Leflunomide

[Taco]

I talked to an AP doctor and will be taking my wife to see him next month. I have a lot to do in the meantime. Going thru wifes medicine. I found she is now on sulfasalazine and Leflunomide. Leflunomide concerns me because of the side effects. My wife has had some pretty bad infections from other immunosuppressants. Not sure what I should do.

[Maz]

@Taco wrote:

I talked to an AP doctor and will be taking my wife to see him next month. I have a lot to do in the meantime. Going thru wifes medicine. I found she is now on sulfasalazine and Leflunomide. Leflunomide concerns me because of the side effects. My wife has had some pretty bad infections from other immunosuppressants. Not sure what I should do.

Hi Taco,

Has your wife been on these meds long and/or currently experiencing any concerning side-effects from the Leflunomide or sulphasalzine? If so, it would be a good idea to voice these issues to the prescribing doctor to ask what actions she needs to take. If she’s currently okay and blood values look good and there is no sign of acute infection, then you may feel better about waiting a month till she sees her new AP doc to ask for his suggestions on tapering off these other meds and if this is necessary to begin the AP he prescribes. The new AP doc is very skilled (has RA himself) and should be able to advise on tapering and necessary washout times in order to begin treatment with AP.

Thing is, abruptly stopping immune-suppressants can lead to significant rebound and disease worsening, which doesn’t provide a very good setting for beginning AP, if herxing is layered on top of that. AP treatment failure can occur in these kinds of situations and patient experience has shown that it’s not pleasant dealing with both. When AP is started, a good regimen is found, and herxing has settled, improved outcomes can be achieved when tapering off other drugs is done in a slow and measured way.

It might help to read Dr. Trentham’s article on this, found on the main site. He was one of the lead researchers in the team that ran the MIRA trials for RA:

https://www.roadback.org/index.cfm/fuseaction/education.display/display_id/508.html

Hang in there!

[jasregadoo]

I read the article by Dr. T, and I noted that he sticks with the 2x per day every day dosing. I was under the impression that this dosing was best for SD, but that for RA, the pulsed dosing was actually superior and more effective.

Should we be working towards the 2x per day dose? I’m on 100mg 1x MWF. I recently thought that as I’ve been on for 4 months now, I might increase my dose and see if anything changed. I increased to 200mg 1x MWF (rather than 100mg 2x a day), and I’ve noticed inprovement. It’s only been a few days of increased dose, but as I said, I’ve been on Mino for 4.5 months now. Don’t know if my feeling a little better is due to the increased dosage, the hot weather, the undenatured collegen ii that I’m taking, or maybe all of the above?

I know none of us here are doctors, but I am curious as to whether others with RA have found improvement by increasing your dosage?

[Maz]

Hi Jas,

@jasregadoo wrote:

I read the article by Dr. T, and I noted that he sticks with the 2x per day every day dosing. I was under the impression that this dosing was best for SD, but that for RA, the pulsed dosing was actually superior and more effective.

Dr. T. was one of the lead authors of the MIRA studies for RA. In research studies, they have to keep the variables as few as possible, so usually patients will need to be taking the same dose of the medication that is being observed right across the board for the period of the study. This is the primary reason that Dr. T. continued using minocycline at this dose and he was never convinced of an infectious cause, though he was impressed by Dr. Brown’s work, which is why he was inclined to study minocycline (much like O’Dell). Nevertheless, he always viewed mino as a DMARD, not for its anti-microbial effects in RA. In the case of MIRA, those patients were also allowed to remain on their usual meds. In any case, this is why the 100mg twice daily dose was dubbed, “The Harvard Protocol,” or as it is labeled on the main RBF site, “The Current Protocol.”

Should we be working towards the 2x per day dose?

