Increased cardiovascular risk in Korean patients with systemic lupus erythematosus: a population-based cohort study.

To determine the increased risk of major adverse cardiovascular events (MACE) in patients with systemic lupus erythematosus (SLE) compared to the general population in Korea. Using data from the National Health Insurance Service database spanning 2008 to 2018, incident SLE patients aged 18 years and above were selected along with a 1:4 age- and sex-matched control group. The crude incidence rate (IR) of MACE was calculated as the number of events per 1000 person-years and the IR ratio (IRR) for MACE was adjusted using generalized estimating equations. Subgroup analysis was conducted to evaluate the risk differences of overall MACE and its composites based on age and sex stratification. The study included 8568 SLE patients and 34,272 controls. The cumulative IR of MACE per 1000 person-years in SLE patients and controls were 4.08 and 1.30, respectively. After adjusting for confounders, SLE patients had a higher risk of MACE compared to the general population (adjusted IRR of 2.40 [95% confidence interval [CI] 1.88-3.05]), with no gender differences observed. The increased risk of MACE in SLE patients was highest in the 18-39 age group (IRR 11.70, 95% CI 5.95-23.01) and gradually decreased with age. The increased risk of ischemic stroke (IRR 2.41, 95% CI 1.84-3.15) and myocardial infarction (IRR 2.19, 95% CI 1.30-3.68) in SLE patients was comparable. The risk of MACE in SLE patients is 2.40 times higher than that of the general population, with a higher relative risk observed in younger individuals.

Cost-of-illness changes before and after the diagnosis of systemic lupus erythematosus: a nationwide, population-based observational study in Korea.

OBJECTIVES: To estimate the direct healthcare cost progression from before to after systemic lupus erythematosus (SLE) diagnosis and to compare healthcare costs by disease severity. METHODS: Patients with incident SLE diagnosed between 2008 and 2018 were identified from the Korean National Health Insurance database. Annual direct healthcare costs for 5 years before and after SLE were estimated and compared with those of age-, sex-, and calendar month-matched (1:4) controls, without SLE. Direct healthcare costs were compared by disease severity of SLE using regression analysis. RESULTS: Among 11 173 patients with SLE and 45 500 subjects without SLE, annual direct healthcare costs per person increased in the year before SLE diagnosis and peaked in the first year after diagnosis. They were 7.7-fold greater in the SLE patients than in the subjects without SLE ($5,871 vs $759). Severe SLE was associated with 3.284-fold (95% CI 3.075-3.507) higher annual costs than mild SLE during the year after diagnosis. Older age (age 60-79 years), lupus nephritis, interstitial lung diseases, and comorbidities such as avascular necrosis and chronic kidney disease were associated with higher annual direct healthcare costs (times [95% CI]) in the first year after diagnosis; aged 60-69, 1.119 [1.034-1.211], aged 70-79, 1.470 [1.342-1.611], 1.794 [1.711-1.881], 1.435 [1.258-1.638], 6.208 [4.541-8.487], and 1.858 [1.673-2.064], respectively. CONCLUSION: Patients with SLE incurred significantly high direct healthcare costs than subjects without SLE during the first year after diagnosis. Disease severity, older age, major organ involvements and comorbidities were associated with increased healthcare costs.

Risk of end-stage renal disease in patients with early-onset lupus nephritis: A population-based cohort study.

