Background Radiographic joint damage progresses in 20-30% of rheumatoid arthritis (RA) patients despite fulfilling clinical remission criteria [1]. Osteitis assessed on MRI predicts subsequent bone damage progression [2]. Therefore, targeting absence of osteitis combined with clinical remission may improve long-term radiographic outcomes. Objectives To investigate whether a 2-year MRI treat-to-target (MRI T2T) strategy targeting absence of osteitis combined with clinical remission, compared to a conventional T2T strategy targeting clinical remission only, could reduce radiographic joint damage progression over 5 years in RA patients. Methods IMAGINE-more was designed as a three-year observational extension study of the 2-year IMAGINE-RA randomized clinical trial [3]. IMAGINE-RA included 200 RA patients in clinical remission (DAS28-CRP<3.2 and no swollen joints), with erosive disease (bone erosion on conventional radiography), and treated with csDMARDs. The objective was to investigate whether an MRI T2T strategy targeting absence of osteitis combined with clinical remission (DAS28-CRP≤3.2 and no swollen joints) as compared to a conventional T2T strategy, targeting clinical remission only, could improve remission rates and prevent radiographic joint damage progression. If treatment target was not met, treatment was intensified stepwise starting with increment in csDMARDs and subsequently adding biologics. Participants in the IMAGINE-more study were managed in routine clinical practice in outpatient clinics. Clinical examinations and radiographs of hands and feet (also obtained at baseline, year 1 and 2 in IMAGINE-RA) were done year 3, 4 and 5. The primary endpoint was the proportion of patients with no radiographic progression (increase in total van der Heijde-modified Sharp score (vdHSS) ≤0) from baseline to year 5. Secondary endpoints were 0-5 years changes in total vdHSS, vdHSS erosion and joint space narrowing (JSN) scores. Dichotomous endpoints were estimated by logistic regression, while median differences were calculated for the continuous outcome measures. Results Informed consent to participation in IMAGINE-more was obtained from 131 patients (59 from the original MRI T2T group). Of these, 14 patients (24%) in the MRI T2T group and 19 patients (26%) in the conventional T2T group had no radiographic progression from baseline to year 5 (OR 0.70 [0.28 to 1.71]). As illustrated in the Table 1 and Figure 1, the median progression in total vdHSS from baseline to 5 years was low, with no differences between treatment groups. Conclusion A 2-year combined MRI T2T and clinical T2T strategy, compared with a conventional clinical T2T strategy alone, did not result in reduced radiographic progression in the long term over 5 years in RA patients with erosive disease in clinical remission. References [1]Lillegraven et al. Ann Rheum Dis 2012[2]Brown et al. Arthritis Rheum 2008[3]Møller-Bisgaard et al. JAMA 2019 Acknowledgements: NIL. Disclosure of Interests Signe Møller-Bisgaard Grant/research support from: Study support from AbbVie, Kim Hørslev-Petersen: None declared, Lykke Midtbøll Ørnbjerg: None declared, Bo Ejbjerg: None declared, Merete Lund Hetland: None declared, Jakob Møllenbach Møller: None declared, Robin Christensen: None declared, Sabrina Mai Nielsen: None declared, Daniel Glinatsi: None declared, Mikael Boesen Shareholder of: Minority shareholder in Image Analysis Group LTD, London UK, Speakers bureau: AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, UCB and Esaote, Paid instructor for: Novartis and Eli Lilly, Consultant of: Novartis, Grant/research support from: AbbVie, Celgene, Novo Nordisk and Novartis, Kristian Stengaard-Pedersen Consultant of: Pfizer, AbbVie, Grant/research support from: Roche, Pfizer, AbbVie and Medoc., Ole Madsen: None declared, Bente Jensen: None declared, Jan Alexander Villadsen: None declared, Ellen Margrethe Hauge Shareholder of: Novartis, AbbVie, Sanofi, Sobi, Grant/research support from: esearch funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, AbbVie, Oliver Hendricks Speakers bureau: Pfizer, Lilly, Novartis, Hanne Merete Lindegaard: None declared, Niels Steen Krogh: None declared, Anne Grethe Jurik: None declared, Henrik Thomsen: None declared, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Novartis and UCB.Table 1Radiographic endpoints at 5 years (change from baseline - year 0)*nMRI T2TnConventional T2TDifference between groupsP valuePrimary endpointNo radiographic progression, No. (%)5914 (24%)7219 (26%)OR=0.70(0.28 to 1.71)0.431Key secondary endpointChange in total vdHSS (0-448)471.0 [0.0-3.0]562.0 [0.0-4.0]0.0 (-1.0 to 0.0)0.515Other secondary endpointsChange in erosion (0-280)471.0 [0.0-2.0]561.0 [0.0-3.0]0.0 (0.0 to 0.0)0.967Change in JSN (0-168)470.0 [0.0-0.5]560.0 [0.0-1.3]0.0 (0.0 to 0.0)0.565Group contrasts are presented as No. (%) for dichotomous data and medians [IQR] for continuous data. OR (95%CI) were estimated from logistic regression adjusted for a propensity score and with non-responder imputation. For endpoints with continuous data median differences (95%CI) were calculated based on the ITT population (no manual imputation)*In addition to the radiographic endpoints, the full IMAGINE-more study includes a clinical co-primary endpoint, and several secondary endpoints.

