Serum Sickness Post Rituxan

Hi All,

I am currently undergoing Rituxan treatment for my ITP because I haven't responded to steroids since my relapse in August. I have handled the Rituxan infusion itself well - no side effects during the infusion. However, last Monday, some 3 days after my 2nd Rituxan infusion, I developed a low grade fever (100.4), extreme joint pain in my knees, ankles, and feet, an the worst petechial rash I've ever had on my lower extremities. I saw the hematologist who ran a blood count. My platelets had crashed to 20, hence the petchechial rash. He felt the joint pain and fever were a Lupus reaction to the Rituxan (I have SLE in addition to ITP)and started me on a Dex Pulse which I finished this past Saturday. I had my 3rd Rituxan infusion last Friday while still on the Dex Pulse. Although I have not had a recurrence of the joint pain, petechia, or fever, I just haven't felt quite right (lymph nodes hurt, throat feels strange, lightheaded).

I am wondering if the reaction I had was actually serum sickness. And if so, I'm concerned about undergoing my final infusion tomorrow. My hematologist is excellent so I would think he would have thought of serum sickness, but with my history of Lupus clouding things. . . .well, I'm not so sure.

I've read if you get serum sickness that you should never have Rituxan again. Is this because you could get serum sickness again or because the reaction could be much worse the next time?

Thanks in advance
~Lauren

Hi Lauren. It's possible that you did have serum sickness. I've had it due to Rituxan, twice, and yes, the second time was much worse. It was misdiagnosed the first time I had it which was why I ended up having Rituxan again.

Over the years, I have seen many doctors overlook serum sickness as a result of Rituxan. Oddly, people with Lupus or people who have symptoms of Lupus seem to get serum sickness more often. If I were you, I would skip that last treatment. Studies have shown that two treatments are enough for ITP anyway, so you've already had all you need. It's not worth the risk.

Hi Lauren,
I agree with Sandi, do not get further Rituxan treatments. It can get much worse, maybe you would stop breathing or get hives in your trachea. And also that the amount of infusions you had should be plenty to kick off a remission, the last treatment shouldn't make a difference in response.
I stopped after two infusions and an allergic reaction and I've been in remission for more than 4 years. Same dx as you.
Erica

Hi lauren and all. My doctor actually keeps recommending that I get the Rituxan treatment because he thinks it will knock my platelet count up higher to a much stabler level. Is it common for that type of sickness and reaction to the treatment? I'm still deciding on whether I want to do it or not since my platelets have been stable around 30-35k, but my doctor thinks I should give it a shot. Hearing about these side effects are making my wary of trying it.

How many and how often is he suggesting it?

hollywood,
If your platelets are at a relatively safe level, you are not having bleeding symptoms and you feel well, then why treat with a major league drug? If you are having bleeding symptoms, or not feeling well, then worth considering. Or if you have a lifestyle or job where counts in the 30s are not safe.
Erica

Erica and Sandi,

Is there anything you 2 do not know??? I am in awe of you two...

Jeffrey

Well mostly my regular doctor keeps recommending it. I haven't seen my hematologist in about 2 years and he didn't say anything about it. I know that automatically should tell me that I don't need this treatment, but my regular doctor won't quit with trying to get me to try it. His daughter had a condition similar to mine and he said she went on the treatment and her platelets went up in the 300k. My mom wants to wait until summer to decide, but she thinks it's something to look into. I'm hoping to meet with my hematologist before then, but yeah. I definitely don't want to do this if I don't have to.

Hollywood,

I'm a big fan of rituxan, having lasting remissions in 2007, and again in 2011. But, my platelets were not stable and would always go down below 30 unless on prednisone. If my platelets were stable at 30 I'm sure my hematologist would not have treated me with rituxan.

I probably wouldn't listen to the advice of a GP. They are not always familiar with ITP. Rituxan is always an option, but if you don't feel you need it, no reason to do it.

Hi All,

Thanks for the advice. I have completed 3 rounds of Rituxan (skipped the 4th) and my count is up to 152! Not as high as I would have liked (I'm still on Prednisone) but I'll take it. Hopefully, after this week, my hematologist will start to taper the Prednisone and we will really see what my counts do. Honestly, I'll be happy if my counts stay in the 80-90 range, like they did for the last 15 years (until August 2013).

Interestingly, though, I saw my rheumatologist last week for a routine follow-up for my Lupus. I filled him in on what has been going on with my counts and he was pleased with my decision to go ahead with the Rituxan. We talked at length about the uses for Rituxan especially in those with Lupus. He told me he would suggest I repeat the Rituxan in 6 months if my platelet count is not in the 200+ range. He frequently does this with his Lupus patients and has found they often get a longer "remission" with their platelet counts. I'm not so sure I want to undergo another round of Rituxan if my counts are stable, but I told him I would certainly consider it if/when the time comes.

