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OBJECTIVES Hospital utilization and costs of female breast cancer have been well documented. However, evidence focusing on male breast cancer is scarce, despite the different clinical characteristics between female and male breast cancer. We aim to estimate hospital length of stay (LOS) and costs associated with male breast cancer in the United States. STUDY DESIGN Retrospective observational study. METHODS We analyzed the 2012-2016 Health Care Utilization Project National Inpatient Sample of 416 hospitalization events of male patients with breast cancer. Patients who had breast cancer diagnoses were selected based on the primary International Classification of Disease, Ninth Revision or Tenth Revision, Clinical Modification codes. A negative binomial regression and a generalized linear model with a gamma distribution and log-link function were conducted to estimate the LOS and hospital costs after controlling for sociodemographics, clinical characteristics (eg, metastatic status, Elixhauser Comorbidity Index [ECI] score), and hospital characteristics. RESULTS On average, male patients with breast cancer stayed for 2.42 days and expensed $9059 per hospital visit. Patients with metastatic status had longer LOS (5.39 vs 3.24 days; P = .005) and higher hospital costs ($11,185 vs $8547; P = .03) than those without. Patients with an ECI score of 3 or more showed longer LOS (4.05 vs 2.68 days; P = .003) and higher hospital costs ($10,043 vs $7022; P

Introduction: Mutation-targeting and immuno-oncology drugs are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). Cost-effectiveness analyses (CEA) of these drugs have be...

What is known and objective Metastatic renal cell carcinoma (mRCC) is the most common type of kidney cancers. Disease-specific survival for mRCC has been significantly improved with the introduction of new targeted agents since 2005. However, there is a lack of head-to-head clinical trials comparing the efficacy between therapies. This study compared indirectly progression-free survival (PFS) and overall survival (OS) among first-line and second-line therapies in patients with mRCC using network meta-analysis (NMA). Methods The PubMed, MEDLINE, Cochrane Library and Web of Science were searched to identify phase II or phase III randomized controlled trials (RCTs) of targeted and biological therapies in patients with mRCC published between January 2000 and June 2020. The Bayesian fixed-effect NMA was performed to evaluate relative PFS and OS of first-line and second-line therapies of axitinib, bevacizumab, cabozantinib, everolimus, lenvatinib, nivolumab, ipilimumab, pazopanib, sorafenib, sunitinib, temsirolimus, tivozanib, avelumab and pembrolizumab, which were approved by the Food and Drug Administration or European Medicines Agency. End points were compared using hazard ratio (HR) and 95% credible interval (CrI). The surface under the cumulative ranking curve (SUCRA) was estimated to assess the probability of being the best treatment. Results and discussion A total of 26 RCTs (first line: 19, second line: 9) with 13 893 patients were included in the NMA. For the first-line therapy, cabozantinib was associated with the highest improved PFS (HR = 0.26, 95% CrI = 0.14-0.44) followed by avelumab + axitinib and pembrolizumab + axitinib (HR = 0.27, SUCRA = 90%). Pembrolizumab + axitinib had a high likelihood of being the preferred treatment when using OS as the outcome measure (HR = 0.41, 95% CrI = 0.16-0.85). Avelumab + axitinib had the lowest HR compared with placebo + interferon on discontinuations due to AE (HR = 1.04, 95% CrI = 0.54-1.86). For second-line therapy, cabozantinib was identified as the most effective treatment option when assessing PFS (HR = 0.17, 95% CrI = 0.12-0.24). Axitinib had the lowest HR of OS and discontinuation due to AE (HR = 0.54, 95% CrI = 0.40-0.71; HR = 0.98, 95% CrI = 0.42-1.97, respectively). Pazopanib was the second choice in terms of OS (HR = 0.56, 95% CrI = 0.28-1.00; SUCRA = 76%) compared with placebo. What is new and conclusion With respect to PFS and OS improvement, cabozantinib, avelumab + axitinib and pembrolizumab + axitinib are likely to be the preferred options for the first-line therapy and cabozantinib and axitinib for the second-line therapy in the management of mRCC. Regarding safety, avelumab + axitinib and temsirolimus were considered preferred treatment options in first-line and second-line therapies. More future research is needed to establish subgroup analyses, allowing evaluation of the impact of some of the differences in patient characteristics, including treatment effect modifiers.

RATIONALE, AIMS, AND OBJECTIVES Previous research has shown inconsistent results regarding the association of depression and screening mammography use behaviours. This study aimed to assess the relationship between women's depression and mammography adherence. METHODS This cross-sectional study used data from the 2016 Behavioural Risk Factor Surveillance System and employed the Health Belief Model (HBM). The primary independent variable was the presence of depression. The dependent variable was adherence to biennial screening mammography based on the US Preventive Services Task Force guidelines. Demographic characteristics and HBM constructs were included as covariates. Univariate and multivariate logistic regressions were used. RESULTS A total of 139 550 women were included (weighted n = 48 712 531). Among them, 23.1% reported the presence of depression (n = 32 247). The unadjusted odds ratio (OR) for mammography use in women with depression was 0.85 (95% confidence interval [CI], 0.80-0.91, P

Introduction Few studies have compared cost-effectiveness of different smoking cessation interventions (SCIs) that include behavioral support, considering smoking-related diseases. Therefore, we compare the cost-effectiveness of SCIs with behavioral support in South Korea using the Benefits of Smoking Cessation on Outcomes (BENESCO) model. Aims and Methods We used the BENESCO model to estimate the cost and utility of the SCIs with behavioral support, including pharmacist counseling with nicotine replacement therapy (pharmacist+NRT), expert counseling with NRT (expert+NRT), and expert counseling with varenicline (expert+varenicline). The target population was adult smokers who wanted to cease smoking within 1 month. We applied transitional probabilities and epidemiological data from the literature. Medical costs and utilities were calculated using claims and national survey data, respectively. Cost-effectiveness was evaluated within the threshold (17 926 USD per quality-adjusted life years [QALYs]) by incremental cost-effectiveness ratio (ICER). Results The model cohort included 1 219 390 male and 298 511 female smokers. The pharmacist+NRT group had 32 842 more QALYs gained and 26 689 958 USD less expended than the expert+NRT group. The ICER for the expert+varenicline group versus the pharmacist+NRT and expert+NRT groups was 27 247 and 4074 USD per QALY, respectively. The robustness of the results was confirmed by sensitivity analyses, except for the discount rate and cost of the expert+varenicline group. Conclusions In Korea, pharmacist counseling with NRT showed higher QALY gains and lower costs than expert counseling with NRT. Expert counseling with varenicline was more effective for smoking cessation and more cost-effective than expert counseling with NRT but was not cost-effective compared with pharmacist counseling with NRT. Implications This study provides evidence for decision-making on smoking cessation programs by evaluating the cost-effectiveness of SCIs. Furthermore, we attempted to use the BENESCO model to compare and evaluate the cost-effectiveness of SCIs with behavioral support. It is meaningful because this study showed the availability of using the BENESCO model in the future cost-effectiveness analysis of various SCIs.

Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision-making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. We searched PubMed and the Cochran Library to identify the published economic evaluation studies of TKIs in NSCLC patients that were published by January 2022. All of the included studies (n = 38) evaluated the cost-effectiveness of epidermal growth factor receptor (EGFR)-TKIs (n = 29) or anaplastic lymphocyte kinase (ALK)-TKIs (n = 9). The cost-effectiveness results were reported as the incremental cost-effectiveness ratio per quality-adjusted life-year, except for three studies. We found that the economic evaluation studies of the first and second generation of EGFR-TKIs and ALK-TKIs varied by the country and study settings, such as comparator and input parameters. In 12 studies, osimertinib (EGFR-TKI) was not cost-effective compared to other first/second EGFR-TKIs, regardless of the study settings. More evidence can be provided about cost-effectiveness of the third-generation TKIs in future research.

