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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.

Rheumatoid arthritis (RA) is a complex disease with a wide range of underlying susceptibility factors. Recently, dysregulation of microRNAs (miRNAs) in RA have been reported in several immune cell types from blood. However, B cells have not been studied in detail yet. Given the autoimmune nature of RA with the presence of autoantibodies, CD19+ B cells are a key cell type in RA pathogenesis and alterations in CD19+ B cell subpopulations have been observed in patient blood. Therefore, we aimed to reveal the global miRNA repertoire and to analyze miRNA expression profile differences in homogenous RA patient phenotypes in blood-derived CD19+ B cells. Small RNA sequencing was performed on CD19+ B cells of newly diagnosed untreated RA patients (n=10), successfully methotrexate (MTX) treated RA patients in remission (MTX treated RA patients, n=18) and healthy controls (n=9). The majority of miRNAs was detected across all phenotypes. However, significant expression differences between MTX treated RA patients and controls were observed for 27 miRNAs, while no significant differences were seen between the newly diagnosed patients and controls. Several of the differentially expressed miRNAs were previously found to be dysregulated in RA including miR-223-3p, miR-486-3p and miR-23a-3p. MiRNA target enrichment analysis, using the differentially expressed miRNAs and miRNA-target interactions from miRTarBase as input, revealed enriched target genes known to play important roles in B cell activation, differentiation and B cell receptor signaling, such as STAT3, PRDM1 and PTEN. Interestingly, many of those genes showed a high degree of correlated expression in CD19+ B cells in contrast to other immune cell types. Our results suggest important regulatory functions of miRNAs in blood-derived CD19+ B cells of MTX treated RA patients and motivate for future studies investigating the interactive mechanisms between miRNA and gene targets, as well as the possible predictive power of miRNAs for RA treatment response.

The aim of the study was to assess RF cross-reactivity to animal antibodies used in immunoassays, and to test if selected commercial immunoassays are vulnerable to interference from RF, causing false test results. Our study included samples from patients with RF-positive rheumatoid arthritis (RA) and controls (patients with RF-negative RA and psoriatic arthritis), included in an early arthritis-cohort. Reactivity to mouse IgG1, mouse IgG2a, rabbit IgG, bovine IgG, sheep/goat IgG and human IgG was analysed using in-house interference assays. RF-positive sera with strong reactivity to mouse IgG1 were analysed in three commercial immunoassays. To reveal interference, results before and after addition of blocking aggregated murine IgG1 were compared. Samples from 124 RF-positive RA patients and 66 controls were tested. We found considerably stronger reactivity toward animal antibodies, particularly mouse IgG1 (73% vs. 12%) and rabbit IgG (81% vs. 6%), in sera from RF-positive RA-patients compared to controls (p

Objective.To examine the 2-year disease course in patients with undifferentiated arthritis (UA) focusing on fulfillment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria.Methods.Data were provided by the Norwegian Very Early Arthritis Clinic study, which included patients presenting with ≥ 1 swollen joint of ≤ 16 weeks’ duration. UA was defined as patients not fulfilling the 2010 ACR/EULAR RA criteria and who did not have a clinical diagnosis other than RA at baseline. The main outcome was fulfillment of the 2010 RA criteria. Secondary outcomes were disease-modifying antirheumatic drug (DMARD) use, resolution of synovitis without use of DMARD during followup, and final clinical diagnosis.Results.We included 477 patients with UA of whom 47 fulfilled the 2010 ACR/EULAR RA criteria during followup (UA-RA) and 430 did not (UA–non-RA). Of the UA-RA patients, 70% fulfilled the criteria within the first 6 months. UA-RA patients were older, more often positive for rheumatoid factor and anticitrullinated protein antibodies, female, and ever smokers, and they more often presented with polyarticular arthritis, small joint involvement, and a swollen shoulder joint. During followup, 53% of UA-RA patients vs 13% of UA-non-RA patients used DMARD (p < 0.001). Overall, 71% of patients with UA achieved absence of clinical synovitis at final followup without use of DMARD. The most frequent final clinical diagnosis was UA (61%).Conclusion.Only 9.8% of patients with UA fulfilled the 2010 RA criteria during 2-year followup. Small joint involvement and swollen shoulder joint were among the factors associated with RA development. In two-thirds of patients with UA, the arthritis resolved without use of DMARD.