Have any of you received or considered receiving Rituxan prophylactically?

Thanks again,
~Lauren

Lauren:

Oh my goodness. Where to start.

I don't believe in prophylactic Rituxan. Here's why. I think my last Rituxan was in 2004. I had one treatment, then got my second serum sickness episode. It was determined then that I should never have Rituxan again, but anyway, counts went up to 150 and have been normal since (that's nearly 9 years of remission). If I'd never had serum sickness, and if I'd had Rituxan prophylactically, say even two treatments a year, I'd have been given 18 Rituxan infusions for absolutely no reason since we'd never have known that my counts would have stayed up without any treatment at all.

Rituxan is a toxic drug that can cause problems over time. It can lower immunity, especially for someone with Lupus. It can raise the risk of cancer (already an elevated risk for someone with Lupus). Most of the time with ITP, there is no real harm in waiting until you need to be treated. I've never seen any real reason to prevent a drop and keep counts in a normal range if a person does respond to treatments. Since ITP can be chronic, the less drugs over time, the better.

Then there is the possibility that you did have serum sickness. It's a shame that you were not properly diagnosed, because you need to take that seriously. Your doctors should be taking a good look at that too. It's not something that should be blown off. After my second serum sickness, I was never the same. It stirred up inflammation that I have never been able to get rid of. If I hadn't been misdiagnosed the first time, I'd be a lot better off right now. Serum sickness reactions can get worse and can cause death.

Also, I've read a lot of studies about Lupus and Rituxan and the reviews are not all that great. It can work for some and do nothing for others.

There was more disappointing news for rituximab (Rituxan) and its potential role as a lupus therapy, however. Rituximab is a monoclonal antibody that depletes CD-20 B cells. Joan T. Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City, presented data from two analyses of an ongoing trial evaluating rituximab in people with moderate-to severe lupus.

In the phase II/III EXPLORER trial, participants were taking immunosuppressants and steroids. They received four infusions over six months of either a placebo or rituximab, during which the steroids were gradually stopped. After 78 weeks, the rate of serious and minor adverse events, including infection and infusion reactions, were similar between the two groups, although there was a higher incidence of viral herpes, neutropenia and serum sickness in the rituximab group.

A study evaluating the subset of participants who showed a response to either placebo or rituximab found that severe and moderate flare rates were similar in both groups during the year they were followed. However, the average flare rate in the rituximab group was significantly lower than in the placebo group, suggesting that rituximab may increase the time to flare compared with placebo.

The results of the EXPLORER trial troubled clinicians, many of whom use rituximab for patients with lupus even though the drug has not been approved for that use yet. When asked how the results should be interpreted, Dr. Merrill replied: "while there is no evidence that rituximab works, I'm dissatisfied with the evidence that it doesn't."

And, in fact, other studies of the drug presented during the meeting show differing results.

A study in 35 African-American and Hispanic patients who received four weekly infusions and were followed for two years showed a significant drop in disease activity throughout the study in all participants, even those with lupus nephritis.
A study in 86 peopled with lupus treated with rituximab with or without other lupus treatments for an average of 15 months found that an estimated 73% of treated patients showed improvement. Overall, 10 people had severe infections and one died from an infection.

What this means for people with lupus? It is quite likely that rituximab works in certain populations of people with lupus. The disappointing results from the large, manufacturer-sponsored clinical trials may be related to the way the trials were designed. The decision to use or not use rituximab is one you should make in conjunction with your doctor.
www.lupusresearch.org/research/acr/latest_advances.html

This is all just my opinion. You have to do what you think is best for you. However, having two autoimmune disorders also, I can tell you that the number of drugs you use will increase in time and that can accumulate to a lot of meds in years to come. I have tried so many and all have come with a price. I've come to the conclusion, if it ain't broke, don't try to fix it.

Sandi and Erica,

Thank you both for the strength of your comments advocating caution with Rituxan and other high-powered drugs. The more I read, the more I believe that the treatment is often far more dangerous than the disease. This is doubly true for Ellen, as she works in an infectious disease clinic, and has a family history of cancer as well. Thanks to you, Ellen is taking a MUCH more conservative wait-and-see approach to her treatment, and has the courage to be firm with her hematologist.

.

Thank you, Sandi, for your insight and opinion. When the rheumatologist suggested Rituxan prophylactically, I was rather surpised. I understand his thought process, but I'm not one for medications unless absolutely necessary. I wrestled with the decision to start Rituxan for my ITP, but after 2 months of Prednisone and no real change in my platelet count, I finally agreed.

I have a follow-up with my hematologist next week and plan to discuss both the rheumatologist's suggestion of prophylactic Rituxan as well as my "reaction" 2 weeks ago that I truly believe was serum sickness.

