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 non-progression 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.Trial registration Clinical trials NCT01205854.

ObjectivesTo compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.MethodsAll patients had symptom duration from first swollen joint <2 years and were DMARD naïve with an indication for DMARD treatment. Patients were stratified as seropositive (positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF− and ACPA−), and disease characteristics were compared between groups.ResultsA total of 234 patients were included, and 36 (15.4%) were seronegative. Ultrasonography (US) scores for joints (median 55 vs 25, p<0.001) and tendons (median 3 vs 0, p<0.001), number of swollen joints (median 17 vs 8, p<0.001), disease activity score (DAS; mean 3.9 vs 3.4, p=0.03) and physician global assessment (mean 49.1 vs 38.9, p=0.006) were significantly higher in seronegative patients compared with seropositive. Total van der Heijde-modified Sharp score, Richie Articular Index and patient-reported outcome measures were similar between groups.ConclusionsSeronegative patients had higher levels of inflammation, assessed both clinically and by US, than seropositive patients. These differences may reflect the high number of involved joints required for seronegative patients to fulfil the 2010 ACR/EULAR classification criteria for RA.Trial registration numberNCT01205854; Pre-results.

ObjectivesRecent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria.MethodsDMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF– and ACPA–) and compared disease activity, radiographic progression, treatment response and remission rates across groups.Results230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24  months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment.ConclusionOur findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.

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.

Our findings indicate that the efficacy of intraarticular glucocorticoid injections varies according to ultrasound findings at the time of injection, supporting the use of ultrasound as a tool to select joints that will benefit from intraarticular injections. However, ultrasound needle guidance was not superior to palpation guidance.

ObjectivesFatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up.MethodsData were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression.Results205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months.ConclusionsFatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.

Objective To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. Methods A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS &lt;1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS &lt;1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. Results MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. Conclusion Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. Trial registration number Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.

BackgroundThe development of the 2010 classification criteria for rheumatoid arthritis (RA) has led to a redefinition of the patient population, including classification of seropositive versus seronegative patients. In our recently published study of DMARD naïve early RA patients fulfilling the 2010 ACR/EULAR criteria, we found seronegative patients to have markedly higher disease activity at time of diagnosis, compared to seropositive patients.[1] There is very limited information about the disease course of seronegative patients classified according to the new criteria.ObjectivesOur aim was to examine the disease course of seronegative early RA patients fulfilling the 2010 ACR/EULAR criteria.MethodsIn the treat-to-target ARCTIC trial, DMARD-naive RA patients classified according to the 2010 EULAR/ACR criteria were randomised 1:1 to follow-up with or without ultrasound. Patients in both arms were treated according to the same DMARD escalation strategy. Patients were assessed at 13 visits during two years of follow-up.[2] We stratified the patients as seropositive (rheumatoid factor (RF)+, anti-citrullinated peptide antibody (ACPA)+, or both) or seronegative (RF- and ACPA-). At 24-month follow-up, measures of disease activity were compared across the groups using independent samples t-test, Mann-Whitney U test or chi square test as appropriate.ResultsA total of 230 patients were included, the mean (SD) age was 51.4 (13.7) years and 61.3% were female; 34 patients (14.8%) were seronegative. The mean age (SD) was 55.4 (2.7)/ 50.8 (0.9) years (p=0.07), mean (SD) disease duration was 7.7 (6.8)/7.0 (5.1) months (p=0.46), and 56/62% were females (p=0.48) in the seronegative/seropositive groups. At 24-month follow-up, measures of disease activity were similar between groups (table). There was a tendency towards more radiographic damage in the seronegative patients. Seronegative patients had a significantly greater reduction (0–24 months) in disease activity measures in terms of DAS, number of swollen joints, physician global and ultrasonography scores (table).ConclusionsIn this study of early RA patients, seronegative patients had more inflammatory activity at baseline and a tendency to more radiographic damage, but disease activity after two years of treat-to-target therapy was similar to the seropositive patients. Our findings suggest that seronegative patients classified according to the new criteria respond to modern treatment strategies, with similar rates of patients reaching remission compared to seropositive patients.References Nordberg LB et al. Annals of the rheumatic diseases 2017;76:341–345.Haavardsholm EA et al., BMJ 2016;354:i4205. Disclosure of InterestL. Nordberg: None declared, S. Lillegraven: None declared, A.-B. Aga: None declared, I. Olsen: None declared, E. Lie: None declared, H. Hammer Consultant for: AbbVie, Pfizer, BMS, Roche, UCB, T. Uhlig: None declared, D. van der Heijde: None declared, T. Kvien: None declared, E. Haavardsholm Grant/research support from: Pfizer, MSD, UCB, AbbVie, Roche