TY - JOUR
T1 - Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis
AU - RAVE-ITN Research Group
AU - Owczarczyk, Kasia
AU - Cascino, Matthew D.
AU - Holweg, Cecile
AU - Tew, Gaik W.
AU - Ortmann, Ward
AU - Behrens, Timothy
AU - Schindler, Thomas
AU - Langford, Carol A.
AU - William, E.
AU - Merkel, Peter A.
AU - Spiera, Robert
AU - Seo, Philip
AU - Kallenberg, Cees G.M.
AU - Specks, Ulrich
AU - Lim, Noha
AU - Stone, John
AU - Brunetta, Paul
AU - Prunotto, Marco
N1 - Funding Information:
FUNDING. The analysis for this study was funded by Genentech Inc.
Funding Information:
We acknowledge the contribution of the RAVE trial site principal investigators, as well as the ITN. Research specimens from the ITN021AI RAVE trial were provided by the ITN and sponsored by the NIAID of the NIH under award no. UM1AI109565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the NIHR, or the Department of Health. See Supplemental Acknowledgments for RAVE-ITN Research Group details.
PY - 2020/8
Y1 - 2020/8
N2 - BACKGROUND. Baseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS. A previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS. Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6, 12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression ≥ 0.01 expression units (termed FCRL5hi) exhibited significantly higher CR rates at 6, 12, and 18 months as compared with FCRL5lo subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively). CONCLUSION. Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner. FUNDING. The analysis for this study was funded by Genentech Inc.
AB - BACKGROUND. Baseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS. A previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS. Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6, 12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression ≥ 0.01 expression units (termed FCRL5hi) exhibited significantly higher CR rates at 6, 12, and 18 months as compared with FCRL5lo subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively). CONCLUSION. Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner. FUNDING. The analysis for this study was funded by Genentech Inc.
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U2 - 10.1172/JCI.INSIGHT.136180
DO - 10.1172/JCI.INSIGHT.136180
M3 - Article
C2 - 32841219
AN - SCOPUS:85091191149
VL - 5
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 18
M1 - e136180
ER -