OBJECTIVE: To compare the risk of end-stage renal disease (ESRD) between patients with early-onset lupus nephritis (EOLN) and those with delayed-onset LN (DOLN). METHODS: This retrospective study of incident cases of systemic lupus erythematosus (SLE) used nationwide Korean claims databases and data from 2008 through 2018. We divided LN patients into two groups: the EOLN group (with LN onset within 12 months of SLE diagnoses) and the DOLN group (with LN onset later than 12 months after SLE diagnoses). Patients were observed from the date of LN diagnosis to the development of ESRD, death, or the last follow-up. Cox proportional hazards modeling was used to predict hazard ratios (HRs) for progression to ESRD with death as a competing risk. RESULTS: We identified 3779 incident SLE patients who developed LN during follow-up: 60 % (n = 2281) had EOLN, and 40 % (n = 1489) had DOLN. Sixty-nine patients with EOLN (3.0 %) and 29 patients with DOLN (1.9 %) progressed to ESRD. After adjusting for confounders, the ESRD risk associated with EOLN was comparable to the risk associated with DOLN (HR 1.10, 95 % confidence interval [CI] 0.57 to 2.11). In the subgroup of patients on aggressive immunosuppressive therapy (670 with EOLN and 179 with DOLN), the ESRD risk was higher in the DOLN group (HR 2.6, 95 % CI 1.11 to 6.10). CONCLUSION: The risk of ESRD was comparable between patients with EOLN and DOLN. However, among patients on aggressive immunosuppressive therapy, compared with EOLN, DOLN was associated with a higher risk of progression to ESRD.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

BACKGROUND/AIMS: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. METHODS: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). RESULTS: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. CONCLUSION: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Increased risk of herpes zoster with tofacitinib treatment in Korean patients with rheumatoid arthritis: a single-center prospective study.

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05-22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

Risk of venous thromboembolism in Korean patients with rheumatoid arthritis treated with Janus kinase inhibitors: A nationwide population-based study.

OBJECTIVE: There was a safety concern about an increased risk of thromboembolic events in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). This study aimed to determine the risk of venous thromboembolism (VTE) in Korean patients with RA treated with JAKis compared with tumour necrosis factor (TNF) inhibitors. METHODS: Using the National Health Insurance Service database between 2015 and 2019, patients with prevalent RA who started JAKi or TNF inhibitor were selected as the study population. All participants were naïve to targeted therapy. Patients that had experienced any VTE event or used anticoagulant agents within 30 days were excluded. Demographic and clinical characteristics were all balanced by stabilised inverse probability of treatment weighting (sIPTW) using propensity score. The Cox proportional hazard model considering death as a competing risk was used to evaluate the risk of VTE in JAKi users compared with TNF inhibitor users. RESULTS: A total of 4,178 patients were included: 871 JAKi users and 3,307 TNF inhibitor users were followed up for 1,029.2 person-years (PYs) and 5,940.3 PYs, respectively. With a balanced sample after sIPTW, the incidence rates (IR) of VTE were 0.06 per 100 PYs (95% confidence interval [CI] 0.00-1.23) in JAKi users and 0.38 per 100 PYs (95% CI 0.25-0.58) in TNF inhibitor users. The hazard ratio was 0.18 (95% CI 0.01-3.47) after adjusting for unbalanced variables after performing sIPTW. CONCLUSION: There is no increased risk of VTE in RA patients treated with JAKis compared with TNF inhibitors in Korea.

Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort.

BACKGROUND: To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD. METHODS: Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients. RESULTS: Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412). CONCLUSIONS: Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Factors associated with selection of targeted therapy in patients with rheumatoid arthritis.

OBJECTIVE: Deciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice. METHODS: We selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis. RESULTS: 145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01-1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95-1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01-0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01-0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51-2.38) and previous tacrolimus use (OR 2.05, CI 1.20-3.51) were factors suggesting selection of JAKis than TNF inhibitors. CONCLUSION: Age, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea.

Association between malignancy risk and Janus kinase inhibitors versus tumour necrosis factor inhibitors in Korean patients with rheumatoid arthritis: a nationwide population-based study.

