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Belimumab combined with mycophenolate mofetil has been proven to be effective for treating systemic lupus erythematosus (SLE) in several randomized controlled trials. Calcineurin inhibitors are also useful in controlling the activity of SLE. However, the safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. Therefore, the current single-center retrospective study aimed to analyze the safety/efficacy profile of belimumab-tacrolimus (B-T) combination therapy in patients with SLE.Patients with SLE administered tacrolimus and belimumab during treatment were included in the study. Samples were analyzed for the drug retention rate, SLE flare rate, infection incidence rate, and glucocorticoid-sparing effect of the B-T combination therapy.Thirty-three patients with SLE were treated with B-T combination therapy at our institution. Four patients discontinued treatment due to insufficient response or adverse events. The drug retention rate was over 90% at week 52 and approximately 80% at day 1000. Only one patient developed serious infection. The lupus low disease activity state (LLDAS) achievement ratio was 9.1% on the day of initiation and improved to 64.0% at 52 weeks after initiation. SLE flares were observed in three patients (9.1%) in the first 52 weeks after initiation, and in five patients (15.2%) throughout the study period. A glucocorticoid-reducing effect was also observed in patients treated with B-T combination therapy.In most patients with SLE, B-T combination therapy is well tolerated with a good efficacy profile and glucocorticoid-reducing effect. Thus, B-T combination therapy represents a feasible option for patients with refractory lupus. Key Points • The safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. • The drug retention rate of belimumab-tacrolimus combination therapy was over 90% at week 52 and around 80% on day 1000 • Almost none of the patients suffered from severe infection after the initiation of belimumab-tacrolimus combination therapy. • Belimumab-tacrolimus combination therapy is efficacious in suppressing lupus activity and achieving LLDAS.

Alternate-day glucocorticoid (GC) therapy is a treatment option that can reduce GC-associated adverse events. We investigated the safety and efficacy of alternate-day GC therapy in patients with immunoglobulin G4-related disease (IgG4-RD). Medical records of patients with IgG4-RD who were followed for at least one year at St. Luke's International Hospital, Tokyo, Japan, from 2004 to 2020 were reviewed. Patients who fulfilled comprehensive IgG4-RD diagnostic criteria were divided into alternate-day or daily GC treatment groups based on their treatment protocol. The effect of alternate-day GC therapy on glucocorticoid toxicity index (GTI) score was evaluated using multilinear analysis with adjustments for cumulative GC doses until each assessment point and propensity scores (PS) for alternate-day GC therapy. Kaplan-Meier curves and Cox proportional hazard models were used to assess the efficacy of alternate-day GC therapy for disease control. Among the 67 patients with IgG4-RD, patients with alternate-day (n = 13) and daily (n = 31) GC treatments were analyzed after excluding 23 ineligible patients. The median (interquartile range) age was 64 (60-70) years, 29 (65.9%) were male patients, 26 (59.1%) patients had positive biopsy results, and the median follow-up period was 1643 days. Significantly more patients with alternate-day GC treatment used concomitant immunosuppressants (11 [84.6%] vs 11 [35.5%]; P = .007). The alternate-day strategy significantly lowered the GTI score after adjusting for cumulative GC dose until the assessment and PS (adjusted coefficient: -29.5 [-54.3, -4.8], P = .021 at 12 months; -20.0 [-39.8, -0.1], P = .049 at 24 months). Serious infections were numerically less frequent in the alternate-day group (incidence ratio [95% confidence interval [CI]: 0.45 [0.05, 3.63], P = .45). Most patients (92.3%) in the alternate-day GC treatment group and all patients in the daily GC treatment group showed treatment responses in the remission induction therapy. The PS-adjusted hazard ratio of alternate-day GC treatment for disease flares was not significant (1.55 [0.53, 4.51]; P = .43). The alternate-day treatment strategy significantly reduced GC-related adverse events regardless of the cumulative GC dose. Alternate-day GC treatment is a feasible option for patients with IgG4-RD, without a significant increase in disease flares particularly when combined with immunosuppressants.

