UCSF Pioneers New Treatment for a Common Childhood Bleeding Disorder

For three decades, the first treatments for a common autoimmune bleeding disorder have remained the same: a short course of oral steroids or an intravenous (IV) infusion.

These therapies used in the first three months of a pediatric immune thrombocytopenia (ITP) diagnosis often have temporary results, making it difficult for children to safely return to the sports field and other physical activities. Side effects ranging from moodiness to severe headaches are a major challenge, especially when treatments need to be repeated.

Now, a major national study, led by the UCSF Department of Pediatrics and published recently in JAMA, has paved the way for a new standard of care that is more effective, better-tolerated, and more convenient for families.

A More Effective Option

The PINES trial, a phase 3 randomized clinical trial, compared the 30-year-old standard of care to eltrombopag, an oral, once-daily pill that is already FDA-approved for chronic ITP (lasting more than one year). 65% of children treated with eltrombopag achieved a sustained platelet response, nearly double the 35% who responded to standard therapy.

"The sustained platelet response without the use of rescue therapy is both statistically significant and clinically relevant," says Kristin Shimano, MD, the principal investigator for the study and a pediatric hematologist-oncologist at UCSF. "This treatment will very much change the way we approach the management of kids with newly diagnosed ITP."

The Benefits for Children

Shimano explains that a stable platelet count allows clinicians to "keep patients at a level where it will be safer for them to participate in activities like sports that are restricted at lower platelet counts.”

This new approach with an oral pill offers a strong alternative to standard care. “For children requiring treatment, the standard therapies raise their platelet count, but very often they fall again,” she says. “So, patients may end up getting multiple courses of treatment, and their counts bounce up and down.”

Eltrombopag should not be used to raise the platelet counts quickly for life-threatening bleeding. It requires monthly liver function monitoring and must be taken apart from food and dairy, but its stable response helps families avoid repeated IVs or steroid courses.

“Logistically, the IV infusions may require a hospitalization,” Shimano notes. One IV therapy can cause severe headaches — a frightening side effect that, in a child with low platelets, can raise concern for a brain bleed and require an emergency room visit. The other common IV option has a black-box warning for causing the breakdown of red blood cells.

By comparison, a well-tolerated oral pill represents a major improvement.

Leading a National Collaboration

This practice-changing trial was the culmination of a nearly decade-long effort, with Shimano designing the protocol and overseeing the multi-site trial. She serves as chair of the Pediatric ITP Consortium of North America (ICON) Operations Committee.

The study, which involved 23 centers across North America, highlights the importance of UCSF’s leadership role within national research consortia. “For rare diseases, you really need to collaborate with other institutions to be able to have a large enough trial to draw meaningful conclusions,” Shimano says. “This is the first trial looking at a new therapy in this phase of ITP in over 30 years.”

The UCSF Advantage

At UCSF, this leadership in national research means our patients are often the first to receive the next generation of treatments and the benefits they bring.

“When our patients have access to these trials, they receive care that the leaders in the field feel are the best treatments available,” Shimano says. “It also gives them a chance to take part in something that can have a positive effect on other kids like them in the future.”

While Shimano points out that many children with newly diagnosed ITP can be safely observed until the disease resolves on its own, this study provides a powerful new option for those who do need intervention. “It’s exciting that we now have a new, more effective, option for our patients.”

This commitment to practice-changing research in the UCSF Division of Pediatric Hematology transforms care for children with blood disorders.

Funding: Novartis provided eltrombopag and funding for the trial.

Authors: For all authors, please see the full publication.