Temporal trend of population structure, burden of diseases, healthcare resources and expenditure in China, 2000-2019.

OBJECTIVES: To explore the evolutionary trend of population structure, disease burden, healthcare resources and expenditure in China, and to identify key domains that are most in need of intervention. DESIGN: A cross-sectional and longitudinal analysis. DATA SOURCE: Population and healthcare data from China Statistical Yearbook, and disease burden attributable to causes and risk factors from the Global Burden of Diseases between 2000 and 2019. MEASURES AND METHODS: We used the Joinpoint Regression Program to measure trends in population composition, population change, dependency ratio, healthcare institution, personnel, expenditure and disease burden from 2000 to 2019. RESULTS: Regarding the population in China between 2000 and 2019, a decreasing trend was observed among youth aged 0-14 years (average annual percent change (AAPC): -1.17), a slow rising trend was observed among individuals aged 15-64 years (AAPC: 1.10) and a rapidly increasing trend was observed among individuals older than 65 years (AAPC: 3.67). Astonishing increasing trends in healthcare institutions (AAPC: 3.97), medical personnel (AAPC: 3.26) and healthcare expenditures (AAPC: 15.28) were also observed. Among individuals younger than 70 years, neoplasms (AAPC: 0.54) and cardiovascular diseases (AAPC: 0.67) remained among the top three causes, while tobacco (AAPC: 0.22) remained a top three risk factor. However, while musculoskeletal disorders (AAPC: 1.88) were not a top three cause in 2000, they are a top three cause in 2019. CONCLUSION: Comprehensive age/cause/risk factor-specific strategies are key to reconcile the tension among the triad of population ageing, disease burden and healthcare expenditure. The disease burden from cardiometabolic diseases, neoplasms and musculoskeletal disorders was identified as key domains that require intervention to reduce an increasing disease burden among individuals currently older than 70 years, as well as those approaching this age group.

A clinical practice guideline for the screening and assessment of enthesitis in patients with spondyloarthritis.

Objective: The aim of this review is to provide guidance on the selection of approaches to the screening and assessment of enthesitis in patients with spondyloarthritis (SpA). Methods: Twenty-four questions regarding the approaches to the screening and assessment of enthesitis and the implementation details were devised, followed by a systemic literature review. The Grading of Recommendations Assessment, Development, and Evaluation methodology was employed in the development of this guideline, with modifications to evaluate non-interventional approaches under comprehensive consideration of costs, accessibility, and evidence strength. A consensus from the voting panel was required for the inclusion of the final recommendations and the strength of each recommendation. Results: Seventeen recommendations (including five strong recommendations) were included in this guideline. The voting panel expressed unequivocal support for the necessity of screening and assessment of enthesitis in patients with SpA. It was agreed unanimously that symptom evaluation and physical examination should serve as the initial steps to the recognition of enthesitis, whereas Maastricht Ankylosing Spondylitis Enthesitis Score is a reliable tool in both clinical trials and daily medical practice. Ultrasound examination is another reliable tool, with power Doppler ultrasound as an informative addition. Notwithstanding its high resolution, MRI is limited by the costs and relatively low accessibility, whereas radiographs had low sensitivity and therefore should be rendered obsolete in the assessment of enthesitis. PET/CT was strongly opposed in the detection of enthesitis. Conclusion: This guideline provides clinicians with information regarding the screening and assessment of enthesitis in patients with SpA. However, this guideline does not intend on dictating choices, and the ultimate decisions should be made in light of the actual circumstances of the facilities.

