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The objective of this study was to compare the efficacy and safety of rituximab in older vs younger patients with rheumatoid arthritis. Data on 367 patients with rheumatoid arthritis treated with rituximab in the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) register were analysed, comparing patients aged ≥ 65 years (n = 91) with patients aged

To assess the 2-year effect on disease activity and health-related quality of life (HRQoL) of implementing a clinical practice treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA).Patients in the Norwegian Very Early Arthritis Cohort 2.0 (NOR-VEAC 2.0), included 2010-2015, were treated according to T2T principles with visits at baseline, 3, 6, 9, 12 months, then every 6 months plus monthly visits until DAS28 2.6. These patients were compared to a pre-T2T cohort of patients included in the Norwegian Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) register 2006-2009. Both groups had a clinical diagnosis of RA (≤1 year) and were DMARD naïve. Disease activity and HRQoL outcomes were analysed, and the primary outcome was SDAI remission (≤3.3) at 2years.The T2T cohort included 293 patients (mean (SD) age 54 (13) years, 66% females, disease duration median (25,75 perc) 98 (57,164) days) and the routine care cohort 392 patients (age 54 (13) years, 68% females, 4 (0,30) days since diagnosis). At 2years, the proportion of patients achieving SDAI remission was 46% in the T2T cohort compared to 31% in the routine care cohort. EQ-5D was similar at baseline, but differed significantly between groups at 2years (median (25,75 perc) 0.77 (0.69, 0.85) vs 0.73 (0.59, 0.80), p 0.001). Methotrexate monotherapy was the dominant DMARD regimen used to achieve SDAI remission in both cohorts.Higher remission rates and better HRQoL were achieved in patients following a T2T strategy in clinical practice compared to routine care.

This randomized trial compares the effects of half-dose conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) vs stable-dose csDMARDs on the risk of flares in patients with rheumatoid arthritis in sustained remission.Importance Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear. Objective To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. Design, Setting, and Participants ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. Interventions Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). Main Outcomes and Measures The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. Results Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred. Conclusions and Relevance Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy.Question In patients with rheumatoid arthritis in remission taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), is reducing the csDMARDs to half dose noninferior to stable csDMARD dosage for the outcome of rheumatoid arthritis flares? Findings In this randomized clinical trial that included 160 patients with rheumatoid arthritis in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs resulted in disease flares in 25% vs 6% over 12 months; this did not meet the noninferiority criterion of a 20% difference. There were significantly fewer patients with flares in the stable-dose group. Meaning These findings do not support the use of half-dose treatment in patients with rheumatoid arthritis in remission taking csDMARDs.

ObjectivesTo investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical inflammation in remission is predictive of future treatment escalation or erosive progression.MethodsIn a 2-year study, 218 patients with disease-modifying antirheumatic drug-naïve early RA were treated by a tight-control treat-to-target strategy corresponding to current recommendations. MRI and ultrasound were performed at regular intervals. Baseline imaging-based inflammation measures were analysed as predictors for early methotrexate failure and erosive progression using univariate and multivariate regression adjusted for clinical, laboratory and radiographic measures. In patients in remission after 1 year, imaging measures were analysed as predictors of treatment escalation and erosive progression during the second year. The added value of imaging in prediction models was assessed using receiver operating characteristic analyses.ResultsBaseline MRI inflammation was associated with MRI erosive progression and ultrasound with radiographic erosive progression. No imaging inflammation measure was associated with early methotrexate failure. Imaging inflammation was present in a majority of patients in clinical remission. Tenosynovitis was associated with treatment escalation, and synovitis and tenosynovitis with MRI/radiographic erosive progression during the second year. Imaging information did not improve prediction models for any of the outcomes.ConclusionsImaging-detected inflammation, both at diagnosis and in remission, is associated with elements of future disease development. However, the lack of a significant effect on prediction models indicates limited value of systematic MRI and ultrasound in management of early RA.

Objective The European guidelines on cardiovascular disease (CVD) prevention advise use of relative risk and risk age algorithms for estimating CVD risk in patients with low estimated absolute risk. Patients with inflammatory joint diseases (IJD) are associated with increased risk of CVD. We aimed to estimate relative risk and risk age across IJD entities and evaluate the agreement between ‘cardiovascular risk age' and ‘vascular age models'. Methods Using cross-sectional data from a nationwide project on CVD risk assessment in IJD, risk age estimations were performed in patients with low/moderate absolute risk of fatal CVD. Risk age was calculated according to the cardiovascular risk age and vascular age model, and risk age estimations were compared using regression analysis and calculating percentage of risk age estimations differing ≥5years. Results Relative risk was increased in 53% and 20% had three times or higher risk compared to individuals with optimal CVD risk factor levels. Furthermore, 20–42% had a risk age ≥5years higher than their actual age, according to the specific risk age model. There were only minor differences between IJD entities regarding relative risk and risk age. Discrepancies ≥5years in estimated risk age were observed in 14–43% of patients. The largest observed difference in calculated risk age was 24years. Conclusion In patients with low estimated absolute risk, estimation of relative CVD risk and risk age may identify additional patients at need of intensive CVD preventive efforts. However, there is a substantial discrepancy between the risk age models.

