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ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

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 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 Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits. Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout., Graphical Abstract

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.

Background Rituximab (RTX), a monoclonal antibody that selectively binds to CD20+ B cells, showed favorable outcomes in patients with idiopathic inflammatory myopathies (IIM) in small case series, but the evidence is still not enough. Our goal was to determine the efficacy and safety of RTX for Korean patients with refractory IIM. Methods We retrospectively analyzed the medical records of 16 patients with refractory IIM treated with RTX in seven tertiary rheumatology clinics in the Korea. The efficacy of RTX was evaluated with the improvement of serum creatine phosphokinase (CPK) level and physician's global assessment (PGA), and daily corticosteroid dose reduction. A > 25% decrease in CPK level, corticosteroid dose, or PGA was considered significant. A complete response (CR) was designated by meeting three efficacy criteria and a partial response (PR) by only two criteria. Results Sixteen patients with IIM were evaluated (13 female; median age, 51.8 years). All patients had received at least one conventional immunosuppressive agent (median, 3.6 [2.0–5.0]) and concomitant corticosteroids. The median CPK level and median dose of prednisolone was 421.0 units/L and 20.0 mg/day respectively. Eleven patients were treated with intravenous immunoglobulin. Seven patients received 2,000 mg of RTX and the others received lower dose. Twenty-four weeks after RTX treatment, 11 patients achieved a > 25% reduction in corticosteroid dose and CPK levels, and nine showed improved PGA. The overall response rate was 68.8% (11 patients). At the end of follow-up (median 24 weeks), 12 (75.0%) patients responded overall: four (25.0%) and eight (50.0%) patients achieved CR and PR, respectively. Baseline muscle enzyme levels were higher in responders than non-responders, but disease duration, RTX dose, ESR and serum CRP were not significantly different between the two groups. The rate of adverse event was 25.4/1,000 person-years. Conclusion RTX could be an effective and relatively safe therapeutic option in patients with refractory IIM., Graphical Abstract

BACKGROUND/AIMS The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSION CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

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.

PURPOSE Although cardiac manifestation of Behcet disease (BD) has been described in sporadic reports, its timely diagnosis remains difficult. The objective of this study was to describe early cardiac manifestations of BD. We also performed a comprehensive classification of systemic BD activity and compared their cardiac manifestations. METHODS A prospective screening using speckle tracking echocardiography was performed in 85 patients with BD who had no history of heart disease. After excluding subjects with left ventricular (LV) ejection fraction (LVEF)

This study was supported by the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). The authors wish to acknowledge the assistance of the following investigators who enrolled patients in KORONA: Joong Kyoung Ahn (Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul), Sung Jae Choi (Korea University Ansan Hospital, Ansan), Minyoung Her (Inje University Busan Paik Hospital, Busan), Chung- Il Joung (Konyang University Hospital, Daejeon), Young Mo Kang (Kyungpook National University Hospital, Daegu), Dong- Yook Kim (Inje University Busan Paik Hospital, Busan), Hae- Rim Kim (Konkuk University Medical Center, Seoul), Hyoun Ah Kim (Ajou University Hospital, Suwon), Choong Ki Lee (Yeungnam University Medical Center, Daegu), Sang- Hoon Lee (Kyung Hee University Hospital at Gangdong, Seoul), Seong- Su Nah (Soon Chun Hyang University Cheonan Hospital, Cheonan), Sung- Hoon Park (Catholic University of Daegu School of Medicine, Daegu), Dong Hyuk Sheen (Eulji University Hospital, Daejeon), Gwan Gyu Song (Korea University Guro Hospital, Seoul), Chang- Hee Suh (Ajou University Hospital, Suwon), and Yoo Wan- Hee (Chonbuk National University Hospital, Jeonju).

Objectives The objectives of this study were to evaluate the long-term effect of anti-platelet treatment on the radiological progression of collagen-induced arthritis in rats. Methods Female Lewis rats with collagen-induced arthritis were divided into three experimental groups: saline, aspirin monotherapy (n = 12), and aspirin-clopidogrel dual therapy (n = 12). Drugs were administered daily and continued up to 70 days after the induction of arthritis. The clinical arthritis index (weight, morphology score, and paw thickness) and radiological scores were evaluated. Results The clinical arthritis index peaked on day 20, while the radiological scores peaked on day 35. No intergroup difference was observed in the clinical arthritis index throughout the experiment. The aspirin-clopidogrel dual therapy group had a significantly higher mean radiological score than the other groups (p = 0.045) on day 35. Further treatments resulted in significantly improved radiological findings in the aspirin monotherapy and aspirin-clopidogrel dual therapy groups on day 70 but no significant improvement in the saline group. Conclusion Anti-platelet agent treatment improved radiological findings on day 70. These observations emphasize the importance of a future long-term study of the effects of anti-platelet agent treatment on arthritis.

Background CT-P10 is a biosimilar of innovator rituximab (RTX), a biological therapy used to treat patients with rheumatoid arthritis (RA) who have responded inadequately to anti-tumor necrosis factor agents. Objective Our objective was to compare the clinical profile of CT-P10 versus RTX in patients with RA who received up to two courses of treatment and were followed for up to 72 weeks. Methods In this multicenter double-blind phase I study, patients were randomized 2:1 to receive CT-P10 1000 mg or RTX 1000 mg at weeks 0 and 2. Based on disease activity, patients could receive a second course of treatment between weeks 24 and 48. Efficacy endpoints, including mean change from baseline in Disease Activity Score using 28 joints (DAS28), safety, immunogenicity, pharmacokinetics, and pharmacodynamics were evaluated. Results In total, 154 patients were randomized to CT-P10 or RTX (n = 103 and 51, respectively); 137 (n = 92 and 45) completed the first course of treatment, of whom 83 (n = 60 and 23) were re-treated. Improvements from baseline in all efficacy endpoints were highly similar between the CT-P10 and RTX groups over both treatment courses. At week 24 after the second course, mean change from week 0 of the first course in DAS28 erythrocyte sedimentation rate was −2.47 and −2.04 for CT-P10 and RTX, respectively, (p = 0.1866) and in DAS28 C-reactive protein was −2.32 and −2.00, respectively (p = 0.3268). The proportion of patients positive for antidrug antibodies at week 24 after the second treatment course was 20.0% and 21.7% in the CT-P10 and RTX groups, respectively. The safety profile of CT-P10 was comparable to that of RTX, and pharmacokinetic and pharmacodynamic properties were similar. Conclusions In patients with RA, efficacy, safety, and other clinical data were comparable between CT-P10 and RTX after up to two courses of treatment over 72 weeks. (ClinicalTrials.gov identifier NCT01534884). Electronic supplementary material The online version of this article (doi:10.1007/s40259-017-0232-7) contains supplementary material, which is available to authorized users.