Although, I'm curious about one thing you mentioned in your last post. You said the Rituxan stirred up inflammation that you've never been able to get rid of. My hematologist mentioned that to me when I was going through the "reaction" a couple of weeks ago. He said he thought my "lupus" was reacting to the Rituxan, thus causing inflammation again in my joints (his explanation for the extreme joint paint I was having). I looked back at lab results and my SED rate has been high for the last several years. 3 days before my "reaction", I had some labs done for the rheumatologist including a SED rate which again was high at 95. Since starting Rituxan, I have had joint swelling and stiffness in my hands and feet every morning, which I haven't had since I was diagnosed with Lupus some 18 years ago. It moderates during the day and isn't causing me any pain at this point, but I find it interesting that I had none of this prior to Rituxan.

Thanks again.

Laura:

My story is a bit different in that I didn't have Lupus prior to Rituxan. I'm sure I was destined to acquire it at one point if the right trigger came along, and that trigger ended up being the serum sickness reaction. After the first time, I had horrible muscle stiffness for months, but it eventually subsided. After the second time, I began to have other symptoms on top of muscle stiffness that to this day, have never gone away. Since it all began at the time of serum sickness, there is no doubt in my mind that it was caused by that. Just like any virus or illness can trigger an autoimmune disorder, that was my trigger. My labs were abnormal after that, but were not before (SED, C3 and C4, ANA, etc).

You have to look at several different things when trying to determine whether it was a Lupus flare or serum sickness. 1) Timing. Serum sickness will always occur 14 to 21 days after starting a drug. That is the typical timeline. Also, if a person uses the drug again, serum sickness will occur 7 to 10 days after starting the drug. The reaction is faster the next time and is exactly when I got it the second time. 2) Severity. Serum sickness hits quickly. One day you are fine and literally the next day, you wake up and can barely get out of bed. Joint pain is severe, like nothing you've ever felt before. I could barely hold a cup or turn over in bed. 3) Length of illness. Serum sickness usually only lasts a few days, although residual pain can last longer. Steroids do help to lessen the pain a lot. Lupus flares can last weeks and normally don't resolve all that quickly.

The fact that you were okay after the third treatment doesn't mean anything. After my first time, I went on to have my fourth treatment and didn't have any problems. However, the following year when I had Rituxan again, I got hit hard.

Even if "lupus was reacting to the Rituxan, thus causing inflammation in joints" as your hemo said, then perhaps Rituxan is not the drug for you anyway. Who wants to risk a Lupus flare by reacting to a drug that is supposed to help Lupus? Either way, Rituxan triggered some sort of bad reaction and it amazes me that it's been suggested that you use it again.

I get a bit ticked off every time I think of the ER doc during my first reaction. I kept telling him that I'd been having Rituxan treatments and asked if it could be related to that. He kept saying, "no, it's a virus". If he'd bothered to look it up, he would have found out that based on my symptoms, I could have had serum sickness. As a result of his laziness, the course of my entire life was altered. As a result though, I now question everything and never blindly believe what a doctor tells me. I look things up for myself before making decisions.

Hi Sandi,

So in my case, I was diagnosed with Lupus approximately 3 years before I developed ITP. My initial symptoms of Lupus were extreme joint pain and swelling in my fingers. This led to doctor's visits, blood tests, and the diagnosis. Ironically, for me, I haven't had joint pain or swelling since I was diagnosed some 18 years ago. All of my "Lupus" symptoms have been ITP or TTP (I've had both).

Re: serum sickness. My reaction hit me when I woke up on a Monday morning. I felt absolutly fine the day before. It was 13 days after my first Rituxan infusion and 3 days post the second the infusion. As the day progressed, the pain in my feet and legs became so bad, I could barely walk and had to hold onto walls for support. In addition, I developed a fever and a vascular/petechial rash (platelets were very low) all over my legs.

After seeing my hematologist, I started the Dex Pulse and felt better after a day, with the joint pain subsiding after a couple of days.

I suppose my anxiety over whether it was a Lupus flare or serum sickness is probably moot at this point because I got my weekly count today and while I was 152 last week, I'm down to 34 this week. Rituxan doesn't seem to be working anyway, so I'm not likely to have it again in the future. My hematologist said we'll need to discuss other options. He is starting to taper my Prednisone (down to 5 mg daily) - as he said, it isn't really regulating my counts and I've been on it since August - so we'll see what happens next week. I'm hoping I level out here soon. I'm not at all interested in the other options my doc mentioned when we were discussing Rituxan.

Thanks,
Lauren

Lauren:

Rituxan usually takes 4 to 12 weeks to work. It's not an immediate response like steroids would be. I'd give it more time before giving up on it.