Is Cytoxan (still) the gold standard?

[csjknits]

Question for you experts out there--
I went to my rheumatologist today for follow up. (DX Apr 2015 with WG, lung and kidney involvement, in addition to sinus, ears, eyes, etc...).

At its highest, my creatinine was over 8. It's down now to just over 2.0 and appears to be holding steady, although I still have blood and protein in my urine. All other counts looks good. Lungs and eyes good. I never needed dialysis.

I asked him what happens should I be lucky enough to get this disease into remission and he said another year on Cytoxan.

I have been reading everyone's posts here and it seems like most doctors have moved away from the long term cytoxan. I do understand that I have significant kidney damage even if this gets into remission, and that maybe cytoxan IS the most appropriate for me.

My rheumatologist worked with Dr. Fauci in the 80s at NIH and was involved in the development of cytoxan as a treatment for WG--but it seems like newer research shows that other drugs work as well if not better.

Can you tell me about your experiences? Point me to research that I can read?

I am working with a nephrologist as well and I will ask him next time I see him. He is newer to the field and I'm curious what he thinks as well. The two (neph + rheum) do not work together (separate issue to be dealt with later:glare:).

[kaysee]

The newest treatment these days is rituxan or rituximab. It is a biologic and was first used for rhuematoid arthritis but has turned out to be very effective for WG. I had treatments in July and again in October and I am now in remission and on no meds for WG. Do a google seach and you will find all kinds of information on it. Search this forum as well as we have had lots of discussions about it since I joined a year ago. I too have kidney involvement and I'm being closely monitored by a nephrologist.

[Pete]

My rheumy at Cleveland Clinic took me off cytoxan after another doc had had me on it for 16 months. She said that it may have damaged my bone marrow. I had blood in the urine about two months prior to going off it. A cystoscopy showed no bladder anomalies, so a round of antibiotics cleared a significant UTI.

I was switched to methotrexate. I've been on it for almost three years with no major side effects. I had kidney involvement in a small flare that happened a couple months after I got off pred. Two infusions of rituxin along with going back to 60 mg of pred took care of that. I'm in remission now. I'll be on methotrexate for the foreseeable future. I'm down to 2.5 mg of pred, and will go to 2 mg next week.

Other maintenance drugs are Azathioprine (immuran) and cellcept. I can't take immuran as my TMPT test contraindicates it. Cellcept for me has not been discussed.

Some people are using rituxin as a maintenance therapy. They get periodic doses at six-month to annual intervals. My rheumy plans to use it only to knock down future flares.

My creatinine is stable at about 1.4. Everything else is normal.

Hope this is helpful.

[morningsunshine]

Hey there! First of all: kudos to you for taking an active interest in your treatment options and for seeking out research.

You asked for articles and so here is some recent research on Cytoxan and Rituximab:

Here's a study about Ritxuimab vs. Cyclophosphamide, finding that RTX is non-inferior to CTX for inducing remission: Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement (http://jasn.asnjournals.org/content/early/2014/11/06/ASN.2014010046.short)

Here's the latest study (November 2014) about using Rituximab vs. Azathioprine for maintenance, finding that RTX was better at sustaining remission: MMS: Error (http://www.nejm.org/doi/full/10.1056/nejmoa1404231)

Here's an excellent and comprehensive article about using Rituximab to treat WG. It includes what trials are going on and what the outcomes of various studies have been: SMW - Swiss Medical Weekly - The role of rituximab in the treatment of ANCA-associated vasculitides (AAV) (http://www.smw.ch/content/smw-2015-14103/)


From personal experience, I have achieved remission twice through RTX and am now getting a dose every 6 months, as in the Ritzarem trial (I'm not participating in the trial though). I've had a very positive experience with RTX, although it is expensive.

