Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
Discuss the article on the Forums.

My ritux experience so far

Discussion in 'Rituximab: News and Research' started by Benji, Aug 4, 2017.

  1. Benji

    Benji Norwegian

    Messages:
    46
    Likes:
    149
    I am confused after 9 months.


    I started off last september/october, with the two initial doses. Both the infusions went fine, no allergic reactions, and no direct worsening. But some worsening from after the second infusion. A little harder to do what I normally do. But still I managed without having do to changes in my life. After two months of that, I find myself much better. So wonderful, being an early responder. Christmas was full of optimism, from now an, it was regaining life I saw ahead.


    Third infusion in January went just as well at the preceding ones. But, the good times slowly came to and end, gradually, over some weeks I deteriorated. So I had som difficult times until it was time for my 4'th infusion, three months after the third. I had read some views like "it's probably better to let the body restituate before having an another dose" and found it sensible. So I postponed the 4'th. I was having a hard time until four months after the third infusion. Worse and worse. But suddenly, from worsening, I got much better very quickly. From worse than ever, to much better, in a week. So I had my response back. And so I thought it was time for another infusion. So I did, and the same happened, gradually worsening, and now it has been a bit over months, no improvement so far.


    I thought maybe the long setbacks were due to the premedication, which is 125mg solumedrol IV. For the last infusion, I asked to have half the dose, and I got 75mg IV. But still , after more than 2 months, I am still no good, so ??
    I'm suspected the cortison was the reason, because Fluge and Mella gives premedication only 8mg dexametason orally, maybe they have good reason to minimize the steroids. Some research from Canada also suggests some of us are tolerating cortison very bad. Next time, I will ask if the doctor can give me too, 8mg dexametason orally, instead of the IV solumedrol.

    The protocol is also 500mg mabthera on the other doses than the initial, 3 months apart. But now, as I have longer periods in between, I have decided to use 1000mg, which the doctor allowed me too, my decision. At the last infusion the doctor was very interested in my experience, and I can come back whenever I want for the next infusion. I think an appropriate time will be 5 monts after the last one. I have read that the B cells begins to come back after 24 weeks. And, I want to go back being a responder before I'm thinking of the next infusion. At least I hope. Now I am just tired of being sick and hope the response comes back soon. We'll see. This is a journey I thought was much easier than it certainly is. But, I just have 7 months more to keep the B cell depletion as long as the phase 2 study. (Last infusion at 15 months) Which had wonderful results.
     
  2. Benji

    Benji Norwegian

    Messages:
    46
    Likes:
    149
    I wonder...if this should be in the memberonly forum, not because of me, but because the phase 3 trial is not out, and we should not discuss ritux experiences in detail before it is out. Many wants to use any argument against it.
     
  3. Hip

    Hip Senior Member

    Messages:
    9,113
    Likes:
    13,937
    Thanks for posting your story. Lots of people have posted their rituximab treatment stories on the public forum, so it's probably not a problem.


    So you responded to the initial two rituximab doses after just 2 months.

    Can I ask, what kind of response did you achieve? If you classify ME/CFS on the scale of mild, moderate and severe, where were you on this scale before your rituximab treatment, and how much improvement did you get from rituximab after 2 months? Were you able to move up 1 level on this scale (for example, from moderate to mild, or from severe to moderate)?



    Strange how you got worse for 4 months after your third infusion, but then suddenly got much better very quickly.

    And now after your fourth infusion, the same thing happened: you got worse again for several months (but hopefully that will turn to an improvement at some point, as happened with your 3rd infusion).
     
    MEMum likes this.
  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,211
    Likes:
    31,647
    I am a bit puzzled by the moving around of doses @Benji. You may know that this protocol was designed originally for RA by me, although Drs Fluge and Mella have made some sensible modifications.

    The most important factor in deciding about when to give another dose is the B cell count and you have not mentioned that. There is actually not a lot of point in having rituximab if your B cell count is still low, unless there is a pre-planned programme designed to keep b cell counts below a certain level. There is no much point in changing doses and timings in that case.

