Building Resistance to Rituxan

[morningsunshine]

Hi everyone,
Has anyone built up a resistance to RTX?

I?ve been on it for 4.5 years now (2000mg every 6 months) and I?ve noticed GPA symptoms come back towards the end of the 6 month intervals. My doctor mentioned something offhand about building antibodies against Rituximab and when I did research on google scholar, it seems this is the case. There is even a blood test for it called ?HACA? which I will ask for the next time I see my doctor. Have you gotten this test?

Has anyone here built up a resistance to RTX? Did you then switch to cytoxan? I?m scared that I?ll have to switch medications because RTX has worked so well for me.

Any insights would be appreciated.

Many thanks!

[whatthewhat]

Alysia and others might have better insight than I. All I know is on FB I had chatted with "Lennie Saurkraut" (did I get that right?) about this same topic, since he and a woman on the WG FB group had been regularly taking Rtx since before it was FDA approved for WG. So, a long time! I am interested in this topic because in the world of pediatric-onset WG, the majority of Drs prescribe Rtx every six months. If you consider that kids are most often get sick at the onset of puberty that would mean several decades of the every-six-months protocol. Basically most indications are that most people will not build up immunity to it - but there is some indication that some people do in fact build up the immunity. In our daughter's case in consultation with her rheumy and his okay, she only receives Rtx as needed, and gets her labs done frequently to monitor that need.

Another concern, at least for pediatrics, is wiping out the immune system so much that the child becomes dependent on IViG and we want to forestall that. Not to mention that the biggest lethality for Weggies comes from infection once the diagnosis period has passed. We wanted to keep her immune system as strong as possible while still hobbling it.

[morningsunshine]

Hi whatthewhat!
I?m sorry to hear that your daughter has this disease, but she?s lucky to have you doing research and keeping on top of it!

It?s definitely encouraging to hear that some people have manage to be on RTX long-term. I?m keeping my fingers crossed that these symptoms are not WG-related. In the meantime, I?m asking my ENT on Thursday for a HACA and a CD-19 blood test. I?m only 30, so I would potentially have decades of every-six-months RTX ahead of me, granted it keeps working.

One other side note: if RTX ever becomes too expensive, call the RA Rituximab copay card hotline?they have been wonderfully helpful.

In terms of IVIG, I?ve have two maximum-strength doses of it and while the infusions themselves didn?t feel great, the next day I felt like a superhero. I have another dose coming up and am looking forward to that afterglow. Still I hope you can keep your daughter?s IGG levels up and her immune system as intact as possible. Keeping my fingers crossed for all of us Weggies!

[Alysia]

I will share what I understood from my WG dr. over the years. Unlike meds which stop working after some time of use, rtx keeps its efficiency over the years. My WG dr. Has experience with it with rheumatic patients more then 10 years.

The problem (which I think is not only rtx related but all immune suppresed meds related) is that over the years the immune system becomes more weak, down to a point where it cant fight infections. For example my IgG levels dropped down significantly from 2013 (when I started rtx) until today. Its getting closer to the "red" line. So my WG dr. and I decided to try to go for my next rtx in an interval of 7 months instead of 6 months. (Below the normal might demand an Igiv).

And thats the second issue, which is not clear enough - the question of how often is it right to go for rtx IV. Until our last meeting, my wg dr. allways said that it is better to go for rtx every 6 months, even without WG symptoms, in order to "reset" the immune system and "make" it "forget" to attack itself. Also in order to prevent flares with all their damages.

BUT, in my last meeting with him, he said that a NEW research compared those who went to rtx every 6 months to those who went according to WG activity and found out that both groups did well, although the second group recieved less rtx. I didnt find the article yet.

I asked him about damages from the wg activity and he said that it is also a point to consider.

It sounds like we need to find a very delicate balance between holding the WG by rtx and allowing the immune system to be high enough to fight infections.

Of course, when one is not in remission, when wg is flaring or smoldering, one should get rtx.

I hope I wrote it clear enough. If I will find the new research I will attach it.

[drz]

I know my treating doctors and my consultant at Mayo both said they would only give me RTX again if it was really necessary since in their experience it can tend to become less effective with frequent use. Of course for many routine maintenance treatments are necessary and this is the only good option for them. Hopefully new treatments will be discovered that become even more effective.

[Alysia]

I found this article:

https://ancavasculitisnews.com/2018/10/15/tailored-rituxan-regimen-for-anca-vasculitis-patients-as-effective-possibly-safer-than-fixed-schedule-treatment-expert-comments/?amp

[Pete]

This looks promising. I’m coming up on 13 months since my last infusion with no known ill effects. Next dose is October 30.