Since its approval for the management of systemic lupus erythematosus (SLE), belimumab has been widely used. However, its pregnancy safety profile has been underinvestigated. We present the pregnancy outcomes of two cases of early placental exposure to belimumab and summarise the pregnancy outcomes in previous reports regarding placental exposure to belimumab. Case 1 describes a 27-year-old woman with an 18-year history of SLE and lupus nephritis class III. We introduced belimumab 19 months prior to conception to control her proteinuria and discontinued its use at 5 weeks and 5 days of gestation. Her lupus activity was stable throughout pregnancy, and at 37 weeks and 1 day of gestation, she delivered a healthy girl with no anomaly. At delivery, the girl was small for gestational age, but at the 1-year follow-up, there was no delay in her growth or any serious infection. Case 2 describes a 32-year-old woman with a 15-year history of SLE. We introduced belimumab 9 months prior to conception and discontinued its use at 7 weeks and 1 day of gestation. Although her lupus was well controlled without belimumab, a missed abortion occurred, which was possibly due to foetal factors. Although there is accumulating data on the safety of belimumab use during pregnancy, it seems necessary to cautiously use this medication in pregnant women, until further analyses are conducted.

Background:Long-term glucocorticoid use in systemic lupus erythematosus (SLE) may have significant side effects; however, glucocorticoid discontinuation is occasionally associated with disease flare-ups. Therefore, we evaluated the risk factors for disease flares and the flare rate upon glucocorticoid tapering in patients with prior severe organ involvement.Methods:Patients with SLE with glucocorticoid tapering at our institution were retrospectively analyzed. We divided the patients according to the presence of prior severe organ involvement and compared flare rates and time to first flare after glucocorticoid discontinuation. Furthermore, we determined risk and protective factors for flares after glucocorticoid discontinuation.Results:A total of 309 patients with SLE were screened; 298 had prednisolone tapered to less than 7.5 mg/day and 75 had glucocorticoid discontinuation. Overall, 73 patients met the inclusion criteria; 49 were classified as SLE with prior severe organ involvement. No statistical differences were noted in the 52-week flare rate and time to first flare after glucocorticoid discontinuation between patients with and without prior severe organ involvement (52-week flare rate: 16.7% vs. 18.2%, p = 1.0; time to first flare: 322 [280, 1169] vs. 385 [304, 2345] days, p = 0.33). Hypocomplementemia, elevated anti-dsDNA antibody titers of more than twice the upper limit of the laboratory reference range, and positive anti-Smith/anti-ribonucleoprotein antibody were negatively associated with flare-free remission.Conclusion:Glucocorticoid discontinuation can often be achieved in patients with SLE without increasing flare risk in most patients with prior severe organ involvement, especially when the disease is clinically and serologically stable.

We evaluated whether thyroid function test (TFT) screening is warranted for patients with autoimmune rheumatic diseases (ARD) by comparing the incidence of hypothyroidism requiring treatment (HRT) in ARD patients and healthy controls (HCs). Medical records of 2307 ARD patients and 78,251 HCs for whom thyroid-stimulating hormone (TSH) levels were measured between 2004 and 2018 were retrospectively reviewed. Cumulative incidence of HRT in ARD patients and HCs was compared. HRT development was evaluated with age- and sex-adjusted Kaplan–Meier curve. Risk factors were identified with Cox proportional hazard models. HRT was significantly more common in ARD patients than in HCs (6.3% vs. 1.9%, P P

Aim Pre-administration screening of active infections is imperative for the safe use of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). However, a standardized screening method is lacking. We therefore implemented a novel systematic screening method with a simple predetermined questionnaire on infections and assessed its effectiveness. Methods We retrospectively reviewed medical records of individuals for whom intravenous bDMARDs were administered for RA from January 2016 to April 2019. We evaluated the performance of the new screening method based on physicians' assessments. In addition, a survey was administered to nurses, regarding their assessment of the usefulness of this new screening. The incidence of infections was also assessed. Results A total of 1636 cases underwent this new screening. The new screening method showed high sensitivity (0.97) and specificity (0.89) with a negative predictive value of 99.9%, as determined based on the physician's decision. Administration of bDMARDs was postponed in 37 (2.5%) patients, and there was only one case in which the screening failed to note an active infection. The nurses' survey demonstrated high agreement (87.5%) about the usefulness of this screening on the grounds of clarity, simplicity, ease, and time-saving effects. There was no significant increase in infections after implementation of this method. Conclusions Systematic screening with a predetermined simple questionnaire is effective as an infection screening method, with a high negative predictive value. This approach contributes to high satisfaction of nurses and a time-efficient practice by focusing on screen-positive cases without increasing infections.