    I am wondering a bit what your physician is doing in this context. Does he/she actually understand the immunology behind it and are they aware of the serious problems that you can run into if you chop and change dosage without proper monitoring? Large number of patients in Spain ran into trouble with rituximab for RA because the physicians did not understand the immunology and the patients became immunodeficient. The immunology is very complicated and the great majority of rheumatologists and physicians dealing with autoimmunity in general do not understand it. This has been a big problem. Fortunately Drs Luge and Mella understand it very well.
     
    Roy S, L'engle, Jo Best and 19 others like this.
  5. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,422
    Likes:
    3,399
    @Jonathan Edwards any idea why she's initially worsening and then improving after each dose? I'd not heard of that continual pattern in other reports
     
    MEMum and Benji like this.
  6. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,211
    Likes:
    31,647
    The patient progress graphs from Fluge and Mella phase II go all over the shop for the first three months. I doubt it tells us anything to be frank. It is much too inconsistent.
     
    cigana, L'engle, Jo Best and 4 others like this.
  7. Benji

    Benji Norwegian

    Messages:
    46
    Likes:
    149
    @Hip, Thank you for your comment.
    I am moderate, and think I went up to mild in the response period. If it lasted longer, I would know for more certain. But I am moderate now. Mostly housebound.

    @Jonathan Edwards Thank you for your comment.
    Unfortunately there is no B cell counts. My GP is backing out of any questions of this, and the ritux doc don't count B cells. (Kolibri)
    They have a protocol like phase 3, but I was allowed to differ, due to my experiences. That would say postpone my 4'th infusion, and have 1000mg instead of 500. (1000mg phase 2, 500mg phase 3, perhaps due to economic issues, we don't know for sure.
    Yes I read you found the treatment for RA, and I have read some quotes from you I don't remember them now. But also I've seen for RA you have Infusions every 24 weeks. That was a part of reason why I was confident enough to ask to have my 4'th infusion to be later, when I was better again (this argument/thinking is totally mine and may be wrong). But the doctor said yes, and I was happy to see my improving came back a month later. And then I took the 4th. I also know people from the clinic who had response two months after the initial doses, and never got it back when doing doses 3 months apart. I didn't want that to be mine faith also.

    @Jesse2233 if you read the reports from phase 2, you'll se there approximately a third who experiences temporarily worsening. I think it was 8 people. But from what I can see, the time is some weeks. Not months, as in my case. That's why I am suspecting the cortison to blame.
     
    Jesse2233 and Hip like this.
  8. neweimear

    neweimear Senior Member

    Messages:
    112
    Likes:
    336
    @Jonathan Edwards if one was to stick to the Fluge and Mella protocol of infusions at 0, 2 weeks, 3mths, 6mths,10mths and 15mths..would that work even if B cell counts were not being checked along the way? I wonder were Fluge and Mella checking all the patient's b cell counts or did they just stick to the timeline outlined in their trial? Also, if phase 3 trial is a success, do you think rheumatologists anywhere in the UK might be willing to treat ME patients privately? Our lives are slipping by waiting.
     
    Jan and Silencio like this.
  9. Benji

    Benji Norwegian

    Messages:
    46
    Likes:
    149
    @neweimear Fluge and Mellq counted B cells in phase 2, which you are referring to. I have seen graphs. For some the B cells start to come after half a year.
    In phase 3, I don't know.
     
    MEMum likes this.
  10. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    9,122
    Likes:
    23,314
    USA
    @Benji thank you for sharing your story and I really appreciate it as I am currently doing Rituximab and just had my second infusion three days ago. In case it is helpful for the future, I did not have solumedrol or any steroid whatsoever. I do not do well with steroids and I did not want a steroid reaction to interfere with the process. I have MCAS and was genuinely concerned about allergic reactions but even in my case, the steroid did not end up being necessary. I took Zyrtec, Pepcid, and Tylenol in pill form and then did 25 mg of IV Benadryl as the main pre-med and that was it.

    I am confused about your protocol and if you are doing an autoimmune protocol (375 mg/BSA or "body surface area" to determine your dose) or if you are doing the "ME/CFS" protocol of the Fluge and Mella study in which everyone gets one gram of Ritux regardless of BSA? I am also confused about the frequency of your doses and how they were determined if B cells were not measured?

    I was very curious, what were the main symptoms that improved for you and then worsened again?

