Adjusting treatment dose may help improve outcomes for children with ITP
Dosing of oral eltrombopag should be guided by drug levels in blood: Study
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Adjusting the dose of oral eltrombopag — the active ingredient in Alvaiz and Promacta — based on how much of the drug is present in the blood may help improve treatment outcomes for children with chronic immune thrombocytopenia (ITP), a real-world study in China suggests.
The researchers found that children whose tablet doses were guided by blood drug levels tended to have better treatment responses, fewer bleeding events, and fewer side effects than those whose dosages were adjusted using standard clinical measures alone.
Healthcare costs also tended to be lower in the individualized treatment group, mostly because more children were able to reduce their medication dose, the scientists noted.
Although the differences observed were not statistically significant overall, the findings suggest that individualized use of eltrombopag based on blood drug levels in children with chronic ITP “has good clinical value,” the team wrote.
According to the researchers, “these findings suggest that … individualized [eltrombopag] therapy may enhance therapeutic efficacy, improve safety profiles, and reduce medical costs, which represents a meaningful step toward precision medicine in the field of pediatric hematology,” where the focus is on diagnosing, treating, and managing blood disorders in children and teens.
The study, “Optimizing pediatric ITP therapy: a real-world study on plasma concentration-guided eltrombopag dosing,” was published in the journal Annals of Hematology.
ITP occurs when the immune system attacks and destroys platelets, the cell fragments responsible for helping blood clot and stopping bleeding after an injury. As platelet levels drop, people with ITP may experience easy bruising and abnormally prolonged bleeding.
One-third of children with ITP require ongoing treatment
While the condition often resolves on its own, about one-third of children develop persistent or chronic disease that requires ongoing treatment to keep platelet levels high enough to prevent bleeding. First-line treatment for ITP usually involves corticosteroids, medications that suppress the immune system, but long-term use of such drugs can cause side effects.
Eltrombopag, the main agent in the approved ITP therapies Alvaiz and Promacta (sold as Revolade in most places outside the U.S.), works by stimulating the body to produce new platelets. The two drugs are often used for children and adults for whom other treatments haven’t worked well enough.
Individual children can process medications differently, however, meaning the same eltrombopag dose may produce widely varying drug levels in the bloodstream — potentially reducing effectiveness when levels are too low or increasing the risk of side effects when they are too high.
Previous research by this team had suggested that adjusting doses based on blood drug levels may improve treatment responses in children with ITP. However, direct comparisons with the conventional approach — where eltrombopag dosing is guided mainly by platelet counts and bleeding events — have been lacking.
To address this gap, the researchers conducted a prospective, real-world study (ChiCTR2400086099) comparing the two approaches. The team enrolled 70 children with chronic ITP at a hospital in China from October 2023 to June 2024.
Half were assigned to received eltrombopag with doses adjusted using the conventional approach. The other half received an individualized dosing strategy, where dose adjustments were also guided by periodic measurements of eltrombopag levels in the blood. The participants were followed for six months.
Children in the conventional dosing group had a mean age of 9.1, with boys making up slightly more than half of the participants. Those in the individualized treatment group had a mean age of 8.1, and slightly less than half were boys. The two groups were similar in terms of disease and eltrombopag treatment duration.
Benefits seen, though not significant, with individualized dosing
Overall, about 83% of children in the individualized treatment group responded to the therapy. That compared with 71% in the conventional dosing group.
Complete responses — defined as platelet levels above a set threshold with no bleeding symptoms — occurred in two-thirds of children in the individualized treatment group and nearly half of those receiving standard dosing, the data showed.
Although the differences were not statistically significant at most time points during follow-up, platelet counts tended to be higher among children whose eltrombopag doses were adjusted based on blood drug levels, the researchers noted. This was despite the conventional dosing group starting with slightly higher platelet counts.
The individualized treatment group also showed fewer bleeding events, according to the team. In that group, the proportion of children experiencing bleeding remained stable at 17% throughout the study. In contrast, bleeding episodes increased from 14% at study start to 26% during follow-up among children receiving conventional dosing. No serious bleeding events were reported in either group.
During follow-up, children receiving individualized eltrombopag dosing were also less likely to require concurrent treatment with other medications used to manage the disease (3% vs. 11%) and rescue therapy for worsening disease (17% vs. 26%) than those receiving conventional dosing.
Dose adjustments were more frequent and of greater magnitude in the individualized treatment group, with 71% of children having their eltrombopag dose reduced compared with 54% in the conventional dosing group. Overall, children in the individualized treatment group were also less likely to require switching therapies due to lack of response to eltrombopag (9% vs. 26%).
Adverse events seen in 17% on individual dosing vs. 37% on conventional
Adverse events occurred in 17% of children in the individualized group compared with 37% of those receiving conventional dosing, the data showed. Most side effects were mild or moderate and resolved after dose reduction or discontinuation of the medication, per the researchers.
While overall healthcare costs were similar between the two groups, the individualized treatment group tended to incur fewer overall costs than the conventional treatment group, likely because more children in this group were able to reduce their medication dose, according to the researchers.
“As the first such evaluation in children, our study shows that [blood] concentration-guided individualized therapy can improve [eltrombopag] efficiency, lower adverse events to some extent, and does not increase direct healthcare costs, supporting its clinical application and promotion,” the researchers concluded.
Still, the team noted the small number of participants and added that larger studies with longer follow-up will be needed to validate the “long-term efficacy, safety and economic evaluation for pediatric ITP clinical practice” of the personalized dosing strategy.