Risk assessment in systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

Objective: This study evaluated the prognostic value of the multivariable risk assessment for systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH). Methods: A multicenter prospective cohort of SLE-associated PAH (CSTAR-PAH cohort) diagnosed based on right heart catheterization (RHC) was established. Baseline and follow-up records were collected. Three methods of risk assessment, including (1) the number of low-risk criteria, based on World Health Organization functional class (WHO FC), 6-min walking distance (6MWD), right atrial pressure (RAP), and cardiac index (CI); (2) the three-strata stratification based on the average risk score of four variables (WHO FC, 6MWD, RAP, and CI); and (3) the four-strata stratification based on COMPARE 2.0 model were applied. A risk-assessment method using three noninvasive low-risk criteria was applied at the first follow-up visit. Survival curves between patients with different risk groups were compared by Kaplan-Meier's estimation and log-rank test. Results: Three-hundred and ten patients were enrolled from 14 PAH centers. All methods of stratification at baseline and first follow-up significantly discriminated long-term survival. Survival rates were also significantly different based on the noninvasive risk assessment in first follow-up visit. Survival deteriorated with the escalation of risk from baseline to first follow-up. Patients with baseline serositis had a higher rate of risk improvement in their follow-up. Conclusion: The risk assessment has a significant prognostic value at both the baseline and first follow-up assessment of SLE-associated PAH. A noninvasive risk assessment can also be useful when RHC is not available during follow-up. Baseline serositis may be a predictor of good treatment response in patients with SLE-associated PAH.

The pattern and trends of disease burden due to low bone mineral density from 1990 to 2019 in China: findings from the Global Burden of Disease Study 2019.

Osteoporosis is becoming increasing important health problem in China. This study shows that the disease burden of low bone mineral density (BMD) in China is large and will remain increasing with the growth of aging population. In addition, male low BMD should not be ignored. Although burden of low BMD is partially representative of the real burden of osteoporosis, the information provided in our study could be used to better inform targeted public health prevention and management programs for osteopososis. PURPOSE: We aim to investigate the pattern and trends of disease burden due to low BMD by gender, year, and age in China from 1990 to 2019. METHODS: Data on summary exposure value (SEV) and disability-adjusted life years (DALYs) due to low BMD was obtained from the Global Burden of Disease Study 2019, and analyzed by gender, age, and years. Average annual percent change (AAPC) and annual percent change (APC) were calculated to qualify the trends of burden due to low BMD. RESULT: In 2019, the age-standardized SEV was higher in females than that in males (23.04, 95% UI = [17.25-29.83] and 12.50, 95% UI = [7.71-19.25], respectively), while the total number of DALYs was higher in males than females with 1,698,705.92 (95% UI = 1,281,580.79 to 2,076,364.25) and 1,621,569 (95% UI = 1,266,284.89 to 2,016,399.16), respectively. Though SEV exhibited decreasing trends during 1990 to 2019 in both sexes, the absolute number of DALYs due to low BMD increased steadily and almost doubled in 2019 compared to that in 1990. CONCLUSION: The burden of low BMD remains large and continues to increase. Although females are prone to low BMD, the disease burden for males should not be ignored.

Pattern and trend of five major musculoskeletal disorders in China from 1990 to 2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: With increasing life expectancy in China, no large population-based studies have been done on the trend for musculoskeletal disorders in China. We have investigated the pattern and trend of five major musculoskeletal disorders in China from the Global Burden of Disease Study 2017 and its association with sociodemographic index (SDI). METHODS: The main outcome measures were incidence, prevalence, and disability-adjusted life years (DALYs) for rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout. Average annual percent change (AAPC) and annual percent change (APC) between 1990 and 2017 were analyzed with Joinpoint regression. RESULTS: The age-standardized rate of incidence, prevalence, and DALYs for the five major musculoskeletal disorders increased with age. For SDI, the age-standardized rate of DALYs was zigzagged increasing for rheumatoid arthritis and curvilinear increasing for gout, curvilinear decreasing for low back pain, and reaching to the highest point for osteoarthritis and neck pain with an SDI value of 0.61. The AAPC in age-standardized rate of DALYs indicated an increasing trend for rheumatoid arthritis (0.20, 95% CI 0.07, 0.34), osteoarthritis (0.26, 95% CI 0.20, 0.31), neck pain (0.09, 95% CI 0.07, 0.12), and gout (0.25, 95% CI 0.23, 0.27), but a decreasing trend for low back pain (- 0.96, 95% CI - 0.98, - 0.93). The AAPC of risk factors indicated a decreasing trend in smoking (- 0.14, 95% CI - 0.24, - 0.04) for rheumatoid arthritis, smoking (- 0.22, 95% CI - 0.24, - 0.19) and occupational ergonomic factors (- 1.25, 95% CI - 1.29, - 1.21) for low back pain, and impaired kidney function (- 0.95, 95% CI - 1.00, - 0.90) for gout, but an increasing trend in high body-mass index for osteoarthritis (3.10, 95% CI 3.03, 3.17), low back pain (3.07, 95% CI 2.99, 3.14), and gout (3.12, 95% CI 3.04, 3.20). Comparing the burden of five musculoskeletal diseases in China with the 19 countries of G20, China ranked first to second in the number of DALYs, and 12th to 16th in age-standardized rate of DALYs. CONCLUSION: There are remarkably complex temporal patterns in disease burden and risk factors for five major musculoskeletal disorders across past three decades. Population-wide initiatives targeting high body-mass index may mitigate the burden of musculoskeletal disorders.