The evidence regarding the impact of individual adjuvant endocrine therapies (AET) on health-related quality of life (HRQoL) is limited. We aimed to assess the association between the type of AET and HRQoL and to examine the relationship between HRQoL and one-year mortality among women with breast cancer in the USA.This retrospective cross-sectional study used the 2006-2017 Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey database to identify older women with early-stage hormone receptor-positive breast cancer. Multivariate linear regressions were used to assess the association between types of AET (anastrozole, letrozole, exemestane, and tamoxifen) and HRQoL scores (physical component summary (PCS) and mental component summary (MCS)). Multivariate logistic regressions were used to predict the impact of PCS and MCS on one-year mortality.Out of 3537 older women with breast cancer, anastrozole was the most commonly prescribed (n = 1945, 55.0%). Regarding PCS, there was no significant difference between the four AET agents. Higher MCS scores, which indicate better HRQoL, were reported in patients treated with anastrozole (vs. letrozole [β = 1.26, p = 0.007] and exemestane [β = 2.62, p = 0.005) and tamoxifen (vs. letrozole [β = 1.49, p = 0.010] and exemestane [β = 2.85, p = 0.004]). Lower PCS and MCS scores were associated with higher one-year mortality, regardless of type of AET initiated, except for tamoxifen in MCS.Although there was no significant difference in physical HRQoL scores between AET agents, anastrozole and tamoxifen were associated with better mental HRQoL scores.

Introduction: With the advent of targeted therapy, the U.S. Food and Drug Administration has recently approved several oral anticancer medications (OAMs) for breast cancer (BC). Despite the improved effectiveness of those OAMs, the high financial burden is an issue. Evidence from cost-effectiveness analysis (CEA) can provide valuable information for decision-makers when deciding whether to use these high-priced medications. Many CEAs on OAMs have been conducted using various analytical approaches and cost-effectiveness thresholds (CETs). However, there is no comprehensive systematic review of CEAs across all OAMs. Area covered: PubMed and Cochrane library were used to select for CEAs of OAM for BC in the U.S. published by May 2019. Among the 25 included studies, studies published between 1993 and 2011 analyzed either early BC (n = 11) or advanced/metastatic BC (n = 5), those between 2012–2019 analyzed advanced/metastatic BC (n = 9). Studies including targeted therapies were published after 2009. The CETs tended to increase over time and were higher in the studies for advanced/metastatic BC (median = $125,000) than those for early BC (median = $50,000). Expert commentary: The target population and medications of interest have changed and the methods of articles have evolved. The range of CETs tends to differ by study setting with an increase over time.

9134 Background: Next-generation sequencing (NGS) has been covered by Korean national health insurance since March 2017 for patients with advanced non-small cell lung cancer (NSCLC). We explored the clinical and socioeconomic impact of NGS compared with that of a single gene test (SGT) alone. Methods: From the nationwide database, we identified patients who 1) are diagnosed with advanced NSCLC classified as a distant disease using Summary Stage between March 1, 2017, and December 31, 2018; 2) had NGS or SGT within 2 months after diagnosis of advanced NSCLC. Patients with squamous cell carcinoma were excluded. We conducted multivariate logistic regression to identify factors (e.g., age, sex, Charlson comorbidity index, insurance type, year of diagnosis, and region and type of hospital with the initial diagnosis) affecting the performance of NGS. Further, we divided the cohort into subgroups based on whether patients received treatment targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations (group A) or not (group B). We conducted 1:5 propensity score matching for each group to minimize the impact of confounding factors. The median overall survival and the adjusted hazard ratio (aHR) for death were estimated using the Kaplan-Meier method and the Cox proportional hazard model, respectively. We calculated the total medical cost, and per patient per year (PPPY) cost adjusted for the survival period. Results: Among 10,247 patients with advanced NSCLC, 768 patients were identified as group A and 1,596 as group B after matching. Old age, low household income, and rural region were factors negatively impacting on having NGS tests. In Group A, we did not find a significant difference in survival outcome between the NGS cohort and the SGT cohort (median survival 31.6 vs. 27.5 months, P =.331; aHR 0.80, P =.204). In contrast, significantly favorable survival was observed for the NGS group in Group B (median survival 14.1 vs. 9.5 months, P =.023; aHR 0.80, P =.009). Although the total medical cost was higher in the NGS group ($39,145) than the SGT group ($36,207) for Group B, the PPPY cost was lower in the NGS group ($57,502 and $63,293, respectively). Conclusions: Socioeconomic factors hampering the implementation of NGS were identified. Lowering the barrier by covering the NGS cost publicly in a specific clinical setting may have survival and cost-benefit in patients with advanced NSCLC.

3602 Background: Next-generation sequencing (NGS) has been covered by Korean national health insurance since March 2017 for patients with advanced colorectal cancer (CRC). We explored the clinical and socioeconomic impact of NGS compared with that of a single gene test (SGT) alone. Methods: From the nationwide database, we identified patients who 1) are diagnosed with advanced CRC classified as a distant disease using Summary Stage between March 1, 2017, and December 31, 2018; 2) had NGS or SGT within 2 months after diagnosis of advanced CRC. Multivariate logistic regression with covariates including age, sex, Charlson comorbidity index, insurance type, year of diagnosis, and region and type of hospital with the initial diagnosis was conducted to identify factors affecting the performance of NGS. We conducted 1:3 propensity score matching to minimize the impact of confounding factors. The median overall survival and the adjusted hazard ratio (aHR) were estimated using the Kaplan-Meier method and the Cox proportional hazard model, respectively. We calculated the total medical cost, and per patient per year (PPPY) cost adjusted for the survival period. Results: Among 5,029 patients with advanced CRC, 655 patients were identified as NGS group and 1,995 as SGT group after matching. Old age, low household income, rural location, and non-tertiary hospital were all characteristics that reduced the likelihood of obtaining an NGS test. The NGS group showed significantly favorable survival compared to the SGT group (median survival 29.2 vs. 24.9 months, P =.031; adjusted hazard ratio [HR] 0.86, P =.034). The total medical cost was lower in the NGS group ($55,445) than the SGT group ($57,989), and the PPPY cost was also lower in the NGS group ($44,879 and $49,734, respectively). Conclusions: We found that some socioeconomic factors such as age, insurance type, region, and hospital type may hamper the implementation of NGS. Also, lowering the barrier of NGS tests by reimbursing NGS in a specific clinical setting may have survival and cost-benefit in patients with advanced CRC.