Aim We designed this study to evaluate the prevalence of comorbidities, their monitoring states and association with treatment medication in Korean rheumatoid arthritis (RA) patients compared with patients from other countries. Methods We analyzed 1050 RA patients from 11 Korean centers and compared them with 3520 patients from 16 other countries using an international, cross-sectional study evaluating comorbidities of RA (COMORA) database. Results Annual evaluations of cardiovascular (CV) risk were less frequently performed in Korea (P = 0.0011). The prevalence of CV-associated morbidity was similar between Korean and international RA patients, although the proportions of current smokers, patients with a family history of CV disease, patients with hyperlipidemia, and patients with Framingham score > 20% were significantly lower in Korea (P < 0.0001 for all), and the antiplatelet agents were more optimally used in Korea (P = 0.0004). Prostate cancer screening was less frequently performed compared to other countries (P < 0.0001). Less than 10% of Korean RA patients were given influenza and pneumococcal vaccinations according to current recommendations. Conclusions There are differences in the prevalence of comorbidities and monitoring states of the risk factors between patients in Korea and in other countries. The prevalence of CV morbidity was similar between the two groups although the prevalence of CV risk factors was significantly low in Korea, suggesting that rheumatologists in Korea need to pay more attention to yearly CV risk monitoring, in addition to the screening of malignancy and vaccination of RA patients against infectious diseases.

Background: There was some reports of seasonal association with myopsitis onset. With the discovery of new myositis-specific autoantibodies (MSA), detailed grouping of idiopathic inflammatory myopathies was possible. Therefore, we evaluated the seasonal patterns in the onset of idiopathic inflammatory myositis (IIM) with MSA in Korea. Objectives: To evaluate the correlation between MSA and seasonal patterns of IIM in Korea. Methods: A total of 90 patients who met the criteria for probable or definite PM or DM and for whom data were collected from 7 referal centers in korea. 16 myositis-specific autoantibodies were detected by immunoblot with patient’s serum. Statistical analyses were performed using a Poisson model that assessed associations of sex, MSA, and month of onset of symptoms or month of diagnosis. Results: There were no significant seasonal patterns of disease onset in total IIM patients. Among MSAs, anti-synthetase (n=18), anti-transcriptional intermediary factor 1 γ (TIF1γ) (n=13), anti-melanoma differentiation-aasocianted protein 5 (anti-MDA5) (n=12), and anti–signal recognition particle (SRP) (n=12) were analyzed. Among 55 patients with dermatomyositis, patients with anti-MDA5 showed a significant peak in winter (n=12, P=0.05). This seasonal association was significant in women (n =10; P=0.045). Patients with anti–synthetase, anti-TIF1 γ or anti-SRP antibodies did not have a significant seasonal onset patterns. There were no significant seasonal patterns in patients without myositis-specific autoantibodies. Conclusion: Patients with anti-MDA5 showed a seasonality of myositis onset, in winter. Disclosure of interests: None declared

Background SinceBohan and Peter first described their diagnostic criteria foridiopathic inflammatorymyopathies (IIM) in 1975, new discoveries suchas myositis-specific and myositis-associated autoantibodies (Abs) have been made. Objectives To investigate correlations between specificmyositis Abs and their frequenciesand clinical associationsacross different IIM groups, collectively demonstrating theutility of the new clinicoserologic classification in Koreanadult patients with IIM. Methods We conducted a multicenter cohort study including 67adult patients (age≥18 years) who have been diagnosed as IIM by ENMC criteria.Immunoblot assay with Euroline strip(EUROIMMUN, Germany)was performed using the sera of definite deramatomyositis (DM, n=36), definite polymyositis (PM, n=25), amyopathic DM (n=4), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (IMNM, n=1). Patients were classifiedbased on three classifications: 1) novel clinicoserologic classification suggested by Troyanov et al. in 2017. 2) 2017 EULAR/ACR classification criteria. 3) 2004 European neuromuscular center (ENMC) criteria.Associations ofmyositis Absand clinical subsets of IIM were investigated. Results The distribution of the various IIM differed strikingly from those using the 3 classifications (Fig1). According to the 2004 ENMC classification and 2017 EULAR/ACR classification criteria, DM and PM was the most and the second frequent entities (DM: 55.2%, 56.7%; PM: 35.8%, 37.3%). But, using the new clinicoserologic classification,overlapmyositis(OM) is the major type of IIM and the frequency of PM is significantly decreased.Anti-ARS Abs specificity included anti-Jo-1(16.4%), -OJ(4.6%), -EJ(6.2%) -PL-7(3.1%), and -PL-12(4.6%). Interstitial lung disease was closely associated with anti-MDA5,and anti-ARS Abs, while DM-specific skin lesion was frequently observed in patients with anti-TIF1γ and anti-ARS Abs. Sevenpatients with cancer-associated DM were identified. They were positive for anti-TIFγ (5/7) and anti- SRP(3/7) (table 1). Conclusion Novel classification based on distinctive features and new myositis Absreflects the clinical phenotype of IIM better. Establishment of a system routinely available to screen myositis Abs is needed. Thiswill be beneficial to providemore precise diagnosis and proper management for patients with IIM. Reference: [1] Jean-Luc Senecal, Jean-Pierre Raynauld, Yves Troyanov. A New Classification of Adult Autoimmune Myositis. Arthritis Rheum2017;69:878-884. Disclosure of Interests None declared

Background: Myositis-specific and myositis-associated autoantibodies (MSA and MAA) have been used for more detailed classification and prediction of clinical course of idiopathic inflammatory myopathies (IIM). Interstitial lung disease (ILD) is known to be complicated with approximately 50% of IIM patients, having poor prognosis. Objectives: The aim of this study is to investigate clinical features of ILD in Korean adult patients with IIM according to the autoantibody profile including MSA and MAA. Methods: We conducted a multicenter cohort study including 108 adult patients (age≥18 years) who have been diagnosed as IIM by ENMC criteria MSA and MAA were screened with Immunoblot assay using Euroline strip (EUROIMMUN, Germany). Clinical information including the time of developing ILD and imaging findings of chest CT was reviewed using by medical record. Results: ILD was found in about half (52.8%, 57 of 108) of enrolled patients and closely associated with the presence of anti-ARS Abs, anti-MDA5 and anti-Ro52. Among 43 patients, Anti-ARS Abs were most common (46.5%) and included anti-Jo-1 (23.3%), -OJ (2.3%), -EJ (9.3%), -PL7 (14%), and -PL12 (7%) (Figure 1). To analyze the correlation of autoantibodies with pattern of ILD onset, we stratified the 43 patients into three groups: into ILD-preceding (7/43, 16.3%), simultaneous (31/43, 72.1%) and myopathy-preceding (6/43, 14%). In the ILD-preceding group, anti-ARS antibodies were frequent. ILD preceded myopathy by 19.5 months on average. The imaging pattern of ILD in the ILD-preceding group were Cryptogenic Organizing Pneumonia (COP) 6, Nonspecific Interstitial Pneumonia (NSIP) 1 and no Usual interstitial pneumonia (UIP). A half of patient in ILD-preceding group had Raynaud`s phenomenon, and one patient had mechanic hand. On the other hand, in myopathy-preceding group, 30% of patients (2/6) were UIP and a half of patients had pulmonary function which required treatment (DLCO Conclusion: In our study, ILDs were accompanied by over half of the cases of IIM and most of them had autoantibodies. There are characteristic clinical features by onset time of ILD, so paying attention to them will help early diagnosis and prognosis prediction of ILDs. Reference [1] Yoshifuji H. Clin Med Insights Circ Respir Pulm Med. 2016 Apr 3;9 (Suppl 1):141-6. Disclosure of Interests: None declared