Cost of Illness, Quality of Life, and Work Outcomes in Active Ankylosing Spondylitis Patients Treated With Adalimumab in China.

Objectives: To access the cost of illness, quality of life and work limitation in active ankylosing spondylitis (AS) patients using adalimumab in China. Methods: A prospective study was performed in 91 patients with active AS in China. Adult patients (aged ≥ 18 years) fulfilled the 1984 New York modified criteria of AS with the Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 were enrolled. All participants received adalimumab (40 mg per 2 weeks) therapy and completed questionnaires about disease characteristics, quality of life and cost. Only patients with pay-work completed the Work Limitation Questionnaire and Work productivity and activity impairment questionnaire in AS. Factors associated with work outcomes were evaluated. Results: A total of 91 patients with mean age of 30 years old (87.8% males) and mean disease duration of 10 years received adalimumab treatment for 24 weeks. The annual estimated cost of each patient was $37581.41 while the direct cost accounted for 84.6%. Seventy-eight percent of patients have a paid job with average work productivity loss of 0.28 measured by work limitation questionnaire, absenteeism and presenteeism were 10.22 and 43.86%, respectively, with a mean work productivity loss of 47.92% measured by Work productivity and activity impairment questionnaire in AS. Patients experienced significantly greater improvements after adalimumab treatment in presenteeism, absenteeism, work productivity, and quality of life. Conclusions: The cost of AS patients with adalimumab therapy was high in China. Disease activity, physical function, quality of life, and work outcomes improved significantly after therapy.

Chinese patients' preference for pharmaceutical treatments of osteoporosis: a discrete choice experiment.

While adherence to osteoporosis treatment is low, patients' preference for osteoporosis treatment is unknown in Chinese patients. Chinese patients are willing to receive treatments with higher clinical efficacy and lower out-of-pocket cost. In addition, annual intravenous infusion and 6-month subcutaneous injection are preferred over weekly oral tablets. PURPOSE: This study was performed to elicit Chinese patients' preferences for osteoporosis medication treatment and to investigate the heterogeneities of the preferences in subgroups. METHODS: A discrete choice experiment comprising 15 choice sets with 4 important attributes was conducted in a Chinese population at risk of osteoporotic fracture. The four attributes were treatment efficacy in reducing the risk of fracture, out-of-pocket cost per year, adverse effects of treatment, and mode of administration. The patients were asked to choose between two hypothetical treatments; they could also choose no treatment. Mixed logit models were used, and any observed heterogeneity in the patients' preferences was further assessed in subgroup analyses. RESULTS: In total, 267 patients were analysed. On average, the patients preferred to receive treatment rather than no treatment. The patients preferred treatment with higher efficacy in preventing fracture and lower out-of-pocket cost. The least preferred adverse effect of medication was gastrointestinal disorders, followed by flu-like symptoms and finally skin reactions. The most preferred mode of administration was annual intravenous infusion, followed by 6-month subcutaneous injection, a weekly oral tablet, and daily nasal spray; daily oral tablets ranked as the least preferred mode of administration. The differences in the patients' preferences among all attributes were statistically significant (p < 0.05). Patients' age was found to contribute to the observed preference heterogeneity in most of the included attributes. CONCLUSIONS: This study revealed Chinese patients' preferences for osteoporosis treatments. Annual intravenous infusion and 6-month subcutaneous injection were significantly preferred over weekly oral tablets in this Chinese population.

