Increased risk of osteoporotic fractures in Swedish patients with rheumatoid arthritis despite early treatment with potent disease-modifying anti-rheumatic drugs: a prospective general population-matched cohort study.

Objective: To study the difference in incidence and risk of fragility fractures between rheumatoid arthritis (RA) patients followed up early in the disease and the general population in Sweden; and the fracture risk changes in RA patients diagnosed in the 1990s and 2000s because of earlier, more potent pharmacological treatment in the later period.Method: Patients with early RA were recruited from the BARFOT cohort, a Swedish multicentre observational study of early RA patients (n = 2557). All patients fulfilled 1987 American College of Rheumatology criteria and were included between 1992 and 2006. Each patient was matched by gender, age, and residential area with four controls from the general population (n = 10 228). Fractures of forearm, upper arm, and hip were identified by ICD-9 and ICD-10 codes through Swedish national medical registries.Results: During follow-up of 12.9 ± 4.7 years (mean ± sd), 14% (n = 470) of RA patients and 11% (n = 1418) of controls experienced a fracture (p < 0.001). When dividing the patients and controls into two groups according to inclusion period, an 8 year follow-up time was used. RA patients included in the 1990s had a higher incidence rate (IR) of hip and other fractures. RA patients included in the 2000s had a higher IR of all fracture sites. The hazard ratio of fractures was 1.4 in the total RA cohort, and the risk was increased in both the 1990s and 2000s.Conclusion: We observed an increased risk of fragility fractures in RA patients diagnosed in both the 1990s and 2000s, despite patients in the 2000s obtaining potent pharmacological treatment early in the disease.

Prognostic factors for change in self-reported anxiety and depression in spondyloarthritis patients: data from the population-based SpAScania cohort from southern Sweden.

OBJECTIVES: Anxiety and depression symptoms are more common in patients with spondyloarthritis (SpA) than in the general population. This study describes prognostic factors for change in self-reported anxiety and depression over 2 years in a well-defined SpA cohort. METHOD: In 2009, 3716 adult patients from the SpAScania cohort received a postal questionnaire to assess quality of life (QoL) and physical and mental functioning. A follow-up survey was performed in 2011. The Hospital Anxiety and Depression Scale indicated 'no', 'possible', and 'probable' cases of anxiety and depression. Transitions between the three different categories were analysed and logistic regression analysis determined prognostic factors (patient-reported outcomes and characteristics) for improvement or deterioration. RESULTS: In total, 1629 SpA patients responded to both surveys (44%) (mean ± SD age 55.8 ± 13.1 years, disease duration 14.6 ± 11.7 years); 27% had ankylosing spondylitis, 55% psoriatic arthritis, and 18% undifferentiated SpA. The proportion of patients reporting possible/probable anxiety decreased from 31% to 25% over 2 years, while no changes in depression were seen. Factors associated with deterioration or improvement were largely the same for anxiety as for depression: fatigue, general health, QoL, level of functioning, disease activity, and self-efficacy. However, reporting chronic widespread pain (CWP) at baseline increased the risk of becoming depressed and decreased the probability of recovering from anxiety. CONCLUSION: Self-reported anxiety and depression is common and fairly stable over time in SpA patients. The association between mental health and CWP indicates that both comorbidities need to be acknowledged and treated in the clinic.

Predictors of work disability after start of anti-TNF therapy in a national cohort of Swedish patients with rheumatoid arthritis: does early anti-TNF therapy bring patients back to work?

OBJECTIVES: To examine predictors of work ability gain and loss after anti-tumour necrosis factor (TNF) start, respectively, in working-age patients with rheumatoid arthritis (RA) with a special focus on disease duration. METHODS: Patients with RA, aged 19-62 years, starting their first TNF inhibitor 2006-2009 with full work ability (0 sick leave/disability pension days during 3 months before bio-start; n=1048) or no work ability (90 days; n=753) were identified in the Swedish biologics register (Anti-Rheumatic Treatment In Sweden, ARTIS) and sick leave/disability pension days retrieved from the Social Insurance Agency. Outcome was defined as work ability gain ≥50% for patients without work ability at bio-start and work ability loss ≥50% for patients with full work ability, and survival analyses conducted. Baseline predictors including disease duration, age, sex, education level, employment, Health Assessment Questionnaire, Disease Activity Score 28 and relevant comorbidities were estimated using Cox regression. RESULTS: During 3 years after anti-TNF start, the probability of regaining work ability for totally work-disabled patients was 35% for those with disease duration <5 years and 14% for disease duration ≥5 years (adjusted HR 2.1 (95% CI 1.4 to 3.2)). For patients with full work ability at bio-start, disease duration did not predict work ability loss. Baseline disability pension was also a strong predictor of work ability gain after treatment start. CONCLUSIONS: A substantial proportion of work-disabled patients with RA who start anti-TNF therapy regain work ability. Those initiating treatment within 5 years of symptom onset have a more than doubled 3-year probability of regaining work ability compared with later treatment starts. This effect seems largely due to the impact of disease duration on disability pension status.

