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ObjectivesThe aim of this article is to investigate the mortality rate of patients with early rheumatoid arthritis (RA) over the past 17 years.MethodsJapanese patients with early RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2001 to 2012 were classified into Groups A (2001–06) and B (2007–12). The standardized mortality ratio (SMR) and 5-year survival rate were calculated.ResultsGroups A and B had 1609 and 1608 patients, of which 167 and 178 patients were lost during follow-up and 47 and 45 deaths were confirmed, respectively. The SMR (95% confidence intervals) for Groups A and B were 0.81 (0.59–1.08) and 0.78 (0.57–1.04), respectively, with the condition that all untraceable patients were alive. Assuming that the mortality rate of untraceable patients was twice as high as that of the general population, the SMR was 0.90 (0.68–1.19) for Group A and 0.92 (0.68–1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for Groups A and B, respectively.ConclusionsThe 5-year mortality of patients with early RA has been comparable to that of the general Japanese population. The 5-year survival rate has been stable over the past 17 years.

Objectives To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). Methods We included 5103 patients with RA and CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45 to Results Of the 5103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalised infections [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.07–2.13, p = .02], especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12–3.13, p = .02). Of all subjects, 2407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with the failure of achieving remission (aHR 0.82, 95% CI 0.68–0.99, p = .04). Conclusions Concomitant CKD was a risk factor for hospitalised infections in Japanese patients with RA and failure of achieving remission in patients with active RA.

Objectives To elucidate the incidence and risk factors of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) in the biologics era. Methods We determined the rate of HZ occurrence among the RA patients that participated in the Institute of Rheumatology, Rheumatoid Arthritis surveys from 2011 to 2015, by assessing medical records. The standardised incidence rate per 1000 patient-years with a 95% confidence interval (CI) was calculated, and risk factors for HZ were analysed using a time-dependent Cox regression analysis. Results Among 7815 patients (female, 84.7%) contributing to 25,863 patient-years of observation, 340 HZ events in 309 patients were confirmed. The standardised incidence rate (95% CI) per 1000 patient-years was 8.5 (6.9–10.5) in total, 6.0 (3.7–9.2) in men, and 11.0 (8.7–13.7) in women. Risk factors for HZ were age per 10 years (hazard ratio 1.14, 95% CI 1.03–1.26, p Conclusions In the era when biologics were frequently used and corticosteroid use and doses were decreasing, methotrexate and biologics increased the risk for HZ.

Objectives To evaluate the differences in patients’ population and efficacy/effectiveness of biological disease–modifying antirheumatic drugs (bDMARDs) between randomized controlled trials (RCTs) and clinical practice in patients with rheumatoid arthritis. Methods We reviewed inclusion criteria in Phase II or III RCTs of bDMARDs conducted in Japan. The Institute of Rheumatology, Rheumatoid Arthritis study participants during the period when each RCT was conducted (Cohort A) and new bDMARD users at our institute in 2016 (Cohort B) were assessed for the fulfilment of the inclusion criteria. The effectiveness of bDMARDs in our cohort and their efficacy in RCTs were compared using the inverse-variance method. Results Nineteen RCTs were selected. The mean proportions of patients fulfilling all inclusion criteria of each RCT in Cohorts A and B were 2.3% and 7.6%, respectively. The pooled proportion ratios (95% confidence interval) for achieving the American College of Rheumatology 20 (ACR20), ACR50, ACR70, and disease activity score 28 remission in non-eligible cases for eight RCTs versus all corresponding RCTs were 0.38 (0.30–0.51), 0.41 (0.30–0.57), 0.54 (0.35–0.82), and 1.28 (1.10–1.56), respectively. Conclusions Few rheumatoid arthritis patients fulfilled the inclusion criteria of the RCTs in clinical settings. There was a difference in the efficacy/effectiveness of bDMARDs between RCTs and clinical practice.

Objectives The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). Methods Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000–04; early biologics, 2005–09; and recent biologics, 2010–13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. Results Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80–1.14) in the pre-biologics period, 0.95 (0.82–1.09) in the early biologics period, and 0.87 (0.75–1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58–5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. Conclusions Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA.

Background:The mortality of patients with rheumatoid arthritis (RA) has been reported to have reduced due to the improved treatment of RA in the last two decades. However, it has not yet been clarified whether the progress of RA treatment improves the prognosis of patients with early RA. We aimed to investigate the mortality rate of patients with early RA over the past two decades.Methods:Patients with RA who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort within two years of disease onset between 2001– 2012 were enrolled and classified into Group A (2001–2006) and B (2007–2012). The standardized mortality ratio (SMR) versus the Japanese general population and five-year survival rate were calculated. A multiple imputation method was employed for the sensitivity analysis of SMR. The five-year survival rates were evaluated using the Kaplan–Meier method.Results:Groups A and B had 1,609 and 1,608 patients, respectively, of which 167 (10.4%) and 178 (11.0%) patients were lost during follow-up, respectively. Overall, 47 and 45 deaths of patients were confirmed in Groups A and B, respectively. The SMR (95% confidence interval) for Groups A and B were 0.81 (0.59–1.08) and 0.78 (0.57–1.04), respectively, with the condition that all untraceable patients were alive for 5 years. Assuming that the mortality rate of patients lost to follow-up was twice as high as that of the general population, the SMR was 0.90 (0.68–1.19) for Group A and 0.92 (0.68–1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for groups A and B, respectively (P=0.83).Conclusions:The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population; the 5-year survival rate has been stable over the past two decades.

Patients with ulcerative colitis (UC) often develop arthropathy. The purpose of this study was to determine the frequency of and risk factors for arthropathy in patients with UC who underwent total colectomy which is the final radical treatment lead to remission.Patients who underwent total colectomy from January 2007 to April 2016 were analyzed for the development of arthropathy. The type of arthropathy and risk factors for developing arthropathy were analyzed by clinical and endoscopic severity classification, extraintestinal manifestations (EIMs) and medical treatment.Total of 219 patients who underwent total colectomy with sufficient medical records were analyzed. Forty-eight cases (21.9%) had EIMs, and 40 cases (18.2%) developed arthropathy (57.0% polyarthropathy; 42.5% peripheral arthropathy). Multivariate analysis showed that severity of Matts classification grade 3 or 4 versus grade 1 or 2 (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.22-4.36,This study showed that approximately one fifth of patients with UC who underwent total colectomy developed arthropathy. The risk factors for the development of arthropathy were preoperative endoscopic disease activity and EIMs.