ObjectiveLong-term glucocorticoid use in SLE may have significant side effects; however, glucocorticoid discontinuation is occasionally associated with disease flare-ups. Therefore, we evaluated the risk factors for disease flares and the flare rate on glucocorticoid tapering in patients with prior severe organ involvement.MethodsData of patients with SLE with glucocorticoid tapering at our institution were retrospectively analysed. We divided the patients by the presence of prior severe organ involvement and compared flare rates after glucocorticoid discontinuation. Furthermore, we determined risk factors for flares after glucocorticoid discontinuation.ResultsIn total, 309 patients with SLE were screened, 73 of whom met the inclusion criteria; 49 were classified as SLE with prior severe organ involvement. No significant differences were noted in the 52-week flare rate after glucocorticoid discontinuation between patients with and without prior severe organ involvement (16.7% vs 18.2%, p=1.0). Hypocomplementaemia, elevated anti-dsDNA antibody titres more than twice the upper limit of the laboratory reference range, positive anti-Smith/anti-ribonucleoprotein antibody, and use of any immunosuppressant on the day of glucocorticoid discontinuation were negatively associated with flare-free remission.ConclusionsGlucocorticoid discontinuation after gradual tapering can often be achieved in patients with SLE, even with prior severe organ involvement, especially when the disease is clinically and serologically stable.

Objective Patients with IgG4-related disease (IgG4RD) usually require steroid-sparing agents due to relapse with tapering glucocorticoids (GC). We aimed to determine the efficacy and safety of mizoribine (MZR) among IgG4RD patients. Methods We retrospectively reviewed records of IgG4RD patients at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. Patients treated with MZR were classified into the MZR group, and those treated with GC alone or with other immunosuppressants were included in the control group. Disease exacerbation, GC dose, IgG-IgG4 titre and adverse events were evaluated using univariate analyses, including the Kaplan–Meier method. The Cox proportional hazard model was used to evaluate risk factors for disease exacerbation. Results A total of 14 and 29 cases were included in the MZR and control group. Multiple organ involvement (three or more organs) was significantly more frequent in the MZR group [10 (71.4%) vs 9 (31.0%), P= 0.021]. Kaplan–Meier analysis revealed a significant reduction inexacerbation in patients with multiple organ involvement (P< 0.001) but not in total (P= 0.42). The adjusted hazard ratios of MZR use and multiple organ involvement for exacerbation were 0.34 (95%CI 0.12–1.01; P = 0.052) and 3.51 (95%CI 1.29–9.51; P= 0.014). The cumulative GC dose (mg per year, interquartile range) tended to be lower in the MZR group [1448 (1003–1642) vs 2179 (1264–3425); P= 0.09]. Conclusion MZR decreased disease exacerbation among IgG4RD patients with multi-organ involvement and showed a steroid-sparing effect. MZR could be a treatment option for IgG4RD.

Background B cells are critically involved in the pathogenesis of systemic lupus erythematosus (SLE), and their increased activity is driven in part by increased levels of growth factors, including B-lymphocyte stimulator (BLyS). Belimumab inhibits activity of BLyS, effectively and safely treats SLE, but data on treatment cessation are lacking. Therefore, we investigated belimumab-free remission in SLE patients. Methods SLE patients receiving belimumab in our institute (1/1/2013–5/31/2019) were retrospectively identified using electronic health records. Eligibility criteria were receiving belimumab for >180 days and discontinuation for any reason. BILAG category A or B in at least one organ system defined disease flares. Follow-up monitoring after 52 weeks post-treatment identified relapse-free and relapse patients. Results 31 patients received belimumab. While 14 patients discontinued, eight were included. Four patients relapsed within 52 weeks. Relapse-free patients received significantly less steroid at discontinuation (prednisolone equivalent, median 3.0 mg/day [IQR 2.75–3.19] vs. 9.5 mg/day [IQR 7.25–13.25], p=0.02), and significantly more of them achieved PSL dosage of Conclusion Belimumab discontinuation after >180 days is recommended for 50% of SLE patients. Steroid dosage (prednisolone equivalent Funding The authors received no financial support for the research, authorship, and/or publication of this article.