Objectives: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. Method: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP <= 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity.

Background:Achieving remission according to stringent criteria such as Simplified Disease Activity Index (SDAI) and ACR/EULAR Boolean remission is associated with a better long-term outcome in patients with RA1. Possible predictors of achieving stringent remission in patients in clinical remission, following targeted treatment strategies, have not been investigated.Objectives:To investigate the predictive value of clinical, radiographic and MRI variables on achieving more stringent remission in RA patients in clinical remission, following MRI and conventional treat-to-target (T2T) strategies.Methods:In this post-hoc study, data were used from 171 RA patients in clinical remission (DAS28-CRP< 3.2 and no swollen joints) on conventional synthetic DMARDs, included in the IMAGINE-RA randomized clinical trial2, where they followed an MRI T2T strategy (targeting absence of osteitis) combined with clinical remission (DAS28-CRP≤3.2 and no swollen joints) or a conventional T2T strategy (targeting clinical remission only). Baseline contrast-enhanced MRIs of the dominant wrist and 2nd-5thMCP joints and radiographs of hands and feet were evaluated according to the OMERACT RAMRIS scoring system and Sharp/van der Heijde method, respectively, by two experienced readers. Potential clinical, radiographic and MRI baseline predictors of remission were first tested in univariate logistic regression analyses with achievement of Clinical Disease Activity Index (CDAI), SDAI, and ACR/EULAR Boolean remission at 24 months as dependent variables. Variables with p<0.25 were subsequently tested in multivariate logistic regression analyses with backward selection, adjusted for age, gender and strategy group. Missing values of covariates were imputed using chained equations.Results:Based on the univariate analyses, tender joint count, patient VAS global, VAS pain, VAS fatigue, physician VAS global, HAQ, MRI osteitis, radiographic and MRI erosion and joint space narrowing scores were included in multivariate analyses (Table).Following the MRI T2T strategy was a positive predictor and high patient VAS global a negative predictor of achieving all definitions of remission. Furthermore, high patient VAS pain was negatively associated with achieving SDAI and ACR/EULAR Boolean remission and high tender joint count negatively associated with achieving CDAI and SDAI remission.Multivariate logistic regression analyses with backward selection, final modelsDependent variables, remission at 24 monthsCDAISDAIACR/EULAR BooleanOR95% CIp-valueOR95% CIp-valueOR95% CIp-valueCovariatesMRI T2T strategy group2.941.25-7.520.0132.461.03-6.350.0435.472.33-14.11<0.001Female0.900.36-2.250.820.800.31-2.050.640.800.32-1.970.63Age1.020.98-1.070.321.020.98-1.070.331.030.99-1.070.15Tender joint count (0-28)0.330.12-0.860.0230.290.10-0.780.013Patient VAS global0.910.88-0.94<0.0010.930.88-0.97<0.0010.930.88-0.980.003Patient VAS pain0.950.91-1.000.0490.920.87-0.980.004Conclusion:In RA patients in clinical remission, poor patient reported outcomes and tender joint count were associated with decreased chance of achieving stringent remission, while following an MRI T2T strategy predicted stringent remission across all definitions thereof.References:[1]Smolen et al. Ann Rheum Dis 2017[2]Møller-Bisgaard et al. JAMA 2019Disclosure of Interests:Signe Møller-Bisgaard Grant/research support from: AbbVie, Consultant of: BMS, Speakers bureau: BMS, Celgene, Pfizer, Stylianos Georgiadis Grant/research support from: Novartis, Kim