Rituximab

I'm in the uk and didn't taper as slowly as said here. I did 10mg for a week, 5mg for a week and then stopped. It was fine.

How long were you on it for prior to that?

Sorry to hear about your thyroid Poseymint. I hope your are Endo gets it sorted asap

It was 126k today . Im having shots almost every 8 days (or a little less ) . And I was on 3.25 mg prednisolone (decided to reduce 1.25 every 2 weeks ) . And a minor cold that maybe had effected counts .
Is 126k good sign ?!
Is Hal right about his tables ?!! According to Hal , I belong to 2B group . but I have not ever heard that type of antibodies can predict response to splenectomy , or other treatments (only here in PDSA there is something about efficacy of corticosteroids in some kinds some kind of itp with specific types of antibodies )

Rituximab turned to be a very bad drug for me .
I had 5 weeks of it . On 4th week , My counts just went from 11k to 13k and I asked doctor to reduce prednisolone a bit . I was on 25 mg at that time . he said ok . I took 20 mg for couple of days and saw some bleeding signs . then I told myself 22.5 mg is good ! But , after a week from the time I had started tapering , I saw symptoms were disappearing and was happy . That night , My mom used garlic in her food and I ate ... I had nausea during the night and didn't sleep . On the morning , I had a vomit which had some blood (not much) in it . I was really afraid , Hopefully my mom was with me . An hour later , my stool was very black and I understood I have had gastrointestinal bleeding , Which sent me to hospital (and counts came below 1k ! ) And got 11 units of platelets . Also doctor told have another rituximab at hospital and I agreed , despite I really didn't want it cause we had not got any result and I knew it's standard schedule is 4 weeks , not 5 . I got the 5th dose at Oncology room of that hospital before I got discharged . It was really sad memory . other people were there for chemotherapy and I felt sorry Any way , I was discharged but a couple of days later , I started having fever . It took a day and my body temp rose to 39 , but then It would come down to less than 36 ! (between 35 and 36 ) . It happened for a week and I was at hospital for another 2 days because of fever . Platelets were 4k at that time (while still on 25mg prednisolone !!! ) . I was there for 2 nights and they took some tests and they failed to detect any specific illness . and their report was unknown viral illness . I was discharged ...
I should had stopped rituximab after 2nd or 3rd week .

Lman wrote: It was 126k today . Im having shots almost every 8 days (or a little less ) . And I was on 3.25 mg prednisolone (decided to reduce 1.25 every 2 weeks ) . And a minor cold that maybe had effected counts .
Is 126k good sign ?!
Is Hal right about his tables ?!! According to Hal , I belong to 2B group . but I have not ever heard that type of antibodies can predict response to splenectomy , or other treatments (only here in PDSA there is something about efficacy of corticosteroids in some kinds some kind of itp with specific types of antibodies )

Just a guess on my part Lman.
I don't recall that you've reported an IVIG response - which is most relevant. Also relevant, are you still on 3 mcg per kg of Nplate?
On the other hand, it is easy to [strike]pick on[/strike], err ahh I mean, 'study' those with full / partial remission via Nplate or Promacta. They end up self identifying easily. As a group, row 2 folks have some unusual attributes compared to others.

It will be interesting to see how things turn out.

No , I have not ever been given IVig (I thought I'd be given once I had GI bleeding , But instead I was given platelets ) And yea I have read some doctors claim Ivig is a good predictor to splenectomy .
Anyway , ITP is still misunderstood and hard to predict which person responds to which treatment . What I can do ? Probably nothing ! Just praying for myself and using drugs with hopeeeeeeee !
At least I know it's not progressive and I'm probably not going to die of it
But , my current doctor is not good with this drug AT ALL and it is me who looks around for information .
But , Through the time which I was using 3mcg/kg of romiplsotim , And also tapering steroids , These were my counts checked every two weeks (plus a 5mg reduction of prednisolone every two weeks )
60 (25mg), 148 (20mg) , 47 (15mg) , 50 (10mg) , 90 (7.5mg) , 203 (5mg) , 128 (3.75mg) And was giving myself shots every 8 days approximately .
And I know I may need to use if for my life (Also chances are much greater that I do not ! )
I was checking internet for platelet count diagrams of those people who achieved remission on romiplostim . Not all followed Amgen's instructions which says if it was above 400k , hold . if it was above 200k for 2 consecutive weeks , reduce by 1mcg/kg .
Is it wise that I try to taper romiplostim to 2mcg now ? I can try it for 2 weeks and check to see if count's are not low too much .
Or another option is breaking 3mcg to two 1.5 mcg and have two consecutive shots on two consecutive days and next one 8 days after the second day shot ?
I could be asking my doctor BUT he does not know anything about it My previous doctor was good , but he said I will not prescribe Nplate for you unless you fail splenectomy . Which then I decided to visit my current doctor for a while .
By the way , About my initial response to steroids : I started at 1 mg/kg for two weeks . it was 6k when I was diagnosed , But 2 weeks later was 105k (I was 80 kg and was on 75 mg) . Then he tapered them to 50 and two weeks later , they came 24k and he told me choose splenectomy or rituximab . I told none , He prescribed me Azathioprine and tapered prednisolone to 25mg . In the next 10 days I found that It's better to avoid Azathioprine and try rituximab before it . One night I slept and when I woke up it seemed I have had nose bleed when I was sleeping which was ended but there was some blood in my mouth . I was scared a went to hospital and it came 7k then (And had my first round of rituximab at hospital ) . After failing rituximab , He told me to do splenectomy which I refused and was on pred for 6 month before start nplate ad taper pred . This is my story until now . I just hope I can avoid anymore hospitals !

