Maria K. Söderlin

Annual incidence of inflammatory joint diseases in a population based study in southern Sweden

Objective: To estimate the annual incidence of inflammatory joint diseases in a population based prospective referral study in an adult population in Kronoberg County in southern Sweden. Methods: The patients were referred from primary healthcare centres to the rheumatology department in Växjö Central Hospital or to the one private rheumatologist in Växjö participating in the study. Additionally, the hospital records for patients with joint aspirates during the inclusion period were checked. The patients were registered as incident cases if the onset of the joint inflammation was between 1 May 1999 and 1 May 2000. A systematic follow up of incoming referrals was conducted up to 31 January 2001. Children under the age of 16 and patients with septic arthritis, crystal arthropathies, and osteoarthritis were excluded from the study. Results: A total of 151 new cases with inflammatory joint diseases were identified during one year, corresponding to a total annual incidence of 115/100 000. Of these, 31 patients (21%) had rheumatoid arthritis, the annual incidence being 24/100 000 (for women 29/100 000, and for men 18/100 000). Reactive arthritis was diagnosed in 37 patients (24%, annual incidence 28/100 000) and 54 patients had undifferentiated arthritis (36%, annual incidence 41/100 000). Eleven patients presented with psoriatic arthritis (7%, annual incidence 8/100 000). The incidence of Lyme arthritis was small in this non-endemic area, and the incidence of sarcoid arthritis corresponded to that in earlier studies. Conclusion: This is the first prospective population based annual incidence study of early arthritis in Sweden. In this population, 36% of the incident cases had undifferentiated arthritis, whereas rheumatoid arthritis and reactive arthritis accounted for 45% of the cases. The incidence figures compare well with figures reported from other countries.

Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register

OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences. METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled. The study period was March 1999 through September 2006. The prospective protocol included information on demographics, clinical characteristics of patients and response measures. Fulfilment of ACR 50-70% improvement and European League Against Rheumatism (EULAR) good response or remission [28-joint disease activity score (DAS28) <2.6] at 3 months were chosen as primary outcome measures. Potential predictors of responses were identified using multivariate binary logistic regression models. RESULTS In total, 1565 patients were included in the study. Gender did not influence treatment response. Consistently, concomitant methotrexate (MTX) was significantly associated with EULAR remission, EULAR good response, ACR50 response and ACR70 response with odds ratios (ORs) 1.97, 2.13, 2.10 and 1.75, respectively. Concurrent treatment with other DMARDs was also significantly associated with EULAR remission, EULAR good response and ACR50 response (OR: 1.96, 2.24 and 1.94, respectively). Likewise, low HAQ at baseline consistently predicted good clinical outcome. Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 (OR: 1.59 and 1.60, respectively), whereas DAS28 score at baseline was inversely associated with EULAR remission (OR: 0.78). CONCLUSIONS In this observational study of patients with established RA, gender did not predict response to anti-TNF therapy, whereas treatment with concomitant DMARDs, especially MTX and low disability were associated with good response. Choice of outcome measures may influence the predictive value of baseline features.

Anxiety and depression in a community-based rheumatoid arthritis population

OBJECTIVE To assess anxiety and depression and their explanatory factors in rheumatoid arthritis (RA) in a community-based population. METHODS The subscales of the Arthritis Impact Measurement Scales (AIMS) for anxiety and depression were used, and the Health Assessment Questionnaire (HAQ) was used for the assessment of disability. Cross-tabulation and multivariate logistic regression analysis were used to evaluate which variables best describe the patients with either high or low depression and anxiety scores. RESULTS Nearly 20% of our patients had probable depression (AIMS depression subscale score > or =4), a figure comparable to earlier hospital-based series. Most of the AIMS anxiety subscale variability was explained by poor physical function and the male sex, while the AIMS depression subscale variability was mostly explained by poor physical function, comorbidities, and social inactivity. CONCLUSION In our cross-sectional, community-based RA series, depression was equal to the figures previously reported from hospital-based series. Poor physical function was a powerful explanatory factor of both depression and anxiety.Objective: To assess anxiety and depression and their explanatory factors in rheumatoid arthritis (RA) in a community-based population. Methods: The subscales of the Arthritis Impact Measurement Scales (AIMS) for anxiety and depression were used, and the Health Assessment Questionnaire (HAQ) was used for the assessment of disability. Cross-tabulation and multivariate logistic regression analysis were used to evaluate which variables best describe the patients with either high or low depression and anxiety scores. Results

Changing pattern in the prescription of biological treatment in rheumatoid arthritis. A 7-year follow-up of 1839 patients in Southern Sweden.

