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.
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.