    Do you know why your GP or the doctor at Kolibri did not measure your B cell count? Was there a clinical reason for this or just not their policy/protocol for some reason? We measured mine after the first infusion and it was zero (prior to even doing the second infusion on Day 14) but my doctor said this is very common and means that my dose (600 mg using the 375 mg/BSA formula) was enough. The goal (for me) is to keep the B cells at zero as I continue the maintenance infusions, in addition to continuing with IVIG, so the auto-antibodies do not have the opportunity to re-grow.
     
    justy, MEMum, Benji and 1 other person like this.
  11. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,211
    Likes:
    31,647
    Somebody needs to monitor B cells if only because if they come back and fail to go down with another dose you are pouring money down the drain having further doses, while potentially damaging the immune system. Immunoglobulin levels must be checked because they can go down suddenly - sometimes way down for no apparent reason. Rituximab is a very useful treatment but it is one of the hardest for doctors to understand and potentially can cause major trouble.

    The relationship between the treatment and symptoms is complicated and there is no sense in altering the protocol because of how things are going if you start off with a protocol designed not to be changed because of how things are going. The original RA protocol does involve waiting to see how things go but then you would not have the 3 monthly top ups.

    I honestly think that anyone considering using rituximab MUST have a physician in charge who understands the mechanism in detail. The very last thing I want is for a treatment I designed to end up causing harm because it is being used by people who do not understand.
     
    justy, Roy S, Orla and 26 others like this.
  12. neweimear

    neweimear Senior Member

    Messages:
    112
    Likes:
    336
    @Jonathan Edwards. This is a basic question but I just wish to be clear as I was considering travelling to Kolibri for treatment as there are no other options. Is the goal of the Fluge&Mella protocol total b cell depletion for an extended period.
    You get it at 0 and 2 weeks. Then at 3 months if your b cells are starting to return, this is presumably the right time for another infusion. If they were still at zero would you wait until they start returning before next infusion?? Sorry for the most basic questions, I just want to understand the process correctly. You mention immunoglobulin levels can go down suddenly, what can be done if this occurs and is it dangerous? Appreciate any info.
     
    Benji likes this.
  13. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    9,122
    Likes:
    23,314
    USA
    This was my understanding as well and my doctor said that we would do "serial B cell levels" probably once a month as I am doing Rituximab. The test he ran was called "Lymphocyte subset panel".

    Can you clarify which tests you would run to check immunoglobulin levels and how frequently? Does the test or panel have a specific name? (I know it might vary between countries or even between labs but I was curious which specific tests you run to make sure that immunoglobulin levels are not dropping). Thank you so much in advance as always!
     
    L'engle and Benji like this.
  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,211
    Likes:
    31,647
    The actual situation is sufficiently complicated that I do not want to give precise instructions. I should not be giving precise instructions because I agree with Drs Fluge and Mella that it is inappropriate to have rituximab outside trials. I am also not keen to give instructions for the benefit of doctors who are not following sensible protocols or know what they are doing. If immunoglobulins go down suddenly, yes, it is dangerous.

    All that is needed is a total IgG level as a routine. How often that is performed is a matter of judgment in the context of the particular patient. I cannot give more detail than that usefully I am afraid. The physician in charge needs to know these things.
     
    L'engle, Jo Best, TrixieStix and 8 others like this.
  15. Benji

    Benji Norwegian

    Messages:
    46
    Likes:
    149
    To be honest I didn't know it was important. But I now more understand my GP. When I told her that I wanted to be treated with ritux, she told me that she didn't want to count B cells and that stuff, I got the impression that she didn't feel competent to do that. I said there was a doc at the clinic and that was ok, I trusted that he did all that was necessary with ritux treatment. The ritux clinic is at another place, have to take plane. So that's probably why they don't do thourouhly following up.

    My symptoms; or what was better. All of it! I was more able to cope with everything and everyone. Didn't get exhausted by being sosial half an hour. Could be at a mall for two hours and when I came home, I was relaxed, and didn't need to lay down. Wonderful! But once, I was sosial for four hours, then I felt the old me coming, wanting to go to bed and rest there. But I tolerated more of everything, didn't get sick from sound, light or bad sleep. I woke up earlier, feeling good, needed less sleep. (Now I need 12-14 hours in bed before doing anything the next day.) I enjoyed the sunlight outside, with no problems.

