The direct and indirect costs of axial spondyloarthritis (axSpA) in Singapore.

OBJECTIVE: To estimate the economic annual direct and indirect costs of axial spondyloarthritis (axSpA) in Singapore, and to identify factors associated with these costs. METHODS: A retrospective, cross-sectional, Institutional Review Board-approved study was conducted. A questionnaire was administered to the patients between 2013 and 2016 from the Singapore General Hospital (SGH) spondyloarthritis registry. Direct medical costs and indirect costs were estimated using the SGH database and the human capital approach respectively. Multivariate analyses using generalized linear model with gamma distribution and a log-linked function was conducted to identify factors associated with these total, direct and indirect costs. All costs were adjusted to 2017 using the Singapore Consumer Price Index and converted to 2017 US dollars (USD) by purchasing power parity. RESULTS: A total of 135 consecutive patients were included in the study, with a mean age of 40.4 ± 13.2 years. The overall annual total economic cost to society was around USD 74 790 820, with annual direct cost being the main component of total cost (90.8%). Annual direct cost was around USD 67 931 457, while annual indirect cost was around USD 6 855 951. Presence of extra-spinal symptoms (ever) was associated with an increase in total and direct costs. Higher education level and Patient Global Assessment were associated with an increase in indirect costs. Lack of employment was associated with a decrease in indirect costs. CONCLUSION: The disease burden of axSpA in Singapore is not trivial given that the disease is relatively common. This highlights the need for measures to accommodate patients with axSpA economically in Singapore.

[Cost of illness in axial spondylarthritis for patients with and without tumor necrosis factor inhibitor treatment: results of a routine data analysis]. / Krankheitskosten bei axialer Spondyloarthritis für Patienten mit und ohne Tumor-Nekrose-Faktor-Inhibitor-Behandlung: Ergebnisse einer Routinedatenanalyse.

BACKGROUND: Tumour necrosis factor-alpha inhibitors (TNFi) are an effective but expensive treatment option in axial spondylarthritis (axSpA) patients who fail to achieve disease control under conventional treatment. OBJECTIVE: The aim of this study was to assess the cost of illness in axSpA patients treated with and without TNFi. METHODS: Using German health insurance data, patients with axSpA who newly received TNFi between 2011 and 2015 were identified and matched by age and sex to a reference group of patients with axSpA without TNFi treatment. Costs for services performed in an outpatient setting, inpatient care, pharmacotherapy and for productivity loss due to absence from paid work were analyzed over a 2-year period. In patients treated with TNFi , the 2­year period included 1 year before and 1 year after the initiation of TNFi. RESULTS: Data from 1455 axSpA patients who received TNFi treatment were included in the analyses. Costs for services performed in an outpatient setting, inpatient care, pharmacotherapy (excluding TNFi) as well as productivity loss significantly decreased after initiation of TNFi. Mean total costs increased from €â€¯6075 in the year prior to TNFi initiation to €â€¯27,871 in the year after TNFi initiation. Excluding costs for TNFi, total costs decreased by 22% to €â€¯4761. Mean total costs among the reference group of 1455 age and sex-matched axSpA patients who did not receive TNFi remained stable over 2 years: €â€¯3939 in the first year vs. €â€¯3832 in the second year. CONCLUSION: Initiation of TNFi treatment led to a sharp increase in the total costs of axSpA patients. Part of this increase was offset by a decrease of costs for services performed in an outpatient setting, inpatient care, pharmacotherapy (excluding TNFi) as well as productivity loss. In patients who did not receive TNFi, the costs remained stable over 2 years.

The costs associated with ankylosing spondylitis/axial spondyloarthritis in Aotearoa/New Zealand.

AIMS: To evaluate costs associated with a diagnosis of spondyloarthritis (SpA) in an Aotearoa/New Zealand cohort. METHODS: Patients with SpA attending specialist SpA clinics in Auckland and Hamilton completed a series of questionnaires on costs associated with ankylosing spondylitis, disease parameters (BASDAI), work productivity (WPAI, WLQ) and quality of life measures (EQ-5D, ASAS-HI). RESULTS: Eighty-one patients (median age 43 years) completed the study. All fulfilled the ASAS criteria for axial spondyloarthritis and 44 (58%) fulfilled the Modified New York Criteria for ankylosing spondylitis. The mean (SD) score on the EQ-VAS was 69mm (24.1). More than half reported difficulties with usual activities and more than 80% had moderate pain or discomfort despite current treatment. Sixty-six (82%) were in the workforce, and the mean work productivity loss was 4.8%. The mean (SD) annual cost was NZ$15,677 (NZ$11,269) with NZ$12,189 direct cost and NZ$3,488 productivity loss. The largest cost driver was use of biologic medications, which were used by 48% patients. CONCLUSIONS: This study has quantified the direct and indirect costs of spondyloarthritis (SpA) in Aotearoa/New Zealand, and demonstrates meaningful reduction in quality of life and work productivity in patients with SpA. The major driver of direct costs in SpA are biologic medications.