Background Damage in SLE is an irreversible change of organ system results from SLE involvement or adverse effects of medications. Recently, the awareness and evidence of subphenotypes in SLE has been increased. In this study, thus we are to identify damage clusters and compare organ damage involvement, demographic and clinical manifestations, mortality and weighted genetic risk score (GRS) between clusters. Methods The study was conducted from Hanyang Bae lupus Cohort. Patients whose disease duration is less than 5 years were excluded to minimize potential confounding effects of disease duration. Patients were grouped into 3 clusters based on SLICC Damage Index (SDI) at last follow-up visit using K-mean cluster analysis. Comparison of characteristics between clusters were performed using ANOVA and Chi-square test. Results A total number of 1130 patients were analyzed. Both the last follow-up visit, musculoskeletal damage was the most frequent damage domain followed by ocular, renal and neuropsychiatric damage. Three separate damage clusters were identified. Cluster 1 included 824 (72.9%) of patients. None of patients in cluster 1 was accompanied by ocular, neuropsychiatric, renal damage and premature gonadal failure. Patients in cluster 1 had significantly less pulmonary damage than cluster 3, significantly less diabetes mellitus than cluster 2, and significantly less musculoskeletal damage than two the other clusters. Cluster 2 (n=195, 17.3%) was represented by prevalent ocular (58.0%) and renal (55.4%) damage. Patients in cluster 2 had significantly more ocular, renal damage than two the other clusters. All the patients of cluster 3 (n=111, 9.8%) was accompanied by neuropsychiatric damage (100%). Patients in cluster 3 had significantly more musculoskeletal (35.1%) damage than two the other clusters. Age of SLE diagnosis and autoantibody positivity were similar among 3 clusters. Adjusted mean SLEDAI (AMS) was highest in cluster 2 (Mean ±SD, 6.7±4.8), and mortality was highest in cluster 3. Weighted GRS showed no significant difference between clusters. Conclusions We classified patients by patterns of damage involvement (damage cluster) within a SLE cohort. Renal and neuropsychiatric damage were the two distinct domain of damage that classified patients into 3 clinically meaningful clusters. Patients in cluster 2 (prevalent renal and glucocorticoid associated damage) had the highest AMS. The highest mortality was recognized in cluster with prevalent neuropsychiatric damage. Therefore, we should be attentive to prevent renal and neuropsychiatric damage to improve the survival. Funding Source(s): Comparison of demographic and clinical characteristics between damage clusters

BACKGROUND Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc). Early detection and prompt treatment of PAH associated with SSc (SSc-PAH) result in better prognosis. We conducted echocardiographic study to presume the prevalence of PAH in Korean adult SSc patients and to diagnose SSc-PAH in their early stages with right heart catheterization (RHC). METHODS We performed free of charge echocardiographic study including 37 adult SSc patients at the Chungnam National University Hospital. The possibility of PAH is determined by the estimation of pulmonary arterial pressure by peak tricuspid regurgitation velocity of > 3.0 m/s. Patients with possible PAH were recommended to undergo RHC to confirm the diagnosis. RESULTS In 37 patients, 8 patients were suspected with PAH. Among them, 6 patients agreed to be examined with RHC, and 4 were confirmed with PAH. The prevalence of possible PAH was 21.6% (8 of 37 patients), and that of confirmed PAH was 10.8% (4 of 37 patients). Four patients who were confirmed with SSc-PAH through RHC have been treated with specific pulmonary vasodilators and maintained stable. CONCLUSION Eight patients (21.6%) were possible PAH and 4 (10.8%) were diagnosed as SSc-PAH by RHC after the echocardiographic screening study of 37 adult SSc patients.

To determine characteristics of rheumatoid arthritis (RA) patients in Korea using disease-modifying anti-rheumatic drugs (DMARDs) for at least 6 months, and to identify factors associated with poor health-related outcomes.A total of 2000 RA patients aged20 years, treated with DMARDs for at least 6 months, and signed informed consent, were enrolled in this non-interventional, multicenter, cross-sectional observational study from December 2012 to June 2013. Health-related quality of life (HRQoL) was measured using EuroQuol 5D (EQ-5D) and functional disability was measured using the Korean Health Assessment Questionnaire (KHAQ). Univariate and multivariate linear regression analyses were used to determine the association between patient characteristics and patient-reported outcomes (PROs).Of all RA patients, 84% were female, patients with low Disease Activity Score of 28 joints erythrocyte sedimentation rate (DAS-28-ESR3.2) was 54%, while moderate (DAS-28-ESR 3.2-5.1) and high disease activity score (DAS-28-ESR5.1) were 38% and 7.6%, respectively. Mean EQ-5D index score and KHAQ score were 0.6 ± 0.28 and 0.7 ± 0.67, respectively. In multivariate analysis with both PROs, average HRQoL and functional disability score appeared to be worse in persons with older age compared to younger age (P0.001), and worse in females compared to males (P0.001). Compared to patients having lower DAS (3.2), those with moderate and highest DAS (3.2-5.1 and5.1) had worse outcome measures (P0.001).In this study, higher DAS was one of the most influential factors for poor PROs among all other factors. Therefore, we could suggest appropriate treatment approaches according to DAS along with other significantly associated factors with PROs in the early stage of RA.

Objective.To develop a genotype-based ankylosing spondylitis (AS) risk prediction model that is more sensitive and specific than HLA-B27 typing.Methods.To develop the AS genetic risk scoring (AS-GRS) model, 648 individuals (285 cases and 363 controls) were examined for 5 copy number variants (CNV), 7 single-nucleotide polymorphisms (SNP), and an HLA-B27 marker by TaqMan assays. The AS-GRS model was developed using logistic regression and validated with a larger independent set (576 cases and 680 controls).Results.Through logistic regression, we built the AS-GRS model consisting of 5 genetic components: HLA-B27, 3 CNV (1q32.2, 13q13.1, and 16p13.3), and 1 SNP (rs10865331). All significant associations of genetic factors in the model were replicated in the independent validation set. The discriminative ability of the AS-GRS model measured by the area under the curve was excellent: 0.976 (95% CI 0.96–0.99) in the model construction set and 0.951 (95% CI 0.94–0.96) in the validation set. The AS-GRS model showed higher specificity and accuracy than the HLA-B27–only model when the sensitivity was set to over 94%. When we categorized the individuals into quartiles based on the AS-GRS scores, OR of the 4 groups (low, intermediate-1, intermediate-2, and high risk) showed an increasing trend with the AS-GRS scores (r2 = 0.950) and the highest risk group showed a 494× higher risk of AS than the lowest risk group (95% CI 237.3–1029.1).Conclusion.Our AS-GRS could be used to identify individuals at high risk for AS before major symptoms appear, which may improve the prognosis for them through early treatment.

