Danazol for ITP

Wowzer D Mann, 130s to 45 in a month is a slowww drop. Keep in mind IVIG doesn't normally do that and Rituxan treatment can do that. If you're still around 45 next month, might want to ask your doc about low dose Danazol (50mg per day) to preserve a partial response. My doc had not heard of that dosage as a maintenance treatment.

If you loose a partial response to Rituxan in a short period of time, the doc may see doing Rituxan again in the future as pointless / not worth it.

I will keep the low dose in mind. My gut feeling right now is unless I drop into 20's I may not do anything and just wait and see for 1 more month. I am still hoping the rituxin kicks in.

Symptoms started up again over the weekend. CBC today and count has dropped to 10 from 45 just 2 weeks ago. IVIG tomorrow and Doc wants me to start Promacta as soon as insurance will approve. Looks like I will skip the Danazol attempt.

That is disappointing D Mann. Sounds like IVIG works unusually well for you.

Getting insurance to cover for Danazol has turned out to be a surprising problem. Working on second appeal now. May end up in court based on what I've read of their public guidelines that they are not following well.

In the mean time, I too am currently waiting on Promacta approval as well. LOL, best of luck for both of us...

So glad we still have an NHS in the UK, none of this jumping through hoops to get treatments...yet !!!

The Danazol was approved yesterday. This is the second time they approved it. Blue Cross seems to be pretty good. They approved the IVIG in less than an hour yesterday afternoon.

Oh my, this is a bit strange. We both have BCBS of Texas and we seem to be getting different approvals. I wonder if the insurance company is able to see that I don't have bleeding issues? What really doesn't make sense to me is that Promacta is vastly cheaper than Danazol.

Hal: Out of interest may I as what the prices are?

Today count 17. Discussed with Haematologist about effectiveness and agreed to give Danazol one last four week chance by increasing dosage from 600mg to 800mg. The count of 17 is amid point between IVIG infusions so there is definitely some effect but I am not sure if I am paying a price in the way of side effects - difficult to pinpoint but I seem to be more fatigued, general aches and pains, slight racing heart an hour after taking, stomach cramps. The capsules need taking with food or mild heartburn occurs.

Looking back (started in January) Danazol caused an immediate and substantial rise (stratospheric for me) in platelet count when combined with weekly IVIG infusions. As soon as we tried to stretch out the infusions the effect was not so good and at three weeks problematic (ITP symptoms returning with a vengeance).

Danazol should become more effective when taken for a period of some months. We are not really seeing this happen.

For me none of this has been a waste of time because I have always had in the back of my mind "how do I get my count up if I ever need an operation" now I know that with a bit of planning high dose Danazol with IVIG might get me there.

I am also going to have a HPSA test. The test I had when first diagnosed with ITP was a blood test and this is the most inaccurate as it only tests for antibodies to H.pylori.

The battle continues.

I hope you find the combo that works for you rjsmyth. I seem to have a great reaction to IVIG, last time I had it I was down to 3 and had the flu. 2 doses of IVIG and I hit 145, of course it did not last but at least I know when I crash the IVIG will work.

Oh my mrsb, I stated Promacta and Danazol cost relation backwards. Should be: Danazol is vastly cheaper than Promacta. Also, I have been using 'goodrx.com' as a cost source. Have you used that? On there, 50mg of Promacta is about $7,000. While 200mgx3 of Danazol is about $200. That's a 35 to 1 ratio.

I dunno rjsmyth. Before giving up on Danazol I would be tempted to retry NPlate with it. The idea being the benefit you are getting from Danazol could also be restoring your response to NPlate. Specifically, I wonder if you have antibodies to TPO receptors - hence only indirect benefits from IVIG.

About the hPylori test. Be aware that you can get false negatives with that (or breath test) if one doesn't follow the preparation guidelines, or know they even exist. There is a long list of things one isn't supposed to take 1 or 2 days before the test. As I recall, you have to avoid all the ulcer / heartburn medications except for just plain calcium carbonate antacid. Also on the same subject, if your original antibody blood test was positive it is unlikely hPylori will go away without being treated for it. Many folks are without symptoms even though they have hPylori. Hope this helps...

