A validation of register-derived diagnoses of interstitial lung disease in patients with inflammatory arthritis: data from the NOR-DMARD study.

OBJECTIVE: There is a lack of knowledge concerning the validity of the interstitial lung disease (ILD) diagnoses used in epidemiological studies on rheumatic diseases. This paper seeks to verify register-derived ILD diagnoses using chest computed tomography (CT) and medical records as a gold standard. METHOD: The Norwegian Anti-Rheumatic Drug Register (NOR-DMARD) is a multicentre prospective observational study of patients with inflammatory arthritis who start treatment with disease-modifying anti-rheumatic drugs. NOR-DMARD is linked to the Norwegian Patient Registry (NPR) and Cause of Death Registry. We searched registers for ILD coded by ICD-10 J84 or J99 among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. We extracted chest CT reports and medical records from participating hospitals. Two expert thoracic radiologists scored examinations to confirm the ILD diagnosis. We also searched medical records to find justifications for the diagnosis following multidisciplinary evaluations. We calculated the positive predictive values (PPVs) for ILD across subsets. RESULTS: We identified 71 cases with an ILD diagnosis. CT examinations were available in 65/71 patients (91.5%), of whom ILD was confirmed on CT in 29/65 (44.6%). In a further 10 patients, medical records confirmed the diagnosis, giving a total of 39/71 verified cases. The PPV of a register-derived ILD diagnosis was thus 54.9%. In a subset of patients who had received an ILD code at two or more time-points and had a CT scan taken within a relevant period, the PPV was 72.2%. CONCLUSION: The validity of register-based diagnoses of ILD must be carefully considered in epidemiological studies.

Psoriatic arthritis, axial spondyloarthritis and rheumatoid arthritis in Norway: nationwide prevalence and use of biologic agents.

OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA) and the use of biologic agents in these diseases in Norway. METHODS: From the Norwegian Patient Registry (NPR), we identified as PsA, axSpA and RA patients ≥18 years those with ≥2 recorded episodes with diagnostic coding for index disease (L40.5, M07.0-M07.3 for PsA; M45, M46.0, M46.1, M46.8 and M46.9 for axSpA; M05-M06 for RA). We calculated the point prevalence of PsA, axSpA and RA as per the 1st of January 2017 in the Norwegian adult population (age ≥18). Dispensed disease-modifying antirheumatic drug (DMARD) prescriptions were obtained from the Norwegian Prescription Database and biologic DMARDs given in hospitals from the NPR. RESULTS: The point prevalence of PsA, axSpA, RA, and any of these diseases in total was 0.46%, 0.41%, 0.78%, and 1.56%, respectively. Among women, the prevalence of PsA, axSpA, and RA was 0.50%, 0.37%, and 1.10%, and among men 0.43%, 0.45%, and 0.46%, respectively. In 2017, 27.3% of RA patients, 25.7% of PsA patients and 35.1% of axSpA patients used biologic DMARDs. Treatment with biologics was more frequent in younger age groups in all three diseases, and became more infrequent especially after age ≥55 years. CONCLUSION: In Norway, the combined prevalence of PsA, axSpA, and RA was over 1.5%. Reflecting the good overall access to highly effective but costly biologic treatments, more than a fourth of these patients used biologic agents, which corresponds to over 0.4% of Norwegian adult population.

Beliefs about medicines in gout patients: results from the NOR-Gout 2-year study.

