Discussion of patient self reported adverse effects of Rituximab

I'm so sorry your daughter is suffering @Perrier. It's worth noting however that Rituximab was the drug that made Whitney Dafoe much, much worse. He said as much in his posts on 'the other forum', that is, until he was unable to type any longer, and had to have his caregiver type in his final question.

 

I don't know how we could possibly know this with 100% certainty? In the 3+ years that I have been on the boards, I have seen constant times when someone posts of an improvement, and they are told that we can't prove why the improvement occurred, or if it was "placebo" or a "spontaneous remission" (which has never happened to me in my entire illness and I was on a purely downward trajectory until I began treatments).

I can trace every med and supplement (even toothpick amounts) and if they were neutral, made be better, or made me worse. I am confused why positive reports are so quickly dismissed but Rituximab is blamed for Whitney getting worse when we really have no idea if he might have gotten worse any way or what other medications or factors he was trying at the same time period. This is not directed at you @dannybex vs. I have seen so many posts like this and don't really understand them! When someone gets better, it is placebo, when someone gets worse it is inherently the medication.

I also feel a little uncomfortable speculating about Whitney who is not able to speak for himself.

 

As a bit of an aside, Mendus is worth looking at in terms of attempting to track ups and downs. It is a Citizen Science/quantified self hobby project run by a neuroscientist who has CFS. You get personal results so no need to worry about whether you do have the same exact problem as other participants. People join at different times so danger of placebo/nocebo may be higher than typical. This isn’t conventional research, it’s an attempt to circumvent the lack of research money for chronic illness conditions.

http://www.mendus.org/

I’ve stopped doing it recently though because I’m fairly convinced I have some problems which are neither ME nor POTS, so I don’t want to muddy group results.

I wrote about the Diet Study here https://tipsforme.wordpress.com/2015/06/17/mendus/

 

@Jenny TipsforME Do you think it would be useful for Mendus to have a thread of its own?

 

@Skycloud yes

 

Trish, thank you so much for your detailed reply and I really appreciate it.

I think this is what bothered me the most, that a statement was made, as if it was fact, that a specific treatment made Whitney worse when he is not here to share his own opinion. I generally feel uncomfortable discussing people who are not here b/c I know it would make me uncomfortable if it was done re: me (not in a factual way and not if someone quoted my own words, but if someone attributed something to me which if I could reply, I might not feel was accurate). I think there was even a post on the other board in which Whitney's mom said she was not certain if Ritux had made him worse, vs. he would have worsened anyway, or he worsened due to a combination of other factor(s). I think sadly, we might never know.

Absolutely, and this is one of the things I love about both boards, that we can celebrate victories and commiserate our misery (both medical and emotional/personal) with each other. I would never want this to change.

Absolutely and if Whitney were here and posted something, I would have no problem with anyone challenging him, as I have no problem with anyone challenging me re: the treatment path that I have chosen (with my doctors), b/c I am here to reply to it myself.

I absolutely want the recent trial outcomes highlighted and I have read every single post re: the Ritux trial on both boards with great interest and agree that it does not seem to be a viable option for ME/CFS (unless there are more to the results that will be coming out later re: potential responders and sub-groups). I have gotten hundreds of PM's over the past 1.5 years of people asking me if they should do IVIG and Ritux and every single time I have told them that 1) I cannot give medical advice 2) I do not know the specifics of their situation 3) And I refer them back to their own doctor(s).

I have no doubt that I am a responder to high dose IVIG and Rituximab but there is no scenario in which I would assume that my results apply to anyone else. I believe there are others out there like me, who are potential responders, and I post in the hopes that some day they will find my posts. But I believe the responder group has B-cell driven auto-antibodies causing their symptoms (and whether this is a sub-group of ME/CFS or a completely different disease, I still have no idea). I don't want to give anyone false hope, and don't even want to give myself false hope, LOL. I have no idea what happens to me once my treatment ends.

There is a part of me that would love for my response to be some kind of spontaneous remission b/c then it would be possible to sustain it once I am completely done with IVIG and Rituximab in the future (although I do not believe that it is spontaneous or random in my case and neither do my doctors). So I report the facts in my IVIG/Ritux thread on PR, and every time I've attempted to stop that thread, people have urged me to please continue it. So I am continuing it, both b/c of the incredible support I have received in it, and b/c I believe the info is something that people can research or take to their own doctor(s) and inquire about (re: high dose IVIG for auto-immunity, paraneoplastic syndromes and the required cancer checks, autoimmune POTS, etc).