OBJECTIVES: Breast cancer and heart failure (HF) are frequently interconnected due to shared risk factors and the cardiotoxicity of breast cancer treatment. However, the association between HF and hospital outcomes among breast cancer patients has not been studied. This study examined the association between HF and hospital outcomes among hospitalized patients with breast cancer. METHODS: This cross-sectional study using the 2015–2018 Healthcare Cost and Utilization Project-National Inpatient Sample data included hospitalized women who were aged 18 years or older and had a primary diagnosis code for breast cancer. Logistic regression, negative binomial regression, and generalized linear models with log-link and gamma distribution were used to assess the associations of HF with in-hospital mortality, length of stay (LOS), and hospital costs. RESULTS: Among 17,335 hospitalized patients with breast cancer, 4.2% (n = 1,021) had HF. Compared to breast cancer patients without HF, those with HF were more likely to die during hospitalization (odd ratio = 1.65, 95% CI = 1.27–2.16, p < 0.001), stay in the hospital longer (incidence rate ratio = 1.22, 95% CI = 1.15–1.30, p

Background: Patients with renal cancer are at increased risk of comorbid congestive heart failure (CHF) due to several shared risk factors and the cardiotoxicity of some medications used for renal cancer treatment. We aimed to examine the relationship between CHF and hospital outcomes among renal cancer patients in the U.S. Methods: In this cross-sectional study, we identified hospitalizations of renal cancer patients using the 2015–2017 National Inpatient Sample. We assessed the relationship between CHF and hospital outcomes in this patient population, including in-hospital mortality, length-of-stay (LoS), and hospital costs. Results: Among the 20,321 hospitalizations of renal cancer patients identified, 6.1% involved patients with comorbid CHF (n = 1,231). The odds of in-hospital mortality did not differ based on CHF presence (odds ratio = 1.21; p = 0.354). Hospitalizations of renal cancer patients with CHF were associated with a greater LoS (incidence rate ratio = 1.44; p Conclusions: CHF in renal cancer patients is associated with increased LoS and higher hospital costs. These findings suggest that optimal management of comorbid CHF may improve hospital outcomes in patients with renal cancer and provides evidence to support the emerging field of cardio-oncology.

Recognizing the value of anticancer treatments based on progression-free survival and overall survival may help decision making in healthcare policy. We aimed to measure and compare the impact of disease progression and terminal state prior to death on healthcare costs in HR+, HER2- ABC patients.We conducted a retrospective study using Korean nationwide health insurance claims database between 1 September 2012 and 31 August 2017. The impact of disease progression was estimated by measuring the average incremental monthly cost per patient during 1 year after progression compared to 1 year before progression. Death-related costs per patient per month (PPPM) were measured for those who died within 1 year after progression. Generalized estimating equation (GEE) was used to estimate the variations in PPPM costs by progression and death with adjustment for clinical factors.After progression, 1,636 patients expensed $2,892 per month more on average than before progression ($3762 vs. $870). The GEE analysis with adjustment for baseline characteristics showed that PPPM costs increased by 3.46 folds (95% CI = 3.06-3.93) after progression. Also, PPPM costs were 1.74 (95%CI = 1.43-2.12) times higher in patients who died within 1 year after progression relative to survived patients. When considering the interaction between progression and death, deceased patients showed higher increased ratio of PPPM costs after progression (4.91;From the payer's perspective, more healthcare costs incurred during the progression state than terminal state in HR+, HER2- ABC patients. The impact of disease progression emphasizes the importance of effectively treating HR+, HER2- ABC patients.

ObjectiveTo explore differences in end-of-life healthcare utilisation and medication costs between patients with haematological malignancies and patients with solid tumours.MethodsData on deceased patients with cancer were selected from the sample cohort data of health insurance claims from 2008 to 2015 in South Korea. They were categorised into two groups: patients with haematological malignancies and patients with solid tumours. Longitudinal data comprised the patient-month unit and aggregated healthcare utilisation and medication cost for 1 year before death. Healthcare utilisation included emergency room visits, hospitalisation and blood transfusions. Medication costs were subdivided into anticancer drugs, antibiotics, opioids, sedatives and blood preparation. Generalised linear mixed models were used to evaluate differences between the two groups and time trends.ResultsOf the 8719 deceased patients with cancer, 349 died from haematological malignancies. Compared with solid tumours, patients with haematological malignancies were more likely to visit the emergency room (OR=1.36, 95% CI 1.10 to 1.69) and receive blood transfusions (OR=5.44, 95% CI 4.29 to 6.90). The length of hospitalisation of patients was significantly different (difference=2.49 days, 95% CI 1.75 to 3.22). Medication costs, except for anticancer treatment, increased as death approached. The costs of antibiotics and blood preparations were higher in patients with haematological malignancies than in those with solid tumours: 3.24 (95% CI 2.14 to 4.90) and 4.10 (95% CI 2.77 to 6.09) times higher, respectively.ConclusionsPatients with haematological malignancies are at a higher risk for aggressive care and economic burden at the end of life compared with those with solid tumours. Detailed attention is required when developing care plans for end-of-life care of haematological patients.

Introduction/Background Adenomyosis is usually benign, but it might also be a precursor of malignant disease. As the incidence of adenomyosis malignant transformation is low, and its clinical manifestations are nonspecific. It may only be confirmed by postoperative pathological examination. We report our experience with case of malignant transformation of adenomyosis with endometrial adenocarcinoma. Methodology This retrospective study was examined using data at Uijeongbu St. Mary’s Hospital from the 2014 to 2018. A total of 27 women has endometrial cancer combined adenomyosis or endometriosis. Ant Only one person has related with elevated CA19-9. Results Sixty-two years-old nulliarous woman visited our department at Jan 2019 due to intermittent vaginal bleeding over 1 month. Ultrasound showed hematometra and adenomyosis. The histological examination of the endometrium yielded adenocarcinoma, moderately differentiated. Magnetic resonance imaging (MRI) revealed focal adenomyosis, hematometra and a few small nonspecific LNs in right external iliac and obturator. Among the pre-operative tumor markers, CA19-9 level was increased (36.80U/ml, normal range Laparoscopic total hysterectomy and bilateral adnexectomy including pelvic lymphadenectomy were performed. The intra-abdominal cytology was negative. In the pathological specimen, poorly differentiated endometrioid adenocarcinoma was present in endometrium with myometrial invasion less then 0.1 cm from endometrial-myometrial junction (T1a, thickness of uninvolved myometrium was 1 cm). Pelvic lymph node metastasis was not found. Very small Foci of adenocarcinoma were observed in adenomyosis (0.1 × 0.1 sized). Although surgical stage was Ia, due to the histologic grade and high risk factors (>60 yrs), recurrence risk was existed. Adjuvant vaginal brachytherapy was performed after surgery. She is currently undergoing follow-up observations. Conclusion From this case, we concluded that if CA19-9 is elevated before surgery, a more detailed histological observation is needed in the adenomyotic foci. Disclosure Adenomyosis, endometrial carcinoma, CA 19-9, malignancy.

Purpose Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is a possible treatment option for chronic heart failure patients with reduced ejection fraction (HFrEF). The aim of this study was to estimate the cost-effectiveness of sacubitril/valsartan use in South Korea for treating patients with HFrEF compared with that of enalapril, an angiotensin-converting enzyme inhibitor, and with angiotensin receptor blockers (ARBs). Methods A Markov model was designed to estimate the lifetime cost-effectiveness of treatment for patients with HFrEF. Cohorts in the alive-state incurred a monthly risk of hospitalization because of deteriorated HF, adverse events (AEs), or death. Transition probabilities of sacubitril/valsartan and enalapril were estimated by using data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. The effectiveness of ARBs (eg, reduction in mortality and hospitalization rates) was assumed to be identical to that of enalapril, according to the results of the meta-analysis. However, there was no comparative evidence for AEs. We therefore conducted a Bayesian network meta-analysis and adjusted the incidence rate of AEs for ARBs. The utility for estimating quality-adjusted life years (QALYs) was elicited by the survey of the general South Korean population by using EuroQol-5 dimensions. We calculated the medical costs, including medication, monitoring, hospitalization, AEs, and terminal care, from the health care sector perspective. Costs and effectiveness were discounted by 5%. One-way sensitivity analyses and a probabilistic sensitivity analysis were conducted to determine the model robustness. Findings The total cost per patient for sacubitril/valsartan and enalapril was $25,832 and $18,295, respectively. Sacubitril/valsartan was associated with an ∼8- month longer life expectancy compared with enalapril and a QALY gain of 0.59. As a result, the incremental cost-effectiveness ratio for sacubitril/valsartan versus enalapril was $12,722 per QALY. The incremental cost-effectiveness ratio of sacubitril/valsartan versus ARB was $11,970 with an incurred cost of $18,741 for the ARB group. The main results and those of various sensitivity analyses were lower than a threshold of $20,000. Implications From a health care sector perspective, sacubitril/valsartan is a cost-effective treatment for HFrEF compared with enalapril and ARBs. This finding could be helpful for cardiologists or decision makers in reaching cost-effective choices regarding the treatment selection process.