To study occurrence of and factors associated with self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) (2010 RA criteria) in patients with ≤16 weeks׳ duration of joint swelling.We applied the 2010 RA criteria in 1118 patients included in a 2-year longitudinal cohort. In all, 256 patients fulfilled the 2010 RA criteria at baseline; outcome was defined as either "self-limiting arthritis" (no DMARD use during follow-up, no swollen joints at last assessment, and no final clinical diagnosis of RA) or "persistent disease." The associations between baseline characteristics, including the components of the 2010 RA criteria score, and outcomes were studied.In total, 36 of 256 patients (14.1%) classified as having RA had self-limiting arthritis. These patients differed from patients with persistent disease according to ACPA positivity (11.1% vs. 65.0%, p0.001), duration of joint swelling (median = 47.5 vs. 66.0 days, p = 0.002), 2010 RA criteria points (median = 6.0 vs. 7.0, p0.001), and ever smoking (52.8% vs. 74.5%, p = 0.01). Having no serology points and no duration points were independent predictors of self-limiting arthritis. The rate of self-limiting arthritis was 2.7% vs. 29.4% among ACPA positive vs. ACPA negative patients (p0.001), and 32.5% when duration of joint swelling was4 weeks vs. 10.6% with longer duration (p0.001).Negative ACPA status, short duration of joint swelling and being a never smoker were factors associated with self-limiting arthritis in early arthritis patients classified as having RA at presentation. Our findings contribute to identify patients who potentially do not need DMARDs and who should not be included in early RA clinical drug trials.

Objectives To describe the diagnostic spectrum, arthritis persistency and clinical outcomes after 2 years in patients with inflammatory arthritis (IA) of less than 16 weeks’ duration. Methods Data from the Norwegian Very Early Arthritis Clinic, a 2-year longitudinal observational study of adults with IA of ≤16 weeks’ duration, were used. Exclusion criteria were arthritis due to crystal deposits, trauma, osteoarthritis and septic arthritis. In all patients who had any follow-up information (population A), clinical diagnoses and persistency of arthritis were described. For patients with 2-year follow-up (population B), we also studied other clinical outcomes (disease activity, pain, fatigue, functional disability and health-related quality of life). Results In population A (n=1017) median (25th–75th percentile) duration of joint swelling was 35.0 (13.0–66.5) days, mean (SD) age 45.7 (14.8) years, 55.2% were females and 17.8% anticitrullinated protein antibodies positive. The most common final diagnoses were undifferentiated arthritis (UA) (41.7%), rheumatoid arthritis (RA) (24.1%) and reactive arthritis (18.1%). After 2 years, the arthritis had resolved in 59% of the patients. The remaining 41.0% had persistent disease defined by disease modifying antirheumatic drug (DMARD) use (32.1%) or persistent joint swelling without DMARD use (8.9%). In population B (n=669), all clinical outcomes improved significantly (P

The present study was undertaken to investigate the joint distribution and 2-year outcome of patients with recent-onset monoarthritis.Adult patients with clinically apparent monoarthritis of ≤16 weeks' duration were included in a multicenter 2-year longitudinal study. Clinical characteristics, joint distribution, development of chronic inflammatory rheumatic disease (CIRD), as well as classification criteria according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria for RA were studied. Predictors for development of CIRD were analyzed by multivariable logistic regression analyses.The knee (49.3%), ankle (16.7%), and wrist (14.1%) were the most frequently affected joints among the 347 included patients. A total of 91 patients (26.2%) developed CIRD during follow-up; 21 (6.1%) were diagnosed with RA, and 16 (4.6%) with psoriatic arthritis. Longer duration of joint swelling, joint localization, and anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) positivity were independent predictors of CIRD. Six of 58 patients (10.3%) with ankle monoarthritis and 21 of 49 patients (42.9%) with wrist monoarthritis developed CIRD during follow-up. The 2010 ACR/EULAR Criteria for RA identified all patients diagnosed with seropositive RA at an early stage, mostly within 3 months.Approximately one-fourth of patients with recent-onset monoarthritis developed CIRD over 2 years. Patients presenting with ankle arthritis rarely developed CIRD, whereas patients presenting with wrist arthritis more frequently did so. Longer duration of joint swelling and ACPA and RF positivity were also predictive of CIRD. Our findings facilitate the early identification of patients with monoarthritis who have an unfavorable prognosis.

