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OBJECTIVES: To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional effect.METHODS: In a double-blind, placebo-controlled trial, 85 disease-modifying antirheumatic drug-naïve patients with ERA were randomised to receive methotrexate, intra-articular glucocorticosteroid injections and placebo/adalimumab (43/42). Contrast-enhanced MRI of the right hand was performed at months 0, 6 and 12. Synovitis, osteitis, tenosynovitis, MRI bone erosion and joint space narrowing (JSN) were scored with validated methods. Dynamic contrast-enhanced MRI (DCE-MRI) was carried out in 14 patients.RESULTS: Synovitis, osteitis and tenosynovitis scores decreased highly significantly (pCONCLUSIONS: A treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid in patients with ERA effectively decreased synovitis, osteitis and tenosynovitis and halted structural damage progression as judged by MRI. The findings suggest that addition of adalimumab is associated with further suppression of osteitis and tenosynovitis.

OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRPMETHODS: In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (RESULTS: Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRPCONCLUSIONS: Adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment did not increase the proportion of patients who reached the DAS28CRP

Objective: To investigate the efficacy of switching to a second biological drug in rheumatoid arthritis (RA) patients. Methods: Since 2000, Danish RA patients (n = 1021) receiving biological therapy have been registered in the nationwide DANBIO database. The first and second treatment series of patients, who switched therapy before 2005 (n = 235), were analysed for their reasons for switching, Disease Activity Score 28 (DAS28), DAS28 improvement, European League against Rheumatology (EULAR) response and drug survival. Most patients switched from infliximab to etanercept or adalimumab. Results: Median survivals for switchers’ first/second treatment were 37/92 weeks (all patients’ first treatment 119 weeks). Reasons for switching were lack of efficacy (LOE; 109 patients), adverse events (AE; 72), other reasons (54). If patients experienced AE to the first drug, 15% had AE to the second. Median DAS28 improvements in first/second treatment at 3 months were: LOE switchers 1.1/1.6; AE switchers 1.5/0.8. In LOE switchers, a good/moderate EULAR response was more prevalent during the second treatment course than during the first (63% versus 54%, p = 0.02). AE switchers achieved similar EULAR responses to both treatments (59% versus 50%, p = 0.38). Conclusion: LOE switchers had a better clinical response to the second treatment. AE switchers responded equally well to both treatments, with a low risk of discontinuing the second drug as a result of AE. Drug survival of the switchers’ second biological therapy was higher than of the first, but lower than that of non-switchers. No difference between various sequences of drugs were found. Danish post-marketing data thus support that RA patients may benefit from switching biological therapy.

Objective: To compare changes in regional bone mineral density (BMD) of the metacarpal joints measured by dual x ray absorptiometry (DXA) and digital x ray radiogrammetry (DXR) in relation to disease activity and radiographic outcome in a two year follow up study of patients with early RA and unclassified polyarthritis. Patients and methods: 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least four weeks and less than two years were included. 51 patients fulfilled the ACR criteria for RA. 21 patients had unclassified polyarthritis. The patients with RA were divided into groups according to mean disease activity, average glucocorticoid dose, and MRI and x ray detected bone erosions in the hands. Clinical and biochemical measurements were made every month and an x ray examination of the hands and BMD of the metacarpal joints every six months. Results: DX R BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease. No changes in BMD measured by DX A were seen in any patient group. Conclusion: DX R is a useful measure of the destructive disease activity in patients with RA and unclassified polyarthritis, providing valuable information about bone changes associated with disease activity and erosive disease in early RA. DX R is better than DX A for detecting and monitoring periarticular osteoporosis of the metacarpal bone.

OBJECTIVES—To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS—One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS—The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. CONCLUSIONS—This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.

Background Magnetic Resonance Imaging (MRI) osteitis and synovitis have been identified as predictors of structural damage progression in rheumatoid arthritis (RA)1,2, but the predictive value of MRI joint space narrowing (JSN, a measure of cartilage damage) and tenosynovitis (TS) needs further investigation. Objectives To investigate the predictive value of baseline MRI inflammatory and damage parameters on 2 year MRI and X-ray damage progression in an early RA (eRA) cohort following a non biologic treat-to-target strategy. Methods In 129 eRA ( Results Independent predictors of structural damage progression are presented in table 1. If MRI JSN was not included in the model, MRI osteitis score was statistically significant independent predictor of X-ray progression (coefficient 0.32, p=0.001, vs TSS progression). Conclusions This trial is the first to report that MRI JSN independently predicts both X-ray and MRI damage progression in early RA. Further studies are needed to confirm early MRI-determined cartilage damage as predictor of progressive joint destruction in RA. References Hetland et al, Ann Rheum Dis 2009 Boyesen et al, Ann Rheum Dis 2011 Haavardsholm et al, Ann Rheum Dis 2007 Disclosure of Interest None declared

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 ( 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

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 naive RA (rheumatoid arthritis) patients. Methods 315 DMARD and steroid naive RA patients with disease duration Results 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

