Low dose Rituximab (Rituxan) research

I think it's from the first dose also. Good luck, Farida. 20k isn't too bad, so if he can stay in that area for now, he should be able to ride out the wait.

You said that he stopped Prednisone on his own? He shouldn't do that.

Hey Everyone:

Back in April of 2013, I had 725 MG times 4 and had no side effects but also no effects at all to my platelet levels! I haven't looked at all the research, but does it make any sense to try the low dosage at this point? Logically if Rituxan had no effect on my levels at 725 MG, why would it at 100 MG's? Have I missed something? Thanks!!

Jerry Spaniol

Lots of people have side effects with rituximab, and some of those side effects decrease or disappear at lower doses. Plus, rituximab is very expensive, so if less will work, why take more?

The purpose of rituximab is the depletion of B-cells, and B-cells are completely depleted at the lower dose. The idea is not to get better results at a lower dose, but rather, comparable results with fewer side effects.

Rob:

Since the higher dose of Rituxan had no effect on my platelet levels whatsoever, therefore, eliminating B cells and the associated antibodies is not a solution that will work for me. If the higher dose doesn't work,the lower certainly won't. I answered my own question. Thanks!

Jerry

6 weeks now for the first low dose my sone took and his plateltes still go down when he decrease the prednisone , he is frustrated ,stressed out , his graduation was today from the university but he couldn't be happy ,he just told me that he feels that platelts go down after the celebration .
he is asking me what shall we do? but i have no answer ,i hope sombody can asnwer me , can he try now the 375 mg since he sresponded very well 2 years ago , and he can finish 3 other dose for 375 mg .

Another study out of China:

www.clinicaltherapeutics.com/article/S0149-2918(14)00026-5/pdf

Is Splenectomy Necessary for Immune Thrombocytopenic Purpura? The Role of Rituximab in Patients With Corticosteroid Resistance in a Single-Center Experience

Cheng Zhang, MD, Huan-Feng Liu, BA, Xing-Hua Chen, MD, Lei Gao, MD, Li Gao, MD, Yao Liu, MD, Pei-Yan Kong, MD, Ai-Hua Sun, BA, Xi Zhang, MDemail
Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, People׳s Republic of China

Objective
We explored the potential role of rituximab as an early therapeutic option for patients with corticosteroid-resistant ITP who preferred to avoid splenectomy in favor of other treatment.

Methods
Twenty-five patients with corticosteroid-resistant ITP were treated with rituximab between May 1, 2009, and June 30, 2012, at a single center. Rituximab was administered at 100 mg/m2 on days 7, 14, 21, and 28. The response to rituximab therapy and adverse effects were observed.

Results
Complete remission was achieved in 19 patients (76%), partial remission in 3 patients (12%), and minimal response in none of the patients; 1 patient was considered a treatment failure (4%). Two patients (8%) were lost to follow-up. Twenty-two patients (88%) achieved a platelet count >50×109/L. The median time from administration of the first rituximab dose to partial remission was 2 months (range, 0.7–3 months) for all the patients. Response classified as sustained was achieved in 21 patients (84%). No serious adverse effects were observed during rituximab therapy.

Conclusions
Rituximab therapy is effective and safe for patients with corticosteroid-resistant ITP before splenectomy, resulting in high complete remission and overall response rates. A multicenter study with a larger sample should be performed to further explore the role of rituximab therapy.

Farida, Please note the response time in the study I just posted:

The median time from administration of the first rituximab dose to partial remission was 2 months (range, 0.7–3 months) for all the patients.

Your son has not yet reached the median, much less the maximum amount of time to respond.
I think it is too early to lose hope that this will work. I think the low dose works more slowly, I read somewhere.

I wish they would do a study about the splenectomy failure rate after treatment failures. It seems as though the people who seem refractory to treatments also do not respond to splenectomy. It might save quite a few spleens.

You may have something there Sandi. It's true of 5 people I know including me. We've either had failed splenectomies or the indium test showing that a splenectomy probably wouldn't work. And 4 ended up on Nplate as a last resort. The 5th didn't even have Nplate work for him. But maybe it's a matter of only knowing about those sorts of people. Hmmm. Shame we can't do the study.

Sandi and Ann,

I think if I'd had several failed treatments, I would try splenectomy. For me, I think it would become more attractive after dealing with all the side effects of other treatments with no response....when a successful outcome of splenectomy would get life back to normal. Even if the odds went down, for more than a few people I suspect it would be worth the risk.