Background:Remission is the preferred treatment target in rheumatoid arthritis (RA), and many patients require biologic DMARDs to reach this state. It is debated whether tapering of tumor necrosis factor inhibitor (TNFi) treatment to discontinuation should be considered in RA patients who sustain remission on treatment (1).Objectives:The primary study objective was to assess the effect of tapering and withdrawal of TNFi on the risk of flares in RA patients in clinical remission.Methods:In the non-inferiority ARCTIC REWIND trial, RA patients in remission for at least 12 months on stable TNFi therapy were randomly assigned to continued stable TNFi or tapering (half-dose TNFi for 4 months, thereafter withdrawal of TNFi), with visits every four months. csDMARD co-medication was kept stable in both arms. Patients had to be in DAS remission at inclusion with 0/44 swollen joints. The primary endpoint was the proportion of patients with disease flare during the 12-month study period (defined as DAS>1.6, change in DAS>0.6 and 2 or more swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Full-dose TNFi was reinstated in case of flares in the tapering arm. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. The inferiority null-hypothesis was tested in the per-protocol population by mixed effect logistic regression. Radiographs were scored by van der Heijde modified Sharp score (0 and 12 months, average of two readers, progression: ≥1 unit change). ClinicaltrialsNCT01881308.Results:We randomised 99 patients, 92 received the allocated treatment strategy, 84 were included in the per-protocol population. Baseline characteristics, clinical and ultrasound disease activity were balanced (Table). csDMARD co-medication was used by 93% in the stable and 88% in the tapering arm. In the primary analysis, 5% of patients in the stable TNFi arm experienced a flare during 12 months, compared to 63% in the tapering TNFi arm. The risk difference (95% CI) was 58% (42% to 74%, Fig 1), with stable treatment being deemed superior to tapering. 90% in the stable and 81% in the tapering arm did not show progression of radiographic joint damage, difference (95% CI) -9% (-24%, 6%). At 12 months, DAS scores, DAS remission and function were similar between groups (Fig 2). The numbers of adverse events (AE)/serious AE in the stable and tapering arm were 57/2 and 50/3, respectively, with 26 and 15 infections.Conclusion:In a randomised clinical trial assessing patients in prolonged and deep RA remission, we observed a large increase in the flare rate in patients who tapered and discontinued TNFi. Patients responded well to reinstated treatment and remission rates in the two study arms were comparable at 12 months.References:[1]Smolen et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. ARD 2020Table 1.Baseline values – n (%), mean (SD), or median (IQR)Stable, n=45Tapering, n=47Age, yrs57 (11)58 (13)Female30 (67%)25 (53%)ACPA+35 (78%)36 (77%)Symptom duration, yrs10 (7)12 (7)DAS0.9 (0.4)0.8 (0.3)CRP mg/L1 (1 – 2)1 (1 – 3)No ulttrasound power Doppler signal in any of 32 joints42 (96%)44 (94%)Disclosure of Interests:Siri Lillegraven: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga: None declared, Joe Sexton: None declared, Inge Olsen: None declared, Åse Lexberg: None declared, Tor Magne Madland: None declared, Hallvard Fremstad: None declared, Christian A. Høili Consultant of: Novartis, Gunnstein Bakland Consultant of: Novartis, UCB, Cristina Spada: None declared, Hilde Haukeland Consultant of: Novartis, Inger M. Hansen: None declared, Ellen Moholt: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Daniel Solomon Grant/research support from: Funding from Abbvie and Amgen unrelated to this work, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD

