"The Cause for a Cure for Crohn's Disease"
Treatment & diagnosis of Crohn's Disease
Anti-MAP treatment for Crohn's Disease
PARA is a group of Crohn's disease patients, their families and friends. We regret that we cannot answer questions or offer any recommendations related to treatment. Please direct questions regarding diagnosis and/or treatment to your health care professional. The information offered on this site is for educational purposes only and should not be used as a basis for diagnosing or treating any illness.
A limited summary of the history and background information regarding anti-mycobacterial treatment for Crohn's disease is detailed below. It should be noted that there is considerable overlapping subject matter in terms of research. Therefore, we would urge you to visit the Research section of this website for additional information.
History of anti-mycobacterial treatment for Crohn's disease
Since Crohn's disease bears significant similarities to known mycobacterial diseases, clinicians have been attempting to treat Crohn's disease with anti-mycobacterial drugs since 1975. Early treatment regimes were composed of antibiotics chosen for their activity against Mycobacterium tuberculosis (MTB), although both in-vitro and in-vivo data for these antibiotics showed that they had little effect against Mycobacterium paratuberculosis, as Mycobacterium avium subspecies paratuberculosis (MAP) was known at that time. If cases of Crohn's disease were caused by infection with MAP, then it is not surprising that these early treatment regimes were, in general, failures. For a full review of this early work, please read Chiodini 98: Antimicrobial Agents and Crohn's disease.
In the 1980's, disease caused by Mycobacterium Avium Complex (MAC) became prevalent. During the 1980's, MAC became the leading cause of lethal infection in patients with Acquired Immune Deficiency Syndrome (AIDS). Clinicians attempted to treat these MAC infections with the only anti-mycobacterial drugs available, namely drugs active against Mycobacterium tuberculosis. Successes with these early regimes were rare, since MAC bacteria were either resistant to anti-MTB drugs, or quickly developed resistance.
The advent of macrolides
The outlook for patients with MAC disease improved greatly in the late 1980's, with the development of a new class of antibiotics, known as macrolides. Two of these macrolides, Clarithromycin and Azithromycin, were highly effective against MAC bacteria, and revolutionized the treatment of MAC infections. Although they were unable to eradicate MAC infections, they had such a strong inhibitory effect that the chances of the host's own immune system bringing the infection under control were greatly enhanced. However, development of macrolide resistance is a common problem, and there are still no antibiotics regimes available which are guaranteed to eradicate a MAC infection. For a thorough review of antibiotic treatment for MAC disease, please read Heifets 96: Clarithromycin against Mycobacterium avium complex infections.
In the 1990's, a group of clinicians in England began treating Crohn's disease patients with anti-mycobacteria regimes which included macrolide antibiotics. The results of their work are discussed below.
Work to date
To date, three groups of investigators have published results of open trials of anti-MAP treatment which includes macrolide antibiotics. These are:
For a discussion of anti-MAP treatment for Crohn's disease, please read An interview with Dr. T. J. Borody.
We would encourage you to visit Dr. Shafran's Crohn's Disease Info Center for extensive information about RMAT treatment.
Endoscopic photos of responses to RMAT
Dr. Ira Shafran has graciously provided endoscopic photographs of intestinal condition before and after Rifabutin and Macrolide Antibiotics Treatment (RMAT) from an award-winning report presented at the Digestive Disease Workshop in San Diego, May 2000. To see a portion of that report and the accompanying photographs click here.
Dr. Thomas Borody has also graciously provided "before" and "after" endoscopic photographs of intestinal condition of patients treated with antimycobacterial therapy. To see those photographs, click here. These photographs are in conjunction with an interim report published by Borody et al in 1998 of their Phase 2 trial, entitled "Treatment of Severe Crohn's Disease (CD) Using Rifabutin-Macrolide-Clofazimine Combination." See the section below entitled "Work to Date" for details about publication of this study in 2002.
Open trials, regardless of the results obtained, do not provide sufficient evidence to recommend the treatment which is being tested. In order for the treatment in question to be proven to be an effective treatment, it must be subjected to a double-blind, placebo-controlled, and preferably multi-center clinical trial, for the following reasons.
Existing clinical trials
A double-blind, multi-center, controlled clinical trial of combination anti-MAP treatment is underway in Australia. For full details see the report on the Antibiotic Clinical Trial section of this site.
Known side effects of treatment
Among the side effects noted with existing anti-MAP treatment regimes are:
In recent years, a number of investigators have conducted studies of anti-MAP treatment for Crohn's disease. Their results are largely unpublished. They have reported treatment failures in between 16% and 33% of patients, i.e. that a subgroup of patients has experienced little or no improvement in their condition. The reasons for such failures may include
Source: http://www.crohns.org/treatment/index.htm Contact PARA: http://www.crohns.org/contact.htm
Paratuberculosis Awareness & Research Association, 1999-2003.
Chiodini: Antimicrobial Agents and Crohn's disease: Do they have a therapeutic role?
List of MAP research papers