TOPIC:

Has anyone experienced loss of response to Nplate and/or had to increase dosage after being on it for a number of years?

I lost response to it after about a year. My count dropped to 6 the day before I was due to have surgery which was of course then cancelled. I was never over happy on it, my counts swung about like a yo-yo. Much happier on Promacta

Thanks MrsB. A year isn't very long. I wish Promacta worked for me. Glad it does for you. Nplate has been great for me. Hopefully this is just an inexplainable phase and I don't have antibodies to Nplate.

I have had to increase my dose of Nplate. I have been on it weekly for 5 years. In the beginning 3mcg kept my counts to 50, now I'm up to 5mcg and my counts are generally in the 20-50 range which is safe for me. Interesting though when I was on Promacta I became more responsive to it over time. Counts climbed to over 100 on 50mg, so I was able to lower the dose to 25mg. But I had difficult side effects so switched to Nplate.

That is really curious about Nplate vs Promacta. It's good hear about you having to increase Nplate dose. Perhaps that's what's going on with me. Was it a gradual increase or did you suddenly have to increase it by a lot?

I have been contemplating that if something opposite is possible? That is, for someone being on these drugs, is it possible that one, after couple of years of receiving them, is able to totally discontinue them?
I just wanted to try reducing my dose and see what happens, but I'm afraid and sometimes (say once a month) I have nosebleeds, but never check platelets when I guess I'm low, LOL
And conversely, I sometimes feel somewhat lightheaded or experience very mild (and short lasting) pulses of headache, which I guess might be due to high platelets, but tests have not ever shown more than normal platelet count (and MPV is on 11 or so I guess).

Poseymint, what side-effects turned you away from Promacta?

Lman, I rarely hear about Promacta or Nplate losing efficacy, but I have often heard/read about people who take these drugs and end up in remission.

bh2- I gradually increased Nplate. But it didn't mean I was losing responsiveness to it completely, things just change. I don't believe its antibodies in my case.

In 2017 I was able to lower my Nplate dose. I was on 495 and 452- the nurses kept switching the doses back and forth trying to overcompensate for counts they thought were not right. They were actually creating wild swings. My counts would be 76 then 3 and 80 then 5. Every time my dose was changed my counts would crash. Even an increase could make my counts crash. So I told my doctor I wanted my dose left alone at 452. I wanted the dose to remain constant and let my immune system do the adjusting. That really worked and my counts leveled out around 50.

So then I caught bronchitis and my counts shot up to 395- wow. I skipped my dose that week. Next week my counts were back to 50. My doctor wanted to give me a dose and asked me what dose I wanted. (hes nice that way) I said I wanted to lower my dose so we decided on 412 which is 5mcg per kilo of my weight. And to our surprise that lower dose worked! It kept my counts at 50 for a long time. Now my dose is 408 because I've lost a bit of weight but its basically been the same lower dose for a couple years.

Remission- yes, a number of people have gone into remission after being on these drugs for a while. Sometimes their counts slowly begin to climb and they lower the dose until they are able to quit.

My side effects from Promacta were unusual. I had brain fog, memory lapses, headaches- trouble with thinking and memory. I quit Promacta 4 times due to side effects and each time my counts held for a while, then slowly drifted down over a period of a couple weeks. so that was nice.

Thanks.
Look at here. almost 2/3 of people on Romiplostim have successfully discontinued it, within 10 years, and of course before they start romiplostim, they had tried other drugs as front line, so they had chronic itp. But, the problem is that the number of patients in this study is too little, and I have not found any other article examining itp patients being on nplate for a long long time (more than 5 years) and also consider if they could stop it.
2/3 is a good number
UPDATE:
here's the link which I had forgotten to share : www.ncbi.nlm.nih.gov/pmc/articles/PMC5479599/

Thanks Poseymint. I agree that reacting to each weekly number by raising or lowering dosing of Nplate is not helpful. I am fortunate in that my hemos have thought it best to keep Nplate dosage stable. It's worked well.