Not sure on the costs for Danazol or Promacta yet.
IVIG billed $17,500 per dose insurance discounted cost $12,500.
Rituxan billed $12,800 per dose insurance discounted cost $6,800.

In the Uk the cost of promacta to the NHS is £1540 for 28 50 mg tablets. They get a special deal.

If I understand the latter part of section 2:4 correctly www.nice.org.uk/guidance/ta293/chapter/2-The-technology the actual cost is unknown but less than £1540. Doubt it will be very much though.

D Mann take a look at this BCBS pdf . Do you have any idea how your doctor got around the Danazol authorization requirements listed in the document (bottom of page 10)?

I guess it must be 3.C. My doc is in the "Cancer Center of Fort Worth" they have 2 ladies on staff that do nothing but chase down insurance approvals for meds. My doc said he currently has 3 patients on Danazol for ITP. They have actually gotten it approved twice and it took less than a week both times.

I think they submit case history's that show benefit along with the request.

Ok, thanks much for that. Since my hema's office has already submitted info for appeal number 1 and 2, I think they are now out of it. I think another appeal has to be done myself. Not sure. Perhaps someone at the Ft Worth office will confide in me the secret to success, LOL.

I was thinking about printing out a few ITP 'clinical studies' that include Danazol data as appeal evidence. Pretty sure it's the very first two sentences in the PDF document (objective section) that is their vulnerability where they must approve Danazol for ITP.

I have another CBC and see the doc Monday. I will ask how they do it and pass on anything they share.

Thanks again D Mann. I see my hema tomorrow and am going to ask who does the next appeal. I think ideally, if I can convince her office to call the Ft Worth office about how to do a Danazol authorization is the easiest path forward. That way the folks in her office will know how to do it next time around.

If your doc has 3 patients on Danazol currently sounds like he must think its pretty good.

Wednesday 12th - count 8. Made the decision to stop Danazol as it is not achieving anything and probably giving me some unpleasant side effects. I hate taking medication for the sake of it. IVIG continues fortnightly and still is the only way to keep my ITP symptom free despite single figure counts.

In combination with weekly IVIG it certainly increased my count but did not extend the period I could exist without IVIG and the higher count gave me no benifit whatsoever.

The "off licence" use of Danazol for ITP obviously has some side effect of suppressing the immune system but this is a powerful synthetic hormone that acts upon the pituitary gland so I believe not worth considering long term.

I await the next revolution in the treatment of chronic refractory ITP!

'Refractory' generally means that a patient does not respond to any treatment. Achieving a response but not maintaining it is where 'chronic' comes in. Keep at it, RJ. You'll get there eventually. You still have other things to try.

Sandi wrote: 'Refractory' generally means that a patient does not respond to any treatment. Achieving a response but not maintaining it is where 'chronic' comes in. Keep at it, RJ. You'll get there eventually. You still have other things to try.

Thank you for your kind words.

I have had in order - Predinisolone, Dexamethazone, IVIG, Rituximab, Azathioprine, MMF, Nplate, Eltrombopag, Danazol and combinations thereof. Refused Cyclophosphamide and Splenectomy. Awaiting the result of the second H Pylori stool test (had one in the beginning and negative ). Bone marrow still normal (recent aspiration) which is good news as I was on Nplate for two and a half years until that stopped working.

Severe refractory ITP was Drew Provan's verdict on my plight.

What have I missed in the way of treatment?

I won't argue with Drew Provan!
I came across this article earlier that might be helpful:

www.bloodjournal.org/content/115/1/29?sso-checked=true

Here is a more recent article I posted previously:

www.bloodjournal.org/content/128/12/1547.full#T2
Adam Cuker and Cindy E. Neunert Blood 2016 128:1547-1554; doi:10.1182/blood-2016-03-603365
How I treat refractory immune thrombocytopenia
..... We use a tiered approach to treat patients who require therapy to increase the platelet count. Tier 1 options (rituximab, thrombopoietin receptor agonists, low-dose corticosteroids) have a relatively favorable therapeutic index. We exhaust all Tier 1 options before proceeding to Tier 2, which comprises a host of immunosuppressive agents with relatively lower response rates and/or greater toxicity. We often prescribe Tier 2 drugs not alone but in combination with a Tier 1 or a second Tier 2 drug with a different mechanism of action. ...