I have really mellowed on this topic. I used to be very rigidly against splenectomy, but part of that was because it would close the WinRho door for me (and others). Now that WinRho's less commonly used, that downside is mitigated. We've seen a lot of people have splenectomies and never come back here (I always think of VaultOSU) who made their own decision to go ahead despite what we said, and presumably many of them never think about ITP any more....which would be very attractive. Of course it's a crap shoot, but I'm not sure it's as tragic a decision as we sometimes make it out to be.

Having said that, OF COURSE more research is always good so that people can make the most informed decisions possible.

Tamar:

I'm not quite sure how I feel about splenectomy any more. I would never try to talk anyone out of it, and there are certainly times when it's worth a shot, but it doesn't come without risks. I agree that if a person has failed all treatments they have nothing left to try but splenectomy. However, after a failed splenectomy, all of those same treatment options that they would try again become much more of a risk. People with ITP are not like the general population who can lose a spleen and only have to worry about sepsis.

I'm seeing more and more articles about spleen saving treatments and some of the top doctors are not recommending it any more. Since the TPO's came out, most can be managed with those and splenectomy can be pushed further down the line. Luckily, there are so many more options than there used to be.

I would still like to see a study done on that. Doctors love to quote the 60% success rate of splenectomy. I'd like to see the success rate after four or five failed treatments.

cbc done today . count is 430k still on 20 mg prednisone ,6'th week of the first low dose of rituximab having hope that the rituximab it will kicked in . :laugh:

I'm in the I don't know how I feel about splenectomy anymore either group. I stopped responding to IVIG, do not respond to steroids and do well with both Nplate and Promacta. However, I am 29 and would like to have a baby in the next few years. I guess in my situation would it be worth having a splenectomy if it meant temporary remission possibly to have a pregnancy with safe counts.

my son is 21 years old got itp when he was 16 years old ,i suffered 2 years relaps every month , doctor convence my son and us as well to do splenectomy ,but it failed , it was so sad , and i had to try rituximab which i denied it before the surgery , but thank God my son was in remetion for almost two years relaps 2 month ago and now he tried low dose 100 mg i still have the hope that it will work for him . every one is different, i hoped i tried the rituximab before the surgery .

Farida, Great News! 430k is a better count than one would expect from 20 mg prednisone alone, especially since your son was 20k on 20 mg not too long ago. It looks hopeful that the Rituxan is working. Have there been any side effects from the low-dose Rituxan?

Sandi wrote: Tamar:

I'm not quite sure how I feel about splenectomy any more.

My view is that splenectomy is fine as long as the doctor can honestly say that the patient has given *informed consent*. Not just consent but has been fully informed about and understood the risks and disadvatages.

Unfortunately it doesn't happen like that very often, or so it seems to me.

i had my splenectomy done in 2010 since i had two remission since then they lasted 2 years in between while keeping the count above 200k so its how everyone views it. i rather have 2 year remission than none at and because to be constantly taking pills and shots take a toll on your body.that being said do i wish i had my spleen back yes am i gonna dwell over my decision and failed result no at the end of the day it our decision not the doctors they should just give options and we should just live with result of the splenectomy good or bad

Ann - I don't believe that many doctors are even aware of the risks or don't take them seriously enough. Remember the teenager who had a splenectomy a few years ago and then had DVT's a few weeks later? He had Factor V Leiden thrombophilia and didn't know it. No one bothers to test for clotting disorders such as APS or Factor V Leiden thrombophilia prior to splenectomy. Granted, these are rare events but not fun for the people who have to juggle blood thinners for life.

Then there are the people who end up with CVID or Lupus and are immunosuppressed due to those disorders. No one knows what the future holds. You try to fix one problem but create another. These disorders are commonly seen with ITP so it's not so far-fetched that they might occur.

Of course everyone has to decide for themselves. Every situation is different and some people, like Valerie, have valid reasoning behind their possible splenectomy choice.

not at all ROB ,he said it is much better than the 375mg which he was on 2 years ago , i hope the low dose works for him i will keep posting his cbc count so give everyone new hope with the low dose

It looks good Farida! Another remission on the way....

