Search

Objectives: To establish a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features compared to those without ILD. Methods: With a multidisciplinary collaborative approach, a single-centre cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 was 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 patients and 410 RA-non ILD patients, 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 the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in comparators (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 coexist with ILD (OR 0.253, 95% CI 0.155-0.412). Conclusions: Higher RA onset age, smoking history, and higher BMI were associated with presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Objectives The primary endpoint of the pivotal phase III study of infliximab (IFX) s.c. demonstrated non-inferiority of s.c. to i.v. IFX, based on 28-joint DAS-CRP (DAS28-CRP) improvement at week (W) 22 (NCT03147248). This post-hoc analysis investigated whether numerical differences in efficacy outcomes at W30/54 were statistically significant, using conservative imputation methods. Methods Patients with active RA and inadequate response to MTX received IFX i.v. 3 mg/kg at W0 and W2 (induction) and were randomized (1:1) to IFX s.c. 120 mg every 2 weeks or i.v. 3 mg/kg every 8 weeks thereafter (maintenance). Patients randomized to IFX i.v. switched to IFX s.c. from W30–54. This post-hoc analysis compared efficacy outcomes for s.c. and i.v. groups pre-switch (W30) and post-switch (W54) using last observation carried forward (LOCF) and non-responder imputation (NRI) methods. Results Of 343 randomized patients, 165 (IFX s.c.) and 174 (IFX i.v.) were analysed. At W30, significantly improved outcomes were identified with s.c. vs i.v. IFX for DAS28-CRP/DAS28-ESR/Clinical Disease Activity Index (CDAI)/Simplified Disease Activity Index (SDAI) scores (LOCF); ACR/good EULAR responses, DAS28-CRP/Boolean remission, and DAS28-CRP/DAS28-ESR/CDAI/SDAI low disease activity and remission (LOCF and/or NRI); and minimal clinically important difference in HAQ score (LOCF and NRI). After switching to IFX s.c. from IFX i.v., fewer significant between-group differences were identified at W54. Conclusion IFX s.c. showed improved efficacy at W30 compared with IFX i.v., and the reduced between-group difference in efficacy outcomes at W54 after switching supports the results suggesting benefits of IFX s.c. compared with IFX i.v. at W30. Trial registration ClincialTrials.gov, http://clinicaltrials.gov, NCT03147248, https://clinicaltrials.gov/ct2/show/NCT03147248.

Objective To assess non-inferiority of s.c. to i.v. CT-P13 in RA. Methods Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46–54) then PFS (W56–64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: −0.6). Results Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. Conclusion CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

Objectives To estimate the prevalence, medical utilization, and recent changes in the economic burden of autoimmune rheumatic diseases (AIRDs) in Korea. Methods Using a nationwide claims database that includes all medical claims made by approximately 50 million Korean residents, the prevalences of seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and others between 2012 and 2016 were calculated. Changes in medical utilization and the direct medical costs of each AIRD from 2012 to 2016 were also evaluated. Results Based on the data for 2016, seropositive RA was the most common AIRD in Korea with 96,330 cases (188.5/100,000 population), followed by AS (30,006, 58.7/100,000 population), SLE (19,441, 38.0/100,000 population), Behcet's disease (BD, 14,943, 29.2/100,000 population), primary Sjogren syndrome (pSS, 12,018, 23.5/100,000 population), and systemic sclerosis (SSc, 3606, 7.1/100,000 population). In terms of medical utilization, patients with eosinophilic granulomatosis with polyangiitis visited outpatient clinics the most frequently (9.8 times/year/patient), while hospitalization was most frequent in microscopic polyangiitis patients (1.0 time/year/patient). Total medical costs for all AIRDs increased from $154,348,011 in 2012 to $262,481,974 in 2016. The annual medical cost per patient in 2016 was the highest in microscopic polyangiitis ($6223/year), followed by psoriatic arthritis ($3,362/year), and granulomatosis with polyangiitis ($2823/year). Conclusions In Korea, the most prevalent AIRD is seropositive RA, followed by AS, SLE, BD, pSS, and SSc. The economic burden of AIRDs has risen substantially in the last 5 years due not only to an increase in their prevalence but also to an increase in medical costs per patient.