ObjectiveThe rheumatoid arthritis impact of disease (RAID) questionnaire comprises seven patient-important domains of disease impact (pain, function, fatigue, sleep disturbance, emotional well-being, physical well-being, coping). RAID was validated as a pooled-weighted score. Its seven individual items separately could provide a valuable tool in clinical practice to guide interventions targeting the patient’s experience of the disease. The aim was to separately assess the psychometric properties of each of the seven numeric rating scale (NRS) of the RAID (RAID.7).Material and methodsPost hoc analyses of data from the cross-sectional RAID study and from the Rainbow study, an open-label 12-week trial of etanercept in patients with RA. Construct validity of each NRS was assessed cross-sectionally in the RAID data set by Spearman’s correlation with the respective external instrument of reference. Using the rainbow data set, we assessed reliability through intraclass correlation coefficient between the screening and the baseline visits and responsiveness (sensitivity to change) by standardised response mean between baseline and 12 weeks.ResultsA total of 671 patients with RA with features of established disease were analysed, 563 and 108 from RAID and Rainbow, respectively. The NRS correlated moderately to strongly with the respective external instrument of reference (r=0.62–0.81). Reliability ranged from 0.64 (0.51–0.74) (pain) to 0.83 (0.76–0.88) (sleep disturbance) and responsiveness from 0.93 (0.73–1.13) (sleep disturbance) to 1.34 (1.01–1.64) (pain).ConclusionThe separate use of the individual NRS of RAID (RAID.7) is valid, feasible, reliable and sensitive to change, representing an opportunity to improve the assessment and treatment of disease impact with minimal questionnaire burden.Trial registration numberNCT00768053.

Background:Sustained remission is the goal of rheumatoid arthritis (RA) care, and more patients reach and maintain this state on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with treat-to-target strategies. The knowledge about whether csDMARDs can be tapered in RA remission is limited.Objectives:The primary objective of the study was to assess the effect of tapering of csDMARDs on the risk of flares in RA patients in sustained clinical remission.Methods:In the open, phase 4, non-inferiority ARCTIC REWIND trial, RA patients in clinical remission for ≥ 12 months on stable csDMARD therapy were randomised to continued stable csDMARD or half dose csDMARD. Patients had to be in DAS remission at inclusion with no swollen joints (of 44). The primary endpoint was the proportion of patients with a disease flare during 12 months (defined as a combination of DAS >1.6, change in DAS >0.6 and ≥2 swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Patients attended visits every 4 months, with extra visits in case of flares. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. Mixed effect logistic regression was used to test the inferiority null-hypothesis in the per-protocol population. Radiographs at 0 and 12 months were scored by van der Heijde Sharp score (average score of two readers, progression: ≥1 unit change/year). Clinicaltrials.govNCT01881308.Results:We enrolled 160 patients, 155 received the allocated treatment strategy. Baseline characteristics were overall well balanced (Table). 78% of patients in the stable csDMARD arm and 84% in the half-dose csDMARD arm used methotrexate monotherapy. In the primary analysis, we observed flares in 6% of patients on stable csDMARD, compared to 25% in the half-dose csDMARD arm, giving a risk difference (95% CI) of 18.3% (7.2% to 29.3%, Fig 1). Non-inferiority could not be claimed, with the results showing superiority of the stable arm over the half-dose arm (Fig 1). Similar results were found in methotrexate monotherapy users. In the stable arm, 2/5 (40%) escalated DMARD medication following the flares, compared to 18/19 (95%) in the tapering arm. No progression of radiographic joint damage was observed in 79.5% of patients on stable DMARDs and 62.7% of those tapering, difference (95% CI) -17.7% (-33.0%, -2.3%, Fig 2E). At 12 months, 92% of patients in the stable and 85% of patients in the tapered arm were in DAS remission (Fig 2C). The frequency of adverse events was 75 in the stable arm and 53 in the tapered arm, with serious adverse events in 2 (2.6%) of patients in the stable and 4 (5.1%, including two serious infections) patients in the tapered arm.Conclusion:In RA patients in sustained remission on csDMARDs, continued csDMARD therapy with stable dosage led to significantly fewer disease activity flares and less frequent radiographic joint damage progression than tapered csDMARD treatment.Table.Baseline values; mean (SD), n (%) or median (IQR)Stable, n=78Tapering, n=78Age, yrs55 (12)56 (12)Female50 (64%)54 (69%)ACPA+57 (73%)63 (81%)Symptom dur., yrs3.7 (1.8)3.4 (1.4)DAS0.8 (0.4)0.8 (0.3)CRP mg/L2 (1, 3)2.0 (1,3)MTX monotherapy61 (78%)65 (84%)Disclosure of Interests:Siri Lillegraven: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga: None declared, Joe Sexton: None declared, Inge Olsen: None declared, Hallvard Fremstad: None declared, Cristina Spada: None declared, Tor Magne Madland: None declared, Christian A. Høili Consultant of: Novartis, Gunnstein Bakland Consultant of: Novartis, UCB, Åse Lexberg: None declared, Inger Johanne Widding Hansen: None declared, Inger M. Hansen: None declared, Hilde Haukeland Consultant of: Novartis, Maud-Kristine A Ljosa: None declared, Ellen Moholt: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Daniel Solomon Grant/research support from: Funding from Abbvie and Amgen unrelated to this work, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD

Patients with inflammatory joint diseases (IJD) have an increased risk of cardiovascular disease (CVD). Our goal was to examine indications for, and use of, lipid-lowering therapy (LLT) and antihypertensive treatment (AntiHT) in patients with IJD. Furthermore, to investigate the frequency of low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) goal attainment among IJD patients.The cohort was derived from the NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR). Indications for AntiHT were: systolic/diastolic BP ≥ 140/90 mm Hg, self-reported hypertension or AntiHT. CVD risk was estimated by the systematic coronary risk evaluation (SCORE) algorithm. LDL-c goals were2.6 mmol/L in case of diabetes, total cholesterol 8 mmol/L or a SCORE estimate ≥ 5%, and1.8 mmol/L for those with established CVD or SCORE ≥ 10%. Comparisons across IJD entities were performed using age and sex adjusted logistic regression.In total, 2277 patients (rheumatoid arthritis: 1376, axial spondyloarthritis: 474, psoriatic arthritis: 427) were included. LLT and AntiHT were indicated in 36.1% and 52.6% of the patients, of whom 37.6% and 47.0% were untreated, respectively. LDL-c and BP targets were obtained in 26.2% and 26.3%, respectively. Guideline recommended treatment and/or corresponding treatment targets were not initiated or obtained in approximately 50%. Rheumatoid arthritis patients were particularly likely to be undertreated with LLT, whereas hypertension undertreatment was most common in psoriatic arthritis.Inadequate CVD prevention encompasses all the three major IJD entities. The unmet need for CVD preventive measures is not only prevalent in RA, but exists across all the major IJD entities.

Objective. To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease-modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population. Methods. Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease-Modifying Antirheumatic Drug [NOR-DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis. Results. A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group. Conclusion. Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed. (Less)

Background Individuals with inflammatory joint diseases (IJD) [rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA)] have increased risk of cardiovascular disease (CVD). In the European guidelines for CVD prevention, calculation of relative risk and risk age is advised in patients with low absolute risk of fatal CVD events the next 10 years estimated by the systematic coronary risk evaluation [SCORE] algorithm; the rational being that low absolute risk may conceal high relative risk and risk ages far beyond chronological age. Thus, more patients needing intensive CVD prevention may be identified. Relative risk is a ratio comparing absolute CVD risk in a specific patient to the risk given optimal CVD risk factor levels (CVDRFs). Risk age denotes the age with similar CVD risk and optimal CVDRFs. To this date, no studies have evaluated relative risk and risk age across IJD entities, neither has the agreement between different risk age models been investigated. Objectives 1) Estimate relative risk and risk age across IJD entities. 2) Investigate agreement between different risk age models. Methods RA/axSpA/PsA patients aged 40≤65 years with low/moderate 10-year risk of fatal CVD were included from a nationwide quality assurance project implementing CVD risk assessment. Relative risk and cardiovascular risk age was calculated in accordance with risk charts published by the European Society of Cardiology (2016) and Cooney et al (2012), respectively. Vascular age was calculated by matching SCORE to estimated risk ages in accordance with Cuende et al (2010). Four different vascular age estimations were calculated, depending on whether the EULAR 1.5 multiplication factor in RA was applied (mSCORE) and if SCORE version with HDL-c (SCORE-HDL-c) was used: SCORE, SCORE-HDL-c, mSCORE and mSCORE-HDL-c. Risk years beyond chronologic age, were calculated. Linear regression models were used to investigate agreement between risk age estimations. Results Relative risk was increased in 53% of all patients and 20% had three times the risk or higher compared to individuals with optimal CVDRF levels. In total, 42% and 20% had a risk age ≥5 years higher than their chronologic age, according to the cardiovascular risk age model and the vascular age model derived from SCORE, respectively. There were minor differences between RA, axSpA and PsA patients in terms of relative risk and risk age. Agreement between cardiovascular risk age and various vascular age models varied (Figure). Discrepancies ≥5 years in estimated risk age were observed in 14–43% of estimations. The largest observed difference in calculated risk age was 24 years. Similarly, linear regression models yielded a R2 of 0.81–0.96. Across all models, median difference between risk age and age increased with advancing relative risk. Moreover, several patients had high relative risk despite a risk age close to their chronologic age. Conclusions Relative risk and risk age may identify several patients at high need of intensive CVD preventive efforts despite low estimated absolute risk. However, there are considerable discrepancies between risk age models. Disclosure of Interest None declared

