Studies suggest that the newly recommended combination therapies help more people reach stable platelet levels without ongoing treatment than steroids alone, at least within the first year. “I think the data is very clear,” says James Bussel, MD, a hematologist at Weill Cornell Medicine in New York City, “that combining steroids with [TPO-RAs] or steroids with rituximab at diagnosis or right after is a very good way to go.”
If these drugs are not available (or you can’t have or don’t want them), the guidelines suggest corticosteroids alone.
The guidelines don’t favor one combination therapy over the other, but the drugs differ in how they work and how they are administered.
Thrombopoietin Receptor Agonists (TPO-RAs)
TPO-RAs work by mimicking thrombopoietin, a hormone that signals bone marrow cells to produce platelets when levels drop.
Dr. Bussel likens the process to a hypothetical factory that’s in charge of maintaining a stable number of cars on the road. If cars start getting wrecked faster than usual, the total number of cars drops below baseline. “One of the ways you can help keep the number of cars on the streets up is by having the factory make more cars,” he says. “And that’s what TPO [and TPO-RA] does: It tells the bone marrow to make more platelets.”
There are three TPO-RAs available today: eltrombopag (Promacta) and avatrombopag (Doptelet), which are daily oral pills, and romiplostim (Nplate), a weekly subcutaneous injection. Unlike rituximab, these drugs don’t suppress the immune system and most people quickly respond to the drugs (their platelet levels return to safe levels), often within a couple of weeks.
B-Cell Depletion Therapy (Rituximab)
Rituximab (Rituxan) works by essentially cutting off the source of antibodies that help destroy platelets. Antibodies are proteins that bind to foreign substances, allowing the immune system to target and remove them from the body. Rituximab is a lab-made antibody that attaches to the CD20 protein on B-cells — immune cells that give rise to plasma cells, which can produce platelet-targeting antibodies — causing the immune system to deplete B-cells.
“The hope, and the way that I talk about it with patients, is that it’s like a hard reset,” says Cindy Neunert, MD, a hematologist at Columbia University Irving Medical Center in New York City. When the B-cells replenish, “they don’t have that memory” to differentiate into autoantibody-secreting plasma cells, she says.
More than half of people initially respond to rituximab. It’s given as a single course of four weekly intravenous infusions, offering the potential for long-term, treatment-free remission.