Rituxan - didn't work well for MPA

[mrtmeo]

My mom had one iv dose 700mg of cyclophosphamide and then, 4 weekly infusions of Rituximab.
She is almost at the 4 month mark from her first rtx infusion and has not reached remission.
Her kidney function has not improved and she is dumping too much protein.
She also, has an internal bleed which is most likely due to the vasculitis and has had this since diagnosis.
She has lung nodules, ground-glass opacities in the lungs, 4th stage renal failure with high proteinuria and hematuria, feet and abdomen swelling, eye pain, livedo reticularis, cough (developed during treatments), fatigue, weakness, SOB, weight loss and neuralgia in bottoms of feet.

During and after the treatments, it was like she was in a constant flare.
She is still anca positive with high mpo antibodies.

Her nephrologist just put her on Mofetil because she didn't tolerate the Imuran and hoping this will help put her into remission.
I think she would have done better on the cyclophosphamide for treatment instead.
I have not found anyone that only had rtx for MPA, so I wanted to present my mom's case to anyone looking for a treatment.

The only improvements have been no more eye pain or feet swelling.
She is now on 8mg prednisone and 750mg mofetil per day.

[annekat]

I'm sorry your mom hasn't done better. I know a lot of the literature for WG/GPA says remission can be expected in 3 months, but I think that is not really typical, from reading this forum. I don't know about for MPA. I also hear RTX works better for some than others, and may take longer for some than others to get the same result. Has she had another infusion, or are they talking about giving her one? I wonder, too, whether CTX might have worked faster and better for her. It worked great for me, but my problems were not as severe, and I don't have MPA. It is disappointing to read the list of your mom's symptoms and lab results and to hear that they haven't improved. I hope something or someone is able to turn things around for her.

[mrtmeo]

I'm sorry your mom hasn't done better. I know a lot of the literature for WG/GPA says remission can be expected in 3 months, but I think that is not really typical, from reading this forum. I don't know about for MPA. I also hear RTX works better for some than others, and may take longer for some than others to get the same result. Has she had another infusion, or are they talking about giving her one? I wonder, too, whether CTX might have worked faster and better for her. It worked great for me, but my problems were not as severe, and I don't have MPA. It is disappointing to read the list of your mom's symptoms and lab results and to hear that they haven't improved. I hope something or someone is able to turn things around for her.

Hi Anne,
Yes, the usual time frame from the studies for remission is 3-6 months and the studies don't list the patients treated and their individual results.
Some have really good results with cyc and some don't, but I have only seen people with MPA have good results with cyc and not rtx.
I see alot of wegs folks not doing well with the cyc but do better on the rtx.
However, they all had cyc first and then rtx, so not sure if it is the combo or not for weg's.

If I remember correctly, Kaysee had only rtx and it worked well until her 4th month from the first infusion and she had to have another.
I hope she gets into remission soon.

I am sure praying that the Mofetil puts her into remission and stops the kidney and lung attacks.

[annekat]

I've had the feeling most WG people have done well with CTX but RTX has become preferable for the reasons of long term toxicity with CTX. I still hear of people being put on CTX initially, perhaps due to it's quicker working time, cost, and ease of use, if their symptoms are fairly severe. A few people are initially put on MTX or one of the other "maintenance" meds, along with pred, of course, if their involvement is fairly light. Many of us had CTX because RTX was not widely available or easily approved at the time we were initially treated. I've seen a lot of variability in how well people with WG do on RTX, although most seem to be quite happy with it. However, many seem to need repeat treatments with it in order to continue to do well. The lucky ones go into at least a medicated remission for a long time and don't need more RTX or CTX but most of these still need a maintenance med and pred for quite awhile.

Your mom may not go into what her docs would call a solid remission, as many of us haven't, and the use of the word "remission" may vary from one doc to another. But you should at least expect her to show a lot more improvement than she has, to the point where even if some symptoms remain, her lab work looks a lot better, showing that the disease has been slowed way down or stopped in its tracks. I really hope this for her. Then, if she has small or more severe relapses and needs more RTX, or CTX if that should be decided, or an adjustment in her maintenance meds, it would be quite normal and what many of us have experienced. That's why I say many of us have not really reached remission, because we end up having these small flares when we try to taper off the meds, typically the pred. But our overall quality of life has improved vastly due to the successful original treatment. It sounds like your mom could use some opinions from other specialists as to to why she is not responding to treatment and what needs to be tried next. I wish we here on the forum had more answers.

[Rose]

I was told when first diagnosed that cyclophosphamide had to be used because of my kidney involvement. My pulmonologist had hoped to avoid it and just treat me with methotrexate but then my blood word showed that my kidney function was rapidly deteriorating and a biopsy confirmed WG She said that because of kidney involvement they had to bring out the big guns. I was referred to a nephrologist who took over my case and was treated with IV cyclophosphamide and went into remission in about 4 months

I am surprised also that cyclophosphamide has not been tried. My understanding is that cyclophosphamide gets you into remission and methorexate, imuram and cellcept maintain remission.

Rose

And I also had pulsed Solumedrol x 3 days before commencing cyclophosphamide. They really threw everything at me but it worked. I think you need another opinion

I see it has been tried but just 700mg. I think an IV protocol of cyclophosphamide is worth a try to get her into remission or even daily tabs since the Rituximab hasn't worked. I was also on high oral doses of pred which were reduced only once I started to respond to treatment. 8mgs seems a very low dose for someone who has not responded to treatment.

