Another EPM question

[Amberley]

I have a younger (6yo) gelding that I half own who developed sudden onset spookiness and possible visual issues and the EPM test showed a titer of roughly 1:2200. The lab they used says <1250 is “negative” and >4000 is high. They also did a serum western blot which was a weak positive which the lab says indicates exposure and is a borderline observation.

The horse is on a trailer coming home to be turned out on pasture until we get to the bottom of this and the plan was to would work with our trusted vet instead of the vet at the training barn who is imho not great. However our vet just let me know they have an emergency and will be gone for a few weeks or possibly more so while we can work with someone else at her practice I don’t know them and I’m turning to COTH for some input. EPM isn’t that common here and I’m not sure of the best course of action.

1. is that an actionable titer?
2. is the spinal tap a good or bad idea? I’m leaning strongly towards not doing it.
3. treatment- is protazil still the recommended best treatment or is it better to go the compounded route? how long are people treating for?
4. No overt neuro signs but NQR, movement is not as good as it was, girthiness and itchiness, uncharacteristic anxiety and likely visual problems. What are the odds of a recovery if this has been going on for a few months? (see above comment on not-great-vet).
5. Is it worth reaching out to an expert for a paid consultation?

This is a really nice horse and a much loved so we want to maximize our chance of success here.

[JB]

Spookiness and possible vision issues, without being neurlogical in a coordination way, would have me leaning towards Lyme, rather than EPM. You can get blood pulled to send off, takes about a week give or take.

What, if any, other diagnostics were done? Tail pull? (not a definitive, but adds to the data)

Spinal tap is the most definitive IF it’s done properly. Contamination isn’t difficult.

Personally, if I were in your questionable shoes, and wanted to treat as if EPM, I’d be getting compounded levamisole/decoquinate and treating for 10 days. It’s inexpensive, and often has better improvement rates over Marquis or ReBalance.

Edited to change 30 days to 10 days because I mis-remembered the duration.

[JB]

Gotcha. So I’d still go with the compound as a first route.

The problem with Marquis is that it only guarantees an improvement of 1 neuro score. That’s fine if you’re at a 1 or 2, but not if you’re much higher. That also doesn’t mean some horses don’t improve multiple scores, for sure they’re out there

I’ve been following several friends’ EPM journeys, as well as a couple of EPM groups for a while, and the general theme is that while some horses absolutely do recover well with Marquis and ReBalance, more don’t, but many of those DO recover well with the compound.

The compound is much cheaper than Marquis. I don’t remember the ReBalance cost to see where it falls

so that’s what I would do, the compound which is basically Orogin-10 from Pathogenes. They don’t yet have FDA approval, but their product has been around a while now, and last I knew they were working on approval. So it’s not just something out of thin air

[Simkie]

I have one in my barn that was just acting … odd. High lyme titer, so figured it was that, and treated, but he didn’t really change. Another horse developed neuro symptoms, so when we tested her for EPM I had them test him, too. Her titer was high, his was not, but treatment with compounded ponazuril is so inexpensive, I went ahead and just ran a course through him. And he pretty immediately improved.

There’s a lot about EPM we don’t know. The Antech titer tests only for S. neurona and not N. hughesii (and who know what other causative things might be out there…) Based on my own experience this year, yeah, I’d try a course of EPM treatment.

[Simkie]

@JB

I’d be getting compounded levamisole/decoquinate and treating for 30 days.

The treatment period for decoquinate/levimasole is 10 days, not 30.

9709bb_0fc63deccd7a4c36a8220812e673a402.pdf

I have read (although can’t put my hands on it atm) that treating with levamisole for 30 days runs the risk of immune suppression.

@JB

The problem with Marquis is that it only guarantees an improvement of 1 neuro score

Marquis doesn’t guarantee ANY improvement. What pharma guarantees ANY outcome following treatment? In study, the researchers counted an improvement of one grade on a neuro exam a successful treatment. That’s all.

[JB]

ah, I did mis-remember the duration of the compound, thanks. I definitely wouldn’t treat longer than required, or longer than has been deemed safe, unless there were extenuating circumstances and a vet said so.

Re improvement - very bad wording on my part.

The study

“Response to treatment was determined by the investigator to be acceptable when a clinical improvement of at least one grade occurred by no later than 3 months after treatment, regardless of whether the CSF by WB was positive or negative.”

That’s how Marquis was approved, under the idea that it improved the horse but only by at least 1 grade.

Marquis - Boehringer Ingelheim Animal Health USA Inc.: Veterinary Package Insert

so no, not a guarantee.

[Simkie]

@JB

The study

“Response to treatment was determined by the investigator to be acceptable when a clinical improvement of at least one grade occurred by no later than 3 months after treatment, regardless of whether the CSF by WB was positive or negative.”

That’s how Marquis was approved, under the idea that it improved the horse but only by at least 1 grade.

Right. Successful treatment = one grade of improvement. They had to set SOME line. That doesn’t mean the horse can’t improve more than one grade (or that it will for certain improve a grade.)

BTW, the FDA warning letter to the Oroquin lady is really something, wow. Hadn’t seen this before but ran across it trying to find the levamisole treatment duration reference (which I recall as on two weeks, off two weeks, but can’t yet pin down where that came from.)

2017-Untitled-Letter-to-Pathogenes--Inc..pdf

[JB]

that’s pretty typical for that sort of violation. Why they haven’t done that with Summit injectable, I have no idea . Or at least, I keep hearing they have, but I’ve never been able to find proof they did. I don’t even know what their company name really is any more. Summit Animal Health? SummitMax? EternaPure? None of those show up in the search for the letters.

