Antibodies against Porphyromonas gingivalis in serum and saliva and their association with rheumatoid arthritis and periodontitis. Data from two rheumatoid arthritis cohorts in Sweden.

Background: Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to Porphyromonas gingivalis (P. gingivalis) and RA has been established, but data on saliva antibodies to P. gingivalis in RA are lacking. We evaluated antibodies to P. gingivalis in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity. Methods: The SARA (secretory antibodies in RA) study includes 196 patients with RA and 101 healthy controls. The Karlskrona RA study includes 132 patients with RA ≥ 61 years of age, who underwent dental examination. Serum Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies and saliva IgA antibodies to the P. gingivalis-specific Arg-specific gingipain B (RgpB) were measured in patients with RA and controls. Results: The level of saliva IgA anti-RgpB antibodies was significantly higher among patients with RA than among healthy controls in multivariate analysis adjusted for age, gender, smoking, and IgG ACPA (p = 0.022). Saliva IgA anti-RgpB antibodies were associated with RA disease activity in multivariate analysis (p = 0.036). Anti-RgpB antibodies were not associated with periodontitis or serum IgG ACPA. Conclusion: Patients with RA had higher levels of saliva IgA anti-RgpB antibodies than healthy controls. Saliva IgA anti-RgpB antibodies may be associated with RA disease activity but were not associated with periodontitis or serum IgG ACPA. Our results indicate a local production of IgA anti-RgpB in the salivary glands that is not accompanied by systemic antibody production.

Cytokines in gingival crevicular fluid in elderly rheumatoid arthritis patients in a population-based cross-sectional study: RANTES was associated with periodontitis.

OBJECTIVE: We studied cytokines in gingival crevicular fluid (GCF) in a cross-sectional population-based cohort of rheumatoid arthritis (RA) patients ≥61 years of age with and without a diagnosis of periodontitis. BACKGROUND DATA: Earlier studies on cytokines in GCF in RA patients have not given clear results. METHODS: In a population-based cross-sectional study of patients ≥61 years of age, 233 RA patients were identified. 132 (57%) dentate RA patients participated. All participants received rheumatological and dental examinations, and had a panoramic radiograph taken. GCF was sampled on each patient. Interleukins 1-ß (IL-1ß), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and chemokines RANTES/CCL5, eotaxin and monocyte chemoattractant protein (MCP-1) were analyzed in GCF. These cytokines were stratified for periodontitis, age, gender, body mass index (BMI), smoking, and anti-cyclic citrullinated protein (anti-CCP) status. Binary logistic regression analyses with periodontitis as outcome were performed adjusting for the above mentioned confounding factors including anti-rheumatic medication, disease duration and the cytokine in question. RESULTS: Periodontitis was diagnosed in 80/132 (61%) of study participants. The 110 RA patients not participating were older, had a higher mean erythrocyte sedimentation rate (ESR), had a higher mean DAS28ESR (Disease Activity Score 28 using ESR) and were less often on biologic treatment. Only RANTES was associated with periodontitis (p = .049, OR 1.001, 95% CI 1.000-1.002) in the binary logistic regression analyses. CONCLUSION: In this population-based elderly RA cohort, neither pro-inflammatory nor anti-inflammatory cytokines in GCF were clearly associated with a diagnosis of periodontitis.

The association between rheumatoid arthritis and periodontal disease in a population-based cross-sectional case-control study.

BACKGROUND: The association between rheumatoid arthritis (RA) and periodontitis remains unclear. METHODS: We studied oral health and periodontitis in a population-based case-control study of individuals with ≥10 remaining teeth ≥61 years of age and either with, or without a diagnosis of RA. 126 dentate individuals with RA were recruited together with age-matched control individuals without RA. The control individuals were recruited from the general population from the same city (n = 249). A dental examination including a panoramic radiograph was performed on all participants. All individuals with RA were examined and medical records were reviewed by a rheumatologist. In the control group, none of the participants presented with symptoms of RA and their medical records were also negative. RESULTS: The RA group included more women (66.7% vs. 55.8%) (p < 0.01). Individuals in the RA group had a higher body mass index (BMI) (p < 0.001). A diagnosis of periodontitis was more common in the RA group (61.1%) than in the control group (33.7%) (p = 0.001). Binary logistic regression analysis identified that a BMI > 25 (OR 6.2, 95% CI 3.6, 10.5, p = 0.000), periodontitis (OR 2.5 95% CI 1.5, 4.2 p = 0.000), and female gender (OR 2.3, 95% CI 1.3-4.0, p = 0.003) were associated with RA. CONCLUSION: RA was associated a diagnosis of periodontitis.

