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.

Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthritis.

OBJECTIVE: To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. METHOD: Patients attending the Jyväskylä Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010-2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward's method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0-100), and total annual health service-related direct costs (€) as clustering variables. RESULTS: Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. CONCLUSIONS: The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.

Social relationships as predictors of extended employment beyond the pensionable age: a cohort study.

The aim is to examine whether characteristics of social relationships predict extended employment beyond the pensionable age among Finnish public sector workers. The study population consisted of 4014 participants (83% women, age 62.56 ± 1.21) of the Finnish Retirement and Aging Study followed between 2014 and 2019. Extended employment was defined as the difference between actual retirement date and individual age-related pensionable date and classified into three groups: no extension (retired on pensionable age or extended by < 3 months), short extension (3 months-< 1 year), and long extension (≥ 1 year) beyond the pensionable date. Characteristics of social relationships and engagement were assessed 18 months prior to the pensionable date. Social engagement was classified into consumptive social participation, formal social participation, informal social participation, and other social participation. Data were analyzed using multinomial regression analysis. Of total study participants, 17.8% belonged to short- and 16.5% belonged to long-extension group. Adjusted for age, occupational status, self-rated health and depression, and having a working spouse (OR 2.34, 95% CI 1.39-3.95) were associated with long extension of employment beyond the pensionable age when compared to no extension among men. Likewise, among women, living alone (OR 1.60, 95% CI 1.28-2.00), having a working spouse (1.85, 1.39-2.45), and high consumptive (1.32, 1.07-1.65), high formal (1.47, 1.17-1.85), and other social participation (0.79, 0.63-0.98) were associated with long extension. Having a working spouse, living alone, and high consumptive social participation were associated with short extension. Several characteristics of social relationships, such as having a working spouse, living alone, and high frequency of social engagement, predicted an extension of employment beyond the pensionable age. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10433-021-00603-z.

Social network ties before and after retirement: a cohort study.

Social networks are associated with individual's health and well-being. Working life offers opportunities to create and maintain social networks, while retirement may change these networks. This study examined how the number of ties in social network changes across the retirement transition. The study population consisted of 2319 participants (84% women, mean age 63.2 years) from the Finnish Retirement and Aging study. Information about social network ties, including the number of ties in the inner, middle and outer circles of the social convoy model, was gathered using annual postal surveys before and after retirement. Three repeat surveys per participant covered the retirement transition and the post-retirement periods. Mean number of network ties was 21.6 before retirement, of which 5.6 were situated in the inner, 6.9 in the middle and 9.1 in the outer circle. The number of ties in the outer circle decreased by 0.67 (95% CI - 0.92, - 0.42) during the retirement transition period, but not during the post-retirement period (0.11, 95% CI - 0.33, 0.12) (interaction period * time, p = 0.006). The pattern of change in these ties did not differ by gender, occupational status, marital status, number of chronic diseases and mental health during the retirement transition period. The number of ties in the inner and middle circles overall did not decrease during these periods. The number of peripheral relationships decreased during the retirement transition but not after that, suggesting that the observed reduction is more likely to be associated with retirement rather than aging.

Comparison of phosphor screen autoradiography and micro-pattern gas detector based autoradiography for the porosity of altered rocks.

This study aims to further develop the 14C-PMMA porosity calculation method with a novel autoradiography technique, the Micro-pattern gas detector autoradiography (MPGDA). In this study, the MPGDA is compared with phosphor screen autoradiography (SPA). A set of rock samples from Martinique Island exhibiting a large range of connected porosities was used to validate the MPGDA method. Calculated porosities were found to be in agreement with ones from the SPA and the triple-weight method (TW). The filmless nature of MPGDA as well as straightforward determination of C-14 radioactivity from the source rock makes the porosity calculation less uncertain. The real-time visualization of radioactivity from C-14 beta emissions by MPGDA is a noticeable improvement in comparison to SPA.

Mobility of daughter elements of 238U decay chain during leaching by In Situ Recovery (ISR): New insights from digital autoradiography.