Objectives We investigated the risk of dementia associated with the use of proton pump inhibitors (PPIs) as compared with the use of histamine-2 receptor antagonist (H2RA). Methods We conducted retrospective propensity score-matched cohort study using the National Health Insurance Service-National Sample Cohort. Subjects were defined as the patients newly prescribed with PPI or H2RA between 2003 and 2013 without prior prescriptions of PPI/H2RA or diagnosis of dementia from their history within the past 1 year. We followed up participants until dementia occurrence, death, or the end of the study, whichever occurred first, with an intention-to-treat approach. A 1-year lag time between exposure and outcome measure was used to reduce protopathic bias. The incidence rate per 1000 person-years was estimated. The incidence rate of PPI was compared with that of H2RA, defined as incidence rate ratio (IRR), calculated with a 95% confidence interval. To control for potential confounds, propensity score matching at a 1:1 ratio was conducted, and the crude IRR was adjusted by risk factors. Results Our propensity score-matched cohort included 87 562 patients on PPIs and 87 562 patients on H2RAs. The IRR was 1.01 (95% confidence interval 0.96-1.06) with 1-year lag time. IRR showed the decreased trend as the longer lag time. Also, no treatment duration or dose-response relationship was observed. Conclusions Our finding demonstrated that PPIs did not associate with dementia more strongly than did H2RA. On this basis, we suggest that the previously reported risk for dementia associated with PPI may have been overestimated.

Background Although elderly patients with asthma have clinical characteristics different from those of young adults, few studies or guidelines have focused on specific treatments for this population. Objective This study compared the effectiveness of leukotriene receptor antagonists (LTRAs) versus inhaled corticosteroids (ICSs) in elderly patients with asthma in real-world settings. Methods We extracted records for elderly patients with asthma who were newly prescribed LTRAs or low-dose ICSs from January 2003 to December 2010 from National Sample Cohort data of Korea. We defined the first prescription date for each medication as the index date. We compared the risks of asthma exacerbation between the 2 groups using Cox proportional-hazard regression after propensity score–based inverse probability of treatment weighting to balance covariates between treatment groups. We also compared asthma-related health care resource utilization and medication compliance in both groups using chi-square test and t test. Results The number of identified patients newly treated with LTRAs and low-dose ICSs was 1571 and 121, respectively. The risks of asthma exacerbation in the LTRA and low-dose ICS groups after weighting were not significantly different (hazard ratio, 0.98; 95% CI, 0.65-1.54). The proportion with high compliance (medication possession ratio ≥ 80%) in the LTRA group was higher than that in the low-dose ICS group. Conclusions The effectiveness of LTRAs was not different from that of low-dose ICSs regarding the risk of asthma exacerbation in elderly patients with asthma in real-world settings. Given the practical benefits gained from convenient administration, LTRAs can be considered a reasonable alternative first-line therapy for elderly patients with mild asthma.

Background Systemic sclerosis (SSc) is a rare autoimmune disease characterised by vasculopathy and fibrosis of various organs including skin. Although SSc has high morbidity and mortality, evidences for disease modifying treatment are still lacking due to difficulties in performing clinical trials. Patient-specific induced pluripotent stem cells (iPSCs), which can differentiate into various cell types, are used in 3D organoid formation. Objectives We generated 3D skin organoid model from SSc-derived iPSCs by differentiating them into keratinocytes and fibroblasts. SSc-mimicking 3D skin organoid can be used in studies for disease modelling and drug screening. Methods Peripheral blood mononuclear cells (PBMCs) from patients with SSc were reprogrammed to iPSCs. SSc-derived iPSCs differentiated into keratinocytes and fibroblasts in vitro. Expression of markers for iPSCs, keratinocytes, and fibroblasts were determined by reverse transcription polymerase chain reaction (RT-PCR) analysis and immunofluorescence assay (IFA). 3D skin organoid using iPSC-derived differentiation cell line was generated by 3D culture system. Histologic analysis was performed on 3D skin organoid. SSc-derived 3D skin organoid was applied to SCID skin defect mice. Histologic analysis was also performed on SCID skin graft model. Results SSc-derived iPSCs formed colonies that resemble embryonic stem cells. Alkaline phosphatase staining showed undifferentiated state of iPSCs. Expression of iPSC markers was increased on SSc-iPSCs. Differentiated keratinocytes and fibroblasts from iPSCs highly expressed their markers for keratinocytes and fibroblasts, respectively. Dermis of SSc-derived 3D skin organoid was thicker and denser than that derived from healthy control. Epidermis and dermis of SCID skin graft model were thickened in those derived from SSc compared to those derived from healthy control. Conclusions Patient-derived 3D skin organoid and animal model well represented the characteristics of SSc. These models can serve as useful research tools to understand the disease and screen new drugs for SSc. Disclosure of Interest None declared

Background Sjogren’s syndrome (SS) is a systemic autoimmune disease that affects exocrine glands and lymphoid organs. B cell hyperactivity and imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells are involved in pathogenesis of SS. Metformin, a commonly used anti-diabetic drug, is found to have immunomodulatory effect via AMP-activated protein kinase enhanced inhibition of mTOR-STAT3 signalling. Objectives We examined the therapeutic effect of metformin on SS by using animal model of SS, non-obese diabetic (NOD) mice. Methods Metformin (50 mg/kg) or vehicle (saline) was given per oral every day from 11 weeks after birth until 20 weeks. Salivary flow rate (SFR) was addressed on every 2 or 3 weeks between 11 weeks and 20 weeks. Histologic analyses of salivary gland and spleen were performed on week 20. Expression of Inflammatory cytokine was determined by immunohistochemistry analysis and real-time PCR. Flow cytometry was performed with peripheral blood to examine Th17 and Treg cells and germinal centre (GC) B cell populations. Serum immunoglobulin level was measured by enzyme-linked immunosorbent assay. Splenic cells of NOD mice were treated with metformin or vehicle in vitro and cultured for 3 days. Results SFRs of metformin-treated mice recovered, whereas SFRs of those treated with vehicle declined. Histologic examination of salivary gland showed decreased infiltration of lymphocytes and reduced expression of IL-6 and TNF-alpha in metformin-treated mice. Relative expression of IL-6, TNF-alpha, and IL-17 mRNA in salivary gland and spleen also declined in metformin-treated mice. Flow cytometric analysis revealed decreased Th1 and Th17 cells and increased Treg cells in peripheral blood of mice treated with metformin. In addition, GC B cells and immunoglobulin levels were reduced in peripheral blood of mice treated with metformin. Decreased Tfh cells and increased Tfr cells were observed from in vitro cultures of splenic cells treated with metformin. Conclusions Metformin controls B cell differentiation and keeps balance between Th17 and Treg cells in NOD mice, in addition to reducing lymphocytic infiltration and inflammatory cytokine expression in salivary gland. Metformin has potential therapeutic effects on SS. References [1] Lee SY, Moon SJ, Kim EK, Seo HB, Yang EJ, Son HJ, et al. Metformin Suppresses Systemic Autoimmunity in Roquinsan/san Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3. J Immunol2017;198–2661–70. [2] Pontarini E, Lucchesi D, Bombardieri M. Current views on the pathogenesis of Sjgren’s syndrome. Curr Opin Rheumatol2017. Disclosure of Interest None declared

