Is Promacta not effective if I crash after I am on it?

I have been on Promacta 75 mg since 9/22/17 when I also got DEX burst of 4 days 40 mg and 1 day of IVIG. My Platelets were at safe levels 103 and higher but went down to 5,000 on 10/16. My doctor said "Promacta hasn't worked" I think because the Promacta drucg company literature says it should work in 2 weeks. But on this PDSA discussion I have read that it sometimes takes 6-8 weeks or longer to normalize to a decent platelet level. But is this case different because I crashed to 5,000 after 3.5 weeks on Promacta?

By the way my preliminary Bone Marrow labs came back with no malignancy. Yay!
Thanks,
Cindy

Cindy
Are you sure you haven't got a slight infection at all. My platelet count crashes whenever I get even the slightest cold.

I think you should stick with the Promacta for at least 3 months Cindy. My experience was a very gradual rise from 1 to 20 over a period of 6 months . Because of my low count I booked a holiday by rail for 9 months after my crash but by the time it came round my count was over 20.. Your initial high count was maybe more to do with the short term effect of Dex and ivig( neither of which made any difference to me) than the start of Promacta. I had previously been on 50mg Promacta daily on which I hovered around 13 .I then tried Nplate to much the same effect. It was a last resort that I was put back on 75mg Promacta and both I and my consultant were surprised and pleased at the gradual but definite improvement.
The rate of platelet increase gradually speeded up for me and now 1 year and 10 months later ,having got to 168 my 75 mg dose is gradually being reduced. I am now at 130 on 75mg 3x week and 50 mg 4x week.

I agree with Margaret, give it more time

I'm not sure why Promacta treatment should be extended heroically if Nplate is known to work.

I think it did not work last time. I need to get some treatment facts together and get back to you. It has been on my to do list.
Anyway now they are saying I might have a mild case of Lupus and want to go to Rituxin speedy quick but I am putting on the breaks for some reason. I have got to figue out do I actually have Lupus and if so s there some reason Lupus should be treated with Rituxin. Head spinning again... I am also getting un upper endoscopy cause why not rule out any infection from Costa Rica before I jump in bed with Rituxin?

I do know a few people ITP who have gotten complete remission from Rituxin??? Your thoughts?
There was a good PDSA newsletter article about low dose Rituxin alonf with Promacta too?
Thanks!
Cindy

My recollection is that they tried a '5' Nplate, instead of doing an '8', and that didn't work for you. LOL, but I wasn't there...
Seems that 5 wasn't strong enough and 8 was too strong.

October 19, 2017
Hi Hal,
I only had the NPLATE 5/19 5mg/kg, 7/12 5mg/kg, 7/28 8mg/kg and 8/9 5mg/kg. But maybe it would have kept the platelets up if I had it every week. What do you think? I think it may be worth a shot before taking Rituxin if the Promacta at 75mg, the UGI and antibiotictcs (which I am not sure I can even get) don't work. How do you feel about Rituxin I forget. I am warming up to it a bit.

Here is my synopsis for my doctors and it has NPLATE and Platelet detail too.
I am wanting to point out and investigate further my 7 week remission after the antibiotic therapy.
Unless there is a compelling reason not to wait to do the Rituxin, I would like to do the following before I do the Rituxin
*Upper GI with biopsies
*Another course of antibiotics since the antibiotics are less intensive medications than the Rituxin

As you can see from this detailed treatment, platelet and remission summary the only time my platelets stayed up for 7 weeks was from 5/20-7/12 which was after the triple antibiotic treatment.

Overview: Time between IVIG Treatment for low platelet count
5/9 to 5/20 11 days
5/20 to 7/12 7 weeks
7/12 to 7/28 16 days
7/28-to 8/12 15 days
8/12 to 8/26 14 days
9/4 to 9/22 18 days
9/22 to 10/16 24 days



Details
5/9 to 5/20 11 day remission
First treatment ever for this condition 39 days after returned from Costa Rica trip.
5/9 -Pt received Dexamethasone 40mg IV Daily x 3 days
-Pt received IVIg 1gm/kg IV x 2 given
-Prednisone 100mg PO Daily
-Plt Count 114 L 05/11 0922



5/20 to 7/12 7 weeks remission
On 5/19 got Nplate5mg/kg mg at Dr Feiners office.
In hospital on 5/20 got one bag of platelets - IVIG X2 days and dexamethasone 40mg IV X3 days PO 40 mgx1 day, Prednisone 100mg for 2 weeks then tapered down quickly, and the following antibiotics.
My platelets went up to 1.1 million and I had a 7 week remission
Got AMOXICILLIN (TRIMOX) 500 MG CAP
1,000 MILLIGRAM ORAL TWICE DAILY Qty = 22