Total cost and cost predictors in systemic lupus erythematosus - 8-years follow-up of a Swedish inception cohort.

OBJECTIVE: To study the annual direct and indirect costs in systemic lupus erythematosus (SLE) and how age, disease manifestations, disease activity, and organ damage influence total costs and predicted costs for SLE. METHODS: Clinical data on all patients with a diagnosis of SLE living in a defined area in southern Sweden during eight years were linked to health authority registries and the social insurance system which contain data on cost. Cost data on four matched population controls for each patient were also extracted. The controls were matched for age, sex, and area of residence. RESULTS: Data from 127 patients with SLE and 508 population controls were extracted. The mean annual total cost for SLE patients was SEK 180,520 ($30,093); the highest costs were found in the subgroup with nephritis SEK 229,423 ($38,246). The total costs for the patient group were significantly higher (p < 0.05) compared to the population controls of SEK 59,985 ($10,000). Of the total costs, 72% were due to indirect costs, 3% to SLE-specific pharmaceuticals, and the remaining 25% were in- and outpatient related costs. During the study period, inpatient days decreased by 60%, while outpatient contacts increased by 25%. Age (inverse relation), increasing disease activity, and acquired organ damage were significant predictors of total costs (all p < 0.05). CONCLUSION: The total annual costs for unselected SLE patients were found to be three times those for matched population controls. Important predictors of total costs were found.

The risk of pneumococcal infections after immunization with pneumococcal conjugate vaccine compared to non-vaccinated inflammatory arthritis patients.

OBJECTIVES: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. METHOD: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagnostic codes. The following infections were considered as serious cases: pneumonia, other lower respiratory infections, meningitis, sepsis, and septic arthritis. The relative risk (RR) of infection was calculated as the number of events after/number of events before vaccination. Ratios of relative risk (RRRs) were calculated between vaccinated and non-vaccinated groups of patients. A generalized estimating equation (GEE) was used to handle correlated data for several events in the same individual. RESULTS: Although statistically non-significant, the point estimate of the RRR [0.55, 95% confidence interval (CI) 0.25-1.22] suggested a reduced risk of serious pneumococcal infections in vaccinated patients compared to the unexposed group. CONCLUSIONS: Vaccination with PCV7 tended to reduce the risk of putative serious pneumococcal infections by about 45% compared to non-vaccinated patients in this observational cohort study.

Treatment patterns with topicals, traditional systemics and biologics in psoriasis - a Swedish database analysis.

BACKGROUND: Little data exist on real-world treatment patterns in psoriasis, especially from European settings. OBJECTIVE: To estimate, for topicals, systemics and biologics, the time to non-persistency, switching, augmentation and insufficient treatment result (only for biologics), as well as to estimate the time to restart, in patients treated with each treatment class in Sweden based on registry data. METHODS: This database analysis utilized data from patients with psoriasis from several Swedish administrative registers. Patients were identified through combinations of diagnoses from two regional registers and filled prescriptions for relevant treatments from the Swedish Prescribed Drug Register. Kaplan-Meier time-to-event ('survival') functions were estimated with relevant treatment events as failure and the proportions of patients having experienced an event at specific time-points were derived from the failure rates. RESULTS: For topicals, systemics and biologics the number of indexed treatment episodes were 25,396, 2963, and 628 respectively. One year after treatment initiation, the proportion of patients who were classed as non-persistent with topicals, systemics and biologics were estimated at 88.3%, 47.9% and 43.2% respectively. Among patients who remained persistent, within 1 year of treatment start the proportions of treatment episodes in which patients were augmented were estimated at 56.0% for topicals, 45.3% for systemics and 58.9% for biologics. In addition, within 1 year of non-persistence, 49.0% of topicals, 60.8% of systemics and 80.2% of biologics treatment episodes were re-initiated, with 35.4-52.5% re-initiated on the non-persistent treatment depending on treatment class. In addition, among patients on biologics, 29.2% of treatment episodes had an insufficient treatment result within 1 year of treatment start. CONCLUSION: Persistency to psoriasis treatments may be sub-optimal and patients who remain persistent relatively frequently receive augmentation therapy or switch to another therapy. Therefore, current treatment options in psoriasis may be insufficient.

