Joint Distribution and Two-Year Outcome in 347 Patients With Monoarthritis of Less Than Sixteen Weeks' Duration.

OBJECTIVE: The present study was undertaken to investigate the joint distribution and 2-year outcome of patients with recent-onset monoarthritis. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Treat to target strategy in early rheumatoid arthritis versus routine care - A comparative clinical practice study.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Higher remission rates and better HRQoL were achieved in patients following a T2T strategy in clinical practice compared to routine care.

Role of erosions typical of rheumatoid arthritis in the 2010 ACR/EULAR rheumatoid arthritis classification criteria: results from a very early arthritis cohort.

OBJECTIVE: To determine how the European League Against Rheumatism (EULAR) definition of erosive disease (erosion criterion) contributes to the number of patients classified as rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/EULAR RA classification criteria (2010 RA criteria) in an early arthritis cohort. METHODS: Patients from the observational study Norwegian Very Early Arthritis Clinic with joint swelling ≤16 weeks, a clinical diagnosis of RA or undifferentiated arthritis, and radiographs of hands and feet were included. Erosive disease was defined according to the EULAR definition accompanying the 2010 RA criteria. We calculated the additional number of patients being classified as RA based on the erosion criteria at baseline and during follow-up. RESULTS: Of the 289 included patients, 120 (41.5%) fulfilled the 2010 RA criteria, whereas 15 (5.2%) fulfilled only the erosion criterion at baseline. 118 patients had radiographic follow-up at 2 years, of whom 6.8% fulfilled the 2010 RA criteria and only one patient fulfilled solely the erosion criterion during follow-up. CONCLUSION: Few patients with early arthritis were classified as RA based on solely the erosion criteria, and of those who did almost all did so at baseline.

Disease Characteristics and Rheumatoid Arthritis Development in Patients with Early Undifferentiated Arthritis: A 2-year Followup Study.

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.

Diagnostic spectrum and 2-year outcome in a cohort of patients with very early arthritis.

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<0.001). Baseline joint pain and fatigue were similar across diagnoses. CONCLUSIONS: Among 1017 patients with IA of ≤16 weeks' duration, UA was the most common diagnosis after 2 years, and less than one-fourth were diagnosed with RA. Arthritis resolved without DMARDs in the majority of the patients. All clinical parameters improved significantly over a 2-year course.

Self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a very early arthritis cohort.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%, p < 0.001), duration of joint swelling (median = 47.5 vs. 66.0 days, p = 0.002), 2010 RA criteria points (median = 6.0 vs. 7.0, p < 0.001), 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 (p < 0.001), and 32.5% when duration of joint swelling was <4 weeks vs. 10.6% with longer duration (p < 0.001). CONCLUSIONS: 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.

Thermal inactivation of infectious pancreatic necrosis virus in a peptone-salt medium mimicking the water-soluble phase of hydrolyzed fish by-products.

Infectious pancreatic necrosis virus (IPNV) (serotype Sp) was exposed to temperatures between 60 and 90°C in a medium mimicking the water-soluble phase of hydrolyzed fish by-products. D values ranged from 290 to 0.5 min, and the z value was approximately 9.8°C. Addition of formic acid to create a pH 4 medium did not enhance heat inactivation. Predicted inactivation effects at different temperature-time combinations are provided.

Should anti-citrullinated protein antibody and rheumatoid factor status be reassessed during the first year of followup in recent-onset arthritis? A longitudinal study.

OBJECTIVE: Presence and levels of antibodies contribute to the classification of rheumatoid arthritis. We investigated the longitudinal course of anti-citrullinated protein antibodies (ACPA) and immunoglobin M (IgM) rheumatoid factor (RF) during the first year after arthritis onset in patients with very short disease duration. METHODS: Patients (aged 18-75 years) with ≥ 1 swollen joint of ≤ 16 weeks' duration had assessments of ACPA (2nd generation anti-cyclic citrullinated peptide antibodies, anti-CCP2) and IgM RF at inclusion and after 3, 6, and 12 months. Frequencies of seroconversions (negative to positive and vice versa) and changes in antibody levels during followup were determined. RESULTS: A total of 281 early arthritis patients (median duration of joint swelling 32 days, 14.2% ACPA positives, 12.8% IgM RF positives) with 978 longitudinally collected serum samples were included. Only 5 patients (1.8%) negative for both antibodies at baseline turned antibody-positive during followup, while 9 antibody-positive patients (3.2%) turned antibody-negative. ACPA was more stable than RF regarding both status and levels. CONCLUSION: Antibody status (ACPA/RF) is a stable phenotype in very early arthritis, as seroconversion was only found in 5% of patients. Repeated measurement of ACPA or RF during the first year after onset of arthritis does not offer major additional information.

The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a longitudinal study of 376 patients with very early undifferentiated arthritis.