[annekat]

It's true that they are trying not to keep people on CTX for as long, not because it isn't effective, but because of risks of long term use. Your rheumy's plan to keep you on it for another year after you achieve remission seems out of date to me. If you are in remission, you should not need to be on CTX with its long term risks. The different courses of maintenance treatment that Pete mentions above would make more sense, and you might need a WG expert to determine the best course of action for you. Here are a couple of links that show lists of well known WG/vasculitis specialists. These docs may be willing to consult with your doc for free. Or they may be able to give you the names of specialists in your area. VF Medical Consultants (http://www.vasculitisfoundation.org/mcm_resources/medical-consultants/) and Vasculitis Journey of Hope - United States (http://www.vasculitispan.org/united-states) . Both of these sites are worth browsing for general info on WG and vasculitis, too.

As for CTX being the "gold standard", I don't know about that, but in some cases it may be the best option for initial treatment. It is said to work faster than RTX for most people, and would thus be appropriate for severe involvement in the lungs or kidneys that needs to be knocked down quickly. It could then be followed by RTX or, if in remission or close to it, one of the maintenance meds listed above. RTX is relatively new and there are variations in how different docs are administering it. It is done by infusion and is usually repeated over a period of time, and yes, it is very expensive. I did well on CTX, though I was probably on it longer than necessary, about a year. I haven't been declared in remission, but my disease activity is quite well stabilized at this point, and remission is a subjective term. I was put on methotrexate for maintenance and have had a couple of minor flares which were dealt with by dosage adjustments. It works well for me. I also take prednisone and Bactrim. I don't have kidney involvement. If that ever happens or I ever have a major flare, RTX might then be the best alternative for me, given the amount of CTX I've already taken in my lifetime. There is supposed to be a lifetime quota. I'll cross that bridge if I come to it.

Best of luck, and stick with the forum... you'll get lots of support and info, and little by little, a lot of useful knowledge will sink in. Keep us posted.

[csjknits]

Thanks everybody!
I've been reading the articles posted and continue to learn. It really seems like once I get this thing in remission that moving off cytoxan is the norm--and I would be very happy to be off it.
Right now I'm tapering off the Prednisone. Is nausea part of that? Lightheadedness? I'm reading all the prednisone threads now. The nephrologist also put me on an ACE inhibitor to protect my kidney--my suspicion is that that is causing the nausea, but he doesn't think so (it's a very low dose). There are so many pills, how does one know which is causing what symptoms??
This forum has been so incredibly helpful for me. Thanks again!

[annekat]

CTX made me feel a little nauseous, but I got over that side effect within maybe 3 weeks. I felt so crummy anyway, as a result of being so sick, that I was in bed most of the time, so it didn't matter as much and wasn't to the point of throwing up or anything. As for prednisone, I never associated the tapering of that with nausea, though I imagine it is possible, and everyone is different.

Your doc probably told you, but I'll say it anyway just in case, you need to drink LOTS of water with CTX and urinate frequently to avoid having it build up in your bladder, which can be a cause of bladder cancer somewhere down the line. I think I've only heard of this happening once on all the WG groups I'm on, but I don't know the true incidence, and it's wise to just drink a lot more water than you normally would, whenever you think of it. I've heard things like a couple of liters a day, but don't remember exactly.

I'm glad you are finding the forum to be so helpful. It's been indispensable to me since the first day I thought I might have WG, a little over 4 years ago.

[brew22]

Will you have to have more infusions of RTX or only is you flare?? thanks Susie

[marta]

Here's my take on the whole thing. It's from personal experience, articles I've read (a long time ago, when all of this was 'top of mind') and other's experiences.

There are two proven 'heavy hitters' we have in our arsenal to beat down a flare: CTX and RTX.

CTX is chemotherapy, which is designed to kill off T-cells, and B-cells, but also kills off any fast reproducing cells (including hair :( ). When metabolized in the body one of it's by-products is a known carcinogen that can cause bladder cancer if not continually flushed through with water. I was attached to my water bottle like a security blanket. I was on CTX for a year. In most studies the max should be 6 months.

RTX is a biologic, designed to target only B-cells. So it's basically B-cell ablation. Once they're ablated, they take between 6-8 months to start repopulating, but now you have the immune system of a newborn. So equally important to stay away from any infectious situations.