The costs associated with ankylosing spondylitis/axial spondyloarthritis in Aotearoa/New Zealand.

AIMS: To evaluate costs associated with a diagnosis of spondyloarthritis (SpA) in an Aotearoa/New Zealand cohort. METHODS: Patients with SpA attending specialist SpA clinics in Auckland and Hamilton completed a series of questionnaires on costs associated with ankylosing spondylitis, disease parameters (BASDAI), work productivity (WPAI, WLQ) and quality of life measures (EQ-5D, ASAS-HI). RESULTS: Eighty-one patients (median age 43 years) completed the study. All fulfilled the ASAS criteria for axial spondyloarthritis and 44 (58%) fulfilled the Modified New York Criteria for ankylosing spondylitis. The mean (SD) score on the EQ-VAS was 69mm (24.1). More than half reported difficulties with usual activities and more than 80% had moderate pain or discomfort despite current treatment. Sixty-six (82%) were in the workforce, and the mean work productivity loss was 4.8%. The mean (SD) annual cost was NZ$15,677 (NZ$11,269) with NZ$12,189 direct cost and NZ$3,488 productivity loss. The largest cost driver was use of biologic medications, which were used by 48% patients. CONCLUSIONS: This study has quantified the direct and indirect costs of spondyloarthritis (SpA) in Aotearoa/New Zealand, and demonstrates meaningful reduction in quality of life and work productivity in patients with SpA. The major driver of direct costs in SpA are biologic medications.

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.

Psychometric validation of the EuroQoL 5-dimension (EQ-5D) questionnaire in patients with spondyloarthritis.

BACKGROUND: Spondyloarthritis (SpA) has a significant impact on patients' quality of life due to functional impairments. Generic health instruments like the EuroQoL 5-dimension (EQ-5D) is important for the cost-utility analysis of health care interventions and calculation of quality-adjusted life years. However, the applicability of the EQ-5D health measure in Chinese patients with SpA is currently unknown. Hence, the aim of the study is to test the psychometric properties and to validate the use of the EQ-5D health measure for utility analyses in Chinese patients with SpA. METHODS: Prospective and consecutive recruitment of 220 Chinese patients with SpA was conducted. Demographic data including smoking and drinking habits, education level, income, and occupation was collected. Disease-associated data including disease duration, the presence of back pain, peripheral arthritis, dactylitis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease was also recorded. Questionnaires regarding disease activity and functional disability (BASDAI, BASFI, BASGI, BASMI, ASDAS, ODI), mental health (HADS depression and anxiety), and the EQ-5D scores were recorded. SF-36 scores were used to verify the findings. Baseline correlations were performed along with test-retest reliability, validity, and internal consistency tests. Specifically, the relationship between EQ-5D and disease activity and functional scores was studied. RESULTS: EQ-5D scores achieved acceptable internal consistency and reliability. A ceiling effect was observed for all domains of the EQ-5D except for pain/discomfort. No floor effect was observed. Significant negative correlations were observed between ODI, HADS, BASFI, BASMI, BASDAI, and ASDAS-CRP and with EQ-5D. A higher disease activity was well-differentiated by EQ-5D, as with the disability and mental health scores. CONCLUSIONS: The EQ-5D demonstrates satisfactory psychometric properties for assessment of SpA patients. It has high utility for demonstrating changes in disease activity and disability.

Burden of severe spondyloarthritis in France: A nationwide assessment of prevalence, associated comorbidities and cost.