Background In the CIMESTRA Study patients with early rheumatoid arthritis (RA) were treated with methotrexate (MTX) and intra-articular glucocorticoid. This led to results comparable to biological trials with 34%/28% of pts in DAS28/ACR remission after 1 year (1,2). Objectives We studied if addition of adalimumab (ADA) to the CIMESTRA strategy is of further therapeutic benefit. Methods DMARD naive early RA patients with disease duration 3.2 after three months. Efficacy was assessed by DAS28(CRP), CDAI, SDAI and ACR/EULAR Boolean remission criteria. Primary analysis was by ITT with last observation carried forward. Completer analysis and ITT without imputations gave similar results (not shown). Values are medians (5%/95% percentiles) or percentage. We used Mann-Whitney or Pearson’s chi-square tests. Results Baseline characteristics were similar between MTX+PLA/MTX+ADA groups: Women: 69%/63%; age: 54.4/56.2 years; disease duration: 83/84 days; anti-CCP positive: 70%/60%; IgM-RF positive: 74%/70%; DAS28(CRP): 5.6/5.5; HAQ: 1.0/1.1 (all NS). Triple therapy was added in 25/17 patients (p=0.25). Treatment target was reached in 46%/58% (MTX+PLA/MTX+ADA) at 1 month, 63%/73% (2 months), 70%/76% (3 months), and 76%/80% (12 months) (NS between groups at all time points). However, in the MTX+ADA group significantly more patients achieved rapid and sustained clinical remission as assessed by DAS28, CDAI, SDAI and ACR/EULAR remission criteria (table). Number needed to treat (NNT) with ADA to achieve remission in one extra patient at 1 year was 4 to 5.9 depending on remission criteria. Conclusions Low disease activity was achieved by $≈ $80% in both groups, but remission rates increased considerably by adding adalimumab to methotrexate and intraarticular glucocorticoid injections in DMARD naive patients with early RA. References Hetland et al: Arthritis Rheum 2006;54:1401-09. Hetland et al: Ann Rheum Dis 2008;67:815-22. Disclosure of Interest K. Horslev-Petersen Grant/Research support from: Abbott, M. Hetland Grant/Research support from: Abbott, Bristol-Meyers Squibb, Roche, Schering-Plough/MSD, UCB-Nordic, and Wyeth/Pfizer, Speakers Bureau: Abbott, Centocor, Roche,Schering-Plough/MSD, UCB-Nordic, and Wyeth/Pfizer, P. Junker: None Declared, J. Podenphant: None Declared, T. Ellingsen: None Declared, P. Ahlquist: None Declared, H. Lindegaard Speakers Bureau: Roche, A. Linauskas: None Declared, A. Schlemmer Speakers Bureau: MSD, Roche, M. Dam: None Declared, I. Hansen: None Declared, H. Horn: None Declared, A. Jorgensen: None Declared, S. Krintel: None Declared, J. Raun: None Declared, C. Ammitzboll: None Declared, J. Johansen: None Declared, M. Ostergaard Grant/Research support from: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth., Speakers Bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth., K. Stengaard-Pedersen Grant/Research support from: Abbott

Background Recently we reported, that DAS28CRP rd month triple therapy with MTX, sulphasalazine (SZS) and hydroxychloroquine (HCQ) 1 . Addition of adalimumab (ADA) at baseline yielded even better clinical responses and remission rates after treatment for one year. Objectives The purpose of the present investigation was to study whether the improved clinical response obtained by adding ADA to MTX + i.a. TRIAM injections can be maintained after withdrawal of ADA. Methods Patients with ERA were randomized to receive i.a. TRIAM (40 mg/ml) in any swollen joint in combination with MTX (20 mg/wk) for two years and placebo-ADA (MTX+PLA) or MTX+ADA (40 mg eow) during the first year. Peroral glucocorticoid was not allowed. After 1 yr, ADA/PLA was withdrawn. If patients had swollen joints and DAS28(CRP)>3.2 during yr 2, SZS and HCQ were added, and if active disease persisted, ADA (40 mg eow) replaced SZS and HCQ in both treatment arms. Clinical response was assessed by DAS28(CRP), CDAI, SDAI and ACR/EULAR remission criteria. Analysis was by ITT with last observation carried forward. Medians (5%/95% percentiles) or percentage. Mann-Whitney or Pearson’s chi-square tests. Results Baseline characteristics were similar in the MTX+PLA and MTX+ADA groups (DAS28(CRP) 5.6 (3.8-7.3) vs. 5.5 (3.8-7.8), NS). Table shows 1 and 2 years results. Serious adverse events were seen in 10 MTX+PLA patients (malignancy: 2, infections: 5, other: 2) and in 16 MTX+ADA patients (malignancy: 3, infections: 5, other: 8). Conclusions Combined MTX and i.a. TRIAM provided excellent disease control at 2 years’ follow-up of ERA patients. The improved clinical responses observed during additional ADA administration could not be maintained after withdrawal of ADA. Radiographic data are needed to evaluate the overall effect of 1 yr of ADA as induction therapy in combination with MTX and i.a. TRIAM in ERA References Horslev-Petersen K et al. Ann Rheum Dis 2012: Disclosure of Interest None Declared