Current and future impact of osteoarthritis on health care: a population-based study with projections to year 2032.

OBJECTIVE: To estimate the current and future (to year 2032) impact of osteoarthritis (OA) health care seeking. METHOD: Population-based study with prospectively ascertained data from the Skåne Healthcare Register (SHR), Sweden, encompassing more than 15 million person-years of primary and specialist outpatient care and hospitalizations. We studied all Skåne region residents aged ≥45 by the end of 2012 (n = 531, 254) and determined the prevalence of doctor-diagnosed OA defined as the proportion of the prevalent population that had received a diagnosis of OA of the knee, hip, hand, or other locations except the spine between 1999 and 2012. We projected consultation prevalence of OA until year 2032 using Statistics Sweden's (SCB) projected age and sex structure and prevalence of overweight and obesity. RESULTS: In 2012 the proportion of population aged ≥45 with any doctor-diagnosed OA was 26.6% (95% confidence interval (CI): 26.5-26.8) (men 22.4%, women 30.5%). The most common locations were knee (13.8%), hip (5.8%) and hand (3.1%). Of the prevalent cases 26.8% had OA in multiple joints. By the year 2032, the proportion of the population aged ≥45 with doctor-diagnosed OA is estimated to increase from 26.6% to 29.5% (any location), from 13.8% to 15.7% for the knee and 5.8-6.9% for the hip. CONCLUSION: In 2032, at least an additional 26,000 individuals per 1 million population aged ≥45 years are estimated to have consulted a physician for OA in a peripheral joint compared to 2012. These findings underscore the need to address modifiable risk factors and develop new effective OA treatments.

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.

Extra-articular manifestations in a community-based sample of patients with rheumatoid arthritis: incidence and relationship to treatment with TNF inhibitors.

OBJECTIVES: To determine the incidence of severe extra-articular rheumatoid arthritis (ExRA) in a community-based cohort of RA patients, and to evaluate whether treatment with tumour necrosis factor (TNF) inhibitors has any effect on the risk of ExRA. METHODS: In a review of clinical records from 1 July 1997 to 31 December 2004, severe ExRA manifestations were classified according to predefined criteria. Patients were censored at the development of ExRA, death, emigration, or 31 December 2004. Exposure to anti-TNF treatment has continuously and independently been recorded as part of a regional follow-up system. RESULTS: During treatment with TNF inhibitors, there were two patients with new onset of ExRA in 408 person-years at risk (pyr) [0.49/100 pyr, 95% confidence interval (CI) 0.06-1.77]. Among those without anti-TNF treatment there were 63 patients with ExRA in 5425 pyr (1.16/100 pyr, 95% CI 0.89-1.49). The relative risk comparing those treated to those not treated with TNF inhibitors was 0.42 (95% CI 0.10-1.73). CONCLUSION: Our data show a lower incidence of ExRA in patients treated with TNF inhibitors but further studies with a larger sample size are needed for a more accurate estimate of the size of the effect.

Education and benchmarking among physicians may facilitate sick-listing practice.