    I was able to walk fast again, that was wonderful. My body and mind much more responsive. Now, I get tired of being sosial half an hour and then need to rest in bed, I can't do much before it is to much, I am mostly in bed or at the couch with a blanket, I need very much to be warm. And rest and rest and rest.. but I am lucky, I don't have much pain and my stomach is ok. The worst thing for me, is the need to be in bed more than 20 hours per day, if I don't want to have much symptoms.

    The treatment; Thank you for sharing, that was a part of what I was hoping for when joining the forum. So interesting you do entirely without steroids! Wow. I will need to google the premedication you take, don't know every medicine you mention. I take 1000mg paracetamol, and 20mg Zyrtec.
    They say they follow phase 3 of Fluge and Mella but they differ in premedication of steroids. Where F and M gives much less.

    Phase 3 is 1000mg mabthera day 0 and 14, and 500mg at 3,6,9 and 12 months. So I did the infusions initally and and the first maintenance dose as scheduled, but when I had this long setback I asked to postpone the 4'th. And I wanted it to have 1000mg mabthera instead of 500. To be sure it is enough.

    Phase 2 Fluge and Melba, had 1000mg day 0 and 14, and then 1000mg at month 3,6,10 and 15.
    I think maybe that phase 2, they did 500mg/BSA. I am not sure. I have not read 375mg/BSA before you wrote it. When they use BSA I suspect they use 500mg/BSA. Then I would some up with 850mg. And since I have to buy it myself, thats 2 bottles, and then I have everything in them. It goes fast. That last infusion was only 2 hours. I may suspect that's why they use the steroid dose they use.

    When I differ from the phase 3 study and clinics protocol about the frequency, I did that because of being a responder but yet experiencing long setback. So now I will probably follow more the phase 2 protocol, they had 4 months between 4 and 5, and 5 monts between 5 and 6. I was having 4.5 months between 3 and 4, though. I would love to have somebody /a doctor to discuss this with. But my GP backs off, and the clinic is too far away to follow up closely/doing blood test. I would have to go private, around where I live. I am making an enquiry now, whether they have a doctor that know's rituximab.
    Do you live near enough to the clinic Gingergrrl? Do you have a "fixes set" of infusions, or how are they determined?
     
    Last edited by a moderator: Aug 5, 2017
    Gingergrrl likes this.
  16. Benji

    Benji Norwegian

    Messages:
    46
    Likes:
    149
    @Jonathan Edwards Do you have any opinion about the premedication cortison? Do you think it matters or not?
     
  17. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,211
    Likes:
    31,647
    I don't think we have good information on that but rituximab has been used without.
     
    Gingergrrl, MEMum and Benji like this.
  18. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    9,122
    Likes:
    23,314
    USA
    I agree that the trial protocol for ME/CFS should not be attempted by random doctors who have no experience with it and do not even monitor the patient's B cells (which shocked me to be honest when I read that)! In my case, we are doing it for auto-immunity and following the autoimmune protocol which is a much lower dose than given in the trial.

    Thank you and this is something I am going to confirm with my doctor (how frequently to monitor IgG levels in my case). I get high dose IVIG every three weeks and assume my levels are not too low but will confirm this.

    I did both infusions of Rituximab without any steroids. Both my doctor and my infusion center (who are separate) said that their policy is to use IV Benadryl as the main pre-med but to have the solumedrol ready to go in case of allergic reaction. I had no allergic reaction to the first infusion and minor to moderate reaction to second infusion which resolved with an additional IV Benadryl combined with stopping the infusion for 15 min, giving plain saline, and then re-starting at a slower speed. I do not do well with steroids so was thrilled to avoid them.
     
    Benji and MEMum like this.
  19. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    9,122
    Likes:
    23,314
    USA
    @Benji

    Monitoring the B cells is extremely important and unless I misunderstood, my doctor will be monitoring them once a month throughout the time I am doing Rituximab.

    I apologize for using the brand names and "Tylenol" is called Acetaminophen in the U.S. and Paracetamol in the UK (and maybe elsewhere)? And Zyrtec (what we both took) is called Cetirizine, Benadryl is called Diphenhidramine, and Pepcid is called Famotidine.

