The effect of smoking on response and drug survival in rheumatoid arthritis patients treated with their first anti-TNF drug.

OBJECTIVES: Smoking has been associated with higher disease activity and poor response to anti-tumour necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). We wanted to study the effect of smoking on response to therapy, disease activity measures, and drug survival in RA patients starting their first anti-TNF drug. METHODS: In 2005, RA patients in a voluntary rheumatology biologics register in Southern Sweden answered a questionnaire that included smoking habits. The primary endpoint comprised the European League Against Rheumatism (EULAR) response criteria at 3, 6, and 12 months. Secondary endpoints were the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) response criteria, and drug survival. RESULTS: Between 1999 and 2005, 23% of RA patients (216/934) in Southern Sweden were current smokers at the start of anti-TNF therapy. Smoking did not influence disease activity at baseline. Heavy smokers had the poorest drug survival. Current smoking was a negative predictive factor for EULAR response at the 3-month follow-up [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.87, p = 0.012], and for SDAI response at 3 months (OR 0.45, 95% CI 0.27-0.77, p = 0.003) and 6 months (OR 0.47, 95% CI 0.25-0.88, p = 0.02). A pack-year history of 11-20 was a negative predictive factor for SDAI response at 12 months (OR 0.30, 95% CI 0.13-0.70, p = 0.005). Smokers had higher visual analogue scale (VAS) global scores, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) at 3 months. CONCLUSION: Current smoking was predictive of poor response to anti-TNF treatment for up to 12 months and heavy smokers had the poorest drug survival.

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 more active treatment has profound effects on the health status of rheumatoid arthritis (RA) patients: results from a population-based RA register in Malmö, 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.

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.

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.

Trends in medication and health-related quality of life in a population-based rheumatoid arthritis register in Malmo, Sweden.

OBJECTIVES: To study trends in treatment, health status and health-related quality of life (HRQL) in two cross-sectional surveys over a 5-yr period and in an observational follow-up sub-cohort based on a population-based rheumatoid arthritis (RA) register in Malmö, Sweden. MATERIAL AND METHODS: A continuously updated population-based RA register was established in Malmö city in southern Sweden in 1997. Patient-administered questionnaires in 1997 and 2002 were used to collect information on demographics, medication and health status. Cross-sectional comparisons were made between 1997 and 2002. A longitudinal analysis was also performed in the RA patients participating in both surveys. RESULTS: Increased proportions of patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) (69 vs 52%), corticosteroids (30 vs 23%), methotrexate (52 vs 29%) and biologics (14 vs 0%) in 2002 compared with 1997. In the cross-sectional analysis, the visual analogue scores (VAS) for pain and general health and the short form 36 (SF-36) domains were slightly better in 2002 than in 1997. In the observational sub-cohort, patients treated with biologics improved significantly in several measures of health status, whereas those starting on methotrexate or undergoing other or no changes in DMARD therapy did not. CONCLUSIONS: In this population-based RA cohort, patients were more actively treated in 2002. Small improvements were seen in health status and these improvements were exclusively attributable to treatment with biologics.

Circulating soluble interleukin-2 receptor level predicts remission in very early reactive arthritis.

OBJECTIVES: To assess the predictive value of serum soluble interleukin-2 receptor (sIL-2R) levels in patients with acute reactive arthritis (ReA). METHODS: The study includes 26 patients with acute ReA who had participated in a prospective population-based cohort study of very early arthritis. The patients had had arthritis of at least one joint with a maximum duration of 3 months. They were assessed by a rheumatologist on presentation and 6 months later. Serum sIL-2R levels on presentation were measured by the Immulite automated immunoassay analyser. Remission at 6 months, defined by the absence of swollen and tender joints, was related to the baseline sIL-2R level using a permutation test with general scores. Bootstrap estimation was used to derive the 95% confidence interval (CI). RESULTS: A total of 17 patients (65%) were in remission at 6 months and nine patients (35%) still had joint symptoms. In patients reaching remission within 6 months, the mean baseline sIL-2R level, 891 U/mL (95% CI: 658 to 1123), was higher than in patients not reaching remission, 501 U/mL (95% CI: 436 to 566), p = 0.022. CONCLUSIONS: A high serum sIL-2R level at baseline is a predictor of remission in patients with acute ReA.

Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity.

OBJECTIVE: To measure serum levels of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and serum cartilage oligomeric matrix protein (COMP) in patients with early joint inflammation, and to study the correlation of these two tests with clinical measurements. METHODS: Adult patients with recent-onset arthritis, of <3 months' duration, were referred from primary healthcare centres to rheumatologists. Serum levels of anti-CCP antibodies and COMP at baseline were analysed by enzyme immunoassay (EIA) and compared with clinical baseline data. RESULTS: Sixty-nine patients were included. The specificity of the anti-CCP antibody test for RA was 96%, and the sensitivity was 44%. There was a significant difference between the four diagnosis groups in the anti-CCP antibody test, probability (p)<0.001, whereas no significant differences were found concerning COMP. The baseline serum COMP test correlated with age (p=0.0001), joint score for swollen joints (p=0.02), and C-reactive protein (CRP) (p=0.02). CONCLUSION: This study confirms the high diagnostic specificity of anti-CCP antibodies for rheumatoid arthritis (RA) in a prospective population-based study of very early arthritis. Raised serum COMP levels were common in all diagnosis groups in this series, indicating cartilage involvement in both self-limiting and non-erosive disease.

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.

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.

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.

Arthritis impact measurement scales in a community-based rheumatoid arthritis population.

The objective of this study was to use the Arthritis Impact Measurement Scales (AIMS) in a community-based rheumatoid arthritis (RA) population to describe the patient population, analyse health status changes and predict survival. The AIMS was assessed in 91 RA patients in a community-based RA population in Kuusamo, Northern Finland. A 5-year follow-up study was performed. The mean AIMS scores in this series of RA patients were comparable to those reported in previous studies. Dexterity correlated with disease duration. Lower extremity function was well preserved and only slightly dependent on disease duration. The AIMS scores changed for the worse in all the subscales over the follow-up period. Of all the AIMS subscale scores, poor functional status, as measured by the AIMS lower extremity function and social activity subscales, best predicted mortality.

Reactive arthritis induced by Clostridium difficile enteritis as a complication of Helicobacter pylori eradication.

Clostridium difficile has recently been established as a cause of reactive arthritis (ReA). We present a case of Clostridium difficile-induced ReA as a complication of Helicobacter pylori eradication, which, to the best of our knowledge, is the first such case reported.

Functional status predicts mortality in a community based rheumatoid arthritis population.

OBJECTIVE: To assess mortality, causes of death, and patient and disease characteristics predicting survival in a 5 year followup of a community based population of 103 patients with rheumatoid arthritis (RA) in the Kuusamo community in Northern Finland. METHODS: Mortality and causes of death were assessed on the basis of official data registers and death certificates. The relation of different baseline patient demographics and disease characteristics to mortality was evaluated. RESULTS: Functional status, measured by the lower extremity component of the Keitel function test, emerged as the most powerful factor predicting mortality. A poor lower extremity function (score > or = 13) increased the relative risk of death (hazard ratio 9.1) compared to well preserved lower extremity function. If the Keitel function test was omitted from the survival analysis, the best predictor of mortality was the Health Assessment Questionnaire. Twenty-one percent of the patients had died during the followup, the most usual cause of death being cardiovascular disease. CONCLUSION: Poor functional status, measured in this series by the Keitel function test, is a powerful predictor of mortality in RA. Our results confirm the importance of measurement of functional status in rheumatology care.

Myocardial infarction in a parturient. A case report with emphasis on medication and management.

Myocardial infarction is rare in pregnancy. We report a 38-year-old woman with a history of smoking and pre-eclampsia in her previous pregnancy, who suffered a non-Q infarction at 18 weeks of gestation. Stenoses in the left coronary artery were verified angiographically. She delivered a healthy child vaginally under epidural anaesthesia.