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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Musculoskeletal Disorders 1/2015

Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis

Zeitschrift:
BMC Musculoskeletal Disorders > Ausgabe 1/2015
Autoren:
Mahmood M. T. M. Ally, Bridget Hodkinson, Pieter W. A. Meyer, Eustasius Musenge, Gregory R. Tintinger, Mohammed Tikly, Ronald Anderson
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12891-015-0587-1) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

MA was responsible for the study design, clinical assessment, analysis, communication of data and drafting the manuscript. PWAM was responsible for the study design and the generation, analysis, communication of data and critical revision of important intellectual content. BH was responsible for the study design, clinical assessment, analysis, communication of data and critical revision of important intellectual content. EM was responsible for the statistical design, data analysis and critical revision of important intellectual content. GT was responsible for study design, analysis of data and critical revision of important intellectual content. MT was responsible for the study design, served as the clinical coordinator, and performed data analysis, critical revision of important intellectual content. RA was responsible for the study design, analysis, critical revision of important intellectual content and coordinator. All authors read and approved the final manuscript.

Abstract

Background

To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries.

Patients and methods

A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE).

Results

Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 – p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, 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 (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident.

Conclusions

The use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value.
Zusatzmaterial
Additional file 1: Table S1. SDAI (Simplified disease activity index) base line disease activity. Table S2. changes in SDAI and circulating biomarker concentrations following 6 months of synthetic DMARD therapy. Table S3. SDAI (Simplified disease activity index) response at 6 months. Table S4. SDAI (Simplified disease activity index) response at 6 months treatment sub-groups. Table S5. SDAI (Simplified disease activity index) response at 6 months risk allele sub-groups.
12891_2015_587_MOESM1_ESM.pdf
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