OBJECTIVE: To determine the risk of malignancy in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis) compared with tumour necrosis factor inhibitors (TNFis). METHODS: A retrospective cohort of patients with RA initiating their first JAKi or TNFi was established using the Korean National Health Insurance database between 2015 and 2019. They were followed up from treatment initiation to the occurrence of malignancy, drug discontinuation, death or until December 2019. Baseline features of the patients were balanced through inverse probability of treatment weighting (IPTW) using a propensity score. A Cox proportional hazard model was established to estimate the HR for malignancy risk in JAKi users compared with TNFi users. RESULTS: A total of 4929 patients (1064 JAKi-treated and 3865 TNFi-treated patients) were included, and the observation periods were 1288.6 person-years (PYs) for JAKi users and 6823.8 PYs for TNFi users. The incidence rates of overall malignancy were 0.54 per 100 PYs (95% CI 0.26 to 1.14) in JAKi users and 0.85 per 100 PYs (95% CI 0.66 to 1.10) in TNFi users. In IPTW analysis with a balanced sample (4101 JAKi-treated and 5131 TNFi-treated patients), HR was 0.83 (95% CI 0.55 to 1.27) for overall malignancy: 0.77 (95% CI 0.50 to 1.19) for solid malignancy and 2.86 (95% CI 0.41 to 20.00) for haematological malignancy. CONCLUSION: Malignancy risk in Korean patients with RA was not increased with JAKi use compared with TNFi use.

Korean LupusPRO: Cross-Cultural validation study for systemic lupus erythematosus.

OBJECTIVE: To establish the reliability and validity of the Korean version of LupusPRO version 1.7 (v1.7) for systemic lupus erythematosus (SLE) patients. METHODS: LupusPRO v1.7 was translated into Korean, followed by pretesting among five native Korean speakers. We administered the LupusPRO v1.7 survey to five SLE patients and made minor changes to clarify the language. Then, 133 SLE patients participated in the validation procedure. In each domain, the internal consistency reliability (ICR) and test-retest reliability (TRR) were assessed using Cronbach's alpha and the intra-class correlation coefficient (ICC), respectively. Criterion validity was evaluated using Spearman's correlation coefficient with the other measures such as SF-36, EQ-5D VAS, and SELENA-SLEDAI PGA. Construct validity was assessed by confirmatory factor analysis (CFA) using the unweighted least square estimation method. RESULTS: The mean age of the 133 patients was 36.14 years, and 97% of them were women. Analysis of 130 returned questionnaires revealed that most ICRs of the Korean LupusPRO v1.7 domains were acceptable, with Cronbach's alphas in the range of 0.579-0.949, and most TRRs were good with ICCs from 0.582 to 0.851. Criterion validities presented significant correlations between the LupusPRO v1.7 and other measures validated. In the analysis of the CFA model, the goodness of fit indices demonstrated an acceptable fit. Factor loadings for most individual items were between 0.548 and 0.985. The average variance extracted (AVE) and composite reliability (CR) of most domains were greater than 0.5 and 0.7, respectively, demonstrating acceptable convergent and discriminant validities. CONCLUSIONS: The Korean version of LupusPRO v.17 had acceptable reliability and validity.

Validation of the Korean Leeds satisfaction questionnaire in rheumatoid arthritis with Rasch models.

OBJECTIVES: We conducted the cross-cultural adaptation and validation of the Leeds Satisfaction Questionnaire (LSQ) for patients with rheumatoid arthritis (RA) in Korea. METHODS: The adaptation of the LSQ from English into Korean was based on guidelines for cross-cultural adaptation for self-report measures. Patients with RA were recruited from an outpatient clinic of a university hospital in South Korea. Validation of the Korean-LSQ with Rasch models was carried out using WINSTEPS. Model fit was determined by Infit and Outfit statistics (≥0.50 and ≤1.50), including the separation index (≥2.00) and reliability index (≥0.80). RESULTS: The data set comprised 125 patients (82.4% female), with median (interquartile range) age 49.0 (37-57) years, and disease duration of 2.5 (1.2-3.8) years. The total and subscale scores of the Korean-LSQ demonstrated excellent or good test-retest reliability (0.88 for total, 0.71-0.82 for subscales), and items in the scale also revealed a high internal consistency (α = 0.93). The six subscales of the Korean-LSQ were found to have a good fit to the Rasch model and good reliability (Person separation index = 2.63 and reliability index = 0.87; item separation index = 37.03 and reliability index >0.99). In addition, the unidimensionality of the scale was confirmed by the principal component analysis based on the Rasch residuals. CONCLUSION: Fit to the Rasch model confirmed that the construct validity, reliability, and unidimensionality of the LSQ were preserved following the adaptation into Korean. The Korean-LSQ is a valid and reliable tool for measuring satisfaction with care in Korean patients with RA.