OBJECTIVE: Adherence to urate-lowering therapy (ULT) in gout is challenging. This longitudinal study aimed to determine 2 year changes in beliefs about medicines during intervention with ULT. METHOD: Patients with a recent gout flare and increased serum urate received a nurse-led ULT intervention with tight control visits and a treatment target. Frequent visits at baseline and 1, 2, 3, 6, 9, 12, and 24 months included the Beliefs about Medicines Questionnaire (BMQ), and demographic and clinical variables. The BMQ subscales on necessity, concerns, overuse, harm, and the necessity-concerns differential were calculated as a measure of whether the patient perceived that necessity outweighed concerns. RESULTS: The mean serum urate reduced from 500 mmol/L at baseline to 324 mmol/L at year 2. At years 1 and 2, 85.5% and 78.6% of patients, respectively, were at treatment target. The 2 year mean ± sd BMQ scores increased for the necessity subscale from 17.0 ± 4.4 to 18.9 ± 3.6 (p < 0.001) and decreased for the concerns subscale from 13.4 ± 4.9 to 12.5 ± 2.7 (p = 0.001). The necessity-concerns differential increased from 3.52 to 6.58 (p < 0.001), with a positive change independent of patients achieving treatment targets at 1 or 2 years. BMQ scores were not significantly related to treatment outcomes 1 or 2 years later, and achieving treatment targets did not lead to higher BMQ scores. CONCLUSION: Patient beliefs about medicines improved gradually over 2 years, with increased beliefs in the necessity of medication and reduced concerns, but this improvement was unrelated to better outcomes. TRIAL REGISTRATION: ACTRN12618001372279.

Serum golimumab concentration and anti-drug antibodies are associated with treatment response and drug survival in patients with inflammatory joint diseases: data from the NOR-DMARD study.

Objectives: This study aimed to identify the therapeutic target concentration and frequency of anti-drug antibodies (ADAbs) in golimumab-treated patients with inflammatory joint disease (IJD).Method: Associations between golimumab concentration, ADAbs, and treatment response were examined in 91 patients with IJD [41 axial spondyloarthritis (axSpA), 20 rheumatoid arthritis (RA), and 30 psoriatic arthritis (PsA)] included in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement in axSpA, European League Against Rheumatism (EULAR) good/moderate response in RA, and improvement of ≥ 50% in modified Disease Activity index for PSoriatic Arthritis (DAPSA) (28 swollen/tender joint counts) in PsA. Serum drug concentrations and ADAbs were analysed using automated in-house assays.Results: At inclusion, 42% were biological disease-modifying anti-rheumatic drug naïve and 42% used concomitant synthetic disease-modifying anti-rheumatic drug. The median golimumab concentration was 2.2 (interquartile range 1.0-3.5) mg/L. The proportions of responders after 3 months among patients with golimumab concentration < 1.0, 1.0-3.9, and ≥ 4.0 mg/L were 19%, 49%, and 74%, respectively. A higher rate of treatment discontinuation was seen in patients with serum golimumab concentration < 1.0 compared to ≥ 1.0 mg/L (hazard ratio 3.3, 95% confidence interval 1.8-6.0, p < 0.05). ADAbs were detected in 6%, and were associated with lower drug concentrations and both reduced treatment response and drug survival.Conclusions: Golimumab concentrations ≥ 1.0 mg/L were associated with improved treatment response and better drug survival, although some patients may benefit from higher concentrations. This study suggests a rationale for dosing guided by therapeutic drug monitoring in golimumab-treated patients with IJD. The results should be confirmed in larger studies including trough samples, and the efficacy of such a strategy must be examined in randomized controlled trials.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Smoking and response to rituximab in rheumatoid arthritis: results from an international European collaboration.

OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries.

OBJECTIVES: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. METHOD: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. RESULTS: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). CONCLUSION: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Frequency of temporomandibular joint osteoarthritis and related symptoms in a hand osteoarthritis cohort.