Background The treat to target (T2T) strategy has provided good results in clinical trials and is part of current management recommendations, but real life data are still needed to support the implementation of T2T in clinical practice. Objectives To investigate 2-year outcomes (DAS28 and EQ-5D) in early RA before and after implementation of the T2T monitoring and treatment strategy. Methods Pts in the Norwegian Very Early Arthritis Cohort (NOR-VEAC) were included from 2010 through 2015 and treated according to T2T with visits at baseline, 3, 6, 9, 12 months and then every 6 months plus monthly visits until DAS28 Results The current analyses included 252 pts from NOR-VEAC (mean (SD) age 54 (14) yrs, 65% females, 73% seropos, duration of joint swelling median (25,75 perc) 97 (57,168) days) and 586 pts from NOR-DMARD (mean (SD) age 55 (13) yrs, 67% females, 74% seropos, median (25,75 perc) 4 (0,67) days since diagnosis). 2-yr follow-up data were available in 56%/67% of pts in NOR-VEAC/NOR-DMARD. Methotrexate monotherapy was the dominant initial DMARD treatment in both groups (93% in NOR-VEAC vs 87% in NOR-DMARD). Proportions of pts achieving remission (DAS28 Conclusions Pts treated according to the T2T strategy achieved lower DAS28 scores and higher (better) EQ-5D scores during follow-up despite similar baseline values. The differences in DMARD use between cohorts were relatively small, however there is a trend towards more use of biologic DMARD in the T2T cohort. Disclosure of Interest G. H. Brinkmann: None declared, E. Norli: None declared, T. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz, UCB, Speakers bureau: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz,UCB, A. Haugen: None declared, L. Grovle: None declared, H. Nygaard: None declared, D. Soldal: None declared, A. Wierod: None declared, H. Gulseth: None declared, M. Mjaavatten: None declared, E. Lie Consultant for: AbbVie, Bristol-Myers Squibb, Hospira, Pfizer, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb

Background Undifferentiated arthritis (UA) is defined as cases of inflammatory arthritis where no definitive diagnosis can be made, and that may evolve into a chronic inflammatory disease over time or result in persistent drug-free remission. Objectives In this study we investigated the 2-year disease course in patients with poly-, oligo- and monoarticular UA, with the main outcomes being 1) fulfillment of the 2010 ACR/EULAR RA classification criteria, 2) absence of clinical synovitis without use of DMARDs and 3) final clinical diagnosis. Methods Patients (18-75 years old) with ≥1 swollen joint of Results Among the 495 patients who were denoted UA, 60 (12.1%) patients had polyarthritis (PA), 179 (36.2%) oligoarthritis (OLA) and 256 (51.7%) monoarthritis (MA) at baseline. Mean (SD) age was 46.6 (14.6) yrs, 54.1% were females and median (25, 75 perc.) duration of joint swelling was 29 (10, 62) days. Only 34 (6.9%) of the 495 UA patients were classified as RA during follow-up, including 8.9% of those presenting as OLA and 13.3% of those presenting as PA. Conversely, among patients later classified as RA, 47.1% were OLA patients and 23.5% PA patients at inclusion. 50.0% of the OLA patients who later fulfilled the RA criteria were seropositive, while none of the PA patients were. The most frequently affected joints in the OLA patients fulfilling the RA criteria were PIP (31.3%), MCP (25.0%), knees (31.3%) and wrists (31.3%). Only 86 of 495 patients used DMARDs during follow-up (38.3% of all PA patients, 20.1% OA patients and 10.4% of MA patients). 41.7%, 63.8% and 76.6% of those presenting as PA, OLA and MA, respectively, achieved absence of clinical synovitis at final follow-up visit without use of DMARDs. The most frequent final clinical diagnosis in PA, OLA and MA patients was UA (40.0%, 50.1% and 68.3%, respectively). Figure 1 shows the distribution of clinical diagnoses at last visit. Conclusions Less than 1/5 of all the UA patients started DMARDs, and only 6.9% of the UA patients were classified as RA during follow-up, including 9% of those presenting as OLA and 13% of those presenting as PA. Nearly half of patients later classified as RA were patients with OLA at inclusion, however, 64% of OLA cases resolved without ever using DMARDs. The proportion with a final clinical diagnosis of UA was high irrespective of poly-, oligo- or monoarticular presentation. Disclosure of Interest None declared