Background Spondyloarthritis (SpA) is inflammatory arthritis, and interleukin (IL) −17 is crucial on pathogenesis of SpA. Type 17 helper T cell (Th17) is one of major IL-17 secreting cells. Signal transducer and activator of transcription (STAT)−3 signalling induces Th17 cell differentiation. Present study investigated the effect of protein inhibitor of activated STAT3 (PIAS3) on SpA pathogenesis. Methods Curdlan was injected to SKG ZAP-70W163C mice for SpA induction. Then PIAS3 or Mock vector was inserted to mice for 10 weeks. Clinical score and histologic scores of paw, spine, and gut were evaluated. Expressions of IL-17, tumour necrosis factor-α (TNF-α), STAT3, bone morphogenic protein (BMP) were measured. Confocal stain and flow cytometry were used to assess helper T cell differentiation. Results PIAS3 significantly diminished the histological scores of paw and gut. PIAS3 group displayed lesser expression of IL-17, TNF-α, and STAT3 in the paw, spine, and gut. BMP-2/4 expressions were lower in spine of PIAS3 group. Helper T cell differentiation was polarised toward upregulation of regulatory T cell (Treg) and downregulation of Th17 in the PIAS3 mice. Conclusions PIAS3 showed preventive effects in mice with SpA by suppressing peripheral arthritis and gut inflammation. Proinflammatory cytokines and Th17/Treg differentiation were controlled by PIAS3. Additionally BMPs were decreased in spine of PIAS3 mice. These findings suggest that PIAS3 could be a potential therapeutic choice of SpA treatment. References [1] Smith JA, Colbert RA: Review: The interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis & rheumatology2014, 66:231–41. [2] O’Shea JJ, Lahesmaa R, Vahedi G, Laurence A, Kanno Y. Genomic views of STAT function in CD4+ T helper cell differentiation. Nature reviews Immunology2011;11:239–50. [3] Miossec P, Korn T, Kuchroo VK: Interleukin-17 and type 17 helper T cells. The New England journal of medicine2009;361:888–98. [4] Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K, Velasco J, Strutton G, Tran A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, Pettit AR, Brown MA, McGuckin MA, Thomas R. beta-glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Arthritis and rheumatism2012;64:2211–22. Acknowledgements None Disclosure of Interest None declared

Utility provides a preference for specific health state in economic evaluation, and they obtained from general population could be useful in respect of societal resource allocation. We aimed to investigate the utilities of health states for heart failure (HF), a major and growing public health problem, related to hospitalization and adverse drug effects by interrogating the general Korean population. Five health states for patients with HF were developed based on literature reviews: stable chronic heart failure (SCHF), hospitalization, SCHF + cough, SCHF + hypotension, and SCHF + hyperkalemia. We selected 100 individuals from the general population through quota sampling by age, sex, and region, and conducted face-to-face interviews. We measured utilities for 5 hypothetical health states of HF using both time trade-off (TTO) and EuroQol-5 dimensions-5 levels (EQ-5D-5L). Repeated-measures analysis of variance compared the utilities between all health states for each instrument. To identify the factors affecting the utility, a linear mixed model (LMM) analysis was performed. The mean utility value for SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization was calculated as 0.815, 0.732, 0.646, 0.548, and 0.360, respectively, by using TTO. The respective values using EQ-5D-5L were 0.871, 0.793, 0.710, 0.589, and 0.215. The utilities for HF significantly differed between all health states in each instrument (p

Introduction: Studies have found an association between the use of proton pump inhibitors (PPIs) and dementia, but these findings may have been confounded by selection biases. Objective: We used prescription sequence symmetry analysis (PSSA) to estimate the sequence ratio (SR) between PPI use and dementia compared with an active comparator, the use of histamine-2 receptor antagonists (H2RAs). Methods: We conducted a PSSA on a nationwide South Korean database between 2002 and 2013. Exposure was defined as new PPI users, and outcome was defined as a new dementia diagnosis (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] codes F00-03, F05.1, G30, G31.1, G31.9, G31.82). In this study, we applied the 3-year time window. So the patients who initiated PPIs 3 years before or after their first diagnosis of dementia were included. The pairs with the time window < 6 months were excluded to minimize the potential protopathic bias. The SR was calculated as the number of patients first diagnosed with dementia after initiating PPI (causal group) divided by the number of patients first diagnosed with dementia before the initiation of PPI (non-causal group). The SR was adjusted (aSR) to avoid the distortion of results due to underlying trends in PPI use and dementia diagnosis over time. We calculated 95% confidence intervals (CIs) for the aSR. The analysis was repeated for initiators of H2RAs. Sensitivity analyses were conducted using 1-, 2-, and 6-year time windows and using the initiation of medication for dementia treatment (Anatomical Therapeutic Chemical code: N06D). Results: Our results showed that the aSR of dementia and PPIs (7342 pairs, aSR 1.21 [95% CI 1.16–1.27]) was not higher than that for dementia and H2RAs (6170 pairs, aSR 1.91 [95% CI 1.80–2.02] ). When we used various time windows and restricted the findings to the use of medication for treating dementia, the results were consistent with the main results. Conclusion: The risk of PPIs being associated with dementia may be overestimated. Further pharmacoepidemiological studies are needed to identify the risk of dementia with PPI use. Refereed/Peer-reviewed

This study examined the effect of feeding heat-killed Lactobacillus cells on the survival of Caenorhabditis elegans nematodes after Salmonella Typhimurium and Yersinia enterocolitica infection. The feeding of heat-killed Lactobacillus plantarum 133 (LP133) and Lactobacillus fermentum 21 (LP21) cells to nematodes was shown to significantly increase the survival rate as well as stimulate the expression of pmk-1 gene that key factor for C. elegans immunity upon infection compared with control nematodes that were only fed Escherichia coli OP50 (OP50) cells. These results suggest that heat-killed LP133 and LF21 cells exert preventive or protective effects against the Gram-negative bacteria Salm. Typhimurium and Y. enterocolitica. To better understand the mechanisms underlying the LF21-mediated and LP133-mediated protection against bacterial infection in nematodes, transcriptional profiling was performed for each experimental group. These experiments showed that genes related to energy generation and ageing, regulators of insulin/IGF-1-like signalling, DAF genes, oxidation and reduction processes, the defence response and/or the innate immune response, and neurological processes were upregulated in nematodes that had been fed heat-killed Lactobacillus cells compared with nematodes that had been fed E. coli cells. Significance and Impact of the Study In this study, the feeding of heat-killed Lactobacillus bacteria to Caenorhabditis elegans nematodes was shown to decrease infection by Gram-negative bacteria and increase the host lifespan. C. elegans has a small, well-organized genome and is an excellent in vivo model organism; thus, these results will potentially shed light on important Lactobacillus-host interactions.

Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied.Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO.In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection.These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

Axial spondyloarthritis (axSpA) is associated with low bone mineral density (BMD) and fractures, although the true fracture risk is unknown. The present study examined BMD and estimated the 10-year fracture risk in axSpA patients and matched controls and identified factors associated with a high fracture risk.In total, 240 axSpA patients and 1200 healthy controls from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V), matched using propensity scores, were included. Dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine and right femur BMD. Ten-year risks of major osteoporotic and hip fractures were calculated using the Fracture Risk Assessment Tool (FRAX) in subjects aged ≥ 40 years. Multivariate linear regression models were used to explore factors associated with the 10-year fracture risk in axSpA patients.Hip and lumbar spine BMDs were lower in axSpA patients than in matched controls. Osteoporosis was present in 17% of axSpA patients and 3% of controls (p 0.001). Low BMD was present in 22% of axSpA patients and 4% of controls aged 50 years (p 0.001). Ten-year major osteoporotic and hip fracture risks were significantly higher among axSpA patients. High 10-year fracture risk was observed in 10% of axSpA patients and 1.7% of controls (p = 0.003). The severity of sacroiliitis was independently associated with both major osteoporotic and hip fracture risks (p = 0.006 and 0.026, respectively).Patients with axSpA presented more frequently with low BMD and a higher calculated 10-year fracture risk than matched individuals. The severity of sacroiliitis was independently associated with a high 10-year fracture risk in axSpA patients.