Brown, on the other hand, did believe in an infectious cause and as is area of focus and research was in mycoplasma, it was his rationale that daily dosing was not required for this bug, as it’s a slow-growing, slow-replicating organism that doesn’t require a constant attack by the antibiotic. He also observed that RAers who had a lot of pre-existing inflammation (and he was seeing patients who needed hospitalization as the drugs of the day weren’t helping these patients and were pretty sick by the time he saw them), couldn’t deal with the degree of herxing/worsening that ensued when they were given daily dosing. So, his approach was to go low and slow with the tetracycline/doxycycline treatment and, later, when minocycline arrived, that became the preferred abx of choice (due to its superior tissue penetration and need to also use less). So, the way Brown used AP was to titrate the dose to patient tolerance, rather than hitting them hard and heavy with daily dosing, because the sickest patients (usually those with long-standing, severe disease) just couldn’t tolerate the higher dose. This is why, on the main site, it was dubbed, “The Historical Protocol.”

These labels – Current and Historic Protocols – often trip people up, because the assumption is that the current protocol is the “improved” protocol, but it’s not necessarily the case, just that it was the dose used in MIRA to prove it’s value as a DMARD. When people are on other DMARDs or a biologic, when they begin AP, they are not receiving the full antimicrobial effects of the tetracycline, because it’s a bacteriostatic abx that requires a functioning immune system to actual work in that capacity. However, it still works well for its immune-modulating DMARD effects in that scenario. If a person begins AP on a clean slate and is not using anything but pred or NSAIDs, then the ideal scenario is to start low and slow and build up to tolerance. More is not always better for every patient, in other words.

Don’t know if my feeling a little better is due to the increased dosage, the hot weather, the undenatured collegen ii that I’m taking, or maybe all of the above?

If you are feeling better at 4 months of being on just your current dosing protocol, this is pretty darn good going! If you go check out the Education section on the main site, the recommendation is usually to wait until the 6-8 month period to gauge whether or not there has been a response to the dose being used. If no change in labs/symptoms, then it is time to go back to the drawing board to readjust dosing or perhaps to add a pulse of a second abx (e.g. if there is a history of strep, a different class of abx that is bacteriocidal would be added).

I know none of us here are doctors, but I am curious as to whether others with RA have found improvement by increasing your dosage?

Well, hope the above helps to understand why dosing are not the same for everyone right across the board. For people with SD who have no inflammatory overlap, they usually want to hit their disease hard and will often not experience any herxing. Degree of herxing is pretty relative to the amount of measurable pre-existing inflammation the person has in the mix. The more inflammation, usually the lighter the dose as the patient doesn’t want to create so much herxing as to also increase the symptoms of the bacterial allergy (and increased tissue hypersensitivity, as described in the book).

Does that help, at all?

[jasregadoo]

Thanks Maz,

I’ve asked these same questions before, and I know that so many others have as well. Thank you and all of the regulars and volunteers here for answering the same questions over and over again, and supporting all of us through the process.

I thought I had it figured out, but them reading that article threw me off a bit. I’m feeling more comfortable with what I’m doing now. I’ll revisit dosage in a few months, and see if I feel like I need to change my dosage or not. My rheumy is good and willing to give me mino, but she’s not an AP doc by any means, and sticks to the 100mg BID dosage, which made me very ill when I tried it at first. So i don’t talk to her about dosage. I just take my rx and try to figure it out from there. This website is my (and so many others) guiding light, and it really helps to have so many people who have been through it.

[Maz]

@jasregadoo wrote:

Thanks Maz,

I’ve asked these same questions before, and I know that so many others have as well. Thank you and all of the regulars and volunteers here for answering the same questions over and over again, and supporting all of us through the process.

I thought I had it figured out, but them reading that article threw me off a bit. I’m feeling more comfortable with what I’m doing now. I’ll revisit dosage in a few months, and see if I feel like I need to change my dosage or not. My rheumy is good and willing to give me mino, but she’s not an AP doc by any means, and sticks to the 100mg BID dosage, which made me very ill when I tried it at first. So i don’t talk to her about dosage. I just take my rx and try to figure it out from there. This website is my (and so many others) guiding light, and it really helps to have so many people who have been through it.