Objective: To study prescription patterns of biological treatment in rheumatoid arthritis (RA) patients in southern Sweden, a region with no formal or economic restrictions for the use of biological treatment in rheumatological diseases. Specifically, we studied conformity with the national Swedish guidelines for biologics in RA. Methods: Rheumatologists in southern Sweden contribute to a voluntary register on the use of biologics in treating arthritis patients (the South Swedish Arthritis Treatment Group (SSATG)). This register covers >90% of all the prescriptions of biologics for arthritis patients in the region. The treatment of 1839 patients (2704 treatment occasions) was recorded in the SSATG register during 1999–2006. Baseline characteristics were analysed. Results: Baseline Health Assessment Questionnaire (HAQ) scores and Disease Activity Scores (DASs) decreased significantly between 1999 and 2006, but disease activity remained high in RA patients. RA patients were treated with biologics earlier, but only 16% of the patients received biologics within 2 years of disease onset in 2006. The percentage of RA patients who were prescribed biologics after only one previous non-biological DMARD (disease-modifying anti-inflammatory rheumatic drug) was 27% in 2006. Thirty-five per cent of all RA patients changed from one biological treatment to another. Conclusions: Baseline DASs in RA patients remained high at the start of biological treatment. The national Swedish guidelines for the prescription of biologics in RA were followed. More patients with early RA were treated with biologics. The proportion of RA patients changing from one biological drug to another increased.

Smoking at onset of rheumatoid arthritis (RA) and its effect on disease activity and functional status: experiences from BARFOT, a long-term observational study on early RA

Objectives: To assess the effects of smoking on disease outcome in a large cohort of patients with early rheumatoid arthritis (RA). Methods: Between 1996 and 2004, 1787 adult patients (disease duration ≤ 1 year) were included in the BARFOT early RA study in Sweden. Smoking status was recorded at inclusion in the study. Disease Activity Score using 28 joint counts (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ) score, rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (anti-CCP), general health (GH) and pain visual analogue scales (VAS), and drug treatment were registered at inclusion and at follow-up at 3, 6, and 12 months. European League Against Rheumatism (EULAR) response and remission criteria were applied at 3, 6, and 12 months. Results: The proportion of patients who smoked at inclusion in the study fell from 29% in 1996 to 20% in 2004. There were no significant differences in disease activity at inclusion stratified according to smoking status. At 12 months of follow-up, 18% of current smokers at inclusion, 12% of previous smokers, and 11% of never smokers had high disease activity (DAS28 > 5.1, p = 0.005). Significantly fewer current smokers were in remission at 12 months (33%) compared to never smokers (36%) and previous smokers (42%) (p = 0.013). Current smoking at inclusion independently predicted poor EULAR response up to 12 months of follow-up. Conclusion: The present study gives some support to earlier data indicating that RA patients who smoke have a more active disease but further studies are needed to confirm this.

A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis

Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. Methods. Two Swedish arthritis populations were examined: 215 patients with early RA (≤ 12 months’ duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (≤ 3 months’ duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. Results were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. Conclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.

A more active treatment has profound effects on the health status of rheumatoid arthritis (RA) patients: results from a population-based RA register in Malmo¨, Sweden, 1997-2005

Objective: Population-based studies on the trends and effects of modern antirheumatic treatment are scarce. The aim of this study was to examine trends in treatment, health-related quality of life (HRQL), and disease outcome in a population-based register of patients with rheumatoid arthritis (RA) in Malmö, Sweden. Methods: A continuously updated population-based RA register was established in the city of Malmö, southern Sweden, in 1997. Self-completed postal questionnaires issued in 1997, 2002, and 2005 were used to collect information on demographics, medication, and health status. Cross-sectional comparisons were made between data from 1997, 2002, and 2005. Results: Between 1997 and 2005, the proportion of patients treated with any disease-modifying anti-rheumatic drug (DMARD) including biologics increased substantially (from 52% to 87%), as well as the proportion treated with methotrexate (from 23% to 52%) and biologics (almost exclusively tumour necrosis factor inhibitors) (from 0% to 20%). Twelve per cent of RA patients received biologics 5 years from disease onset in 2005. In parallel with changes in treatment, mean Health Assessment Questionnaire (HAQ) scores (1.19 vs. 0.89) and all Short Form 36 (SF-36) subscales improved from 1997 to 2005 (non-overlapping confidence intervals). Conclusion: Between 1997 and 2005, there was a substantial increase in the use of DMARDs, which was accompanied by improved mean HAQ and SF-36 scores in cross-sectional comparisons. These results support the concept that more intensive treatment with DMARDs and biologics can have profound effects on the overall health status in RA patients at the population level.