To analyze the proportion of successful biological disease-modifying antirheumatic drugs (bDMARDs) discontinuation and related factors in patients with rheumatoid arthritis (RA) in clinical settings. Among 1775 RA patients who started bDMARDs between 2003 and 2012, 43 patients with DAS28-ESR p = .04). The BS group experienced a larger decrease in average glucocorticoid (GC) dose during bDMARD use than the BF group (−3.0 mg/day vs 0 mg/day; p = .01). bDMARDs were discontinued without flare up of RA in 58.1% of patients with RA in clinical settings. A lower DAS28-ESR at initiation and reduction of GC dose before discontinuation of bDMARD were important factors associated with bio-free success.

Background Some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) also have positivity of rheumatoid factor (RF). However, the clinical significance of this occurrence remains unknown in AAV patients. The aim of this study was to clarify an association between the presence of RF and clinical features in patients with AAV. Results Forty-seven patients diagnosed with AAV who were not complicated with RA were enrolled in this study. We compared clinical manifestations of AAV between an RF-positive subset (n = 29) and an RF-negative subset (n = 18). The Birmingham Vasculitis Activity Score (BVAS) was higher (P = 0.026) in the RF-positive subset than in the RF-negative subset. The levels of CRP and ESR were higher in the RF-positive patients (P = 0.020 and P = 0.007, respectively) compared to the RF-negative subset. IgM-RF titers were significantly correlated with the BVAS (r = 0.50, P = 0.0004). In addition, the IgM-RF titers had significant correlations with the levels of CRP (r = 0.41, P = 0.004), ESR (r = 0.39, P = 0.016), IgM (r = 0.36, P = 0.016) and IgG (r = 0.37, P = 0.015). The frequency of commencement of dialysis therapy, usage of mechanical ventilation and mortality were higher in the RF-positive subset than in the RF-negative subset. Conclusions In patients with AAV, RF titers were significantly correlated with disease activity and the levels of inflammatory markers. The presence of RF could be a poor prognostic factor in patients with AAV.

The patient was a 62-year-old man with anticitrullinated protein antibody-positive rheumatoid arthritis (RA) and a history of repeated respiratory tract infections and organizing pneumonia for eigh...

Background:Patients with elderly-onset rheumatoid arthritis (EORA) are on the rise in the aging or super-aging society, especially in Japan. Patients with EORA have more comorbidities than those with younger-onset RA, a higher risk of adverse drug reactions due to reduced drug metabolism, and a higher risk of infections1). Therefore, patients with EORA tend to receive suboptimal treatment, resulting in insufficient control of disease activity2). Although several studies reported treatment responsiveness in patients with EORA, many of them have a limited observation period3-8), and long-term treatment responses and their associated factors need to be clarified.Objectives:We retrospectively evaluated treatment responses of patients with EORA for 3 years and their associated factors in a clinical setting.Methods:The Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort is a large, single institute-based, observational cohort of RA patients established at Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. The subjects were RA patients who first enrolled in the IORRA cohort from 2010 to 2014, were over 60 years old with less than 1-year disease duration, and had a DAS28-ESR over 3.2 at entry. The primary endpoint was DAS28-ESR Results:Among a total of 250 patients in this study, 152 patients (60.8%) achieved DAS28-ESR Conclusion:The majority of the patients with EORA achieved DAS28-ESR References:[1]Nat Rev Rheumatol 2013;9:604-613[2]Ann Rheum Dis 2006;65:1226-1229[3]Ann Rheum Dis 2009;68:1470–1473[4]Joint Bone Spine 2015;82:25-30[5]J Rheumatol 2016;43:1974-1983[6]Rheumatology 2015;54:798-807[7]Rheumatology 2014;53:1075-1086[8]Japanese Journal of Geriatrics 2018;55:251-258Acknowledgments:We thank all patients who participated in the IORRA survey and all of the members of the Institute of Rheumatology, Tokyo Women’s Medical University, for the successful management of the IORRA cohort.Disclosure of Interests:Mai Abe: None declared, Eiichi Tanaka Consultant of: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, Moeko Ochiai: None declared, Yoko Shimizu: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari Speakers bureau: Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Background Randomized controlled trials (RCTs), which are currently considered to provide the highest level of evidence, include patients with high disease activity and exclude those with comorbidities often seen in the real world. With the increasing recognition of the importance of real-world evidence, attention is being paid to discrepancies between RCT-based evidence and the patient population in routine clinical practice; however, few reports assessing these gaps in the context of rheumatoid arthritis (RA) are available. Objectives We investigated the discrepancy between the efficacy of biological DMARDs (bDMARDs) in RCTs and the effectivenessof bDMARDs in routine clinical practice in patients with RA based on the IORRA cohort. Methods The effectiveness of bDMARDs (etanercept [ETN; n=33], golimumab [GLM; n=20], certolizumab [CZP; n=17], abatacept [ABT-subcutaneous injection {sc}; n=14], and tocilizumab [TCZ-sc; n=24]) in RA patients who newly initiated bDMARD therapy in our hospital in 2016 was compared with the efficacy reported in phase 2 or 3 trials (8 total RCTs: ETN, 1; GLM, 2; CZP, 2; ABT, 1; TCZ, 2) during the RCT’s observational periods. Effectiveness was evaluated by percentages of patients achieving ACR20, ACR50, and ACR70 and clinical remission based on DAS28 remission criteria using the IORRA cohort database. We also compared treatment responses between IORRA eligible and non-eligible patients in the MATSURI study, a phase 2 trial that evaluated TCZ-sc efficacy and safety and had relatively lenient inclusion criteria, since some RA patients in the IORRA cohort belonged to both the eligible and non-eligible groups. Results In 7 RCTs (excepting the MATSURI study), very few patients fulfilled the IORRA inclusion criteria (Table). The ACR achievement rates were higher among patients in RCTs, while remission rates were higher among IORRA patients (Table). The average DAS28 at baseline in the RCTs group was significantly higher than that in the IORRA group (Table). In the MATSURI study, 13 of 24 patients who newly initiated TCZ-sc met the inclusion criteria in the IORRA. Although the percentages of patients achieving ACR20, ACR50, and ACR70 and clinical remission among eligible patients were similar to those of patients in the MATSURI study, those of non-eligible patients were lower than those of MATSURI patients (Table). This indicates better effectiveness in eligible patients than in non-eligible patients. Conclusion Although RA patients in RCTs experienced a better ACR achievement rate than those in routine practice, clinical remission was difficult to achieve. This might be due to the difference in disease activity at the time of bDMARD introduction, suggesting that it is necessary to interpret the efficacy of RCTs based on differences in patient background. References Disclosure of Interests Eri Sugano: None declared, Eiichi Tanaka Speakers bureau: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue: None declared, Mai Abe: None declared, Mika Kawano: None declared, Kumiko Saka: None declared, Naohiro Sugitani: None declared, Yoko Shimizu: None declared, Moeko Ochiai: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari: None declared, Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio

Background Recent advances in rheumatoid arthritis (RA) treatment including the introduction of biologics have greatly affected treatment strategies for RA, achieving remission as a realistic treatment target. However, few reports have been concerned chronological changes in long-term physical dysfunction among large numbers of RA patients in daily practice. Objectives To evaluate chronological changes in Japanese version of Health Assessment Questionnaire score (J-HAQ) score and J-HAQ remission rates at 5 years after RA onset using the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. Methods RA patients who developed RA between 2000 and 2010 and who first visited our hospital during the year of RA onset were divided into two groups: 1) former onset group (RA onset between 2000 and 2005) and 2) recent onset group (RA onset between 2006 and 2010). J-HAQ scores and J-HAQ remission rates at baseline and at 5 years after onset were investigated for each group, and factors associated with J-HAQ remission after 5 years were assessed by logistic regression analysis. Methotrexate (MTX), corticosteroid (steroid) and biologic DMARDs user (bDMARDs) was defined as the patients if they were used each medication during the observation period. Results The former onset group and recent onset group included 357 and 291 RA patients, respectively. For the former onset group, the average J-HAQ score/J-HAQ remission rate at baseline and 5 years after the onset were 0.659/54.6% and 0.430/71.4%, respectively. The recent onset group showed significant improvements relative to the former onset group in J-HAQ score/J-HAQ remission rates at baseline and 5 years of 0.705/52.2% and 0.316/78.4%, respectively (p=0.011/0.044). The percentage of MTX and bDMARDs users was significantly higher in the recent onset group (former vs. recent onset group; MTX: 70.9% vs. 86.6% [p Conclusion In daily practice, J-HAQ scores for RA patients remarkably improved with recent advances in RA treatment strategies. To achieve J-HAQ remission at 5 years of RA onset, beginning treatment in the early disease stage is needed to prevent deterioration of J-HAQ and treatments that avoid steroid use appear to be important. Acknowledgement We thank all patients who participated in the IORRA survey and all of the members of the Institute of Rheumatology, Tokyo Women’s Medical University, for the successful management of the IORRA cohort. Disclosure of Interests Mai Abe: None declared, Eiichi Tanaka Speakers bureau: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue: None declared, Mika Kawano: None declared, Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, Yoko Shimizu: None declared, Moeko Ochiai: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari: None declared, Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio

Background: Patient-reported outcomes are important for evaluating the disease status of patients with rheumatoid arthritis (RA). The EuroQol five-dimensional descriptive system (EQ-5D) has been used to assess health-related quality of life (QOL) in clinical research and pharmacoeconomic studies. RA is a chronic disease associated with pain, fatigue, disability, and functional loss, which can markedly decrease patient QOL. The treatment strategies for RA and the QOL of RA patients, which is evaluated in daily practice using the EQ-5D, have changed significantly since the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs). Objectives: To identify patient subsets with distinct EQ-5D trajectories among RA patients taking bDMARDs, and to examine the clinical features of patients whose QOL improved since bDMARD use in daily practice. Methods: Since October 2000, we have established a large observational cohort of RA patients at our institute Institute Of Rheumatology, Rheumatoid Arthritis (IORRA). Essentially, all RA patients who attend our clinic are given questionnaires, including the EQ-5D, Disease Activity Score 28 (DAS28), and the Japanese version of the Health Assessment Questionnaire (J-HAQ), every 6 months. More than 5,000 RA patients are included in this cohort, of whom 785 patients who received bDMARDs for at least 3 years were enrolled in this study. The EQ-5D scores of these 785 patients were recorded biannually for 3 years, and latent class analysis of the temporal trends in the EQ-5D score based on posterior probabilities was performed after initiation of bDMARDs. The clinical characteristics of each latent class were then compared. Results: The 785 patients (107 taking infliximab, 341 etanercept, 100 tocilizumab, 131 abatacept, 90 golimumab, and 16 certolizumab pegol) were classified into four classes based on time-related changes in their EQ-5D scores: Class 1 (n = 160), patients with a consistently low score Conclusion: The results of this study suggest that QOL is less likely to improve in patients with RA whose disabilities and QOL deterioration have already become established despite use of bDMARDs. We also determined the clinical features of RA patients whose QOL improved after initiation of bDMARDs. Disclosure of Interests: Kumiko Saka: None declared, Eiichi Tanaka Speakers bureau: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue: None declared, Mai Abe: None declared, Mika Kawano: None declared, Eri Sugano: None declared, Naohiro Sugitani: None declared, Moeko Ochiai: None declared, Yoko Shimizu: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari: None declared, Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio

