In children with new ITP, Promacta works better than standard care
Sustained platelet response seen for twice as many participants in trial
In a large, investigator-initiated clinical trial, about twice as many children and adolescents with newly diagnosed immune thrombocytopenia (ITP) achieved a sustained platelet response when treated with Promacta (eltrombopag) versus standard therapy, new data show.
Additional data from the now-completed Phase 3 PINES trial (NCT03939637) demonstrated that Promacta also worked better than standard care in reducing the need for rescue therapy for these teens and youngsters.
Further, the use of the approved oral therapy was also found to improve health-related quality of life in a clinically meaningful manner relative to standard care.
“The findings from this trial are applicable to real-world settings and support use of [Promacta] in the subset of newly diagnosed children who require pharmacological treatment,” the researchers wrote, also noting that “approximately half of patients in this trial had experienced at least [one] prior treatment failure” before being given Promacta.
The trial results were detailed in “Eltrombopag for Newly Diagnosed Pediatric Immune Thrombocytopenia Requiring Treatment,” a study published in JAMA, the journal of the American Medical Association. Novartis, which markets Promacta, funded the trial.
ITP is an autoimmune disease in which the immune system mistakenly attacks platelets, the circulating cell fragments that help blood to clot. Such attacks lower platelet counts, which increases the risk of internal or external bleeding.
ITP treatment, tied to immunosuppression, unchanged for 30 years
Treatment of newly diagnosed ITP patients has remained relatively unchanged for three decades, with first-line therapies typically consisting of corticosteroids, intravenous immunoglobulin therapy (IVIG), and anti-D immunoglobulin therapy.
Yet, these treatments are limited to variable and short-term responses, and all are associated with various immunosuppressing side effects, particularly with prolonged use.
Promacta, sold as Revolade in most countries outside the U.S., is approved as a second-line therapy for children and adults with ITP whose disease doesn’t adequately respond to first-line therapies. The medication has been shown to sustainably boost platelet counts, without the immunosuppression associated with other treatments.
To learn more about Promacta’s effectiveness versus first-line therapies in children and adolescents with newly diagnosed ITP, a research team from multiple institutions in the U.S. and one in Canada launched PINES (Pediatric ITP Newly Diagnosed Patients Eltrombopag vs Standard Therapy).
A total of 118 newly diagnosed ITP patients, split nearly evenly by sex, were enrolled at 27 sites across the U.S. The participants needed drug treatment but did not have severe bleeding or the need for a rapid platelet boost.
Enrollment was stratified across three age groups: children ages 1-5 (39%), those ages 6-11 (35.6%), and adolescents aged 12-17 (25.4%). Slightly more than half of the participants were treatment-naive, meaning they had not received prior therapy, while the remaining 44% did not adequately respond to previous treatment.
All were randomly assigned to receive Promacta or a first-line therapy chosen by the investigator. Such therapies were glucocorticoids, intravenous immunoglobulin, or anti-D immunoglobulin.
Promacta outperformed standard therapy for health-related quality of life
According to the results, twice as many children with ITP who received Promacta achieved a sustained platelet response — defined as three or more platelet counts greater than 50 × 109/L over six to 12 weeks without rescue treatment — compared with those on standard therapy (67% vs. 35%).
Similar results were obtained for a composite score assessed at 12 weeks (67% vs. 44%), which combined a platelet count greater than 30 × 109/L, a minimum twofold increase in platelet count, and no bleeding. The mean time to reach the composite score outcome was longer with Promacta than standard therapy (35.5 vs. 20.2 days).
In both groups, the proportion of patients with high bleeding scores was similar at all time points and declined over time.
Fewer than half as many Promacta-treated patients required rescue therapy as those receiving standard treatment (17% vs. 38%), with a shorter median time to rescue therapy (16 vs. 21 days). The proportion of patients who received an off-label second-line therapy or platelet transfusion was also lower in the Promacta group than in the standard therapy group (6% vs. 15%).
Promacta outperformed standard therapy in achieving clinically meaningful improvements in health-related quality of life by 12 weeks, or about three months. This was assessed by Kids’ ITP Tool (KIT) scores, a validated quality-of-life tool for youth with ITP. This calculated improvements in both the child-reported and parent-reported impact KIT scores.
Similar to traditional therapies, [Promacta] is ineffective in a subset of patients (about one-third), but unlike standard first-line treatments, the drug can achieve sustained platelet elevations (albeit with ongoing dosing).
The safety profile of Promacta was similar to that found in prior pediatric studies. Here, more than twice as many Promacta-treated patients experienced severe adverse events (14 vs. 6) and nonserious adverse events. The most common were headaches and nosebleeds. No blood-clotting events were reported.
The researchers noted that, because the trial excluded ITP patients with severe bleeding due to a known slower response to Promacta, “this treatment strategy should not be extrapolated to that patient population.”
“In pediatric patients with newly diagnosed immune thrombocytopenia requiring pharmacological treatment, [Promacta] resulted in a higher rate of sustained platelet response compared with standard therapy,” the team concluded. “[Promacta] may be an effective option for pediatric patients with newly diagnosed immune thrombocytopenia with nonsevere bleeding who warrant medical intervention.”
According to an editorial that accompanied this study, Promacta “can now be considered, at the least, as an option for children who are likely to benefit from therapy.”
The authors of that editorial, also published in JAMA, added that “similar to traditional therapies, [Promacta] is ineffective in a subset of patients (about one-third), but unlike standard first-line treatments, the drug can achieve sustained platelet elevations (albeit with ongoing dosing).”
About the Author