Sorry this got so long-winded and I hope it made sense!

 

Good points @Gingergrrl. Of course we don't know if he would've declined without Rituximab. But the difference before and after is so striking, plus he himself did say in several different posts, that 'such and such' was worse after starting the drug.

Since links to the other site are permitted, I'll see if I can find his posts and will add links if I can. I hope at the same time that you don't think I'm trying to dismiss your positive reaction, as I'm not. I was just responding to @Perrier's post re severe patients.

 

I am still confused if we are allowed to link from PR to here? I have not done it, but someone did it to me a couple weeks ago and I was a bit taken aback (b/c in theory I might have shared something there that I did not want posted over here or vice versa). In my case, I have solid reasons for this preference and am trying to only post in Member's Only threads but I know this one is public. Maybe my preference is unrealistic but I am hoping that one of the moderators can clarify if it is allowed to quote between the two boards?

I absolutely did not think that and no worries. I was more concerned seeing something attributed as a cause of Whitney's decline when truthfully we do not know if it was the single cause, one of several causes, or not the cause at all. It also bothered me b/c he is not able to reply and we are speculating about someone who is not here.

 

Yes, I saw on another thread that one of the moderators said it's okay to post links to the other site.

Okay, Whit's post from 'the other site'. It is also worth noting that it looks like he was prescribed a CPAP machine, and also thiamine injections (which had no effect for him), so there indeed could've been other factors. But this post, in his own words, he says several times that things were worse after Rituximab.

http://forums.phoenixrising.me/index.php?threads/swollen-throat-bad-sleep-cfs-wrse-aftr-rtxn.25183/

Here's one a month or so later where he says he can't handle the CPAP.

http://forums.phoenixrising.me/inde...orse-with-cpap-bipap.24567/page-2#post-395371

And this post a month later -- November 2013 -- had to be written by his caregiver:

http://forums.phoenixrising.me/inde...pressions-for-dental-appliance-at-home.26639/

Again, his worsening could've been due to a combination of things, but he seems to emphasize in these posts that Ritux was a key factor, maybe 'the' key factor.

 

I guess that answers my question and really makes me want to only post in Member's Only sections but I also want to keep posting in the Rituximab section. I checked that the three things you quoted of Whitney's were not from a Member's Only section of PR and wanted to thank you for being mindful of that.

To me it seems challenging to know if the reactions were to Rituximab, a new CPAP machine, or the thiamine injections (or possibly other new treatments that he did not even mention on the board). In my case, when I've been asked how I know if my most recent improvements were from Ritux, vs. the fact that I have continued to do IVIG, the truth is that I don't know.

I have strong suspicions b/c my improvements from IVIG plateau'd until I added Ritux, I stopped tolerating the IVIG as well and we reduced the interval from 3 wks to 5 wks, and two of the last three IVIG cycles, I only did 55 grams (vs. 82 grams) and yet I have had amazing improvements that began 2-3 months after Ritux and matched the time frame that my doctor described (before doing them). I believe they're working synergystically in my case, as does my doctor. But obviously I cannot "prove" it any more than I can prove the improvements that I had from the MCAS meds or moving away from mold (which pre-date the Rituximab by two years).

I cannot wait to hear all of their data and it would not surprise me if there was a group who were already immunocompromised (vs. autoimmune) that ended up getting worse. To me, Ritux is a treatment for B-cell driven auto-antibodies and without absolute proof that I had them, I actually would not have taken the risk to try Ritux myself. But once it was proven by labs from Stanford, Mayo, OMI, Quest and Cell Trend, and my quality of life was close to zero, I felt the risk was worth it. But if my labs showed zero auto-antibodies and that I was still IgM+ for viruses or if I'd had low IgG sub-classes, I probably would have made a different choice.

 

[ETA: The following post is not directed to @Gingergrrl specifically, but simply to the issues that she has raised, especially since they have been raised by others as well.]

I think that the key is in the following quotes by Whitney, all dated June 12, 2013, and contained in @dannybex's first post reference:

The last statement is in the same entry as the previous three, and I think it's really the smoking gun, as the word "immediately" is used. In the 19+ years I've been disabled with this illness, whenever I've had a significant problem arise immediately after a new treatment (and Whitney's listed several here), the new treatment has always been the problem. Although it's not possible to prove with 100% certainty that Rituxan was the cause of the problems that Whitney listed, I think that the evidence that he provided is pretty overwhelming. And again, the word "immediately" is key. He makes no reference to any other new treatments, and this is four months before he started using the CPAP machine. In fact, the third quote seems to imply that Rituxan was the reason that he eventually needed the CPAP; in the September 12 update in the same post, he mentions that his sleep apnea is worse, as well as his CFS in general.