Background: Randomized controlled trials (RCTs), which are currently considered to provide the highest level of evidence, include patients with high disease activity and exclude those with comorbidities often seen in real-world settings. With the increasing recognition of the importance of real-world evidence, attention is being paid to discrepancies between RCT-based evidence and the patient population in routine clinical practice; however, few reports assessing these gaps in the context of rheumatoid arthritis (RA) are available. Objectives: To evaluate the proportion of patients meeting the inclusion criteria in RCTs of biologics for the treatment of RA conducted in Japan using the real-world IORRA cohort. Methods: The inclusion criteria used in Phase 2 or Phase 3 RCTs of the following biological DMARDs (bDMARDs) were extracted: infliximab (IFX), etanercept (ETN), adalimumab (ADA), golimumab (GLM), certolizumab (CZP), abatacept (ABT), tocilizumab (TCZ), and infliximab BS (IFX-BS). Patients participating in the IORRA study during the period when each RCT was conducted (Cohort A) and those who initiated treatment with each bDMARD at our institute in 2016 (Cohort B) were included in the analysis. The proportion of RA patients in Cohorts A and B who met the RCT inclusion criteria was assessed. Results: A total of 19 RCTs were conducted in Japan (IFX, 2; ETN, 1; ADA, 2; GLM, 2; CZP, 3; ABT, 2; TCZ, 6; IFX-BS, 1). Key trial inclusion criteria were age, RA duration, tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), methotrexate (MTX) use, corticosteroid use, and prior bDMARD therapy. The number of patients participating in the IORRA analysis during the period when each RCT was conducted ranged from 1,777 to 6,843 (mean: 5,470) (Cohort A). The median/average [range] proportion of RA patients meeting all RCT inclusion criteria was 0.6%/2.3% [range: 0.0%-16.2%]. The proportion by criterion was 93.9%/92.4% [59.7%-99.9%] for age, 68.9%/57.1% [9.0%-99.6%] for RA duration, 11.6%/16.0% [4.5%-33.0%] for SJC, 14.6%/17.2% [3.7%-33.9%] for TJC, 27.8%/32.1% [20.1%-49.8%] for CRP, 60.2%/58.7% [43.7%-66.8%] for ESR, 14.8%/40.6% [13.1%-73.9%] for MTX use, 99.5%/99.3% [98.5%-99.8] for prednisolone (PSL) use, and 91.9%/92.0% [85.6%-98.0%] for prior bDMARD use. In Cohort A, the proportion of RA patients meeting the RCT inclusion criteria was low, particularly with respect to SJC, TJC, and MTX use. Among 337 patients who initiated bDMARD therapy at our institute in 2016, a total of 139 biologic-naive patients (IFX, 3; ETN, 33; ADA, 11; GLM, 21; CZP, 17; ABT, 25; TCZ, 28; IFX-BS, 1) were included in the analysis (Cohort B). In Cohort B, the median/average [range] proportion of RA patients meeting all RCT inclusion criteria was 0%/8.2% [0.0%-54.2%]. The proportion by criterion was 100%/99.1% [94.1%-100%] for age, 20.8%/26.5% [0.0%-57.1%] for SJC, 11.8%/17.0% [0.0%-50.0%] for TJC, 33.3%/34.9% [0.0%-66.7%] for CRP, 58.3%/57.3% [0.0%-75.0%] for ESR, 23.5%/35.5% [0.0%-100%] for MTX use, and 100%/100% [100%] for PSL use. As in Cohort A, the proportion of RA patients meeting the inclusion criteria was low in Cohort B, particularly with respect to SJC, TJC, and MTX use. Conclusion: It is important to note that evidence from RCTs of bDMARDs is based on a limited RA population in real-world settings. Disclosure of Interests: Eri Sugano: None declared, Eiichi Tanaka Speakers bureau: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue: None declared, Mai Abe: None declared, Mika Kawano: None declared, Kumiko Saka: None declared, Naohiro Sugitani: None declared, Yoko Shimizu: None declared, Moeko Ochiai: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari: None declared, Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio

Background Evaluation of rheumatoid arthritis (RA) activity is crucial measurement in achieving remission or low disease activity. Visual analogue scale (VAS) by patient’s evaluation has been used for the outcome measure for RA patients because of its feasibility, reliability, sensitivity to change, and it directly reflects the patient’s overall perspective. Patient’s evaluation is a component of multiple composite indices used in assessing RA activity and treatment response. There are two measurements that patient’s evaluation. One is patient’s global assessment of disease activity (PtGA), and the other is patient’s assessment of global health (PtGH)1). PtGA was originally developed as a component of American College of Rheumatology Core Set and used for Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI); while PtGH was originally developed as a component of 28-joint Disease Activity Score (DAS28). PtGA and PtGH have been considered equivalent in a large scale of study2). In daily practice or observation, “patient’s VAS” is usually used without specifying whether it refers to PtGA or PtGH. The factors which influence the change in PtGA or PtGH have not been demonstrated concomitantly in daily practice. Objectives We investigated the difference between PtGA and PtGH, especially each change obtained after intensification of treatment in 12 weeks and identified the factors that influence on each measurement in RA patients. Methods Consecutive patients were enrolled to this retrospective study at our hospital from October 2017 to September 2018. Demographic and clinical data at enrollment as well as treatment regimens were collected by review of medical charts. At first, we examined the baseline data and the changes in 12 weeks of PtGA and PtGH in their relations. The second, we divided those patients into two subsets according to medications intensified by methotrexate (MTX) subset and biological disease-modifying antirheumatic drugs (DMARDs) or janus kinase (JAK) inhibitor (B/J) subset. We compared the difference of the changes in PtGA from the baseline to 12 weeks (ΔPtGA) and those in PtGH (ΔPtGH) between MTX subset and B/J subset. Finally, the logistic regression analysis was performed to identify factors that differently influence for each scale in 12 weeks. Results Consecutive 38 RA patients were enrolled. Women were 76%. The median age [IQR] was 66.5 [55-75] years old. Disease duration was 2.5 [1-15] years. DAS28 was 2.61 [2.02-3.17]. SDAI was 16.8 [11.1-24.6] and CDAI was 15.3 [9.38-23.9]. MTX was initiated or increased in 24 patients (63%). The baseline median dose of MTX was 6 [3.5-8] mg/week. Biologics or JAK inhibitor were initiated in 8 patients (21%); tocilizumab (n=5), golimumab (n=1), abatacept (n=1) and tofacitinib (n=1). Other DMARDs were used in 6 patients (16%). ΔPtGH in 12 weeks was -1.68 (p Conclusion Intensification of treatment significantly improved in both ΔPtGA and ΔPtGH but we need to pay attentions that there were different improving factors between these two patient’s measuremet. References [1] Koevoets R, et al. Simplified versions of the original disease activity score: validation in BeSt trial. Ann Rheum Dis2011; 70: 1471. [2] Khan NA, et al. Patient’s global assessment of disease activity and patient’s assessment of general health for rheumatoid arthritis activity assessment: are they equivalent?Ann Rheum Dis2012; 71: 1942. Disclosure of Interests Naohiro Sugitani: None declared, Yuki Mizutani: None declared, Kentaro Noda: None declared, Yasuo Suzuki: None declared, Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation.

