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      Estimating the response and economic burden of rheumatoid arthritis patients treated with biologic disease-modifying antirheumatic drugs in Taiwan using the National Health Insurance Research Database (NHIRD)

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          Abstract

          Background

          Previous studies in Taiwan utilizing the Taiwan’s National Health Insurance Database (NHIRD) have estimated the direct healthcare costs of RA patients, but they have not focused on patients on bDMARDs, or considered patients’ response to therapy.

          Objectives

          The objective of this study was to estimate the rate of inadequate response for patients newly treated with biologic disease-modifying antirheumatic drugs (bDMARDs) as well as their costs and resource use.

          Methods

          Data were from the catastrophic illness file within the NHIRD from 1/1/2009 to 12/31/2013. Patients with RA, which was categorized by the presence of a catastrophic illness card, that were previously bDMARD-naïve, were included in this study if they initiated their first bDMARD during the index period. The index period included all of 2010, a pre-index period consisting of the index date– 365 days, and a follow-up period including the index date to 365 days post-index, were also included. Previously biologically-naïve patients were indexed into the study on the date of their first claim for a bDMARD. A validated algorithm was used to examine the rate of inadequate response (IR) in the biologically-naïve cohort of patients. Inadequate responders met one or more of the following criteria during their year of follow-up: low adherence (proportion of days covered <0.80); switched to or added a second bDMARD; added a new conventional synthetic DMARD (csDMARD); received ≥1 glucocorticoid injection; or increased oral glucocorticoid dosing. All-cause mean annual direct costs and resource use were measured in the year of follow-up. Costs were converted from NT$ to USD using 1 NT$ = 0.033 USD.

          Results

          A total of 818 patients with RA initiated their first bDMARD (54% etanercept and 46% adalimumab) in 2010. After one year of follow-up, 32% (n = 258) were classified as stable, 66% (n = 540) had an IR, and 2% (n = 20) were lost to follow-up. During the follow-up period mean annual total direct costs were $16,136 for stable patients compared to $14,154 for patients with IR. Mean annual non-medication direct costs were $937 for stable patients and $1,574 for patients with IR. Mean annual hospitalizations were higher for patients with IR (0.46) compared to stable patients (0.10) during the one year follow-up period.

          Conclusions

          The majority of patients that were previously naïve to bDMARDs had an IR to their first bDMARD during the year of follow-up. Patients with an IR had numerically increased all-cause resource utilization and non-medication costs during the follow-up period compared to patients with stable disease. This level of IR suggests an unmet need in the RA treatment paradigm.

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          Most cited references21

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          The pathogenesis of rheumatoid arthritis.

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            Prevalence of rheumatoid arthritis in low– and middle–income countries: A systematic review and analysis

            Background Rheumatoid arthritis (RA) is an autoimmune disorder that affects the small joints of the body. It is one of the leading causes of chronic morbidity in high–income countries, but little is known about the burden of this disease in low– and middle–income countries (LMIC). Methods The aim of this study was to estimate the prevalence of RA in six of the World Health Organization's (WHO) regions that harbour LMIC by identifying all relevant studies in those regions. To accomplish this aim various bibliographic databases were searched: PubMed, EMBASE, Global Health, LILACS and the Chinese databases CNKI and WanFang. Studies were selected based on pre–defined inclusion criteria, including a definition of RA based on the 1987 revision of the American College of Rheumatology (ACR) definition. Results Meta–estimates of regional RA prevalence rates for countries of low or middle income were 0.40% (95% CI: 0.23–0.57%) for Southeast Asian, 0.37% (95% CI: 0.23–0.51%) for Eastern Mediterranean, 0.62% (95% CI: 0.47–0.77%) for European, 1.25% (95% CI: 0.64–1.86%) for American and 0.42% (95% CI: 0.30–0.53%) for Western Pacific regions. A formal meta–analysis could not be performed for the sub–Saharan African region due to limited data. Male prevalence of RA in LMIC was 0.16% (95% CI: 0.11–0.20%) while the prevalence in women reached 0.75% (95% CI: 0.60–0.90%). This difference between males and females was statistically significant (P < 0.0001). The prevalence of RA did not differ significantly between urban and rural settings (P = 0.353). These prevalence estimates represent 2.60 (95% CI: 1.85–3.34%) million male sufferers and 12.21 (95% CI: 9.78–14.67%) million female sufferers in LMIC in the year 2000, and 3.16 (95% CI: 2.25–4.05%) million affected males and 14.87 (95% CI: 11.91–17.86%) million affected females in LMIC in the year 2010. Conclusion Given that majority of the world’s population resides in LMIC, the number of affected people is substantial, with a projection to increase in the coming years. Therefore, policy makers and health–care providers need to plan to address a significant disease burden both socially and economically.
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              Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets.