The month-long thiamine injections, from which Whitney felt nothing, ended two months before the June 12 quotes listed above. [ETA: The injections were actually given starting about 2 1/2 months after the Rituxan, as can be seen from the first quote and from Whitney's posts on the injections.] It's really hard to see how the injections could have played any role in causing the reactions that Whitney described.

It's important to remember that Rituxan is an extremely powerful black box drug with many possible serious side effects, including many that can lead to death, and many of these side effects can start as early as the time of the first infusion. (See the prescribing information, especially sections 5 and 6, for more details on these.) As there is very little clinical experience using Rituxan for treating ME/CFS, it's impossible to know for sure how many of these side effects apply to our population, or whether there may be additional side effects, not currently listed, that apply only or primarily to us.

Admin note: Text, that is now off topic for this thread, discussing PEM/PENE can be found here, https://www.s4me.info/index.php?threads/phase-iii-rituximab-trial-news.1153/page-11#post-20815

 

I am not actually trying to prove anything. My main point was that I felt uncomfortable with people discussing someone who is not a member of this board and cannot reply (but I think I am the only one who feels this way).

It absolutely can have fatal infusion reactions with the #1 being anaphylaxis and can occur within 48 hours of the first infusion. Usually after that, you are in the clear and 80% of fatal infusion reactions are with the first infusion vs. later ones. The other fatal reaction is the risk of PML which has no cure. But, in my own case, it was one of the easiest meds I have tried and actually much easier to tolerate than high dose IVIG. I had near fatal reactions from Levaquin, from a food dye, and from IV saline infused too fast. Anyone can react to anything. I have no agenda and I have no idea why I tolerated Rituximab so well. I am just sharing my story and I would want any patient who tries it to read the full prescribing info as I did (in addition to many journal articles) and to do so with full informed consent of potential side effects.

I agree and I am not saying that anyone else should try it and I am not saying that it did not make Whitney worse. I am just saying that I do not know and will have to leave it at that.

 

I don't think we will ever be able to know what happened here. However, I would caution against emotive language like 'powerful black box drug'. As you know I spent ten years studying the use of this drug in my patients. It has very few side effects in comparison to a lot of very standard drugs - even anti-inflammatory painkillers. There are some potential problems but in skilled hands they are uncommon. The prescribing information was made rather alarmist for political reasons by the drug company who have never been keen on its use outside cancer. Allergic reactions will occur immediately but we have no reason to think that was involved. Otherwise rituximab has little or no immediate effect. It destroys cells that are not actively doing very much - B cells. The cells that produce antibodies are the offspring plasma cells and they do not change for weeks. An immediate worsening after receiving rituximab seems to me pretty unlikely to have anything to do with the drug.

In any event it looks as if rituximab is no longer relevant to ME/CFS.

 

I am concerned that quotes are taken from Whitney from another board and are now in a thread on S4ME that is not a Member's Only thread. I may be alone in this, but I feel very protective of Whitney, even though I have never met him. I had a few incidents in which I had a negative reaction to a treatment and I wrote on PR what I believed it was due to and at the time, I believed 100% what I was writing and wrote it in good faith. But several years later, with new information, I now have a different opinion. I am around to share this opinion (re: my own case) but Whitney is not able to speak for himself.

Maybe he still feels his condition worsened b/c of Rituximab, but maybe he does not. We do not know for sure and (as an example), research shows that patients who take fluoroquinolone antibiotics can get serious adverse reactions, including tendon rupture, up to six months after taking the antibiotic and many never associate their reaction to the true cause b/c so much time has passed and associate it with whatever they might be doing at that moment.

I would agree with this and the percentage of drugs (at least in the U.S.) that have an FDA Black Box warning is incredibly high. I have had reactions to benign things that nearly killed me and Rituximab was one of the easiest drugs I have ever tried. It is much easier to tolerate than even IVIG. I have had worse reactions from NSAIDS like Advil (Ibuprofen) which would be considered benign to most people.