[Simkie]

Man, no. It’s egregious. It’s not just selling unapproved drugs. It’s ruining your research data:

“Since contacting FDA about getting approval for your products, you repeatedly submitted documents whose purposes are unclear, but which appear to modify the product development plan and deviate from the agreed upon path for approval of these drugs. You also explain that you had issues with population sampling and inclusion criteria. You appear to be defining a disease by assessing individual case responses to unproven treatments, then using those responses to unproven treatments to then define the case population to demonstrate effectiveness. The effectiveness data needed for approval cannot be accomplished this way. All of the evidence CVM has to date suggests you are collecting “use” data with the sale of the product, and not conducting a study that could be justified as investigational use.”

Just wow…

Yeah, it’s easy to show great outcomes when the great outcomes are the only ones you’re counting in your disease cohort. All those other horses must not have EPM…

[JB]

I don’t know anything about how they’ve operated, done “case studies”, or anything. I DO know enough properly documented/confirmed EPM horses who, under the information support from several EPM experts, have gone from truly undrideable, high EPM titers, to fully competing (including 50-100m endurance work) after using the lev/decoq compound (through their vet and a compounding pharmacy, not Pathogenes)

So it does work. And when used as directed, hasn’t caused issues in these horses. Did it fix all of them? No. Nothing can do that. But it does work to the point I wouldn’t hesitate to use it, and don’t hesitate to recommend it as an option to consider.

[Simkie]

I’m talking specifically about Pathogenes, their research and the warning letter.

It’s a damned shame there’s no actual published research on decoquinate/levamisole (I don’t think?) beyond what Ellison has produced, because hers seems pretty questionable. Without actual research, it’s impossible to have any ability to make educated comparisons between this treatment option and others.

[IPEsq]

A friend’s horse also had “borderline” titers (though both types of Protozoa were tested). After going down various other rabbit holes and spending a fortune, they finally did the compounded Marquis equivalent. Horse had chronic ulcer like symptoms but scoped clean. Weird spookiness. Digestive issues including fecal water syndrome. Could not build topline. Shifting mild lameness but no orthopedic problems found. I can’t remember with certainty, but I think they did 2 months of treatment and then retested. Horse did improve a lot, and titers did go down significantly. He seemed to handle the treatment well.

[JB]

@Simkie

I’m talking specifically about Pathogenes, their research and the warning letter.

Yes, so was I.

@IPEsq

the compounded Marquis equivalent.

what was that, since Marquis is FDA-approved, and a compound shouldn’t be allowed unless it was somehow different? Maybe you don’t know since it wasn’t your horse, but I’m curious

[Simkie]

@JB

what was that, since Marquis is FDA-approved, and a compound shouldn’t be allowed unless it was somehow different? Maybe you don’t know since it wasn’t your horse, but I’m curious

There are all sorts of compounded ponazuril options available, from a variety of sources.

https://www.farmvet.com/search?keywords=Ponazuril

https://www.heartlandvetsupply.com/search/SearchSpringResult?q=Ponazuril

https://www.wedgewoodpharmacy.com/medications/ponazuril/

https://www.chewy.com/dp/397887

Etc etc etc etc

The FDA doesn’t seem to care much. Marquis has been on and off backorder.

[JB]

I get the powders and liquids as viable legal options. I wonder if the pastes are any different concentration, or of their legal difference is that they seem to be flavored (apple, pepperment, etc) and maybe Marquis itself isn’t?

Just curious, since the legality seems to be pretty clear on compounds when there’s an FDA-approved drug, but maybe that’s also not something the FDA really wants to fight about

[Simkie]

@JB

maybe that’s also not something the FDA really wants to fight about

Off the top of my head, I can’t think of the FDA issuing a warning letter to a veterinary compounder for duplicating the format of a market drug.

Settling rx stuff without an rx? (Like horseprerace, Abler etc) Sure. Compounders with adulterated meds? Yup. But a compounded paste when the market drug is a paste? Especially in the face of backorder & shortage? Nothing pops to mind.

Can you recall them stepping in on that scenario for anything else?

[IPEsq]

It was a paste from Wickliffe. Her vet called it in. That’s all I’ve got.

[JB]

From an FDA page, top of p7

"If a compounded drug product is identical or nearly
identical to an approved drug that is not on FDA’s drug shortage list at the time of
compounding, distribution, and dispensing, the compounded product is essentially a
copy, and an outsourcing facility may not produce it under section 503B. "

Whether that really applies only to human drugs, I can’t say. My impression, speaking a few vets over the years, is it doesn’t matter. It will be a great question to ask my vet when she comes in a month.

So compounded omeprazole powder is legally allowed, since GG/UG are in paste form. Compounded Prascend is legal if it’s a capsule, or a pill that’s not 1mg.

I honestly don’t know if flavoring ponazuril paste as a compound makes it legal. But, like other things, it’s probably not a big enough deal for the FDA to get involved. And maybe it’s only legal to flavor a paste ponazuril due to the off/on shortage of Marquis itself.

https://www.fda.gov/media/98964/download

[Simkie]

I think it’s pretty clear the FDA doesn’t have the bandwidth to care about this. I was getting compounded paste omeprazole over 10 years ago.

Yes, technically speaking it’s not permitted. They seem to be looking the other way, and have for a LONG time.

[EmilyM]

I’ve had great success w protazil, and it’s almost half the cost of marquis.