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Abstract Number: 423

Circulating Anti-Citrullinated Peptide Antibodies and Cytokines As Biomarkers of Response to Disease-Modifying Antirheumatic Drugs Therapy in Early Rheumatoid Arthritis

Mahmood MTM Ally1, Pieter Meyer2, Bridget Hodkinson3, Eustasius Musenge4, Gregory Tintinger2, Mohammed Tikly5 and Ronald Anderson1, 1University of Pretoria, Pretoria, South Africa, 2university of pretoria, pretoria, South Africa, 3Rheumatology, University of the Witwatersrand, Johannesburg, South Africa, 4University of Witwatersrand, Johannesburg, South Africa, 5Rheumatology Wits University, C H Baragwanath Hospital, Johannesburg, South Africa

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ACPA, DMARDs, Early Rheumatoid Arthritis, Genetic Biomarkers and cytokines

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Session Information

Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity

Session Type: Abstract Submissions (ACR)

Background/Purpose

Serial measurement of circulating anti-citrullinated peptide antibodies (ACPA) and cytokines is of potential importance in the management of patients with rheumatoid arthritis (RA). However, the utility of this strategy in monitoring responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA is largely untested.

Methods

A cohort of 140 predominantly (88.5%) black female South African patients with early RA median (IQR) symptom duration 9.7 (11.4) months was treated with synthetic DMARDs, mostly methotrexate (MTX), either as monotherapy  or combination DMARD therapy, mostly combined with low-dose oral corticosteroids (CS).  The simple disease activity index (SDAI) was used to evaluate clinical response, while circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured using immunofluorimetric and multiplex suspension bead array procedures respectively at baseline and after 6 months of therapy. Shared epitope genomic analysis was done using PCR typing of the HLA-DRB1 allele.

Results

Following 6 months of therapy, the median SDAI declined from a baseline of 41.39 to 16 (p=0.0001) for the entire cohort. This decline in disease activity was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.65 units, p=<0.0001) and several of the circulating cytokines (IL-4, IL-6, IL-7, IL-8, G-CSF, VEGF, CCL4; p<0.023 – p<0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. No significant correlations between these biomarkers and disease activity were observed. Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (594.1 vs. 255.7 units, p<0.05), while no associations with ACPA and a smoking history were evident.

Conclusion

The use of synthetic DMARDs in early RA is associated with significant decreases in SDAI, paralleled by a decrease in ACPA and predominantly pro-inflammatory cytokines. However, the lack of correlation of ACPA and the other biomarkers with therapy-associated alterations in disease activity in the short term appears to preclude the utility of serial measurement of these biomarkers to monitor early responses to therapy, while the long-term, prognostic potential remains to be established.


Disclosure:

M. M. Ally,
None;

P. Meyer,
None;

B. Hodkinson,
None;

E. Musenge,
None;

G. Tintinger,
None;

M. Tikly,
None;

R. Anderson,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-anti-citrullinated-peptide-antibodies-and-cytokines-as-biomarkers-of-response-to-disease-modifying-antirheumatic-drugs-therapy-in-early-rheumatoid-arthritis/

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