Background Ulcertive colitis (UC) is associated with a variety of extraintestinal manifestations (EIMs) that may have negative effects on performance status and quality of life. EIMs frequently affect musculoskeltal systems (peripheral and axial arthropathies), skin, hepatobiliary tract and eyes1,2. Previous studies showed that peripheral and axial arthropathies were seen 4-23% patients with UC and they tend to have peripheral rather than axial arthropathies3. UC is generally thought to become in remission when patients undergo total colectomy. However, in clinical practice, patients often suffered from arthropathy which is thought as EIMs even after total colectomy. The distribution and risk factors for the occurrence of peripheral and axial arthropathies among UC patients after total colectomy have not been investigated yet. Objectives In this study, we aimed to clarify frequency and distribution of arthropathy and to investigate risk factors for developing arthropathy among UC patients after colectomy. Methods In this retrospective, single center, observational study, we investigated the backgrounds and risk factors for arthropathy using patients underwent total colectomy from January 2007 to February 2016 in Mie University. As backgrounds, age, sex, presence and distribution of arthropathy, other EIMs, and duration after colectomy, clinical activity (mild/moderate/severe), Matts classification (grade 1+2 vs 3+4), presence of massive hemorrhage and toxic megacolon, previous therapies for UC were collected from electronic medical records. Arthropathy was defined as joint pain or swelling without definite cause which was improved by using glucocorticoid. Background factors were described as median (IQR) for continuous variables or as percentage (%) for categorical variables and difference was analyzed by Wilcoxon for continuous variables and by chi-square for categorical variables. Factors with p-value Results We enrolled 219 patients (female; 40.2% and median age at operation; 38.0 [27.0, 53.0] years). Among them, 40 (18.3%) patients had arthropathy, peripheral type in 23 (57.5%), axial type in 3 (7.5%), mixed type in 14 (35.0%). Duration from operation to onset of arthropathy was 0.7 [0.4, 1.2] years. The risk factors for developing arthropathy by univariate analyses were Matts classicification (grade 3+4 vs 1+2) (p Conclusion About one fifth patients with UC who underwent colectomy developed arthropathy presenting predominantly peripheral type. Long follow up period, High disease activity by endoscopic classification, and ileal pouchitis were risk factors of developing arthropathy in UC patients after total colectomy. The frequency and risk factors for developing arthropathy even after colectomy was demonstrated in this study for the first time. References [1] Paraskevi VV, et al. Ann Gastroenterol. 2011; 24: 173-80. [2] Orchard TR, et al. Gut. 1998; 42: 387–91. [3] Das KM, et al. Dig Dis Sci1999;44:1–13. Disclosure of Interests Kentaro Noda: None declared, Yuki Mizutani: None declared, Naohiro Sugitani: None declared, Yasuo Suzuki: None declared, Toshimitsu Araki: None declared, Masato Kusunoki Grant/research support from: Chugai Pharmaceutical Co., Shionogi Pharmaceutical Co., Taiho Pharmaceutical Co., and Mitsubishi Tanabe Pharma Co., Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation.

Background Periodontitis (PD) is considered to be one of the triggers for rheumatoid arthritis (RA) 1. Several reports demonstrated the associations between the disease activity of RA and presence of PD, however, most of them are based on small population, and results are inconsistent 2, 3. Furthermore, impact of PD on physical function and safety is not known. Thus, a study using a large cohort database is warranted to clarify the relationship between patients’ outcomes and PD among patients with RA. Objectives To demonstrate the influence of PD on the outcome of RA, an established cohort IORRA database was used to compare the disease activity, physical function and prevalence of infection between patients with PD and those without. Methods IORRA database is an established cohort database with RA in our institute since 2000. Trough biannual data collection including patient’s questionnaire, physician’s evaluations and laboratory data in more than 5,000 RA patients, a database with a total 91,884 patient-year observation period was established by 2018. In this IORRA database, RA patients who answered to all the questionnaires about PD in October 2016 were extracted. Among those, we defined patients with PD (PD group) as having diagnosis of PD during the last 6 months, and those without PD (non-PD group) as having no present and previous PD. Using the data set from April 2016 to October 2016, we compared Disease Activity Score 28 (DAS28), Japanese Health Assessment Questionnaire (J-HAQ) score, and the prevalence of patients self- reported infections required hospitalizations or hospital visits between the two groups. For background data comparisons, we used chi-squared test for categorical data and Mann-Whitney U-test for continuous data. To investigate associations between PD and remission or PD and infection, we calculated adjusted odds ratio (OR) of PD using a logistic regression model. Results At baseline, patients in the PD group (n=925) were significantly older, had higher DAS28 and J-HAQ than those in the non-PD group (n=2,583). DAS28 and J-HAQ at 6 month in the PD group were significantly higher than those of the non-PD group (DAS28, 2.60 in PD group, 2.42 in non-PD group, p Conclusion RA patients with PD had similar treatment response with those in the non-PD group, however, had higher disease activity, poorer physical function, and higher risk of infections compared to those without. These results may indicate that oral management is important for the better outcomes of patients with RA in the daily practice. References [1] Nat Rev Rheumatol. 2017:606-20 [2] J Clin Rheumatl. 2012:180-4 [3] Med J Islam Repub. Iran. 2017:44 Acknowledgement We thank all patients who participated in the IORRA survey and all of the members of the Institute of Rheumatology, Tokyo Women’s Medical University, for the successful management of the IORRA cohort. Disclosure of Interests Mayuko Hayashi: None declared, Ryoko Sakai Grant/research support from: Tokyo Women’s Medical University (TWMU) has received unrestricted research grants for Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases from Ayumi Pharmaceutical Co. Ltd., Bristol Meyers Squib, Chugai Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., and with which TWMU paid the salary of R.S. RS has received a research grant from Bristol-Meyers Squibb. Eiichi Tanaka Speakers bureau: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Takefumi Furuya Speakers bureau: the Asahi Kasei Pharma Corporation, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and UCB Japan Co. Ltd, Eisuke Inoue: None declared, Mai Abe: None declared, Mika Kawano: None declared, Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, Moeko Ochiai: None declared, Yoko Shimizu: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari: None declared, Atsuo Taniguchi: None declared, masayoshi harigai Grant/research support from: Tokyo Women’s Medical University (TWMU) has received unrestricted research grants for Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases from Ayumi Pharmaceutical Co. Ltd., Bristol Meyers Squib, Chugai Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., and with which TWMU paid the salary of MH. MH has also received research grants from AbbVie Japan GK, Eisai Co. Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio

Background:The risk of some types of malignancy is increased in patients (pts) with rheumatoid arthritis (RA), compared with the general population. We have previously reported the incidence of malignancy in Japanese pts with RA.1-4Objectives:This analysis further evaluated the incidence of malignancy in Japanese pts with RA using recent data from the large prospective observational study, IORRA.Methods:This analysis included all pts with RA aged ≥18 years who were enrolled in IORRA from April 2013 to October 2018, with follow-up through October 2019, and participated in ≥2 surveys. Index was defined as the date of the first entry in the IORRA database, with baseline defined as the 6-month period prior to the index date. Malignancies were identified in pt reports of biannual IORRA surveys and confirmed using medical records. Age- and sex-standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated.Results:In total, 8020 pts were included. At baseline, the majority (85.0%) of pts were female; mean disease duration was 12.8 years, 5.8% and 4.8% of pts had a past history of malignancy or comorbid malignancy at baseline, respectively, and the majority (75.9%) of pts were receiving methotrexate (Table). The SIR (95% CI) was 0.90 (0.80, 1.01). SIRs (95% CI) of site-specific malignancies were: breast cancer, 0.91 (0.69, 1.18); lung cancer, 0.67 (0.44, 0.97); colon cancer, 0.93 (0.62, 1.32); stomach cancer, 0.82 (0.56, 1.14); and lymphoma, 3.74 (2.73, 4.96).Table 1.Patient demographics and baseline disease characteristicsPatients with RA (N=8020)Age (years), mean (SD)59.3 (13.8)Female, n (%)6816 (85.0)Duration of RA (years), mean (SD)12.8 (10.3)Never smoked, n (%)5086 (66.2)DAS28, mean (SD)2.8 (1.1)J-HAQ, mean (SD)0.60 (0.72)Malignancy status, n (%)Past history of malignancy467 (5.8)Comorbid malignancy at baseline386 (4.8)Medication use, n (%)MTX6088 (75.9)Tacrolimus787 (9.8)Corticosteroids2641 (32.9)bDMARD use1508 (18.8)TNFi1163 (14.5)Tocilizumab311 (3.9)Abatacept106 (1.3)JAK inhibitors4 (0.05)bDMARD, biological disease-modifying antirheumatic drug; DAS28, Disease Activity Score in 28 joints; JAK, Janus kinase; J-HAQ, Japanese Health Assessment Questionnaire; MTX, methotrexate; N, the number of patients included in the analysis, the number of patients assessed for each characteristic may be fewer than N; n, the number of patients with each characteristic; SD, standard deviation; TNFi, tumour necrosis factor inhibitorConclusion:Overall risk of malignancy was similar to that in the general Japanese population, although a significantly higher risk of lymphoma was identified.References:[1]Sugimoto et al. Rheumatol Int 2017; 37: 1871-1878.[2]Shimizu et al. Clin Rheumatol 2017; 36: 1237-1245.[3]Askling et al. Ann Rheum Dis 2016; 75: 1789-1796.[4]Yamada et al. Rheumatol Int 2011; 31: 1487-1492.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:masayoshi harigai Speakers bureau: AbbVie Japan, Ayumi, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly Japan, GlaxoSmithKline, Kissei, Pfizer Japan Inc, Takeda, Teijin, Consultant of: AbbVie Japan, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Kissei, Teijin, Grant/research support from: AbbVie Japan, Asahi Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Kissei, Mitsubishi Tanabe, Nippon Kayaku, Sekiui Medical, Shionogi, Taisho, Takeda, Teijin, Naohiro Sugitani: None declared, Ryoko Sakai Speakers bureau: Bristol-Myers Squibb, Eisuke Inoue Speakers bureau: Pfizer Japan Inc, Bristol-Myers Squibb, Michika MOCHIZUKI Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shigeyuki Toyoizumi Employee of: Pfizer R&D Japan, Noritoshi Yoshii Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Eiichi Tanaka Speakers bureau: AbbVie Japan, Asahi Kasei, Astellas, Ayumi, Chugai, Eisai, Eli Lilly Japan, GlaxoSmithKline, Kyowa, Janssen, Mochida, Pfizer Japan Inc, Takeda, Teijin, Hisashi Yamanaka Speakers bureau: Astellas, Bristol-Myers-Squibb, Pfizer Inc, Mitsubishi Tanabe, Teijin, YLBio, Consultant of: Corrona, LLC