Background Patients with inflammatory joint diseases (IJD) have increased risk of cardiovascular disease (CVD). Our aim was to compare CVD risk profiles in patients with IJD, including rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) and evaluate the future risk of CVD. Methods The prevalence and numbers of major CVD risk factors (CVD-RFs) (hypertension, elevated cholesterol, obesity, smoking, and diabetes mellitus) were estimated in patients with RA, axSpA and PsA. Relative and absolute risk of CVD according to Systematic Coronary Risk Evaluation (SCORE) was calculated. Results In total, 3791 patients were included. CVD was present in 274 patients (7.2%). Of those without established CVD; hypertension and elevated cholesterol were the most frequent CVD-RFs, occurring in 49.8% and 32.8% of patients. Patients with PsA were more often hypertensive and obese. Overall, 73.6% of patients had a minimum of one CVD-RF, which increased from 53.2% among patients aged 30 to

Published version. Source at http://doi.org/10.1136/rmdopen-2016-000325. License CC BY 4.0. Objective: To develop and validate a responsive and feasible ultrasound inflammation score for rheumatoid arthritis (RA). Methods: We used data from cohorts of early RA (development) and established RA starting/switching biologic therapy (validation). 4 tendons and 36 joints were examined by a grey scale (GSUS) and power Doppler semiquantitative ultrasound (PDUS) scoring system (full score). Ultrasound score components were selected based on factor analyses of 3-month change in the development cohort. Responsiveness was assessed by standardised response means (SRMs). We assessed the proportion of information retained from the full score by linear regression. Results: 118 patients with early and 212 patients with established RA were included. The final ultrasound score included 8 joints (metacarpophalangeal 1–2–3, proximal interphalangeal 2–3, radiocarpal, metatarsophalangeal 2–3) and 1 tendon (extensor carpi ulnaris) examined bilaterally. The 6-month SRMs for the final score were −1.24 (95% CI −1.47 to −1.02) for GSUS, and −1.09 (−1.25 to −0.92) for PDUS in early RA, with 87% of total information retained for GSUS and 90% for PDUS. The new score performed somewhat better than formerly proposed scores in the validation cohort. Conclusions: The Ultrasound in Rheumatoid Arthritis 9 joint/tendon score (USRA9) inflammation score showed good responsiveness, retained most of the information from the original full score and overall performed better than previous scores in a validation cohort.

OBJECTIVES The aim of this study was to assess the overall prevalence of pulmonary hypertension (PH) in an unselected MCTD cohort and review the current knowledge with a systematic database search. METHODS A nationwide multicentre cohort of 147 adult MCTD patients were initially screened for PH by echocardiography, high-resolution computed tomography (HRCT), pulmonary function tests and N-terminal pro-brain natriuretic peptide (NT-proBNP) and then followed up for a mean of 5.6 years. Right-sided heart catheterization was performed when estimated pulmonary artery systolic pressure was >40 mmHg on echocardiography. PH was diagnosed according to the 2009 European Society of Cardiology and European Respiratory Society guidelines. RESULTS At inclusion, 2.0% (3/147) had established PH. Two additional PH patients were identified during follow-up, giving a total PH frequency in the cohort of 3.4% (5/147). All five had elevated serum NT-proBNP. Two had isolated pulmonary arterial hypertension (PAH) and three PH associated with interstitial lung disease (PH-ILD). Three PH patients died during follow-up. Nine other patients in the cohort also died, but none of them had echocardiographic signs of PH prior to death. CONCLUSION The data from the current unselected MCTD cohort suggest that the prevalence of PH is much lower than expected from previous studies but confirm the seriousness of the disease complication.

Published version. Source at http://dx.doi.org/10.1136/bmj.i4205 Objective: To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design: Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting: Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants: 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions: 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures: The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and nonprogression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results: 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions: The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology.