Lman, 2/3 is great. There is hope!

b2h, Just put the link, I had forgotten to do so!
by the way, it seems like Neve is doing fine! I have not heard from her for a while.

Lman, the last paragraph mentions '~30%' as the remission figure. Where are you seeing 2/3?
The wording is confusing. I take treatment 'not indefinite' to mean remission.

Hal, do you see figure one? eventually around 60 percent are able to successfully discontinue romiplostim.
That makes sense, take a look at this well known itp article : www.bloodjournal.org/content/97/9/2549.long?sso-checked=true
where it says: " Another factor that might contribute to the discrepancy with other studies is the long follow-up that increased the chance to observe late responses. In line, in 10 of 15 patients with treatment failure, Picozzi demonstrated spontaneous normalization of platelet counts after an average of 7.5 years"
I think some people will achieve this remission, and perhaps it's regardless of the maintenance treatment they are receiving.

onlinelibrary.wiley.com/doi/full/10.1111/bjh.15803
This might be of interest

I Had seen it before, but as I see In the charts, follow up is at most 3 years?
And Anne, that was why I had asked you about have you got better during these years?
This might not be very scientific article: www.self.com/story/6-things-you-should-know-if-you-live-with-chronic-itp
But, there, Doctor Naik (which from John Hopkins center) claims this :
"Most adults with chronic ITP see their symptoms become stable within five years of getting diagnosed, according to the Merck Manual, and some people even spontaneously recover. But if that’s not you (yet), remember that although chronic ITP isn’t curable, doctors do consider it to be a very treatable condition. “[ITP] tends not to be this very dramatic thing for your entire life,” Dr. Naik says. “It does get better.”
Related"
She had been conservative on saying that, but her reference was www.ncbi.nlm.nih.gov/pubmed/16885043.
My question is that, does getting better, or having stable symptoms really means that you are able to discontinue any treatments? and still be +10k?
Also here, interprets that : www.msdmanuals.com/en-gb/professional/hematology-and-oncology/thrombocytopenia-and-platelet-dysfunction/immune-thrombocytopenia-itp
in the prognosis part, again with reference to www.ncbi.nlm.nih.gov/pubmed/16885043 , it says :
"In adults, spontaneous remission occurs in 30% of patients in the first year, and up to 75% of patients improve within 5 years (1). "
So again that is my question, if improvement means that one is able to discontinue all drugs and remain +10k ?

Lman, after reading closely, there are two numbers given. The first is 12 of 43 patients (28%) and is the remission rate. Then, further down, 19 (of 43) patients (44.2%) who continued to need Romiplostim after up to 10.4 years. This second number is shown in Figure 1. What is behind the different numbers is confusing.

As I understand, the (100-44=) 56% includes treatment discontinuations for reasons other than Romiplostim treatment response. For example, if one took Rituximab or had a splenectomy, while taking Romiplostim, then those folks are in the 56% and are not included in the 28% number. Also, if there was ITP relapse and Romiplostim lost its efficacy, then those folks too are part of 56% population.

Make sense?

Sad reading about the deaths in those articles…

“…remission in patients with newly diagnosed or persistent ITP before it becomes chronic”

Does anyone think that with a particular treatment, ITP will not become chronic?

It is interesting how and when remission is talked about by various doctors and patients. I am surprised that a number of newly diagnosed people are talking about how to go into remission after only a few months. Then there are many others who have had ITP for years and their doctors are concerned about maintaining rather than achieving remission. There are all these stages (physical, emotional, spiritual) to chronic (or any) illness....

Of course remission would be great for anyone. I'd be really happy to not have to go to the lab and infusion center every week or two, but there doesn’t seem to be a particular formula for it and more needs to be known about ITP and why certain treatments work for some and not for others.

Anyway, onward we all go the best we can.

Yeah Hal.
But how do you interpret Picozzi study and Thomas Sailer study which both had around 2/3 of patients achieving remission?
Do you think the drug matters?

Lman, not familiar with those studies. I guess my point is that one has to pay close attention to what a study's author is trying to present.

