Low plasma rituximab concentration appears highly associated with the risk of major relapse in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), according to an article published in Arthritis & Rheumatology.
This ancillary study of the MAINRITSAN 2 trial analyzed the relationship between rituximab plasma concentration, genetic polymorphisms in pharmacokinetic/pharmacodynamic candidate genes, and clinical outcomes in 135 patients with AAV.
Study participants were treated with a 500 mg fixed-schedule rituximab infusion or an individually tailored regimen. The researchers measured rituximab plasma concentrations after 3 months and genotyped 53 DNA samples for single nucleotide polymorphisms within 88 presumed pharmacokinetic/pharmacodynamic candidate genes.
According to the results, the number of patients with a rituximab plasma concentration lower than 4 μg/mL was significantly lower in the fixed-schedule group compared with the tailored-infusion group.
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Low rituximab plasma concentration at 3 months was found to be an independent risk factor for major relapse at month 28. Specifically, rituximab plasma concentration lower than 4 μg/mL at 3 months was identified by sensitivity survival analysis as an independent risk factor for both major relapse and relapse.
Moreover, researchers found STAT4 rs2278940 and PRKCA rs8076312 to be significantly associated with rituximab plasma concentration at 3 months but not with major relapse at 28 months.
“Our results highlight the need to identify rapid metabolizers who do not achieve sustained adequate rituximab plasma concentrations and therefore could be at high risk of major relapse. Regular plasma rituximab monitoring could be helpful in identifying these patients over time and refining their dosing schedule according to their actual rituximab clearance,” Khoudour and colleagues wrote.
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“Overall, this study paves the way toward a personalized dosing approach based on therapeutic drug monitoring to precisely individualize rituximab dosing during maintenance therapy.”
Although researchers have established the effectiveness of rituximab for the treatment of AAV, the interindividual variability in response to rituximab remains unclear.
Khoudour N, Delestre F, Jabot-Hanin F, et al. Association between plasma rituximab concentration and the risk of major relapse in antineutrophil cytoplasmic antibody-associated vasculitides during rituximab maintenance therapy. Arthritis Rheumatol. Published online May 3, 2023. doi:10.1002/art.42556