This document discusses romiplostim, a thrombopoietin receptor agonist approved for the treatment of chronic immune thrombocytopenia (ITP). Key points:
- A clinical trial found romiplostim significantly increased platelet counts in patients with chronic ITP compared to placebo, allowing over 70% of patients to reduce or discontinue other ITP medications.
- Common adverse events included headache, fatigue, and joint pain. Serious risks included bone marrow fibrosis and potential progression to myelodysplastic syndrome or leukemia.
- Romiplostim is a fusion protein that mimics thrombopoietin to stimulate platelet production. It provides an alternative to other ITP therapies like cortic
4. Efficacy and safety of
romiplostim in patients
with primary immune
thrombocytopenia
Lancet. 2008 February ,volume
371 Number 9610
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5. 5
PURPOSE- The safety
and efficacy of romiplostim were
evaluated.
double-blinded placebo controlled
Study group –
125 patients with chronic ITP
Completed at least one prior
therapy
Baseline platelet counts
≤ 30,000/mcL.
6. 6
STUDY GROUP 1
Non-splenectomised
Inadequate response or were
intolerant to prior therapies.
Diagnosed with ITP for
approximately 2 years .
STUDY GROUP 2
Splenectomised and continued to
have thrombocytopenia.
Diagnosed with ITP for
approximately 8 years
Both placebo-controlled groups -
allowed to continue receiving
previous medical treatments
throughout the study
7. INTERVENTION
• Starting dose of romiplostim
1 μg/kg or placebo.
• Patients received single
subcutaneous weekly
• Injections for 24 weeks.
• Doses were adjusted to
maintain (50 to 200 x 109
/l)
platelet counts.
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8. RESULTS
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OutcomeOutcome
Study 1Study 1
ssplenectomyplenectomy
Study 2Study 2
nonnon
splenectomysplenectomy
PlaceboPlacebo RomiplostimRomiplostim PlaceboPlacebo RomiplostimRomiplostim
OverallOverall
PlateletPlatelet
ResponceResponce
(%)(%)
00 79%79% 14%14% 88%88%
All p-values < 0.01
11. Summary of efficacy
100% splenectomised patients
who were receiving romiplostim
were able to reduce the dose by
more than 25% or discontinue
the concurrent ITP medical
therapies
73% non-splenectomised
patients were able to reduce
the dose by more than 25% or
discontinue concurrent ITP
medical
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12. Summary of the safety
profile
The most serious adverse
reactions that may occur during
Romiplostim treatment include:
reoccurrence of
thrombocytopenia
bleeding after cessation of
therapy
increased bone marrow
reticulin,
thrombotic/thromboembolic
complications,
progression of existing MDS to
AML.
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14. DOSE
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• The initial dose of romiplostim
is 1 μg/kg based on actual
body weight
Average dose: 2
mcg/kg/wk
Max dose: 10
mcg/kg/wk
Administered at weekly
intervals s/c
The goal the count
above 50,000 per cubic
millimeter (mm3
) of blood
15. Mechanism of Action
Fc-peptide fusion protein
Binds to thrombopoietin
receptor.[JAK STAT]
Activates intracellular
transcriptional pathways
Increased platelet
production 15
16. Indication[2008]
For the treatment of
thrombocytopenia in adult
patients with chronic ITP:
• who are non-splenectomized
and have an insufficient
response or are intolerant to
corticosteroids and/or
immunoglobulins.
• who are splenectomized and
have an insufficient response
to splenectomy.
.
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17. Pharmacokinetics:
- Peak: 7 to 50 hr (median 14 hr)
- t1/2
:1-34 days (median 3.5 days).)
Elimination
•Dependent on the TPO receptor on
platelets.
•High platelet counts are
associated with low serum
romiplostim concentrations.
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Contraindications
1.Hypersensitivity
2.Within 24 hr of receiving
myelosuppressive
chemotherapy or radiation
therapy
3.>10% leukemic myeloid
blasts in bone marrow or
peripheral blood
Interactions
No formal drug interaction
studies to date.
20. Preclinical Safety Data
Reversible myelofibrosis
has been observed in the
bone marrow of rats
Formation of neutralising
antibodies.
Evidence of increased
post-implantation LOSS
Cross the placental
barrier in rats
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Warnings:
- Risk for bone marrow
fibrosis
- Hematologic malignancies
-Thromboembolism
-Immunogenicity
Precautions
- Hepatic impairment
- Renal impairment
- Pediatrics – no data available
- Pregnancy – Category C
22. Long-term safety and
tolerability of romiplostim
in patients with primary
immune thrombocytopenia:
a pooled analysis of 13
clinical trials.
CONCLUSION
long-term romiplostim
treatment is well tolerated,
with no new safety signals,
even in patients treated for
up to 5 yr.
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