Belimumab is an effective and safe treatment option for systemic lupus erythematosus (SLE). However, data on treatment cessation are lacking. Thus, we investigated belimumab-free remission in SLE patients. SLE patients receiving belimumab in our institute (May 1, 2013–May 31, 2019) were retrospectively identified using electronic health records. Eligibility criteria included receiving belimumab for > 180 days and discontinuation for any reason. BILAG category A or B in at least one organ system indicated a disease flare. Follow-up monitoring during post-treatment at week 52 identified relapse-free and relapse patients. Thirty-one patients received belimumab, and 8 patients were included. Of the 8 patients, 4 relapsed within 52 weeks. At belimumab discontinuation, relapse-free patients achieved lower SELENA-SLEDAI (1 [IQR, 0–2] vs. 7 [IQR, 5.5–8] (p = 0.03)), received significantly less steroid (prednisolone equivalent, 3.0 mg/day [IQR, 2.8–3.2] vs. 9.5 mg/day [IQR, 7.3–13.3], p = 0.02) than relapse patients, and significantly more relapse-free patients achieved SELENA-SLEDAI less than 4 and received prednisolone less than 5 mg/day than relapse patients. Furthermore, on discontinuation day, relapse-free patients tended to have higher C3 (91.0 mg/dL [IQR, 78.8–102.3] vs. 56.0 mg/dL [IQR, 39.8–73.0], p = 0.15) and C4 levels (22.0 mg/dL [IQR, 19.00–26.00] vs. 11.0 mg/dL [IQR, 6.00–16.00], p = 0.08) and less anti-dsDNA antibody (5.2 IU/mL [IQR, 3.8–7.8] vs. 48.0 IU/mL [IQR, 11.5–137.3], p = 0.08) than relapse patients. Belimumab discontinuation can be considered for patients who achieved good responses. Normalization of complement, anti-dsDNA antibody, SELENA-SLEDAI less than 4, and steroid dosage less than 5 mg/day might be prognostic markers for belimumab-free remission.

Background:IgG4-Related Disease (IgG4RD) is known to cause multiple organ lesions with infiltration of IgG4-positive plasma cells, and patients often have relapses with tapering treatments despite an initial good response to glucocorticoids therapy. Mizoribine (MZR) is an immunosuppressant working as an inhibitor of purine synthesis, which mechanism of action is similar to mycophenolate mofetil. Data regarding the efficacy and safety of MZR on IgG4RD is limited although some previous case reports1showed effectiveness for IgG4RD.Objectives:This study aims to assess the efficacy and safety of MZR in patients with IgG4RD.Methods:We retrospectively reviewed charts of IgG4RD patients who used MZR between January 2004 and December 2019 at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. We investigated basic demographics, involved organs, results of blood tests including IgG and IgG4 titer, and medications used including glucocorticoid and other immunosuppressants (IS). We followed IgG4 titer, dose of glucocorticoid, flare of disease and retention of MZR at the beginning, 6 and 12months after starting MZR. We compared changes in PSL (prednisolone) doses and IgG4 titers over time using Friedman test with Bonferroni correction. We also checked adverse events during follow up.Results:Twenty-two patients with IgG4RD who used MZR were included. Median age was 62 years old, and 15 (68.2%) patients are male. Lacrimal and salivary glands, pancreatitis and retroperitoneal fibrosis were common lesions. All patients were initially treated with glucocorticoids. Flare was observed in 5 (22.7 %) patients before initiation of MZR. The number of patients who continued MZR without flare are 19 (86.4 %) at 6 months, and 14 (73.7 %) at 12 months. IgG4 titer significantly declined at 6 and 12 months from baseline although significant consecutive decrease in PSL dose (Figure 1, 2). Liver dysfunctions are commonest adverse events (n=16, 72.7%) but mild (grade1; n=15, 68.2%) and most cases are apparently due to other reasons. Serious infection (SI) occurred in 3 (13.6%) patients in total follow up, however no SI were observed during 1 year after MZR treatment.Conclusion:MZR can be safely used in patients of IgG4RD with high retention rate, and seemed to have steroid-sparing effect. Prospective comparative studies are needed.References:[1]Nanke Y, Kobashigawa T, Yago T, Kamatani N, Kotake S. A case of Mikulicz’s disease, IgG4-related plasmacytic syndrome, successfully treated by corticosteroid and mizoribine, and then by mizoribine alone. Intern Med 49: 1449-1453, 2010.Table 1.Patient characteristics Table 2.Disease and treatment status before and after initiation of MZR Figure 1.Serum IgG4 level changesFigure 2.Changes in the PSL dose over timeDisclosure of Interests:None declared