OBJECTIVE: The prevalence of osteoarthritis (OA) in the temporomandibular joints (TMJs) in hand OA patients is largely unknown. Our aims were to explore (1) The frequency of TMJ-related symptoms and clinical findings; (2) The TMJ OA frequency defined by cone beam computed tomography (CBCT); and (3) The relationship between TMJ-related symptoms/clinical findings and CBCT-defined TMJ OA, in a hand OA cohort. METHODS: We calculated the frequencies of TMJ-related symptoms, clinical findings and diagnosis of TMJ OA by CBCT and clinical examination in 54 patients from the Oslo hand OA cohort (88% women, mean (range) age 71 (61-83) years). Participants with and without CBCT-defined TMJ OA were compared for differences in proportions (95% confidence interval (CI)) of symptoms and clinical findings. Sensitivity and specificity of the clinical TMJ OA diagnosis were calculated using CBCT as reference. RESULTS: Self-reported symptoms and clinical findings were found in 24 (44%) and 50 (93%) individuals (93%), respectively, whereas 7 (13%) had sought healthcare. Individuals with CBCT-defined TMJ OA (n = 36, 67%) reported statistically significantly more pain at mouth opening (22%, 95% CI 4-40%), clicking (33%, 95% CI 14-52%) and crepitus (25%, 95% CI 4-46%). By clinical examination, only crepitus was more common in TMJ OA (33%, 95% CI 29-77%). Clinical diagnosis demonstrated low sensitivity (0.42) and high specificity (0.93). CONCLUSIONS: CBCT-defined TMJ OA was common in hand OA patients, suggesting that TMJ OA may be part of generalized OA. Few had sought healthcare, despite high burden of TMJ-related symptoms/findings. Clinical examination underestimated TMJ OA frequency.

Sleep disturbance in patients with rheumatoid arthritis is related to fatigue, disease activity, and other patient-reported outcomes.

OBJECTIVES: To explore factors related to sleep disturbance in patients with rheumatoid arthritis (RA). METHOD: Cross-sectional data from 986 patients in the Oslo RA Register (ORAR) collected in 2009 were included. Sleep problems were assessed by four measures: the Medical Outcomes Study (MOS) sleep disturbance scale, and the sleep components of the Rheumatoid Arthritis Impact of Disease (RAID) score, the Multi-Dimensional Health Assessment Questionnaire (MDHAQ), and the 15-dimensional quality of life questionnaire (15D). Patient-reported outcomes (PROs) were recorded using standard questionnaires for physical and mental function [the HAQ and the MOS 36-item Short-Form Health Survey (SF-36), disease activity (the RA Disease Activity Index, RADAI), utility (SF-6D), and visual analogue scales (VAS) for pain, fatigue, and disease activity]. Demographics including comorbidity were collected. Information on use of medication for RA and sleep disturbance was obtained using checklists. Multivariate analyses were used to identify factors independently associated with sleep problems by four different measures. RESULTS: The mean (standard deviation, SD) age of the patients was 59.4 (12.5) years, 76.9% were females, and the mean (SD) disease duration was 13.7 (10.7) years. The correlation between the various sleep measures was high (r2 = 0.71-0.78). Sleep disturbance was moderately correlated to pain (r2 = 0.41-0.61), fatigue (r2 = 0.44-0.58), physical function (r2 = 0.33-0.48), RADAI (r2 = 0.42-0.55), and utility (r2 = 0.49-0.61). RAID sleep demonstrated the highest correlation with other PROs. RADAI, fatigue, the mental component score of SF-36, physical function, body mass index (BMI), and use of Z-drugs/benzodiazepines were independently associated with two or more measures of sleep problems (all p < 0.001). CONCLUSIONS: Sleep disturbance measured by four different measures was independently related to other PROs including fatigue, pain, and disease activity in RA patients.

Smoking and alcohol use are associated with structural and inflammatory hand osteoarthritis features.

OBJECTIVES: To explore whether smoking and alcohol use are associated with hand osteoarthritis (OA) features in two different OA cohorts. METHOD: We studied 530 people with radiographic hand OA from the Musculoskeletal pain in Ullensaker STudy (MUST) and 187 people from the Oslo hand OA cohort [mean (sd) age 65 (8.0) and 62 (5.7) years, 71% and 91% women, respectively]. Smoking, alcohol use and hand pain were self-reported. Participants underwent conventional hand radiographs and ultrasound examination of 30 hand joints. The Kellgren-Lawrence sum score for radiographic OA severity (0-120 scale) and the proportion of participants having at least one joint with grey-scale synovitis (grade ≥1) were calculated. We studied whether smoking and alcohol use were cross-sectionally associated with radiographic OA, synovitis, and pain using adjusted linear and logistic regression analyses. RESULTS: Smoking was associated with less radiographic OA in both cohorts [ß = -4.71, 95% confidence interval (CI) -8.36 to -1.06 for current smoking in MUST and ß = -0.15, 95% CI -0.29 to -0.02 for smoking pack-years in the Oslo hand OA cohort]. Stratified analyses indicated that the association was present in men only. Being a monthly drinker (examined in MUST only) was significantly associated with present synovitis compared to never drinkers (odds ratio = 2.35, 95% CI 1.27 to 4.34) (no gender differences). Neither smoking nor alcohol was associated with hand pain. CONCLUSIONS: Smoking was associated with less radiographic hand OA whereas alcohol consumption was associated with present joint inflammation in hand OA. Future longitudinal studies are needed to explore the causal associations and explanatory mechanisms behind gender differences.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Synovitis and radiographic progression in non-erosive and erosive hand osteoarthritis: is erosive hand osteoarthritis a separate inflammatory phenotype?

