Keith’s GoutPal Story 2020 › Forums › Please Help My Gout! › Your Gout › Nice to meet you all!!
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June 17, 2010 at 12:52 pm #3294
My name is John (no, that's not a pseudonym) and I have had gout for almost 25 years now. My first attack came when I was 17, and I am 41 now. My first few attacks weren't diagnosed property, as I was an athelete, and the assumption was that I'd somehow traumatised the knee or ankle I was having an attack in. I was finally diagnosed and 19 and have been struggling ever since. I am completely intolerant of Allopurinol, Uloric and Probenicid, as they very negatively affect my liver. I have treated each flare over the years with Indocin, to the point that I am extremely tolerant of it, and probably was getting to a point of being unsafe with it. About three years ago, I was involved in a study for Krystexxa, which hasn't been approved yet. My uric acid levels went from the high sevens down to zero and stayed there for almost two years, during which I was completely attack-free. Unfortunately, the study ended, and my last uric acid level bloodwork came back at 7.8. It's extremely frustrating, waiting for approval, and then if the drug does get approved, seeing if my insurance will cover it, and then if I will be able to affort the drug or the co-pay even if it is covered. But this is the only thing that's ever prevented me from having attacks. Before the study started, I found out that the years of attacks have left me with osteoarthritis in both ankels and both knees, in addition to having pain issues from the years of attacks in those joints as well as both feet, my right big toe and both elbows. I have tried every holistic remedy and diet I've heard, with no positive results. Anyway, that's a little about me and my history. Nice to meet you all, and I hope to be an active memeber of the community, getting and giving advice where I can!!
JohnJune 18, 2010 at 7:53 am #8997
I am sorry to hear of your failures with Allopurinol, Uloric, and probenecid. Were the failures actually demonstrable with symptoms or merely the result of aberrant liver function dyscrasias… often they can be of little significance. It seems more than a bit odd that ALL these very different types of drugs produced the same liver ailment.
Well as you know, but maybe some here don't Krystexxa is an articficial uricase, an enzyme lacking in humans but present in many animals that breaks down uric acid to a more soluble compound easily disposed of. It is delivered by injection or IV drip a couple times a month. It was developed by Savient Pharmaceuticals in 2008 and submitted to the FDA early last year lyear. Becasue of high side effects it was REJECTED in the Summer and resubmitted.
Nearly a quarter of patients taking the drug in a study suffered a serious side effect, compared to just 12 percent of patients who were taking inactive placebo pills, researchers said. Six patients died while taking Krystexxa in the study, but just three patients who were given placebo pills died. Many of the patients who died had pre-existing heart conditions, but still, twice as many died while on Krystexxa than on placebo, which is concerning.
The patient injuries and deaths apparently raised questions at the FDA.
it really lowered your uric acid to ZERO…that seems hard to believe, and a bit of overkill. It does not seem possible to attain a zero. Perhaps the testing used too high a dose and thus enhanced the side effects if anything approaching zero was the goal of treatment.
Of course people who have shown resistance to ALL treatments DO need something else but I suspect that number is small, that a lifetime of an intravenous drug administered twice a month is more than a little cumbersome, hideously expensive, and seemingly dangerous.
You aren't iinvolved with Savient are you or a stockholder?
If all is as it seems I can recommend two things for you: benzbromarone from any of a dozen countries overseas (but beware some liver issues,) or losartan (Cozaar) a weak angiotensin receptor blocker drug that is coincidentally uricosuric.
Failing all of that, your only remaining answer seems to be a purine-free diet…appalling though it sounds.
Given all the evidence, it seems to me that the chances of the FDA approving Krstexxa for drug resistant gouties is less than the likelihood of their approving benzbromarone.
Appropos of nothing:
Savient had a 50% stock runup on Friday after being mentioned by the FDA according to this article but the numbers I checked didn't warrant that claim:
As the old miner said: “There's gold in them thar hills.”
The skeptic in me has my ears up.