Background:Thyroid disorders are known as common comorbidities of rheumatic diseases(RD) [1]. However, data regarding prevalence of hyperthyroidism with treatment indication in RD patients are limited.Objectives:This study aims to reveal and compare the frequency of newly developed hyperthyroidism with treatment indication between RD patients and healthy controls (HC), and identify risk factors to identify patients whose thyroid function should be followed up carefully.Methods:We retrospectively reviewed charts of RD patients and HC who had thyroid stimulating hormone (TSH) measured at least once between 2004 and 2018 from immuno-rheumatology center and preventive medicine center in St. Luke’s International Hospital, Japan. We compared frequency of hyperthyroidism requiring treatment (TSH ≦ 0.1μU/mL or for which physicians started treatment) with Kaplan-Meier curve and log rank test. Cox regression multivariate analysis was performed to reveal risk factors for the new onset of hyperthyroidism with treatment indication in participants without treatment-indicated hyperthyroidism at initial assessments.Results:Overall, 2307 RD patients and 78251 HC were included. Newly detected hyperthyroidism with treatment indication were significantly more frequent in RD patients at initial assessment (1.3% vs 0.5 %, p < 0.001) and in total (2.9% vs 1.7%, pTable 1.Patients characteristics and results of hyperthyroidismRheumatic Disease (n = 2307)Control (n = 78251)p.valueAge(yr)53.7 (16.2)46.1 (11.9)Female (%)1826 (79.2)38632 (49.4) Rheumatoid arthritis (%)1091 (47.3)-NA Spondyloarthritis161 (7.0)-NA ANA associated disease (%)944 (40.9)-NA SLE(%)363 (15.7)-NA SS (%)396 (17.2)-NA PMDM(%)104 (4.5)-NA SSc (%)222 (9.6)-NA MCTD (%)43 (1.9)-NA Vasculitis (%)202 (8.8)-NA Others (%)244 (10.6)-NATimes of TSH measurement2.0 [1.0, 5.0]5.0 [3.0, 9.0]Follow up of TSH (days)258.00 [0, 1315]1992 [958, 3632]Baseline TSH (μU/mL)2.28 (3.21)2.15 (4.07)0.137 ≦0.45 μU/mL (%)86 (3.7)1371 (1.8) ≦0.1 μU/mL (%)29 (1.3)389 (0.5)Baseline FreeT4 (μU/mL)1.16 (0.24)1.30 (0.20)≧1.65 μU/mL (%)17 (0.8)2355 (3.0)TSH level in follow up ≦0.45 μU/mL (%)231 (0.0)3926 (5.0) ≦0.1 μU/mL (%)84 (3.6)1388 (1.8)Newly detected hyperthyroidism with treatment indication (%)68 (2.9)1350 (1.7) At initial assessment (%)29 (1.3)389 (0.5) In follow up (%)39 (1.6)961 (1.2)Treatment for hyperthyroidism (%)21 (0.9)325 (0.4)0.002Figure 1.Hyperthyroidism with treatment indication in rheumatic patients and controlTable 2.Risk factors for newly detected hyperthyroidism with treatment indicationAdjusted HRp valueAge0.99 (0.98-0.99)< 0.001Female2.68 (2.31-3.12)< 0.001BMI1.04 (1.02-1.06)< 0.001Baseline TSH ≦ 0.455.71 (4.47-7.30)< 0.001Baseline Free T4 ≧ 1.651.16 (0.79-1.69)0.45Rheumatoid arthritis1.05 (0.50-2.21)0.90ANA associated diseases-- SLE2.29 (1.11-4.71)0.025 SS1.91 (0.91-4.01)0.089 PMDM12.90 (5.50-30.22)< 0.001 SSc0.67 (0.18-2.43)0.541 MCTD8.02 (2.62-24.51)< 0.001Vasculitis1.44 (0.35-5.92)0.610Spondyloarthritis3.04 (0.74-12.52)0.120Others1.98 (0.67-5.81)0.214Conclusion:Hyperthyroidism with therapeutic indications are considerably more frequent in RD patients (particularly with SLE, PMDM and MCTD) both at initial assessment and during follow up. We recommend routine screening at initial assessment and careful follow up of thyroid function test in those patients.References:[1] Rev Bras Rheumatol 2012;52(3):417-430Disclosure of Interests:None declared