COX-2 Inhibitor Use as an Early Treatment Option for Knee Osteoarthritis Patients in Korea: A Population-Based Cross-Sectional Study.

BACKGROUND: To investigate the use of cyclooxygenase-2 (COX-2) inhibitors as an initial drug treatment for knee osteoarthritis (OA) patients. METHODS: From 2013 to 2015, patients with knee OA were identified from the Korean nationwide claims database. Among them, we extracted incident cases of knee OA to identify the initial drug treatment. Trends in the use of non-steroid anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors were analyzed during the first year after their diagnosis. Associated factors for COX-2 inhibitor use were examined using a multivariate logistic regression model. RESULTS: We identified 2,857,999 incident knee OA patients (955,259 in 2013, 981,314 in 2014, and 921,426 in 2015). The mean ± standard deviation age of patients was 64.2 ± 9.8 years. The frequency of COX-2 inhibitor use as initial treatment increased from 3.5% in 2013 to 7.2% in 2015 (P < 0.01). In patients taking the medication regularly for one year after diagnosis (medication possession ratio ≥ 50%), COX-2 inhibitor use also rapidly increased from 5.5% in 2013 to 11.1% in 2015 (P < 0.01). However, the frequencies of non-selective NSAID and analgesic use did not decrease remarkably. Factors associated with patients using COX-2 inhibitors on initial drug treatment were older age (odds ratio [OR], 1.08), female (OR, 1.24), and comorbidity (OR, 1.03). Type of institution, physician speciality, and insurance type of patients were also associated. CONCLUSION: In Korea, COX-2 inhibitors have rapidly increased as an initial treatment for knee OA patients, but it has not appeared to reduce the use of non-selective NSAIDs and analgesics.

Risk factors for herpes zoster in Korean patients with rheumatoid arthritis treated with JAK inhibitor: a nested case-control study.

OBJECTIVE: To determine the risk of herpes zoster (HZ) in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis). METHODS: We performed a nested case-control study with 1:10 matching for sex and age using single-centre prospective cohorts of patients with RA receiving targeted therapy in Korea. Then we performed conditional logistic regression analyses to determine the risk associated with JAKi use compared with biologic disease-modifying antirheumatic drug (bDMARD) use, with adjusting for various factors. We also used logistic regression analysis to identify other risk factors for the development of HZ in JAKi users. RESULTS: From a total of 1147 patients, 61 cases and 610 matched controls were selected. In conditional logistic regression analysis, JAKi use did not increase the risk of HZ development (OR 1.35, 95% CI 0.70 to 2.61) after adjusting for other factors. Rather, duration of RA less than 10 years (OR 0.54, 95% CI 0.30 to 0.97) and having had three or more previous targeted therapies (OR 5.29, 95% CI 1.45 to 19.31) were risk factors for HZ. Among JAKi users, higher disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) (OR 1.44, 95% CI 1.06 to 1.97) was identified as a risk factor in addition to three or more previous targeted therapies (OR 10.12, 95% CI 1.92 to 53.49). CONCLUSIONS: The number of previous targeted therapies, but not JAKi use, was identified as a risk factor for HZ development in Korean patients with RA in a real-world setting. High disease activity was an additional risk factor for JAKi users.

Comparative Effectiveness of Azathioprine Versus Cyclosporine as an Initial Treatment for Idiopathic Inflammatory Myopathies: A Population-Based Observational Study.