INTRODUCTION: Assessing work ability and sickness certification are considered problematic by many physicians and education and implementation of guidelines to improve knowledge and skills has been requested. Our aim was to study the association between such interventions and physicians' sick-listing practices. METHODS: A web-based questionnaire was sent to all physicians working in primary care, psychiatry, orthopedics/rheumatology in the southern region of Sweden before (in 2007 to 1,063 physicians) and after (in 2009 to 1,164 physicians) educational interventions in insurance medicine were offered. RESULTS: With a response rate of 58%, half of the physicians (51%) reported to work at a clinic with a sick-listing policy in 2009 compared with 31% in 2007. Primary care physicians (OR 12.4) and physicians who had participated in educational interventions in insurance medicine (OR 2.4) more often had a sick-listing policy at the clinic. Physicians with a longer medical experience (OR 0.7) and those with support at the clinic (OR 0.3) and the possibility to extend time if needed (OR 0.4) were less likely to report of problematic cases while primary care physicians were (OR 2.9). On the contrary, physicians who reported to rarely have the possibility to extend time when handling problematic cases were more likely to issue a higher number of sickness certificates. CONCLUSIONS: The sick-listing process is often viewed as problematic and more often by primary care physicians. Benchmarking and education in insurance medicine together with the possibility to allocate extra time if encountering problematic cases may facilitate sick-listing practice.

Prevalence of spondyloarthritis and its subtypes in southern Sweden.

OBJECTIVE: To estimate the prevalence of spondyloarthritis and its subtypes. METHODS: The Swedish healthcare organisation comprises a system where all inpatient and outpatient care is registered by a personal identifier. For the calendar years 2003-7, all residents aged ≥ 15 years in the southernmost county of Sweden (1.2 million inhabitants) diagnosed by a physician with spondyloarthritis (ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory arthritis associated with inflammatory bowel disease (Aa-IBD) or undifferentiated spondylarthritis (USpA)) were identified. To obtain valid point estimates of prevalence by the end of 2007, identification numbers were cross-referenced with the population register to exclude patients who had died or relocated. RESULTS: The authors estimated the prevalence of spondyloarthritis (not including chronic reactive arthritis) as 0.45% (95% CI 0.44% to 0.47%). The mean (SD) age of patients with prevalent spondyloarthritis by the end of 2007 was 53 (15) years. Among the component subtypes, PsA accounted for 54% of cases, AS 21.4%, USpA 17.8% and Aa-IBD 2.3% with a prevalence of 0.25%, 0.12%, 0.10% and 0.015%, respectively. The remaining 6.4% had some form of combination of spondyloarthritis diagnoses. The prevalence of spondyloarthritis at large was about the same in men and women. However, the subtype PsA was more prevalent in women and AS was more prevalent in men. CONCLUSION: In Sweden the prevalence of spondyloarthritis leading to a doctor consultation is not much lower than rheumatoid arthritis. PsA was the most frequent subtype followed by AS and USpA, and the two most frequent subtypes PsA and AS also display some distinct sex patterns.

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.

The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of extra-articular disease and predicts radiographic progression of joint destruction over 5 years.

OBJECTIVE: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome. METHODS: In a cohort (n = 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0-448). RESULTS: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression. CONCLUSION: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage.

Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial.

BACKGROUND: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis. METHODS: We undertook a randomised trial in 15 rheumatology units in Sweden. We enrolled patients with early rheumatoid arthritis (symptom duration <1 year) and administered methotrexate (up to 20 mg per week). After 3-4 months, those who had not achieved low disease activity but who could tolerate methotrexate were randomly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab. Primary outcome was achievement of a good response according to European League Against Rheumatism (EULAR) criteria at 12 months. Patients were followed up to 24 months; here, we present findings at 12 months. Analysis was by intention to treat and we used non-responder imputation. The Swefot (Swedish Pharmacotherapy) study is registered in the WHO database at the Karolinska University Hospital, number CT20080004. FINDINGS: 487 patients were initially enrolled. Of 258 who had not achieved low disease activity with methotrexate, 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab. 32 of 130 (25%) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 (39%) assigned infliximab (risk ratio 1.59 [95% CI 1.10-2.30], p=0.0160). Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used. No deaths occurred in either group. INTERPRETATION: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. FUNDING: Swedish Rheumatism Association, Schering-Plough.

Rapid and sustained health utility gain in anti-tumour necrosis factor-treated inflammatory arthritis: observational data during 7 years in southern Sweden.

BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondylarthritides impose a great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry-independent health economic studies should complement studies sponsored by industry. OBJECTIVE: To study secular trends in baseline health utilities in patients commencing tumour necrosis factor (TNF) blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures and to compare them across diagnostic entities. METHODS: EuroQoL 5 dimensions (EQ-5D) utility data were collected from a structured clinical follow-up programme of anti-TNF-treated patients with RA (N = 2554), PsA (N = 574) or spondylarthritides (N = 586). Time trends were calculated. Completer analysis was used. RESULTS: There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and spondylarthritides. The maximum gain in utilities had already occurred after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. The first and second anti-TNF courses performed similarly. CONCLUSIONS: Utilities at inclusion remained largely unchanged for RA, PsA and spondylarthritides over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and spondylarthritides. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.

