Your Questions Answered by Dr. William Chamberlin:
How long does it take before I notice improvement after first starting AMAT?
The time it takes to appreciate a clinical response varies considerably depending on the extent of the disease and variables that are unknown to me. I tell patients that they may feel worse for a few weeks to a month. I warn them about a “flu-like illness” where they experience high fevers and generally feel lousy. Without truly knowing, I attribute this response to an “immune reconstitution syndrome” whereby the immune system begins to battle the infection. The major clinical symptoms are abdominal pain, diarrhea, fatigue and a decrease in the overall sense of well-being.
Improvement in these parameters may take months, but some patients start to feel better within a week or two. If there is no improvement after 6 months, I generally say that they are not responding.
What are the side effects I should expect when I start AMAT?
I warn about a flu-like illness. Joint pains are common. Nausea from the pills may occur. I follow the tests of a Complete Blood Count and a Complete Metabolic Panel to be sure there are no idiosyncratic reactions to the bone marrow and liver. Although I have never seen it, eye inflammation (uveitis) and heart dysrhythmias are a theoretical concern.
Which side effects would require me to discontinue AMAT?
Any that the individual finds intolerable. Of course, uveitis, heart dysrhythemias, liver inflammation and bone marrow suppression would warrant stopping therapy.
What are the risks of AMAT?
Reaction to the drugs, Clostridium difficile infection on a theoretical basis, although I have rarely seen it occurring due to AMAT therapy. In general, the risks of AMAT therapy are similar to the risks of treating Tuberculosis with antibiotics. AMAT is cheaper, safer and more effective in the long run when compared to treatment with TNF antibodies.
Are there any tests or blood work I should have done prior to starting AMAT?
You should have a Complete Blood Count (CBC) and Complete Metabolic Panel (CMP) as part of your initial evaluation. Nobody knows the optimum drug regimen against MAP. My standard regimen includes clarithromycin, rifampin and levofloxicin. The RedHill Study uses clarithromycin, Rifabutin and Clofazimine. Other combinations of drugs chosen for their efficacy against non-tuberculosis mycobacteria will probably work and have been used.
Each of these drugs carry the risk of side effects, and while severe side effects are rare, it would be prudent to have your prescribing doctor order a CBC and CMP after 3 weeks and then every 3 months to guard against effects on the bone marrow and liver. In rare cases, the interaction between clarithromycin and levofloxicin can cause cardiac arrhythmia. If you have a previously existing heart condition, you should discuss this risk with your doctor. Around two weeks after starting AMAT, I would advise having an EKG test to rule out arrhythmia. This should be repeated once a year.
I've heard some doctors start all of the medication at full strength on the first day, and some start with lower doses and gradually increase over time to the full dose. What are the benefits and drawbacks to each method?
I start my patients on the full dose on Day 1 to minimize the risk of bacterial resistance. This produces more common side effects, including nausea and feeling like you have the flu for a few weeks, but I believe this approach works well for the majority of patients. The doctors who choose to slowly increase the dosage over a period of weeks do so to minimize side effects for the patient. There may be some cases of patients who have recurrent obstructions or more severe side effects initially where I would consider a ramp up method, but no studies have been done to compare these methods side by side. Therefore, which method is superior is up to each practitioner’s opinion.
What is the difference between Rifabutin and rifampin, and which is better for AMAT?
Rifampin and Rifabutin are related drugs in the same family. A major difference is the cost. Rifampin is a generic which is generally cheaper. Rifabutin may or may not be more effective against M. paratuberculosis in-vivo and it may be more prone to adverse reactions.
My doctor told me this therapy isn't approved and I shouldn't consider it. Is AMAT an effective treatment for Crohn's disease?
Many doctors will be wary of AMAT since it is currently not an FDA approved treatment pathway for Crohn’s disease. Large scale studies are being done now to acquire this certification. However, there is a 20 year body of peer reviewed research which indicates that AMAT is as effective as other Crohn’s therapies in inducing remission. Additionally, all of the medications used for AMAT are antibiotics that are FDA approved. The doctors who hesitate to prescribe AMAT are generally concerned about medical malpractice liability issues, and have not read the body of research advocating AMAT for Crohn’s disease patients.
Your doctor also may have heard of the Selby study, which concluded that AMAT was not effective in Crohn’s disease patients. That study had many flaws, but the data in fact showed that the regimen of clarithromycin, Rifabutin and Clofazimine was beneficial in treating Crohn’s disease. Straight-up Intention-to-treat analysis of the raw data showed that AMAT was beneficial. In fact, the percentages of subjects responding to AMAT in the Australian study were higher than the percentages responding to Infliximab in the original studies used to get Infliximab approved.
Current dogma is based on poor science and is internally inconsistent. Current dogma says that anti-mycobacterial antibiotics are not effective, but the same dogma says that Ciprofloxacin and Metronidazole may work and encourages their use. These two drugs are both great anti-mycobacterial drugs. The inconsistencies are ignored rather than addressed. For a more thorough analysis of the Selby study, please see the Treatment of Crohn’s via Anti-MAP on this site.
I tell patients that AMAT is effective in some patients but not everyone. The same is true when treating drug resistant Tuberculosis. Every patient becomes their own “therapeutic trial.” This is also true of all other therapies recommended for treating Crohn’s disease.
