Did I make the correct choice after all

Good morning everyone. So after much trepidation, information and my doctor's advice I took the Rituxan.
The first wo weeks were not too bad, feeling very tired after the second day, for about 2-3 days. So I rested.
Then after the third infusion, the fatigue came again but so did a world of hurt. My body feels like it has been
beaten or run over....I saw my rheum last Wednesday she said I was in a lupus/fibre flare.
She gave me muscle relaxants and anti-inflammatories. Took them alternating for two days and felt quite a bit better.
But anti-inflammatories can cause all kinds of GI stuff that includes bleeding....anytime, as it is written in the description.
So I can't imagine it is a good idea to stay on it. The muscle relaxants are a bandaid so I can sleep, they can't fix the pain and where it's coming from.
I am now wondering about the Rituxan. As many others have questioned, the ITP is less invasive than the side effects
from the treatment.
I can't get out of bed, my ankle bone and tissue is so swollen, and my hip joint is so painful I struggle to walk.
My neck, jaw and shoulder is a constant ,stabbing pain that keeps my hands numb.
Headache and I am sooo tired and can't seem to think worth a darn....or care....
So guys, have any of you traded one problem for another after Rituxan? Platelets for pain?
Is this normal stuff with Rituxan? Maybe it's the infusion it's self and it will taper off now I am finished the infusions?
Last infusion on the 14th, platelets 428 yesterday on my replacement dose of prednisone 7.5mg for Addison's Disease.
I wonder if I should up the prednisone again a bit, this time for the lupus/fibre flare? Thanks, Sandy Too.

Sandy - only you can decide if Rituxan was worth it for you. Most people do quite well. I ended up like you, traded platelets for pain so for me, it wasn't worth it. It's been about 11 years now and I've had daily chronic pain since. You might be able to get it under control soon...I hope that is the case. I think I did mention that people with Lupus tend to have more problems with Rituxan; it's just a pattern that I've noticed here over the years. There are no easy answers when it comes to treatments.

I'd wonder if you ended up with serum sickness since the timing seems about right, but that pain is much more severe than Lupus flare pain.

Sandi,

Have there been others here who had chronic problems such as yours after Rituxan?

Do you consider your chronic pain to have been rituximab-induced serum sickness (RISS)? Everything I have read indicates serum sickness resolves once the offending agent is removed. One study of RISS showed that of 33 cases, all resolved within 3.5 days.

Are you thinking of Drug-Induced Lupus Erythematosus (DILE)? It is expected to resolve days to months after removing the culprit drug (of which there are many possibilities). Here is a thorough article on DILE:
emedicine.medscape.com/article/1065086-overview

Or is this more what you had in mind?:

The BAFFling effects of rituximab in lupus: danger ahead?
Abstract
Suboptimal trial design and concurrent therapies are thought to account for the unexpected failure of two clinical trials of rituximab in patients with systemic lupus erythematosus (SLE). However, in this Opinion article we propose an alternative explanation: that rituximab can trigger a sequence of events that exacerbates disease in some patients with SLE. Post-rituximab SLE flares that are characterized by high levels of antibodies to double-stranded DNA are associated with elevated circulating BAFF (B-cell-activating factor, also known as TNF ligand superfamily member 13B or BLyS) levels, and a high proportion of plasmablasts within the B-cell pool. BAFF not only perpetuates autoreactive B cells (including plasmablasts), particularly when B-cell numbers are low, but also stimulates T follicular helper (TFH) cells. Moreover, plasmablasts and TFH cells promote each others' formation. Thus, repeated rituximab infusions can result in a feedback loop characterized by ever-rising BAFF levels, surges in autoantibody production and worsening of disease. We argue that B-cell depletion should be swiftly followed by BAFF inhibition in patients with SLE.
PMID: 26888554 DOI: 10.1038/nrrheum.2016.18 www.ncbi.nlm.nih.gov/pubmed/26888554