Background Mixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown cause. Objective To assess the prevalence, pattern and severity of interstitial lung disease (ILD) in a cross-sectional study of the nationwide, Norwegian MCTD cohort. Methods 126 patients with MCTD were systematically examined for ILD by high-resolution CT (HRCT), pulmonary function tests (PFT), 6 min walk test (6MWT) and by the New York Heart Association (NYHA) functional classification of dyspnoea. The extent and type of HRCT lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society. Results All 126 patients were Caucasian, 75% women. At the time of the cross-sectional ILD study, the patients had a mean disease duration of 9.0 years. 52% of the patients had abnormal HRCT findings, most commonly reticular patterns consistent with lung fibrosis (35%). Lung fibrosis was quantified as minor in 7%, moderate in 9% and severe in 19% of the patients. Fibrosis was uniformly concentrated in the lower parts of the lungs and was not associated with smoking. Patients with severe lung fibrosis had lower PFT values, shorter 6MWT and a higher mean NYHA functional class. After a mean 4.2 years9 follow-up, overall mortality was 7.9%. Mortality in patients with normal HRCT was 3.3%, as compared with 20.8% in patients with severe lung fibrosis (p Conclusions Severe lung fibrosis is common in MCTD, has an impact on pulmonary function and overall physical capacity and is associated with increased mortality.

Objective.To examine the frequency of 6 definitions for remission and 4 definitions for low disease activity (LDA) after starting a disease-modifying antirheumatic drug (DMARD) in patients with rheumatoid arthritis (RA) in clinical practice, and to study whether predictors for achieving remission after 6 months are similar for these definitions.Methods.Remission and LDA were calculated according to the 28-joint Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), the Routine Assessment of Patient Index Data (RAPID3), and both the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission definitions 3 and 6 months after 4992 DMARD prescriptions for patients enrolled in the NOR-DMARD, a 5-center Norwegian register. Prediction of remission after 6 months was also studied.Results.After 3 months, remission rates varied between definitions from 8.7% to 22.5% and for LDA from 35.5% to 42.7%, and increased slightly until 6 months of followup. DAS28 and RAPID3 gave the highest and ACR/EULAR, SDAI, and CDAI the lowest proportions for remission. Positive predictors for remission after 6 months were similar across the definitions and included lower age, male sex, short disease duration, high level of education, current nonsmoking, nonerosive disease, treatment with a biological DMARD, being DMARD-naive, good physical function, little fatigue, and LDA.Conclusion.In daily clinical practice, the DAS28 and RAPID3 definitions identified remission about twice as often as the ACR/EULAR Boolean, SDAI, and CDAI. Predictors of remission were similar across remission definitions. These findings provide additional evidence to follow treatment recommendations and treat RA early with a DMARD.

ObjectiveThe European League Against Rheumatism recommends implementing cardiovascular disease (CVD) risk assessments for patients with inflammatory joint diseases (IJDs) into clinical practice. Our goal was to design a structured programme for CVD risk assessments to be implemented into routine rheumatology outpatient clinic visits.MethodsThe NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR) started in April 2014 as a quality assurance project including 11 Norwegian rheumatology clinics. CVD risk factors were recorded by adding lipids to routine laboratory tests, self-reporting of CVD risk factors and blood pressure measurements along with the clinical joint examination. The patients’ CVD risks, calculated by the European CVD risk equation SCORE, were evaluated by the rheumatologist. Patients with high or very high CVD risk were referred to their primary care physician for initiation of CVD preventive measures.ResultsData collection (autumn 2015) showed that five of the NOCAR centres had implemented CVD risk assessments. There were 8789 patients eligible for CVD risk evaluation (rheumatoid arthritis (RA), 4483; ankylosing spondylitis (AS), 1663; psoriatic arthritis (PsA), 1928; unspecified and other forms of spondyloarthropathies (SpA), 715) of whom 41.4 % received a CVD risk assessment (RA, 44.7%; AS, 43.4%; PsA, 36.3%; SpA, 30.6%). Considerable differences existed in the proportions of patients receiving CVD risk evaluations across the NOCAR centres.ConclusionPatients with IJD represent a patient group with a high CVD burden that seldom undergoes CVD risk assessments. The NOCAR project lifted the offer of CVD risk evaluation to over 40% in this high-risk patient population.