No problem, jas. There are mixed signals on the old website with the “Historical” and “Current” protocols. I’ve always thought these labels should really read, “MIRA/Harvard” and “Dr. Brown’s” protocols. 😉 It was wonderful when minocycline got the recognition it deserved when rheumatologists like O’Dell and Trentham studied its value for rheumatics, but as they are/were both rheumatologists, they both view mino as another DMARD and immune-modulator in the artillery for treating rheumatic diseases. Nothing wrong in that, except minocycline (and older tetras) do have the rather important property of also being antimicrobial in effect. As the field of rheumatology still hasn’t wrapped its head around infectious potentials (not surprisingly, as we now know there are many potential infectious triggers, not just mycoplasma), it is still only used in the “standard of care” way with a one-size-fits-all approach. This isn’t necessarily the case for anyone with a lot of inflammation, though, which produces confusion for both patient and prescribing doc when the person on a high daily dose winds up being worse off after starting AP in a high dose manner. I think this is one of the reasons folks give up early, thinking they are getting worse and their rheumy reinforcing this by saying “it’s a weak DMARD and we have better drugs today.” Rheumies are looking to palliate symptoms and bring patients comfort as quickly as possible. Again, nothing wrong in that, but if one really wants to go after a root cause, then the Brown way makes better sense to the person….i.e. to “kill the pathogens, not the patient.” Where it gets a bit more complex is when a person begins AP who is already on immune-suppressant therapy, as there is less antimicrobial and more DMARD effect from the minocycline a higher initial dose makes better sense in those instances. Then there are also those starting on a clean slate, newly diagnosed, with mild disease and little inflammation and these folks tend to be able to tolerate higher doses right out of the gate. This is why it’s recommended to read the book to grasp Brown’s rationale, as described in the book, and there is great info near the end about titrating doses to the individual.

Hopefully, when the brand new website is up and functioning (soon, we hope!), there will be some new peer-to-peer FAQs and answers that should help people who are asking these types of questions and it will save volunteers and old-timers the need to chime in with the whys and wherefores. 😉 It’s really not anyone’s fault…just that the old site became a bit of a patchwork quilt over the years and newcomers have to really dig to find the info.

The reason I posted the Trentham article for Taco is because his wife is already on DMARDs and it was to help alleviate concerns he had about starting AP while she was on these. Trentham says in the article that mino can be taken with any other rheumatologic drug quite safely and the goal is to eventually taper off the other drugs to the more benign antibiotic. This has to be done in a careful, measured way, because when people stop their other drugs, cold turkey, it can lead to horrible rebound and then to start AP on top of all that inflammation can lead to treatment failure when the herxing begins and amplifies all the symptoms even more. I hope that helps explain that a bit better.

[PhilC]

Hi,
@jasregadoo wrote:

I read the article by Dr. T, and I noted that he sticks with the 2x per day every day dosing. I was under the impression that this dosing was best for SD, but that for RA, the pulsed dosing was actually superior and more effective.

Not exactly. Pulsed dosing can be helpful at the start of treatment, but that’s because it is easier to tolerate, not because it is more effective.

@jasregadoo wrote:

Should we be working towards the 2x per day dose?

Generally speaking, yes (in my opinion). Although pulsed dosing is easier to tolerate, it is also easier on the bacteria. And that is not such a good thing because it may increase the risk that the bacteria develop resistance to the antibiotic, with the risk increasing the longer one is on the antibiotic. Although Dr. Brown wrote that bacteria cannot become resistant to the tetracycline antibiotics, that is simply not true. I don’t know why he claimed that; perhaps it was what doctors believed at the time.

For a good article about antibiotic resistance, see:
Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

By the way, I believe this problem has affected some members of this forum, myself included. After I was on doxycycline for 19 months, it rapidly lost most of its effectiveness against one of the chronic infections I’ve been battling. Knowing what I know now, if I could do it over again I never would have stayed on a 100 mg MWF dose of doxy as long as I did. I would have increased my dose to at least 100 mg per day much sooner, and if I’d had trouble tolerating that dose I would have reduced my dose to 50 mg per day.

Phil

P.S. I meant to post this reply sooner, but I put it aside after starting it and it took me awhile to get back to finishing it.

"Unthinking respect for authority is the greatest enemy of truth."
- Albert Einstein

[Author]

Posts