This Is MS Multiple Sclerosis Community: Knowledge & Support

An abstract from the AAN meeting about the combination trial of doxycycline and Avonex. The preliminary, small sample results look promising.



Combination Therapy with Intramuscular Interferon Beta-1a and Oral Doxycycline in Patients with Multiple Sclerosis: An Open-Label Trial

Alireza Minagar, J. Steven Alexander, Rhonda Brooks, Roger E. Kelley, Robert N. Schwendimann, Eduardo Gonzalez-Toledo, Dana Merrill Bryan, Shreveport, LA

OBJECTIVE: To determine the safety, tolerability, and efficacy of doxycycline combined with intramuscular (IM) interferon beta-1a (IFNb-1a) in multiple sclerosis (MS) patients experiencing breakthrough disease

BACKGROUND: Doxycycline is a potent matrix metalloproteinase (MMP) inhibitor that can potentially suppress destruction of the extracellular matrix and therefore limit the transendothelial migration of activated leukocytes in MS. Additionally, because MMP-9 is capable of cleaving IFNB potentially contributing to relapses during therapy, doxycycline may be expected to reduce the frequency of relapses

DESIGN/METHODS: This was an open-label, single-center, single-arm, cross-over study. Patients aged 18 to 55 years with relapsing MS, an EDSS score of 1.5 to 4.5, one or more gadolinium-enhancing (Gd+) lesions on MRI, continuous treatment with IM IFNb-1a for a minimum of 6 months, and a relapse within 60 days of their baseline visit (month 3) were eligible. Patients underwent MRIs at months -3, -2, -1, 0, +1, +2, +3. Daily oral doxycycline 100 mg combined with weekly IM IFNb-1a 30 mcg, began at month 0

RESULTS: To date, 15 patients have been enrolled and 11 have completed the study. The patients had a mean age of 42.013.3 years and 9 were female. An interim analysis included 11 patients with 1 pre-treatment and 1 on-treatment MRI and neurologic examination. During pretreatment (months 3, -2, -1, and 0), the mean number of Gd+ lesions was 10.36.6, decreasing to 6.25.4 during combination therapy (p=0.001). Mean pretreatment EDSS was 3.90.4 decreasing to 1.40.5 (p=0.001) during treatment. One patient had transiently elevated hepatic enzymes on combination therapy, none have withdrawn. Final results of MRI and clinical measures will be presented

CONCLUSIONS/RELEVANCE: Combination therapy with doxycycline 100 mg daily and IM IFNb-1a 30 mcg weekly appears to be safe and effective in patients with relapsing MS.

So, obviously, some neurologists also think that adding antibiotics is a good idea. Would they have changed their minds or did I miss something?
Carole

great posting, dignan. A drop of 2.5 points in EDSS over 6 months is rather remarkable.

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

Remarkable yes Arron, but in a small (n=15) and open label trial (subjects expect to get better) is it statistically significant? As always isnt it the case that more research is required??

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John
I am what I am

indeed...

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

The trial I'd be most interested in seeing is the doxycycline alone versus placebo. I'd love to see even a short term, open label trial on doxycycline alone to stir the pot. I post this gripe like a broken record, but gosh. I know pharmaceutical companies are not interested, but can't some foundation, some government that provides socialized medicine, some rich individual scrape up the money to run this study? How much would it really cost? There is the doctor oversight and all those MRIs, probably 70 or more. At least the tested drug won't be expensive. I wish I could just win a lottery and fund it myself.

Lisa

There are also the ethical reviews. Study sponsors have to justify having so many people on placebo for an extended period of time.

Then an answer to any ethical criticism would be to run the antibiotic only (instead of interferon only) and the antibiotic + interferon. They could even do it as a blinded study (although it is hard to truly blind for interferon, due to side effects, etc.) There's already a lot of data on interferon-only, but not on antibiotic-only. If the antibiotic only is as good or even better than the interferon, that would be critical to know from a scientific standpoint. And we would all love to know the answer to that one for a treatment decision standpoint. There is a bunch of people out there who would jump to be on the antibiotic-only arm - I don't think recruitment would be a problem.

Lisa

Totally agree with you Lisa.

I know it's a small sample but given the results surely the next most logical step is to test the antibiotics alone??!!

The penny has to drop at some point!!


J.

On a related note, the same can be said for the Minocycline + Copaxone trial, although in that case they did try minocycline by itself first (albeit in a very small trial)

http://www.thisisms.com/modules.php?name=News&file=article&sid=112

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

I'm surprised that Anecdote hasn't chimed in yet regarding the ABX. It does seem that ABX seems to be a treatment you can gain some EDSS points back on, even though a lot of what you hear is anecdotal. Could MS be of infectious cause?

Well, I didn't chime in before because I have only just seen this. You have only to look in the Antibiotics and Regimens forums to know what I might have said. I never would have been prescribed one of the CRABs, even with doxycycline, so I had to go the full abx route. I'm glad I did. That's all.

Sarah

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An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.

It, or at least some subset of the illness(es) collectively known today as "Multiple Sclerosis" certainly *could* have an infectious cause and/or trigger.

These studies are exceedingly interesting since they use cheap medicines that are readily available, however remember that tetracyclines (such as doxycycline and minocycline) have their own neuroprotective affects via their action on MMP, among other things. A nice, eloquent summary of that can be found here:

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Discerning the effect of the anti-microbial versus the neuroprotective should be high on the agenda.

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

That sounds like it might be similar to the function of lipoic acid as studied by the Oregon Health Sciences University.

NHE

Arron, very good point. That is the 1,000,000 dollar/pound question at hand. Is it the neuroprotective or the anti-microbial action that is making the difference? I wonder if we might get a clue as to what the answer to this question is once Paratek releases the non-antibacterial tetracycline? If those who see beneift with ABX started taking this and still see the benefit, that would almost answer that question? Of course it would be much more complicated than that because you would have to do a double-blinded clinical trial on those who have and also those who haven't taken ABX.