Hørslev-Petersen: None declared, Bo Ejbjerg: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Lykke Ørnbjerg: None declared, Daniel Glinatsi: None declared, Jakob Møllenbach Møller: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Kristian Stengaard-Pedersen: None declared, Ole Rintek Madsen: None declared, Bente Jensen: None declared, Jan Villadsen: None declared, Ellen Margrethe Hauge: None declared, Philip Bennett: None declared, Oliver Hendricks: None declared, Karsten Asmussen: None declared, Marcin Kowalski: None declared, Hanne Merete Lindegaard: None declared, Henning Bliddal Grant/research support from: received research grant fra NOVO Nordic, Consultant of: consultant fee fra NOVO Nordic, Niels Steen Krogh: None declared, Torkell Ellingsen: None declared, Agnete Nielsen: None declared, Lone Balding: None declared, Anne Grethe Jurik: None declared, Henrik Thomsen: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB

Background:The effect of different treatment escalations on MRI inflammation in rheumatoid arthritis (RA) patients following an MRI treat-to-target (T2T) strategy has not previously been investigated.Objectives:To compare the effect of different treatment escalations on MRI inflammation, physical function and disease activity in RA patients in clinical remission, following an MRI T2T strategy.Methods:One hundred RA patients in clinical remission (DAS28-CRP<3.2 and no swollen joints), on conventional synthetic (cs) DMARDs following an MRI T2T strategy targeting DAS28-CRP≤3.2, no swollen joints plus absence of MRI osteitis, were followed for 2 years with clinical and MRI (wrist and 2nd-5thMCP joints) evaluation every 4 months1. If target was not met, a predefined treatment escalation algorithm dictated: First: increase in csDMARDs (A), second: adding a TNF inhibitor (TNFi) (B), third and onwards: switch between biologics (C). If target was met, no change in baseline csDMARDs was done (D). Outcomes were assessed 4 months after treatment change. MRIs were evaluated with known chronology by one experienced reader. Repeated measures mixed linear models were used to express estimates of group differences on predefined co-primary outcomes (MRI osteitis, HAQ) and key secondary outcomes (MRI combined inflammation, Simplified Disease Activity Index (SDAI)).Results:Escalation to first TNFi (B) or to 2ndor later biologic (C) compared to csDMARDs (A) was consistently more effective on all outcomes (e.g. in group B osteitis was reduced with 1.8 units more than A) (Table). Unchanged (D) compared to escalation in csDMARD (A) treatment did not differ, except for HAQ-score. Escalation to a 2ndor later biologics (C) compared to the first TNFi (B) was more effective suppressing MRI inflammation. Escalation to TNFi treatment (B) or to 2ndor later biologic (C) compared to unchanged treatment (D) was more effective on all outcomes except from HAQ-score (no difference between groups).Comparisons of treatment escalations1A: Increment in csDMARD mono/combination therapy (n=73)); B: Switch from csDMARD combination therapy to TNFi (n=39); C: Switch from TNFi to 2ndbiologic/switch between biologics (n=21); D: No change in csDMARDs from baseline (n=58)A vs BA vs CA vs DB vs CB vs DC vs DOutcomesPrimaryMRIOsteitis1.8 (1.0; 2.6) p3.6 (2.3; 4.8) p0.3 (−0.3; 1.0)p=.321.8 (0.8; 2.9) p=.0006−1.4 (−2.4; −0.5) p=.0045−3.3 (−4.6; −1.9) pHAQ0.081(0.033; 0.13) p=.00110.091(0.031; 0.15) p=.00320.054(0.014; 0.095) p=.00910.0092(−0.051; 0.070) p=.77−0.027(−0.082; 0.028) p=.33−0.037(−0.10; 0.031) p=.29Key secondaryMRI combined inflammationa2.5 (0.9; 4.1) p=.00185.4 (3.1; 7.7) p0.4 (−0.9; 1.8)p=.522.9 (0.8; 4.9) p=.0064−2.1 (−4.0; −0.2) p=.032−5.0 (−7.5; −2.4) p=.0002SDAI2.7 (1.9; 3.5) p2.4 (1.4; 3.4) p0.5 (−0.2; 1.2)p=.14−0.3 (−1.3; 0.7)p=.60−2.2 (−3.1; −1.3) p−1.9 (−3.0; 0.8) p=.00061Estimates of group differences (least squares means (95% CI)).aSum score of synovitis, osteitis and tenosynovitisConclusion:T2T-based treatment escalations to biologics compared to csDMARD-escalations more effectively improved MRI inflammation, physical function and disease activity. Further optimization of the treatment in RA patients in clinical remission may improve long-term outcomes.References:[1]Møller-Bisgaard et al. JAMA 2019Disclosure of Interests:Signe Møller-Bisgaard Grant/research support from: AbbVie, Consultant of: BMS, Speakers bureau: BMS, Celgene, Pfizer, Kim Hørslev-Petersen: None declared, Bo Ejbjerg: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Robin Christensen: None declared, Lykke Ørnbjerg: None declared, Daniel Glinatsi: None declared, Jakob Møllenbach Møller: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Kristian Stengaard-Pedersen: None declared, Ole Rintek Madsen: None declared, Bente Jensen: None declared, Jan Villadsen: None declared, Ellen Margrethe Hauge: None declared, Philip Bennett: None declared, Oliver Hendricks: None declared, Karsten Asmussen: None declared, Marcin Kowalski: None declared, Hanne Merete Lindegaard: None declared, Henning Bliddal Grant/research support from: received research grant fra NOVO Nordic, Consultant of: consultant fee fra NOVO Nordic, Niels Steen Krogh: None declared, Torkell Ellingsen: None declared, Agnete Nielsen: None declared, Anne Grethe Jurik: None declared, Lone Balding: None declared, Henrik Thomsen: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB

Objective: To investigate the clinical and radiographic status, and to identify baseline predictors of functional status and erosive progression at 11 years' follow-up of early rheumatoid arthritis (RA) patients. Methods: Patients enrolled in the Danish investigator-initiated randomized controlled CIMESTRA trial, which investigated a 2 year treat-to-target intervention with methotrexate and intra-articular glucocorticoids with or without cyclosporine, were followed up. The 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) score, and total Sharp van der Heijde score (TSS) were assessed at baseline and 11 years. Baseline magnetic resonance imaging (MRI) of unilateral wrists was scored (OMERACT RAMRIS). Multivariable linear regression analyses of baseline variables [TSS, HAQ, DAS28, age, anti-cyclic citrullinated peptide (anti-CCP) status, gender, MRI erosion score, MRI synovitis score, MRI bone marrow oedema score] were performed in 96 patients with HAQ(11yrs) and increment TSS0-11yrs as dependent variables. Since outcomes were similar in the two treatment arms, data were pooled. Results: In total, 120 of 160 patients completed 11 years' follow-up. They were 63 (55-72) years old, 68% were in DAS28 remission (<= 2.4), HAQ(11yrs) was 0.25 (0-0.75), mean increment TSS0-11yrs was 0.96 +/- 1.52 units/year; 53%, 20%, and 27% received conventional treatment, biologics, and no treatment, respectively; and 34% had not progressed radiographically since baseline. Increased DAS28 (p = 0.02) and anti-CCP (p = 0.03) predicted HAQ(11yrs), whereas anti-CCP (p = 0.03) and MRI bone marrow oedema (p = 0.01) predicted increment TSS0-11yrs in multivariable analyses. Conclusions: Early and strict synovitis suppression with methotrexate and intra-articular glucocorticoids led to persistently high remission rates and limited erosive progression at 11 years. In this well-treated cohort, baseline anti-CCP status, DAS28, and MRI bone marrow oedema predicted functional status and/or erosive progression.

