Risk factors of mortality in patients with rheumatoid arthritis-associated interstitial lung disease: a single-centre prospective cohort study.

OBJECTIVES: To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). METHODS: Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth's penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. RESULTS: A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16-3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11-45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00-57.36) were identified as risk factors for mortality in RA-ILD patients. CONCLUSION: Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Effectiveness of Korean Red Ginseng on fatigue in patients with rheumatic diseases: a randomized, double-blind, placebo-controlled study.

BACKGROUND: To evaluate the effectiveness of Korean Red Ginseng (KRG) in managing fatigue in Korean patients with rheumatic diseases. METHODS: Patients were randomly assigned to KRG (2 g/day, n = 60) or placebo (n = 60) groups for 12 weeks of blind phase and then open-label KRG from weeks 12 to 24 (placebo-KRG, continuous-KRG). The primary outcome was the improvement rate in fatigue, defined by an increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at 12 weeks. Secondary outcomes included changes in FACIT-Fatigue and fatigue visual analog scale (VAS) between 0 and 12 weeks and those changes in both indices at 24 weeks. RESULTS: The study enrolled 120 patients (Sjogren syndrome [n = 53], rheumatoid arthritis [n = 43], or both diseases [n = 24]). The mean age was 50.9 ± 11.6 years, with 97.5% being female. Baseline characteristics were similar between the two groups. The improvement rate in FACIT-Fatigue after 12 weeks was higher in the KRG group than in the placebo group, but the difference was statistically insignificant (38.3% vs. 26.7%, p = 0.242). Improvement in fatigue was observed in both groups by increases in FACIT-F (4.6 vs. 4.0) and reductions in fatigue VAS (-16.0 vs. -12.2) scores at 12 weeks. The most frequently reported adverse events during KRG use were pruritus and urticarial, with no significant difference between the two groups. CONCLUSION: Both KRG and placebo groups showed significant reductions in fatigue. KRG treatment for 24 weeks did not reduce fatigue symptoms more than the placebo in patients with rheumatic diseases.

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis.

OBJECTIVES: We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA). METHODS: Female patients with RA aged 20-50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs. RESULTS: A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs. CONCLUSION: Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy.

Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis.

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10-3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

Comparative effectiveness of tofacitinib and tumour necrosis factor inhibitors in patients with rheumatoid arthritis in real-world practice: a prospective observational study.

OBJECTIVE: To assess the effectiveness of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in Korean patients with rheumatoid arthritis (RA). METHODS: The study used data from a single academic referral hospital's registries of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and tofacitinib and examined remission rates based on the disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders. RESULTS: This analysis included 665 patients (200 on tofacitinib and 455 on TNFi) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, p = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% confidence interval [CI] 0.720-2.013). In the subpopulation naïve to JAKi and bDMARD, tofacitinib showed better remission rates than TNFi (OR 1.867, 95% CI 1.033-3.377). Tofacitinib had more adverse events (AEs) but similar rates of serious AEs (SAEs) to TNFi. CONCLUSION: In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of AEs compared with TNFi, while the occurrence of SAEs was comparable between the groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704.

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.

Epidemiology of systemic lupus erythematosus in Korea.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse organ system disabilities, predominantly affecting young females. The clinical manifestations of SLE encompass various organs, including the kidney, cardiovascular system, and central nervous system. Young females with SLE experience higher mortality rates than the general population, making it imperative to gain insights into the disease patterns and associated factors. The current review examines the epidemiological studies to analyze the prevalence, incidence, and mortality trends of SLE in Korea and compares them with the findings from other countries. We aim to identify potential similarities, differences, and factors contributing to the burden of SLE in different populations by exploring the comparative epidemiological aspects. The knowledge derived from this comparison would aid in advancing the overall management of SLE in Korea.

Transcriptomic network analysis reveals key drivers of response to anti-TNF biologics in patients with rheumatoid arthritis.