I was also disheartened to not be abvole to find a single mention of how the studies were done, how long, how many people, how compared, etc.. I thought the FDA last year DEMANDED release of drug tests whether or not they met with the drug coompanies hopes. I guess good ideas are quickly dashed in this non-regulatory environment.June 18, 2010 at 10:00 am #9002
I know how it may sound, but no, I have no financial or other connection to Savient, not even as a stock holder. While I don't discount the possibility that the side effects could be linked, I know for me there were absolutely no abberant side effects. And yes, it was a 2 hour IV ever other week, which, while combersome, completely changed my quality of life. Prior to the study, I walked with a cane most days and had many more physical issues than I have now. I realize that there is a chance that Krystexxa (or puricase as it was called during the study) could never hit the market, and even if it does, I may not be able to afford it, but I have to say, the end of the study left me feeling very scared about my future, considering how fast my gout has accelerated over the years and how relatively young I am. I will say that one patient who went through the study (a woman in her 70's), eventually developed a resistance to the treatment and found no positive effects by the end of the study. I also realize that I am in a vast minority of people who can't take any of the maintenance drugs. Needless to say, I've been on an almost completely purine free diet for over 5 years. My understanding about FDA approval was that it was rejected due to concerns with the manufacturing process, not the side effects or efficacy of the drug. But that's neither here nor there. I am leary at this point of taking anything that may mess with my liver, given my obvious sensitivities, but I will research the other option you mentioned. I know it may sound like I work, or at least am pimping for, Savient, but when you've lived in misery for over two decades and something comes along that completely changes your life, it's hard not to sound like a commercial for it. I'm sure the market for it wouldn't be extraordinarily large. As to my liver enzymes, I only noticed that I had a markedly increased sensitivity to alcohol (which I rarely, rarely indulge in) but even a single glass of wine would make me ill. But that was just the latest one, previously, I had no symptoms, just exceedingly elevated liver enzymes. Febuxostat accually got approval while I was still in the trial, so I hadn't tried it until about six months ago. The 40mg dose didn't even slow down my rapidly accelerating Uric acid levels, but the 80 actually kept it at about 3.9 for a couple of months, but then updated blood work concerned all my doctors concerning my liver and they took me off it altogether.June 18, 2010 at 10:33 am #9003
Which liver enzymes got elevated on febuxostat? How high? Your uric acid response to the drug was superb.
Did you REALLY mean to say you got uric acid values of ZERO with the uricase? ZERO to me sounds like a lab error.
Often times in a study, a caring company will offer their volunteers a lifetime of FREE treatment. It seems only fair since you are risking life and limb for their potential financial windfall. Ask them.
Do you have ANY idea how the study was structured? How long, how many people. Those extra three cardiac deaths might be insignificant in a study of 10,000 people but QUITE significant in 100 people. Their excuse that those extra deaths occurred in SICK people is disingenuous at best…if the study was random and double blinded there were sick people in both groups.
DO check into benzbromarone, some Europeans SWEAR by it, and also make sure that any liver irregularities exhibited during the febuxostat trial are evaluated INDEPENDENT of the uricase people. A lot of people walk aroound with slightly abnormal liver readings. I feel pretty strongly that marginal liver enzyme irregularities, which can be quite common, are very often FAR less damaging than a life of untreated gout.
What problems did you have with allopurionol? Did you go to higher doses?
If all else fails, perhaps you can get the uricase in some country that approves the drug even if it means you must administer it yourself…ugh!
I REALLY hate the fact that Savient isn't publishing these results.June 18, 2010 at 12:44 pm #9005
I know that the study group wasn't exceptionally large, but I do know that the double blind was split into 3 groups, one group got the placebo, one got the drug every two weeks, and one alternated between getting the drug and the placebo with every other treatment. The first two groups made up 20% of the participants, each. The third group was 60%. So 80% of the participants were getting the drug on some level. I was in the third group, as evidenced by my GP continuing to do SUA level checks on me throughout the study, but that was only for the first 12 months. After that, everyone, including myself, was offered the opportunity to go onto an extended study, where we knew we were getting the drug. After 18 months, the plug was pulled on that part of the study, and I haven't had the drug since. It's been close to 8 months now, and while I haven't had a flare yet, by SUA levels are back up in the high sevens and rising with each test. Yes, I am sure that the SUA levels were zero, because my primary confirmed it with her own tests. Also, during the first part of the study, we would see values start to return after about three weeks, but never getting over three, but then when I'd get the treatment, by my next bloodwork, they'd be back to zero. During the 18 months of getting it every two weeks, it never went above zero. I can't tell you why they aren't publishing the results, and honestly, even though I have no affiliation with them beyond being a volunteer to recieve the treatment, I wouldn't care if there were risks, especially given the results that I saw. Once there is FDA approval, I will definitely inquire about the lifetime supply, but I've gotten the impression that that isn't really a possibility, especially considering the way they abruptly pulled the plug on the continuation study.June 18, 2010 at 12:47 pm #9006
Oh, and with Allopurinol, 300mg wasn't enough to control my SUA, and like with the febuxostat, any time we tried to go to a higher dose, my liver enzymes got out of whack. Now, it's my fault for not knowing which ones, but I've had three different doctors scare the crap out of me with their reactions to my liver enzymes, whichever ones they are. I'm not naive enough to believe that a single doctor can't be wrong or over react, but when you've seen it from three seperate, totally unrelated doctors, it shakes you a little.June 19, 2010 at 3:14 am #9010
I understand the zero now. Uricase converts uric acid to allantoin. I never realized it was so effective, but I've now seen (from rasburicase info in Australia) that conversion is dose dependent. Zero seems acheivable, but I'm at a loss to know if it is safe. I've also seen, in other studies, that uric acid test results have been unreliable as the enzymes continue converting uric acid after the blood is drawn, so can be artificially low unless precautions are taken.