The Effect of Socioeconomic Class and Immigrant Status on Disease Activity in Rheumatoid Arthritis: Data from BARFOT, a Multi-Centre Study of Early RA.

BACKGROUND: There have been no reports on the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden. METHODS: Between 1992 and 2006, 2,800 patients were included in the BARFOT study on early RA in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire (HAQ), treatment and European League Against Rheumatism (EULAR) response criteria were registered. In 2010, 1,430 patients completed a questionnaire enquiring about demographics and lifestyle factors. RESULTS: One hundred and thirty-nine of the 1,430 patients (9.7%) were immigrants. At baseline immigrants had higher mean HAQ (1.2 vs 0.97 for non-immigrants, p=0.001), DAS28 (5.6 vs 5.2, p=0.000), visual analog scale (VAS) pain (56 mm vs 45 mm, p=0.000), VAS global health (53 mm vs 44 mm, p=0.000) and tender joint count (TJC) (10 vs 8, p=0.000). These differences persisted for up to 2 years of follow-up (for HAQ, for up to 8 years of follow-up). Immigrant status did not have any effect on swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did not have any effect on treatment or outcome. CONCLUSIONS: Immigrants scored worse in pain, function and TJC for up to 2 years of follow-up, but they did not differ from non-immigrants in objective measures of inflammation or EULAR outcome. This could be due to different perceptions of health and pain and/or the stress of immigration. Socioeconomic class had no effect on treatment or outcome, and this could be due to the relatively egalitarian society in Sweden.

Alcohol consumption is associated with lower self-reported disease activity and better health-related quality of life in female rheumatoid arthritis patients in Sweden: data from BARFOT, a multicenter study on early RA.

BACKGROUND: Earlier studies have found a positive effect of alcohol consumption, with a reduced disease activity in rheumatoid arthritis (RA). The aim of this study was to assess alcohol consumption and its association with disease activity and health related quality of life (HRQL) in Swedish RA patients. METHODS: Between 1992 and 2005, 2,800 adult patients were included in the BARFOT study of early RA in Sweden. In 2010 a self-completion postal questionnaire was sent to all 2,102 prevalent patients in the BARFOT study enquiring about disease severity, HRQL, and lifestyle factors. Alcohol consumption was assessed using the validated AUDIT-C questionnaire. RESULTS: A total of 1,238 out of 1,460 patients answering the questionnaire had data on alcohol consumption: 11% were non-drinkers, 67% had a non-hazardous drinking, and 21% were classified as hazardous drinkers. Women who drank alcohol reported lower disease activity and better HRQL, but there were no association between alcohol consumption and disease activity in men. For current smokers, alcohol use was only associated with fewer patient-reported swollen joints. The outcome was not affected by kind of alcohol consumed. CONCLUSIONS: There was an association between alcohol consumption and both lower self-reported disease activity and higher HRQL in female, but not in male, RA patients.

The effect of snuff (smokeless tobacco) on disease activity and function in rheumatoid arthritis: experiences from the Better Anti-Rheumatic FarmacOTherapy, a longitudinal multicenter study on early rheumatoid arthritis.

BACKGROUND: It is not known whether snuff (moist smokeless tobacco) affects disease activity in rheumatoid arthritis (RA). OBJECTIVE: This study aims to study the effect of snuff on disease activity and function in Swedish patients with early RA. METHODS: Between 1992 and 2005, 2800 adult patients were included in the Better Anti-Rheumatic FarmacOTherapy (BARFOT) early RA study in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire, visual analog scale for general health, and drug treatment were registered at inclusion and at follow-up after 1, 2, and 5 years. European League Against Rheumatism response and remission criteria were applied at 1 year. In 2010, a self-completed postal questionnaire was sent to 2102 patients in the BARFOT study enquiring about lifestyle factors such as smoking and use of snuff. Three controls for each patient using snuff were identified. RESULTS: Fifty-one patients who used snuff were identified, together with 145 controls. When we adjusted for socioeconomic class, disease duration, and previous antirheumatic medication, the snuff users had lower DAS28 values at up to 6 months of follow-up than patients who had never smoked, and they had lower DAS28 values than previous smokers at up to 2 years of follow-up. No effect of snuff use on European League Against Rheumatism response was seen at up to 1 year. CONCLUSIONS: Snuff users initially had lower DAS28 levels than never smokers and previous smokers.