To examine the temporal relationship between malignancies and idiopathic inflammatory myopathies (IIMs) and its impact on mortality.A retrospective cohort for IIM patients was conducted using the Korean National Health Insurance Service databases. We observed more than 5 years before and after the diagnosis of IIM (2002~2016) to identify IIM patients who developed any malignancy and classified these patients into two groups: the cancer-associated myositis (CAM) group, who developed malignancy within 3 years before or after the diagnosis of IIM and the cancer-not-associated myositis (CNAM) group, who developed malignancy beyond 3 years of IIM onset. The survival rates of the two groups were compared.We identified 1072 incident cases of IIM between 2007 and 2011. A total 225 patients of these patients were diagnosed with malignancy. The development of malignancy was frequent within 1 year before and after the time of IIM diagnosis. The common sites of malignancies in the CAM group differed from those in the CNAM group: the lung, hematologic malignancy, and the liver were common in both groups, but thyroid and oropharynx followed them in CAM while prostate, stomach, breast, and thyroid followed them in CNAM. CAM patient mortality was worse compared with CNAM patients (log-rank test, p 0.01).Among IIM patients with malignancy, common sites of malignancy were different between the CAM and CNAM groups, and patients with CAM had poor prognosis compared with CNAM patients. Key Points • The malignancies commonly occurred in incident idiopathic inflammatory myopathy (IIM) patients, especially within 1 year before and after the initial IIM diagnosis. • Patients with malignancy had poor survival compared with patients without malignancy. • Among the IIM patients with malignancy, patients who developed malignancy within 3 years of IIM diagnosis (cancer-associated myositis, or CAM, group) showed higher mortality than cancer-not-associated myositis, CNAM group. • We also found that the common types of malignancy were different between the CAM and CNAM groups.

ObjectiveTo determine the risk of herpes zoster (HZ) in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis).MethodsWe 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.ResultsFrom 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).ConclusionsThe 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.

Introduction: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology, and approximately 60-70% of patients develop a chronic form. Up to 20-30% of patients who are refractory to conventional therapy need biologic agents. Recently, anti-cytokine biologic agents according to pathophysiology have resulted in significant progress in the treatment of AOSD. Area Covered: Due to rarity and heterogeneous features of the disease, treatment of AOSD is not based on the controlled study but on case-based retrospective data. Here, we review the current status of the pathogenesis, limitations of therapeutic guidelines and outcome measures, utility of biologic agents, and future perspectives for treatment. Expert opinion: IL-1 inhibitors are more effective for systemic manifestations and IL-6 inhibitors for both joint disease and systemic features. Anti-TNF agents would be useful for patients with the pure rheumatoid subgroup. Systemic manifestations respond rapidly, but arthritis shows rather slow response. Clinical response must be obtained within 2 to 3 months, and biologics with different mechanisms of action are required for non-responders. For patients in prolonged remission, we need to try tapering of biologics. Randomized controlled studies, new therapeutic agents, and composite biomarkers are required to improve the outcome of patients with AOSD.

Objective To evaluate the efficacy and safety of CT-P10, a rituximab biosimilar after a single switch, during a multinational, randomized, double-blind Phase 3 trial involving patients with RA. Methods Patients received 48 weeks’ treatment with CT-P10 or United States- or European Union-sourced reference rituximab (US-RTX and EU-RTX, respectively). Patients entering the extension period (weeks 48–72) remained on CT-P10 (CT-P10/CT-P10; n = 122) or US-RTX (US-RTX/US-RTX; n = 64), or switched to CT-P10 from US-RTX (US-RTX/CT-P10; n = 62) or EU-RTX (EU-RTX/CT-P10; n = 47) for an additional course. Efficacy endpoints included Disease Activity Score using 28 joints (DAS28), American College of Rheumatology (ACR) response rates, and quality of life-related parameters. Pharmacodynamics, immunogenicity and safety were also assessed. Results At week 72, similar improvements were observed by disease activity parameters including DAS28 and ACR response rate in the four extension period treatment groups. Quality of life improvements at week 72 vs baseline were similarly shown during the extension period in all groups. Newly developed anti-drug antibodies were detected in two patients following study drug infusion in the extension period. Similar pharmacodynamic and safety profiles were observed across groups. Conclusion Long-term use of CT-P10 up to 72 weeks was effective and well tolerated. Furthermore, switching from reference rituximab to CT-P10 in RA was well tolerated and did not result in any clinically meaningful differences in terms of efficacy, pharmacodynamics, immunogenicity and safety. Trail registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT02149121.