Two drugs that can be effective when others fail:
Sirolimus (rapamycin, rapamune):

www.bloodjournal.org/content/127/1/17
Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial

and dapsone:

onlinelibrary.wiley.com/doi/10.1002/ajh.22266/full
Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab
Francesco Zaja*, Luciana Marin, Marianna Chiozzotto, Simona Puglisi, Stefano Volpetti and Renato Fanin First published: 21 December 2011
If compared with [Rituximab and Nplate], dapsone is satisfactory as to toxicity. In this study, the incidence of hemolysis or methemoglobinemia was not significant and none of the patients experienced important side effects or interrupted therapy because of treatment intolerance. Other authors showed the development of reversible side effects requiring cessation of therapy in 2–10% of patients [4, 6].
In conclusion, dapsone appears to be a cheap medical alternative for patients with ITP and is active also in patients who failed previous rituximab therapy. The response is achieved in most cases after nearly 1 month of therapy, and it is generally maintained during therapy. Even if dapsone has a good safety profile, it is necessary to monitor the level of MHb and hemolysis particularly during the first weeks of therapy and to be aware of factors that may precipitate dapsone-induced methemoglobinemia as anemia, pneumonia, or lung diseases and to know how to manage this complication. A better comprehension of ITP pathophysiology and of dapsone mechanism of action will allow in the future a better and rational integration of this agent into the treatment algorithm of primary ITP.

Sorry Danazol has not worked out for you rjsmyth. It sure looked like a safe option with great potential.

IMHO, once researchers come up with an established treatment regimen for the specific type of ITP you have, will better outcomes from harsh drug treatment be possible. It's a guessing game with the current state of the art.

That's about it...a guessing game which exposes patients to a lot of toxicities along the way. Things are getting better though. When I was diagnosed, all we had were steroids, IVIG, Win-Rho, Danazol and splenectomy. Rituxan wasn't even used yet until about five years after my diagnosis. The TPO's have also helped many people and have been a huge advance for ITP. I know you guys think that things have to get better and they do, but you came into this far better off than many of us did. I've seen a lot of new research and improvement with ITP since I hopped aboard the ITP train.

Yea, I think it is little known that George J. had ITP.
www.youtube.com/watch?v=gTZ91YtKLN4
For him, it didn't really seem like a train. Nor like a roller coaster. But it did resemble a treadmill in his world. A treadmill that could get out of wack but could be brought back into control - with help.

I was just sitting here trying to brain storm this terrible situation. As I understand the antibodies at play, I can't see a reason why IVIG shouldn't restore a loss of NPlate response when one has developed antibodies to NPlate. The response should last only as long as the IVIG, but who cares. Rj, might ask your doc to give it a shot, LOL, literally. A safe option.

If IVIG doesn't restore the response then NPlate is being destroyed in the liver instead of the spleen. And in that case, Tamiflu has a chance in restoring the NPlate response.

It may be of interest that recently the drug Fostamatinib has been submitted for FDA approval.
pdsa.org/products-a-publications/e-news/2017-enews/item/1405-pdsa-e-news-april-26-2017.html#Rigel-Fostamatinib-NDA

It will be interesting to read studies about the drug. Perhaps they may provide information of which first line therapies work well with it.

Hal9000 wrote: It may be of interest that recently the drug Fostamatinib has been submitted for FDA approval.
pdsa.org/products-a-publications/e-news/2017-enews/item/1405-pdsa-e-news-april-26-2017.html#Rigel-Fostamatinib-NDA

It will be interesting to read studies about the drug. Perhaps they may provide information of which first line therapies work well with it.

I thought this had already failed phase 3 studies. There was a lady here who was on the trial.