CLARITHROMYCIN (BIAXIN) 500 MG TAB
500 MILLIGRAM ORAL TWICE DAY Qty = 22

metroNIDAZOLE (FLAGYL) 500 MG TAB
500 MILLIGRAM ORAL FOUR TIMES A DAY
Qty = 52
Platelet count: 5/31-392, 6/5-1,179, 6/12-502, 6/16-185, Platelet count continued: 6/19-101, 6/22-62, 6/23- 50

predniSONE (predniSONE) 50 MG TAB
100 MILLIGRAM ORAL DAILY
took for 2 weeks and weaned off quickly by 6/10ish

5/31 Moved care to Dr. Lind on 5/31


7/12 to 7/28 16 day remission
On 7/12 got IVIG 1,000mg/kg X1 day, Nplate 5mg/kg, Dex 20mgX4 days for 7,ooo platelet count.
Platelets up to 430,000 on 7/21 down to 2,000 on 7/28.


7/28-to 8/12 15 day remission
On 7/28 got Nplate 8mg/kg and Dex 20mg/kg X 4 days for platelet count of 2,000.
On 8/6 started Promacta 50mg/day
8/9 Nplate 5mcg/kg
Platelets went up 7/31 -7,000, 8/4 -178, 8/7- 102, 8/9-24, 8/11-6


8/12 to 8/26 14 day remission
On 8/12 got IVIG 1,000mg/kgX 1 Day for 6,000 platelet count. ,


8/26 to 9/4 10 day remission
On 8/26 got IVIG 1,000mg/kg X1 day
Platelets up to 114,000 on 8/28


9/4 to 9/22 18 day remission
On 9/4 got 40mg of dexX4 days and IVIG


9/22 to 10/16 24 day remission
On 9/22 got 40mg of DexX4 days and IVIG 1,000mg/kgX1day
9/22 Started Promacta 75mg /day
9/22 started multiple homeopathics targeting immune system modulation, anti viral and anti fungus.
Rife sound therapy for parasite eradication and took Parastroy medication for 2 weeks.

Bone marrow biopsy 10/12 at 103,000 platelets
Sore throat Virus 10/13 and 10/14

10/16 to ???
IVIG and Dex 40mgX4 days for platelet count of 5,000

Thanks for you efforts to help me Hal,
Cindy

Cindy, love that data. Probably clearer now for you too going through it all.
About the 7 weeks. I have read that certain antibiotics can block the action of steroids. I had a Dex pulse, immediately followed by 10 day PrevPac treatment for h-pylori, and got a 55 (baseline 12) count. That high count for me could have come from the remanence of the blocked Dex pulse. For you, it looks like counts went through the roof when antibiotics was stopped. Would you agree? If you want an upper GI to make sure the h-pylori is gone just convince your doctor to do it.

If steroids were indeed blocked then that suggests a steroid response. If one compares the 8/26 and 9/4 treatments there is more evidence of steroid response. Adding the Dex pulse to IVIG almost doubled the length of the response. Yes? It looks like you have a steroid response (and definitely a IVIG response). So you seem to be a good candidate for Rituxan.

The 7/28 treatment suggest a 4-5-6 range may be an appropriate Nplate level. Almost 2 week response with a Nplate 8 dose and Dex pulse. One week would be 4 and then remove the Dex pulse by adding 1, to give a 5 dose. Yes?

Have I addressed everything? Hope this helps...

You are way smarter than me and my head is a little understanding and a little spinning. You would do the Rituxin before another dose of antibiotics even though they looked like they helped the remission and they have safer side effects than Rituxin? My dr thinks next step is Rituxin. I am dragging my feet to find someone to give me abx? sigh

I don't know, Cindy. It's impossible to weed through all of that and figure it out because they gave you way too many treatments at the same time from the very beginning. Some of those shouldn't have been given at the same time (Prednisone and Dex) and (N-Plate and Promacta).

It's not clear if you even had a steroid response. I've never seen things done that way and it's obviously not working with the kitchen sink approach. You've been doing this since May and still have no idea what you truly respond to other than IVIG.

I don't see that Promacta is working for you, although you haven't been on 75 mg's very long. It might be worth it to give it another week or two. Or, as you are thinking, you could try N-Plate.

As for the push for Rituxan....I'm not sure why they are pushing that. It's not even clear that you have Lupus and even though Rituxan is a Lupus treatment, studies show that it has not been a successful treatment. Rituxan was actually what triggered Lupus for me. I had a bad reaction (serum sickness) and was never the same after that. Immediately after the reaction, I began to have Lupus symptoms. We've talked about this here before, but it seems as though the people who have Lupus or are predisposed to Lupus tend to have serum sickness more often than those who don't. It's a hypersensitivity reaction to the mouse gene in Rituxan. I agree with you that it is a heavy duty treatment not to be taken lightly.

Objectives

To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies.