Objectives To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). Methods Patients were included in one of two cohorts from 2010 to June 2013: disease-modifying antirheumatic drug naive early RA or established RA starting/switching biologics. An extensive US examination was performed by experienced sonographers using a validated grey-scale (GSUS) and power Doppler (PDUS) semiquantitative scoring system with scores 0–3 for both GSUS and PDUS in 36 joints and four tendons. We performed factor analysis in the early RA US data and selected candidate joint/tendon sets based on these results. The proportion of information in the total US scores retained in these candidate sets was assessed by R 2 from linear regression analysis. Finally, the candidate sets and previously proposed joint scores were tested in the established RA cohort, and we also evaluated the sensitivity to change with standardised response means. Results 227 patients with early RA and 212 patients with established RA were included. We identified two candidate sets of joints/tendons: candidate set A consisted of seven joints/two tendons (meatacarpophalangeal 1 (MCP1), MCP2, proximal interphalangeal 3, radiocarpal, elbow, metatarsophalangeal 1 (MTP1), MTP2, tibialis posterior tendon, extensor carpi ulnaris tendon) and set B of nine joints/two tendons (MCP5 and MTP5 added to set A). Unilateral reduced scores retained 78%–85% of the information in total score, while bilateral reduced scores retained 89%–93%, and both sets performed better than previously proposed reduced joint scores, and similar or slightly better regarding sensitivity to change. Conclusions The reduced GSUS and PDUS scores retained most of the information from the total score and performed well in a validation cohort of established RA. Trial registation number NCT01205854, ACTRN12610000284066.

Background The role of co-medication with tumour necrosis factor inhibitors (TNFi) is well established in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis (PsA) there is little evidence available on this issue. Material and methods The analyses were based on data from the Norwegian longitudinal observational study on disease-modifying antirheumatic drugs (NOR-DMARD). Patients with PsA starting their first TNFi, either as monotherapy or with concomitant methotrexate (MTX), were selected. Baseline characteristics, responses after 3, 6 and 12 months, and drug survival were compared between those with and without MTX co-medication. A secondary analysis was performed on patients who had confirmed swollen joints at baseline. Cox regression was used to identify predictors of discontinuation. Results We included 440 patients, 170 receiving TNFi as monotherapy and 270 receiving concomitant MTX. The groups had similar baseline characteristics, except for number of swollen joints, which was higher in the concomitant MTX group. Responses were similar in the two groups in both analyses. Drug survival analyses revealed a borderline significant difference in favour of patients receiving co-medication (p=0.07), and this was most prominent for patients receiving infliximab (IFX) (p=0.01). In the Cox regression analysis lack of concomitant MTX and current smoking were independent predictors of discontinuation of TNFi. Conclusions We found similar responses to TNFi in patients with and without concomitant MTX, but drug survival was superior in patients receiving co-medication. The effect of MTX on drug survival was most prominent in patients receiving IFX. Smoking at baseline and use of TNFi as monotherapy were identified as independent predictors of drug discontinuation.

Background Tumour necrosis factor inhibitors (TNFi) are efficacious in patients with psoriatic arthritis (PsA), but some patients do not respond or do not tolerate their first TNFi, and are switched to a different TNFi. Evidence supporting this practice is limited, and we wanted to investigate the effectiveness of switching to a second TNFi. Material and methods From a longitudinal observational study (LOS) we selected patients with PsA who were starting their first TNFi, and identified patients who had switched to a second TNFi (‘switchers’). Three-month responses and 3-year drug-survival were compared between switchers and non-switchers, and within switchers. Results Switchers (n=95) receiving their second TNFi had significantly poorer responses compared with non-switchers (n=344) (ACR50 response: 22.5% vs 40.0%, DAS28 remission: 28.2% vs 54.1%). There was a trend towards poorer responses to the second TNFi compared with the first TNFi within switchers. Estimated 3-year drug-survival was 36% for the second TNFi compared with 57% for the first TNFi overall. Conclusions 20–40% of patients had a response on a second TNFi after having failed one TNFi in this LOS. This observation highlights the need for treatments with other mechanisms of action than TNF inhibition in patients with PsA.

Background Application of ultrasound (US) in the management of patients with rheumatoid arthritis (RA) is rapidly growing. Objectives The randomized controlled ARCTIC trial (ClinicalTrials.gov NCT01205854) examined if the use of a treatment strategy based on structured US assessment 1 would lead to improved outcomes in RA, compared to a conventional strategy based on clinical and laboratory assessments alone. Methods Newly diagnosed DMARD naive RA patients were randomized 1:1 to A) an ultrasound tight control (UTC) strategy targeting clinical and imaging remission (no ultrasound power-Doppler signal) or B) a conventional tight control (CTC) strategy targeting clinical remission. Patients in both arms were treated according to the same DMARD escalation strategy, starting with MTX, then triple therapy MTX/SSZ/HCQ, then biologic DMARD if target was not reached. The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints and non-progression of radiographic joint damage. Results A total of 238 patients were randomized, and patients with at least one follow-up visit were included in the full analysis set (UTC n=118, CTC n=112). Twenty-six patients (22.0%) in the UTC arm and 21 patients (18.8%) in the CTC arm reached the primary endpoint (mean difference 3.3%; 95%CI -7.1% to 13.7%). No significant differences were found between the groups for the components of the primary outcome, and secondary endpoints were similar (table). Conclusions The implementation and systematic use of ultrasound in the follow-up of early RA patients treated with an aggressive treat-to-target strategy is not justified based on the results of the ARCTIC trial. References Hammer HB et al Ann Rheum Dis 2011 Disclosure of Interest E. Haavardsholm Grant/research support from: Pfizer, MSD, UCB, AbbVie, Roche, A.-B. Aga: None declared, I. Olsen: None declared, S. Lillegraven: None declared, H. Hammer Consultant for: AbbVie, Pfizer, BMS, Roche, UCB, T. Uhlig: None declared, H. Fremstad: None declared, T. Madland: None declared, A. Lexberg: None declared, H. Haukeland Consultant for: UCB, AbbVie, E. Rodevand: None declared, C. Hoili: None declared, H. Stray: None declared, A. Bendvold: None declared, I. Hansen: None declared, G. Bakland Consultant for: AbbVie, Pfizer, L. Nordberg: None declared, D. Heijde: None declared, T. Kvien: None declared

