MADRID — No association was observed between pharmacokinetic levels of rituximab and clinical response in patients with ANCA-associated vasculitis, according to findings presented at the EULAR Annual Congress.
Divi Cornec, MD, of the Mayo Clinic in Rochester, Minn., and of the Department of Rheumatology at CHRU Brest in France, said clinical response to rituximab (Rituxan, Genentech) has been historically heterogeneous in ANCA-associated vasculitis (AAV). Although around 75% of patients reach remission after infusion, Cornec noted that 30% of those complete responders relapse the following year.
“Our objective was to describe the pharmacokinetics of rituximab in patients with AAV and its determinants,” he said. They also aimed to study the association of rituximab pharmacokinetics with relevant outcomes.
Cornec and colleagues used a novel assay based on mass spectrometry known as the monoclonal immunoglobulin rapid accurate mass measurement.
“This assay was first developed for myeloma,” Cornec said.
The study included 89 patients from the RAVE data set. These participants received at least four infusions of rituximab at 375 mg/m2. The researchers assessed serum levels of the drug at weeks 2 and 4 and then at months 2, 4 and 6.
“Rituximab levels were highly variable after four infusions in AAV patients,” Cornec said. “Some patients have low exposure to serum levels, while other patients have high exposure levels.”
The most important determinant of rituximab levels was gender, with lower levels appearing in men. Another strong correlation with low rituximab levels was new diagnosis of AAV. Body surface area was also a determinant of rituximab levels, and a weak correlation was noted for inflammation.
“More inflammation was associated with lower levels of rituximab,” Cornec said. “Also, in patients with more B cells, rituximab decreased after therapy.”
There was no difference between responders and non-responders at 6 months for any of the different measurements that were done for rituximab quantification, according to Cornec.
The group hypothesized that quantifying rituximab could predict relapse risk.
“There was no association between quantification of rituximab and risk of relapse during the following years,” Cornec concluded. “Simpler dosing protocols could be used in patients with AAV.” — by Rob Volansky
Cornec D, et al. Abstract #OP0320. Presented at: EULAR Annual Congress; June 14-17, 2017; Madrid.
Disclosure: Cornec reported that the data were taken from the RAVE study, which was supported by Genentech.