We investigated obstetric outcomes and comorbidities during pregnancy in females with preexisting lupus nephritis (LN) and identified predictors for renal flare. In cases of renal flare during pregnancy, we assessed the long-term post-delivery renal outcome. We performed a retrospective analysis of 183 systemic lupus erythematosus (SLE) pregnancies including blood chemistry, urinalysis, urinary protein, and disease activity recorded at prepregnancy, during pregnancy, and at one month, six months, and one year post-delivery. Pregnancies with preexisting LN had a greater frequency of adverse obstetric outcomes and maternal comorbidity. Renal flares occurred in 50.7% of pregnancies with preexisting LN, 89.2% of which were reactivations. Renal flare among pregnancies with SLE was predicted based on preexisting lupus nephritis (OR 17.73; 95% CI, 5.770–54.484), an active disease prior to pregnancy (OR 2.743; 95% CI, 1.074–7.004), and prepregnancy eGFR 2 (OR 11.151; 95% CI, 3.292–37.768). Persistent LN one year after delivery was observed in 33.3% of pregnancies. The median follow-up time after delivery was 5.9 (3.1–9.7) years and chronic kidney disease (CKD) occurred in 21.4% of pregnancies with renal flare. In patients with renal flare, failing to achieve a ≥ 50% reduction in urine protein levels within six months, longer total duration of renal flare, and acute kidney injury at renal flare was associated with CKD development. Females with preexisting LN should achieve remission before pregnancy. When patients experience renal flares during pregnancy, it is important to reduce the proteinuria level by >50% within six months and to achieve early remission for excellent long-term renal outcomes.

Background CT-P13 is approved in both European Union and United States, and licensed for use in 79 countries around the world as a biosimilar to innovator infliximab (INX). The independent registries of CT-P13 have been conducted in a number of European countries and Korea [1]. Objectives To evaluate safety and effectiveness of CT-P13 when administered in a real-life setting in active RA patients. Methods This study collected data of patients who were treated with CT-P13 from 2013 December to 2016 June. Efficacy was assessed at baseline and every 6 months thereafter using DAS28 (ESR) and/or DAS28 (CRP) and collection of adverse events (AEs) was performed. Immunogenicity was assessed at baseline, Week 30 and every year during CT-P13 treatment period. Results Total 125 patients were enrolled; 104 patients started treatment with CT-P13 (Naive group) and 21 patients (8 from INX, 13 from other anti-TNFs) switched treatment to CT-P13 (Switching group). The mean (SD) duration since RA diagnosis was 6.5 (±6.85) years for all patients. Of all patients treated with CT-P13, only 4.8% (6/125) of patients changed to other anti-TNFs. Two of six patients changed treatment within 8 month after starting CT-P13. The proportion of patients achieving clinical remission by DAS28 (ESR/CRP) increased gradually (Figure 1). DAS28 (ESR/CRP) value decreased from baseline at 6 months and it maintained thereafter (Table 1). Switching group also showed similar results that remission rate by DAS28 (CRP) was 42.9% (3/7) and mean actual value was 2.85 at 12 months. For Naive group, 50% (52/104) of patients had at least one positive anti-drug antibody result and it is consistent to other published study [2]. Overall safety summarized as the percentage of patients with at least one treatment emergent AE (TEAE) was similar or lower after switching to CT-P13 (Table 2). No cases of active tuberculosis were reported. Conclusions The overall safety profile revealed that CT-P13 is well-tolerated in patients with RA and remission rate for 24 months also showed that CT-P13 is efficacious under real world practice. References Glintborg et al. ACR 2016. Krintel et al. Rheumatology 2013. Disclosure of Interest None declared

Background There have been several studies which demonstrated the impact of birth on the risk of certain diseases such as asthma or cardiovascular diseases. However, rheumatic diseases have not yet been thoroughly investigated in terms of association with birth month. Objectives In this study, we sought to determine whether birth month or season could affect the risk of rheumatologic diseases. Methods The birth month patterns of patients with rheumatic diseases were compared with to those of general population. We utilized the claims data of Health Insurance Review and Assessment Service (HIRA) which covers nearly 90% of total population in Korea. The associations between birth month/season and 32 diseases were investigated using logistic regression. Results Our dataset included 17,247,458 (male 8,224,670; female 9,022,788) individuals from HIRA database from January, 1997 to August, 2015. Among 27 rheumatic diseases, 8 diseases including Crohn9s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus, polymyalgia rheumatica (PMR), ankylosing spondylitis (AS), multiple sclerosis, gout, fibromyalgia (FMS) were significantly associated with birth month (P Conclusions We found significant impacts of birth month/season on various rheumatic diseases. Seasonal variation of infective agents, sun exposure or food ingestion during gestation or early infancy may explain the association between birth month/season and certain disease development. Disclosure of Interest None declared

Non-destructive testing on wire rope is in great demand to prevent safety accidents at sites where many heavy equipment using ropes are installed. In this paper, a research on quantification of magnetic flux leakage (MFL) signals were carried out to detect damages on wire rope. First, a simulation study was performed with a steel rod model using a finite element analysis (FEA) program. The leakage signals from the simulation study were obtained and it was compared for parameter: depth of defect. Then, an experiment on same conditions was conducted to verify the results of the simulation. Throughout the results, the MFL signal was quantified and a wire rope damage detection was then confirmed to be feasible. In further study, it is expected that the damage characterization of an entire specimen will be visualized as well.

Introduction: In order to look beyond the cost-effectiveness analysis, this study used a multi-criteria decision analysis (MCDA), which reflects societal values with regard to reimbursement decisions. This study aims to elicit societal preferences of the reimbursement decision criteria for anti cancer drugs from public and healthcare professionals. Methods: Eight criteria were defined based on a literature review and focus group sessions: disease severity, disease population size, pediatrics targets, unmet needs, innovation, clinical benefits, cost-effectiveness, and budget impacts. Using quota sampling and purposive sampling, 300 participants from the Korean public and 30 healthcare professionals were selected for the survey. Preferences were elicited using an analytic hierarchy process. Results: Both groups rated clinical benefits the highest, followed by cost-effectiveness and disease severity, but differed with regard to disease population size and unmet needs. Innovation was the least preferred criteria. Conclusions: Clinical benefits and other social values should be reflected appropriately with cost-effectiveness in healthcare coverage. MCDA can be used to assess decision priorities for complicated health policy decisions, including reimbursement decisions. It is a promising method for making logical and transparent drug reimbursement decisions that consider a broad range of factors, which are perceived as important by relevant stakeholders.