OBJECTIVE: To compare the prevalence of synovitis, pain and radiographic progression in non-erosive and erosive hand osteoarthritis (HOA), and to explore whether the different rate of disease progression is explained by different levels of synovitis and structural damage. DESIGN: We included 31 and 34 participants with non-erosive and erosive HOA at baseline, respectively. Using Generalized Estimating Equations, we explored whether participants with erosive HOA had more synovitis (by MRI, ultrasound and clinical examination) independent of the degree of structural damage. Similarly, we explored whether pain at baseline and radiographic progression after 5 years were higher in erosive HOA, independent of the levels of synovitis and structural damage. All analyses were adjusted for age and sex. RESULTS: Power Doppler activity was found mainly in erosive HOA. Participants with erosive HOA demonstrated more moderate-to-severe synovitis, assessed by MRI (OR = 1.73, 95% CI 1.11-2.70), grey-scale ultrasound (OR = 2.02, 95% CI 1.25-3.26) and clinical examination (OR = 1.80, 95% CI 1.44-2.25). The associations became non-significant when adjusting for more structural damage. The higher frequency of joint tenderness in erosive HOA was at least partly explained more structural damage and inflammation. Radiographic progression (OR = 2.53, 95% CI 1.73-3.69) was more common in erosive HOA independent of radiographic HOA severity and synovitis (here: adjusted for grey-scale synovitis by ultrasound). CONCLUSION: Erosive HOA is characterized by higher frequency and more severe synovitis, pain and radiographic progression compared to non-erosive HOA. The higher rate of disease progression was independent of baseline synovitis and structural damage.

Health status has improved more in women than in men with rheumatoid arthritis from 1994 to 2009: results from the Oslo rheumatoid arthritis register.

OBJECTIVE: To examine changes in patient reported outcome measures (PROs) over 15 years in a representative population of patients with rheumatoid arthritis (RA), with a particular focus on gender differences. PATIENTS AND METHODS: Patients in the Oslo RA register filled in questionnaires including the Modified Health Assessment Questionnaire (MHAQ), the Short-Form 36 (SF-36) with physical (PCS) and mental component summaries and derived utility (SF-6D), visual analogue scales (VAS) for pain, patient global assessment of disease (PtGA) and fatigue, and checklists of medication commonly used in the treatment of RA. Data were collected at five time points during a 15-year period from 1994. Mixed model analyses were used to analyse longitudinal changes in PROs from 1994 to 1996, 2001, 2004 and 2009. RESULTS: Data were available from 829-1025 RA patients at each time point. PROs were statistically significantly improved from 1994 to 2009 (MHAQ, SF-36 PCS, SF-6D, pain VAS, PtGA VAS and fatigue VAS; all p<0.001), and also with clinically important improvement. Men reported significantly better health status than women in 1994, but women improved significantly more than men over 15 years with a reduction of the gender gap in 2009. Antirheumatic medication was increasingly used over 15 years with no gender differences. CONCLUSIONS: RA patients reported statistically significantly improved health status for most PROs from 1994 to 2009. Women improved most, and although they still reported higher disease impact than men, the gender differences were small at the final data collection in 2009.

Systemic inflammation in patients with inflammatory joint diseases does not influence statin dose needed to obtain LDL cholesterol goal in cardiovascular prevention.