Background:The mortality of patients with rheumatoid arthritis (RA) had been reported as being worse than that of the general population [1, 2], but is expected to have improved over time because the progress in treatment of RA during the past twenty years has been actively adopted to RA management [3, 4]. However, the change in the mortality still remains controversial in patients with early RA [5, 6].Objectives:To investigate whether the vital prognosis of patients with early RA has changed in the past twenty years.Methods:The IORRA cohort is a large observational cohort established in 2000 at the Institute of Rheumatology, Tokyo Women’s Medical University. Essentially, all Japanese patients diagnosed with RA at our institute were registered and clinical parameters were assessed biannually. As there is no National Death Registry in Japan, we obtained death report from residual families who responded to our mail query to patients who failed to conduct the subsequent IORRA survey, from physicians of affiliated hospitals and from police in case they found dead patient outside of a hospital. In this study, the patients with early RA (less than 2 years of disease duration) who participated in the survey for the first time from 2001 to 2012 were included and observed for five years from the date of the initial survey. We classified patients into group A (enrolled in 2001-2006) and B (enrolled in 2007-2012). Five-year survival rate and standardized mortality ratio (SMR) were calculated for each group. SMR was calculated using the life tables in Japanese general population reported by the Ministry of Health, Labour and Welfare, Japan. The effects of loss to follow-up cases were evaluated by multiple imputation method as a sensitivity analysis of SMR.Results:A total of 3,217 patients with early RA were analyzed. The number of patients was 1,609 (79.4% female) in the group A and 1,608 (81.8% female) in B. The median age at baseline was 55 in both groups. Among a total of 3,217 patients, 486 (15.1%) patients were lost during 5-year follow-up; 213 (13.2%) in the group A and 273 (17.0%) in B, respectively. During the observational period, deaths were confirmed in 47 cases (2.9%) in the group A and 45 (2.8%) in B. Major causes of death included malignancies (28% in the group A, 38% in B), respiratory involvement (23% in the group A, 40% in B), cerebrovascular disorders (11% in the group A, 2% in B), and cardiovascular disorders (11% in the group A, 0% in B). The five-year survival rate was 88.8% for the group A and 87.8% for B, and the SMR was 0.81 (95%CI: 0.59-1.08) for the group A and 0.78 (0.57-1.04) for B when assuming all the lost to follow-up patients were alive for 5 years. In the sensitivity analysis assuming that the mortality rate of patients who were lost to follow-up was twice as that of the general population, the SMR was 0.90 (0.68-1.19) for the group A and 0.92 (0.68-1.23) for B.Conclusion:The mortality of patients with early RA in the past twenty years has been comparable to that of the Japanese general population. In addition, the SMR and the five-year survival rate did not change overtime.References:[1]Cobb, S., et al. N Engl J Med 1953; 249(14): 553-556.[2]Nakajima, A., et al. Scand J Rheumatol 2010; 39(5): 360-367.[3]Smolen, J. S., et al. Ann Rheum Dis 2014; 73(3): 492-509.[4]Singh, J. A., et al. Arthritis Care Res 2016; 68(1): 1-25.[5]Lacaille, D., et al. Ann Rheum Dis 2017; 76(6): 1057-1063.[6]Humphreys, J. H., et al. Arthritis Care Res 2014; 66(9): 1296-1301.Disclosure of Interests:Naohiro Sugitani: None declared, Eiichi Tanaka Consultant of: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Mai Abe: None declared, Eri Sugano: None declared, Kumiko Saka: None declared, Moeko Ochiai: None declared, Yoko Shimizu: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari Speakers bureau: Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Background:It has been reported that female rheumatoid arthritis (RA) patients have a longer time to pregnancy than healthy women (1), and that high Disease Activity Score with 28 joint count (DAS28) -CRP in preconception increases the frequency of infertility (2). Before the era of biologics, RA treatment tended to be inadequate from pregnancy planning to the end of lactation. And it was not uncommon for female RA patients to be unable to get pregnant or develop physical dysfunction as a result of insufficient control of the disease. There are some reports of disease activity during pregnancy and postpartum in RA patients, and the effects of RA disease activity on pregnancy and childbirth outcomes (3-5), but there are few reports focusing on the physical function during pregnancy planning of RA patients.Objectives:To investigate disease activity and physical function in female patients with RA who planned and didn’t plan pregnancy.Methods:The IORRA cohort is a large, single institute-based, observational cohort of RA patients established at the Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. We identified female RA patients aged 20-49 years who answered ‘pregnant’ or ‘delivered’ in the IORRA survey in 2010-2015 and whose pregnancy and the pregnancy planning time was confirmed in the medical records, and defined them as the pregnancy planning (PP) group. Matched control was extracted at 1:3 ratio from patients without pregnancy plan based on entry time, age, RA disease duration, DAS28-CRP, Japanese version of Health Assessment Questionnaire (J-HAQ) score, and comorbidities. The primary endpoint was J-HAQ at 3years from the baseline, which was defined as the most recent IORRA survey before planning pregnancy. The mixed-effect model for repeated measures was used to analyze group difference.Results:There were 40 patients in the PP group (average 32.2 years, disease duration 5.7 years, DAS28-CRP 1.7, J-HAQ 0.26), and 120 patients in the control group (average 32.4 years, disease duration 5.9 years, DAS28-CRP 1.7, J-HAQ 0.21). The proportion of user and dosage of MTX and glucocorticoid (GC) and bDMARDs user at baseline were comparable between the groups (MTX: PP 87.5% [9.8 mg/week], control 85.0% [8.8 mg/week]; GC: PP 32.5% [3.6 mg/day], control 27.5% [4.4 mg/day]; bDMARDs: PP 40.0%, control 27.5%). DAS28-CRP at year 3 of the PP group elevated and was higher than the control group (PP 2.3, control 1.7, pConclusion:Physical function in pregnancy planning patients with RA did not deteriorate as well as the control patients in clinical settings.References:[1]Arthritis Rheum. 2011;63:1517-1521.[2]Ann Rheum Dis. 2015;10:1836-1841.[3]J Rheumatol. 2015;42:1376-1382.[4]J Rheumatol. 2019;46:245-250.[5]Arthritis Care Res. 2017;69:1297-1303.Disclosure of Interests:Moeko Ochiai: None declared, Eiichi Tanaka Consultant of: ET has received lecture fees or consulting fees from Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Speakers bureau: ET has received lecture fees or consulting fees from Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Mai Abe: None declared, Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, higuchi yoko: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Ikari Katsunori Speakers bureau: KI has received speaker’s fee from Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Background Lung diseases, such as airway disease and interstitial lung disease (ILD), are often complicated in patients with rheumatoid arthritis (RA). The presence of those pre-existing lung diseases is one of the poor prognostic factors and risk factors for infectious pneumonia in patients with RA. There have been several concerned issues regarding pulmonary complications in RA patients with pre-existing lung diseases during treatment with disease-modifying antirheumatic drugs (DMARDs) because of infectious pneumonia or acute exacerbation in ILD, occasionally resulting in fatal outcome. Objectives We identified risk factors for serious pulmonary complications in patients with pre-existing lung disease during treatment with DMARDs in RA. Methods This study enrolled consecutive 487 RA patients at our hospital from 2005 to 2016 retrospectively. 110 of those 487 patients had pre-existing lung disease at the first visit to our hospital. At first, we divided those 110 patients into two subsets, one with development of serious pulmonary complication and the other without that during observational periods. We defined hospitalisation due to lung disease as a serious pulmonary complication regardless of the causes. Demographic and clinical data at enrollment as well as treatment regimens were collected by review of medical charts. We conducted a univariate analysis to compare the differences of clinical characteristics between the subsets. In multivariate analysis, the Cox proportional hazard model was employed to identify factors independently associated with serious pulmonary complication. The explanatory variables were chosen based on candidates (p Results In 110 RA patients with pre-existing lung disease, the median age and disease duration at enrollment was 70 and 3 years, and 71% were female. Rheumatoid factor and anti-cyclic citrullinated protein antibody (anti-CCP) were detected in 97 (88%) and 95 (86%) patients. Methotrexate (MTX), sulfasalazine (SSZ), bDMARDs and corticosteroid were prescribed in 37 (34%), 48 (44%), 42 (38%) and 65 (59%) patients. During the median observation periods of 11 months, 17 (15%) patients had serious pulmonary complications due to pulmonary infection in 11, exacerbation of ILD in 5, and drug-induced pneumonia in 1. The univariate analysis identified candidate variables for serious pulmonary complications as follows: use of MTX and bDMARDs, and no use of SSZ. In multivariate analysis, use of bDMARDs (HR 2.9, 95% CI 0.99–9.0; p=0.05) was identified as the independent risk factor. In 42 patients during treatment with bDMARDs, the univariate analysis identified candidate variables as follows: elder age, male, higher levels of anti-CCP, use of MTX, and no use of SSZ. In multivariate analysis, the higher levels of anti-CCP (HR 1.002, 95% CI 1.0003–1.004; p=0.0007) and no use of SSZ (HR 441.8, 95% CI 1.1–4658460.2; p=0.04) were identified as the independent risk factors. Conclusions Serious pulmonary complications should be more careful for RA patients with pre-existing lung disease during treatment with bDMARDs, particularly those with higher levels of anti-CCP or no use of SSZ. Disclosure of Interest None declared