Anti-tumor necrosis factor biosimilars and intended copies in rheumatology: Perspective from the Asia Pacific region.

Although anti-tumor necrosis factor (TNF) agents have greatly improved the management of rheumatic diseases, their cost limits access to many patients throughout the world. As a result, patients and clinicians have turned to biosimilars to provide similar efficacy at a lower cost. Many of the regulatory guidelines in the Asia Pacific region are largely based on those of the European Medicines Agency and the World Health Organization; however, there are variations between countries. Additionally, in some countries, intended copies are available that were approved prior to the development of guidelines and have not fulfilled the requirements of a biosimilar. We review the various regulatory requirements for biosimilars in the Asia Pacific region, the anti-TNF biosimilars and intended copies approved in the region, and whether clinical data are available for these agents. We discuss concerns about the need for additional regulations and education, and we provide recommendations for a multidisciplinary pharmacovigilance approach that closely monitors the safety of biosimilar use.

An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS.

INTRODUCTION: In a previous phase, 12 draft definitions for clinically important worsening in axial spondyloarthritis (axSpA) were selected, of which 3 were based on absolute changes in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP (ASDAS). The objective here was to select the best cut-off for ASDAS for clinically important worsening in axSpA for use in clinical trials and observational studies. METHODS: An international longitudinal prospective study evaluating stable patients with axSpA was conducted. Data necessary to calculate ASDAS were collected at two consecutive visits (spaced 7 days to 6 months). Sensitivity and specificity of the three cut-offs for change in ASDAS were tested against the patient's subjective assessment of worsening as the external standard (ie, the patient reporting that he had worsened and felt a need for treatment intensification). Final selection was made by a consensus and voting procedure among Assessment of SpondyloArthritis International Society (ASAS) members. RESULTS: In total, 1169 patients with axSpA were analysed: 64.8% were male and had a mean age of 41.7 (SD 12.4) years. At the second visit, 127 (10.9%) patients judged their situation as worsened.Sensitivity and specificity for an increase of at least 0.6, 0.9 and 1.1 ASDAS points to detect patient-reported worsening were 0.55 (Se) and 0.91 (Sp), 0.38 (Se) and 0.96 (Sp), and 0.33 (Se) and 0.98 (Sp), respectively. The ASAS consensus was to define clinically important worsening as an increase in ASDAS of at least 0.9 points. CONCLUSION: This data-driven ASAS consensus process resulted in an ASDAS-based cut-off value defining clinically important worsening in axSpA for use in trials.

Cost-effectiveness of raloxifene in the treatment of osteoporosis in Chinese postmenopausal women: impact of medication persistence and adherence.

AIMS: Raloxifene treatment of osteoporotic fractures is clinically effective, but economic evidence in support of raloxifene reimbursement is lacking in the People's Republic of China. We aimed at evaluating the cost-effectiveness of raloxifene in the treatment of osteoporotic fractures using an osteoporosis health economic model. We also assessed the impact of medication persistence and adherence on clinical outcomes and cost-effectiveness of raloxifene. METHODS: We used a previously developed and validated osteoporosis state-transition microsimulation model to compare treatment with raloxifene with current practices of osteoporotic fracture treatment (conventional treatment) from the health care payer's perspective. A Monte Carlo probabilistic sensitivity analysis with microsimulations was conducted. The impact of medication persistence and adherence on clinical outcomes and the cost-effectiveness of raloxifene was addressed in sensitivity analyses. The simulated patients used in the model's initial state were 65-year-old postmenopausal Chinese women with osteoporosis (but without previous fractures), simulated using a 1-year cycle length until all patients had died. Costs were presented in 2015 US dollars (USD), and costs and effectiveness were discounted at 3% annually. The willingness-to-pay threshold was set at USD 20,000 per quality-adjusted life year (QALY) gained. RESULTS: Treatment with raloxifene improved clinical effectiveness by 0.006 QALY, with additional costs of USD 221 compared with conventional treatment. The incremental cost-effectiveness ratio was USD 36,891 per QALY gained. The cost-effectiveness decision did not change in most of the one-way sensitivity analyses. With full raloxifene persistence and adherence, average effectiveness improved compared with the real-world scenario, and the incremental cost-effectiveness ratio was USD 40,948 per QALY gained compared with conventional treatment. CONCLUSION: Given the willingness-to-pay threshold, raloxifene treatment was not cost-effective for treatment of osteoporotic fractures in postmenopausal Chinese women. Medication persistence and adherence had a great impact on clinical- and cost-effectiveness, and therefore should be incorporated in future pharmacoeconomic studies of osteoporosis interventions.