In highly permeable sedimentary rock formations, U extraction by in-situ leaching techniques (ISR - In-Situ Recovery) is generally considered to have a limited environmental impact at ground level. Significantly, this method of extraction produces neither mill tailings nor waste rocks. Underground, however, the outcome for 238U daughter elements in aquifers is not well known because of their trace concentrations in the host rocks. Thus, understanding the in-situ mobility of these elements remains a challenge. Two samples collected before and after six months of ISR experiments (Dulaan Uul, Mongolia) were studied with the help of a digital autoradiography technique (DA) of alpha particles, bulk alpha spectrometry, and complementary petrographic observation methods. These techniques demonstrate that before and after leaching, the radioactivity is concentrated in altered and microporous Fe-Ti oxides. Most of the daughter elements of U remain trapped in the rock after the leaching process. DA confirms that the alpha activity of the Fe-Ti oxides remains high after uranium leaching, and the initial secular equilibrium of the 238U series for 230Th to 210Po daughter elements (including 226Ra) of the fresh rocks is maintained after leaching. While these findings should be confirmed by more systematic studies, they already identify potential mechanisms explaining why the U-daughter concentrations in leaching water are low.

Patients with rheumatic diseases share similar patterns of healthcare resource utilization.

Objectives: Healthcare service needs have changed with the use of effective treatment strategies. Using data from the modern era, we aimed to explore and compare health service-related direct costs in juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and axial spondyloarthritis (AxSpA). Methods: We linked a longitudinal, population-based clinical data set from Finland's largest non-university hospital's rheumatology clinic with an administrative database on health service-related direct costs in 2014. We compared all-cause costs and costs of comorbidities between adult patients with JIA, PsA, RA, and AxSpA (including ankylosing spondylitis). We also characterized patients with high healthcare resource utilization. Results: Cost distributions were similar between rheumatic diseases (p = 0.88). In adulthood, patients with JIA displayed a similar economic burden to much older patients with other inflammatory rheumatic diseases. A minority were high utilizers: among 119 patients with JIA, 15% utilized as much as the remaining 85%. For PsA (213 patients), RA (1086), and AxSpA (277), the high-utilization proportion was 10%. Both low and high utilizers showed rather low disease activity, but in high utilizers, the patient-reported outcomes were slightly worse, with the most distinct differences in pain levels. Of health service-related direct costs, index rheumatic diseases comprised only one-third (43.6% in JIA) and the majority were comorbidity costs. Conclusions: Patients with JIA, PsA, RA, and AxSpA share similar patterns of healthcare resource utilization, with substantial comorbidity costs and a minority being high utilizers. Innovations in meeting these patients' needs are warranted.

Healthcare costs and outcomes in adult patients with juvenile idiopathic arthritis: a population-based study.

OBJECTIVES: Evidence of the economic burden and long-term outcomes of juvenile idiopathic arthritis (JIA) remains scarce. Our aim was to explore healthcare costs and long-term outcomes in adult patients with JIA. METHOD: We identified all adult patients (≥ 18 years) with JIA who visited Jyväskylä Central Hospital rheumatology unit between May 2007 and March 2016. We considered individual medians of time-dependent clinical variables. These data were linked to administrative data from the area from the fiscal year 2014, which include information on all public healthcare contacts. Healthcare utilization is presented as direct costs in euros (EUR). Factors affecting direct costs were assessed with a generalized linear model. RESULTS: In 218 patients, median 28-joint Disease Activity Score with three variables (DAS28-3) was < 2.6 in 88.6% in those aged < 30 and in 72.9% in those aged ≥ 30 years, and median Health Assessment Questionnaire (HAQ) score was < 0.5 in 85.7% and 45.4%, respectively. In the utilization data (four municipalities, 137 patients), the total annual health services-related direct costs were 432 257 EUR (mean = 3155 EUR/patient/year). Thirty-six patients (26.3%) used biological disease-modifying anti-rheumatic drugs (bDMARDs) in 2014 for a total of 355 months, and the annual cost of bDMARDs was estimated at 355 000 EUR. Those with active disease had mean costs 2.4-fold higher than those with low or no disease activity. A one-point increase in median raw HAQ incurred an average 228 EUR increase in annual costs (p = 0.03). CONCLUSION: Most adult patients with JIA seem to manage well with their arthritis, bearing in mind that there still is room for improvement in long-term outcomes.