Your situation is really frustrating, because rasburicase (sold as Elitek in the States, and Fasturtec elsewhere) looks like it could be an option, but it is restricted to patients on chemotherapy. I don't know if your doctors have any leeway on that, and it is very expensive.
Looking elsewhere, I see that BioCryst are recruiting for a new PNP inhibitor with the enchanting name of BCX4208. I know nothing of this drug, but there are trials in Dayton. If you follow the link on the Biocryst site you can see the recruiting criteria at clinicaltrials.gov. You can also search for other trials. There does not seem to be much else relevant in Ohio, but other nearby states may have something. Search for 'gout OR uric' for best results.June 19, 2010 at 3:31 am #9011
If all else fails, perhaps you can get the uricase in some country that approves the drug even if it means you must administer it yourself…ugh!
I REALLY hate the fact that Savient isn't publishing these results.
I can't find pegloticase (Krystexxa) pricing, but rasburicase online from Canada is $500 for 3 doses.
Not sure if this means 3 days, 3 weeks or what, but it certainly aint cheap.
On the Krystexxa front, Savient have resubmitted their application for FDA approval. We will know one way or the other on 14th September 2010. 87 days to go.
The revised briefing material isn't available yet, but last years application is still on the FDA site (BLA 125293). As it's public domain, an email might get access sooner, but finding the right person might take longer than just waiting for the meeting notes!June 19, 2010 at 7:11 am #9014
Just a couple more thoughts John:
Thanks for spelling out the study, I understand completely.
A problem I see is that it was sounds UNBLINDED, which would makes it a poor study. Do I have that right, or was the information withheld from doctor and patient UNTIL such time as part one of the study was complete? (Pity the poor souls that had to go for months getting shots of SALINE every two weeks.)
But IF you can get the stuff in the future, your being in group 3, in essence getting a shot a month and being able to control to 3 mg/dL, it would seem that is all you would need and perhaps could get by with a shot every 6 or 8 weeks and still remain below 6 mg./dL.
It would seem to me that the first thing the company should do to mtitigate side effects, especiially annoying ones like extra deaths, is to lower the dose to that minimumm doseage to control gout. Certtainly taking uric acid to zero (still skeptical) is certainly massive overkill.
While you are waiting I have ONE STRONG RECOMMENDATION: take 300 mg. allopurinol daily, a dose at which your liver enzymes seemed to remain okay. Even if you are not able to assure yourself of readings below 6.0 I guarantee you will lower your uric acid by at least a couple points which might keep you away from any major attacks or lessen their severity. Check your liver enzymes regualrly to make sure you stay in safe margins.
Ask your doctor for a copy of your liver enzyme results from any time period he/she/they have. With them in hand we can talk about their significance. By law they must keep them and by law you are entitled to them.
Now from super-skeptic: I can envision a situation where a doctor is eager for study money…it is sometime $$$HUGE$$$ and I HAVE heard of a doctor or two who are eager for cash, I know, hard to believe. Such a doctor MIGHT be tempted to submit patients for study who do poorly on allopurinol “Oh goodness, his SGPT is a bit high.” “Oh goodness, he is only getting a 6.1 SUA on 300 mg. allopurinol.” Etc., etc. “Ca-ching.”