And another question .
Is that right that combination of nplate and steroids and immunosuppressants give people higher chance of remission ?

Hal9000 wrote:

Lman wrote: On the other hand, it is easy to [strike]pick on[/strike], err ahh I mean, 'study' those with full / partial remission via Nplate or Promacta. They end up self identifying easily. As a group, row 2 folks have some unusual attributes compared to others.

.

You mean their count's consistently rises once on nplate ? Or all discontinue nplate according to amgen's instructions ?
You have found a pattern ?

Lman wrote: ... These were my counts checked every two weeks (plus a 5mg reduction of prednisolone every two weeks )
60 (25mg), 148 (20mg) , 47 (15mg) , 50 (10mg) , 90 (7.5mg) , 203 (5mg) , 128 (3.75mg) And was giving myself shots every 8 days approximately .

The 50 rise to 90, rise to 203 all on the same Nplate dose, while taking a bit of steroids, would be consistent with a row 2b response. The row 2 antibody resolved during the time and the row 1 antibody remains problematic.

... Is it wise that I try to taper romiplostim to 2mcg now ? I can try it for 2 weeks and check to see if count's are not low too much .
Or another option is breaking 3mcg to two 1.5 mcg and have two consecutive shots on two consecutive days and next one 8 days after the second day shot ?...

As you probably know, the most desired long term count on Nplate or Promacta is 50 or a bit more. Just taper down with 50 as the target. If you are actually a row 2b then:
If you get down to a 1 dose, and counts remain 40 or more, there is a good chance that you can stop taking Nplate and your counts will remain in a 40 to 60 range. If counts do fall below 40, keep with the 1 dose for a few weeks or months until you can stop.

... By the way , About my initial response to steroids : I started at 1 mg/kg for two weeks . it was 6k when I was diagnosed , But 2 weeks later was 105k (I was 80 kg and was on 75 mg) . Then he tapered them to 50 and two weeks later , they came 24k ...

Right. That looks like a week steroid response. Counts didn't get up in the normal range after 2 weeks - which one would expect for a single antibody row 1 response.

Lman wrote: And another question .
Is that right that combination of nplate and steroids and immunosuppressants give people higher chance of remission ?

For row 2 (only) no. The steroids just speeds the time to remission. If one just stays on Nplate alone, it can take many months (eg years) to get to (partial or full) remission.

Lman wrote: You mean their count's consistently rises once on nplate ? Or all discontinue nplate according to amgen's instructions ?
You have found a pattern ?

For row 2a, after some time Nplate is reduced/tapered to zero as counts go up to the normal range. For row 2b, after some time Nplate is reduced/tapered to zero as counts rise, but will stay in the 40 to 60 range with no treatment.

Thanks a million Hal ! You provided me very useful information
I will try to update later (if any other issue happened)
And by the way , I gave two other testes (1 injection every 8 days) :
128 k (3.25 mg) , 122k (2.5 mg) And soon im going to stop pred ! I hope anyone who is on pred can once quit it forever !

With those counts, sounds like you're doing well Lman.
I would note at this point that a third of a 3 dose is a 1 dose. And, a third of a 120k count is a 40k count. Coincidence? We will find out soon.
This ITP thing is one big puzzle. The bad part is one is always uncertain as to what truly is part of the puzzle and what isn't related at all. It takes a lot of ITP'ers to see trends and even more to verify them.

And one more question : You think I should resume prednisone ? I was going to stop it tomorrow , but if it makes remission more possible or more closer I might change my Idea .
Look at this :
"Reduced use of corticosteroids,
which are known to alter the balance of
T-helper subsets (e.g. regulatory T cells) (Libert & Dejager,
2014), may also contribute to immune tolerance; however,
the number of prior treatments was not significantly associated
with remission in our study."
Which is here : onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.13827

And second thing , is that as I told once I used to exercise a lot . of course doing exercise is good on it's own , but which kind of exercise is better ? weightlifting or aerobics ?
Before I get this itp , I used to do a lot of weightlifting which I'm going to resume again !