Second-hand exposure to tobacco smoke and its effect on disease activity in Swedish rheumatoid arthritis patients. Data from BARFOT, a multicenter study of RA.

OBJECTIVES: We studied the prevalence and effect on disease activity of ever having had second-hand exposure to tobacco smoke in Swedish rheumatoid arthritis (RA) patients who had never smoked. METHODS: Between 1992 and 2005, 2,800 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), general health and pain visual analogue scales (VAS), and drug treatment were registered at inclusion and at follow-up at 3, 6, and 12 months and 2 and 5 years. EULAR response criteria were applied at the same follow-up points. In 2010, a self-completion postal questionnaire was sent to 2,102 patients in the BARFOT study enquiring about lifestyle habits such as whether they had ever been exposed to tobacco smoke as a result of someone else smoking. RESULTS: A total of 963/1,421 patients (68%) had had second-hand exposure to tobacco smoke. At 3, 6, and 12 months, at 2 years, and at 5 years of follow-up, there were no differences in EULAR response between patients who had never smoked and who had been exposed or had not been exposed second-hand to tobacco smoke (p=0.91, p=0.88, p=0.84, p=0.61 and p=0.85, respectively). CONCLUSIONS: We did not find any association between second-hand exposure to tobacco smoke and disease activity in RA.

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.

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.

Patient-reported events preceding the onset of rheumatoid arthritis: possible clues to aetiology.

AIMS: Patients with rheumatoid arthritis (RA) often report events that they believe may have caused their disease. We attempted to characterize such causal events and the possible relationship between these and outcomes. METHODS: Between 1996 and 2004, 1,787 adult patients were included in the Better Anti-Rheumatic FarmacOTherapy (BARFOT) early RA study in Sweden. Six possible causal events at baseline were predefined. Disease Activity Score 28-joint count (DAS28) and treatment were registered at inclusion and at three, six and 12 months. The European League against Rheumatism (EULAR) response criteria were used. RESULTS: A total of 1,652 patients (92%) answered the question about possible causal events. Thirty per cent (490) of the patients believed that some event in particular had caused their RA. Sixteen per cent of the patients thought that infection, 4.4% psychological trauma, 4.1% physical trauma, 2.8% surgery, 1.5% pregnancy and 1.2% vaccination had been the cause. Younger patients attributed previous infection to their RA more often than older patients. There were no differences in EULAR response up to one year between patients who reported some event or infection and patients who did not. RA thought to be caused by infection showed a seasonal trend in the month of onset. Women reported that trauma had been a cause of their RA more often than men. CONCLUSION: Thirty per cent of the patients reported some causal event and 16% reported infection to be the cause of their RA. There were differences in gender and age in what patients reported as the cause of their RA.

Differences in longitudinal disease and treatment characteristics of patients with rheumatoid arthritis replying and not replying to a postal questionnaire. Experience from a biologics register in southern Sweden.

OBJECTIVE: Studies on patients not answering postal questionnaires are scarce. We assessed the demographics and longitudinal disease and treatment characteristics of patients with rheumatoid arthritis (RA) in a Swedish biologics register who replied and who did not reply to a postal questionnaire. METHODS: In the South Swedish Arthritis Treatment Group register, we have detailed disease severity characteristics at baseline and at followup for rheumatology patients taking biologic drugs. In 2005 a questionnaire on smoking, comorbidities, education, and ethnicity was sent to 1234 RA patients who had started their first biologic drug. RESULTS: In total, 989 subjects (80%) answered the questionnaire. The 245 (20%) who did not answer generally had more severe RA [higher Disease Activity Score, worse Health Assessment Questionnaire score, higher visual analog scale scores for general health and pain at baseline and at followup, and stopped the drug treatment more frequently (72% vs 53%; p=0.0001)]. There were no statistically significant differences in gender and disease duration between those who replied and those who did not reply, but in general the patients who did not reply were younger. CONCLUSION: Patients with RA in a Swedish biologics register not replying to a postal questionnaire had more severe RA and stopped biological drug treatment more frequently. Thus a detailed analysis of prospectively collected data can clarify selection bias introduced by subjects who do not answer a postal questionnaire, which may influence the validity and interpretation of results from postal survey studies.