OBJECTIVE: To compare the effectiveness of azathioprine (AZA) and cyclosporine (CsA) as initial treatments for patients with idiopathic inflammatory myopathies (IIM). METHODS: A retrospective cohort study was conducted using information from the National Health Insurance Service database of Republic of Korea. Patients with IIM who had started AZA or CsA as initial treatment between January 2007 and December 2011 were selected for the study. They were followed from the day of treatment initiation to the occurrence of study outcomes or the end of the study until December 2016. Effectiveness outcomes, defined as switching the drug or adding immunosuppressants, and discontinuation of corticosteroids, were compared between the two groups. The Cox proportional-hazards model was used to calculate the adjusted relative risk (aRR) with 95% confidence interval (CI) between the AZA and CsA groups. RESULTS: A total of 376 patients with incident IIM who used AZA (n = 288) or CsA (n = 88) were identified. The aRR of switching the drug or adding immunosuppressants (1.45 [95% CI 0.99-2.11]) was not significantly different between the CsA and AZA groups. Among patients who were treated with corticosteroids at baseline, the rate of discontinuation of corticosteroids was not different between the two groups (1.69 [95% CI 0.82-3.47]). CONCLUSIONS: The effectiveness of AZA and CsA as initial treatments for the management of IIM was comparable.

Increased risk of malignancy in patients with systemic lupus erythematosus: population-based cohort study in Korea.

BACKGROUND: This study aimed to evaluate the crude incidence rates and relative risk of malignancy in Korean patients with SLE. METHODS: We conducted a retrospective nationwide cohort study using databases from the National Health Insurance Service in Korea. All prevalent SLE patients aged over 19 were identified from January 2012 to December 2014 and observed until the diagnosis of malignancy, death, or end of the study, December 2015. The crude incidence rates (IRs) and standardised incidence ratios (SIRs) of overall and site-specific malignancies in SLE patients were estimated. RESULTS: We identified 17,854 SLE patients and during the observation period (60,511 person-years [PYs]), 768 solid malignancies (126.9/10,000 PYs) and 68 haematologic malignancies (11.2/10,000 PYs) occurred in SLE patients. In SLE patients, breast and reproductive system and thyroid cancers occurred predominantly, followed by liver and colon cancers. The SIRs of overall, solid, and haematologic malignancies of SLE patients compared to the general population were 1.8 (95% confidence interval [CI] 1.6-1.9), 1.7 (95% CI 1.5-1.8), and 5.9 (95% CI 4.8-7.3), respectively. In solid malignancies, head and neck (2.7, 95% CI 1.1-4.2), bladder (2.4, 95% CI 1.1-3.8), liver (1.9, 95% CI 1.4-2.3), pancreas (1.9, 95% CI 1.3-2.6), lung (1.8, 95% CI 1.2-2.4), colon (1.7, 95% CI 1.3-2.2), thyroid (1.6, 95% CI 1.3-1.8) and breast and reproductive system (1.5, 95% CI 1.2-1.7) cancers are at increased risk in SLE patients. CONCLUSION: An increased risk of haematologic and solid malignancies was observed in Korean patients with SLE compared to the general population.

Comparison of healthcare resource utilization and medical costs between patients with seropositive and seronegative rheumatoid arthritis.

OBJECTIVES: To compare healthcare utilization and medical costs between patients with seronegative (SN) and seropositive (SP) rheumatoid arthritis (RA). METHODS: We conducted a nationwide population study using the Korean health insurance claims database in 2016. We divided patients with RA into SN and SP groups and compared healthcare utilization including medications, medical utilization, and direct medical costs for 1 year between the groups in a cross-sectional analysis. Differences in costs between patients with SPRA and SNRA were assessed using the quantile regression model. We performed longitudinal analysis using data from 2012 and 2016 to examine changes over time. RESULTS: A total of 103,815 SPRA and 75,809 SNRA patients were included in the analyses. The SPRA group used significantly more methotrexate (73.2% versus 30.3%) and biologic agents (7.9% versus 2.9%) than the SNRA group. The number of RA-related outpatient visits [6.0 ± 3.7 versus 4.4 ± 4.0 times/year, standardized difference (SD) = 0.41] and annual medical costs per patient ($1027 versus $450/year, SD = 0.25) were higher in the SPRA group than the SNRA group. Quantile regression results indicated that the incremental cost of seropositivity on total medical costs of RA patients gradually increased as medical costs approached the upper quantile. The annual direct medical costs for each patient between 2012 and 2016 increased in both groups: by 25.1% in the SPRA group and 37.6% in the SNRA group. CONCLUSION: Annual RA-related direct medical costs and RA-related healthcare utilization per patient are higher in patients with SPRA than those with SNRA.