[Pete]

Infusion #13 went well yesterday at CC. I also had a good checkup with Dr Villa Forte. My labs have been normal and stable. We got out of the infusion suite just before 5:00. CC is near Cleveland’s Little Italy neighborhood, so we found a nice restaurant (Angelo’s Nida Italia on Mayfield Rd) for dinner and to wait for rush hour to clear out.

It was a long day (13 hours from the time we left home until our return), and the pre-infusion drug cocktail has me feeling tired, but I did not sleep well. Today will be a pajama day, and I expect to be “normal” tomorrow.

[[email protected]]

Replying to this thread with some resources. It seems the newest way to treat us may be to use Rituxan every 4 months following initial induction.
Link to Nov 2018 paper by UCLA Group: https://www.researchgate.net/publication/329112372_Antineutrophil_cytoplasmic_antibody-associated_vasculitis_update_on_molecular_pathogen esis_diagnosis_and_treatment
Link to 2017 paper - RITAZAREM study - with this as a plan: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341185/;
Link to another published in 2014: https://cjasn.asnjournals.org/content/9/4/736;
yet another from 2015: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322237 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322237/)
As a very personal decision I would refuse any further treatment with Cytoxan, Imuran, CellCept or Prednisone. Although earlier treatment with each of these drugs may have saved my life many years ago when Rituxan wasn’t available, I now judge each of them to have caused unacceptable side effects & complications of underlying disease. Also I now refuse all medically prescribed potentially addictive oral pain or sedative medications.
Rituxan every 4 months has revolutionized treatment in my humble opinion & both my son & myself have decided to stick with this. We have each had 6 Rituxan “induction” infusions separated by over a year due to inadequate medical follow up (difficult to get in Nashville, TN - necessitates returning to Los Angeles for care) & now will receive yet another induction followed by the latest recommendations for 4 month follow up in first RITAZAREM study above.
Hope this helps! Feel free to contact me!

[Bing505z]

Replying to this thread with some resources. It seems the newest way to treat us may be to use Rituxan every 4 months following initial induction.
Link to Nov 2018 paper by UCLA Group: https://www.researchgate.net/publication/329112372_Antineutrophil_cytoplasmic_antibody-associated_vasculitis_update_on_molecular_pathogen esis_diagnosis_and_treatment
Link to 2017 paper - RITAZAREM study - with this as a plan: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341185/;
Link to another published in 2014: https://cjasn.asnjournals.org/content/9/4/736;
yet another from 2015: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322237 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322237/)
As a very personal decision I would refuse any further treatment with Cytoxan, Imuran, CellCept or Prednisone. Although earlier treatment with each of these drugs may have saved my life many years ago when Rituxan wasn’t available, I now judge each of them to have caused unacceptable side effects & complications of underlying disease. Also I now refuse all medically prescribed potentially addictive oral pain or sedative medications.
Rituxan every 4 months has revolutionized treatment in my humble opinion & both my son & myself have decided to stick with this. We have each had 6 Rituxan “induction” infusions separated by over a year due to inadequate medical follow up (difficult to get in Nashville, TN - necessitates returning to Los Angeles for care) & now will receive yet another induction followed by the latest recommendations for 4 month follow up in first RITAZAREM study above.
Hope this helps! Feel free to contact me!


Thanks for the links, and I agree with you and I do not take maintenance drugs. I stay clear of these drugs and will only receive Rituxan based on how I feel. Cheers!

[BenHornsby]

Hay,

i started rtx every 6 months and about 2 years ago started suffering at 4.5 to 5 months and got put on 4 month infusions, 8 months ago I stared suffering at 3 to 3.5 months and now staying on 4 month infusions x2 two weeks apart and 3 months ago now take methotrexate weekly to try and level things out some more.

6 years in and still finding out what works, I know I work too hard in a stressful environment IT environment, but love my job.

;-)

Sent from my SM-G930F using Tapatalk

[[email protected]]

That’s quite a history Ben! ‘I’m sorry you had to go through all that to discover what worked for you.
Although both my son and Iwere treated with Cyclophosphamide, Methotrexate, high dose prednisone and more over the 20 years since our diagnosis, Rituxan has been the drug of choice since to avoid the physiological damage from the other drugs.
we’ll see what the Rituxan effects are this time. Since I’m in very bad shape and it takes at least 5 weeks to work, no telling right now what the future holds. If the beta blockers don’t work on my Malignant Hypertension or the CT Angiogram shows anything today things could change.
This situation is crazy now as my son needs Rituxan but has lost his insurance coverage for any out f network coverage due to across the board policy changes even with his best possible instance coverage! He has serious GI involvement. So a big stressful x country move has now been added to the mix.
Best of luck Ben in the future for your successful treatment. Systemic Vasculitis is not an easy disease!