Natural course of knee osteoarthritis in middle-aged subjects with knee pain: 12-year follow-up using clinical and radiographic criteria.

OBJECTIVE: To explore the natural course of knee osteoarthritis (OA) in a middle-aged population with chronic knee pain. METHODS: A population-based sample of 143 subjects (mean age 45 (range 35-54), 44% women) with knee pain (>3 months) at inclusion was studied. Weight-bearing posteroanterior tibiofemoral (TF) radiographs were obtained at baseline and 12 years later, and classified according to Kellgren/Lawrence (K/L). Patellofemoral (PF) OA was determined at 5- and 12-years' follow-up using a skyline view and a cut-off point of <5 mm joint space width. The ACR clinical criteria were used at baseline. RESULTS: Seventy-six (53%) had no TF OA (K/L 0) at baseline, but 49 had clinical OA. Overall, 65/76 (86%) developed incident TF OA over 12 years (K/L >or=1): 44/49 (90%) of the subjects with clinical OA and 21/27 (78%) without clinical OA. Progression was found in 65/67 (97%) with TF OA at baseline. Of the 84 with no PF OA at the 5-year examination, 26 (31%) developed PF OA over 7 years. CONCLUSION: A majority of the subjects with chronic knee pain developed knee OA over 12 years. It is concluded that knee pain is often the first sign of knee OA.

Comorbidity between pain and mental illness - Evidence of a bidirectional relationship.

BACKGROUND: Pain from various locations in the body and mental illness are common and the comorbidity between the two is well-known although the temporal relationship remains to be determined. Our aim was to follow patients over time to study if pain (here dorsalgia/abdominal pain) or fibromyalgia lead to an increased risk of developing mental illness (here depression/anxiety) and/or the reverse, that is whether patients with mental illness have an increased risk to develop pain or fibromyalgia, compared to the rest of the population. METHODS: This prospective cohort study used the Skåne Healthcare Register, covering all care in the region of Skåne, southern Sweden (population ~1.3 million). The cohort included healthcare consultations in primary care, outpatient specialized care and inpatient care between 2007 and 2016 for all patients without prior registered diagnosis of mental illness or pain, aged 18 or older (n = 504,365). RESULTS: The incidence rate ratio (IRR) for developing mental illness after pain was 2.18 (95% CI = 2.14-2.22) compared to without pain. IRR for developing pain after mental illness was 2.02 (95% CI = 1.98-2.06) compared to without mental illness. Corresponding IRR for developing mental illness after fibromyalgia was 4.05 (95% CI = 3.58-4.59) and for developing fibromyalgia after mental illness 5.54 (95% CI = 4.99-6.16). CONCLUSIONS: This study shows a bidirectional influence of similar magnitude of pain and mental illness, respectively. In monitoring patients with pain or mental illness, a focus on both conditions is thus important to develop appropriate, targeted interventions and may increase the likelihood of improved outcomes. SIGNIFICANCE: We followed a population-based cohort over a period of 10 years, including incident cases of both exposure and outcome and found a bidirectional relationship between pain and mental illness. Clinicians need to pay attention on both conditions, in patients seeking care due to mental illness or pain.

Presence of peripheral arthritis and male sex predicting continuation of anti-tumor necrosis factor therapy in ankylosing spondylitis: an observational prospective cohort study from the South Swedish Arthritis Treatment Group Register.