ObjectiveTo demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents.MethodsIn this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration–time curve from time zero to last quantifiable concentration (AUC0–last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24.Results103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%–125% (AUC0–last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles.ConclusionsCT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety.Trial registration numberNCT01534884.

Aim There is growing evidence that cold-inducible RNA-binding protein (CIRP) promotes inflammatory responses. This study investigated the relationship between CIRP and rheumatoid arthritis (RA). Methods Peripheral blood and synovial fluid were collected from 15 patients with RA and from 16 patients with osteoarthritis (OA). The concentration of CIRP was measured with the sandwich enzyme-linked immunosorbent assay (ELISA). Results The concentration of serum CIRP was significantly elevated in the RA patient group (RA patients = 26.39 ± 10.48 pg/mL, OA patients = 17.14 ± 7.24 pg/mL, P = 0.009). Furthermore, the RA patient group had a significantly higher CIRP concentration than that of the OA patient group in synovial fluid (153.56 ± 108.93 pg/mL vs. 23.63 ± 16.18 pg/mL, P < 0.001). The mean synovial fluid concentration of CIRP was significantly higher than that of the serum concentration in the RA patient group (serum concentration = 26.39 ± 10.48 pg/mL, synovial fluid = 153.56 ± 108.93 pg/mL, P < 0.001). Disease Activity Score of 28 joints (DAS28)-ESR (erythrocyte sedimentation rate) and DAS28-CRP (C-reactive protein) were positively correlated with the synovial fluid concentration of CIRP (DAS28-ESR: r = 0.582, P = 0.023; DAS28-CRP: r = 0.541, P = 0.037). Conclusion The serum and synovial concentrations of CIRP in the RA patients were increased compared to the OA patients. Additionally, the synovial concentration of CIRP in RA patients correlated well with disease activity, that is, the DAS28-ESR/CRP. Based on these results, CIRP mediates inflammation and is a potential marker for synovial inflammation.

ObjectivesTo evaluate equivalence in efficacy for rheumatoid arthritis (RA) and compare the safety of the biosimilar HD203 with innovator etanercept (ETN) plus methotrexate (MTX) (ClinicalTrials.govNCT01270997).MethodsPatients with active RA received 25 mg HD203 or ETN subcutaneously twice-weekly with MTX for 48 weeks in a phase III, multicentre, randomised, double-blind, parallel-group design. The primary end point was the proportion of patients achieving the American College of Rheumatology 20% response (ACR20) at week 24 for per-protocol study completer set (PPS). Secondary end points included ACR response criteria, ACRn, European League against Rheumatism (EULAR) response, change in Disease Activity Score 28 (DAS28), patient-reported outcomes, safety and immunogenicity.ResultsOf the 294 randomised patients (HD203, n=147; ETN, n=147), 233 comprised the 24-week PPS (n=115 and 118, respectively). ACR20 at week 24 was achieved by 83.48% and 81.36% of PPS patients, respectively, demonstrating equivalent efficacy within predefined margins of ±20% (treatment difference 2.12%, 95% CI −7.65% to 11.89%). Outcomes for secondary end points were consistent with the primary efficacy findings. Groups were comparable for overall incidences of treatment-emergent (all-causality) adverse events (AEs) (HD203 113 (76.9%) vs ETN 114 (78.1%) (p=0.804)), adverse drug reactions, serious AEs and discontinuations due to AEs. Few patients (HD203, n=8; ETN, n=3) tested positive for anti-drug antibodies.ConclusionThe study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN. HD203 was well tolerated, with safety comparable with ETN in this population of patients with RA.Trial registration numberNCT01270997; Results.

Background:Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease, which is characterized by the enthesitis, peripheral arthritis, and chronic inflammation of the spine, leading to bony ankylosis. Signal transducer and activator of transcription (STAT) family proteins are latent cytoplasmic transcription factors that convey signals to the nucleus. It is activated by IL-6, IL-23, and IL-22 through JAK-mediated phosphorylation. Moreover, genetic studies implicate interleukin-23 (IL-23) receptor signal, including STAT3 in the development of AS. IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in AS. It was reported that STAT3 is a regulatory factor that induces Th17 cell development from naive CD4 T cells.Objectives:The aim of this study is to investigate whether the STAT3 phosphorylation (stat3-p) inhibitor has a therapeutic effect on inflammation and new bone formation in AS.Methods:Eight weeks after curdlan injection, SKG mice were treated with stat3-p inhibitor or mock as a control. Clinical and histologic scores for arthritis and enthesitis were evaluated. Synovial fluid mononuclear cells (SFMC) samples were obtained from AS patients. Inflammatory cytokine producing cells were analyzed using flow cytometry. Bone tissue samples were obtained from the facet joints of patients with AS at surgery. Primary bone-derived cells (BdCs) were isolated and cultured. The osteogenic differentiation was assessed in vitro for 3 weeks using ALP activity, Alizarin red S (ARS), Type I collagen, von kossa,and hydroxyapatitestains. Statistical analysis was performed using Prism 5.0 Software. A p < 0.05 was considered statistically significant.Results:The stat3-p inhibitor significantly suppressed peripheral arthritis and enthesitis in SKG mice (figure 1). Inflammatory infiltration around the tendon–bone insertion site and along the tendon, as well as bony involvement were all reduced in stat3-p inhibitor-treated mice compared to control mice. We found that the levels of IFN-±, IL-17, TNF-± were higher in AS Synovial fluid. A significantly decreased frequencies of IFN-±, IL-17, TNF-± producing cells in AS SFMC were shown after stat3-p inhibitor treatment (P < 0.01).In vitro experiment of bone formation, the stat3-p inhibitor suppressed ALP activity. In addition, there were significant decrease in Alizarin red S (ARS), Type I collagen, von kossa staining scores due to stat3-p inhibitor at a concentration of 5 μM.Light intensity of hydroxyapatitestaining was also decreased by stat3-p inhibitor in a dose dependent manner (figure 2). Intriguingly, the stat3-p inhibitor suppressed osteogenesis in both early phase and late phase in AS-BdCs, down-regulating osteoblast-involved genes.Conclusion:The stat3-p inhibitor had beneficial effects on reducing inflammation and new bone formation in AS animal model. In addition, stat3-p inhibitor suppressed bone formation in vitro experiment. These findings suggest that the stat3-p inhibitor could be a potential therapeutic agent for AS.References:[1]Arthritis Res Ther 2018;20:115.[2]Nat Med 2012;18:1069-76.[3]Rheumatology (Oxford) 2017;56:488-493.[4]Nat Rev Immunol. 2011;11:239–50.[5]J Exp Med 2005;201:949–60.Acknowledgments:NoneDisclosure of Interests:None declared