Validation of the Pain Coping Questionnaire in Finnish.

OBJECTIVE: The Pain Coping Questionnaire (PCQ), the first validated pain coping measurement developed specifically for children, has lacked proper validation in Finnish. The original PCQ by Reid et al. (Pain 1998; 76; 83-96) comprises eight-first-order and three higher-order scales. The aim herein was to determine the factor structure and validity of the Finnish PCQ translation in Finnish children. METHODS: Exploratory factor analysis was used for the first-order and higher-order classification of 91 recruited patients aged 8-15. Cronbach's alpha was used for reliability. Relationships between the Children's Depression Inventory, patient-reported pain frequency and pain coping strategies were examined. RESULTS: Analyses were executed with 38 items; one was excluded. A structure of eight-first-order (Internalizing/Catastrophizing [IC], Positive Self-Statements [PSS], Information Seeking [IS], Seeking Social Support [SSS], Cognitive Distraction [CD], Externalizing [EXT], Behavioural Distraction [BD], Problem Solving [PS]) and three higher-order scales (Approach [APP], Emotion-Focused Avoidance [EFA], Distraction [DIS]) proved the most consistent. Four first-order scales (PSS, CD, EXT, BD) emerged as identical to the original solution. Internal consistency reliability coefficients for all individual first- and second-order scales were satisfactory. A higher CDI score was positively related to EFA and negatively to DIS, and pain frequency positively related to APP and EFA. CONCLUSION: The exploratory factor analysis of the PCQ provided a both culturally and statistically satisfactory structure in the Finnish translation. This supports the reliability and validity of the PCQ in future national use and the value of the questionnaire also outside English-speaking countries. SIGNIFICANCE: This study showed both culturally and statistically satisfactory factor structure of PCQ in the Finnish translation. This result supports reliability and validity of the PCQ in the national use in the future. The result shows that the PCQ is a reliable method to be used in different linguistic and cultural surroundings and, thus, encourages using it in various countries. The data consist of two patient groups, adolescents with JIA and musculoskeletal pain. Pain and specifically coping with pain are important aspects of clinical work. A valid pain coping scale may enhance distinguishing vulnerable pain coping style in children and adolescent before pain becomes chronic.

Imaging connected porosity of crystalline rock by contrast agent-aided X-ray microtomography and scanning electron microscopy.

We set out to study connected porosity of crystalline rock using X-ray microtomography and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) with caesium chloride as a contrast agent. Caesium is an important radionuclide regarding the final deposition of nuclear waste and also forms dense phases that can be readily distinguished by X-ray microtomography and SEM-EDS. Six samples from two sites, Olkiluoto (Finland) and Grimsel (Switzerland), where transport properties of crystalline rock are being studied in situ, were investigated using X-ray microtomography and SEM-EDS. The samples were imaged with X-ray microtomography, immersed in a saturated caesium chloride (CsCl) solution for 141, 249 and 365 days and imaged again with X-ray microtomography. CsCl inside the samples was successfully detected with X-ray microtomography and it had completely penetrated all six samples. SEM-EDS elemental mapping was used to study the location of caesium in the samples in detail with quantitative mineral information. Precipitated CsCl was found in the connected pore space in Olkiluoto veined gneiss and in lesser amounts in Grimsel granodiorite. Only a very small amount of precipitated CsCl was observed in the Grimsel granodiorite samples. In Olkiluoto veined gneiss caesium was found in pinitised areas of cordierite grains. In the pinitised areas caesium was found in notable excess compared to chloride, possibly due to the combination of small pore size and negatively charged surfaces. In addition, elevated concentrations of caesium were found in kaolinite and sphalerite phases. The findings concerning the location of CsCl were congruent with X-ray microtomography.