Some docs use RTX as a maintenance drug once remission is achieved, but my doc doesn't believe this to be prudent (and keep in mind it's a drug that's less than 10 years old, so everyone's a Maverick) as it's the only option I now have to beat down a flare. It's our Ace in the pocket. So we use Imuran (AZA) for maintenance, knowing that if the poo hits the fan again, I have RTX to take care of the problem. CTX is completely out of the question for me now... I've had my life's quota, and then some.

I hope my ramblings make some sense and help a little.

[Pete]

I'm in agreement, Marta. I'm on mtx for maintenance. Can't take immuran. Haven't discussed cellcept. My rheumy is keeping rtx in the holster to be used if I have a flare. It's been over 18 months since my last infusion. I've been in a stable remission for over a year and can do whatever I want (except keep up with you). I was on ctx for 16 months and have also used up my lifetime quota...

[csjknits]

Thank you, this post helps me to understand a bit better. I have a basic idea of T-cells but don't know much about B-cells. Now I have more to read!

My doctor is not in favor of RTX but I'm not certain if it's an overall feeling (like you mention above, the idea of the mavericks) or a sense that in my specific case it's not the best option. I am only now in the midst of my first round of treatment, and the plan as I understand it is that he would like me to stay on cytoxan a year after I achieve remission. I am gathering all of the articles I can find (I work at a university so I have really good access) and am trying to understand what the literature says regarding best practice/evidence-based practice. I don't want to stay on cytoxan if I don't have to.
It seems that the discussion is really in the risk-benefit category. I'm less likely to flare if I stay on Cytoxan, but I have to deal with the long term effects of ctx. Flares may be more common on other maintenance drugs, but the risks from the drugs are lower. Oh the choices!:cool1:

[annekat]

Me, too, on the lifetime quota of CTX, I think. I use MTX for maintenance and have knocked down mild to moderate flares by increasing the dose of it and the pred. But for a big flare, I'd probably need RTX. I'm curious, though, Marta and Pete, does using RTX for maintenance somehow make it less effective in the case of a big flare? And does that question even make sense, since it should theoretically prevent the flare in the first place? I don't know to what extent its dosage, or frequency of infusions, might then be increased in the case of a big flare, or if there's any reason that wouldn't work... but then, I know nothing, and realize they don't yet have all the answers.

In any case, though I wish I'd gotten less CTX, it did work, and the MTX is working, and I'm happy, so far, to not have to face the possibility of RTX at this time. Saving it for the big one seems like a good plan to me.

[Pete]

Me, too, on the lifetime quota of CTX, I think. I use MTX for maintenance and have knocked down mild to moderate flares by increasing the dose of it and the pred. But for a big flare, I'd probably need RTX. I'm curious, though, Marta and Pete, does using RTX for maintenance somehow make it less effective in the case of a big flare? And does that question even make sense, since it should theoretically prevent the flare in the first place? I don't know to what extent its dosage, or frequency of infusions, might then be increased in the case of a big flare, or if there's any reason that wouldn't work... but then, I know nothing, and realize they don't yet have all the answers.

In any case, though I wish I'd gotten less CTX, it did work, and the MTX is working, and I'm happy, so far, to not have to face the possibility of RTX at this time. Saving it for the big one seems like a good plan to me.

I dunno. I hope there's an effective "big gun" when I need one.

[annekat]

I dunno. I hope there's an effective "big gun" when I need one. Well, you were just on RTX for a short time, right, when your kidneys started to show involvement, and it worked, right? So if you have a big flare at some point, I would think RTX would again be the appropriate "big gun". Of course, I hope that never happens, but if it does, maybe by that time they will know a lot more and maybe there'll even be a better "big gun"!

I'm just a bit confused about this business of "saving" RTX for a big flare, for those of us who shouldn't take more CTX, and not understanding why using it for maintenance in the meantime would rule out using it for the big flare. If that's what's being implied. Just being analytical... it's not that I have any desire to use it when other things are working fine. I'd rather avoid all the hassle and whatever expense I'd incur in getting the infusions, unless they are the only option at some point. The pills we take may not be perfect or the most pleasant, but they sure are a lot easier to get ahold of and use.