OBJECTIVES: There is a lipid paradox in rheumatoid arthritis describing that despite low lipids related to systemic inflammation, there is an increased cardiovascular (CV) risk. Our aim was to evaluate if baseline lipid levels or baseline systemic inflammation were associated with the statin dose sufficient to achieve lipid targets in patients with inflammatory joint diseases. METHODS: In this longitudinal, short-term follow-up observational report, we evaluated 197 patients who did and 36 patients who did not reach the recommended low density lipoprotein cholesterol (LDL-c) target. The patients were, after CV risk evaluation, classified to either primary or secondary CV prevention with lipid lowering treatment (LLT). LLT was initiated with statins and adjusted until at least two lipid targets were achieved. Intensive LLT was defined as rosuvastatin ≥20 mg, atorvastatin and simvastatin at the highest dose (80 mg), and conventional LLT were defined as all lower doses. RESULTS: In an independent sample t test, systemic inflammation or lipid levels at baseline were not associated with the statin dose (intensive or conventional) needed to achieve recommended LDL-c target (C reactive protein/erythrocyte sedimentation rate: p=0.10 and p=0.11, and LDL-c/total cholesterol: p=0.17 and p=0.34, respectively). The baseline inflammatory status and lipid levels in patients who did and did not obtain LDL-c goal were comparable (C reactive protein/erythrocyte sedimentation rate: p=0.32 and p=0.64, and LDL-c/total cholesterol: p=0.20 and p=0.83, respectively). CONCLUSIONS: Systemic inflammation or lipid levels did not influence the intensity of statin treatment needed to obtain guideline recommended lipid targets in CV prevention. Whether the background inflammation in patients with inflammatory joint diseases over time influences the CV risk reduction related to statins is yet unknown.

Body mass index and progressive hand osteoarthritis: data from the Oslo hand osteoarthritis cohort.

OBJECTIVES: Few longitudinal studies have studied the association between body mass index (BMI) and hand osteoarthritis (OA). We aimed to explore the association between BMI and progressive hand OA in a longitudinal study of the Oslo hand OA cohort. METHOD: Participants with existing hand OA had hand radiographs and BMI data taken at baseline and 7-year follow-up (n = 103). The radiographs were read according to the Kellgren-Lawrence (KL) scale. First, we examined the association between baseline BMI and incident OA (KL grade ≥ 2) in joints without OA at baseline (adjusted for age and sex) using generalized estimating equation (GEE) analyses. Second, we examined whether changes in BMI from baseline to follow-up were associated with increasing KL sum score from baseline to follow-up using linear regression. We repeated the analyses using changes in number of joints with symptomatic OA and patient-reported pain and physical function as the outcome. RESULTS: The mean (SD) age at baseline was 61.6 (5.6) years and 91 (94%) of the cohort were women. The mean (SD) BMI was 25.7 (4.0) kg/m(2) at baseline and the mean (SD) BMI change was 1.1 (2.0) kg/m(2). There was no relationship between baseline BMI and development of more joints with OA during follow-up. Similarly, there was no association between change in BMI and hand OA progression, increasing hand pain or disability. CONCLUSIONS: In the Oslo hand OA cohort, higher BMI was not related to hand OA progression.

Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: a cross-sectional comparative study.

