Rituxan time frame

Am trying not to get discouraged as my Dr told me it can take 6 - 8 weeks, but my numbers have done nothing but drop since after the first treatment.

I started at 25 before treatment, (after being on various doses of prednisone for the past 2 years, a final dosage of 80 mg that was doing nothing, and one emergency IVIG and one dexamethasone treatment.) After my first treatment I jumped to 143. Subsequent weeks went as follows:

55, 42, 120, 93, 68.

Doctor wants to keep me at 50 or above. So next week's CBC will be pivotal. Was rejected for Promacta but can re-apply in January. Or have splenectomy, which I've been trying to avoid.

I guess my question is: Are my numbers apt to go back up this far after the Rituxan treatments, since they've been going steadily down and the 4 treatments are complete?

I was told that it could take up to 12 weeks for any improvement although some, including myself, saw more immediate results.

I was also told that it would take up to 12 weeks to see any results but Rituximab did not work for me and on the morning of my 4th treatment my count had actually dropped to 0. Unfortunately we all seem to respond differently to the various treatments.

Gosh Robert. Looking over past threads, you've had quite the (extreme) roller coaster ride while on NPlate following Rituxan. Wow, just Wow. With those kind of count extremes seems Rituxan may have contributed in some way, yes?

NPlate following Rituxan, interesting. Have you seen others do so well with that sequence?

I actually think your counts are quite good. My counts during Rituxan treatments were below 10k the entire time until they finally went up to 150k the fourth week. Your counts are still above treatment level and might just level out to at least a partial remission. Some people have seen a rise up to 12 weeks after the first infusion. See what happens over the next few weeks.

If you'd get Promacta or N-Plate, the goal is to keep counts around 50k - you're already there.

I know you see a dropping trend at the moment, so hang in there and see what happens. Yes, your counts could still go up.

Thank you everyone. I've been discouraged because I was hanging around 9 and 13 before the prednisone. It worked for about 18 months and then just stopped altogether and I was back below 15 all the time, hence the Rituxan. Plus the prednisone is making me crazy and I can't take the weight gain! It just seemed odd to me that weeks AFTER the 4 treatments the number could go back UP.

Fortunately, I have always felt fine, which almost makes it worse, because I don't "feel" like there is anything wrong.

I appreciate your responses!

Feeling fine is good!

If Prednisone stopped working, I'd almost consider that a blessing in a way. You were on it for a long time and it's best to end that before long term problems occur. It worked great for me so I ended up using it on and off for years until I finally said, "Enough" and tried something else.

Rituxan doesn't work fast like IVIG and steroids. It destroys B cells and T cells and that takes time. It keeps going even after the treatments end.

It would be hard to say if the Rituximab did work in conjunction with the NPlate (and I had also had such a concoction of other treatments prior to that) but whatever it was, it finally worked. The NPlate ride was certainly extreme and thankfully I did not have adverse effects from the high counts.
It was almost impossible to balance my count to the 50K goal as even the smallest dose would have a dramatic effect on my platelets and I would then lose 150K per week when I didn't have the treatment and so it was a real juggling act.
I had my 2 year remission last month and thankfully remain treatment free.

I think any count above 30 is acceptable and would be loathed to try anything else if it holds at that

Right. But most ITP treatments ramp up in a week or two to work - or to fall off. Isn't Rituxan the only one that is known to take a month or two, or even longer for a response?

LOL, in some sense, you have had a 'combination' therapy...

Dapsone can have an even slower time to response, up to 15 weeks.

www.ncbi.nlm.nih.gov/pubmed/24512442
Dapsone for immune thrombocytopenic purpura in children and adults.
Abstract
Dapsone is one of the second line treatments of immune thrombocytopenic purpura (ITP). Dapsone is cheap and has response rates comparable to other second line treatment options like azathioprine, danazol, cyclophosphamide, cyclosporine, and vincristine. This retrospective analysis includes 38 patients (out of total 313 patients) of ITP treated with dapsone from 2004 to 2012. All male patients were screened for G6PD deficiency before starting dapsone. Out of 38 patients (12 children and 26 adults), one was newly diagnosed ITP, seven were persistent ITP, and 30 were chronic ITP. Five patients had side effects of dapsone; two required discontinuation due to skin rashes. The average dose of dapsone was 1.57 mg/kg/day and time to response was 57 days (19-108 days). The response was irrespective of previous treatments and response to them. The response rate was 48.6% (complete response = 40.5%). Only two adult patients had sustained response (> 6 months) after dapsone discontinuation. There were no predictors identified for dapsone response. Dapsone is a safe and cheap second-line therapy for ITP with a response rate of about 50% (majority being CR). A response to dapsone is slow, sustained, and relapses are uncommon on therapy. Dapsone withdrawal leads to relapse in most of the patients.

I was also taking 100mg of Dapsone over the 4 weeks that I was given Rituximab. After that I was given Cyclosporine both during my 4 day Dexamethasone pulse and into the first 10 weeks of my 5 month NPlate treatment. My specialist advised at the time that she had been discussing a combination therapy with other specialists (maybe even Amgen - unfortunately I can't remember) and that was the approach that she was adopting.
So all in all I am not sure whether it was the NPlate alone or the combination of all the treatments that eventually resulted in my remission. I can say however that Prednisone was the worst of all the treatments I was given!