Biological disease-modifying antirheumatic drugs (bDMARD) have constituted a major advance in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). In Norway, access to these therapies has been good since their introduction, with full reimbursement and no requirements of disease activity measures above certain cut-offs. With increasing focus on early and aggressive therapy, one could expect increasing prescription of bDMARDs, including use in patients with moderate disease activity. Our objectives were to examine if prescription rates of bDMARDs in RA, PsA and axSpA continue to increase or have reached a plateau, and whether disease activity at initiation of therapy has changed over the years. Data for these analyses were provided by the NOR-DMARD register, which was established by three Norwegian rheumatology departments in 2000, with two more centres joining in 2002. The register has aimed for longitudinal follow-up of all patients with inflammatory joint diseases starting a new DMARD regimen.1 For the current analyses we included all prescriptions of bDMARDs in previously bDMARD-naive patients with …

Background Clinical remission (REM) is the treatment target in rheumatoid arthritis (RA), and there are several composite REM criteria available. Knowledge is limited on how disease duration affects REM in daily clinical practice, and whether predictors of REM depend on the method for assessment of REM. Objectives To study the rates of REM after 3 and 6 months with DMARD treatment applying different criteria, and to study predictors of REM after 6 months. Methods Data from 4992 patients in the NOR-DMARD study, representing real life rheumatology practice, were analysed. All patients started with a synthetic or biological DMARD and had 6-month follow-up data available,. Mean (SD) age was 54.6 (14.9) yrs, disease duration was 8.5 (7.9) yrs, 73.2% females. Disease duration (mean 7.9 [9.6] yrs) was grouped into: 0.5-1 yr (n=321), >1-5 yrs (n=992), >5-10 yrs (n=750), and >10 yrs (n=1532). The applied definitions for clinical REM were Disease Activity Score28 (DAS28)

Background Anti-citrullinated protein antibody (ACPA) reactivities precede clinical onset of rheumatoid arthritis (RA), and it has been suggested that ACPA reactivities towards distinct target proteins may be associated with differences in RA phenotypes. We aimed to assess the prevalence of baseline ACPA reactivities in an inception cohort of patients with early RA, and to investigate their associations with disease activity, treatment response, ultrasound findings and radiographic damage. Methods Disease-modifying antirheumatic drug (DMARD)-naïve patients with early RA, classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, were included in the ARCTIC trial and assessed in the present analysis. During follow up, patients were monitored frequently and treatment was adjusted according to a predetermined protocol, starting with methotrexate monotherapy with prednisolone bridging. Analysis of 16 different ACPA reactivities targeting citrullinated peptides from fibrinogen, alpha-1 enolase, vimentin, filaggrin and histone was performed using a multiplex chip-based assay. Samples from 0, 3, 12 and 24 months were analysed. Controls were blood donors with similar characteristics to the patients (age, gender, smoking status). Results A total of 217 patients and 94 controls were included. Median [25, 75 percentile] number of ACPA reactivities in all patients was 9 [4, 12], and were most prevalent in anti-cyclic citrullinated peptide /rheumatoid factor-positive patients 10 [7, 12]. Disease activity measures and ultrasound scores at baseline were lower in ACPA reactivity-positive compared to ACPA reactivity-negative patients. ACPA reactivity levels decreased after 3 months of DMARD treatment, most pronounced for fibrinogenβ 60–74 to 62% of baseline antibody level, with least change in filaggrin 307–324 to 81% of baseline antibody level, both p