OBJECTIVES: Insight into the most important inflammatory pathways in ankylosing spondylitis (AS) could be of importance in risk stratification and the development of treatment strategies. Therefore, we aimed to compare circulating levels of inflammatory biomarkers between AS patients and controls, and explore associations between these biomarkers and clinical measures of disease activity. METHOD: In a cross-sectional study, 143 AS patients were compared with 124 population controls. Blood samples were analysed by immunoassays for interleukin (IL)-6, IL-17a, IL-23, soluble tumour necrosis factor receptor 1 (sTNF-R1) and 2 (sTNF-R2), and osteoprotegerin (OPG). Disease activity was measured by the AS Disease Activity Score (ASDAS) and the Bath AS Disease Activity Index (BASDAI). RESULTS: Analysis of covariance (ANCOVA) demonstrated elevated plasma levels of sTNF-R1 [geometrical mean 0.94 (95% CI 0.88-1.00) vs. 0.83 (95% CI 0.78-0.89) ng/mL, p < 0.01] and OPG (2.3, 95% CI 2.1-2.4 vs. 2.0, 95% CI 1.9-2.2 ng/mL, p = 0.02) and, although not significant, of IL-23 (122, 95% CI 108-139 vs. 106, 95% CI 93-120 pg/mL, p = 0.07) in AS patients vs. CONTROLS: More AS patients had a high level of sTNF-R2 than controls (22 vs. 1, p < 0.01). No differences between the groups were seen for IL-6 and IL-17a. In patients, no significant associations were seen between inflammatory markers and disease activity measures after adjusting for personal characteristics. CONCLUSION: Significantly higher plasma levels of sTNF-R1, sTNF-R2, and OPG and numerically but non-significantly higher levels of IL-23 were found in AS patients compared to controls, indicating that these cytokines and cytokine receptors are important inflammatory pathways. Clinical measures of disease activity were not significantly correlated with circulating inflammatory markers.

Treating axial and peripheral spondyloarthritis, including psoriatic arthritis, to target: results of a systematic literature search to support an international treat-to-target recommendation in spondyloarthritis.

BACKGROUND: Current recommendations for the management of axial spondyloarthritis (SpA) and psoriatic arthritis are to monitor disease activity and adjust therapy accordingly. However, treatment targets and timeframes of change have not been defined. An international expert panel has been convened to develop 'treat-to-target' recommendations, based on published evidence and expert opinion. OBJECTIVE: To review evidence on targeted treatment for axial and peripheral SpA, as well as for psoriatic skin disease. METHODS: We performed a systematic literature search covering Medline, Embase and Cochrane, conference abstracts and studies in http://www.clinicaltrials.gov. RESULTS: Randomised comparisons of targeted versus routine treatment are lacking. Some studies implemented treatment targets before escalating therapy: in ankylosing spondylitis, most trials used a decrease in Bath Ankylosing Spondylitis Disease Activity Index; in psoriatic arthritis, protocols primarily considered a reduction in swollen and tender joints; in psoriasis, the Modified Psoriasis Severity Score and the Psoriasis Area and Severity Index were used. Complementary evidence correlating these factors with function and radiographic damage at follow-up is sparse and equivocal. CONCLUSIONS: There is a need for randomised trials that investigate the value of treat-to-target recommendations in SpA and psoriasis. Several trials have used thresholds of disease activity measures to guide treatment decisions. However, evidence on the effect of these data on long-term outcome is scarce. The search data informed the expert committee regarding the formulation of recommendations and a research agenda.

NOR-DMARD data management: implementation of data capture from electronic health records.

OBJECTIVES: The use of electronic health records (EHR) is an essential part of modern health care, and electronic data capture (EDC) has become essential for managing clinical trials. Usually, these two entities are independent of each other, and transfer from one system to another is done manually. Our aim was to develop a method to capture data directly from the EHR system and transfer them into an EDC system for the NORwegian Disease-Modifying Anti-Rheumatic Drugs (NOR-DMARD) registry. METHODS: All rheumatology departments contributing to NOR-DMARD had implemented a structured EHR system. Data are extracted locally and securely transferred to the study data management once a month. The study data management then parse the data into a readable format for the EDC and import the data. Once the data is in the EDC, they are available to all authorized researchers and downloadable in a preferred format. RESULTS: From May 2012 to August 2014 almost 6400 visits in 3400 patients treated with biologics have been successfully registered in the EDC system. Previously, NOR-DMARD used standard paper-based case report forms (CRFs), with a substantial cost for data entry. Setting up and maintaining the EDC system required some investments, but the amount saved from avoiding paper handling has made the shift into EDC profitable. In addition to this, gains have been made in administration and data quality. CONCLUSIONS: The transition from paper and pencil format to a fully electronic data management system in NOR-DMARD has had obvious advantages regarding feasibility, cost, data quality and accessibility of the data.