Effectiveness of bazedoxifene in preventing glucocorticoid-induced bone loss in rheumatoid arthritis patients.

OBJECTIVE: To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs). METHODS: In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations. RESULTS: A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm2, P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003-0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group. CONCLUSION: In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704 .

Uptake of Biosimilars and Its Economic Implication for the Treatment of Patients with Rheumatoid Arthritis in Korea.

BACKGROUND: We aimed to examine the uptake of infliximab and etanercept biosimilars in patients with rheumatoid arthritis (RA) and its economic implication for healthcare expenditure. METHODS: Using Korean Health Insurance Review and Assessment Service National Patient Samples, we extracted RA patients who used biologic disease modifying anti-rheumatic drugs (bDMARDs) between 2009 and 2018. Descriptive statistics were used to explain the basic features of the data. We calculated the proportion of users of each bDMARD among total patients with bDMARDs half-yearly. We assessed changes in the utilization proportions of bDMARDs including 4 tumor necrosis factor inhibitors (TNFis) and 2 non-TNFis, which have been approved for RA in Korea: etanercept, infliximab, adalimumab, golimumab, tocilizumab, and abatacept, and analyzed the changes in market share of biosimilars among the bDMARDs after their introduction. Overall trends of medical costs for each bDMARD were presented over the 10-year period. RESULTS: Since the introduction of the biosimilar TNFis in 2012, the proportion of their use among bDMARDs steadily increased to 15.8% in 2018. While there has been a gradual increase in the use of biosimilar TNFis, the use of the corresponding originators has been decreasing. The introduction of biosimilar TNFis has resulted in a decrease in the medical costs of patients using either originator or biosimilar TNFis. CONCLUSION: In Korea, the proportional use of biosimilar TNFis has gradually increased since their introduction. The availability of less expensive biosimilar TNFis seems to have brought about a decrease in the medical costs of users of the originators.

Risk of Tuberculosis Development in Patients with Rheumatoid Arthritis Receiving Targeted Therapy: a Prospective Single Center Cohort Study.

BACKGROUND: Patients with rheumatoid arthritis (RA) undergoing targeted therapy have a higher risk of developing tuberculosis (TB). This requires diagnosis and treatment of latent tuberculosis infection (LTBI). We aimed to evaluate whether diagnosis and treatment of LTBI in RA are effective in Korea, and to estimate the risk of TB development by calculating the incidence rate of active TB among RA patients receiving targeted therapy. METHODS: We analyzed data from two prospective cohort studies of RA patients who received biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitor. We selected new starters of targeted therapy and classified them into three groups receiving tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and JAK inhibitor, respectively. We then compared LTBI prevalence, treatments, and active TB incidence during first-line therapy in each group. RESULTS: A total of 765 RA patients (574 TNF inhibitor users, 132 non-TNF inhibitor users, and 59 JAK inhibitor users) were included in this study. Observation periods were 1,255.2 person-years (PYs), 264.7 PYs, and 53.3 PYs, respectively. All 765 patients underwent LTBI screening, and the positivity rate was 26.5% (n = 203). Of the 203 LTBI-positive patients, 189 (93.1%) received treatment. Only one patient, who was in the TNF inhibitor group, and was negative for the interferon gamma release assay (IGRA), did not receive LTBI treatment and developed active TB during follow-up. CONCLUSION: Although the prevalence of LTBI in RA patients who started targeted therapy was slightly elevated, the Korean guidelines specifying LTBI screening and treatment were effective in preventing latent TB from becoming active.