Ultomiris dosing, for some, may go beyond recommended levels
Data study into real-world practice favors evaluating PNH treatment response
Almost 6 out of 10 people with paroxysmal nocturnal hemoglobinuria (PNH) living in the U.S. may be being given a higher initial loading dose of Ultomiris (ravulizumab) than is recommended on the medication’s label, a database study into its clinical use reports.
Researchers also observed that maintenance doses, given after the loading dose for as long as treatment lasts, also may be higher than recommended in almost 3 of every 10 patients, suggesting that Ultomiris may not be working as intended for everyone.
“Deviations from label-recommended dosing regimens occur with [Ultomiris] dosing patterns in real-world clinical practice, highlighting the need for further investigations of treatment response,” the scientists wrote.
The study, “Dosing Patterns of Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Ravulizumab in the United States: A Retrospective Claims-Based Analysis,” was published in the journal Advances in Therapy. The work was funded by Apellis Pharmaceuticals, which markets Empaveli (pegcetacoplan), and its one pharmaceutical researcher is an Apellis employee. Its other scientists work for Analysis Group in Boston.
Ultomiris is designed to allow for less frequent dosing than Soliris
PNH occurs when blood cells become liable to attack by the complement system, a cascade of proteins that work together with the immune system to protect against infection and remove damaged cells from tissues.
Medications approved to treat PNH work by blocking certain proteins of the complement system. This prevents the complement system from breaking down healthy blood cells, thereby helping to ease disease symptoms.
Soliris (eculizumab), the first medication approved for adults with PNH in the U.S., reduces the breakdown of red blood cells by targeting the C5 complement protein. It also has been shown to reduce blood clotting and the need for regular transfusions.
In real-world clinical practice, however, “some patients still experience symptoms with approved [Soliris] doses and may need to receive larger or more frequent doses than recommended,” the researchers wrote.
While Ultomiris works in a way similar to Soliris, it is designed to last longer in the body, allowing for less frequent dosing. Approved in the U.S. for both adults and children with PNH, it is dosed based on a patient’s body weight. However, real-world data on Ultomiris dosing patterns are lacking.
To determine those patterns, researchers drew on data from insurance claims covering people with PNH, ages 12 and older, who received at least two infusions of Ultomiris between June 21, 2019, and May 6, 2021.
Their study included 433 patients with a mean age of 47.4. More than half (54.3%) previously had been treated with Soliris. Patients’ most common symptoms were anemia, referring to low red blood cell numbers (39.7%), and fatigue (10.2%).
The mean loading dose of Ultomiris was 3,316.3 mg, which exceeded the maximum recommended loading dose of 3,000 mg for patients weighing at least 100 kg (about 220 lbs) by slightly more than 10%.
Mean maintenance doses fell between recommended doses based on weight
Over a mean period of 11.8 months, patients received a mean of 5.8 infusions. The mean maintenance dose per infusion was 3,403.7 mg, falling between the 3,300 mg recommended dose for patients weighing at least 60 kg (about 132 pounds) but less than 100 kg, and the 3,600 mg recommended dose for those weighing at least 100 kg.
Because insurance claim records lacked data on body weight, researchers estimated the proportions of patients receiving the recommended doses based on scenarios created from data collected from the U.S. general population.
The estimated proportions of patients receiving the recommended loading and maintenance doses were 23.1% and 39.2%, respectively. But 59.1% of patients were estimated to be given a higher-than-recommended loading dose and 28.4% a higher maintenance dose, the study reported.
“Larger than recommended [Ultomiris] doses may have been administered to some patients with PNH,” the researchers wrote, noting that “more studies are needed to evaluate treatment response to complement inhibitors.”
They added that “the greater than label-recommended loading doses observed in this study were driven by greater loading doses administered to [Soliris]-naive patients compared with [Soliris]-experienced patients,” noting that definitive reasons for this could not be determined from the data at hand.
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