Background It is known that ultrasound detects synovitis with higher sensitivity than physical examination in rheumatoid arthritis (RA), and the residual inflammation detected by ultrasound even in the patient achieving clinically remission well correlates with progression of erosion.1 However, It is impossible to perform ultrasound evaluation on all the joints in all the patients in terms of time and human resource. Therefore, ultrasound use in RA should be more focused on situations when the physical findings and ultrasound findings likely to dissociate. Hirata et al showed the concordance between swelling or tenderness joint and ultrasound-detected synovitis are low in the PIP, MCP, and wrist joint.2 Objectives To investigate the factors that can predict dissociation between clinical and ultrasound-detected synovitis in the patient with rheumatoid arthritis. Methods Patients aged 18 years or older who satisfied ACR/EULAR 2010 criteria who visited St. Luke’s International Hospital from June 1, 2018 to November 9, 2018 and were performed ultrasound on PIP, MCP, and wrist joints were eligible for this study. We retrospectively reviewed the electronic medical chart and ultrasound data, and analyzed the dissociation of clinical synovitis defined as existence of swelling or tenderness and ultrasound-detected synovitis defined as both of power doppler grade and gray scale grade ≧1 or gray scale grade ≧2. Clinical evaluation was done by the attending physician who ordered the ultrasound evaluation. Ultrasound evaluation was done using standard scan technic3 by the sonographers who are blinded to the clinical evaluation. The correlation between patient’s characteristics and dissociation was analyzed using χ2 test, Mann-Whitney U test and logistic regression analysis. Results 51 joints in 32 patients (4 males, 28 females) were included in the study. Among the 32 patients, 18 was classified in the dissociation group (DG) and 14 in the non-dissociated group (NDG). No significant difference was observed in the patient’s characteristics of DG and NDG. In the univariate analysis, the absence of swelling in the target joint had tendency to be the risk of dissociation. The same tendency was preserved in the multivariate analysis with the presence of tenderness in the target joint assigned as a covariate (OR 3.68, 95% CI = 0.85 - 15.90, p = .08). Conclusion There was a numerical tendency that no swelling on the joint is a risk factor for the dissociation between clinical synovitis and ultrasound-detected synovitis. Future study with increased number of participants may identify more sensitive risk factors for dissociation, and enable to make an effective indication of ultrasound evaluation in the care of RA. References [1] Kawashiri S, et al. Rheumatology 53.3, 2013: 562-569. [2] Hirata A, et al. Arthritis Care & Research Vol. 69, No. 6, June 2017: 801–806 [3] Naredo E, et al. Annals of the rheumatic diseases 64.3, 2005: 375-381. Disclosure of Interests Takahiro Asano: None declared, Masei Suda: None declared, Ryo Rokutanda: None declared, Haruyuki Yanaoka: None declared, Sho Fukui: None declared, Haruki Sawada: None declared, Yukihiko Ikeda: None declared, Ayako Koido: None declared, Rui Imai: None declared, Hisanori Shimizu: None declared, Hiromichi Tamaki: None declared, Tokutarou Tsuda: None declared, Mitsumasa Kishimoto Consultant for: Kyowa Hakko Kirin Co., Ltd., Kenichi Yamaguchi: None declared, Masato Okada: None declared