Methods

A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0.

Results

In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5 yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögren’s syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05 d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00 d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34 d.

Conclusion

It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms.

www.sciencedirect.com/science/article/pii/S0049017215001808

Hal wrote I have read that certain antibiotics can block the action of steroids.
Please can you supply an evidence base Hal ?

Hi Sandi,

I know my doctors think I'm crazy but I am worried about the Rituxin neurogenic disease even though it is rare. I really appreciate your response and am surprised to hear Rituxin actually gave the Lupus a jump start on you. That stinks!
I want to share what I just wrote the following to my doctor. I also asked them to please clarify why he thinks I have Lupus...what lab confirmations has he received. I'll let you know if I get that info.
Dear Dr. Deane,
The reason I am worried about taking Rituxin is the possible side effect of a serious neurologic disorder called PML.
Is there a way to test me for the latent JC virus? If I don't have it then I think the Rituxin is safe. (But Sandi now I am worried about the Lupus situation.)

I read that PML is caused by the reactivation of the JC virus, a polyomavirus that remains latent in up to 80% of healthy adults, typically only causing PML in immunocompromised patients. There is no known effective treatment for PML.
Thanks, Sandi.
Cindy

Cindy:

Just to be clear, I don't think Rituxan actually caused Lupus but rather the side effect did. Just like illnesses sometimes trigger ITP, serum sickness caused wide-spread inflammation that stirred up the antibodies. Serum sickness generally goes away after a few days, but I was left with constant problems after it happened. Serum sickness is a horrible thing to go through and I wouldn't wish it on anyone. I've had it twice. I know a doctor's initial response would be, "No, Rituxan can't cause Lupus because it is used to treat Lupus". It didn't work that way for me.

I don't think you are crazy at all for worrying about potential side effects. I wish I had been more cautious before jumping into it. I didn't realize at the time how bad some side effects can be and I never even looked at them. Before ITP, I didn't even think meds could be dangerous. I was so naive. They push these drugs on people but do not have to deal with the consequences when things go wrong. Sometimes they don't even know about it because you end up seeing another specialist for the next set of problems.

I'm glad that you sent that e-mail to your doctor and would like to see the response.

mrsb04 wrote: Hal wrote I have read that certain antibiotics can block the action of steroids.
Please can you supply an evidence base Hal ?

It's been awhile. My recollection is that I read it on drugs.com. Let me see what I can do.
This page on Dex drug interactions says:
"Antibiotics: Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see Drug Interactions: Hepatic Enzyme Inducers, Inhibitors and Substrates)."
This page on Clarithromycin (one of the PrevPac antibiotics) drug interactions says:
"Corticosteroids (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. Monitor therapy"

Here we see that Clarithromycin may increase the blood serum concentration of Dex as Dex is not an exception, as Prednisone is an exception.

If I'm not mistaken about CYP3A4 inhibitors , that means that the liver cannot metabolize Dex in the presence of the antibiotic. Hence the increased blood levels. So, perhaps I should have said: some antibiotics block the metabolism of Dex and this leads to prolonged action.

Have I got it?

Cindy1 wrote: ... You would do the Rituxin before another dose of antibiotics even though they looked like they helped the remission and they have safer side effects than Rituxin? My dr thinks next step is Rituxin. I am dragging my feet to find someone to give me abx? sigh

Cindy, as far as I know antibiotics is barking up the wrong tree. It wasn't the antibiotics that caused the 7 week response. It was antibiotics plus Dex plus Pred plus IVIG plus Nplate that did it. As you probably know, it's a miracle a clot didn't spin out of that concoction.

It seems Rituxan or Nplate is your best options. I may have said before: as others will point out (coughSandicough) there are significant cautions with Rituxan. Yes, ITP sucks. To say nothing about a bone marrow biopsy giving one a sore buttocks, heh?

Ok, I can't believe I'm going to suggest this and I'm definitely going to deffer to others since the topic is steroids.

It seems like the problem with all these IVIG and Dex rescues while your trying to start Promacta is immune system instability. It seems the rescues turn off your immune system and then it gradually turns back on to full blast destruction after a few days. It's sort of oscillating between full off and full on. So perhaps a 50 or something floor is not being seen because another rescue is immediately started before the immune system slows down again.

Might I suggest that instead of IVIG/Dex rescues you try to find a low dose of Prednisone in an attempt to find a floor along with Promacta. The advantage of this is the immune system is not ramping on and off like it is with these back to back IVIG/Dex rescues. I suppose it is possible Promacta is actually working all along and it just can't be seen.

Perhaps you can remember. Didn't your counts crash towards zero between earlier Nplate injections? So if you went back to Nplate these same back to back rescues could obliterate the results of treatment success.