Background Raised levels of serum rheumatoid factors (RFs) of different immunoglobulin classes had been reported in a high proportion of patients with rheumatoid vasculitis. RF used to be studied and was shown elevated in some forms of vasculitides. Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are often positive for RF. However, the clinical significance of RF has been seldom examined in AAV. Objectives The aim of this study was to investigate association between the presence of RF and clinical features and outcomes in AAV. Methods Eighty-one patients were diagnosed with AAV from 2006 to 2015 in our hospital. Among 81 patients, forty-seven patients (17 males, median age 67 years) who were not complicated with rheumatoid arthritis and in whom RF was measured before the treatment, were studied, retrospectively. Patients were classified using the European Medicines Agency vasculitis classification algorithm. AAV included eosinophilic granulomatosis with polyangitis (n=10), granulomatosis with polyangitis (n=14), microscopic polyangitis (n=16) and unclassifiable vasculitis (UV) (n=7). Patients with UV with MPO-ANCA or PR3-ANCA were included in this study. IgM-RF was measured using a latex agglutination assay. Disease activity was assessed with Birmingham vasculitis activity score (BVAS). IgM-RF, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, IgG, IgM, IgA, MPO-ANCA and PR3-ANCA were obtained from hospital records. Clinical manifestations between RF-positive subset (n=29) and RF-negative subset (n=18) were analyzed using Fisher9s exact and Wilcoxon rank sum tests. Correlation coefficients were established with Spearman9s correlation coefficient. Data were shown as medians (interquartile range). Results BVAS was higher (14 (12–22) vs 12 (6–16), P=0.026) in the RF-positive subset than the RF-negative subset. CRP and ESR were higher (P=0.020 and 0.007, respectively) in the RF-positive patients. IgM-RF titers significantly correlated with BVAS (r=0.50, P=0.0004). In addition, CRP, ESR, IgM and IgG also had a significant correlation with IgM-RF titers. The frequency of initiation of dialysis therapy (14% vs 6%), usage of mechanical ventilation (14% vs 0%) and mortality (10% vs 0%) were higher in the RF-positive subset than in the RF-negative subset although no significant differences were shown. Conclusions In AAV, IgM-RF titers are significantly correlated with disease activity and inflammatory markers. Presence of RF could be a poor prognostic factor in patients with AAV. References Watts R, Lane S, Hanslik T, et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007;66:222–227. Westedt ML, Herbrink P, Molenaar JL, et al., Rheumatoid factors in rheumatoid arthritis and vasculitis. Rheumatol Int 1985;5:209–14. Kronbichler A, Kerschbaum J, Grundlinger G, et al. Evaluation and validation of biomarkers in granulomatosis with polyangiitis and microscopic polyangiitis. Nephrol Dial Transplant 2016;31(6):930–6. Disclosure of Interest None declared