              Biologic therapies that target pathogenic cytokines such as TNF, IL-1β or IL-6 have greatly improved the treatment of RA. Unfortunately, not all RA patients respond to current biologic therapies and responses are not always maintained, suggesting that there are alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. Discovery of the new Th17 subset of Th cells, and their role in autoimmune disease development, has implicated the proinflammatory IL-12 and IL-17 families of cytokines in RA disease pathogenesis. Members of these cytokine families are elevated in the blood and joints of RA patients and have been shown to remain elevated in patients who do not respond to current biologics. In addition, these cytokines have been shown to play roles in joint destruction and erosion. A new subclass of biologics that target the IL-12 and/or IL-17 signalling pathways are under development. Here we review evidence for a role of Th17 cells as well as IL-12 and IL-17 cytokines in RA pathogenesis as the rationale for a subsequent discussion of the ongoing and completed clinical trials of newly emerging biologic therapies directed at IL-12 or IL-17 pathway inhibition.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 April 2018
                2018
                : 13
                : 4
                : e0193489
                Affiliations
                [1 ] Eli Lilly & Co., Shanghai, China
                [2 ] National Taiwan University, Taipei, Taiwan
                [3 ] Eli Lilly & Co., Budapest, Hungary
                [4 ] Elysia Group Ltd., Taipei, Taiwan
                [5 ] Eli Lilly & Co., Indianapolis, Indiana, United States of America
                [6 ] Eli Lilly & Co., Taipei, Taiwan
                [7 ] Taipei Medical University, Taipei, Taiwan
                VU University Medical Center, NETHERLANDS
                Author notes

                Competing Interests: The authors have read the journal's policy and have the following conflicts: QS is an employee of Eli Lilly and owns stock in Eli Lilly. KL is a paid consultant for Eli Lilly. TT is an employee of Eli Lilly and owns stock in Eli Lilly. BW is an employee of Elysia Group and a paid consultant for Eli Lilly. CG is an employee of Eli Lilly and owns stock in Eli Lilly. CL is an employee of Eli Lilly. WW is an employee of Eli Lilly and owns stock in Eli Lilly. WF is an employee of Elysia Group and a paid consultant to Eli Lilly. CT is a paid consultant for Eli Lilly. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

                Article
                PONE-D-17-27392
                10.1371/journal.pone.0193489
                5889158
                29624580
                ae8677fc-3c59-4b4b-a0d3-6dafd15ef0a9
                © 2018 Shi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 July 2017
                : 12 February 2018
                Page count
                Figures: 3, Tables: 3, Pages: 13
                Funding
                Funded by: Eli Lilly & Co
                Award Recipient :
                This study was funded by Eli Lilly and Co ( https://www.lilly.com/). Eli Lilly provided financial support in the form of salaries for QS, TT, CG, CL, WW. Eli Lilly paid the following authors as consultants: KL, BW, WF, CT. Elysia Group provided financial support in the form of salaries for BW and WF. The specific roles of these authors are articulated in the author contributions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Rheumatology
                Arthritis
                Rheumatoid Arthritis
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Autoimmune Diseases
                Rheumatoid Arthritis
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Autoimmune Diseases
                Rheumatoid Arthritis
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
                Autoimmune Diseases
                Rheumatoid Arthritis
                People and Places
                Geographical Locations
                Asia
                Taiwan
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Medicine and Health Sciences
                Health Care
                Patients
                Outpatients
                Social Sciences
                Economics
                Health Economics
                Medicine and Health Sciences
                Health Care
                Health Economics
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Receptor Antagonist Therapy
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Custom metadata
                The NHIRD data that supports the findings of this study were available from The National Health Research Institutes (NHRI) before December 31st, 2013 upon request from researchers for research purpose. The NHRI stopped providing this service after December 31st, 2013. The data underlying this study has been transferred to the Health and Welfare Data Science Center (HWDC). Interested researchers can obtain the data through formal application to the HWDC, Department of Statistics, Ministry of Health and Welfare, Taiwan ( http://dep.mohw.gov.tw/DOS/np-2497-113.html).

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