Dapsone and Rituxan. Cyclosporine and Dex. That sounds like some leading edge ITP therapy. I wonder if they stumbled upon these combinations are there is a rhyme to the reason.

Some quick research shows Dapsone is used to treat Gluten sensitivity. Oh my. May need to go on a gluten free diet again and retest myself.

Have you ever tried gluten free diet Robert ?

These combo therapies certainly payed off for you! Nice.

www.ncbi.nlm.nih.gov/pubmed/11719360

cyclosporine is mentioned here.

Interesting find jay.

I note that the date seems to be in 2001. One would think that would predate Promacta/NPlate. Odd. Do you suppose cyclosporine would be helpful if one develops TPO antibodies after taking NPlate?

I have no clue Hal.

Now Iam learning TPO can also have anti bodies like platlets.

Hey, guys. Cyclosporin has been around for a while and actually isn't used often for ITP. I have seen it used here once in a while, but it's not common. This drug is generally used for organ transplant rejection and is a heavy duty med. It has risks.

As in patients receiving other immunosuppressants, those patients receiving Cyclosporine are at increased risk for development of lymphomas and other malignancies, particularly those of the skin. Patients taking Cyclosporine should be warned to avoid excess ultraviolet light exposure. The increased risk appears related to the intensity and duration of immunosuppression rather than to the use of specific agents. Because of the danger of oversuppression of the immune system resulting in increased risk of infection or malignancy, a treatment regimen containing multiple immunosuppressants should be used with caution. Some malignancies may be fatal. Transplant patients receiving Cyclosporine are at increased risk for serious infection with fatal outcome.

Of course, the higher the dose the greater the risk, but the risk is there with any dose. Length of time on the drug also matters. It's also not something that might show up right away...it could take 10 to 20 years to develop a malignancy. Any and all immunosuppressants carry that risk, including steroids, Rituxan, CellCept, Cytoxin, Imuran, and Cyclosporin.

The thing you always have to keep in mind is benefit vs. risk. Sometimes you don't need a jackhammer to drive in a nail. I know the tendency is to want to fix things now, but you also have to look at the big picture and remember that your health will also be important years from now.

It sounds to me like there might be some confusion about TPO and antibodies.

Thrombopoietin is a natural hormone that triggers platelet production. Recombinant thrombopoietin (TPO) os thrombopoietin that has been created in a lab using DNA recombination (whatever that means).

We sloppily refer to Promacta and Nplate as TPOs. They are not. They are thrombopoietin receptor agonists (TPO-RAs) which means they are molecules that trigger the same receptors that thrombopoietin triggers in order to stimulate platelet production.

Before Nplate and Promacta, research was done to attempt to stimulate platelet productions using TPO, but sometimes a very dangerous response happened, where antibodies to recombinant TPO occurred, and the patient's own thrombopoietin was attacked as well. The result was that these patients were much worse off than before treatment. Nplate and Promacta were created to get around that problem.

Since then, it has been shown that it is possible to develop antibodies to Nplate, but this does not result in sensitization to one's own thrombopoietin. I don't believe antibodies to Promacta have yet been discovered.

That's reassuring Rob as I think Promacta will be my next attempt achieving a safe count.

Hello Rob,

www.ncbi.nlm.nih.gov/pubmed/11719360

The above study was making the claim that -
"Thrombocytopenia caused by the development of antibodies to thrombopoietin."

Rob16 wrote:
Since then, it has been shown that it is possible to develop antibodies to Nplate, but this does not result in sensitization to one's own thrombopoietin. I don't believe antibodies to Promacta have yet been discovered.

So why does coming off Nplate after a few years result in a worsening of the platelet count which in my case (nine months) has not yet recovered?

RJ,

I don't have any answer to your question,... only some thoughts:

The fact that you also don't respond to Promacta makes me think that your problem is not with antibodies to Nplate or to your own thrombopoietin. Rather, I would think that either you have other platelet production problems, or your platelet autoimmunity has worsened, such that increased production from TPO-RAs cannot compensate. Your unremarkable bone marrow biopsy, and your non-response to immunosuppressants, on the surface seem to rule out all of the possibilities!

The immune system is far more complicated than I can understand, but I am aware that there are multiple mechanisms for an immune response, and that not all immunosuppressants act against the same mechanisms. If Rituxan doesn't work, then the problem might not be CD20⁺ B-cells. It might not even be B-cells at all. For example, there is a subset of lupus patients for whom natural killer cells (NK) play a significant role.
www.jimmunol.org/content/196/1_Supplement/194.5.short

Medicine is not yet able to target every potential autoimmunity with narrowly acting immunosuppressants. But there is rapid progress being made.

rjsmyth wrote: So why does coming off Nplate after a few years result in a worsening of the platelet count which in my case (nine months) has not yet recovered?

Probably because the drug kept counts up and if it's not being used, counts dropped back down. The manufacturer states that stopping the drug could, and probably will, result in low counts. some people might achieve remission over time but if that doesn't happen, you're back where you started.