But again…you must do something besides just waiting for FDA approval. Look on the bright side of the FDA delay/inaction…perhaps you are being protected from having a heart attack.
Doing nothing is NOT really an option for you.June 21, 2010 at 8:38 am #9039
My liver enzymes were an issue long before the study came around. I'd tried allopurinol years ago, and actually had a primary who would put me on 300mg for a while, then when my liver enzymes got out of whack, take me off. So basically I was starting and stopping allopurinol about every six months, which felt like it was causing more attacks than it was helping! I do understand your skepticism. The study was blind, but I have a very involved GP who did her own blood work during the trial and found out which group I was in. Savient never told me. But my GP could tell by the bloodwork when I was getting the treatment and when I wasn't. She's the one I trust. And I have to say, if there are any negative side effects to having a zero uric acid level, I really didn't see them in the almost two years that I was there. But I agree, if this gets approved, especially if its fairly cost prohibitive, I'd be happy getting the IV every 8-10 weeks, whatever is required for maintenance!
I will definitely check out that study. I actually live half-way between Cincinnati and Dayton, and while I work in Cincinnati, it just seems easier to tell people that's where I live since it gives most people a sense of reference. I'm excited to check it out and see if I can qualify! Thanks for the info!
JohnSeptember 13, 2010 at 4:15 am #9952trevParticipant
Just to clarify John, from a post in the main site here- your liver is OK on severely lowered SUA under all conditions, but reacts badly to the treatments getting it lower, apart from the Krystexxa you trialled?September 13, 2010 at 7:22 am #9955
Just to recap a point. GP said that the FDA will rule on the uricase on September 14…that's TOMORROW so lets keep our eyes peeled.
Second point (I knew I couldn't stop at one…just like a can of beer.)
Liver enzyme abnormalities: Speaking generally, they have ranges clearly shown on printouts. Let's say normal is considered 1.0-4.0. Lots of uninformed doctors panic if they see a 4.6, even though disease conditions typically show 10, 20 or 100 times that amount. These printouts are often just a way for a lazy uninformed doctor to SOUND like he knows what he is talking about. “Aha your SGPT is eblevated” but then pin him down on what that means and you get a lot of hemming and hawing. What slightly elevated liver numbers usually means is that you are in the top or bottom 10% or some other arbitrary figure.September 13, 2010 at 9:05 am #9956
With Allopurinol and Uloric, by the time my SUA gets under control, my liver enzymes are far enough out of scale to worry the doctor's I've seen. Not to mean that they could all be overly cautious, but it has been three different GP's and two Rhumatologists who I've been through this with. I have yet to get the exact numbers, I really need to do that soon. Krystexxa was the only pro-active treatment I've ever had that didn't effect my liver at all, and I was on it for just over three years.
I'm keeping my fingers crossed that there's good news tomorrow! And that my insurance will cover it and it won't be cost prohibitive! I discussed your second point in my address to trev above. I've been remiss in not following up on my numbers. I'll see what I can do about that!
JohnSeptember 13, 2010 at 11:28 am #9959trevParticipant
I was interested in this as my Serum Bilirubin is slowly drifting up over the months of using AlloP. and now SulfinP. for 17 to 20.
A slow but steady drift slightly above optimal max [17 on the lab form] which maybe due to altered liver function.
30 is a working limit though ,to start worrying , and 50 when Jaundice would be apparent, from what I read on this. The fact that jaundice is mentioned on drugs side effects doesn't make be likely to happen early in, unless one is already compromised.
So that coincides with Zips comment about sloppy thinking on marginal results- but in an admittedly sensitive area.
The Docs DO know we only have ONE !!
PS : Regular monitoring of bloods is often mentioned on treatment guides, but not always stuck to, it seems. It matters.September 16, 2010 at 1:45 am #9986
On the uricase / pegloticase issue – Krystexxa has now been approved.September 16, 2010 at 9:58 am #9979azasadnyParticipant
I have a liver ailment known as “NASH” with elevated liver enzymes and I've had my liver enzymes under control by modifying my diet for a few years now. I'm going to see my liver specialist on the 23rd of this month and he'll check my liver enzymes (AST and ALT and GGTP) to be sure they aren't going up after starting on 100mg of Allopurinol each day. I'll post the results and hopefully, that will help you…
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