Quality of life and economic burden of illness in very early arthritis. A population based study in southern Sweden.

OBJECTIVE: To measure health related quality of life (HRQOL) in patients with very early arthritis in a population based study in southern Sweden, and to compare HRQOL at baseline between the different diagnostic groups. Further, we investigated whether HRQOL at baseline correlated with the costs the patients incurred during the study. METHODS: Seventy-one adult patients with arthritis of less than 3 months' duration were referred from primary health care centers to rheumatologists. HRQOL was measured with the Arthritis Impact Measurement Scales (AIMS) and EuroQol at baseline. A comparison of HRQOL measures at baseline and the costs the patients incurred during the study was conducted in 56 of the patients. RESULTS: Twenty-seven (38%) patients had reactive arthritis (ReA), 17 (24%) undifferentiated arthritis, 15 (21%) rheumatoid arthritis (RA), 4 (6%) psoriatic arthritis, and the rest (11%) other diagnoses. Statistically significant differences were found between the 4 patient groups concerning the AIMS subscales of dexterity, household activity, activities of daily living (ADL) and pain, the patients with RA being most severely affected. There were no statistically significant differences between the 4 diagnosis groups concerning the EuroQol utility and EuroQol visual analog scale (VAS) scores. Of the AIMS subscales, the mobility, physical activity, household activity, ADL, and pain subscales correlated significantly with the incurred costs. Also the EuroQol utility scores and EuroQol VAS scores correlated significantly with the costs. Only the AIMS household activity subscale predicted the costs in the regression analysis. CONCLUSION: Patients with RA had significantly worse scores in the AIMS dexterity, household activities, ADL, and pain subscales compared to patients with other arthritides very early in the disease. The EuroQol generic quality of life instrument was less sensitive in detecting differences between patients with early arthritis than the disease-specific AIMS instrument. There was a correlation between the costs and the EuroQol utility scores and EuroQol VAS scores during the very first months of the disease, as well as with costs and the AIMS subscales of mobility, physical activity, household activity, ADL, and pain.

Infections preceding early arthritis in southern Sweden: a prospective population-based study.

OBJECTIVE: To detect evidence of infections preceding early arthritis in Southern Sweden and to compare the clinical outcome of remission during a 6-month followup for patients with and without signs of prior infection. METHODS: Adult patients with arthritis of less than 3 months' duration were referred from primary health care centers to rheumatologists. All patients were systematically screened for infections caused by Salmonella typhimurium and Salmonella enteritidis, Yersinia enterocolitica, Campylobacter jejuni, Borrelia burgdorferi, Chlamydia trachomatis, Chlamydia pneumoniae, and parvovirus B19. RESULTS: Seventy-one patients were included in this study. Twenty-seven (38%) patients had reactive arthritis (ReA), 17 (24%) undifferentiated arthritis, 15 (21%) rheumatoid arthritis (RA), 4 (6%) psoriatic arthritis, and the rest (11%) other diagnoses. Of all the patients, 45% had evidence of a recent infection preceding the arthritis, as indicated by laboratory tests and/or disease history. C. jejuni dominated the ReA group. The occurrence of recent C. trachomatis, B. burgdorferi, C. pneumoniae, and parvovirus B19 infections was low. Overall, 58% of the patients went into remission during the 6-month followup. Of the patients with a preceding infection, 69% went into remission as compared to 38% of the patients without a preceding infection (p = 0.011). Thirty-three percent of the patients with RA were in remission after 6 months. CONCLUSION: In this population-based cohort, 45% of the patients presenting with a new-onset arthritis had had a prior infection. Campylobacter ReA dominated the ReA group. There were only a few cases preceded by infections by C. trachomatis, B. burgdorferi, C. pneumoniae, and parvovirus B19 infections. Remission during the first 6 months was especially frequent in the group of patients with a prior infection, but the remission rate was relatively high even for arthritis without prior infection.