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Retrospective on Long-term Methotrexate and Cyclosporine Therapies
from Stealth

Hello Ed! I just finished reading your diary on your Cyclosporine therapy. I feel compelled to respond to that. Let me start by reminding you that I'm the crazy guy that sent you the Flaker's version of the Star Spangled Banner! Now you remember me, right? [Flake HQ Anthem! The venerated librettist of our very own anthem ... How could we forget? -Ed] Anyway, I found your diary article very interesting and I would like to share my own experiences with you regarding MTX and Cyclosporine.

Seventeen years ago I was on a methotrexate (MTX) regimen. My derm insisted I have a liver biopsy prior to allowing me to start MTX. Under a local, it's like being stabbed with an ice pick twice! Not one of the most favorite days in my life. As with you, MTX worked remarkably well for the first year or so. Then my Derm got scared, didn't like my liver enzyme numbers and referred me to a renowned researcher located sixty miles from my home. Because (as you probably already know) there is a finite amount of MTX you can ingest over your entire lifetime (it's something like four grams) the new Derm was ready to put me on a study drug. I was on the study drug for two years and did relatively well with the exception of unsightly skin peeling of the palms of my hands and soles of my feet. Additionally, my fingernails got very deformed and sore — so badly, that I consciously hid my nails from view of others as much I could. That study drug was eventually approved, it is now known as Soriatane. I take 25mg every other day, that's all I can tolerate or my nails begin to deform in less than two weeks. I doubt that it helps much. The main therapy that I was on — until just this morning, as a matter of fact — was Cyclosporine.

Let me tell you about Cyclosporine. Over the many years, I have been on and off this stuff with varying degrees of response. As you have found out, if you don't ingest enough daily, you might as well flush it down the toilet! Because I perceive that you and I are similar in the severity of P (minus the arthritis), age, weight, and professional background, I think you'll be able to make some interesting analogies between my experience with the drug and what you can probably expect. I'll try to give you a synopsis here:

On June 22, 2000, during a routine visit, my Derm decided that I needed to get some blood work done, she had been neglecting to do that for a hell of a long time! The creatinine level was 2.5. That's way over the the level docs like to see of say 1.0. She cut my dosage back to 100 mg/day. I immediately (from June 29 to present, July 22) began to acquire new, tiny red spots here and there. They grew to 1/4 inch size in a few days. After a few days on the 100 mg dose I also got a 24 hour kidney function test done and another blood test. The creatinine dropped down to 1.8, still too high. So now, I'm off the Cyclo and the terror begins!

The last time I was abruptly removed from Cyclo I had an incredible rebound. Within four months I was 90% covered head to toe, fire engine red! You see, I was on 200 mg/day and it was not keeping up with the P. That was, 200 a day for about one year. Therefore, I volunteered to go on yet another drug study my Derm was conducting for the Xoma Corp. It involved intravenous infusion of a new monoclonal antibody called Anti-CD11a. At first the study looked promising, but in the end it appeared to only delay the ravishing rebound I suffered from the abrupt withdrawal of 200 mg/day of Cyclo for a year. I can’t believe they are still studying this drug. It did nothing positive for me. I wouldn’t try it again even if it got approved. I don’t know if it actually helped anyone else involved in the study. After four hellish months crying in agony to the derm, I begged him to put me back on Cyclo. He did, without reservation, and at the level I requested! That dosage was 400 mg a day. In six weeks I was almost completely clear minus a little on one knee and hardly noticeable on the elbows. Definitely, tolerable. I didn't even use topicals at all. I was free to not think about P. My new Derm bought out the old Derm's practice and she continued to allow me to use Cyclo. Last month she asked me if I thought I had been on it for a year or so. I said, "About a year." I lied Ed, I had been on it for two years.

I hope I haven't permanently damaged my kidneys by this. I watched my poor dog die of kidney failure, not a pleasant sight. Plus, now I go through the horror of waiting to see how bad it is going to get THIS time.

The Derm started me today on something I never tried before, it's called Tabloid. The generic name is Thioguanine. Derm made an analogy to MTX. Like MTX is an analogue of folic acid, quote the PDR: "thioguanine is an analogue to purine which interferes with nucleic acid biosynthesis, and has been found active against selected human neoplastic diseases." The product is shown in the Physicians' Desk Reference (PDR) 1993 edition and it's manufactured by Wellcome under the trade name of Tabloid. I'm taking one 40 mg tab/day with weekly blood tests for marrow suppression and CBC. Today is my second day on it. No notable side effects during the first 24 hours. Per the PDR, it's a chemotherapy drug used for leukemia. Can you believe that? I'm back using the topicals too.

For your enlightenment, here are some side effects I experienced with Cyclo after my long term use of 300 mg/day. Most of these have disappeared when I cut back to 100 mg/day — which was a worthless dosage.