OBJECTIVE: To examine clinical characteristics as possible predictors of long-term treatment continuation with adalimumab, etanercept, and infliximab in ankylosing spondylitis (AS) patients who had never taken biologics treated in clinical practice. METHODS: Patients in southern Sweden with active AS starting biologic therapy for the first time between October 1999 and December 2008 (n = 243, 75% men) were included in a structured clinical followup over 2 years. Patients with clinical spondylitis had not responded to at least 2 nonsteroidal antiinflammatory drugs, whereas patients who also had peripheral arthritis (n = 121) had additionally failed at least 1 conventional disease-modifying antirheumatic drug (DMARD) treatment course. The mean ± SD age at inclusion was 43 ± 12 years, with a mean ± SD disease duration prior to treatment of 16 ± 12 years. RESULTS: The 2-year drug continuation rate was 74%. Male sex (hazard ratio [HR] of premature discontinuation 0.36 [95% confidence interval (95% CI) 0.19-0.68]) and the presence of peripheral arthritis (HR 0.49 [95% CI 0.27-0.88]) were found to be significant predictors of better drug survival. Furthermore, a trend was seen for more favorable drug continuation on treatment with etanercept as compared with infliximab (HR 0.50 [95% CI 0.25-1.04], P = 0.062), whereas no differences were found comparing the 3 anti-tumor necrosis factor agents in other ways. Higher baseline C-reactive protein level (HR 0.99 [95% CI 0.97-1.00], P = 0.12) and concomitant treatment with nonbiologic DMARDs (HR 0.61 [95% CI 0.34-1.10], P = 0.10) also showed trends to entail better drug adherence. CONCLUSION: AS patients in this study have an excellent 2-year drug survival rate of 74%. Significant predictors for treatment continuation in this study were male sex and the presence of peripheral arthritis.

Smoking is a strong risk factor for rheumatoid nodules in early rheumatoid arthritis.

OBJECTIVE: To examine whether smoking is a risk factor for rheumatoid nodules in early rheumatoid arthritis, and if so to determine the quantitative effect of smoking. METHODS: From a cohort (n = 1589) in a structured programme for follow up of newly diagnosed cases of rheumatoid arthritis (symptoms of swollen joints < or =12 months), 112 individuals with rheumatoid nodules at inclusion were identified. Nodular patients were each compared with two age and sex matched controls without nodules from the same cohort. A detailed self administered tobacco use questionnaire was answered by 210 patients (63%). RESULTS: Seventy patients were current smokers, 71 former smokers, and 69 had never smoked. Current smoking and former smoking were more common in patients with rheumatoid nodules compared with controls (86% v 59%) in both sexes. Positive rheumatoid factor (RF) was found more often among cases with nodules than controls (78% v 64%). Using detailed information from the questionnaires with conditional logistic regression analyses, ever having smoked was associated with an increased risk of the presence of rheumatoid nodules (odds ratio (OR) = 7.3 (95% confidence interval, 2.3 to 23.6); p = 0.001). The risk of having nodules was not obviously dose dependent when smoking duration as well as smoking amount were examined. A stratified analysis showed that only RF positive smokers had an increased risk of rheumatoid nodules. Smoking was associated with rheumatoid nodules among both men (p = 0.006) and women (p = 0.001). Tobacco use other than smoking (n = 31) was not associated with an increased risk of nodules (OR = 0.8 (0.2 to 3.4); p = 0.813). CONCLUSIONS: There is a strong association between smoking and rheumatoid nodules in early seropositive rheumatoid arthritis.

Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with knee osteoarthritis or rheumatoid arthritis.

OBJECTIVE: To monitor changes in serum concentrations of cartilage oligomeric matrix protein (COMP) during a 24-h period to determine any diurnal variation, and to estimate the half life of COMP in the circulation in patients with symptomatic knee osteoarthritis and in those with rheumatoid arthritis. METHODS: Serum samples were drawn every 4 h (7 samples/patient over 24 h) in 10 patients with knee osteoarthritis and 14 patients with rheumatoid arthritis. Osteoarthritis was defined radiographically and clinically (American College of Rheumatology (ACR) criteria) and rheumatoid arthritis according to the 1987 ACR criteria. Serum COMP was measured by sandwich ELISA. A statistical model for the diurnal variation in the COMP levels was developed using the computer program NONMEM. RESULTS: No considerable changes in COMP levels were observed during the day between 08:00 and 21:00 in either group. A significant decrease in serum COMP was apparent during bed rest at night, reaching the lowest levels between 04:00 and 05:00 (p<0.03 or better v all other time points) in patients with osteoarthritis and in those with rheumatoid arthritis. From the rate of decreasing serum COMP levels, a putative half life of COMP in the circulation was estimated to be 7.4 h. CONCLUSION: During normal daytime activities, serum COMP levels are constant. The decrease during the night indicates a rapid elimination of COMP once it has reached the circulation. The stable COMP levels during the day suggest that it is not necessary to further standardise the time of serum sampling in clinical practice.