OBJECTIVES: To estimate the number of patients with severe spondyloarthritis (SpA) in France, describe their comorbidities and document and value their healthcare resource consumption. METHODS: Data were retrieved from an insurance claims database covering a 1/97 random sample of the French population. All patients benefiting from full insurance coverage ("ALD") for severe SpA in 2012 (including cases with structural damage and/or frequent flares) were identified, together with a control group frequency-matched by age and gender. Severe comorbidities were documented through ALD categories. Healthcare resource consumption was documented and valued from the payer's perspective. Rates of comorbidities and costs were compared in SpA patients versus controls using non-parametric testing. RESULTS: Overall, 827 patients with ALD status for severe SpA were identified (control group: n=2.481), corresponding to a prevalence rate of 0.18% [0.17-0.19] for SpA with ALD in the general population. Severe comorbidities more frequent in patients with SpA than in controls included inflammatory bowel disorders (odds ratio: 15.0 [6.2-36.2]), hypertension (2.5 [1.6-3.9]), atrial fibrillation (4.3 [1.9-9.6]) and major depressive disorder (2.1 [1.3-3.6]). Mean per capita annual direct healthcare expenditure was 3.6 [3.2-4.1]-fold higher in SpA patients (€6,122 [€5,838-€6,406]) than in controls (€1,682 [€1,566-€1,798]). Extrapolating to all patients in France, total healthcare cost attributable to severe SpA patients was €391 [€355-€426] million, with medication accounting for 53.8% of this cost. CONCLUSIONS: The burden of severe SpA in France is substantial, due to the high prevalence, high direct costs and associated comorbidities.

Atlas of axial spondyloarthritis in Spain 2017: Study design and population.

OBJECTIVE: Atlas of Axial Spondyloarthritis in Spain 2017 aims to better understand the reality of the patients suffering from this disease from an integrated approach. METHODS: The Atlas 2017 based its results on an extensive cross-sectional patient survey conducted in Spain (2016), validated by a multidisciplinary group of experts on spondyloarthritis. RESULTS: Data from 680 patients with axSpA were obtained, most of them suffered from AS, were HLA-B27 positive, older than 45 years, and live as part of a couple. A large percentage had university studies, were disabled and members of a patient association. Patients reported a diagnostic delay of 8.5 years, high disease activity (BASDAI 5.5±2.2), moderate-important stiffness (61.0%), medium-high functional limitation (74.9%), and psychological distress (GHQ 5.7±4.5). A total of 54.7% reported taking NSAIDs, 28.4% DMARDs, 36.3% biological therapy and 32.2% were not receiving pharmacological treatment. CONCLUSIONS: The Atlas survey data reveals still a long diagnostic delay, high disease activity, psychological distress, while an important proportion could be undertreated.

Direct medical costs and their predictors in the EMAR-II cohort: "Variability in the management of rheumatoid arthritis and spondyloarthritis in Spain". / Costes médicos directos y sus predictores en la cohorte "Variabilidad en el manejo de la artritis reumatoide y las espondiloartritis en España".

OBJECTIVE: To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve. METHODS: A cross-sectional study was performed in a sample including all regions and hospitals throughout the country. Sociodemographic data, disease activity parameters and treatment data were obtained. Resource utilization for two years of study was recorded and we made costs imputation. Correlation analyzes were performed on all RA patients and those treated with biological and biological naïve, to estimate the differences in resource utilization. Factors associated with increased resources utilization (costs) attending to treatment was analyzed by linear regression models. RESULTS: We included 1,095 RA patients, 26% male, mean age of 62±14 years. Mean of direct medical costs per patient was €24,291±€45,382. Excluding biological drugs, the average cost per patient was €3,742±€3,711. After adjustment, factors associated with direct medical costs for all RA patients were biologic drugs (P=.02) and disease activity (P=.004). In the biologic-naïve group, the predictor of direct medical costs was comorbidity (P<.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007). CONCLUSION: Our data show a remarkable economic impact of RA. It is important to identify and estimate the economic impact of the disease, compare data from other geographic samples and to develop improvement strategies to reduce these costs and increase the quality of care.

Efficacy, safety and cost per responder of biologics in the treatment of non-radiographic axial spondyloarthritis.

