ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 595

Discovery of Serum Protein Biomarkers of Response to Adalimumab in Rheumatoid Arthritis and Their Relationship to Biomarkers of Response to Infliximab

Ignacio Ortea1, Bernd Roschitzki2, Eva Tomero3, Juan G. Ovalles-Bonilla4, Javier Lopez-Longo5, Inmaculada de la Torre5, Isidoro Gonzalez-Alvaro6, Juan J Gomez-Reino7 and Antonio Gonzalez8, 1Maimónides Health Research Institute (IMIBIC), Cordoba, Spain, 2Functional Genomics Center Zurich, University and ETH Zurich, Zurich, Switzerland, 3Rheumatology, Hospital Universitario de La Princesa. IIS La Princesa, Madrid, Spain, 4Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain, 5Gregorio Marañon Hospital, Madrid, Spain, 6Hospital Univ. de La Princesa, IIS Princesa, Madrid, Spain, 7Instituto Investigacion Sanitaria- Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain, 8Laboratorio Investigacion 10 and Rheumatology Unit, Instituto Investigacion Sanitaria- Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

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

Background/Purpose:

Biomarkers of
response to treatment in rheumatoid arthritis (RA) are sorely needed
given the large inter-individual variability in efficacy of the
available drugs. However, some authors think it will be difficult to
distinguish between response to the different drugs. The doubts on
biomarkers are based in the broadly similar efficacy of all bDMARDs
and the lack of validated biomarkers to date, although the
best-established, as seropotivity, show clear drug-specific
association.
Methods:


Discovery of biomarkers of response to adalimumab
(ADM) was based in combined depletion of the most abundant serum
proteins, 8-plex iTRAQ labeling, two-dimensional LC fractionation,
protein identification and relative quantification with a hybrid
Orbitrap mass spectrometer. The results were compared and combined
with an identical study of response to infliximab (INX) (1).

Results:

262
proteins were identified in all the samples with at least 2 peptides
and 95% confidence. Nine proteins presented differences between
non-responders (NR) and responders (R) (P
< 0.05), representing candidate biomarkers of
response to ADM. None of them was coincident with the previously
identified 14 candidate biomarkers of response to INX. In addition,
the NR/R differences in response to ADM and to INX were not
correlated (rspearman=
0.07; P=
0.40), and were inversely correlated when only the significant
proteins were considered (rspearman=
-0.69; P=
0.0023) as shown in Fig. 1.

The
combined analysis of response to ADM and to INX, however, identified
eight proteins (ADAMTSL2, A2M, APOB, APOC3, F9, C3, C8A and PF4),
showing that discordance was not universal.
Conclusion:


Potential biomarkers of response to ADM were identified. This panel
was independent of the previously obtained in response to INX. The
pathways highlighted in the two studies were also different. These
results suggest that mechanisms of inter-individual variability are
partly drug-specific, and that it will be possible to obtain
biomarkers orienting the election of drugs.

  1. Ortea I, et al. J Proteomics. 2012;77:372-82.

Supported by
PRIME-XS of the 7th Framework Program of the European Union, and
grants of the Instituto de Salud Carlos III (Spain), which are
partially financed by the European Regional Development Fund of the
European Union.

Disclosure: I. Ortea, None; B. Roschitzki, None; E. Tomero, None; J. G. Ovalles-Bonilla, None; J. Lopez-Longo, None; I. de la Torre, Eli Lilly and Company, 3; I. Gonzalez-Alvaro, None; J. J. Gomez-Reino, None; A. Gonzalez, None.

To cite this abstract in AMA style:

Ortea I, Roschitzki B, Tomero E, Ovalles-Bonilla JG, Lopez-Longo J, de la Torre I, Gonzalez-Alvaro I, Gomez-Reino JJ, Gonzalez A. Discovery of Serum Protein Biomarkers of Response to Adalimumab in Rheumatoid Arthritis and Their Relationship to Biomarkers of Response to Infliximab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/discovery-of-serum-protein-biomarkers-of-response-to-adalimumab-in-rheumatoid-arthritis-and-their-relationship-to-biomarkers-of-response-to-infliximab/. Accessed .

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