I like the 28% remission number as it aligns with my very cursory understanding of the ITP population sizes of the four antibody types/rows. Roughly:
row 1 - 25%
row 2 - 20%
row 3 - 20%
row 4 - 20%
row combination - 15%
total = 100%
My rough calculation of remission via TPO-RA treatments only is: All of row 2, which is 20% of the population, plus 5% from row 1 would make 25% - which is very close to the studies 28%.

If you are asking Nplate drug verses Promacta drug, I haven't seen a difference. A row 2 response goes into remission with either drug. Similarly, if one has a splenectomy, that doesn't influence the outcome too. A row 2 response will go into remission with or without a splenectomy before hand. No difference.

When I first started on the ITP roundabout, the consultant said that ITP tends to burn itself out eventually. So when people get into some sort of remission, either full or partial, was it the drug or natural progression?

That is interesting. Did they say what 'eventually' means? I think for many it doesn't seem to burn itself out. I wish it would though...

JJ, they say the TPO-RAs have some (positive) effect on the immune system. Breg balance as I recall. I would contend that it is the immune system consuming a higher number of (Flu virus free) platelets, and not the drug itself, is what is affecting the immune system B cell balance. For whichever reason, I think this effect explains why it appears row 2 folks seem to have a quicker recovery/remission time when counts are kept at higher levels.

With that thought. It's always a 'natural progression' with TPO-RA treatment remission. These drugs just speed the process.

On a related note. For row 3 and 4, there are no natural/spontaneous remissions. Immune suppression drugs are needed for remission. AFAIK, either Danazol, MMF, Cyclosporine, or a combination of these. Splenectomy works occasionally for row 3, but not for row 4.

Did I make any sense?

I don't seem to fit your rows, Hal. For me, platelets are sequestrated in the liver, I have a really good response to steroids and very poor response to IVIG. Nplate put me into a partial but fluctuating remission and I now seem to be in a more stable remission with counts around 120, from the rituximab I had last year with chemotherapy.

JJ
I wouldn't worry about it. I have never received IVIg so haven't a hope of fitting anywhere in his table

JJ, ok. Interesting story.
Do you have the data on those responses that I can look at? Especially the steroid and IVIG responses. On Rituxan. Counts were what before and what after? Also, is it correct to say that you haven't taken steroids or IVIG since you started Nplate?

By your story, I'm wondering if you are the first person here on PDSA forum to be row 2/1 who went on and took Rituxan AFTER achieving Nplate partial remission. All others have taken Rituxan before Nplate - leaving them with a partial remission only.

It's complicated because steroids are part of chemotherapy. While doing that my counts were over 200, 230, 280 etc. presumably because of the steroids. That's my normal steroid response. Then when that stopped count came sharply down to 8 for a week and then up to 120 so we are guessing that the ritux is now keeping it up. My Nplate remission had my counts varying between 30 and 80 with a couple of times falling to zero or 1 and so using the Nplate again for a few weeks.

Oh IVIG took my count from 4 to 24 for two days then back down to 4. I haven't done it since except I do 10g of IG each week subcutaneously. It's not a high enough dose to have any effect on platelets.

JJ, is it correct to say that your steroid response was the single issue for not fitting into my ITP treatments table? You know, row 2 is just really odd compared to others. It has all these peculiarities that cause me to put special notes in the table for that row only. Perhaps a steroid response note for row 2/1 is needed.

When I looked back at user 'EmilyK' (also row 2/1) she too has an odd steroid response. It is like it started out as a partial (~50) response. But then. When she stayed on steroids for awhile, counts continued to climb. And recently. I think 'ecoclayton' is following the same course. Counts continue to rise over time while on steroids alone.

So let me ask you. Thinking back to when you first started with steroids for ITP, is that what happened to you? That counts started out low and then eventually climbed higher into the normal range?

To answer your question, I had a good response to steroids from the start.

I have had little response from N Plate and Rituxan, so Promacta has been ordered.
I was told that with Medicare and supplemental insurance, the co pay



would be $2000. A month. I an a retired educator. That is definitely not in my budget. Any ideas? Is it really a better drug?