T. Ellingsen

Mannose-Binding Lectin Gene Polymorphisms Are Associated with Disease Activity and Physical Disability in Untreated, Anti-Cyclic Citrullinated Peptide-Positive Patients with Early Rheumatoid Arthritis

Objective. To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). Methods. Patients with early RA (n = 158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position −221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). Results. Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p = 0.02), and physical disability by HAQ (p = 0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs. Conclusion. The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

FRI0607 Effect of Methotrexate and Intra-Articular Betamethasone with or Without Additional Cyclosporine on Magnetic Resonance Imaging (MRI)-Determined Inflammatory and Destructive Changes in Very Early Rheumatoid Arthritis – Results from a 24-Months' Randomised Double Blind Placebo Controlled Trial

Background MRI has been shown to be more sensitive than clinical examination and x-ray for detection of inflammatory and destructive joint changes in early rheumatoid arthritis (RA) and to discriminate between treatment arms in clinical trials using the semi-quantitative Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI scoring (RAMRIS) system. Objectives To investigate whether MRI-determined measures of disease activity and joint destruction were suppressed in very early RA patients following a treat-to-target strategy with methotrexate (MTX) and intraarticular (i.a.) betamethasone and to investigate whether concomitant cyclosporine (CYA) had an additional effect on MRI determined inflammatory and destructive findings over 2 years. Methods In the 2-year randomised, double-blind, multicentre, clinical, treat-to-target trial, CIMESTRA, 160 patients with early (<6 months) RA were treated with MTX, i.a. betamethasone and CYA/placebo CYA. 129 patients participated in the MRI substudy, and had contrast-enhanced MRIs at months 0, 6, 12 and 24 that covered the non-dominant wrist (wrist-only group) and if technically possible both wrist and metacarpophalangeal (MCP) joints (wrist+MCP group). MRIs were evaluated by an experienced radiologist blinded to patient identity, clinical and biochemical data but not to chronology, using the RAMRIS scoring system assessing inflammatory (osteitis, synovitis, tenosynovisits) and destructive (erosions, joint space narrowing) changes. Observed data, without any data imputations, are reported. Non-parametric statistics were used. A value of p<0.05 was considered statistically significant. Results MRI-results from the wrist-only group are shown in table 1. The data in the wrist+MCP group were overall similar (data not shown). No statistically significant differences between the treatment groups were observed in any MRI characteristics at baseline or at any follow-up time point. Both the wrist-only group and the wrist+MCP group showed significant reductions compared to baseline in osteitis, synovitis and tenosynovitis at 6 months (all parameters) and 12 and 24 months (synovitis and tenosynovitis). Statistically significant, but numerically low, increases in erosion and JSN scores from baseline to 6, 12 and 24 months were seen. Conclusions A treat-to-target strategy with MTX and i.a. betamethasone reduced MRI inflammatory findings significantly, with no additional effect of CYA, but minor structural damage progression was still observed. References Hetland ML, et al. 2006. Arthritis Rheum 54:1401-1409. Hetland ML, et al. 2009. Ann Rheum Dis 68:384-390. Disclosure of Interest None declared

AB0001 Genotype and Haplotype Effects of 7 Single-Nucleotide Polymorphisms in the CRP Gene on Levels of C-Reactive Protein and DAS28 in Two Cohorts of Treatment NaÏVe, Recent Onset Rheumatoid Arthritis Patients

Background Single nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene are implicated in the regulation of the constitutional CRP expression and its response to pro-inflammatory stimuli. Previous reports suggest that these effects may influence instruments for clinical decision-making based on CRP, e.g. DAS28. Objectives To investigate the associations between 7 CRP SNPs, their haplotypes, the serum level of CRP and DAS28 in recent onset, treatment naïve RA (rheumatoid arthritis) patients. Methods 315 DMARD and steroid naïve RA patients with disease duration <6 months were included from two randomized controlled trials (CIMESTRA (n=135), OPERA (n=180)). The genotype and haplotype associations to CRP and DAS28 at baseline and after one year of active treatment were evaluated using linear regression analysis adjusted for age, sex and treatment. Genotyping were analyzed by the TaqMan OpenArray system. The results from the combined cohorts are presented. Results Table 1. Genotype associations to CRP and DAS28 Rs-no. CRP [β (P)] DAS28 [β (P)] Baseline Year 1 Baseline Year 1 rs11265257 −0.14 (0.19) −0.01 (0.91) −0.09 (0.31) −0.06 (0.49) rs1130864 0.15 (0.21) 0.03 (0.78) 0.16 (0.10) 0.14 (0.12) rs1205 −0.26 (0.03) −0.09 (0.38) −0.08 (0.39) −0.09 (0.32) rs1800947 −0.34 (0.14) −0.12 (0.57) 0.02 (0.91) 0.23 (0.21) rs2808632 0.18 (0.15) −0.04 (0.73) −0.04 (0.71) −0.08 (0.40) rs3093077 −0.10 (0.69) 0.30 (0.16) −0.26 (0.21) −0.02 (0.90) rs876538 0.15 (0.28) −0.05 (0.66) 0.02 (0.86) −0.02 (0.87) β, β coefficient; P, P-value. Table 2. CRP haplotype build, frequency and effect on CRP and DAS28 Haplotype Frequency CRP [Effect (CI)] DAS28 [Effect (CI)] Baseline Year 1 Baseline Year 1 H1 (CACT) 30.5% 96% (73;126) 99% (77;126) 102% (98;107) 105% (97;113) H2 (TGCT) 25.7% 74% (55;99) 91% (70;118) 99% (94;103) 97% (89;106) H3 (CGCG) 31.4% 100% 100% 100% 100% H4 (CGCT) 6.2% 66% (41;107) 121% (80;184) 95% (88;103) 102% (89;116) H5 (TGGT) 5.5% 64% (40;103) 86% (56;134) 101% (93;108) 110% (95;124) Haplotype defining SNPs (rs1205, rs1130864, rs1800947, rs2808632). Effects are stated relative to the most frequent Haplotype H3 (= reference, 100.) The minor allele of rs1205 C>T was associated with decreased CRP levels at baseline (p=0.03). The TT genotype showed a 50% reduction in CRP from 16.7 to 8.4 mg/l (p=0.005) compared to the CC genotype. This association was not observed after one year of active treatment (p=0.38) (Table 1). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (p=0.04), but no effect was observed at year 1 (p=0.47) (Table 2). No other SNP or haplotype were associated with CRP at baseline or year 1 (p≥0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or year 1 (p≥0.10) Conclusions This study shows that DAS28 can be used for clinical decision-making without adjustment for CRP gene variants, as CRP genotypes and haplotypes were only marginally associated with CRP levels and without any association to the DAS28 score. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1357