Background To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) (2.6 ≤ DAS28 < 3.2). Results Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (−0.38 vs. −0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended., Graphical Abstract

Background Response prediction of certain biologic agents for the treatment of rheumatoid arthritis (RA) remains an unmet need in real-world clinical practice. The contribution of patient-reported components to the 28-joint Disease Activity Score (DAS28) was termed DAS28-P and investigated as a predictor of response to biologic agents, mostly tumor necrosis factor inhibitors. We aimed to evaluate DAS28-P as a predictor of the European League Against Rheumatism (EULAR) response to abatacept in patients with RA. Methods The study population was a prospective, observational, multicenter cohort of Korean patients with RA, who were followed up for a nationwide post-marketing surveillance study of abatacept. Correlation of DAS28-P with DAS28, change of DAS28, and EULAR response groups were evaluated. Logistic regression analysis was used to predict good-to-moderate EULAR response to abatacept in the study population. Results A total of 341 patients were involved in the analysis stratified on the EULAR response criteria. Presence of comorbidities, previous exposure to biologic agents, baseline DAS28, three of its components (tender joint counts, global health visual analog scale, erythrocyte sedimentation rate), and baseline DAS28-P were significantly associated with EULAR response to abatacept at 6 months. Stratified upon EULAR response, a group with good-to-moderate response had a higher baseline value and lower interval change for DAS28-P. Logistic regression analysis showed that a DAS28-P cut-off of > 0.44 was more positively associated with good-to-moderate EULAR response with abatacept treatment than naivety to biologic agents. Conclusions The DAS28-P could be predictive of response to abatacept. A higher baseline DAS28-P is associated with a favorable therapeutic response to abatacept. Trial registration Trial name, Korean Post-marketing Surveillance for Orencia®. Trial registration number, NCT01583244. Registered on April 20, 2012. Electronic supplementary material The online version of this article (10.1007/s40271-018-0347-z) contains supplementary material, which is available to authorized users.

This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration-time curve (AUC) from time zero to last measurable concentration (AUC

Background The recent studies about gout demonstrated the correlation between gout and cardiovascular disease (CVD). The urate lowering therapy (ULT) ameliorates the outcomes of CVD. The poor adherence with ULT in patients with gout is the main obstacle. It is induced mainly due to a lack of adequate information about the efficacy of ULT. Objectives This study was performed to analyse the effects of the education for patients with gout. Methods 116 patients with gout were enrolled and categorised by two groups, education and non-education. The face to face education was conducted by the specially educated nurse. And all participants in two groups received an leaflet about general information of gout including lifestyle advice, nutrition and drugs of ULT. The patients in non-education group were also educated by nurse on their second visit (after two or three month from first visit). The score of patients’ satisfaction using the visual analogue scale (from 0 to 100 mm) and questionnaire about satisfaction and questionnaire of patients’ knowledge about disease (gout) were assessed. And we analysed patients’ serum uric acid level and drug compliance. Results A total of 116 patients were randomised to education or non-education group equally. Patients’ satisfaction in visual analogue scale was significantly higher in education group (education group: 82.7±21.0 mm, vs. non-education group: 72.8±20.7 mm, p Patients’ satisfaction questionnaire was significantly higher in education group (education group: 3.89±0.5, vs. non-education group: 3.69±0.4, p=0.017). The level of knowledge about gout was higher in education group (education group: 7.4±2.0, vs. non-education group: 6.2±2.3, p=0.004). The serum uric acid level on second visit is decreased after education (baseline: 5.97±1.93 mg/dL, vs. second visit: 5.32±1.35 mg/dL, p=0.001). Besides drug compliance on second visit is improved after education (baseline: 89.6%±16.4%, vs. second visit: 94.3%±9.9%, p=0.018). Conclusions The face to face education for gout improved the patients’ satisfaction, drug adherence and serum uric acid level. The education is very important part in treatment of gout. References [1] Singh JA, Strand V. Gout is associated with more comorbidities, poorer health-related quality of life and higher healthcare utilisation in US veterans. Ann Rheum Dis2008;67:1310–6. [2] Reesi F, Jenkins W, Doherty MPatients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis201372: 826–830. [3] Cho SK, Kim D, Choi J, et al. Impact of Patient Education on the Satisfaction of Rheumatoid Arthritis Patients: A Randomized Trial of Nurse-led Versus Medical Docter-led Education. J Rheum DisVol. 23, No. 2, April, 2016. Disclosure of Interest None declared

This study compared the performance of the newly proposed 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria to the 2002 American-European Consensus Group (AECG) and 2012 ACR classification criteria for primary Sjogren's syndrome (pSS) in well-characterized Korean patients. Patients with pSS from 12 university-affiliated hospitals in Korea were enrolled from October 2013 to January 2017. Clinical and laboratory data were reviewed. For the validation set, patients who underwent evaluation tests to rule out pSS at Seoul St. Mary's hospital from November 2016 to December 2017 were analyzed. Baseline registry data were available in 458 patients, and 328 patients had sufficient data to determine the fulfillment of each criteria set. All three sets of criteria were met by 307 patients (93.6%). The newly proposed 2016 ACR/EULAR criteria were met by 325 patients (99.1%). The 2002 AECG and 2012 ACR criteria were met by 325 (99.1%) and 310 patients (94.5%), respectively. In a validation cohort consisting of 161 patients with pSS-related symptoms/signs, the sensitivity and specificity of the 2016 ACR/EULAR criteria were 100% [95% confidence interval (CI), 96.11-100.00] and 81.8% [95% CI, 76.15-94.26], respectively. Agreement between the 2016 criteria and 2012 or 2002 criteria was high (Cohen's kappa 0.736 and 0.769, respectively). The newly proposed 2016 ACR/EULAR criteria were met by most patients diagnosed with pSS according to previous criteria and showed higher sensitivity and lower specificity compared with both previous criteria sets.