I dunno about prednisone Lman. This is unchartered water. I suspect the earlier count rise to 203 means you could stop prednisone and Nplate tomorrow and counts would fall to the 40 to 60 range, but, I don't know. All those here, that I recall, with row 2b were on Nplate/Promacta for months before achieving partial remission. Steroids had been tapered long ago. I think most doctors don't want to mix the two. But you have - apparently with great success.

I see you have found exactly the right study for remissions via Nplate. Nice.

On exercise. My theory for row 2 is that exercise, a Folate (vitamin B9) deficiency, and the Flu virus, all combined together at the same time, triggers the ITP. So, with that in mind, to keep from going out of remission, it is probably best to be taking a B-complex vitamin regularly. Maybe you can get your doctor to check the level. Probably little else one can do. No way to stop getting the Flu. Can't put one's life on hold.

Thanks Hal.
I visited my doctor yesterday . He told me to take 7.5 mg of prednisone daily (Not because he knows this combination work) . He told because I do not want your counts to drop more and the second thing because prednisone effects veins and reduces bleeding . I told no , I have had enough of prednisone ! And he said ok . But if I see counts are not improving , I may start taking a bit (although I hate ... )

Yeah I have found several other studies indicating successful Romiplostim discontinuation .
This is so promising :
www.ncbi.nlm.nih.gov/pmc/articles/PMC4378205/

And there are several others I found :
www.ncbi.nlm.nih.gov/pubmed/23451917
www.ncbi.nlm.nih.gov/pmc/articles/PMC5485313/

Also I found this interesting . Mechanism of action of Nplate and it's durability and dose-time dependency :
ac.els-cdn.com/S1474667016434932/1-s2.0-S1474667016434932-main.pdf?_tid=09e80375-825e-4396-a613-02a601179308&acdnat=1541592112_c8ec33dd1bbece129d60906a35e75bf3

For me , That was the case Hal I was exercising much , Also a simple cold 1 month before my itp onset (In fact , I observed my first unusual bleeding at the end of Jan , and was diagnosed at the first days of Mar . a cold weather ! and I was sure before my first unusual bleeding my platelets were not low , because I used to lift heavy weights and there were plenty of hits on my body due to weights , but there was no bruising before ...) and also some mental pressure I wish I had never gone through . And not sure about Folate deficiency because I have not ever checked That.
Thanks a lot ! I will consider adding B-complex to my regimen.
Also doctor said because you were unresponsive to rituximab , perhaps your bone marrow is getting attacked by your immune sysyem (not the platelets ) But I told him it is still possible that platelets are getting attacked and rituimab does not work and explained him your table And told him GPIb-IX is still possible and I think I might belong to that
He said you know much

Uh oh. Sounds like the doc has no intent in lowering the Nplate dose for a 50 count target. Maybe he isn't aware that some folks can have a partial remission from Nplate/Promacta. That is, maintain a sub normal count with no treatment. Also, that 50 is the recommended count for the long term.

It's been awhile since I've looked at those papers. Don't think I've seen the last two before.

I need to update my table. It should be changed to reflect that row 2b is a combination of row 1 and row 2. Both antibodies.

Oh one other thing. Has your liver AST and ALT levels been checked during any of this? If so, were they in normal range?

If fact , He talked about trying to taper . but he meant to have more waiting intervals between shots . What I am currently doing . I postpone shots for 6 hrs each week and go for blood test for every other shot . to is if they have really dropped or not ? That was why I was concerned about time-dose platelet count , Because I might be missing some low counts . Thereby , this time I may go for test couple of days after I had my new shot , to see before this new shot is going to work , Have they dropped much ?
And the reason I would prefer to delay shots instead of merely lowering the dose is that Nplate is expensive for me , so the later the better (Each vial costs 300 dollars for me ) and if I merely lower the dose , I must dispose the rest of drug .
And also there's a good news that in my country they have made biosimilar of Romiplostim which they said have worked as Romiplostim but still might be in clinical trial or in industrialization phase . That will cost much less .

As I think you are concerned of antibodies , take a look at this :
www.haematologica.org/content/91/8/1041
where it says : "Other factors, such as sex, age and the presence of a plateled antibody did not
predict for late responses in our patients."

Also , In those who undergone splenectomy and did not achieve remission while they were taking prednisone , still Splenectomy's success rate was two third as they mentioned . And if antibody presence was correlated with Splenectomy's success rate , They would had mentioned .

About AST and ALT , Yes I checked them two weeks ago and they were normal . Also had checked once more while on Nplate and was normal too . the only time they were not normal , Was after dexamethasone administration after my diagnosis .