Thanks for your reply.
This is why I was apprehensive to begin with. I am not against drugs at all, I could not be without them.
It is the un-known with SLE or any auto-immune complication with regard to these drugs.
As far as serum sickness, as described by Sandi and others, I don't feel I suffered that. At first more just
terrible fatigue and nausea, but it did go away in about 3 days.
But by the third treatment it was clear that those symptoms were now being dwarfed by the soft tissue pain and now joint/bone pain.
The abstract sure makes one think. A few months of this will be very difficult, and I will work hard to minimize damage, but still if the ITP goes into remission for a good long time and I can get back to my life I may still think it was the right choice.
If my platelets drop again then certainly not. But I guess one has to do it to find out.
I only wish (as I was so bad at trying to get across before), that I could have been told this before by my hemo or rheumy. I feel it unfair to be blindsided even if there are only abstracts.
Also my hemo seems a bit awol, I have not seen her since October, even though I had called re sinus infection, muscle pain, bone pain.
I called today and talked with a nurse at the cancer centre, she questioned that as well. I don't have an answer. I know my hemo had told me repeatedly that other than the ITP, I would be under the care of my rheumy. So although my hemo ordered the Rituxan it is my rheumy that I call for any concerns? Doesn't seem right to me...and you know I am to darn tired and feeling not great, I don't really need to sort out who is responsible for the patient. Thanks again, Sandy Too

Rob:
No, I didn't mean to imply that people with Lupus have chronic problems due to Rituxan....they tend to have more acute problems like serum sickness or hives. In my case, serum sickness triggered Lupus; hence the chronic pain. The serum sickness did go away but I was left with residual muscle pain and other symptoms that I did not have before serum sickness. It started immediately, so I would imagine that it triggered an inflammatory response. I suppose that same response could be triggered for others who already have Lupus. We haven't had anyone in a while, but over the years, nearly every Lupus patient who has had Rituxan ended up with either serum sickness or hives as I said. It was too much to be coincidental.

Sandy:
I don't think that either of your doctors could have predicted any side effects. All you can do when you consider a new drug is to look at the drug inserts, be aware of potential adverse effects, and make your decision based on that. The list is too long for a doctor to go over every single one with each patient, and they have no way of knowing if a patient will experience a problem. It's too bad that healthcare puts that on patients these days, but that's the way it is. We have to be our own advocates. I was blind-sided by side effects too but it wasn't anyone's fault. It was just part of the risk.

We live in a world of specialists now and each one deals with their own disorder. So yes, you would see your Rheumatologist for a flare and you would see your GP for a sinus infection. My doctors are very specific like this too. Your Hemo is not knowledgeable enough to treat a Lupus flare even though he may have administered the drug that triggered it. He will deal with platelet problems and that's it. They all have their own areas of expertise.

Sandy Too,

Yes, the abstract does seem to have been written about someone like you. It is only an opinion article; it discusses a phenomenon which hasn't even been proven to exist (exacerbation of SLE by B-cell depleting agents like Rituxan); but, it does seem to provide a plausible mechanism by which that exacerbation might occur. It is a little confusing to me that there are studies showing beneficial effects of Rituxan for treating SLE, but for others Rituxan apparently exacerbates SLE.

I am interested to know more about BAFF and its inhibitors, especially the argument, "that B-cell depletion should be swiftly followed by BAFF inhibition in patients with SLE." The only BAFF inhibitor I find is belimumab (Benlysta). There is some evidence it might be useful in treating ITP in some patients, but I have found no clinical trials for this.

I know SLE well. I know SLE and me even better. It is a life changing illness.
I believe so far the Rituxan has done the job it was meant to do. I am not in danger at this point from low platelets for which I had been for almost a year. I am grateful for it.
But I know that the drug has put me into this current SLE flare. At this point I can only be hopeful and do the best I can to trust or have it settle down and get on with my life.
I already had SLE, I guess having Rituxan sending me into a flare is just part of the norm that is SLE, like going into a flare from too much sun, working to hard, or too much stress and so on. It would be great if the abstract thinking could help with minimizing the possiblility of a flare.
But if I did not have SLE and knew there was a possibility of ending up with it after treating ITP with Rituxan I would in no way take the risk. The trade is just not anywhere near even.
I would choose watchful waiting and as low a dose of prednisone as possible for the ITP.
To think you both ended up with Lupus and life long pain from Rituxan is so very sad.
I guess it depends allot on the severity of Lupus too.
But is it possible, you already have Lupus and didn't yet know it? Maybe the Rituxan can make a hidden illness like Lupus awaken? It took years to for me and my doctors to learn that the numerous diagnosis I had and the painful symptoms had a reason, that was called SLE.
I will talk with my rheumy this week about how bad the flare has gotten and talk with her about Benlysta. Thanks Sandy Too

I think that I had a genetic predisposition to acquire Lupus and it just needed a trigger. It may have occurred at some point without Rituxan or it may not have. I'll never know and I can't change what happened, but i am much more cautious about medications now than I used to be.

I'm one of those Lupus patients who had serum sickness to Rituxan - twice.

