Abstract | INTRODUCTION: METHODS: AMPLE was a phase IIIb, 2-year, randomized, head-to-head trial of abatacept versus adalimumab. Post hoc analyses of baseline anti-cyclic citrullinated peptide-2 (anti-CCP2, an ACPA surrogate) positive (+) status and ACPA fine-specificity profiles over time, as well as transcriptional profiling (peripheral whole blood), were performed. RESULTS: Of 646 patients treated ( abatacept, n = 318; adalimumab, n = 328), ACPA and gene expression data were available from 508 and 566 patients, respectively. In anti-CCP2+ patients (n = 388), baseline fine specificities for most ACPAs were highly correlated; over 2 years, levels decreased with abatacept but not adalimumab. By year 2, expression of genes associated with T cell co-stimulation and antibody production was lower for abatacept versus adalimumab; expression of genes associated with proinflammatory signaling was lower for adalimumab versus abatacept. Treatment modulated the expression of T- and B-cell gene signatures, with differences in CD8+ T cells, activated T cells, plasma cells, B cells, natural killer cells (all lower with abatacept versus adalimumab), and polymorphonuclear leukocytes (higher with abatacept versus adalimumab). CONCLUSIONS: In AMPLE, despite similar clinical outcomes, data showed that pharmacodynamic/genetic changes after 2 years of abatacept or adalimumab were consistent with drug MoAs. Further assessment of the relationship between such changes and clinical outcomes, including prediction of response, is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00929864.
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Authors | Omar Jabado, Michael A Maldonado, Michael Schiff, Michael E Weinblatt, Roy Fleischmann, William H Robinson, Aiqing He, Vishal Patel, Alex Greenfield, Jasmine Saini, David Galbraith, Sean E Connolly |
Journal | Rheumatology and therapy
(Rheumatol Ther)
Vol. 9
Issue 2
Pg. 391-409
(Apr 2022)
ISSN: 2198-6576 [Print] England |
PMID | 34878629
(Publication Type: Journal Article)
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Copyright | © 2021. The Author(s). |