The costs of early inflammatory joint disease: a population-based study in southern Sweden.

Objective: To study the costs and use of healthcare for patients during the first months with early joint inflammation, in a population‐based prospective referral study in Southern Sweden. Methods: Adult patients with arthritis for <3 months and with onset of symptoms between 1 May 1999 and 1 May 2000 were referred from primary health centres to rheumatologists. Four clinical assessments were performed during a 6‐month follow‐up period. The direct medical costs for inpatient stays, outpatient visits, visits to general practitioners, and visits to health professionals, as well as costs for medication, radiographs, and laboratory tests were recorded from the onset of the disease up to 6 months of follow‐up. Indirect costs for sick leave were also recorded. Results: Fifty‐six of 71 referred patients agreed to participate. Thirteen (23%) had RA, 21 (38%) had reactive arthritis (ReA), 14 (25%) had undifferentiated arthritis, and eight (14%) had other arthritides. The median cost per patient in the entire group was USD 3362. The median cost per patient in the RA group was USD 4385, and USD 4085 in the ReA group. There was no statistically significant difference in the median costs per patient in the different diagnostic groups. Sick leave accounted for 44% of the total costs in the entire group, and 46% and 47%, respectively, in the RA and ReA groups. Conclusion: The costs of early arthritis are already considerable during the first months of the disease following the onset of the symptoms. The indirect costs due to sick leave accounted for nearly half of the costs.

The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA

Objective: We studied the effect of stopping smoking on disease activity in patients with RA. Methods: Between 1992 and 2005, 2,800 adult patients were included in the BARFOT early RA study in Sweden. Disease Activity Score 28 joints (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), rheumatoid factor (RF), anti-CCP, general health and pain visual analog scales (VAS), EULAR response and treatment were registered at inclusion and at follow-up 2, 5 and 8 years. In 2010, a self-completion postal questionnaire was sent to 2,102 patients, enquiring about lifestyle factors, including cessation of smoking. Results: A total of 1,460 adult RA patients with disease duration ≤2 years were included in this study. Seventeen percent smoked in 2010. In total, 127 patients stopped smoking after inclusion in the study. Smoking cessation after inclusion in the study was negatively associated with EULAR good outcome at 8 years (OR 0.44, 95% CI 0.22–0.86, p=0.02), controlled for age, disease duration, sex, socioeconomic class, smoking status, RF, and DAS28 at inclusion. Conclusion: Seventeen percent of the RA patients smoked in 2010 in this large Swedish RA cohort. Stopping smoking after onset of RA did not change the poor prognosis of smokers with RA, but all RA patients need to stop smoking because of the high risk of cardiovascular mortality and morbidity and the association of smoking with vasculitis and noduli in RA.

Absent “Window of Opportunity” in Smokers with Short Disease Duration. Data from BARFOT, a Multicenter Study of Early Rheumatoid Arthritis

Objective. To study the effect of disease duration and smoking on outcome in early rheumatoid arthritis (RA). Methods. Between 1996 and 2004, 1587 patients were included in the BARFOT early RA (disease duration ≤ 1 year) study in Sweden. European League Against Rheumatism (EULAR) response, Health Assessment Questionnaire (HAQ), rheumatoid factor (RF), and antibodies to cyclic citrullinated peptide (anti-CCP) were recorded at study start and at 3, 6, and 12 months. Results. In total, 180 RA patients (11%) had disease duration ≤ 12 weeks. These patients achieved good EULAR response significantly more often at 3 and 12 months than patients with a longer disease duration despite having more aggressive disease [EULAR good response was achieved by 35% and 35% at 3 and 12 months, respectively, among the patients with disease duration ≤ 12 weeks, by 35% and 41% of patients with disease duration of 13–24 weeks, and by 28% and 33% of patients with disease duration of 25–52 weeks (p = 0.02 for 3 months; p = 0.02 for 12 months)]. There was a significant correlation between improvement in Disease Activity Score-28 (DAS28), its individual variables, and Health Assessment Questionnaire (HAQ) and disease duration up to 12 months after study start. For smokers, no such trend was seen. Conclusion. Up to 12 months after inclusion in the study, there was a significant correlation between improvement in DAS28, its individual components, and HAQ and disease duration, with patients who had a shorter disease duration improving most. Smokers had poorer EULAR response and showed no improvement with regard to disease duration.