Anti-tumour necrosis factor (TNF) agents are recommended as second-line therapy for patients with axial spondyloarthropathies. This analysis reviewed data on studies investigating the efficacy and tolerability of anti-TNF agents in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who had failed first-line non-steroidal anti-inflammatory (NSAID) treatment. Efficacy data from RCTs were used to calculate the number needed to treat (NNT) for individual anti-TNFs and then the cost per responder was determined to provide an indication of the value of each therapy. A systematic literature review and analysis of search results over the period January 2008 to September 2014 identified four randomised placebo-controlled trials that were included in the analysis. Adalimumab, etanercept and certolizumab pegol were all effective and well tolerated in patients with nr-axSpA. A patient was more likely to reach ASAS20 or ASAS40 when treated with etanercept or adalimumab, the NNT was lowest for adalimumab, and the risk of adverse events was higher with certolizumab pegol 200 mg every 2 weeks. The cost per responder (NNT) was lowest for adalimumab, followed closely by certolizumab 400 mg every 4 weeks, intermediate for certolizumab 200 mg every 2 weeks and highest for etanercept. Although all anti-TNF agents were associated with clinical improvement in patients with nr-axSpA, adalimumab presented a better cost per responder than etanercept and certolizumab pegol.

Study protocol for a cluster randomized controlled trial to evaluate a referral strategy for axial spondyloarthritis in young primary care patients with chronic low back pain; an impact study.

BACKGROUND: Axial spondyloarthritis (axSpA) is a disabling inflammatory joint disease with chronic low back pain (CLBP) as leading symptom. Recognizing axSpA in the large amount of CLBP patients is difficult for general practioners (GP). This evaluation aims to assess the effect of a referral strategy for axSpA in young primary care patients with CLBP by comparing the use of the strategy with usual care. The effect is measured at three different levels; by patient reported outcomes (the clinical effect), process and costs evaluation. METHODS/DESIGN: This study design is a cluster randomized controlled trial with GP as clusters. GPs throughout the Netherlands are invited to participate and randomized to either the intervention or the control group. Patients from participating GPs are invited to participate if they have ever been registered with low back pain, without radiation (ICPC L03) and aged 18-45 years. To be included in the study, patients need to have current low back pain and chronic low back pain (>12 weeks). In the intervention arm a referral strategy for axSpA will be applied in CLBP patients, in the control arm care as usual will be provided for CLBP patients. The referral strategy consists of four easy to use variables. All are questions about the back pain complaints of the patients. Data is prospectively collected in an online database at baseline (T0), 4 months (T1), 12 months (T2) and 24 months (T3). After time point T1 (4 months) patients from the control group will also receive the intervention i.e. the application of a referral strategy for axSpA. The effect of the referral strategy is measured at three different levels, by patient outcomes (e.g. pain scores, quality of life), process measures (e.g. number of axSpA diagnoses by rheumatologists) and by costs (work productivity and health care resources use). Our primary outcome is the Roland Morris Disability Questionnaire after 4 months, secondary outcomes are pain and quality of life. Costs will be assessed before and after the use of the referral strategy, to estimate if the use of the strategy will lead to a reduction in health care costs and improvement in work participation. DISCUSSION: It is anticipated that using the axSpA referral strategy for primary care CLBP patients will increase the quality of life of CLBP patients, will result in more (correct) diagnoses of axSpA by the rheumatologists, and will be cost-effective. Ultimately, the results of this study may contribute to the startup of a national implementation of the axSpA referral strategy to identify timely CLBP patients with axSpA. TRIAL REGISTRATION: NCT01944163 , date of registration; September 6, 2013 (Clinicaltrials.gov).

Chronic widespread pain in spondyloarthritis.

The pain associated with spondyloarthritis (SpA) can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP) that characterises fibromyalgia (FM). The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF) inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

[Off-label therapy of rheumatoid arthritis and spondyloarthritis]. / Off-Label-Therapie bei rheumatoider Arthritis und Spondyloarthritiden.

For rheumatoid arthritis (RA) and diseases of the spondyloarthritis group (SpA) a large number of approved medications are available. Nevertheless, in Germany even for these diseases several off-label risks exist for the rheumatologist prescribing antirheumatic drugs which have recently led to a series of recourses or threats of recourse. In RA as well as SpA first of all biologicals are the target of recourse imposed mainly by health insurances. In RA monotherapy (when labeled only in combination with methotrexate), combination with leflunomide (instead of methotrexate) and dose deviations are the most important causes. In SpA TNF inhibitors are labeled only for the definite diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) leaving aside patients with severe peripheral spondyloarthritis including enthesitis which does not exactly meet the diagnostic criteria of AS and PsA. The same applies to early AS not fulfilling the 1984 New York criteria which still lacks labeled use of TNF inhibitors. In these cases, however, based on successful randomized controlled trials and changed diagnostic criteria a label extension is expected in the near future. Until then it seems suitable to apply for permission for this treatment from insurers in each case.