[Pete]

I'm just a bit confused about this business of "saving" RTX for a big flare, for those of us who shouldn't take more CTX, and not understanding why using it for maintenance in the meantime would rule out using it for the big flare. If that's what's being implied. Just being analytical... it's not that I have any desire to use it when other things are working fine. I'd rather avoid all the hassle and whatever expense I'd incur in getting the infusions, unless they are the only option at some point. The pills we take may not be perfect or the most pleasant, but they sure are a lot easier to get ahold of and use.

I'm reading between the lines a bit here, but in my conversations with Dr Villa Forte, I think there is some research behind the "big gun" theory.

[annekat]

I'm reading between the lines a bit here, but in my conversations with Dr Villa Forte, I think there is some research behind the "big gun" theory. So it sounds sort of like saving it until it's really needed makes it more of a "big gun", somehow. Maybe Marta will have some insights, too. I'm certainly content to wait. Good to know it is there, as it may well be the best and only option at some point.

[drz]

My doctors are on the same page for the reasons outlined below. RTX is my plan for a serious flare but otherwise it is AZA for maintenance till they find a cure for Wegs or better treatment alternative.


Here's my take on the whole thing. It's from personal experience, articles I've read (a long time ago, when all of this was 'top of mind') and other's experiences.

There are two proven 'heavy hitters' we have in our arsenal to beat down a flare: CTX and RTX.

CTX is chemotherapy, which is designed to kill off T-cells, and B-cells, but also kills off any fast reproducing cells (including hair :( ). When metabolized in the body one of it's by-products is a known carcinogen that can cause bladder cancer if not continually flushed through with water. I was attached to my water bottle like a security blanket. I was on CTX for a year. In most studies the max should be 6 months.

RTX is a biologic, designed to target only B-cells. So it's basically B-cell ablation. Once they're ablated, they take between 6-8 months to start repopulating, but now you have the immune system of a newborn. So equally important to stay away from any infectious situations.

Some docs use RTX as a maintenance drug once remission is achieved, but my doc doesn't believe this to be prudent (and keep in mind it's a drug that's less than 10 years old, so everyone's a Maverick) as it's the only option I now have to beat down a flare. It's our Ace in the pocket. So we use Imuran (AZA) for maintenance, knowing that if the poo hits the fan again, I have RTX to take care of the problem. CTX is completely out of the question for me now... I've had my life's quota, and then some.

I hope my ramblings make some sense and help a little.

[MikeG-2012]

and the plan as I understand it is that he would like me to stay on cytoxan a year after I achieve remission.

From what I gathered from all the sessions at the Symposium last week, a year on Cytoxin is NOT the standard any more--six months tops! The preferred big gun for this disease is Rituxan.

I would really recommend having your doc consult with one of the leading wegs specialists. I know if I were asked to go back on cytoxin again, I'd definitely get a second opinion. That long of a dose can wreak havoc on your body and predispose you to bladder cancer.

[csjknits]

Glad to have news to post to this thread. I'm now about four months post hospitalization for GPA. I hesitate to say first "attack" because I suspect I've had them before but didn't know that's what was happening. My creatinine is down to 1.2 and my gfr is 55, just about normal again on both counts. I feel pretty good. I'm down to 10 mg pred daily and will keep decreasing.
I've changed doctors and now the person I've put in charge of my care is my nephrologist. I was not comfortable with the rheumatologist's plan for cytoxan long term, nor was I enjoying the rapid taper of prednisone (to say the least).
My new plan is to stay on the cytoxan for about another month, just to make sure things stabilize, and then to try Imuran, with Rtx as the next step if Imuran does not work.
In the meantime, I have dosing questions regarding cytoxan. Is there published info anywhere about what dosing should be, or a general sense of how much people take? I know it's based on body weight. I'm on 250mg a day and that seems like a lot.... I'm a little overweight but not much. this is the same dose I've been on for four months.