We investigated the clinical and laboratory characteristics of pregnancies with systemic lupus erythematosus (SLE) and identified lupus flare predictors during pregnancy. Additionally, we examined lupus activity and pregnancy outcomes in SLE patients who continued, discontinued or underwent no hydroxychloroquine (HCQ) treatment during pregnancy. We retrospectively analyzed 179 pregnancies in 128 SLE patients at Seoul St. Mary’s Hospital, Korea, between 1998 and 2012 and then assessed the clinical profiles and maternal and fetal outcomes. Overall, 90.5% of pregnancies resulted in a successful delivery and were divided into two groups: those who experienced lupus flares (80 pregnancies, 44.7%) and those who did not (99 pregnancies, 55.3%). Increased preeclampsia, preterm births, low birth weight, intrauterine growth restriction (IUGR), and low 1-minute Apgar scores occurred in pregnancies with lupus flares compared to pregnancies in quiescent disease. Lupus flares were predicted by HCQ discontinuation, a history of lupus nephritis, high pre-pregnancy serum uric acid and low C4 levels. Our study indicates that achieving pre-pregnancy remission and continuing HCQ treatment during pregnancy are important for preventing lupus flares.

Objective The objective of this paper is to identify the risk factors for development of symptomatic osteonecrosis (ON) and predictors of total hip replacement (THR) among systemic lupus erythematosus (SLE) patients in Korea. Methods The medical records of 1051 patients with SLE were reviewed, and 73 patients with symptomatic ON were identified. Among them, 64 patients were eligible for the analysis. Sixty-four age- and sex-matched SLE patients without apparent ON were included as disease controls. The risk factors for development of symptomatic ON were identified by logistic regression analyses. The predictors of THR were determined by Cox proportional hazards regression analyses. Results Among 64 patients with ON, 59 had ON of the hip and 36 underwent THR. Independent risk factors for development of symptomatic ON included Cushingoid body habitus (OR 21.792 (95% confidence interval (CI) 2.594–183.083)), use of cyclophosphamide (OR 2.779 (95% CI 1.106–6.981)) and azathioprine (OR 2.662 (95% CI 1.143–6.200)). In the Cox proportional hazards model, only advanced radiological stage of ON (Association for Research on Osseous Circulation (ARCO) stage) was a statistically significant predictor of THR. In subgroup analysis with stage I–III ON, multivariate Cox regression analysis showed neuropsychiatric SLE (NPSLE) (HR 6.295 (95% CI 2.178–18.192)) and cumulative prednisolone dose in the first six months after ON diagnosis > 0.9 g (HR 3.238 (95% CI 1.095–9.58)) to be independent predictors. Conclusions Advanced ARCO stage at the onset of ON is an independent risk factor for THR in SLE patients with ON. In ARCO stage I–III ON, patients with NPSLE and those receiving > 0.9 g prednisolone during the first six months after the ON diagnosis are likely to require THR.

Renal relapse in patients with lupus nephritis (LN) is a risk factor for poor renal function. Therefore, there is a need to identify clinical and serological risk factors for renal relapse. A total of 108 patients with LN were enrolled in this study. All the subjects had achieved complete remission or partial remission following six months of induction therapy. We retrospectively analyzed their clinical and laboratory indices, final renal function, and kidney biopsy findings. The median follow-up period after LN diagnosis was 81 months. Renal relapse had occurred in 36 patients; it occurred in 38% and 46% of patients within five and 10 years after achievement of renal remission, respectively. There was no difference between the relapsed rate in patients with complete remission and that in those with partial remission. Clinical variables at LN onset and renal biopsy findings in the patients with sustained remission and relapsed patients were also not different. The probability of renal relapse was significantly higher in patients with an earlier age of onset of systemic lupus erythematosus (SLE) (≤ 28 years versus >28 years; HR 7.308, P = 0.001), seronegativity for anti-Ro antibody (seronegativity versus seropositivity; HR 3.514, P = 0.007), and seropositivity for anti-dsDNA antibody at six months after initiation of induction therapy (HR 8.269, P = 0.001). Our study demonstrated that early onset of SLE, seronegativity for anti-Ro antibody and increased anti-dsDNA antibody following six months of induction therapy independently predict renal relapse among the LN patients.

The purpose of this study was to compare the discontinuation rates of tofacitinib and biologics (tumour necrosis factor inhibitors (TNFi), abatacept, rituximab, and tocilizumab) in rheumatoid arthritis (RA) patients considering inadequate responses (IRs) to previous treatment(s).Randomised controlled trials of tofacitinib and biologics - reporting at least one total discontinuation, discontinuation due to lack of efficacy (LOE), and discontinuation due to adverse events (AEs) - were identified through systematic review. The analyses were conducted for patients with IRs to conventional synthetic disease-modifying anti-rheumatic drugs (cDMARDs) and for patients with biologics-IR, separately. Bayesian network meta-analysis was used to estimate rate ratio (RR) of a biologic relative to tofacitinib with 95% credible interval (CrI), and probability of RR being1 (P[RR1]).The analyses of 34 studies showed no significant differences in discontinuation rates between tofacitinib and biologics in the cDMARDs-IR group. In the biologics-IR group, however, TNFi (RR 0.17, 95% CrI 0.01-3.61, P[RR1] 92.0%) and rituximab (RR 0.20, 95% CrI 0.01-2.91, P[RR1] 92.3%) showed significantly lower total discontinuation rates than tofacitinib did. Despite the difference, discontinuation cases owing to LOE and AEs revealed that tofacitinib was comparable to the biologics.The comparability of discontinuation rate between tofacitinib and biologics was different based on previous treatments and discontinuation reasons: LOE, AEs, and total (due to other reasons). Therefore, those factors need to be considered to decide the optimal treatment strategy.

The aim of this study was to determine whether the incidence of cancer has increased among patients with systemic sclerosis (SSc) in Korea.The study subjects consisted of 112 patients who had been consecutively evaluated for at least 6 months between 1990 and 2007. We retrospectively reviewed their medical records, investigated the incidence rate of cancer and compared it with that of the Korea National Cancer Centre database.Nine out of 112 patients developed cancer (four males and five females). The average age at diagnosis of cancer was 56.4 years and the mean disease duration was 8.9 years. The standardized incidence ratio (SIR) for SSc patients was 4.2 [95% confidence interval (CI) 2.3-6.1], 3.7 for women (95% CI 1.2-6.2) and 6.4 for men (95% CI 1.6-11.2). Lung cancer was the most common cancer (n = 4), followed by oesophagus (n = 1), stomach (n = 1), liver (n = 1), pancreas (n = 1), and squamous cell carcinoma of unknown origin (n = 1). All patients who developed lung cancer were female and non-small cell carcinoma in origin. The SIR of lung cancer in female patients was 23.0 (95% CI 6.0-40.0). Two out of four lung cancer patients had concomitant interstitial lung disease (ILD); all were non-smokers. Treatment agents, autoantibodies, smoking, and lung involvement were not significantly different between SSc patients with or without cancer.The SIR of cancer was significantly higher in SSc patients, and especially in those who were male, than in the general population. Lung cancer was the most common cancer. Active surveillance for the detection of cancer should be performed in all SSc patients.

The 5-HT3 receptor is a ligand-gated cation channel located in the central and peripheral nervous system; it has also been detected on a variety of other cells. In the periphery, it is found on autonomic neurons and on neurons of the sensory and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in the dorsal horn ganglia. Further extraneuronal locations include among others lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself. They have been demonstrated to be involved in sensory transmission, regulation of autonomic functions, integration of the vomiting reflex, pain processing and control of anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and difficult to detect, it plays a key role in certain pathologic situations related to increased serotonin release. Clinical development of 5-HT3 receptor antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists do not modify any aspect of normal behaviour in animals or induce pronounced changes of physiological functions in healthy subjects. Clinical efficacy was shown for various forms of emesis like chemotherapy-induced, radiotherapy-induced, and postoperative emesis, diarrhoea-predominant irritable bowel syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3 receptor antagonists are effective for the treatment of other rheumatic diseases such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial pain. Other possible indications under discussion are chronic heart pain and bulimia. Unfortunately, experimental findings do not yet provide a homogenous conception of the significance of 5-HT3 receptors in all investigated fields; in nociception, for example, contradictory observations are still inadequately explained and complicated by bell-shaped dose-response curves. Further elucidation and better understanding of the serotonergic neuronal network remains a task for the next decade.