Three out of four disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients meet 28-joint Disease Activity Score remission at 12 months: results from the FIN-ERA cohort.

OBJECTIVE: To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland. METHOD: Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function. RESULTS: In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment. CONCLUSION: Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Drug survival on tumour necrosis factor inhibitors in patients with rheumatoid arthritis in Finland.

OBJECTIVE: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1 year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA. METHODS: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36 months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12 months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy. CONCLUSIONS: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

Psychiatric and cardiovascular comorbidities as causes of long-term work disability among individuals with recent-onset rheumatoid arthritis.

OBJECTIVES: With the ameliorating prognosis of rheumatoid arthritis (RA), the role of comorbidities as causes of work disability (WD) may increase. The aim of this study was to determine the contribution of psychiatric and cardiovascular (CV) comorbidities as the leading causes of long-term WD among patients with recent-onset RA. METHOD: Between 2000 and 2007, all incident, working-age and non-retired RA patients were identified from a Finnish nationwide register. From other registers, we identified the RA patients who were granted a permanent or temporary disability pension by 31 December 2008. The incidences of disability pensions with CV diseases (ICD-10 codes I00-I99) or psychiatric disorders (F20-F69) as the leading causes were assessed and compared with the general population. RESULTS: We identified a cohort of 7831 patients with RA. During follow-up, 1095 patients were granted a disability pension. After adjusting for competing risks, the 9-year cumulative incidence of WD caused by RA, a psychiatric comorbidity, or a CV disease was 11.9, 1.3, and 0.5%, respectively. Compared to the general population, the age- and sex-specific standardized incidence ratio (SIR) of WD due to psychiatric comorbidities was 0.99 [95% confidence interval (CI) 0.80-1.23] and due to CV disease 1.75 (95% CI 1.23-2.51). CONCLUSIONS: In the study cohort with recent-onset RA, the 9-year cumulative incidence of disability pensions caused by psychiatric or CV comorbidities was only 11% or 4%, respectively, of that caused by RA itself. Compared to the general population, the risk of WD due to CV disease was increased.

Fall-related risk factors and heel quantitative ultrasound in the assessment of hip fracture risk: a 10-year follow-up of a nationally representative adult population sample.

UNLABELLED: Maximal walking speed and quantitative ultrasound index (QUI) were significant and independent predictors of hip fracture among subjects aged ≥ 55 years. A model including readily available variables along with simple fall-related factors may be clinically useful in the assessment of hip fracture risk even without a QUI measurement. INTRODUCTION: This study assessed fall-related risk factors along with heel bone quantitative ultrasound (QUS) measurements for the prediction of hip fracture during a mean follow-up of 9.8 years in a nationally representative population sample. METHODS: The study population consisted of 2,300 subjects (1,331 women and 969 men) aged 55 years or over, who had participated in a comprehensive health survey in 2000-2001. Information on the subjects' health and fall-related risk factors was obtained with interviews, questionnaires and tests carried out by specially trained professionals. QUS measurements were made by means of the Hologic Sahara device. First emerging cases of hip fracture were identified from the National Hospital Discharge Register. RESULTS: During the follow-up, 96 subjects sustained a hip fracture. Slow maximal walking speed, low quantitative ultrasound index (QUI), high age, tallness, short waist circumference, Parkinson's disease and the number of central nervous system active medication were significant and independent predictors of hip fracture. The model including all of these risk factors explained 68 % of the variation in hip fracture risk. Excluding QUI from this model reduced the percentage to 66%. CONCLUSIONS: Maximal walking speed and QUI were significant and independent predictors of hip fracture. A model including readily available variables such as age, gender, height and waist circumference along with simple fall-related factors may be of clinical use in the assessment of hip fracture risk even without a QUS measurement.