Thanks guys for this info!
Way back when I was on the triple antibiotics, I did read that Clarithromyacin can cause increased effect of the Prednisone. And believe me it did! I was a walking balloon with leg rashes. Very toxic things were going on.
So that might have also meant it wasn't be cleared who knows? I'm glad I'm going to get an Upper GI before I do any Rituxin just in case we can find something underlying.
I have decided after reading a REALLY good article 2017 U of Penn that I have to share once I can get the address again, that
1. Need to look for underlying stuff
2. Promacta and Nplate are least serious side effect issues and have just as effective remission rates as Rituxin.

Hal, you are too funny! I really appreciate all the thought you are putting into my situation.
What you are saying does make some sense that there is too much of a suppression and resulting immune system instability.
I am glad I have a homeopathic dr and his meds that target immune balance among other things.
I did look back at the Nplate and I did crash.
*On 7/12 Nplate 5mg/kg at 7,000 but also got 20mg dexx4 and IVIG and on 7/28 was 2,000.
*On 7/28 8mg/kg Nplate but also got 20mg dexx4 and IVIG and on 8/12 was at 6,000
Thanks for trying so hard to help me figure this out!

Hi Cindy- For me Promacta and Nplate were more effective than Rituxin. Good luck with what you decide on that.

Hal, I agree, in my experience with the TPO drugs stability is the key. Also like you said, in Cindy's case there is an instability being created with several power-packed drugs being taken at once. Nplate needs to be given every 7 days (not 2 weeks) over a period of time- start low and increase gradually until the counts reach 50. You know all this of course, just saying I see how the way the drugs are being administered is causing counts to shoot up then crash. Oh well, doctor knows best (?!) I took a low dose prednisone while waiting for Promacta to work once and also while waiting for Nplate. I agree for many people it can be a pretty good way to go as you can fine-tweak it.

You guys...
This is making so much sense to me. As much as I hate to do it maybe I need to be on low dose prednisone. Humm.

Maybe the homeopathic immune balancers will be enough? The were holding me strong this last 24 day remission until I had the bone marrow biopsy assult and the slight virus. I would rather not do the prednisone but it is better than another IVIG rollercoaster ride.

I don't know when I would start the prednisone maybe 10 days after last IVIG which was 10/16. and how much to take maybe 5 or 10 mg? What do you think?

I am trying not to do so many blood tests cause I feel I am scarring my veins at this pint. Also, last two times knew from blood streaked mucous that counts were low. But need the prednisone before they get that low.

Thanks for this new treatment idea.

Cindy

Maybe low dose Pred is the answer. Much as I hate the wretched stiff I'm staying on 3mg a day for a while.

Have you been on the 3 mg a day with the Promacta for a while? 3mg doesn't sound so bad. Are you having many side effects?
I guess I should pitch this to my dr.

Cindy1 wrote: ... I don't know when I would start the prednisone maybe 10 days after last IVIG which was 10/16. and how much to take maybe 5 or 10 mg? What do you think? ...

I dunno. Way out of my element when it comes to steroids. With any luck your doc has a good idea here.

Cindy1 wrote: ... I am trying not to do so many blood tests cause I feel I am scarring my veins at this pint.

Yea, nothing nice about the evil rescue monster. Statistics are, it wants to give you clots too. Where I'm at they do IVIG through veins in the hand.

I've been tapering off steroids for yonks but have stayed on 3mg a day for almost 2 months whilst trying to stabilise count with Eltrombopag at 25mg/50mg on alternate days. I have had absolutely no side effects on this dose of Pred.

Thanks! I think I am going to suggest that 3mg a day of Prednisone. It beats massive ups and downs and IVIG and dex pulses!

I don't know if 3 mg's would do anything for counts. That dose is less cortisol than the body produces on its own. It's a very low dose.

Sorry I was not very clear this morning. I had just come off a very busy 11 hour night shift. !!
You may well need more pred but as low a dose as is needed because
a] the side effects of high dosing are horrendous, I started on 45mg a day over 3 years ago.
b] you will end up having to taper off it, that takes ages and needs very carefully managing.

I am beginning to come to the conclusion that I may never get completely off it as my adrenals will never wake up enough to cope without the little boost 3mg gives me.

My Rheumatologist just cut my script from 12.5 to 10. She refuses to give me any more 1 mg pills. I argued that it is NOT a safe taper (with the nurse) who said, "I don't know what to tell ya!" I was fuming. I asked for an appointment to see the doctor (who I haven't seen since last January because she was out on leave), and was told that there are no open appointments until January. I'm looking for a new Rheumatologist. I am really feeling the effects of that missing 2.5 mg's after being on the drug for 12 years! It's so not fair.

That's outrageous Sandi. Anyone who has steroid tapered knows full well 1mg tabs are essential. My GP (who has just retired so I've now got a new one to train ) and to be fair my haemo too always ask if I have sufficient 1mg tabs