OBJECTIVE Anti-transcriptional intermediary factor 1 (TIF1) antibody is associated with idiopathic inflammatory myopathies (IIMs). The aim of this study was to investigate the expression of TIF1s in IIMs. METHOD TIF1α, β or γ expression in the skin and muscle of patients and controls was studied by immunohistochemistry. Serum myositis-specific autoantibodies were detected by immunoblot. RESULTS TIF1α was expressed in the skin of most dermatomyositis (DM) patients but not in the controls (80% vs 0%, P

OBJECTIVES: This study aims to examine the effects of tocilizumab therapy on serum levels of interleukin (IL)-33 and IL-6 in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: Interleukin-33 and IL-6 levels in serum samples from 83 RA patients (10 males, 73 females; mean age 51.9 years; range, 26 to 77 years) and 12 healthy controls (2 males, 10 females; mean age 52.2 years; range, 39 to 62 years) were compared by cross-sectional, case control analysis. Of the RA patients, 40 received 24 weeks of tocilizumab therapy and were assigned to the prospective cohort. These 40 patients were then divided into two subgroups as responders and non-responders according to the American College of Rheumatology (ACR) 20. The remaining 43 RA patients did not receive tocilizumab therapy. Serum cytokine levels were analyzed at baseline and after 24 weeks of tocilizumab therapy in these patients. RESULTS: Interleukin-33 and IL-6 concentrations were significantly higher in RA patients than in healthy controls (p

N-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and were considered useful for the treatment of rheumatoid arthritis (RA). Recently, several studies suggested that n-3 PUFAs attenuated arthritis in animal model and human, however the mechanism is still unclear. Interleukin 17 (IL-17) is a pro-inflammatory cytokine mainly produced by T helper 17 (Th17) cells which cause tissue inflammation and bone erosion leading to joint destruction. In contrast, regulatory T (Treg) cells down-regulate various immune responses by suppression of naive T cells. The imbalance between Th17 cells and Tregs cell is important for the pathogenesis of RA. Here, we investigated whether n-3 PUFAs attenuate arthritis in collagen antibody-induced arthritis (CAIA) model. We used fat-1 transgenic mice expressing the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids, leading to abundant n-3 fatty acids without the need of a dietary n-3 supply. Clinical arthritis score was significantly attenuated in fat-1 mice compared to wild type (WT) mice on day 7 (1.6±1.8, p = 0.012) and day 9 (1.5±1.6, p = 0.003). Ankle thickness also decreased significantly in fat-1 mice compared to WT mice (1.82±0.11, p = 0.008). The pathologic finding showed that inflammatory cell infiltration and bone destruction were reduced in fat-1 mice compared to WT. The expression levels of IL-17 and related cytokines including IL-6 and IL-23 decreased in the spleen and ankle joint tissue of fat-1 mice compared to WT mice. Furthermore, Treg cells were expanded in the spleen of fat-1 mice and Treg cell differentiation was significantly higher in fat-1 mice than in wild type (p = 0.038). These data suggest that n-3 PUFAs could attenuate arthritis through increasing the expression of FoxP3 and the differentiation of Treg, while reducing IL-17 production. Therefore, dietary supplementation of n-3 PUFAs could have a therapeutic potential for the treatment of RA.

746 Copyright c 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 2015. 7. 13 Revised: 2015. 7. 20 Accepted: 2015. 8. 17

Background CT-P10 is a biosimilar candidate of innovator rituximab (RTX) that demonstrated a comparable clinical profile to RTX in a phase I randomized controlled trial (RCT) in rheumatoid arthritis (RA) (ClinicalTrials.gov identifier: NCT01534884). Objective This open-label extension (OLE) study (NCT01873443) compared the efficacy and safety of CT-P10 in patients with RA who received CT-P10 from the outset (i.e., from the start of the RCT and also in the OLE; ‘maintenance group’) with those who received RTX during the RCT and switched to CT-P10 during the OLE (‘switch group’). Methods Patients who completed the RCT were recruited. Based on the Disease Activity Score using 28 joints (DAS28) and predefined safety criteria, patients could receive up to two courses of CT-P10 during the OLE. Efficacy [DAS28 and European League Against Rheumatism (EULAR) response], safety and immunogenicity were assessed. Results Eighty-seven patients were enrolled; 58 and 29 had previously received CT-P10 or RTX, respectively, in the RCT. Of these, 38 (65.5%) and 20 (69.0%) were treated with CT-P10 in the OLE and therefore comprised the maintenance and switch groups, respectively. The mean change in DAS28-erythrocyte sedimentation rate (ESR) from baseline (week 0 of RCT) at week 24 of the first OLE treatment course in the maintenance and switch groups was −2.7 and −2.4, respectively. The proportion of patients with good/moderate EULAR responses was also comparable between groups. Antidrug antibodies were detected in 13.2 and 15.0% of patients in the maintenance and switch groups, respectively, at week 24 of the first OLE course. CT-P10 treatment was well-tolerated when administered for up to 2 years or after switching from RTX. Conclusion In this study population, comparable efficacy and safety profiles were observed in patients who switched from RTX to CT-P10 and those maintained on CT-P10 throughout treatment. Electronic supplementary material The online version of this article (doi:10.1007/s40259-017-0233-6) contains supplementary material, which is available to authorized users.

Background In phase 1 trials (NCT01534884 and NCT01873443), pharmacokinetic equivalence of CT-P10, biosimilar of rituximab, to innovator rituximab (RTX) was demonstrated. In the phase 3 study, equivalence of PK and efficacy up to week 24 were achieved between CT-P10 and RTX (US and EU sourced) 1,2 . Objectives To investigate the long-term efficacy, pharmacodynamics, immunogenicity and safety of CT-P10 up to week 48. Methods Patients with rheumatoid arthritis were randomly assigned to CT-P10, US-RTX or EU-RTX, in combination with MTX. The patients received 2 treatment courses at Week 0 and 24, each consisting of 2 infusions of 1000mg study drug at 2-week interval. Results A total of 372 patients were randomised, and 330 patients completed the 2nd course treatment. DAS28 scores through Week 48 were comparable between CT-P10 and US/EU-RTX (Figure), as well as the proportion of ACR responses at Week 48 between the CT-P10 and combined rituximab groups; 81.3% and 79.8% for ACR 20, 55.4% and 53.9% for ACR50, and 31.7% and 33.7% for ACR 70, respectively. B-cell depletion was comparable from after the 1st infusion and up to Week 48. Number (%) of patients with positive anti-drug antibodies in the CT-P10, US-RTX, and EU-RTX was 7 (4.9), 13 (9.4), and 5 (8.6), respectively at Week 48. The safety profile was also similar across groups (Table). Conclusions This phase 3 randomised controlled trial demonstrated the comparability of CT-P10 with two rituximab in terms of efficacy, pharmacodynamics, immunogenicity and safety for 1 year. References Suh CH, et al. 2016 ACR Abstract No. 1634. Yoo DH, et al. 2016 ACR Abstract No. 1635. Disclosure of Interest C.-H. Suh Consultant for: Celltrion, Inc., E. Chalouhi El Khouri Grant/research support from: Celltrion, Inc., P. Miranda Grant/research support from: Celltrion, Inc., F. F Cons Molina Grant/research support from: Celltrion, Inc., P. Shesternya Grant/research support from: Celltrion, Inc., F. Medina-Rodriguez Grant/research support from: Celltrion, Inc., P. Wiland Grant/research support from: Celltrion, Inc., S. Jeka Grant/research support from: Celltrion, Inc., J. Chavez-Corrales Grant/research support from: Celltrion, Inc., T. Linde Grant/research support from: Celltrion, Inc., P. Hrycaj Grant/research support from: Celltrion, Inc., I. Hospodarskyy Grant/research support from: Celltrion, Inc., M. Abello-Banfi Grant/research support from: Celltrion, Inc., J. Jaworski Grant/research support from: Celltrion, Inc., M. Piotrowski Grant/research support from: Celltrion, Inc., W. Park Consultant for: Celltrion, Inc., S. C. Shim Consultant for: Celltrion, Inc., S. J. Lee Employee of: Celltrion, Inc., S. Y. Lee Employee of: Celltrion, Inc., D. H. Yoo Consultant for: Celltrion, Inc.

