Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor

www.ncbi.nlm.nih.gov/pubmed/25852848

Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice.

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As I have been saying there are two models of ITP-
1. Traditional model where people have antibodies to platlets and gets sequestered in the spleen. TPO Agents like Nplate\promacta helps somewhat but does not put them into remission. People in this category need rituximab\prednisone\splenectomy to achieve remission.

2. TPO model where people have issues with Thrombopoetin production or anything related to thrompoesis. These people will be greatly benefited by Nplate\Promacta and eventually can put them into remission.

There are also people who have both problems.

Hey Jay, ran across the full text version of the study you linked.
www.ncbi.nlm.nih.gov/pmc/articles/PMC4378205/

Population breakdown summary:
5 lost response to NPlate within 11 months nominally
2 respond but sustain only with continued treatment
13 discontinued treatment with sustained counts

This seems a bit odd. 65% (=13/20) discontinue treatment with sustained counts.

Hello Sandi,

As people say in statistics Correlation does not mean Causation.
In my opinion having Platelet antibodies and Thrmobopoetin issues are more coincidence than causal.

I would be more inclined believe that people with Platlet production could have Red blood and White blood cell production issues because all of them share the same pathway.

I thought the orginal sample size was 30?
Overall, 27/30 patients (90%) responded to romiplostim according to IWP criteria.13 Of the 27 responders: 1 patient (#4) was lost to follow-up; 1 patient (#5) discontinued romiplostim due to acute myocardial infarction, at the time of SAE, romiplostim dose was 10 µg/kg/week and platelet counts were 84×109/L; in 5/27 patients (#6-10) romiplostim was used as bridge to splenectomy; 5/27 patients (#11-15) lost response at 11, 6, 11, 12 and 11 months respectively; neutralizing anti-romiplostim antibodies could be searched for in 3/5 patients; in three (#13, 14 and 15) the test yielded a positive result; the remaining two patients could not be tested; in 2/27 patients (#16 and 17) romiplostim administration is ongoing (56 and 12 months respectively); 13/27 patients (#18-30) achieved stable, safe platelet counts and were able to stop romiplostim after a mean of 43.3 weeks (range 12-122) on therapy with sustained response maintained at a mean of 28.8 months (range 15-55).

Here it is in a more readable format:

Overall, 27/30 patients (90%) responded to romiplostim according to IWP criteria.
Of the 27 responders:
1/27 responders was lost to follow-up;
1/27 responders discontinued romiplostim due to acute myocardial infarction; at the time the romiplostim dose was 10 µg/kg/week and platelets were 84×109/L;
5/27 responders used romiplostim as bridge to splenectomy;
5/27 responders lost response at six to twelve months; three of five patients tested positive for neutralizing anti-romiplostim antibodies; the remaining two patients could not be tested;
2/27 responders romiplostim administration is ongoing (56 and 12 months respectively);
13/27 responders achieved stable, safe platelet counts and were able to stop romiplostim after a mean of 43.3 weeks (range 12-122) on therapy with sustained response maintained at a mean of 28.8 months (range 15-55).

Overall, 13/30 patients (39%) were eventually able to stop romiplostim and achieve a remission, sustained for at least 15 months.
By the end of the study, only 2/30 patients were still being treated with romiplostim.

Jay:
I think it's one heck of a coincidence then.

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by autoantibodies against platelet glycoproteins (GP). These autoantibodies are detected in only 40-60% of ITP patients even when sensitive techniques are used.

Among patients with active ITP, 36/42 (86%) had antibodies to TPO or c-Mpl: 4/42 (10%) had anti-TPO autoantibodies only and 5/42 (12%) had anti-cMpl autoantibodies only and 15/42 (36%) had both. Among patients with ITP in remission, 8/15 (53%) had autoantibodies to TPO or cMpl.

They don't mention anything about red/white cell problems in this group, although some did have HIT, APS or TTP.
www.bloodjournal.org/content/128/22/2548?sso-checked=true

Immune thrombocytopenia (ITP) is an autoimmune disease affecting adults and children, in which most patients have autoantibodies that accelerate platelet destruction and may also impair megakaryocyte platelet production. 3⇓–5 Cytotoxic effects of CD8+ T lymphocytes are also thought to cause thrombocytopenia in an apparently small number of cases, perhaps by impairing megakaryocytopoiesis. Thrombopoietin levels are normal or only slightly elevated in patients with ITP, suggesting that the lack of compensatory stimulation of megakaryocytes may contribute to impaired platelet production. If thrombocytopenia is sufficiently profound, it can result in bleeding, which is infrequently severe.

www.bloodjournal.org/content/117/21/5723?sso-checked=true