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.

Backgrounds/Aims: The aim of this study was to evaluate the usefulness of serum interleukin (IL)-37 and IL-18 as disease activity markers of adult-onset Still’s disease (AOSD) and to compare their related clinical features. Methods: Forty-five patients with a set of high and subsequent low disease activity status of AOSD that fall within a 12-month period were enrolled. Modified Pouchot (mPouchot) score and serologic disease activity markers including serum levels of IL-37 and IL-18 were compared between high and low disease activity status. The relationships between disease activity parameters and differences in serum levels of IL-37 and IL-18 according to the presence of each disease manifestation of AOSD were evaluated in high disease activity status. Results: mPouchot score and all serologic disease activity markers including ESR, CRP, ferritin, IL-37, and IL-18 significantly declined in low disease activity status (pConclusions: Both IL-37 and IL-18 can be useful serologic markers of AOSD activity, but their pathologic roles in disease activity might be different.

International audience; Objectives: There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).Methods: Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621).Results: The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advan-tage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/ Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections, and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept.Conclusion: CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.

Background To evaluate the incidence of fractures and fracture risk factors in Korean patients with polymyalgia rheumatica (PMR). Methods All PMR patients who visited a rheumatology clinic at a tertiary referral hospital between March 2005 and March 2018 were retrospectively assessed. We estimated bone mineral density (BMD) screening rate within 6 months of the first visit and classified the patients according to the performance and results of BMD screening. Incidence rates (IRs) of fractures were calculated in each group and risk factors for fractures were identified using Poisson regression analysis. Results A total of 95 PMR patients with median (interquartile range) age of 64.0 (56.0–72.0) years were included. Baseline BMD was assessed in only 55.8% of these patients (n = 53); 24 patients with osteoporosis, 20 with osteopenia, and 9 with normal BMD. During 433.1 person-years (PYs) of observation, 17 fractures occurred in 12 patients (IR, 3.93 [95% confidence interval (CI), 2.46–6.26]/100 PYs); 8.32 (95% CI, 4.09–16.90)/100 PYs in the osteopenia group, 3.40 (95% CI, 1.30–8.90)/100 PYs in the osteoporosis group, and 3.37 (95% CI, 1.53–7.39)/100 PYs in the no BMD test group. Risk factors for fractures were female sex, advanced age (≥ 65 years), longer follow-up duration, initial glucocorticoid dose ≥ 10 mg/day, and higher cumulative glucocorticoid dose over the first 6 months. Conclusion The incidence rate of fractures in Korean patients with PMR was 3.93/100 PYs. Female sex, advanced age, longer follow-up duration, and increased glucocorticoid dose are risk factors for osteoporotic fracture., Graphical Abstract

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., Graphical Abstract

Background: Patients with ankylosing spondylitis (AS) have increased levels of protein phosphatase magnesium-dependent 1A (PPM1A) and autoantibodies. We evaluated the usefulness of serum anti-PPM1A antibodies as a biomarker for AS. Methods: Serum samples from 58 AS patients were obtained from a multicenter registry prior to the initiation of anti-TNF agents. The serum levels of anti-PPM1A antibodies were measured using ELISA. Spinal radiographic progression was defined as an increase in the modified stoke ankylosing spondylitis spinal score (mSASSS) by &ge, 2 units or a newly developed syndesmophyte. The role of exogenous PPM1A on bone mineralization was evaluated using primary osteoprogenitors acquired from patients with AS and non-inflammatory controls. Results: The baseline levels of anti-PPM1A antibodies and mSASSS were higher in the radiographic progression group than in the non-progression group. In logistic regression analysis, baseline mSASSS and serum anti-PPM1A antibodies were associated with a higher risk of progression. The level of anti-PPM1A antibodies for predicting progression had an AUC of 0.716 (cut-off value: 43.77 ng/mL). PPM1A stimulation increased matrix mineralization in AS-osteoprogenitors but not in controls. Conclusion: Along with mSASSS, the serum levels of anti-PPM1A antibodies might be useful as a predictor of radiographic progression after treatment with anti-TNF agents.