  • Hypertension: As high as 140/100. My internist prescribed Cardura 1 mg/day. Don't know if it helps though.
  • At first I had tingling in the fingertips most noticeable when I washed my hands in fairly hot water. That went away after a few months on Cyclo.
  • Constant upset stomach. Ate Rolaids like mints. Graduated to Gaviscon at night to sleep through the night. - Haven't had either since I stopped Cyclo.
  • Could not sleep on my back — something with regurgitation, my dinner would try to come back up during sleep. That side effect has completely disappeared.
  • Leg, foot, and toe cramps in the middle of the night that woke me up in agony. - Have had only one more incident of this since the dose was cut.
  • Sleepiness during the day, especially in the afternoon. Sometimes totally brain dead! Much better during the last week or so.
  • Most insidious of all, I gained 20 lbs without changing my eating habits at all. Time will tell on the lasting effect of this side effect.
  • A lot of hair growth on the back side of the upper arms and upper back. I had very little hair on my back before Cyclo.

One more thing Ed, there is now a generic form of Neoral (I also took the predecessor to Neoral, Sandimmune) by: Eon Labs, simply called Cyclosporine Capsules, USP (Modified). My co-pay on this was 33% less, it worked just as well as Neoral and a whole lot easier to get out of the little packaging tubs. Neoral is made in Germany or Switzerland, therefore more dollars.

I haven't been back to FlakeHQ in a long time because I had two years of my life back that I didn't have to think about P so much. I did buy and read your book. I enjoyed it very much. I'm glad to see you are still plugging along with FlakeHQ and hope you continue.

Good luck with your own Cyclo regimen. I hope I'm not singing the FlakeHQ Anthem again any time soon. -Stealth

*****

Ed’s Response: How wonderful to hear from you, and thanks for taking the time to share your experiences with MTX and Cyclo. As you anticipated, I’ve read and re-read the above with intense interest. My P is only a decade old, and I’ve pursued systemics (first MTX, now Cyclo) for less than 2 years, so reading about your experiences with these regimens, spread across nearly 2 decades, is very valuable to me.

First, I’m glad the prefatory liver biopsy appears to be the exception rather than the rule now. I was told biopsies these days are only conducted if blood work-ups after non-evasive corrective regimens (reduced dosages or drugs) and/or eating and drinking behavior changes are ineffective, and that questionable enzyme levels prior to commencing one of these therapies usually just dissuade patient and derm from attempting the therapy. (In the early nineties, when I was still drinking alcohol, and before my diabetes had been diagnosed, my liver enzymes were elevated and systemic therapies for my P were simply dropped from consideration.)

Your report about rebounds underscores my own suspicion (addressed in my Cyclo Diary) that my worsening condition through the first few weeks on cyclo was at least in part rebound from the sudden cessation of MTX. Also, the too-low dosage did me no good. My derm and I have already discussed tapering off and up — overlapping — when it’s time again to change meds.

Regarding dosage: Now that I’m doing well at 325 mg/day of Cyclo, it will be interesting to see when/if my derm recommends lowering the dosage to experiment with a less potent "maintenance level." This is recommended in the Novartis literature accompanying the Neoral.

Speaking of which, thanks for the info about the generic equivalent. I’m definitely going to mention this to my derm. His prescript form says "no substitutions" in big letters and I’m not sure my pharmacist — even if he knew about the Eon Labs generic form — would push it instead of Neoral. Even though I, like you, enjoy prescription insurance with a bearable co-pay, the high cost of Neoral disturbs me.

I had not heard about any "lifetime maximum dosage" of MTX and, in a quick review of the literature just now, did not see any mention of this. You might have heard an opinion rather than an established maxim. In the National Psoriasis Foundation’s booklet, "MTX," which was re-copyrighted in 2000, they point out that liver biopsies are often recommended when the accumulated dosage reaches 1-1.5 grams, and then again at 3 or 4 grams. (Yes, I know this seems to contradict what I’ve heard about liver biopsies in general.) But they do not suggest 4 grams is a limit to the therapy. Then again, it may not be mentioned in what I’m reading because at normal prescription dosages it would take several years to ingest 4 grams. By my math, at 20 milligrams per week, it would take almost 4 years to ingest 4 grams. Many flakers have been on MTX regimens longer than this, but I don’t know about variations in dosage level.

Be sure and let us know what happens on the Tabloid. This is a new one on me, too. MTX was initially a drug for cancer, so I guess we shouldn’t be surprised that other chemotherapies may help P. Do keep us apprized!

Some of the side effects you noted ring quite true for me, too:

  • Blood pressure did elevate on Cyclo and I am taking Norvasc to control it.
  • Tingling in feet and hands upon emersion in hot water (or in the shower) is still happening for me (now into my third month on Cyclo).
  • Sleepiness during the day is a big problem. Sometimes I simply must take a nap. For me this may be exacerbated by the diabetes.
  • Since starting on these systemic regimens about 18 months ago, I have gained 20 lbs.

Those are the side effects we have in common.

Again, thanks for dropping by to share all this, Stealth. I can’t mind infrequent visitors if they’re not dropping by because they don’t need to. I would be overjoyed to have to decommission FlakeHQ because no one flaked anymore. -Ed


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