Background Few RCTs have investigated long-term (>10 years (yrs)) outcomes of goal-directed synovitis suppression in early rheumatoid arthritis (RA). The CIMESTRA trial was a 2-year double-blinded Danish multicenter study on aggressive treatment with csDMARDS (methotrexate (MTX) versus MTX and cyclosporine) in combination with intra-articular glucocorticoids (1+2). Disease control after 2 yrs was excellent with $≈ $50% in remission and halted radiographic progression in both groups. We present 11 yr follow-up data. Objectives The aims were to 1) investigate the clinical and radiographic status and 2) identify baseline predictors of functional status and erosive progression. Methods Of 160 patients (pts) included, 130 pts also had MRI of the wrist performed at baseline. 17 pts had died since baseline. All living pts were contacted and 120 signed informed consent to participate in a 11 yrs9 follow-up visit assessing e.g. treatment, disease activity (DAS28, CRP, 4 variables), physical function (HAQ), X-ray of hands and feet. Baseline MRI was scored by OMERACT rheumatoid arthritis MRI scoring (RAMRIS) system, X-rays by Sharp-van der Heijde total Sharp Score (TSS). Multivariable linear regression analyses of a panel of baseline variables (see foot note in table) with backward selection were performed with HAQ at 11 yrs (HAQ11) and radiographic progression since baseline (ΔTSS0–11) as dependent variables. Results 120 of 160 pts (75%) completed the 11 yrs visit. 96 pts with available baseline MRI and X-rays of both time points were included in the prediction models. Withdrawal analysis comparing the 160 pts with the 40 and 64 pts who were not included showed similar baseline characteristics except for higher DAS28 and HAQ score for withdrawers. Follow-up was after 11.6 yrs (10.7–12.2) (median (IQR)). Pts were 63 yrs (55–72) and 70% females. 20% received biologics (+/- csDMARD), 53% csDMARD alone, 27% were in drug free remission. DAS28 was 2.0 (1.5–2.6); pain score: 1 cm (0.3–3); pt. global: 1.1 cm (0.2–2.9); swollen joint count (28SJC): 0 (0–0); tender joint count (28TJC): 0 (0–1). 76% of pts were in DAS28 remission; HAQ-score was 0.25 (0–0.75); ΔTSS0–11(median (IQR)):4 (0–13); ΔTSS0–11(mean±SD): 10.9±16.9). The annual progression rate since baseline was median (IQR):0.4 (0–1.1); mean±SD:0.96±1.52. Multivariable linear regression analyses are shown in Table. Conclusions 11 years after diagnosis 75% were in DAS28 remission. HAQ-score was low, and mean radiographic progression was <1 TSS unit/year. High DAS28 and positive anti-CCP at baseline were independent predictors of poorer functional status. Baseline MRI bone marrow edema and anti-CCP positivity were independent predictors of radiographic progression. References Arthritis Rheum 2006; 54: 1401–9. Ann Rheum Dis 2008; 67: 815–22. Disclosure of Interest M. L. Hetland Grant/research support from: AbbVie, BMS, MSD, Pfizer, Orion, Novartis, Biogen, Eli Lilly, K. Stengaard-Petersen: None declared, P. Junker: None declared, H. Lindegaard: None declared, T. Ellingsen: None declared, J. Pødenphant: None declared, H. Skjødt: None declared, A. Vestergaard: None declared, B. Ejbjerg: None declared, S. Jacobsen: None declared, N. S. Krogh: None declared, M. Østergaard Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, K. Hørslev-Petersen: None declared

Background Methotrexate (MTX) is considered the anchor drug in RA, both as monotherapy, as well as for its ability to increase the efficacy of biologic agents when used in combination [1]. Some RA patients have to discontinue DMARD therapy. Thus, it is important to define the optimal biological monotherapy in RA patients. Objectives To review the evidence for short-term efficacy and safety of biologic monotherapy in RA. The aim was to define the optimal biological monotherapy in RA patients without concomitant use of any DMARD therapy. Methods Systematic review and Network Meta-Analysis of RCTs with DMARD inadequate responders (IR) and DMARD naïve RA patients, comparing biologic agents in monotherapy with either placebo (no DMARD) or DMARD, were considered eligible for inclusion. The co-primary outcomes were the number of patients achieving an ACR50 response, and the number discontinuing therapy due to adverse events (AE) [2] preferably after 6 months (3-12 months), respectively. The network meta-analysis was based on mixed-effects logistic regression (GLMM modelled in SAS) [2]; combining statistical inference from both direct and indirect comparisons of the treatment effects between biologics. All dosages applied