CT-P10 is the first biosimilar of rituximab (RTX) for the treatment of rheumatoid arthritis (RA). The application of valuable biosimilar for the treatment of RA may decrease economic burden of society, and disease activity of RA. Thus, it is worthwhile to identify the economic advantage and further requirement for the proper use of CT-P10 in real world.Literature searching was performed to identify suitable references written in English for this review article. Rituximab, biosimilar, CT-P10, and rheumatoid arthritis were used as keywords. Current state of RA treatment, position of RTX in the recommendations for the treatment of RA, current status of RTX biosimilar development were assessed before evaluating CT-P10 itself. Physicochemical property, pharmacokinetic profile through phase I to phase III studies, pharmacodynamics, toxicology data, clinical efficacy, and safety were reviewed.As the first biosimilar to originator RTX, CT-P10 may be a useful alternative for the treatment of RA in all indications for originator RTX. In addition, more studies are required to identify long-term effectiveness and safety of CT-P10 in real world. It is also important to find out new indications of CT-P10 and effective mechanisms to lessen nocebo effect against biosimilar including CT-P10.

Objective The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. Methods In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. Results Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (− 2.7 and − 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. Conclusion CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. ClinicalTrials.gov identifier NCT02149121. Electronic supplementary material The online version of this article (10.1007/s40259-018-00331-4) contains supplementary material, which is available to authorized users.

Background/Aims: The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheu matoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Se rial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, re spectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

The infliximab biosimilar CT-P13 has widely received regulatory approval in all indications of reference infliximab, including rheumatoid arthritis (RA) and ankylosing spondylitis (AS). This retrospective analysis investigated drug survival and long-term safety and effectiveness of CT-P13 in patients with RA or AS in the Republic of Korea. This non-interventional, retrospective, multicenter analysis collected medical record data for adult patients with RA or AS who received CT-P13 treatment at five Korean referral hospitals (2012–2017). Drug survival and long-term safety were primary outcomes. The secondary outcome was long-term effectiveness, assessed by disease activity measures. Overall, 491 patients were treated with CT-P13 (154 patients with RA [135 infliximab-naive; 19 switched from reference infliximab]; 337 patients with AS [219 infliximab-naive; 118 switched from reference infliximab]). Drug survival was similar in naive and switched patients. Treatment-emergent adverse events (TEAEs) occurred in 31.8% and 29.4% of patients with RA and AS, respectively; incidence was similar in naive and switched groups. Upper respiratory tract infection, influenza-like illness, and urticaria were the most common TEAEs. Overall, nine (1.8%) patients experienced serious adverse events (SAEs) deemed potentially drug-related; SAEs led to permanent CT-P13 discontinuation in five (1.0%) patients, including three with tuberculosis. Disease activity decreased over time. Up to 5 years of CT-P13 treatment was safe and effective in patients with RA and AS, based on drug survival, incidence of TEAEs, and disease activity. Drug survival and safety were similar in naive patients and switched groups, supporting switching from reference infliximab to CT-P13.

ObjectiveGenome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case–control population.MethodsWe newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.ResultsWe identified six new RA-risk loci (SLAMF6, CXCL13, SWAP70, NFKBIA, ZFP36L1 and LINC00158) with pmeta−8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.ConclusionThis study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.