Background Hypothyroidism is known as a common complication of rheumatological diseases(RD). Thyroid hormone supplementation is important not only in clinical hypothyroidism but subclinical one for cardiovascular events in the future1. But the data about prevalence of hypothyroidism requiring treatment and it’s changes with follow up in patients with RD is limited. Objectives To reveal the prevalence and risk factors of hypothyroidism, especially which requires thyroid hormone supplementation, in patients with RD and compare it with that of general population. Methods We retrospectively reviewed charts of RD patients and healthy controls in preventive medicine center, at St. Luke’s International Hospital from January 2004 to July 2018. We investigated basic demographics, underlying diseases, blood tests including thyroid functions and treatment with thyroid hormones. We compared the number of hypothyroidism requiring treatment (Thyroid stimulating hormone: TSH 10 μU/mL or physician started treatment) and it’s changes in follow up using univariate analysis and Kaplan–Meier method with log rank test. Cox proportional hazard model was performed for evaluating the risk of hypothyroidism which needs treatments in all patient and only RD patients. Results 2307 RD patients and 78251 controls without past medical history of hypotyroidism with therapeutic indications are included. Newly-detected hypothyroidisms requiring treatments are significantly frequent in RD patients (6.9%vs2.0%, P When focus on RD patients, patients with older age, ANA (Anti-nuclear antibody)80, higher Cre and TSH, and baseline positive anti-thyroid peloxydase(TPO-Ab) or anti-thyrogloburin antibodies(Tg-Ab) have higher risk of hypothyroidism requiring treatment after adjusting confounders in Cox’s proportional hazards model (Table.2). Conclusion Hypothyroidism with therapeutic indication is more frequent in RD patients, even if screening TSH is within normal range. We encourage active routine measurement of thyroid function tests in patients with RD, especially with above risk factors. References [1] Nicolas Rodondi, et al. Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality: JAMA. 2010;304(12):1365-1374. Disclosure of Interests Sho Fukui: None declared, Yukihiko Ikeda: None declared, Haruki Sawada: None declared, Mitsuru Watanabe: None declared, Ayako Koido: None declared, Rui Imai: None declared, Masei Suda: None declared, Haruyuki Yanaoka: None declared, Hisanori Shimizu: None declared, Ryo Rokutanda: None declared, Hiromichi Tamaki: None declared, Tokutarou Tsuda: None declared, Kenichi Yamaguchi: None declared, Mitsumasa Kishimoto Consultant for: Kyowa Hakko Kirin Co., Ltd., Masato Okada: None declared

Background Complement is a biomarker known to be correlate with disease activity of systemic lupus erythematosus (SLE). However, it is not well-known how complement level changes after starting hydroxychloroquine(HCQ), one of the key drugs for the treatment of SLE, in patients with SLE. The aim of this study is to investigate the effect of HCQ on complement levels over a 12 month period in a large single center cohort of SLE in Japan. Methods We retrospectively collected the data of all the 244 lupus patients treated with HCQ from the electrical medical recordat St Lukes International Hospital, Tokyo, Japan. We extracted the following parameters during the period between April 2008 and March 2018; baseline characteristics, complements levels (C3 and C4) at baseline1 month, 3 months, 6 months, 9 months, and 12 months after starting HCQ. Statistical analysis was performed using SPSS Statistics Version 21 (IBM Corp., Armonk, NY, USA). Mauchly’s sphericity test and analysis of variance with Greenhouse-Geisser correction was used. Results Total 244 patients on HCQ were included but 130 patients were excluded due to lack of sufficient data. The mean age of these 114 patients was 40.2 years and 108 patients (94.7%) were female. The level of C4(mg/dL) increased significantly (p Conclusions The level of complements increases after initiating HCQ therapy in real-world patients with SLE in Japan. The effect tends to emerge 3 months after starting HCQ. We will show the data between disease activity and the elevation of complements. Funding Source(s): None