[Alysia]

That’s quite a history Ben! ‘I’m sorry you had to go through all that to discover what worked for you.
Although both my son and Iwere treated with Cyclophosphamide, Methotrexate, high dose prednisone and more over the 20 years since our diagnosis, Rituxan has been the drug of choice since to avoid the physiological damage from the other drugs.
we’ll see what the Rituxan effects are this time. Since I’m in very bad shape and it takes at least 5 weeks to work, no telling right now what the future holds. If the beta blockers don’t work on my Malignant Hypertension or the CT Angiogram shows anything today things could change.
This situation is crazy now as my son needs Rituxan but has lost his insurance coverage for any out f network coverage due to across the board policy changes even with his best possible instance coverage! He has serious GI involvement. So a big stressful x country move has now been added to the mix.
Best of luck Ben in the future for your successful treatment. Systemic Vasculitis is not an easy disease!

Sorry your son have lost his insurance. Please check in this link if there is a way to help him get rtx

https://www.wegeners-granulomatosis.com/forum/threads/5640-Rtx-co-pay-card

I also tag whatthewhat - I remember that years ago she posted something about rtx for those who can't pay for it... I hope I remember correctly.

[[email protected]]

Thanks for your concern about my son’s Rituxan. He has great private insurance which covers all his medical but it’s in California. All medical insurance has cut out out-of-network coverage, with exception of emergencies. We may be able to get the it covered as an emergency.....

[whatthewhat]

Thanks for tagging me back in the thread, Alysia. I have heard that the Healthwell Foundation (pediatric wing of Genentech) no longer gives grants to Pediatric WG patients for Rituxan. :-(

[Eduardo]

In agreement what Alysia said, my WG dr. in 2014, my first flare, decided to use RTX only after the symptons begins. I received 3 RTX infusion until now, two years of interval from one to another. He uses this medical procedure trying to avoid hipogamaglobulinemy, IgG falls. In al three times the WG didn't make damage, only initial and inespecific symptons, never lungs or kidneys. To me it is working, thank godness. When you find the research, please, send it for us, Alysia.

[Alysia]

In agreement what Alysia said, my WG dr. in 2014, my first flare, decided to use RTX only after the symptons begins. I received 3 RTX infusion until now, two years of interval from one to another. He uses this medical procedure trying to avoid hipogamaglobulinemy, IgG falls. In al three times the WG didn't make damage, only initial and inespecific symptons, never lungs or kidneys. To me it is working, thank godness. When you find the research, please, send it for us, Alysia.

I posted it also above.
Here it is

https://ancavasculitisnews.com/2018/10/15/tailored-rituxan-regimen-for-anca-vasculitis-patients-as-effective-possibly-safer-than-fixed-schedule-treatment-expert-comments/?amp

[Eduardo]

Thanks! Did you see, Loic Guillevin's research? My Doc. follows French line. Thank once more.

[[email protected]]

Thanks! Did you see, Loic Guillevin's research? My Doc. follows French line. Thank once more.
If I’m reading the 2014 study for the French Vasculitis Study Group Dr. Guillevin appears to recommend RTX. Will look into his other research. Thanks.

[freakyschizogirl]

I may be late to this party but I am in this boat right now.
I've had RTX for at least 7 if not 8 years in various protocols under Addenbrookes. Last June I have the new generic brand of RTX called Truxima. I reacted to it and felt no better following the infusion. I went back in October and had another armful of RTX but the old MabThera RTX. I then reacted to this. Again I didn't find it made me feel much better so had one last go this past January and reacted to it again.
I'm still having symptoms but no active signs of disease in my sinuses or my bloods but I feel like I'm about to flare.
Prof Jayne is hoping to get me on the Orencia trial once the RTX is out of my system so I am holding on for that. The plan is to get me off RTX for a few years and hopefully I will then be able to go back to it.

[drz]

I may be late to this party but I am in this boat right now.
I've had RTX for at least 7 if not 8 years in various protocols under Addenbrookes. Last June I have the new generic brand of RTX called Truxima. I reacted to it and felt no better following the infusion. I went back in October and had another armful of RTX but the old MabThera RTX. I then reacted to this. Again I didn't find it made me feel much better so had one last go this past January and reacted to it again.
I'm still having symptoms but no active signs of disease in my sinuses or my bloods but I feel like I'm about to flare.
Prof Jayne is hoping to get me on the Orencia trial once the RTX is out of my system so I am holding on for that. The plan is to get me off RTX for a few years and hopefully I will then be able to go back to it.

I love the quote from Jack. I will always treasure his advice and support he gave me when I first started on this forum.

[freakyschizogirl]

Hi drz. Ita amazing how even now Jack is often thought of and spoken of. He will always be remembered fondly by me as he was the main reason I went to Addenbrookes and its been the best thing I've done for myself and the disease.