Long-term hetrombopag safe, effective for ITP in children: Study
Drug may be option for patients for whom first-line therapy fails
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Hetrombopag appears to be a safe and effective option for treating children with immune thrombocytopenia (ITP), with better outcomes linked to younger age and newly diagnosed disease, a study finds.
The study findings also highlight that hetrombopag “may serve as a viable option for patients for whom first-line therapy fails,” researchers wrote.
The study, “Long-term efficacy and safety of hetrombopag in paediatric patients with immune thrombocytopenia,” was published in the British Journal of Haematology.
Hetrombopag stimulates bone marrow to produce more platelets
ITP is caused by the immune system mistakenly attacking and destroying platelets, cell fragments that help with blood clotting. This leads to symptoms such as excessive internal or external bleeding and easy bruising.
Hetrombopag is a thrombopoietin receptor agonist (TPO-RA) that stimulates the bone marrow to produce more platelets. It was developed and approved in China, where it’s marketed as Hengqu, as a second-line treatment for primary ITP.
To address the use of hetrombopag in children with ITP, researchers in China analyzed safety and efficacy data from 93 children with ITP treated at a starting dose of 0.15 mg/kg (up to age 5), 3.75 mg (6 to 11), or 5 mg once daily (12 or older).
Enrolled children had a median age of 42 months (3.5 years), and most (55.9%) were boys. About two-thirds were newly diagnosed with ITP (which means they had the disease for less than three months), and all had previously received at least one other treatment, including other TPO-RAs. These included eltrombopag, sold as Alvaiz and Promacta, in eight children, or both eltrombopag and Doptelet (avatrombopag) in one.
Five of these patients switched to hetrombopag because they did not respond to eltrombopag, two patients due to relapse after discontinuing eltrombopag, and two for financial reasons.
More than 75% of children acheived an overall response
During a median of eight months of treatment with hetrombopag, 76.3% of the children achieved overall response, including complete response (61.3%) — defined as platelet counts of at least 100 billion/L and no bleeding events. Most children (76.1%) achieved a durable treatment response, meaning that elevated platelet levels were maintained for at least six months.
A total of 19 children relapsed, defined as a decrease in platelet counts to lower than 30×109/L after treatment response had been achieved. There was a trend toward higher relapse rates among children who received three or more drugs before hetrombopag than in those previously treated with two or one drugs (50% vs. 29.3% vs. 10%).
Among the 71 patients with overall response, 52.1% achieved a treatment-free response (TFR) for 13.5 months. TFR is defined by a platelet count of 50 billion/L or higher for at least six months following hetrombopag discontinuation.
This study demonstrated that hetrombopag is a safe and well-tolerated treatment option for paediatric patients with ITP for whom first-line therapies have failed.
Those with newly diagnosed ITP had a significantly higher TFR rate than children with chronic disease (60.4% vs. 34.8%). Further analysis demonstrated that for newly diagnosed ITP, treatment response was significantly higher in children younger than 5 years than in those 5 years and older (84.4% vs. 55.6%).
These results indicate “that hetrombopag had a better therapeutic effect in patients younger than 5 years in the newly diagnosed ITP group,” the researchers wrote.
Almost one quarter (22 children) did not respond to hetrombopag. Eleven of them switched to other TPO-RAs — four to Doptelet and seven to eltrombopag — and one to mycophenolate mofetil. The remaining children within this group went back to their first-line medications.
Thirty-five children experienced mild to moderate adverse events, most commonly those younger than 7 years. The most frequent were upper respiratory tract infections (19.4%), followed by higher-than-normal platelet levels (6.5%). Bleeding events occurred in 23.7% of the children.
According to the researchers, “this study demonstrated that hetrombopag is a safe and well-tolerated treatment option for paediatric patients with ITP for whom first-line therapies have failed.”
However, “the possibility of spontaneous remission cannot be completely ruled out,” making it necessary to increase the number of participants in studies and “extend the hetrombopag treatment time and follow-up time in future research,” they added.