[annekat]

Sounds like you have a good handle on things and I agree with your switching docs away from one who'd have you on long term CTX. I still feel, though, that CTX is a valuable drug that may be the best initial choice in some cases, as long as time on it is limited. As for dosage per weight, that seems a little harder to find on the web than when I was dx'ed in 2011, but what I have found is 2mg per kg per day. 100 lbs is about 45kg, so a person of that weight would take 90mg/CTX/day according to that formula. And a 200lb person would take 180mg., and so on. These would likely be rounded up to 100 and 200, respectively, especially considering that a person would likely be a few pounds over those weights. In my case, the weight formula said I should take 125mg., but the doc had me on 100mg most of the time. I did get better on that slightly reduced amount. But he had me on it too long, as I may have said above... around a year, with a reduction to 50mg/day toward the end as he transitioned me to MTX and overlapped the two for awhile. Though there are things about my treatment I disagree with in retrospect, I have done well and am presently in good shape, though still on meds. I hope this helps with the dosage question.

[csjknits]

Thanks, Anne. I don't weigh anywhere near 200 pounds and I'm on 250 mg. Time to ask more re: dosing. Even if I'm coming off this drug soon, I would like to be on the minimal amount necessary to stay well.

[annekat]

Thanks, Anne. I don't weigh anywhere near 200 pounds and I'm on 250 mg. Time to ask more re: dosing. Even if I'm coming off this drug soon, I would like to be on the minimal amount necessary to stay well. Well, I hope my info is correct, but I think it is. Too bad we have to struggle with docs on these things, and check up on them all the time... I agree that if you are considerably less than 200lbs, 250mg. of CTX is too much, not only because of the inherent long term risks, but because of the side effects. Good luck convincing your doc, and with your continued recovery.

[annekat]

Here is a link to a nephrology page which confirms the CTX dosage by weight that I gave. You have to scroll down to Induction Therapy, and it is in the first paragraph there. http://jasn.asnjournals.org/content/13/7/1953.full You might want to find other resources to back you up. Or your doc might want to confer with one of the experts listed here: VF Medical Consultants (http://www.vasculitisfoundation.org/mcm_resources/medical-consultants/) . Good luck!

[csjknits]

Ok, I made a mistake. I double checked my prescription--I'm only on 100mg a day. Phew!!! I have no idea where I got 250 from. I'll blame the prednisone and its effects on my brain. :rolleyes1: Still, time to get off this drug.

[annekat]

Forgot to include a link above. It's there now. I do that all the time!

[annekat]

Ok, I made a mistake. I double checked my prescription--I'm only on 100mg a day. Phew!!! I have no idea where I got 250 from. I'll blame the prednisone and its effects on my brain. :rolleyes1: Still, time to get off this drug. Oh, well that's a lot better! You might make sure it's even enough, though as I said, I did well on a bit less than the formula called for. Don't worry too much if you've only been on it four months. Just try not to go longer than 6. Different literature says different things. But true, the lower the effective dose and the less time, the better. Yes, the pred, the disease itself, and the CTX all mess with our brains.

[Birdie]

Ok, I made a mistake. I double checked my prescription--I'm only on 100mg a day. Phew!!! I have no idea where I got 250 from. I'll blame the prednisone and its effects on my brain. :rolleyes1: Still, time to get off this drug.

At 175lbs I did 150mg of cytoxin for a year and a half. At the time I had so many issues there was no way of knowing what issue came from where. My rheumatologist started off claiming the cytoxin would be short lived, maybe a couple months. I didn't respond well and stayed on it for so long out of fear of nothing else working at all. I switched to 150mg azathioprine in desperation due to cytoxin side effects. It was like suddenly coming out of a very long tunnel into the light of day. I don't know what is best for you, but holy cow... for me the change was a major event with no unfortunate result.

Also, you can safetly blame prednisone for anything, even earthquakes. I did 80mg for nearly a year. Every time the dose was reduced I was in the hospital ER within days. Keep your head clear, be involved, take care.

Good luck,
Gary

[kaysee]

Also, you can safetly blame prednisone for anything, even earthquakes.
Good luck,
Gary

Love your sense of hummor Gary. Your posts make me smile. :biggrin1:

[Birdie]

Love your sense of hummor Gary. Your posts make me smile. :biggrin1:

Thanks, I have plenty to spare.

When you're sick it's laugh or cry. I suggest laughing, it's much better therapy and helps keep your head clear to evaluate whatever comes up.