treatments of proven effectiveness, this review aims to help with commonly asked questions and highlights our own approach for the use of anti-MAP in specific circumstances.
Insights
Mycobacterium avium subspecies paratuberculosis (MAP) is debated in Crohn's disease (CD) pathogenesis. Emerging research, including novel formulations and vaccine trials, explores anti-MAP therapy (AMT) effectiveness for CD, despite current guideline limitations.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- The association between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease (CD) remains a significant area of debate.
- MAP is the causative agent of Johne's disease, a chronic enteritis in livestock, raising questions about its potential role in human inflammatory bowel diseases.
- Current international guidelines do not recommend anti-MAP therapy (AMT) for CD due to limited high-quality data and inconclusive previous trials.
Purpose of the Study:
- To provide a comprehensive overview of the evidence supporting and refuting the role of MAP in CD pathogenesis.
- To discuss the ongoing research and clinical trials investigating novel anti-MAP therapies and vaccines for CD.
- To address common questions and outline an institutional approach to considering AMT in specific CD cases.
Main Methods:
- Review of existing literature, including uncontrolled and controlled trials, evaluating the association between MAP and CD.
- Analysis of evidence regarding the effectiveness of anti-MAP therapy (AMT) in CD patients.
- Focus on updates from current research, including ongoing trials with RHB-104 formulation and MAP vaccine studies.
Main Results:
- While a major randomized trial of AMT did not show sustained benefits, questions persist regarding its design, dosing, and formulation.
- Multiple lines of evidence, including retrospective reviews, suggest a potential association between MAP and CD, with some trials indicating therapeutic effectiveness.
- Ongoing research with novel formulations like RHB-104 and MAP vaccine trials may provide further insights into AMT's role.
Conclusions:
- Despite controversy and current guideline limitations, the potential role of MAP in CD warrants continued investigation.
- Emerging research and novel therapeutic strategies, including updated AMT formulations and vaccines, offer promising avenues for future CD treatment.
- A nuanced approach is necessary when considering AMT for CD, balancing existing evidence with ongoing research findings and patient-specific circumstances.
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