Background The 2010 ACR/EULAR classification criteria for rheumatoid arthritis (2010 RA criteria) have made it possible to classify RA earlier. The criteria yield a score from 0-10 points, with the cut-off for definite RA set at ≥6 points. In general, diagnostic certainty increases with an increasing number of criteria points, and some patients with only 6 points may not have RA, but rather a self-limiting condition. Objectives To study the 2-year outcome of patients with arthritis of less than 16 weeks duration fulfilling the 2010 RA criteria at study inclusion, according to the number of criteria points. Methods 1118 patients (pts) (age 18-75 yrs) with inflammatory arthritis of ≤16 weeks duration were included in the NOR-VEAC (Norwegian Very Early Arthritis Clinic) study from 2004 to 2010, i.e. before the 2010 RA criteria were implemented. The 2010 RA criteria were retrospectively applied. We defined two outcome groups: Pts prescribed with DMARDs and pts who had one or more swollen joints or a clinical diagnosis of RA at last visit were defined as “persistent disease”, whereas pts with no DMARD use ever and no swollen joints at last visit were defined as “resolving arthritis”. Independent samples t-tests, Mann-Whitney-Wilcoxon tests or chi-square tests were used to compare outcome groups, as appropriate. Results 261 of 1118 pts (21.6%) fulfilled the 2010 RA criteria at baseline. 254 of these had follow-up data, and were included in the current study. Duration of joint swelling [median (25-75 perc.)] was 63 (39-83) days, mean (SD) age 53 (14) yrs, 64% were females, 58% anti-CCP positive, and 70% anti-CCP and/or RF positive. 70 pts (27.6%) had 6 criteria points at baseline. The corresponding numbers for 7, 8, 9 and 10 points were 73 (28.7%), 43 (16.9%), 20 (7.9%) and 48 (18.9%). As expected, the majority (87.0%) of the pts fulfilling the 2010 RA criteria at baseline developed persistent disease. Nevertheless, in the group with only six criteria points, the arthritis resolved without DMARDs in 24.3% of the pts. Fewer pts with >6 points had resolving arthritis – 15.1%, 9.3%, 5.0% and 0.0% among pts with 7, 8, 9 and 10 points, respectively. Pts with resolving arthritis thus had significantly fewer criteria points than pts with persistent disease (median 6 vs 7, p=0.002) as well as lower frequency of anti-CCP positivity (12.1 vs 64.7%, p Conclusions The majority of the pts with arthritis of less than 16 weeks duration fulfilling the 2010 RA criteria at baseline had persistent disease, including all pts with 10 criteria points, but in a quarter of pts with only 6 criteria points the arthritis resolved without DMARDs. These results underline the importance of clinical judgment when making the diagnosis of RA, especially in early disease. If DMARD treatment is started in a patient with short disease duration and a somewhat uncertain RA diagnosis, a trial of DMARD discontinuation after a certain period of time should be considered to avoid overtreatment. Disclosure of Interest None declared