I was absolutely prepared for anaphylaxis when I had the first Rituximab infusion and knew this is a risk, even in someone without MCAS. I read the full prescribing info, as well as the full instructions that the nurses read at my infusion center (b/c they gave me a copy). I had IV Benadryl as a pre-med and we had IV prednisone on the counter ready to go in a syringe if I should need it, but I never did. I was told that 80% of fatal allergic reactions occur with the first treatment (and not with later treatments) and I had a minor allergic reaction that completely reversed w/additional IV Benadryl. When I did my third Rituximab (on 10/31), I had zero adverse reaction of any kind either during or after the infusion.

This was my understanding as well. My doctor has patients who fly in from other countries, do their Ritux infusion, and fly home the same day. I am nowhere near that level of functioning and have not been well enough to fly since 2013. But it shows how most patients tolerate this infusion. I am not endorsing that anyone do this treatment or that it is a viable treatment for ME/CFS in the absence of known pathogenic auto-antibodies. I just want this to be more balanced discussion since Whitney is not here to speak for himself and quotes from another board are now being shared in a non-members only section of this board.

 

I'm really sorry this has upset you so much @Gingergrrl. That certainly wasn't my intention, nor was it my intention to put words in Whit's mouth. I was just trying to make a point to @Perrier who seemed to put so much of his faith/hope on that one drug. I feel protective of him too, as I became so close to becoming bedridden a couple years back, and couldn't help think of his situation.

I guess I look at it from a complete different perspective, that perhaps -- and of course I don't know for sure -- but perhaps Whit's posts about the drug were his way of letting people know of his result, of being able to leave a record when he was losing the ability to write anything. I don't know, but that's just my opinion.

And I don't know if this helps at all, but the posts I quoted were all posted in the 'public' sections on that other site. Not one was copied from a Member's only section.

Anyway, we'll have to agree to disagree and move on. I hope only the best for you as you seem to be doing so well w/the drug.

 

You didn't upset me and what I said was not directed toward you (nor to any specific person). I was just surprised to find this new thread b/c I thought that the prior thread (with Whitney's quotes and my replies) had been in a "Member's Only" section of S4ME but is now moved to a public section? (Unless I am wrong about that and sincerely apologize but can't figure out why it was moved although I know there must be a reason).

I am typing in another thread where I included some very personal details and it concerns me re: if the other thread could be moved to a public section in the future. I know that there is no privacy on-line, and that I type at my own risk, but it makes me uncomfortable and I have to figure out how to proceed.

I mostly replied earlier b/c I had wanted to respond to what Dr. Edwards had written re: Rituximab b/c I found it interesting. I am talking to 4-5 people from PR, and several people from my auto-antibody groups and IVIG groups (several with ME/CFS diagnoses and several with other diagnoses but who had been given a "CFS" diagnoses at one point in their lives) who have all been helped by Rituximab and it is not just me. Even though the Fluge & Mella Rituximab study was negative, I believe there is a group of people who could be helped by it and I am now afraid that group will fall through the cracks and become lost forever.

Prior to these treatments (IVIG and Rituximab), I could not take a shower without assistance from my husband, my mother, or a caregiver and I did it once a week at best. Now I can take a shower 4-5x a week, I have the muscle strength to turn on the faucets and pump the shampoo bottles by myself, and feel energized afterward. I know this must sound very small to the people who could always shower without assistance but for me it is life-changing. I want people to know that there is either a sub-group (or a misdiagnosed group) who are potential responders.

I acknowledged that in the other thread and was grateful that you were mindful of that. I was just surprised to see the thread moved and am uncomfortable with continued speculation re: Whitney who is not here to speak for himself. But I get it that I am the only one who feels this way and just have to accept it. One of my very close friends is friend's with his mother and there are so many treatments that he has tried which have never been posted about, and I don't know how we would ever know what ultimately made him better or worse, beyond speculation, unless Rituximab was the only treatment tried which is wasn't.

Thank you and I know that you wish me the best, and likewise I truly do for you as well.

 

Dr John Whiting from Brisbane Australia, has just tweeeted:
“A patient of mine is doing well on rituximab. This drug is not dead......even if the data shows a null effect in a randomised trial, then I’m guessing that the cases were ineffectively stratified, given that subgroups are evident in our own work.”

 

I regard that sort of message as unhelpful. The fact that a patient is doing well on rituximab does not mean they are doing well because of rituximab. I also worry when he refers to 'our own work'. That sounds suspiciously like playing around with the drug without proper methodology - pretty much like the PACE people did with CBT. The Norwegians who raised the issue of using rituximab in ME have consistently asked for others not to use it except in properly designed trials. A the person who introduced rituximab for autoimmune disease in general I feel the same.

Guessing is not good enough if people's lives are stake.