Again from China, this time for SLE patients

www.ncbi.nlm.nih.gov/pubmed/21571767
Rheumatology (Oxford). 2011 Sep;50(9):1640-4. doi: 10.1093/rheumatology/ker176. Epub 2011 May 13.
Low-dose rituximab therapy for refractory thrombocytopenia in patients with systemic lupus erythematosus--a prospective pilot study.
Chen H1, Zheng W, Su J, Xu D, Wang Q, Leng X, Zhang W, Li M, Tang F, Zhang X, Zeng X, Zhao Y, Zhang F.
Author information
1Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.
Abstract
OBJECTIVES:
To evaluate the safety and efficacy of low-dose rituximab therapy for refractory thrombocytopenia in patients with SLE.
METHODS:
Ten adult SLE patients with severe refractory thrombocytopenia (mean platelet count 10.4 × 10(9)/l) were enrolled in this prospective pilot study. All patients had failed traditional high-dose CSs and immunosuppressants including methylprednisolone pulse therapy. Patients were scheduled to receive i.v. rituximab at a dose of 100 mg once weekly for 4 weeks. Previous dose of CSs were gradually tapered, and immunosuppressants were withdrawn. Patients were followed at Weeks 4, 12, 24 and 36.
RESULTS:
All patients completed four courses of low-dose rituximab infusion. At Week 4, two (20%) patients achieved complete responses (CRs, platelet count >100 × 10(9)/l). The CR rate increased to 60% (six patients) at Week 12, was maintained at Week 24 and began to drop at Week 36 (four patients, 40%). Overall response (OR, platelet count >50 × 10(9)/l) was achieved in 5/10, 6/10, 7/10 and 5/10 patients at Weeks 4, 12, 24 and 36, respectively. Peripheral CD19(+) B cells were depleted (<5 × 10(6)/l) in all patients at Week 4, and gradually increased at Weeks 24 and 36. Serum C3, IgG, IgA and IgM levels did not change significantly (P < 0.05). Infusion reaction was observed in two patients. One patient developed pulmonary thrombosis at Week 14 and active tuberculosis at Week 25.
CONCLUSIONS:
Low-dose rituximab therapy is effective in treating severe thrombocytopenia in SLE patients who do not respond to vigorous glucocorticoid plus immunosuppressants, and in most cases is safe.
PMID: 21571767 [PubMed - indexed for MEDLINE] Free full text

i hope sandy , i will update when he do his cbc again and stope the prednison .thanks

I just started retuning therapy also take high dose prednisone wondering if that's what I have to look forward to , you know same medicine different day forever. :blush:

I think everyone fears that, Wayne, but it's not true. Most people do have drug-free remissions at some point. Those who choose N-Plate or Promacta which can be long term can still live normal, side effect-free lives. Forever is a loooooong time.

Rob16 wrote: I have only found one study - in children - where a single dose was given. " A single dose of rituximab resulted in a response rate similar to that reported for cases in which 4 doses of rituximab were used." The dose was 375 mg per sq meter.
www.haematologica.org/content/90/2/281.abstract?ijkey=78873704fe05255bc16d48afd15c9d680f85e6e1&keytype2=tf_ipsecsha

Rob, I was web-surfing today and came across this abstract which mentions the same single 375 dose, and it isn't referring to just children.
The fifth sentence is the relevant one - "A single 375 mg/m2 infusion may be as efficacious as the classical four infusions cycle."

www.ncbi.nlm.nih.gov/pubmed/?term=Rituximab+Off+Label+Use+for+Difficult-To-Treat+Auto-Immune+Diseases%3A+Reappraisal+of+Benefits+and+Risks

That's good to hear. The less, the better! Really, what's the harm in trying?

This is another link to the article Janet mentioned, but showing the first two pages of the actual article:
link.springer.com/article/10.1007%2Fs12016-007-8020-7#page-1
It refers to a study of 22 children given a single dose of rituximab, which is the same as the study I cited earlier:
www.haematologica.org/content/90/2/281.full.pdf+html (full text online)

This is my pet peeve, that our tax dollars go to pay for these studies, but we cannot read the full text of many of them without paying through the nose!

I would love to see a study comparing 4 X 100 mg vs. 1 X 375 mg/m2. The 4 X 100 is actually a smaller dose for most adults, but the single dose would be much more convenient. Until then, we will stick with the 4 X 100 mg protocol as it is better proven.

... and Ellen starts her low dose Rituxan treatment a week from Monday, on August 11!

Oh, sorry. I didn't realize it was the same article you were talking about.
I agree with being frustrated not having access to an entire publication.

Best of luck to Ellen!

I just want to comment on the reason that full articles have a price....they have a cost. Though it is sometimes (not always) tax money that pays for the studies, it is almost always the publication that pays for the peer review. If we want high quality, peer-reviewed studies, there has to be a price for reading them when they are new.

If you want to read the study for no charge, find your nearest medical library that carries the journal and read it there or have them make you a copy of it. At the UofM medical library, I can get a copy of any article from any of the journals they subscribe to for 10 cents/page.

EDIT: there are even ways to get articles that aren't available in the local medical library. One time I had my brother (who's a psychiatrist) request a copy of an article from another medical library, and one time I emailed a study author directly (in Israel) and explained why I wanted a copy of the article, and he sent it within a few days.