for all of the nine biologics. Results are reported as odds ratios (OR [95%CI]). For sensitivity, in terms of the included patients, we compared DMARD IR responder trials with DMARD Naïve trials. Results From the literature search 27 individual studies (7,938 patients) were included: abatacept [Aba:1], adalimumab [Ada:5], anakinra [Ana:2], certolizumab [Cer:2], etanercept [Eta:6], golimumab [Gol:3], infliximab [Inf:1], rituximab [Rit:1] and tocilizumab [Toc:6]. The network only included one ‘closed loop’ with biologics head-to-head: ADACTA (Toc vs. Ada) [3]. Benefit (ACR50): Ana was statistically less likely than Ada, Eta, Gol, and Toc, respectively, to have a clinical response (p<0.05). The odds for responding was statistically higher (p<0.05) for Toc compared to Aba (3.9[1.2;12.4]), Ada (2.1[1.2;3.6]), and Inf (7.7[1.8;32.4]), respectively. Finally, Eta was statistically more likely to result in a response than Inf (5.6[1.3;23.9]). Harm (Withdrawal d/t AEs): Gol seemed less likely to cause withdrawal from side effects (p<0.05) compared to Ada (0.4[0.1;0.9]), Ana (0.3[0.1;0.8]), Cer (0.3[0.1;1.0]), Inf (0.2[0.1;1.0]), and Toc (0.4[0.1;0.8]). For sensitivity, the ACR50 estimates were compared with the direct comparison of Ada vs. Toc [3]; the model apparently did not build on incoherence, as data from the ADACTA study reported a comparable effect size (OR=2.3 [1.5; 3.7]). Conclusions All biologics are not equal. In RA patients who need biologic therapy without concomitant use of DMARDs, some biologics are better than others with respect to ACR50 responses. References Smolen J, et al. Ann Rheum Dis. 2010;69(6):964-75. Singh JA, et al. CMAJ. 2009;181(11):787-96. Gabay C, et al. Lancet (Accepted, 2013) Acknowledgements Musculoskeletal Statistics Unit, The Parker Institute receives support via research grants from the Oak Foundation. Disclosure of Interest R. Christensen Grant/research support from: This particular study, including both the protocol and subsequent manuscript, has been supported by a grant from Roche; the grant was provided as an unrestricted grant to Musculoskeletal Statistics Unit, The Parker Institute., Speakers bureau: Abbott, BMS, Pfizer, Roche, MSD, Expanscience, Biogen Idec, Ipsen, Novartis, Bayer, S. Tarp: None Declared, D. Furst: None Declared, M. Østergaard: None Declared, T. Lorenzen: None Declared, M. Hansen: None Declared, J. Singh: None Declared, E. Choy: None Declared, M. Boers: None Declared, M. Suarez-Almazor: None Declared, B. Ejbjerg: None Declared, L. Kristensen: None Declared, H. Bliddal: None Declared

Background Joint space narrowing (JSN), reflecting cartilage damage, is an important aspect of joint damage in rheumatoid arthritis (RA). A scoring system of JSN on magnetic resonance imaging (MRI) has been developed as an OMERACT initiative. However, further validation is needed before the system can be implemented in clinical trials and clinical use. Computed tomography (CT) provides optimal depiction of bone surfaces and is well suited as standard reference for assessment of JSN by MRI and X-ray. Objectives To validate the OMERACT MRI JSN scoring system (1) for RA wrist and MCP joints by investigating its agreement with CT and X-ray, and its intrareader and interreader reliability. Methods MRI and CT images of wrist and MCP2-5 from 14 RA patients and 1 healthy control were assessed independently twice for JSN by three readers. X-rays were scored by a single reader by the Sharp-van der Heijde method. Reliability was assessed by intraclass correlation coefficients (ICC). Images came from a clinical trial and represented a broad range of JSN on X-ray. Results The median (range) JSN score of the assessed hand was on MRI: 13 (0-57), CT: 23 (0-58) and X-ray: 14 (0-29). MRI scores of JSN were very highly correlated with CT scores (MCP: 0.94; wrist: 0.92; MCP+wrist: 0.92). X-ray JSN scores correlated with MRI and CT (MCP2-5: 0.49 and 0.56; wrist: 0.55 and 0.43), see table. On MRI and CT, high intraobserver (ICCs≥0.91 and ≥0.75, respectively) and interobserver (ICCs≥0.82 and ≥0.66, respectively) reliability was observed. In general, lower agreement was found in MCP joints compared to the wrist. Conclusions The OMERACT-RAMRIS MRI JSN scoring system showed very high agreement with CT assessment, whereas X-ray scores were moderately correlated. Both MRI and CT scores showed a high intra- and interreader reliability. The MRI JSN score may, after further validation, become a useful tool in RA clinical trials. References Østergaard M, et al.: Development and preliminary validation of a magnetic resonance imaging joint space narrowing score for use in rheumatoid arthritis: potential adjunct to the OMERACT RA MRI scoring system. J Rheumatol. 2011;38:2045-50. Disclosure of Interest None Declared