Costs and work limitation of patients with ankylosing spondylitis in China.

OBJECTIVES: To access the annual direct, indirect costs and work limitation of AS patients in Chinese population and explore the determinants of cost. METHODS: A retrospective, cross-sectional study was performed in 257 patients with AS in China. The participants completed questionnaires about disease characteristics, quality of life and direct and indirect costs. Only the patients with paid-work completed the Work Limitation Questionnaire (WLQ), a 25-item questionnaire that accesses the impact of chronic health conditions on job performance and productivity. Functional impairment and disease activity were assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Akylosing Spondylitis Disease Activity Index (BASDAI). Quality of life was measured by the Short Form-36. RESULTS: Of the 257 patients who completed the questionnaires, the mean age was 28.5 (SD=0.5) with mean disease duration of 6.52 years (SD=0.44). The mean BASDAI and BASFI score was 3.28 and 1.3, respectively. Among the 257 patients, 21.8% are students, 64.2% have a paid job and 10.5% without a job because of AS. 165 participants finished the WLQ with a mean WLQ index of 0.19 which corresponds to a 17% decrease in productivity. The annual estimated costs of each patient was $2714.18 while the indirect cost accounted for 64.7%. The annual direct cost significantly correlated with disease activity. CONCLUSIONS: Our research is the first to provide information about the burden of AS and the work status of AS patients in mainland China, which may help to establish the treatment strategy and a policy of support.

Evaluation of Assessment of Spondyloarthritis International Society classification criteria for axial spondyloarthritis in Chinese patients with chronic back pain: results of a 2-year follow-up study.

OBJECTIVE: To evaluate the diagnotic value of the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (SpA) in Chinese patients with chronic back pain and without radiographic sacroiliitis in a 2-year follow-up study. METHODS: Patients with chronic back pain ≥ 3 months, onset age ≤ 45 years and without radiographic sacroiliitis were enrolled, and then received 2-year follow-up. All the clinical parameters associated with SpA were recorded. The patients were followed for 2 years and the final diagnosis of axial SpA or non-SpA was confirmed by rheumatologists. Diagnostic concordance between the initial classification according to three classification criteria (ASAS criteria for axial SpA, European Spondylarthropathy Study Group (ESSG) criteria and Amor criteria) and final diagnosis was compared. Diagnostic sensitivity and specificity were compared between the two subsets of ASAS criteria (set 1: sacroiliitis plus more than one SpA feature; set 2: HLA-B27 plus two more SpA features). RESULT: One thousand and sixty-eight patients entered the study and 867 completed the 2-year follow-up (455 axial SpA and 412 non-SpA). The concordance of ASAS criteria was better than ESSG and Amor criteria. Three hundred and thirty-three patients and 335 patients were classified as axial SpA according to the ASAS set 1 and set 2 of criteria, respectively. Further, set 1 of criteria (318/333) showed higher specificity than set 2 critera (279/335) (P = 0.000). CONCLUSION: The ASAS classification criteria for axial SpA showed good concordance in diagnosing Chinese axial SpA patients in this prospective study. Set 1 criteria involving sacroiliitis plus more than one SpA feature had better diagnosing value.