Background M-ficolin is a soluble pattern recognition molecule that activates the complement system. We recently reported a factor 300 difference in the synovial fluid M-ficolin concentration between rheumatoid arthritis (RA) and osteoarthritis, suggesting a pathogenic role of M-ficolin 1 . Objectives To assess M-ficolin in DMARD naive early RA patients, investigate correlations between M-ficolin and disease activity markers, and analyze the predictive value of M-ficolin. Methods 180 DMARD naive RA patients with disease duration Results The highest M-ficolin levels were measured in the OPERA cohort at baseline (2.84μg/l, CI 2.63-3.09), and during treatment the level decreased 24% (CI 18-31%, p At baseline M-ficolin correlated to DAS28 (rho=0.29, p Logistic regression analysis determined M-ficolin as the strongest predictor of DAS28 Low baseline M-ficolin level was the only variable associated with low disease activity at year one, and this was further analyzed by comparing the group with the 25% lowest baseline M-ficolin levels with the remaining 75% of patients (cutoff 2.00 μg/l). This resulted in a sensitivity of 29%, a specificity of 96%, and a positive predictive value of 98% in determining a DAS28 score Conclusions The elevated baseline M-ficolin levels in early RA correlated consistently to disease activity markers, most notably DAS28 and HAQ, thus reflecting essential parts of the disease activity. Low M-ficolin levels at baseline predicts a positive predictive value of 98% of a DAS28 References Ammitzboll CG, et al. Rheumatol Int 2011. Disclosure of Interest None Declared

Background Response to anti-TNF therapy is highly variable in patients with rheumatoid arthritis (RA). Predictors of treatment response have been identified, but their ability to predict response in individual patients is poor (1). MicroRNAs (miRNAs) have been suggested to influence susceptibility to RA and disease severity (2). Objectives To identify predictive miRNAs associated with treatment response in 180 patients with RA (disease duration Methods Patients received methotrexate 7.5 mg weekly (increased to 20 mg/week within two months) in combination with adalimumab (n=89)/placebo-adalimumab (n=91) 40 mg subcutaneously every other week. If swollen joints were present, they were injected with triamcinolone. Treatment response after 1 year was assessed according to EULAR response (good vs. moderate/poor), DAS28(CRP) remission, and ACR/EULAR Boolean remission criteria. MiRNAs were purified from pretreatment whole blood. Expressions of miRNAs were determined using TaqMan® Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Raw Cycle threshold (Ct) values of each miRNA were pre-processed using quantile normalization. Interaction between miRNAs and treatment was tested for each miRNA, and potential predictive miRNAs (p-values Results In the adalimumab-group/placebo-group 82%/74% achieved EULAR good response, 74%/49% achieved DAS28(CRP) remission, and 48%/30% EULAR/ACR Boolean remission. After backwards elimination a low expression of miR-22 in the adalimumab group was associated with response using EULAR response (OR: 12.18, 95% CI: 2.30-140.45, p=0.01) and DAS28(CRP) remission (OR: 44.74, 95% CI: 5.99-736.18, p=0.001) as outcome parameters. Similarly, high expressions of miR-23b (OR: 0.48, 95% CI: 0.24-0.86, p=0.03) and miR-758 (OR: 0.20, 95% CI: 0.03-0.86, p=0.05) in the adalimumab group were associated with response using DAS28(CRP) remission as outcome parameter. A high expression of miR-629 in the adalimumab group (OR: 0.45, 95% CI: 0.23-0.82, p=0.01) was associated with response using ACR/EULAR remission. Conclusions We identified several miRNAs in whole blood from patients with early RA associated with treatment response to adalimumab. Validation studies are needed to assess the utility of these miRNAs as predictive biomarkers in patients with RA. References Prajapati R et al. Pharmacogenomics 2011;12:1571-85. Trenkmann M et al. Clin Rev Allergy Immunol 2010;39:10-9. Horslev-Petersen K et al. Arthritis Rheum 2011; 63 (Supplement 10): 394. Disclosure of Interest S. B. Krintel: None Declared, C. Dehlendorff: None Declared, M. Hetland: None Declared, K. Horslev-Petersen: None Declared, K. Andersen: None Declared, P. Junker: None Declared, J. Podenphant: None Declared, T. Ellingsen: None Declared, P. Ahlqvist: None Declared, H. Lindegaard Consultant for: MSD, Merck, Roche, A. Linauskas: None Declared, A. Schlemmer: None Declared, M. Dam: None Declared, I. Hansen: None Declared, H. C. Horn: None Declared, A. Jorgensen: None Declared, J. Raun: None Declared, C. Ammitzboll: None Declared, M. Ostergaard: None Declared, K. Stengaard-Pedersen: None Declared, J. Johansen: None Declared