Background High body mass index (BMI) is known to be associated with inadequate clinical response to anti-TNF agents in rheumatoid arthritis (RA) patients. 1 However, there are limited data on the effect of high BMI on the response to rituximab in RA patients, who showed an inadequate response or intolerance to anti-TNF agents. Objectives To investigate the impact of BMI on clinical response in the post-hoc analysis of randomized controlled trial that demonstrated clinical equivalence between a biosimilar of rituximab, CT-P10 and innovator rituximab, RTX 2 (NCT02149121). Methods A total of 332 patients who received two courses of either CT-P10 or RTX were included in this analysis. Patients were classified into 3 groups; normal weight ( 2 ), overweight (≥25 kg/m 2 ) and obesity (≥30 kg/m 2 ) as per WHO BMI category. Improvement in disease activity by the Disease Activity Score using C-reactive protein (DAS28-CRP), remission (≤2.6), low disease activity rate (LDA, ≤3.2) and ACR response at Week 24 (Week 24 of 1st course) and Week 48 (Week 24 of 2nd course) and duration of sustained LDA (from the first LDA observed to the last LDA observed up to Week 48) were analysed by BMI categories in the each and combined group of CT-P10 and RTX. Results In the pooled group of CT-P10 and RTX, the mean weights were 59 kg in normal weight, 73kg in overweight and 91kg in obesity. All other baseline characteristics were comparable among BMI groups including baseline disease activity based on DAS28; Moderate disease activity, 22.3% vs. 22.8% vs. 25.7%, respectively; High disease activity, 77.7% vs. 77.2% vs. 74.3%, respectively. There was no statistical difference among BMI groups in terms of DAS28 change from baseline and ACR 20/50/70 response (Table). No particular trend was observed in remission and LDA rate by DAS28 at Week 24 and Week 48 among BMI groups (Figure). Mean duration of sustained LDA (months) were also comparable among the groups (4.5 vs. 4.7 vs. 5.0, respectively). Additionally, similar trends in all analyses were observed in each treatment group; CT-P10 and RTX. Conclusions The BMI does not affect the clinical response in RA patients with rituximab treatment. Therefore, this result supports that rituximab could be a reasonable therapeutic option for obese RA patients with inadequate response to anti-TNF agents. References Gremese E et al. Arthritis Care Res (Hoboken) 2013;65:94–100. Yoo DH, et al. American College of Rheumatology 2016; Abstract No. 1635. Disclosure of Interest D. H. Yoo Consultant for: Celltrion Inc., W. Park Consultant for: Celltrion Inc., C. H. Suh Consultant for: Celltrion Inc., S. C. Shim Consultant for: Celltrion Inc., S. J. Lee Employee of: Celltrion Inc., Y. J. Bae Employee of: Celltrion Inc., C. Park Employee of: Celltrion Inc., J. H. Koo Employee of: Celltrion Inc.

We evaluated the COX-2 inhibitors, etoricoxib and celecoxib, in Korean patients with osteoarthritis (OA).This study included patients (≥ 40 years of age) with a clinical and radiographic diagnosis of knee OA. Patients were randomized to etoricoxib 30 mg (qd) or celecoxib 200 mg (qd) in a 12 week randomized, controlled, double-blind study. Prior NSAID users were to demonstrate a worsening of symptoms upon withdrawal of medication. Efficacy endpoints included the time-weighted average change from baseline in the WOMAC VA 3.0 Pain Subscale (100 mm Visual Analog Scale [VAS]; primary endpoint), the WOMAC VA 3.0 Physical Function Subscale (100 mm VAS), and Patient Global Assessment of Disease Status (PGAD) (100 mm VAS). The primary hypothesis was that etoricoxib 30 mg is non-inferior to celecoxib 200 mg as assessed by the primary endpoint (the non-inferiority margin was set at 10 mm VAS). Adverse events (AEs), laboratory parameters, and vital signs were monitored.There were 239 patients (89.5% female; mean age: 63.3 years) randomized to etoricoxib 30 mg (n = 120) and celecoxib 200 mg (n = 119). The differences (etoricoxib vs celecoxib) in least square (LS) mean change (95% CI) for WOMAC Pain, WOMAC Physical Function, and PGAD were -1.63 mm (-5.37, 2.10), -1.32 mm (-4.88, 2.23), and -1.09 mm (-5.48, 3.30), respectively. Drug-related clinical AEs occurred in 6.7% (etoricoxib) and 2.5% (celecoxib) of patients. This study was limited because it was not designed or powered to adequately capture and evaluate rare AEs associated with NSAID treatment.Etoricoxib 30 mg administered once daily in Korean patients with knee OA demonstrated non-inferior clinical efficacy to celecoxib 200 mg over 12 weeks of treatment as assessed by all primary and secondary outcomes. Etoricoxib 30 mg qd and celecoxib 200 mg qd were generally safe and well tolerated.NCT01554163.

The objectives of the study are to demonstrate the non-inferiority of PG201 (Layla®) 600 mg in comparison with celecoxib 200 mg for the treatment of symptomatic knee osteoarthritis (OA). In total, 309 patients were randomly assigned to receive either the test drug, PG201 600 mg (n = 154) or celecoxib 200 mg (n = 155). The primary efficacy variable was improvement in mean 100-mm pain VAS score from baseline to the final visit (week 8), and this value was compared between the 2 treatment groups. Secondary outcome variables included changes from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain VAS score and subscale score, patient’s global assessment of disease status quality of life (short form-36) and responder index at weeks 4 and 8. For safety assessment, adverse events were recorded at each clinical visit. At weeks 8, the 100-mm pain VAS scores were significantly decreased in patients receiving both PG201 600 mg (p

Dermatomyositis (DM) and polymyositis (PM) are representative idiopathic inflammatory myopathies characterized by symmetric and progressive proximal muscle weakness. Especially, DM is identified by characteristic skin lesions and has many extramuscular manifestations including various cardiac abnormalities, interstitial lung disease, and malignancy. However, involvement of peripheral nervous system in DM/PM is very rare and less known. The term “Neuromyositis” was introduced by Senator in 1893 to describe the concomitant involvement of the peripheral nervous system in DM/PM. Since then, a very few cases of neuromyositis have been reported mainly in the United States and Europe. Therefore, the pathogenetic mechanism and disease progression are unclear. In recent years, a few more cases were reported in Asia, specifically, China and Japan; however, none in Korea. Here, we describe a case of DM-associated neuromyositis in a 42-year-old man in Korea and review previous publications through literature research. (J Rheum Dis 2019;26:211-218)

Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). However, little is known about factors associated with susceptibility to rheumatoid arthritis-related lung diseases (RA-LD). The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 and HLA-DRB1 alleles were associated with RA-LD. Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA-LD was diagnosed using high-resolution computed tomography of the chest. All patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles and analyzed for full amino acid sequence of the HLA protein corresponding to a 4-digit HLA typing. Data were analyzed by independent t test (or Mann–Whitney test) for continuous variables, Chi-square test (or Fisher’s exact test) and trend test for categorical variables, and logistic regression analysis. Ninety-four (81.0 %) RA patients had LD, of which eight (6.9 %) had interstitial lung disease (ILD) and 92 (79.3 %) had airway abnormalities in which 64 (55.2 %) showed bronchiectasis and 47 (40.5 %) revealed bronchial wall thickening. The recessive genotype of padi4_92 was susceptible to airway abnormalities (OR = 2.22, 95 % CI = 1.05–4.49, p = 0.034). Tryptophan at position 9 of HLA-DRB1 sequence was associated with the susceptibility to RA-ILD (OR = 22.89, 95 % CI = 1.20–432.56, p = 0.037). PADI4 polymorphisms and HLA-DRB1 alleles could attribute differently to the development of airway abnormalities and ILD, respectively, in RA.

Backgrounds Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors. Methods Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually. Findings Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8-66.7] months). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis.

Objective. To estimate the prevalence of non-adherence to rheumatoid arthritis (RA) medication and identify the associated factors for non-adherence in RA patients. Methods. Among the KORean Observational study Network for Arthritis 3,523 patients who completed a questionnaire about the adherence to RA medication were analyzed. The patients were divided into two groups: 1) adherent group, patients who skipped medication ≤5 days within the past 2 months; and 2) non-adherent group, patients who skipped ≥6 days of medication. The baseline characteristics were compared, and multivariable regression analysis was performed to identify the associated factors for non-adherence. Results. The non-adherent group had 339 patients (9.6%). The common causes of non-adherence were forgetfulness (45.8%), absence of RA symptoms (24.7%), and discomfort with RA medication (13.1%). Younger age (odds ratio [OR] 1.02, p＜0.01) and higher income (OR 1.70, p＜0.01) were associated with an increased risk of non-adherence. Whereas higher functional disability (OR 0.68, p＜0.01) and oral corticosteroid use (OR 0.73, p=0.02) were associated with a decreased risk of non-adherence. The associated factors differed according to cause of non-adherence. Having adverse events (OR 2.65, p=0.02) was associated with the risk of non-adherence due to discomfort with RA medication while a higher level of education (OR 2.37, p=0.03) was associated with the risk of non-adherence due to an absence of RA symptoms. Conclusion. The 9.6% of Korean RA patients were non-adherent to RA medication. The associated factors differed according to the cause of non-adherence. Therefore, an individualized approach will be needed to improve the adherence to RA medication. (J Rheum Dis 2018;25:47-57)

The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ-DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80 % of the data) and a validation set (20 % of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R (2) as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5D = 0.95-0.21 × HAQ-DI-0.24 × pain VAS/100-0.01 × DAS28 (adjusted R (2) = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured.

Objective.Rheumatoid arthritis (RA) is a chronic autoimmune disease that is often painful and debilitating. Patients with RA are increasingly receiving complementary and alternative medicine (CAM). We aimed to identify the patient characteristics and disease-specific factors associated with Korean patients with RA who decide to start treatment with CAM.Methods.Among the total 5371 patients with RA in the KORean Observational study Network for Arthritis (KORONA), 2175 patients who had no experience with CAM were included in our study. In our study, we assessed the frequency of new incident CAM use, its patterns, and the predictive factors of new CAM use.Results.Of the 2175 patients, 229 patients (10.5%) newly started receiving CAM within a year of enrolling in the cohort. Of those who started treatment with CAM, 17.0% received only herbal medicine, 54.6% only acupuncture treatments (7.0% used a combination of both), and 21.4% “Other” (e.g., physical therapy and placental extract injections). Women (OR 1.89, 95% CI 1.13–3.14) and patients with depression (OR 3.52, 95% CI 1.65–7.50) were significantly more likely to be treated with CAM. Regarding household types, patients who lived in an extended family (OR 1.78, 95% CI 1.08–2.95) or as part of a couple (OR 1.55, 95% CI 1.07–2.24) were more likely to be treated with CAM than patients living in a nuclear family.Conclusion.Our study found, within a year, an incidence rate of 10.5% for new CAM use among patients with no previous experience with CAM. Sex, depression, and household type were significantly associated with new CAM use.

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα agents according to JCR and BSR guidelines, respectively. The main discrepancy was the higher active joint count required by the KNHI eligibility criteria. In the opinion of treating rheumatologists, the KNHI reimbursement criteria ineligibility accounted for 15.3 % (n = 213) of the reasons for not initiating anti-TNFα agents in anti-TNFα-naive group. The anti-TNFα user group showed significantly higher disease activity than the anti-TNFα-naive group based on DAS28 score. In comparison with the ACR recommendations and JCR and BSR guidelines, fewer patients met KNHI reimbursement eligibility criteria for anti-TNFα agents. The current amendment of the KNHI criteria based on DAS28 score will improve an access to biologic agents including anti-TNFα treatment for South Korean patients with active RA.

T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%,P=0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks(P=0.045)and 24 weeks(P=0.046)after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

To the Editor: Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by progressive and destructive arthritis of the spine and pelvis1. B cells are involved in the pathogenesis of autoimmune diseases through antibody production, cytokine release, and antibody presentation to auto-reactive T cells. In AS, the role of B cells in the pathogenesis is still incompletely understood2. It has been hypothesized that the production of high affinity monoreactive autoantibodies in autoimmune disease could arise from intrinsic abnormalities in the generation of immunoglobulin genes3. Immunoglobulin gene usage can be regarded as an important factor of pathogenesis of autoimmune diseases. Investigation of variable heavy chain (VH) gene usage is important for determining whether usage of particular gene families is distorted. Several studies have investigated the VH gene usage in various autoimmune diseases, including systemic lupus erythematosus4, myasthenia gravis5, rheumatoid arthritis (RA)6, Sjogren syndrome7, and AS8 … Address correspondence to Dr. S-C. Shim, Division of Rheumatology, Department of Medicine, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, 6 munwha-ro Jung-gu, Daejeon, South Korea. E-mail: shimsc{at}cnuh.co.kr

Background and Object Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS. Methods A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke’ Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates. Results We identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74×10−4) and rs1235192 [OR 1.92, p = 1.17×10−3]) adjusted by covariates. Conclusion This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.