OBJECTIVE: Anti-TNF biologics have been widely used to ameliorate disease activity in patients with rheumatoid arthritis (RA). However, a large fraction of patients show a poor response to these agents. Moreover, no clinically applicable predictive biomarkers have been established. This study aimed to identify response-associated biomarkers using longitudinal transcriptomic data in two independent RA cohorts. METHODS: RNA sequencing data from peripheral blood cell samples of Korean and Caucasian RA cohorts before and after initial treatment with anti-TNF biologics were analyzed to assess treatment-induced expression changes that differed between highly reliable excellent and null responders. Weighted correlation network, immune cell composition, and key driver analyses were performed to understand response-associated transcriptomic networks and cell types and their correlation with disease activity indices. RESULTS: In total, 305 response-associated genes showed significantly different treatment-induced expression changes between excellent and null responders. Co-expression network construction and subsequent key driver analysis revealed that 41 response-associated genes played a crucial role as key drivers of transcriptomic alteration in four response-associated networks involved in various immune pathways: type I interferon signalling, myeloid leucocyte activation, B cell activation, and NK cell/lymphocyte-mediated cytotoxicity. Transcriptomic response scores that we developed to estimate the individual-level degree of expression changes in the response-associated key driver genes were significantly correlated with the changes in clinical indices in independent patients with moderate or ambiguous response outcomes. CONCLUSIONS: This study provides response-specific treatment-induced transcriptomic signatures by comparing the transcriptomic landscape between patients with excellent and null responses to anti-TNF drugs at both gene and network levels.

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.

Nationwide patterns of hydroxychloroquine dosing and monitoring of retinal toxicity in patients with systemic lupus erythematosus.

This study identified trends in hydroxychloroquine (HCQ) prescription and retinopathy screening in patients with systemic lupus erythematosus (SLE) according to clinical practice guidelines to minimise the risk of HCQ retinopathy. We used data from patients diagnosed with SLE between 2004 and 2019 from the National Health Insurance Service in Korea. To assess trends of daily dose per actual body weight (ABW), we performed an interrupted time-series analysis and identified effects after revision of guidelines. Among 38,973 patients with SLE, 28,415 (72.9%) were prescribed HCQ from 2004 to 2019. The proportion of patients using HCQ among SLE patients was 63% in 2004 and increased to 76% in 2019. The median daily dose per ABW for HCQ users decreased from 5.88 mg/kg in 2004 to 3.98 mg/kg in 2019, and from 5.45 mg/kg in 2005 to 4.17 mg/kg in 2019 for HCQ new users. The annual implementation rate of screening tests among HCQ new users increased from 3.5% in 2006 to 22.5% in 2019. Study results indicated that HCQ dosing management was adequate based on the revised guidelines. Although the implementation rate of retinal screening has increased, it is necessary to enhance awareness of retinal screening in clinical settings.

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.

The lessebo effect in randomized controlled trials of rituximab in patients with rheumatoid arthritis: a meta-analysis.

OBJECTIVE: The goal of this study was to assess the impact of negative expectations associated with receiving a placebo (the lessebo effect) on efficacy outcomes in randomized clinical trials (RCTs) of rituximab in patients with rheumatoid arthritis (RA). METHODS: We performed a meta-analysis on the American College of Rheumatology 20%, 50%, and 70% (ACR20, 50, 70) response rates in the placebo and active (biosimilar)-controlled groups (reference-pbo and reference-bs) of rituximab showing an insufficient response to methotrexate or tumor necrosis factor. We evaluated the difference in ACR20, 50, 70 response rates between the two groups (reference-bs vs. reference-pbo). RESULTS: Nine RCTs included a total of 2734 patients with RA. The pooled incidence of ACR20 response rate in the placebo- and active-controlled groups of the rituximab RCTs for RA was 53.1% (95% confidence interval [CI] 49.9-56.3%) and 75.0% (95% CI 71.2-78.4%), respectively. The difference in the ACR20 response rate between the placebo- and active-controlled groups was -20.9% (95% CI -26.9 to 61.9%, p < 0.001). The pooled incidence of ACR50 response rate in the placebo- and active-controlled groups of the rituximab RCTs for RA was 29.0% (95% CI 26.2-32.0%) and 47.4% (95% CI 43.2-51.6%), respectively. The ACR50 response rates were significantly higher in the active-controlled groups than in the placebo-controlled groups (-18.4%; 95% CI -18.4 to -13.4%, p < 0.001). The difference in the ACR70 response rate between the placebo- and active-controlled groups was -14.9% (95% CI -22.2 to -7.6%, p < 0.001). The ACR20, 50, 70 response rates were significantly higher in the active-controlled groups than in the placebo-controlled group. CONCLUSION: This study shows that the use of a placebo can be associated with a clinically significant reduction in the magnitude of change of the ACR20, 50, 70 response rates in rituximab RCTs for RA. The lessebo effect has potential implications for the development of new treatments and appraisal of current treatment options for RA.