First time was in 2013 but that was misdiagnosed (in my opinion) as a Lupus flare (from the Rituxan). I took Dex and it resolved my symptoms (muscle and joint pain and rash) within 12 hours. In 2014, I received Rituxan (again) and developed serum sickness (again) after the 2nd infusion. Pain was much worse this time and I could barely move. Dex once again resolved my symptoms within 12 hours. However, I still went for infusion #3 because, at that time, it was again thought to be a Lupus flare. However, during infusion #3, I developed a severe allergic reaction (hives and throat swelling) that required IV Cortisone and Solu-Medrol. I did not finish round #3 and did not receive #4.

After that experience, I will not have Rituxan again. Whether it exacerbates my Lupus or not, I am clearly allergic to this medication. And while it does wonders for my platelets (still in remission today), the risk is not worth it for me.

I do agree with Sandi - I think there is definitely a link between people with Lupus who have reactions to Rituxan. It definitely caused an auto-immune response in me. I wish I had gotten my Lupus marker blood work done during the serum sickness episode. I bet my numbers would have been through the roof.

~Lauren

Hi Lauren! I remember you and I remember when that happened. It amazes me how many patients have been misdiagnosed when they have serum sickness during Rituxan. It is clearly a listed side effect and that misdiagnosis has led to people using Rituxan again when they should NOT have touched it. My second round with serum sickness was also worse than the first, and using the drug again could result in death. I have also seen doctors keep pushing people to finish the four infusions after this reaction which blows my mind. Having all four infusions is not that important, in fact studies show that two may be enough to work. So patients are pushed to continue the drug when the risk of dying from the drug is much greater than the risk of dying from ITP. Makes no sense to me.

I stay away from all biologics at this point. I never want to go through that again. I'm glad you are still in remission.

Thanks Sandi. My hematologist truly thought the first episode was a Lupus flare, primarily because of the horrific petechial rash I developed all over my legs and the fever. I forgot to mention that, but I always developed a low grade fever after each Rituxan infusion as well. But, after the second episode and subsequent reaction, he definitely agrees it was serum sickness.

I agree with you about the biologics. My rheumatologist mentioned in passing that I would be a good candidate for Benlysta if needed, and I told him no thanks. While I understand Benlysta and Rituxan are different drugs, I'm not interested. I'd honestly rather take Prednisone or Dex (as terrible as they both are) then go through that again.

~Lauren

I agree. My Rheumatologist pushed Benlysta too every single time I saw her. I kept saying no. She eventually agreed that I was right to stay away from it.

It is my understanding that the serum sickness from Rituxan is because of it being a murine (mouse-based) monoclonal antibody. Benlysta is entirely human, so there should not be the same risk of serum sickness. In addition, I can find no cases in the literature of belimumab causing serum sickness.
Is this correct?

Edit: In fact, one of the articles I posted above suggests that a BAFF-inhibitor (like Benlysta) should be used immediately after Rituxan in SLE patients.

"Thus, repeated rituximab infusions can result in a feedback loop characterized by ever-rising BAFF levels, surges in autoantibody production and worsening of disease. We argue that B-cell depletion should be swiftly followed by BAFF inhibition in patients with SLE."
www.ncbi.nlm.nih.gov/pubmed/26888554

Rob:

You are correct, the difference is murine vs human monoclonal antibodies. The reason that my Rheumatologist eventually agreed that I should not use Benlysta is because she came across an article about Benlysta and serum sickness. I do not have the reference. My main reason for staying away is because I think that I went into Rituxan far too easily, believing that it was safe. I didn't take the side effects seriously enough. I won't make the same mistake again. This was all I needed to see, because a hypersensitivity reaction was exactly what I had. There have been deaths due to Benlysta and unless it is a life or death situation, there is no point to taking the risk.

Hypersensitivity Reactions, Including Anaphylaxis

Acute hypersensitivity reactions, including anaphylaxis and death, have been reported in association with BENLYSTA. These events generally occurred within hours of the infusion; however they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema, have been reported and typically occurred up to a week following the most recent infusion. Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of BENLYSTA…

Hypersensitivity Reactions, Including Anaphylaxis

Hypersensitivity reactions, including anaphylaxis and death, have been reported in association with Benlysta. Delay in the onset of acute hypersensitivity reactions has been observed.
Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk.

Warnings and Precautions, Serious Infections

risk of Progressive Multifocal Leukoencephalopathy (PML) in patients with Systemic Lupus Erythematosus (SLE)


www.fda.gov/Safety/MedWatch/SafetyInformation/ucm299628.htm

I have tried so many medications over the years and from my experience, the side effects have always been worse than the benefits. I'm done taking risks with these meds.