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. @*Conclusions@#Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

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.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis

Objective@#To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). @*Methods@#We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. @*Results@#In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. @*Conclusion@#Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

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 personyears (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.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis

Objective@#To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). @*Methods@#We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. @*Results@#In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. @*Conclusion@#Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

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 personyears (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.

Intervention Thresholds for Treatment in Patients with Glucocorticoid-Induced Osteoporosis: Systematic Review of Guidelines

Background@#In this study, we aimed to evaluate and compare the treatment indication for patients with glucocorticoid-induced osteoporosis (GIOP) in various clinical practice guidelines. @*Methods@#We searched for potentially relevant studies conducted from January 2000 to March 2020 using online databases, including PubMed, Ovid-EMBASE, Guidelines International Network, National Institute for Health and Clinical Excellence, KoreaMed, KMbase, and KoMGI. We reviewed and analyzed the guidelines that included recommendations on GIOP and fulfilled the inclusion criteria. @*Results@#A total of 94 articles were selected based on review of the title and abstract; 14 guidelines were assessed upon reviewing the full text. The bone mineral density score for therapeutic intervention of GIOP in postmenopausal women was presented in 7 guidelines, among which 3 guidelines set a T-score of −2.5 or lower and the other 4 guidelines proposed a less stringent cut-off point of −1.5 or lower. Among the 10 guidelines published since 2012 after the emergence of the fracture risk assessment tool (FRAX), 6 guidelines included FRAX in their criteria for defining intervention thresholds. However, they were further divided into fixed-probability (n=3) and age-dependent (n=3) thresholds based on the country. @*Conclusions@#Recently developed guidelines use FRAX as the criterion for establishing the treatment of patients with GIOP. However, these intervention thresholds need to be adapted for each country.

A Case of Prosthetic Valve Endocarditis with Cerebral Hemorrhage Caused by Rothia mucilaginosa / 대한임상미생물학회지

Rothia spp. are aerobic, gram-positive cocci belonging to the family Micrococcaceae, and are a part of the normal microbial flora of the human oropharynx and upper respiratory tract. We present the first case of the prosthetic valve endocarditis with cerebral hemorrhage caused by Rothia mucilaginosa in South Korea. A 65-year-old man with a prosthetic aortic valve visited the outpatient clinic with a complaint of fever. R. mucilaginosa was identified in one among four sets of blood culture bottles obtained on the on day 30 of fever onset. Brain magnetic resonance imaging (MRI) showed multiple micro-hemorrhages suggesting septic emboli in both the hemispheres, corticomedullary junctions, and cerebellum. Rothia spp. should be considered as a possible pathogen in the cases of infective endocarditis with intracranial hemorrhage.

Intervention Thresholds for Treatment in Patients with Glucocorticoid-Induced Osteoporosis: Systematic Review of Guidelines

Background@#In this study, we aimed to evaluate and compare the treatment indication for patients with glucocorticoid-induced osteoporosis (GIOP) in various clinical practice guidelines. @*Methods@#We searched for potentially relevant studies conducted from January 2000 to March 2020 using online databases, including PubMed, Ovid-EMBASE, Guidelines International Network, National Institute for Health and Clinical Excellence, KoreaMed, KMbase, and KoMGI. We reviewed and analyzed the guidelines that included recommendations on GIOP and fulfilled the inclusion criteria. @*Results@#A total of 94 articles were selected based on review of the title and abstract; 14 guidelines were assessed upon reviewing the full text. The bone mineral density score for therapeutic intervention of GIOP in postmenopausal women was presented in 7 guidelines, among which 3 guidelines set a T-score of −2.5 or lower and the other 4 guidelines proposed a less stringent cut-off point of −1.5 or lower. Among the 10 guidelines published since 2012 after the emergence of the fracture risk assessment tool (FRAX), 6 guidelines included FRAX in their criteria for defining intervention thresholds. However, they were further divided into fixed-probability (n=3) and age-dependent (n=3) thresholds based on the country. @*Conclusions@#Recently developed guidelines use FRAX as the criterion for establishing the treatment of patients with GIOP. However, these intervention thresholds need to be adapted for each country.

A Case of Prosthetic Valve Endocarditis with Cerebral Hemorrhage Caused by Rothia mucilaginosa / 대한임상미생물학회지

Rothia spp. are aerobic, gram-positive cocci belonging to the family Micrococcaceae, and are a part of the normal microbial flora of the human oropharynx and upper respiratory tract. We present the first case of the prosthetic valve endocarditis with cerebral hemorrhage caused by Rothia mucilaginosa in South Korea. A 65-year-old man with a prosthetic aortic valve visited the outpatient clinic with a complaint of fever. R. mucilaginosa was identified in one among four sets of blood culture bottles obtained on the on day 30 of fever onset. Brain magnetic resonance imaging (MRI) showed multiple micro-hemorrhages suggesting septic emboli in both the hemispheres, corticomedullary junctions, and cerebellum. Rothia spp. should be considered as a possible pathogen in the cases of infective endocarditis with intracranial hemorrhage.

A Case of Hepatic Inflammatory Pseudotumor Occurred in a Patient with Lupus Nephritis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting various organs. Among its manifestations, inflammatory pseudotumor (IPT) is an extremely rare disease about which no case has been reported of it occurring in the liver. We present a case of a SLE patient with hepatic IPT (hIPT) successfully treated with immunosuppressants. A 16-year-old male with elevated liver enzymes visited our clinic and was diagnosed as SLE. Although no lesion was observed in the initial abdomen ultrasonography, the abdominal CT on hospital day 7 revealed a new hepatic mass resembling an abscess. Despite 5 weeks of antibiotics treatment, the hepatic mass remained, and was re-diagnosed as hIPT secondary to SLE with an abdominal MRI. After high dose prednisolone and mycophenolate mofetil treatment, lupus activity subsided and hIPT disappeared in the follow-up CT. This case suggests that hIPT should be considered as a differential diagnosis among hepatic mass in SLE patients.