Quantitative ultrasound measurements and vitamin D status in the assessment of hip fracture risk in a nationally representative population sample.

SUMMARY: Adjusted for age, gender, height and weight, calcaneal quantitative ultrasound (QUS) and serum 25-hydroxyvitamin D (S-25(OH)D) proved to be significant predictors of hip fracture among subjects aged ≥50 years. Even if their contribution to the predictive power was modest, they may be useful in the assessment of hip fracture risk in the elderly. INTRODUCTION: This study assessed calcaneal QUS measurements, S-25(OH)D and several other factors for the prediction of hip fracture risk in a nationally representative population sample. METHODS: The study population consisted of 3,305 subjects (1,872 women), aged 50 years or over, who had participated in a comprehensive health survey. QUS measurements were made by means of the Hologic Sahara device. S-25(OH)D was measured by radioimmunoassay. Emerging cases of hip fracture were identified from the National Hospital Discharge Register. RESULTS: During a mean follow-up of 8.4 years, 95 subjects sustained a hip fracture. After adjusting for age, gender, height, weight and each other, a 1 standard deviation increment in the quantitative ultrasound index (QUI) (21.7) and in S-25(OH)D (17.5 nmol/L) reduced the risk of hip fracture by 40 % (hazard ratio [HR] = 0.60, 95 % confidence interval [CI] = 0.42-0.86) and by 31 % (HR = 0.69, 95 % CI = 0.55-0.87), respectively. The predictive power of a model including age, gender, height and weight was improved by about 8 % after the addition of QUI and S-25(OH)D. Among subjects aged 75 years or over, the corresponding improvement was about 130 %. CONCLUSIONS: QUI and S-25(OH)D were significant and independent predictors of hip fracture. However, their ability to increase the predictive power of a statistical model including readily available simple variables such as age, gender, height and weight was rather modest. Still, our findings suggest that QUI and S-25(OH)D may be of clinical use in the assessment of hip fracture risk particularly in the elderly.

Cost-effectiveness modelling of sequential biologic strategies for the treatment of moderate to severe rheumatoid arthritis in Finland.

OBJECTIVE: The main objective was to compare the cost-effectiveness of therapeutic options in moderate or severe rheumatoid arthritis (RA) when a clinical response to a first TNF-blocker, either etanercept (ETA), adalimumab (ADA), or infliximab (INF), is insufficient. METHODS: Effectiveness criteria were defined as remission (RS), low disease activity (LDAS), and moderate to high disease activity (MHDAS). Cost-effectiveness was derived as cost per day in RS and in LDAS using simulation modelling to assess six sequential biologic strategies over 2 years. Each sequential treatment strategy was composed of three biologic agents and included a first anti-TNF agent, ETA, ADA or INF, followed by either abatacept (ABA) or rituximab (RTX) as a second therapeutic option in case of an insufficient response, followed by another anti-TNF agent in case of further insufficient response. RESULTS: Over two years and taking into account biologic costs, the following estimated mean costs per day in RS and LDAS were respectively of €829 and €428 for the biologic sequence composed of ADA-ABA-ETA, €1292 and €516 for the sequence ADA-RTX-ETA, €829 and €429 for the sequence ETA-ABA-ADA, €1292 and €517 for the sequence ETARTX- ADA, €840 and €434 for the sequence INF-ABA-ETA, and €1309 and €523 for the sequence INF-RTX-ETA. CONCLUSION: The treatment sequences including ABA as the second biologic option appear more cost-effective than those including RTX in a patients with moderate to severe RA and an insufficient response to a first anti-TNF agent.

Cost-effectiveness of adalimumab, etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis.

OBJECTIVE: The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland. RESEARCH DESIGN AND METHODS: The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed. MAIN OUTCOME MEASURES: Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI). RESULTS: bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60-93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230-2182). CONCLUSIONS: Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values. LIMITATIONS: Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.

Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis.

OBJECTIVE: To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis. METHODS: Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls. RESULTS: The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP). CONCLUSIONS: The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.