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Abstract Number: 0038

Protein Biomarkers May Differentiate Responders and Non-Responders to Adalimumab, a Tumour Necrosis Factor Inhibitor, in Ankylosing Spondylitis Patients – The Bioefficacy SpA Study

Ana Fernandes1, Atlas Mashayekhi Sardoo2, Miguel Bernardes3, Patrícia Pinto4, Helena Santos5, João Lagoas Gomes6, José Tavares-Costa7, José A. P. da Silva8, João Madruga-Dias9, Alexandra Bernardo10, Jean-Charles Gaillard11, Lúcia Domingues12, Sara Maia12, Jean Armengaud11, Jaime C. Branco13, Ana Varela Coelho14 and Fernando Pimentel-Santos15, 11.Instituto de Tecnologia Química e Biológica, Universidade NOVA de Lisboa; 2.Universidade de Trás-os-Montes e Alto Douro, Vila Real, Portugal, Oeiras, Portugal, 23. CEDOC, NOVA Medical School, Faculdade de Ciências Médicas da Universidade NOVA de Lisboa, Lisboa, Portugal, Lisbon, Portugal, 34.Centro Hospitalar de S. João (Rheumatology Department) , Porto, Portugal, Porto, Portugal, 45. Centro Hospitalar de Vila Nova de Gaia/Espinho (Rheumatology Department), Vila Nova de Gaia, Portugal, Vila Nova de Gaia, Portugal, 56.Instituto Português de Reumatologia (Rheumatology Department), Lisboa, Portugal, Lisboa, Portugal, 67.Hospital Egas Moniz (CHLO) (Rheumatology Department), Lisboa, Portugal, Lisboa, Portugal, 78.Unidade Local de Saúde do Alto Minho (Rheumatology Department), Ponte de Lima, Portugal, Ponte de Lima, Portugal, 89.Centro Hospitalar e Universitário Coimbra (Rheumatology Department), Coimbra, Portugal, Coimbra, Portugal, 910.Centro Hospital Médio Tejo (Rheumatology Department), Torres Novas, Portugal, Dublin, Ireland, 105.Centro Hospitalar de Vila Nova de Gaia/Espinho (Rheumatology Department), Vila Nova de Gaia, Portugal, Vila Nova de Gaia, Portugal, 1111.Centre d énergie atomique (Laboratoire Innovations technologiques pour la Détection et le Diagnostic (Li2D), Service de Pharmacologie et Immunoanalyse (SPI)), Avignon, France, Avignon, France, 123.CEDOC, NOVA Medical School. Faculdade de Ciências Médicas da Universidade NOVA de Lisboa, Lisboa, Portugal, Lisboa, Portugal, 133.CEDOC, NOVA Medical School, Faculdade de Ciências Médicas da Universidade NOVA de Lisboa, Lisboa, Portugal; 7.Hospital Egas Moniz (CHLO) (Rheumatology Department), Lisboa, Portugal, Lisboa, Portugal, 141.Instituto de Tecnologia Química e Biológica, Universidade NOVA de Lisboa, Oeiras, Portugal, Oeiras, Portugal, 153.CEDOC, NOVA Medical School, Faculdade de Ciências Médicas da Universidade NOVA de Lisboa, Lisboa, Portugal; 7.Hospital Egas Moniz (CHLO) (Rheumatology Department), Lisboa, Portugal, Lisbon, Portugal

Meeting: ACR Convergence 2020

Keywords: Ankylosing spondylitis (AS), Anti-TNF Drugs, proteomics

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Session Information

Date: Friday, November 6, 2020

Title: Genetics, Genomics & Proteomics Poster

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Axial Spondyloarthritis (AS) is amongst the most common forms of inflammatory arthritis. Widely used in the treatment of axSpA, adalimumab is an engineered antibody holding only human peptide sequences with high affinity and specificity to soluble and transmembrane TNFα, blocking its interaction with receptors p55 and p75. However, the response to TNFi is heterogeneous and might be linked with some side effects. A priori identification of patients more propense to respond to TNFi is critical in clinical practice.

Methods: The proteomic analysis involved 33 patients with AS from the Bioefficacy SpA Study, of which 19 responders and 14 non-responders after 14 weeks treatment with adalimumab, according to ASAS20 criteria. Serum samples were collected at baseline, 3-5 days, 2 weeks and 14 weeks after treatment. The experimental workflow combined immunoaffinity depletion of the high-abundant serum proteins, tryptic digestion of the proteins extracted from the depleted serum, HPLC separation of tryptic peptides, MS/MS based identification and MS quantification of the detected proteins. Uni- and multivariate statistical analysis of the differentially abundant proteins was used to select the more sensitive and specific serum biomarkers related with therapeutic response. Protein function association network analysis of differential proteins was performed with STRINGdb.

Results: LC-MS/MS method allowed the identification of 333 proteins with at least 2 non-ambiguous peptides. A set of new putative biomarkers was identified with 8 proteins displaying differences between R and NR (p < 0.05) at baseline. Of these, 3 proteins were highly linked with a good clinical response, while the other 5 proteins were strongly related with a non-response to adalimumab therapy at W14. This set of proteins was confirmed to be predictive of the type of response to treatment with an area under the Receiver Operating Characteristics (ROC) curve of 1. Additionally, our analysis showed that the pathways dysregulated in both groups were relatively similar.

Conclusion: Proteomic approaches constitute a very promising strategy to the identification of biomarkers to predict a therapeutic response. These results provide evidence that a panel of biomarker proteins might be identified even before the beginning of treatment which is of utmost importance for clinical practice.


Disclosure: A. Fernandes, None; A. Mashayekhi Sardoo, None; M. Bernardes, None; P. Pinto, None; H. Santos, None; J. Lagoas Gomes, None; J. Tavares-Costa, None; J. da Silva, MyFibromyalgia®, a webcompany delivering services to patients with Fibromyalgia, 9; J. Madruga-Dias, None; A. Bernardo, None; J. Gaillard, None; L. Domingues, None; S. Maia, None; J. Armengaud, None; J. Branco, None; A. Varela Coelho, None; F. Pimentel-Santos, None.

To cite this abstract in AMA style:

Fernandes A, Mashayekhi Sardoo A, Bernardes M, Pinto P, Santos H, Lagoas Gomes J, Tavares-Costa J, da Silva J, Madruga-Dias J, Bernardo A, Gaillard J, Domingues L, Maia S, Armengaud J, Branco J, Varela Coelho A, Pimentel-Santos F. Protein Biomarkers May Differentiate Responders and Non-Responders to Adalimumab, a Tumour Necrosis Factor Inhibitor, in Ankylosing Spondylitis Patients – The Bioefficacy SpA Study [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/protein-biomarkers-may-differentiate-responders-and-non-responders-to-adalimumab-a-tumour-necrosis-factor-inhibitor-in-ankylosing-spondylitis-patients-the-bioefficacy-spa-study/. Accessed .
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/protein-biomarkers-may-differentiate-responders-and-non-responders-to-adalimumab-a-tumour-necrosis-factor-inhibitor-in-ankylosing-spondylitis-patients-the-bioefficacy-spa-study/

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