INTRODUCTION For successful switching of bio-originators to biosimilars, confidence in the switch is an important criterion. To promote confidence, scientific evidence is critical, but still there are insufficient data for the majority of approved biosimilars. Areas covered: Scientific evidence for switching from bio-originator DMARDs to biosimilars is derived from randomized controlled trials (RCTs) for switching, extension studies of RCTs for the approval process, and real-world observational studies. To identify candidate studies, PubMed was searched to collect appropriate studies in all approved biosimilars for the treatment of rheumatic diseases. In addition, abstracts for scientific meetings were reviewed to discover abstracts focused on switching. To date, we have identified 17 extension studies of RCTs, 1 RCT, and 17 real-world observational studies. Most real-world studies have originated from CT-P13 and SB4. Switching was definitively safe and effective in most of studies, but some nocebo effects were observed. Expert commentary: Clear guidelines for switching and data from post-marketing surveillance and registries will be required to confirm existing results on the safety and efficacy of switching from bio-originators to biosimilars. To lessen the nocebo effect against biosimilars, effective educational programs should be provided for all stakeholders, including patients and physicians.

CT-P13 is an infliximab biosimilar approved for indications including ankylosing spondylitis (AS), the approved maintenance regimen is 5 mg/kg infused every 6–8 weeks. In clinical practice, modifications to infliximab dose and/or infusion interval can be beneficial to the patient. For CT-P13, real-world data on dose and/or interval adjustment are lacking. This analysis investigated the impact of such treatment pattern changes on effectiveness and drug survival up to five years for adult (≥18 years old) patients with AS in the Korean, real-world, retrospective rheumatoid arthritis and ankylosing spondylitis (RAAS) study. Overall, 337 patients with AS were identified: 219 who initiated infliximab treatment with CT-P13 (‘naïve’) and 118 who switched from reference infliximab to CT-P13 (‘switched’). Overall, 18/235 (7.7%), 110/224 (49.1%), and 101/186 (54.3%) evaluable patients had dose, infusion interval, or combined treatment pattern changes, respectively. More naïve (61.0%) versus switched (42.6%) patients had treatment pattern changes. Overall, Bath Ankylosing Spondylitis Disease Activity Index scores decreased from baseline to week 54, then remained stable, improvements were greater for patients with than without treatment pattern changes. Drug survival did not differ significantly between patients with or without treatment pattern changes. Findings suggest that adjusting dose and/or infusion interval can improve clinical outcomes for CT-P13-treated patients with AS.

The first biosimilar infliximab, CT-P13 (infliximab-dyyb) has been used for the treatment of inflammatory diseases for 4 years. CT-P13 has highly similar efficacy and safety profiles with a lower price than the originator infliximab and has been approved in 81 countries. Despite approval for clinical use, some knowledge gaps still limit the widespread and pertinent use of biosimilar CT-P13. One of the most important factors for proper utilization of CT-P13 for the treatment of immune-mediated inflammatory diseases is confidence in CT-P13, which could be enhanced by scientific evidence supporting the biosimilarity of CT-P13. Overall, five randomized controlled studies have been performed. For the other extrapolated indications, many observational induction and switching studies also support the utility of CT-P13 in the treatment of inflammatory diseases. Here, we review profiles of CT-P13 including physicochemical properties, clinical efficacy and safety data in all indications and current status.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been suggested as a reliable imaging technique for monitoring of disease activity in patients with adult-onset Still's disease (AOSD). Therefore, we investigated the clinical significance of 18F-FDG PET/CT in Korean AOSD patients.Thirteen AOSD patients were included in the study. The PET/CT images were evaluated with visual and semiquantitative method using standardized uptake values (SUVs).The presence of increased 18F-FDG uptake was noted in 90% of clinically active AOSD patients. 18F-FDG uptake was located in the lymph node, spleen, and bone marrow. Visual grade and SUV intensity of lymph node was significantly correlated with the systemic score of AOSD. Visual grade of spleen was significantly correlated with the systemic score, erythrocyte sedimentation rate (ESR), and ferritin. Additionally, visual grade and SUV intensity of bone marrow was significantly correlated with the systemic score, ESR, leukocyte, and neutrophil.Visual grade and SUV intensity of lymph node, spleen, and bone marrow on 18F-FDG PET/CT scan showed significant correlations with known disease activity markers. The data suggest that 18F-FDG PET/CT scan may be a useful imaging technique for evaluation of disease activity in AOSD patients.