INTRODUCTION: We wanted to assess the importance of the levels of anti-citrullinated peptide antibody (anti-CCP) and immunoglobulin M (IgM) rheumatoid factor (RF) in predicting development of persistent arthritis from undifferentiated arthritis (UA), and to investigate whether there is an added predictive value for persistent arthritis in testing for both anti-CCP and IgM RF. METHODS: Patients with UA (exclusion of definite non-rheumatoid arthritis (RA) diagnoses) included in the Norwegian very early arthritis clinic were assessed for development of persistent arthritic disease. The effect of antibody level on the likelihood of persistent arthritis was investigated, and the sensitivity and specificity for persistent arthritis for anti-CCP and IgM RF, separately and combined, was determined. RESULTS: A total of 376 UA patients were included (median arthritis duration 32 days). 59 (15.7%) patients were IgM RF positive, and 62 (16.5%) anti-CCP positive. One hundred, seventy-four (46.3%) had persistent disease after one year. Overlap of anti-CCP and IgM RF positivity was 58%. Sensitivity/specificity for persistent arthritis was 28/95% for IgM RF alone, 30/95% for anti-CCP alone, and 37/92% for positivity of both anti-CCP and IgM RF. The likelihood for persistent disease increased with increasing levels of both anti-CCP and IgM RF. CONCLUSIONS: The likelihood of developing persistent arthritis in UA patients increases with the level of anti-CCP and IgM RF. Testing both anti-CCP and IgM RF has added predictive value in UA patients. This study suggests that antibody level should be taken into account when making risk assessments in patients with UA.

Positive anti-citrullinated protein antibody status and small joint arthritis are consistent predictors of chronic disease in patients with very early arthritis: results from the NOR-VEAC cohort.

INTRODUCTION: The current 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) have proven less useful in early arthritis. The objective of this study was to identify and compare predictors of three relevant outcomes of chronic arthritis in a cohort of very early arthritis patients. METHODS: The Norwegian Very Early Arthritis Cohort (NOR-VEAC) includes adult patients with at least one swollen joint of < or = 16 weeks' duration. Patients are followed for 2 years with comprehensive clinical and laboratory examinations. Logistic regression analyses were performed to determine independent predictors of three outcomes: persistent synovitis, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and established clinical RA diagnosis within one year. RESULTS: Of 384 patients eligible for one year follow-up (56.3% females, mean (SD) age 45.8 (14.7) years, median (IQR) duration of arthritis 31 (10-62) days), 14.4% were anti-CCP2 positive, and 11.2% were IgM RF positive. 98 patients (25.5%) had persistent synovitis, 106 (27.6%) had received DMARD treatment during follow-up, while 68 (17.7%) were diagnosed with RA. Consistent independent predictors across all three outcomes were positive anti-citrullinated protein antibody (ACPA) status (odds ratio (OR) 3.2, 5.6 and 19.3), respectively, and small joint arthritis (proximal interphalangeal joint (PIP), metacarpo-phalangeal joint (MCP), and/or metatarso-phalangeal joint (MTP) joint swelling) (OR 1.9, 3.5, and 3.5, respectively). CONCLUSIONS: Positive ACPA status and small joint arthritis were consistent predictors of three relevant outcomes of chronic arthritis in very early arthritis patients. This consistency supports DMARD prescription as a valid surrogate endpoint for chronic arthritis. Importantly, this surrogate is used in ongoing efforts to develop new diagnostic criteria for early RA.

Pattern of joint involvement and other disease characteristics in 634 patients with arthritis of less than 16 weeks' duration.

OBJECTIVE: To investigate the distribution of joint involvement in a cohort of patients with very recent onset arthritis and describe the disease characteristics in these patients. METHODS: A very early arthritis clinic (NOR-VEAC) was established as a multicenter study. General practitioners were asked to refer patients presenting with at least 1 swollen joint of maximum 16 weeks' duration. Clinical and laboratory markers were examined. RESULTS: We included 634 patients during the first 3 years, with mean (25th-75th percentile) arthritis duration of 30 (11-63) days. Monoarthritis was present in 243 (38.3%) patients, 216 (34.1%) had oligoarthritis, and 175 (27.6%) polyarthritis. Patients with polyarthritis were older, had longer duration of arthritis, and were more frequently anti-cyclic citrullinated peptide antibody and rheumatoid factor-positive. Patients in all 3 joint pattern groups (mono-/oligo-/polyarthritis) reported substantial effect on physical function, pain, and fatigue and had elevated levels of acute-phase reactants. Knee or ankle arthritis was most frequent in patients with mono- and oligoarthritis, whereas small joint involvement was most frequent in patients with polyarthritis. CONCLUSION: Patients with recent-onset arthritis report a substantial influence on health status. Mono- and oligoarthritis are at least as frequent as polyarthritis. Polyarthritic patients more frequently exhibit features associated with a worse outcome.

Molecular analyses of Salmonella enterica isolates from fish feed factories and fish feed ingredients.

Isolates of the most commonly observed salmonella serovars in Norwegian fish feed factories from 1998 to 2000 (Salmonella enterica serovar Agona, S. enterica serovar Montevideo, S. enterica serovar Senftenberg, and S. enterica serovar Kentucky) were studied by pulsed-field gel electrophoresis (PFGE) and plasmid profile analysis and compared to isolates of the same serovars from fish feed ingredients, humans, and other sources (a total of 112 isolates). Within each serovar, a variety of distinct PFGE types (with similarity levels less than 90%) were observed in the feed ingredients and other sources, while only two distinct types of each serovar were identified in the factories. The combined results of PFGE and plasmid analyses showed that each factory harbored only a few S. enterica clones. Some of these clones persisted for at least 3 years in the factories, indicating that there was long-lasting contamination probably due to inadequate decontamination procedures.