ACG Turns a Blind Eye to Mycobacterial Therapy in Crohn’s Disease
The American College of Gastroenterology (ACG) recently released the 2018 Guidelines for the treatment of Crohn’s Disease (CD). Such guidelines can profoundly influence how practitioners treat CD and how younger physicians perceive CD pathophysiology. It is therefore intensely disappointing to read the ACG’s mistaken and blatantly unsupported conclusions in regard to mycobacteria and Atypical Mycobacterial Antibiotic Therapy (AMAT) for CD.
In regard to the use of mycobacterial therapy in CD, the Guidelines state (page 498):
“The relationship of mycobacterial disease to the development of CD has been extensively evaluated. The absence of mycobacteria in all tissue (even when assessed by PCR) and the lack of significant patient benefit when treated with multi-drug regimens has led to the recommendation that anti-mycobacterial therapy should not be used to treat patients with active CD. Anti-mycobacterial therapy has not been shown to be effective for induction or for maintenance of remission or mucosal healing in patients with CD.”
While admittedly categorized as an area of emerging research, there is ample support in literature for further investigation into the role of mycobacteria, and the use of AMAT in CD. Case in point: RedHill Biopharma is currently conducting a Phase III trial using combination anti-mycobacterial therapy, with final results due in mid-2018. It is irresponsible and damaging of the ACG to make a final judgment on this subject immediately prior to the release of those results.
Even more baffling, the ACG cites two meta-analyses in support of their recommendations, which DO NOT SUPPORT THEIR CONCLUSION, but rather lend support to the use of AMAT in CD as follows:
CONCLUSIONS: These results suggest that antimycobacterial therapy is effective in maintaining remission in patients with Crohn’s disease after a course of corticosteroids combined with antimycobacterial therapy to induce remission. Treatment of Crohn’s disease with antimycobacterial therapy does not seem to be effective without a course of corticosteroids to induce remission. Because of the small number of studies included in this meta-analysis, the results should be interpreted with caution.
CONCLUSIONS: Long-term treatment with nitroimidazoles or clofazimine appears to be effective in patients with Crohn’s disease.
The comment that mycobacteria have not been identified in all affected tissue, even when assessed with PCR, is misleading. After all, M. tuberculosis is similarly identified in some, but not all, affected tissue.
In 2008 the American Academy of Microbiology put this controversy to rest with their thorough review of the subject:
“One acknowledged potential microbial agent of CD is Mycobacterium avium subspecies paratuberculosis (MAP), a microorganism that causes a gastrointestinal disease similar to CD in ruminants, including dairy cattle, called Johne’s disease (or paratuberculosis). People with CD have 7:1 odds of having a documented presence of MAP in blood or gut tissues than those who do not have CD, thus the association of MAP and CD is no longer in question. The critical issue today is not whether MAP is associated with CD, but whether MAP causes CD or is only incidentally present, not an inciter or participant in the disease process.”
Concerned that this misrepresentation of published data would mislead practitioners, to the detriment of CD patients, a group of doctors wrote to the authors of the Guidelines on April 7, 2018. They requested that this mistake be promptly corrected, and offered to provide additional evidence on testing showing systemic mycobacterial infections in over 90% of CD patients. The goal of this letter was to achieve a rapid correction of the misinformation presented to the public on mycobacteria. While not expecting the ACG to wholly endorse the use of AMAT, an acknowledgement that this therapy was actively being trialed and may benefit particular CD patients who had exhausted conventional treatments, was desired. The response deadline of April 20, 2018 passed without any communication or acknowledgement on behalf of the ACG leaders.
Human Para then contacted the ACG directly, and were instructed to submit a letter to the editor to the journal in which the guideline was published if we would like our concerns addressed. While we plan to submit such a letter in the near future, we thought it important to make our subscribers aware of this issue at this juncture.
The direct, negative impact on patient care and the indirect, negative effects of dissuading funding for future research on the role of pathogenic mycobacteria in intestinal inflammatory diseases now necessitates a strong and well publicized response. It is unfortunate that a major industry leader like the ACG has failed to address these valid concerns, but has instead taken a hard-line stance on the role mycobacteria in CD that is unsupported by the proffered evidence.
Attached below is the April 7, 2018 letter submitted to the ACG in it’s entirety.