| Eltrombopag Improves
Thrombocytopenia in Patients with Cirrhosis Thrombocytopenia,
or low platelet count, can lead to easy bruising and prolonged bleeding. People
with advanced fibrosis or cirrhosis, who may develop portal hypertension and reduced
synthesis of blood clotting factors, often develop thrombocytopenia. The condition
can also be a side effect of treatment with interferon, and patients with pre-existing
thrombocytopenia are typically advised against using interferon-based therapy.
 Research
has shown that blood cell growth factors can help manage the hematological side
effects of HCV treatment. Use
of granulocyte colony-stimulating factor (G-CSF) for interferon-induced neutropenia
and erythropoietin (EPO) for ribavirin-induced anemia can help patients stay on
full-dose hepatitis C therapy.
At the recent Digestive Disease Week
conference in Los Angeles, John McHutchison, MD, presented promising safety, efficacy,
and tolerability data for a new oral blood platelet growth factor, eltrombopag
(SB-497115).
In this double-blind multicenter Phase II study, 33 chronic
hepatitis C patients with compensated cirrhosis and baseline platelet counts between
20,000 and 70,000/microliter (mcL) were randomly allocated into four arms:
 | 30
mg once-daily eltrombopag | | 50
mg once-daily eltrombopag | | 75
mg once-daily eltrombopag | | Placebo
|
|
Therapy
continued for four weeks. Patients who achieved platelet counts greater than 70,000/mcL
after the 28 days were then eligible to start treatment with pegylated interferon
plus ribavirin, while eltrombopag was continued.
Results
| After
28 days, the proportion of responders, defined as achieving a platelet count ?
100,000/mcL, was higher in all eltrombopag dose groups compared with placebo.
| | The
highest response rate was observed in the 75 mg eltrombopag group, with 9 out
of 10 responders (90%); there were no responders in the placebo arm. | |
After 28 days, median platelet counts were higher in the eltrombopag groups than
in the placebo group. | | No
serious adverse events were reported in any group, and no discontinuations occurred
due to side effects. | | The
most common side effects were fever, chills, flu-like symptoms, and headaches.
|
|
|
|
Placebo
n=5 |
30mg
n=8 |
50mg
n=9 |
75mg
n=11 |
|
Age
(median, years) |
54 |
49 |
56 |
51 |
| Gender, male
(n, %) |
3/5
(60%) |
7/8
(88%) |
6/9
(67%) |
8/11
(73%) |
|
Responders at Day 28*
(n,
%) |
0/5 |
4/6
(67%) |
7/9
(78%) |
9/10
(90%) |
|
Platelet count at baseline, x103/ul
(median,
min/max) |
47
(38,62) |
61
(42,94) |
45
(26,66) |
56
(28,75) |
|
Platelet count at Day 28, x103/ul
(median,
min/max) |
38
(34,55) |
119
(58,214) |
174
(47,252) |
246
(78,478) |
|
Subjects who experienced an AE
(n,
%) |
3/5
(60%) |
7/8
(88%) |
7/9
(78%) |
9/11
(82%) | *
proportion of evaluable subjects with an increase in platelet count from baseline
to > 100,000/mcL after four weeks of SB-497115 treatment |
|
Conclusion
The
researchers concluded that the limited interim data from this ongoing study show
that eltrombopag can increase platelet counts and enable the initiation of treatment
with pegylated interferon in subjects with HCV-related cirrhosis and associated
thrombocytopenia.
6/09/06
Reference
JG
McHutchison, N Afdhal, ML Shiffman ML, and others. Efficacy and safety of eltrombopag,
an oral platelet growth factor, in subjects with HCV associated thrombocytopenia:
preliminary results from a phase II multicenter, randomized, placebo controlled,
Double-blind, dose-ranging study. Abstract 338. Digestive Disease Week 2006. May
20-25, 2006. Los Angeles, California.
|
