Halvor Nygaard

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.

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

IntroductionWe 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.MethodsPatients 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.ResultsA 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.ConclusionsThe 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.

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.

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.

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.

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.

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.

Joint distribution and 2-year outcome in 347 patients with monoarthritis of less than 16 weeks’ duration

The present study was undertaken to investigate the joint distribution and 2‐year outcome of patients with recent‐onset monoarthritis.

SAT0055 Two-Year Outcome in 495 Patients with Undifferentiated Arthritis of Very Short Duration

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 <16 weeks duration were included in the multi-center observational study NOR-VEAC (Norwegian Very Early Arthritis Cohort) and followed for 2 years. Patients with arthritis due to trauma, septic arthritis, crystal arthritis and osteoarthritis were excluded. The study included 1118 patients in total. Patients with a clinical diagnosis of a rheumatic disease other than RA (N=338) or fulfilling the 2010 ACR/EULAR RA criteria (N=261) at baseline and those without follow-up data (N=24) were excluded from the current analyses. Absence of clinical synovitis was defined as no swollen joints at last visit. 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

SAT0069 Rate of Remission Without Dmards in 254 Patients with Very Early Rheumatoid Arthritis According to the Number of 2010 ACR/EULAR Classification Criteria Points: Results from a 2-Year Longitudinal Study

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<0.0005), shorter duration of joint swelling (median 47 vs 65 days, p=0.001), less joint pain (mean 46.3 vs 56.6 mm, p=0.013) and lower proportion of ever smokers (51.5 vs 73.8%, p=0.014). 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