Prevalence of anti-rituximab antibodies in autoimmune forms of glomerulonephritis and podocytopathies
Jan Miroslav Hartinger, Martin Šíma, Zdenka Hrušková, Alena Pilková, Irena Francová, Helena Posová, Romana Ryšavá, Eva Jančová, Marek Mysliveček, Vladimír Tesař, Ondřej SlanařAbstract
Anti-drug antibody (ADA) formation against rituximab (RTX) may affect treatment efficacy, safety, and B-cell depletion kinetics, yet data across different immune-mediated diseases remain limited. We evaluated ADA formation in 1312 blood samples from 300 patients with various autoimmune systemic and kidney-affecting diseases treated by rituximab (RTX) to describe the formation frequency and titers of ADA.
ADA positivity was found in 54 patients and typically paralleled B-cell reconstitution. ADAs were significantly more frequent in diagnoses with overall worse response to RTX treatment (membranous nephropathy (MN), systemic lupus erythematosus, focal-segmental glomerulosclerosis (FSGS) and other less frequent diagnoses) compared with standard-response diagnoses (ANCA associated vasculitis (AAV) and minimal change disease). The pattern of ADA formation differed between diagnoses—in AAV ADAs were usually detected in low titers and transiently, in MN ADA titers were higher and more sustained and in FSGS ADA titers were sometimes unmeasurably high and occurred rather early during the treatment. We were not able to evaluate the interference of ADA formation or their titers with clinical response as some of our patients obtained robust response even after formation of unmeasurably high ADA titers. ADA formation frequency and titers markedly differ between different autoimmune diseases, therefore the frequency of their formation and their clinical significance should be evaluated separately in patients with different diagnoses.