Background:Coronary periarteritis is one of the clinical manifestations of IgG4-related disease. It can cause serious conditions such as angina and ruptured aneurysms. Therefore, it is important to recognize the clinical and radiological characteristics, which was little known.Objectives:We report four patients with IgG4-related coronary periarteritis with a systematic literature review.Methods:We identified four patients with IgG4-related coronary periarteritis at the St. Luke’s International Hospital in Tokyo, Japan from 2014 to 2020. A systematic literature review was conducted for English articles on IgG4-related coronary periarteritis cases with a full text or abstract available. We summarized patient demographics, IgG and IgG4 titers, the site and morphological type of coronary lesion, and other organ involvements.Results:Our 4 cases and 38 cases identified by the literature review were assessed. Coronary artery lesions were detected by a coronary CT in all but two cases. Wall thickening was the most common type of the lesion. Moreover, there were 32 (76.1%) patients with other organ involvements. The commonest other lesion was peri-aortitis in 21 (50.0%) patients. In cases with peri-aortitis, IgG and IgG4 titers were significantly higher than those without peri-aortitis (IgG4; 1540 [705.0, 2570.0] vs 246.0 [160.0, 536.3]; p = 0.001, IgG; 3596.5 [2838.3, 4260.0] vs 1779.0 [1288.3, 1992.8]; p =0.040). In addition, 15 (71.4%) patients of them had three or more IgG4 related organ involvements.Conclusion:Coronary CT was a useful imaging modality for the diagnosis of IgG4-related coronary periarteritis, and wall thickening was the most common lesion. Moreover, about half cases coexisted with peri-aortitis. Peri-aortitis and other organ involvements should be screened in those with higher IgG and IgG4.Table 1.Characteristics of our cases and the literature review cases.RCA: right coronary artery, LAD: left anterior descending artery, LCx: left circumflex arteryDisclosure of Interests:None declared

Background:Currently it is hypothesized that many systemic autoimmune diseases occur due to environmental risk factors in addition to genetic risk factors. Anti-Neutrophil Cytoplasmic Antibody (ANCA) is mainly associated with three systemic autoimmune disease including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA). It is known that ANCA can be positive before clinical symptoms in patients with known diagnosis of GPA and ANCA titers rise before clinical manifestations appear. However, prevalence of ANCA among general population is not well known. It has not been described as well how many of people with positive ANCA eventually develop clinical manifestations of ANCA associated Vasculitis.Objectives:This study aims to estimate prevalence of ANCA in general population without ANCA associated Vasculitis. It also describes natural disease course of people with positive ANCA without ANCA associated Vasculitis. Risk factors for positive ANCA are also analyzed.Methods:This is a single center retrospective study at Center for Preventive Medicine of St. Luke’s International Hospital in Tokyo. ANCA was checked among the patients who wished to between 2018 and 2019. St. Luke’s Health Check-up Database (SLHCD) was utilized to collect the data. The patients whose serum was measured for ANCA were identified. The data for basic demographics, social habits, dietary habits and laboratory data were extracted. The charts of the patients with positive ANCA were reviewed.Results:Sera of total 1204 people were checked for ANCA. Of these 1204 people, 587 (48.8%) are male and the mean age was 55.8 years (32.6 to 79). There were total 11 patients with positive ANCA. Myeloperoxidase ANCA (MPO-ANCA) was positive for 3 patients and proteinase 3 ANCA (PR3-ANCA) was positive for 8 patients. Of these 11 patients, 5 were male (45.5%) and the mean age was 54.6 years. Two patients had history of autoimmune disease (primary biliary cirrhosis and ulcerative colitis). Five patients were evaluated by rheumatologists with the median follow-up period of 274 days. None of them developed clinical signs and symptoms of ANCA associated Vasculitis. Four out of five patients had ANCA checked later, two of which turned negative. The prevalence of ANCA in this cohort was 0.9% (95% confidence interval [95% CI]: 0.5% to 1.6%). Univariate analysis was performed to identify risk factors of positive ANCA. The variables analyzed include age, gender, body mass index (BMI), smoking habits, alcohol intake, dietary habits (fruits, fish, red meat), hypertension, dyslipidemia, and laboratory data. None of these variables demonstrated statistically significant differences except for positive rheumatoid factor (ANCA positive group: 33 % vs ANCA negative group: 9.1%, p value = 0.044).Conclusion:The prevalence of ANCA in this cohort was 0.9% (95% CI: 0.5% to 1.6%). None of them who had a follow-up developed ANCA associated Vasculitis during the follow-up period. Longer follow-up and more patients are necessary to determine natural course of people with positive ANCA.Disclosure of Interests:None declared