The formation of spinal syndesmophytes is an important outcome measure in ankylosing spondylitis (AS) but the predictors of new syndesmophyte development in female AS patients are unknown. This longitudinal study aimed to assess the rate and predictors of development of new syndesmophytes over a 2-year period in female AS patients.Clinical and radiographic data were collected at baseline and after 2 years in 67 female AS patients. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Univariate logistic regression analyses were performed to identify predictors associated with new syndesmophyte development.Eleven (16%) patients had syndesmophytes at baseline. Nine (13.4%) patients had developed new syndesmophytes in their lumbar spines after 2 years. In the univariate logistic regression analyses, older age, longer disease duration, severe sacroiliitis, elevated C-reactive protein (CRP) levels at baseline, and one or more pre-existing syndesmophytes were associated with the occurrence of new syndesmophytes. After adjustment for baseline SASSS, increases in SASSS were statistically significantly higher in patients with elevated baseline CRP levels (p = 0.002) than in patients with normal CRP at baseline.Older age, longer disease duration, severe sacroiliitis, the baseline presence of syndesmophytes, and elevated levels of CRP are predictors of the development of new syndesmophytes in female AS patients.

We have investigated HLA region microsatellite polymorphisms in rheumatoid arthritis (RA) which are known to be associated with HLA class II alleles in the Korean population. Ninety patients with RA and 106 controls were employed for this study, in which TAP1CA, DQCAR, D6S273, HLA-DRB1, -DQA1 and -DQB1 allele typing were performed. DQCAR 113 (RR = 3.2, P

Alternative tumor necrosis factor-α (TNF-α) inhibitors and non-TNF biologics are available as treatment options for rheumatoid arthritis patients who exhibit inadequate response to TNF-α inhibitor (TNF-IR patients). These agents have considerable efficacy compared with placebo, but head-to-head comparisons among these agents have not been performed. The objective of this study was to use Bayesian approach to compare the effectiveness of cycling TNF-α inhibitors versus switching to non-TNF biologics in TNF-IR patients. A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 and the health assessment questionnaire (HAQ) score change at six months. Bayesian outcomes were calculated as the probability that OR is greater than one and HAQ score change difference is less than zero. Compared with TNF-α inhibitors, non-TNF biologics were associated with higher ACR response rates; in ACR20, the OR was 1.639 for abatacept [P(OR > 1) = 90.7 %], 1.871 for rituximab [P(OR > 1) = 96.2 %] and 3.52 for tocilizumab [P(OR > 1) = 99.9 %]. Similar trends were shown in the HAQ change comparison; the median differences (MD) were −0.259 for abatacept [P(MD

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE. Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses. The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization. Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

Purpose In south Korea, the price of biologics has been decreasing owing to patent expiration and the availability of biosimilars. This study evaluated the cost-effectiveness of a treatment strategy initiated with etanercept (ETN) compared with leflunomide (LFN) after a 30% reduction in the medication cost of ETN in patients with active rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR). Methods A cohort-based Markov model was designed to evaluate the lifetime cost-effectiveness of treatment sequence initiated with ETN (A) compared with 2 sequences initiated with LFN: LFN-ETN sequence (B) and LFN sequence (C). Patients transited through the treatment sequences, which consisted of sequential biologics and palliative therapy, based on American College of Rheumatology (ACR) responses and the probability of discontinuation. A systematic literature review and a network meta-analysis were conducted to estimate ACR responses to ETN and LFN. Utility was estimated by mapping an equation for converting the Health Assessment Questionnaire-Disability Index score to utility weight. The costs comprised medications, outpatient visits, administration, dispensing, monitoring, palliative therapy, and treatment for adverse events. A subanalysis was conducted to identify the influence of the ETN price reduction compared with the unreduced price, and sensitivity analyses explored the uncertainty of model parameters and assumptions. Findings The ETN sequence (A) was associated with higher costs and a gain in quality-adjusted life years (QALYs) compared with both sequences initiated with LFN (B, C) throughout the lifetime of patients with RA and MTX-IR. The incremental cost-effectiveness ratio (ICER) for strategy A versus B was ₩13,965,825 (US$1726) per QALY and that for strategy A versus C was ₩9,587,983 (US$8050) per QALY. The results indicated that strategy A was cost-effective based on the commonly cited ICER threshold of ₩20,000,000 (US$16,793) per QALY in South Korea. The robustness of the base-case analysis was confirmed using sensitivity analyses. When the unreduced medication cost of ETN was applied in a subanalysis, the ICER for strategy A versus B was ₩20,909,572 (US$17,556) per QALY and that for strategy A versus C was ₩22,334,713 (US$18,753) per QALY. Implications This study indicated that a treatment strategy initiated with ETN was more cost-effective in patients with active RA and MTX-IR than 2 sequences initiated with LFN. The results also indicate that the reduced price of ETN affected the cost-effectiveness associated with its earlier use.

Background Adherence to systemic medication may vary between patients (pts) from different geographic areas. Objectives To explore differences in self-reported adherence and attitudes to systemic medications in different geographical regions, and identify factors associated with high adherence in pts with rheumatoid arthritis (RA) from the ALIGN study. Methods ALIGN was a global, cross-sectional, non-interventional study in adult pts with 6 inflammatory diseases, including RA. Clinical data were collected and validated pt questionnaires, including 4-item Morisky Medication Adherence Scale (© MMAS-4) and Beliefs About Medicines Questionnaire (BMQ), were administered at a routine visit. Results were compared between the following regions: West, including 16 countries from Western Europe, Canada, Australia and New Zealand; Eastern Europe (EE), including 6 countries; Middle East (ME), including Saudi Arabia and Lebanon; Latin America (LA), including 4 countries; Asia, including Korea and Taiwan. Associations between various factors, including geographic location, and medication adherence were assessed by multiple regression analysis. Results Data from 1943 pts [West, 1011 pts; EE, 322 pts; ME, 109 pts; LA, 367 pts; Asia, 134 pts; overall mean±SD age: 54.8±13.5 years (y); mean±SD disease duration, 9.2 ± 8.8 y] were analysed. 38.3–51.7% of pts had completely responded to current RA treatment. Duration of current treatment was longest in West region pts and shortest in Asian pts (6.1±5.6 y vs 2.3±2.0 y, P P Conclusions There were more RA pts reporting high medication adherence in the West vs other regions, with the fewest in LA and Asia. Asian pts may be less adherent to RA medication due to higher concerns and lower necessity beliefs towards systemic medication. Reasons for the low adherence rate in LA pts need to be explored further. Acknowledgement AbbVie: Study sponsor, design, data collection, analysis, interpretation; writing, review, approval of abstract. Medical writing: Naina Barretto of AbbVie. Permission for MMAS: Donald Morisky, UCLA. Study contribution: Nicole Selenko-Gebauer and Fabrice Gillas, both of AbbVie Disclosure of Interest J. Smolen Grant/research support from: AbbVie, D. Gladman Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Pfizer, Novartis, UCB, H. McNeil: None declared, J. Weinman Consultant for: AbbVie, Employee of: Atlantis Healthcare, Speakers bureau: AbbVie, S. Park: None declared, J. Sommer Employee of: GKM Gesellschaft fur Therapieforschung mbH, P. Nurwakagari Shareholder of: AbbVie, Employee of: AbbVie