Lman
You may find this recently published and well referenced article interesting.
www.bloodjournal.org/content/bloodjournal/131/11/1172.full.pdf?sso-checked=true

Thanks mrsb04.
and bout antibodies , this is also remarkable :
" and ITP may enter remission despite the continued presence of anti-platelet antibodies"
www.ncbi.nlm.nih.gov/pmc/articles/PMC3672858/#R10

Ah, good that your liver is doing fine Lman. Some row 2 folks have mentioned alcohol as a possible contributing factor to ITP trigger.

If Nplate is costing you, maybe doing it the way 'jayinchicago' (also row 2b) did it would work for you too. As I recall, he did a 3 Nplate dose and then waited 3 weeks for both count testing and another shot. He and his doc had an agreement that he would only get a shot if count was below 40. Maybe he will chime in and comment, or, you can search through his old posts for additional details.

On that study. One thing I'd note is that it was in 2006. At that time only two antibodies were known. Today, it is believed that there are four, but that opinion doesn't seem to be broadly held. Or at least, broadly known.

Be aware. Just because one has antibodies doesn't mean they go away (when tested for) when one is in remission. The evidence is that they remain but are in 'regulation' or in 'balance'.

Hey.
I did not have shot and went for test 13 days after my last shot . They came 10-11 k
I'm wondering that is this my untreated count or still Nplate's effect ? Cuz according to Platelet count diagram with Nplate during time and my doses I should'nt had dropped this much . But last time when I did this , I was on 25 mg prednisolone and counts came 148 a week , Then I skipped the next shot and 14 days after my last shot they came 16k , Which was my baseline with 25mg prednislone . Anyway , I'm not taking prednisone now and that's good enough ... And about symptoms , It was only a small bruise on my thigh . If it is my baseline , I'm delighted then ! I see many people skip a week and drop to 2-3 k ... and some don't .
I had my shot again . Let's see how things go on

Oh no Lman, a count crash.
It was looking very good with the 120+ counts too. At least there is the victory of no Pred. Maybe stopping the Pred was a bit of a shock and caused this.

Time to go back to the 7-8 day Nplate schedule for awhile? Get counts back up to 120 again? LOL, lather, rinse and repeat?

Lman..I know you are a Pred hater and believe me I understand why (after 4 years of the wretched stuff I'm down to 2mg a day) but it is ok to take say 10mg a day for a couple of days just to get counts up a bit. I have done this a couple of times and it works.

Happy new year everyone !
Wish you a year full of platelets and empty of meds
I'm on my 10 day schedule of shots . Last count on 11th day (couple of hours after my next shot) were 38k . not so bad .

Day 10 : 95k
on 10 day schedule
" lather, rinse and repeat" !?
Lol

It's been a while Lman. Nice count. Taking a '3' dose every 10 or 11 days?
As I recall, jayinchicago would just wait till counts were low before another shot. Eventually the time just got longer and longer, and then no shot and count stayed above 40.

Yes Hal . Im on 3 dose every 10 days and I give blood count every 2 months !
Last time I gave test on 10 day schedule (about 2 months ago) it came 38k . I don't know if it's an improvement or just "a fluctuation in the darkness !".
But now , My latest count which was 95k , was 2 days ago (at 10th days) And I have not yet used my next shot (so day 12 just finished)
Do you think I shall try it today , or wait for 14th day , or even 17th day (7+10=17 , a week later from my latest count ) To check it again ? If I could reduce it's use , It's great , But Im also afraid of bleeding . Currently , I have no blister or bruise , but when I itch myself so hard , a red sign remains there for couple of days . That makes me worried
According to the chart , I'ts safe to wait a week more , Cuz in 10th day it must be rising , But I really wonder if that chart is true for everyone
ac.els-cdn.com/S1474667016434932/1-s2.0-S1474667016434932-main.pdf?_tid=09e80375-825e-4396-a613-02a601179308&acdnat=1541592112_c8ec33dd1bbece129d60906a35e75bf3
Do you think Romiplostim is my way to salvation ?

Hi Lman, Really great to hear about your counts.

Wondering if you can tell when your counts are dropping or are getting too low with symptoms other than bruising and bleeding or do you rely on the CBC? By 'too low' I mean single digits or whatever 'too low' means to you.

Hey b2h.
I think people with itp are believed to know their counts based on their symptoms . I think it is true most of the time . what makes me really worried is wet purpura , eg blood blisters or blood in mucus . or also red dots in my mouth .
Surprisingly , I know a big exception for myself : once I have been under 1k and had NO SYMPTOM ! no bruising , and nothing else . that eventually led to slightly bleeding in my guts however . thereby , sometimes im also worried about having no symptom !

That makes sense.

ITP varies so much between individuals and, as you stated, symptoms don’t always correspond the same way each time to the platelet count.

Mouth and gastrointestinal bleeding are definitely not fun.

Thanks