    I am confused that when you had the set back that you asked to postpone the 4th infusion vs. doing it as scheduled? I am also confused why the doctor at Kolibri did not check your B cell count at that time and why he or she allowed you to determine to raise the dose to 1000 mg vs. 500 mg? This makes me a little concerned what they are doing there. My doctor (and I am always paraphrasing from memory and NEVER a direct quote from him) said that if 600 mg was enough to get my B cells to zero (which it did after the first infusion, before I even had the second), then there was no reason to give a higher dose b/c there is nothing additional that it would add beyond B cell depletion.

    The autoimmune dosing formula is 375 mg of Ritux/BSA or "body surface area". There is no formula to my knowledge for autoimmunity other than that one (but am hoping Dr. Edwards will correct me if I am wrong)! Fluge and Mella did not use the autoimmune formula and all patients got one gram (1000 mg) of Ritux regardless of their BSA.

    In my case, the infusion center has a pharmacy which prepares my IVIG (and Rituximab) and all meds so the patient never sees the bottles and it is delivered to the nurse already in the IV bag. But it sounds like what you are saying is that each bottle contains 500 mg of Ritux and I assume you are correct.

    I am in awe that you tolerated 1000 mg of Ritux in two hours! I did 600 mg of Ritux in eight hours (not counting the before and after of putting in the IV, taking the pre-meds and IV Benadryl, etc) and in total I was at the Infusion Center for almost ten hours. My nurse said that in "normal" patients who can tolerate a faster infusion speed, they will give the second infusion in three hours, but that would be the absolute fastest rate. Now I understand why you had to have the solumedrol/steroids in order to have such a fast infusion. My MCAS doctor wrote on the order that 80 ml per hour was the absolute fastest speed that I was to be given based on my history (and my main doctor was in agreement and deferred the infusion speed to him).

    I live about 45 min from the infusion clinic where I have IVIG and Rituximab and it is connected to the hospital where my MCAS doctor practices so he is the prescribing doctor. My doctor at OMI (which is about 7 hrs north of me) did the insurance Auth and ensuing battle for approval with my insurance. He calculated my dose of Ritux and is monitoring my B cells and all other aspects. But he is collaborating with my MCAS doctor who is the prescriber which allows me to go to his infusion center. My MCAS doctor knows a lot about pre-meds and infusion speeds to decrease allergic reaction risk for someone with MCAS and they are a perfect team IMO.

    Edit: I missed your last question re: if I have a "fixed set" of infusions. Ideally I do, but it will ultimately depend on my insurance approval. We will be requesting the first maintenance infusion at 3 months b/c insurance only authorized the initial two (which I understand b/c they had no idea if I would even tolerate it). Now that I did, we can make a solid case for the 3-month infusion in early Nov (assuming B cell counts line up). But based on my insurance, they will deny it and we will appeal so we will have to put in the request in advance to allow time for this.
     
    Last edited: Aug 5, 2017
    Benji likes this.
  20. Murph

    Murph :)

    Messages:
    399
    Likes:
    2,167
    This Fluge Mella slide contains a graph in the upper right that shows a hypothesis for how Rituximab works in ME?CFS. It seems like you are experiencing fluctuation in the 'x-factor' that determines responses. (With Rituximab the b cells are gone straight away and something they produce, perhaps antibodies, is hypothesised to cause symptoms.)

    My simplistic reading of your story is that the initial dose got your x factor under the response threshold quickly. But the subsequent ones didn't.

    Screen Shot 2017-08-06 at 4.22.35 PM.png

    Your experience is not too dissimilar to the response of the patients in their 2009 trial. They are all over the place. sometimes they react swiftly to the treatment, other times it takes a while (especially patient 3).

    Screen Shot 2017-08-06 at 4.39.38 PM.png

    I would be very interested to hear how your reactions develop over the next two months. If I read you right your last infusion was in early June, a little over two months ago. I suspect a good response is likely in the next month or so.

    EDIT: Incidentally, when the Rituximab paper finally arrives hopefully we'll all be cheering not just the yes/no on Rituximab effectiveness, but the much more difficult question of whether they've been able to find and measure the x factor. I'm sure Haukeland hospital is monitoring dozens of cytokines, metabolites, antibodies and other assorted serum flotsam. If one of them tracks closely with patient response, we will hopefully have not just a treatment but a clue that will help us find an even better treatment in future!
     
    Last edited: Aug 6, 2017

See more popular forum discussions.

Share This Page