ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0057

Molecular Profiling of Radiographic Axial Spondyloarthritis Patients Reveals an Association Between Innate and Adaptive Cell Populations and Therapeutic Response to Adalimumab

Rita Torres1, Daniel Sobral2, Ana Fernandes3, Atlas Sardoo4, Miguel Bernardes5, Patrícia Pinto6, Helena Santos7, João Gomes8, Jose Tavares-Costa9, José Silva10, João Dias11, Alexandra Bernardo5, Jean Gailard12, Jean Armengaud13, Vladimir Benes14, Lúcia Domingues15, Sara Maia16, Jaime Branco17, Ana Varela18 and Fernando Santos19, 1Rheumatology Department, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal, 2Faculdade Ciências e Tecnologia, Lisboa, Lisboa, Portugal, 3Instituto de Tecnologia Química e Biológica, Lisboa, Portugal, 4CEDOC, NOVA Medical School, UNL, Lisboa, Lisboa, Portugal, 5Rheumatology Department, Centro Hospitalar Universitário de São João EPE, Porto, Portugal, 6Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal, 7Portuguese Institute of Rheumatology, Lisbon, Portugal, 8Hospital Egas Moniz, Lisboa, Lisboa, Portugal, 9Rheumatology Department - Unidade Local de Saude do Alto Minho, Ponte de Lima, Portugal, 10Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, 11Centro Hospitalar Médio Tejo, Abrantes, Portugal, 12Centre dénergie atomique; Service de Pharmacologie et Immunoanalyse (SPI), Paris, France, 13Service de Pharmacologie et Immunoanalyse (SPI), Paris, France, 14The European Molecular Biology Laboratory, Heidelberg, Germany, 15CEDOC - Chronic Diseases Research Center - Nova Medical School|Faculdade de Ciências Médicas, Lisboa, Lisboa, Portugal, 16NOVA Medical School, Nova University of Lisbon, Lisboa, Lisboa, Portugal, 17EpiDoC Unit, CEDOC, Nova Medical School, Comprehensive Health Research Centre (CHRC), Lisbon, Portugal, 18Instituto Tecnologia Química e Biológica; Universidade NOVA de Lisboa, Lisboa, Lisboa, Portugal, 19Hospital Egas Moniz, Lisboa, Portugal

Meeting: ACR Convergence 2021

Keywords: , ,

Session Information

Date: Saturday, November 6, 2021

Session Title: Spondyloarthritis Including PsA – Basic Science Poster (0046–0068)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: The response to treatment in spondylarthropaties is heterogeneous, due to factors yet to be better described. For that reason, it is important to find tools that might help clinicians to decide what is the best available therapeutic option for each patient.

The goal of this study is to use comprehensive molecular profiling to characterize clinical response to therapy in a real-world setting. Specifically, to identify molecular biomarkers differentiating good responders and non-responders to TNF inhibitors (TNFi) treatment, using adalimumab, in radiographic axial spondyloarthritis | ankylosing spondylitis (r-axSpA|AS) patients context.

Methods: Whole-blood mRNA and plasma proteins were measured in a cohort of biologic naïve r-axSpA|AS patients (n = 35) from the Bioefficacy study (Biomarkers identification of anti-TNF alpha agent efficacy in AS patients using RNA sequencing and mass spectrometry), pre and post (14 weeks) TNFi treatment using adalimumab. Response to treatment was categorized according to ASAS20. Results of differential expression analysis were used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi.

Results: A treatment-related signature, independent of the type of response, suggests a reduction in inflammatory disease activity. We found genes and proteins robustly differentially expressed between baseline and week 14 in responders, including the GWAS AS-associated genes TNFRSF1A, FCGR2A, TYK2, TBKBP1, IL1R1, IL6R, ICOSLG, IL7R, HHAT and LTBR. Moreover, CRP and HP proteins showed strong and early decrease in the plasma of AS patients, while a cluster of apolipoproteins (APO1, APO2, APO3) showed an increased expression at week 14. Good responders to TNFi treatment tend to have higher expression of innate immunity genes at baseline, and lower expression of markers associated with adaptive immunity, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender and Gene x, the top differentially expressed gene at baseline between responders and non-responders, enabled an accurate prediction of response to adalimumab in our cohort (AUC=0.97).

Conclusion: Differences in disease activity and/or innate/adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in r-axSpA|AS. Alternatively, a model including clinical and gene expression variables could be considered, particularly in patients with mild disease activity.

Disclosures: R. Torres, None; D. Sobral, None; A. Fernandes, None; A. Sardoo, None; M. Bernardes, Lilly, 1, Janssen, 1, Abbvie, 1; P. Pinto, None; H. Santos, None; J. Gomes, None; J. Tavares-Costa, None; J. Silva, None; J. Dias, None; A. Bernardo, None; J. Gailard, None; J. Armengaud, None; V. Benes, None; L. Domingues, None; S. Maia, None; J. Branco, None; A. Varela, None; F. Santos, None.

To cite this abstract in AMA style:

Torres R, Sobral D, Fernandes A, Sardoo A, Bernardes M, Pinto P, Santos H, Gomes J, Tavares-Costa J, Silva J, Dias J, Bernardo A, Gailard J, Armengaud J, Benes V, Domingues L, Maia S, Branco J, Varela A, Santos F. Molecular Profiling of Radiographic Axial Spondyloarthritis Patients Reveals an Association Between Innate and Adaptive Cell Populations and Therapeutic Response to Adalimumab [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/molecular-profiling-of-radiographic-axial-spondyloarthritis-patients-reveals-an-association-between-innate-and-adaptive-cell-populations-and-therapeutic-response-to-adalimumab/. Accessed February 3, 2023.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/molecular-profiling-of-radiographic-axial-spondyloarthritis-patients-reveals-an-association-between-innate-and-adaptive-cell-populations-and-therapeutic-response-to-adalimumab/