[mrtmeo]

I was told when first diagnosed that cyclophosphamide had to be used because of my kidney involvement. My pulmonologist had hoped to avoid it and just treat me with methotrexate but then my blood word showed that my kidney function was rapidly deteriorating and a biopsy confirmed WG She said that because of kidney involvement they had to bring out the big guns. I was referred to a nephrologist who took over my case and was treated with IV cyclophosphamide and went into remission in about 4 months

I am surprised also that cyclophosphamide has not been tried. My understanding is that cyclophosphamide gets you into remission and methorexate, imuram and cellcept maintain remission.

Rose

And I also had pulsed Solumedrol x 3 days before commencing cyclophosphamide. They really threw everything at me but it worked. I think you need another opinion

I see it has been tried but just 700mg. I think an IV protocol of cyclophosphamide is worth a try to get her into remission or even daily tabs since the Rituximab hasn't worked. I was also on high oral doses of pred which were reduced only once I started to respond to treatment. 8mgs seems a very low dose for someone who has not responded to treatment.

Hi Rose,
My mom was not doing well with the prednisone and it wasn't doing anything for her symptoms but make them worse.
She was given some salumedrol the same day as the cytoxan.
Her biggest problem is the protein dumping in her urine and the ARB(angiostensin renin blocker) is not helping much.
She still has blood in her urine also, indicating the disease is not stopped yet.
I don't know if the Dr will let her get cytoxan because her creatinine has been stable at 2 and hasn't gotten worse the past few weeks.

Because of my mom's lungs, she wouldn't be able to go thru surgery if she needed a kidney transplant and she could never handle dialysis.
At her worst, her creatinine was 3.3 and at its best was 1.8.
Her Neph said he could get her kidney function back to at least 1.2 and would be disappointed if it stayed above 1.5.
There is a kid that has his video on the vasculitis foundation's website that had a creatinine of 9 at his worst and it 1.2 four years later when he did the video. He has MPA and had cytoxan, plasma exchange and dialysis with Imuran for 2 years maintenance.

I wish they could use plasma exchange for people with creatinine of <5.6, so some can have a better chance at recovering their kidney function.

My mom also, has some kind of internal bleed that the treatments have failed to slow down or stop, so she needs Epogen shots and lots of protein to get her hemoglobin up.

[mrtmeo]

Rose,
If I forgot to thank you for your valuable info on the mofetil and Imuran, thank you!

[Wegetarian]

I see alot of wegs folks not doing well with the cyc but do better on the rtx.
However, they all had cyc first and then rtx, so not sure if it is the combo or not for weg's.

My understanding is about the same as Rose mentioned, that if you have a serious outbreak of Weg's then CYC is preferred as it is the fastest way to stop the disease. When I was DX'd last year I only had Weg's in my nose, and was treated with just prednisone at first, and a few weeks later started on MTX. However when I got a flare this summer and my lungs and kidney were attacked they wanted to use CYC IV's. I was still on 25mg of MTX/week which I stopped as we started using the cyclos.

There are some studies on the effectivenes on MTX compared to CYC. Here is one, not too recent, but dunno if much has changed as these are old drugs.
http://www.medscape.org/viewarticle/712891_5

[mrtmeo]

My understanding is about the same as Rose mentioned, that if you have a serious outbreak of Weg's then CYC is preferred as it is the fastest way to stop the disease. When I was DX'd last year I only had Weg's in my nose, and was treated with just prednisone at first, and a few weeks later started on MTX. However when I got a flare this summer and my lungs and kidney were attacked they wanted to use CYC IV's. I was still on 25mg of MTX/week which I stopped as we started using the cyclos.

There are some studies on the effectivenes on MTX compared to CYC. Here is one, not too recent, but dunno if much has changed as these are old drugs.
http://www.medscape.org/viewarticle/712891_5

Hi Weget,
From what I have read in the literature, GPA and MPA can start out mild, meaning it doesn't effect the lungs or kidneys.
This is when they like to use the milder drugs.
However, even when treated, those who flare (that have kidney involvement), usually end up with either kidney attacks around the 2-3 year mark.
This is not to scare people into thinking they are going to lose kidney function, but to keep people on the alert that the possibility of kidney involvement can happen fast, if it does and to be aware by checking cmp and urinalysis or urine dipsticks just incase.

Many never have lung or kidney involvement, thank God.
If the creatinine is >5.6 they will use plasma exchange with cytoxan, but you can't get the plasma exchange unless your creatinine is that high.
I would really have liked to have the option of plasma phoresis to help my mom's kidneys and lungs, but her creatinine didn't qualify.
There is a study underway plexivas to see if it would be good for those with less severe kidney involvement.

How many months were u on the cytoxan?

[annekat]

Hi Weget,
From what I have read in the literature, GPA and MPA can start out mild, meaning it doesn't effect the lungs or kidneys.
This is when they like to use the milder drugs.
However, even when treated, those who flare, usually end up with either kidney attacks around the 2-3 year mark.

I go more by what I read here on the forum than by "literature", since I know the latter can be all over the place, depending on where you read, can be based on studies which may not represent an accurate cross section of the WG population, and can be overly alarmist. My sense is not that people with light involvement who flare will "usually" end up with lung or kidney problems at the 2-3 year mark. Some will. Many, or I would say most, will not. Or if they do, it may take a lot longer than 2-3 years. Everyone's case is different. If most "mild" WG sufferers did follow this scenario, I think we'd hearing about it a lot more than we have. This is not to overlook the unpredictability of WG or to hide from the fact that anything can happen at any time.