Objective: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA).Methods: Patients with early RA (n = 130) were treated with methotrexate, intra-articular betamethasone and ciclosporin/placebo-ciclosporin. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only group, n = 130) or MRI of wrist and metacarpophalangeal (MCP) joints (wrist+MCP group, n = 89) (OMERACT RAMRIS), x-ray examination of hands, wrists and forefeet (Sharp/van der Heijde Score (TSS)), Disease Activity Score (DAS28), anti-cyclic citrullinated peptide antibodies (anti-CCP), HLA-DRB1-shared epitope (SE) and smoking status were assessed. Multiple regression analysis was performed with delta-TSS (0-2 years) as dependent variable and baseline DAS28, TSS, MRI bone oedema score, MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and gender as explanatory variables.Results: Baseline values: median DAS28 5.6 (range 2.4-8.0); anti-CCP positive 61%; radiographic erosions 56%. At 2 years: DAS28 2.0 (0.5-5.7), in DAS remission: 56%, radiographic progression 26% (wrist+MCP group, similar for wrist-only group). MRI bone oedema score was the only independent predictor of delta-TSS (wrist+MCP group: coefficient = 0.75 (95% CI 0.55 to 0.94), p < 0.001; wrist-only group: coefficient = 0.59 (95% CI 0.40 to 0.77), p < 0.001). Bone oedema score explained 41% of the variation in the progression of TSS (wrist+MCP group), 25% in wrist-only group (Pearson's r = 0.64 and r = 0.50, respectively). Results were confirmed by sensitivity analyses.Conclusion: In a randomised controlled trial aiming at remission in patients with early RA, baseline RAMRIS MRI bone oedema score of MCP and wrist joints ( and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet after 2 years. MRI synovitis score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender were not independent risk factors.

This paper presents the wrist joint MR images of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0–3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system—that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0–3 of bone oedema are illustrated, and for bone erosion, grades 0–3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system.

This article updates the work and results of the OMERACT MRI in RA Working Group as presented at the OMERACT 7 meeting in May 2004, focusing on the development of the EULAR-OMERACT rheumatoid arthritis magnetic resonance imaging reference image atlas, and on areas for future research.

Magnetic resonance imaging (MRI) has now been used extensively in cross-sectional and observational studies as well as in controlled clinical trials to assess disease activity and joint damage in rheumatoid arthritis (RA). MRI measurements or scores for erosions, bone edema, and synovitis have been developed and validated by several groups. The OMERACT criteria require that outcome measures demonstrate adequate validity, discriminative power, and feasibility if they are to be useful in clinical trials. Specific performance targets for these criteria depend on the scientific, regulatory, logistical, and financial context of the study in question. We review the extent to which MRI assessments of joint erosion, bone edema, and synovitis fulfil these criteria, particularly as they relate to proof-of-concept RA clinical trials.

This paper outlines the most important pitfalls which are likely to be encountered in the assessment of magnetic resonance images of the wrist and metacarpophalangeal joints in patients with rheumatoid arthritis. Imaging artefacts and how these can be recognised using various sequences and views are discussed. Normal structures such as interosseous ligaments and nutrient foramina may appear prominent on certain images and need to be identified correctly. Pathological change in the rheumatoid hand involves many tissues and when substantial damage has occurred, it may be difficult to identify individual structures correctly. Bone erosion, bone oedema, synovitis, and tenosynovitis frequently occur together and in close proximity to each other, potentially leading to false positive scoring of any of these. Examples are given to illustrate the various dilemmas the user of this atlas may face when scoring the rheumatoid hand and suggestions are made to assist correct interpretation of what can be very complex images.