Help! My doctor won't prescribe AMAT. What do I do?
This is currently one of the most common practical questions I get. First try providing your GI or general practice doctor with the Core Research Pack on this site, and then requesting that they consider prescribing AMAT once they are fully informed. Better still, have them view the videos on the website. Of course, I would be happy to evaluate you in my office in New Mexico if you are able to travel to see me. If that is impossible, check the RedHill trial sites for a location near you. There are supervising doctors at each site, many of whom have their own GI practices. They would be familiar with AMAT and would be able to discuss it with you. Alternatively, integrative or functional health doctors are generally open minded practitioners and many patients have had success once they are provided the research. If you have exhausted all of these options, please contact TheCrohnsInfection.org as we are building a private database of practitioners and will assist if possible.
How long do I take AMAT?
This question is yet to be resolved. John Hermon-Taylor’s work may provide the tools required to follow a bacterial response to therapy. How long do you stay on Humira? The answer is “until it stops working.”
I usually suggest patients continue for 3-6 months. If there is no improvement in clinical symptoms then I say that there is no evidence that it is working. If there is clinical improvement then I recommend full dose therapy for 2-3 years. At that point we feel our way forward. I simply do not know how long to treat. One man has been on AMAT for 17 years, and refuses to discontinue therapy because he does not want to risk relapse. You should discuss the benefits and risks of discontinuing therapy with your prescribing doctor.
Will my Crohn's come back if I stop AMAT?
In most cases, yes. This is true of all currently available Crohn’s medication. There are five cases where all medication were discontinued and patients remained symptom free for more than five years, but most who stop AMAT will eventually relapse. There is no way to know whether it will be months or years before relapse, or if you may be one of those lucky patients who do not have a recurrence of symptoms for an extended period of time.
What is the remission rate of AMAT?
Of the patients I’ve treated with AMAT, about 70% respond and 50% achieve full clinical remission. Younger patients seem to do better.
Does AMAT work for ulcerative colitis?
AMAT does not seem to be as effective in ulcerative colitis.
Is AMAT better than the Anti-TNF medications like Remicade or Humira?
In my opinion, yes. AMAT has fewer side effects than the Anti-TNF medications, and the risks associated with immunosuppressive medications like Remicade or Humira can be serious. Additionally, AMAT has a better remission rate than the Anti-TNF medications. (See the chart on the Treatment of Crohn’s via Anti-MAP Therapy page.) The biggest different between AMAT and the Anti-TNF medications is that AMAT attempts to correct what I believe to be the root cause of Crohn’s disease, while Anti-TNF drugs only mitigate the symptoms of Crohn’s disease.
I've been on AMAT for a couple of months and I feel great, but I still have loose bowel movements. Does this mean AMAT is not working?
No. Success of AMAT is best judged by how the patient feels overall. Loose bowel movements are only part of that analysis. Certainly, the goal is to have a full remission of all Crohn’s symptoms, but some patients continue to experience loose bowel movements depending on their individual bodies or because it takes time to heal long term damage. If you otherwise notice an improvement of symptoms, I would be less concerned about loose stools.
One risk of AMAT is infection with C. Difficile. This causes severe, watery diarrhea and greater than normal gut pain. If you notice these type of symptoms, it is best to contact your prescribing physician or seek immediate medical attention.
I tried AMAT for 6 months and I don't feel any better. Does this therapy work for all Crohn's patients?
Unfortunately, this therapy will not work for all Crohn’s patients. For some, the side effects are too severe to continue treatment or they get recurrent obstructions or C. Difficile infections. It may not work in some due to previously built resistance to the mycobacterial strain thought to be at work in many Crohn’s disease patients. About 10-15% will notice no improvement after 6 months, at which point I advise them to discontinue treatment and seek an alternative therapy.
Can AMAT be used to treat diseases other than Crohn's disease?
There is a trial by RedHill Biopharma testing AMAT in multiple sclerosis patients. Other classic autoimmune diseases may be shown to have a mycobacterial cause, and AMAT may be successful for those patients as well. We will see.
The mycobacteria we believe is responsible for some cases of Crohn’s disease has also been cultured from patients with other autoimmune diseases. The research is in the infancy stages for diseases other than Crohn’s disease, but new trials can be expected in the future. Obviously, I do not like the term “autoimmune diseases.” In some cases the term may be accurate, but this term was indiscriminately applied to any chronic inflammatory disease of unknown cause. Many of these disorders may in fact be due to an underlying infection that has not yet been identified.
At the end of the initial 4 month AMAT trial period, is it normal to see elevated values for CRP and ESR? Does this mean AMAT is not working?
The CRP is an acute phase reactant and can be elevated for any reason that stimulates inflammation. CRP and ESR are often elevated after 4 months and should not be used to say that AMAT is not working. AMAT is working if the original symptoms are improved, if patients feel better overall and if they are able to diminish the other immune suppressive meds without the symptoms getting worse.
Can I take AMAT while pregnant?
I cannot recommend beginning or staying on AMAT if pregnant. The FDA has recommendations against taking the antibiotics used in AMAT while pregnant.