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ObjectivesWe investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants.MethodsSELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA.ResultsS100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers.ConclusionHCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.

Background:Connective tissue disease-associated pulmonary hypertension (CTD-PH) is constructed by a variety of pathologies, including cardiac, pulmonary, and vascular involvement, as well as immune abnormalities. Because of its various constructs, it is difficult for many respiratory physicians, cardiologists, and rheumatologists to determine a treatment strategy for CTD-PH. In addition, CTD-PH has different pathologies from iPAH, and there are cases in which immunosuppressive therapy is effective. These suggests that the two PAHs may have different pathogenesis, including inflammation in the pulmonary artery. However, there are not enough biomarkers to distinguish pathologies. On the other hand, it has been reported that various cytokines such as TIMP-1, Interleukin (IL)-6, IL-17, and IL-21 are involved in the pathogenesis of CTD-PH or vasculitis. (1,2) However, the relationship between these cytokine expression and the pathogenesis or treatment of CTD-PH has not been fully clarified.Objectives:To clarify the relationship between cytokine profile and clinical features, change in cytokines and hemodynamics by treatment, association with the effectiveness of immunosuppressive therapy.Methods:Patients suspected PH was included. At the time of cardiac catheterization(RHC), sera in pulmonary pre and post-capillary were collected and TIMP-1, MCP-1, IL-17 and IL-21, IL-12p70 and IL-6 were analyzed by ELISA(ABCAM UK, Ella simple plex USA). The following clinical data were collected: age, gender, underlying disease, complication of interstitial lung disease, treatment (immunosuppressant and pulmonary vasodilator), hemodynamics. Furthermore, we investigated the relationship between cytokines and clinical data.Results:15 cases of CTD-PH, 13 cases of non-CTD-PH, and 6 cases of non-PH were analyzed. (SSc 12 cases, MCTD 7cases, SLE 2 cases, and others 13 cases) 28 cases were diagnosed with PH by RHC. There was a positive correlation between IL-6 and mean pulmonary arterial pressure in all PH case. In addition, MCP-1, IL-6, and TIMP-1 tend to be high in SSc-PH cases. On the other hand, in Non-SSc-PH, IL-12p70 and IL-17 were high. In cases who pulmonary vascular hemodynamics improved by treatment, IL-17, IL-21, and TIMP-1 decreased.Conclusion:Biomarker profiles in pulmonary capillaries may differ depending on the disease. Furthermore, it suggested that IL-17, IL-21 and TIMP-1 may be biomarkers of therapeutic effect.References:[1]Hashimoto-Kataoka T. et al. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2677-86.[2]Jun Ishizaki et al. Arthritis Res Ther. 2017 Sep 29;19(1):218.Disclosure of Interests:None declared.

Background:It is known that most of ANCA-associated vasculitis (AAV) patients are elderly. A cohort study showed that the mean age of onset was 71.1 years, especially in patients with microscopic polyangiitis (MPA)1). However, the characteristics and prognosis of age-depended AAV patients are still unclear.Objectives:To clarify the differences in age-related characteristics and prognosis between Japanese patients with AAV.Methods:We enrolled 44 patients with AAV who underwent remission induction therapy at our hospital from January 2016 to December 2020. They were divided with under 70 years old group (Results:Mean age were 61.9 ± 9.74 years old in (n=12)≥70 yo (n=32)p valueAge (year)61.9 ± 9.7477.5 ± 4.61< 0.01*Female, n (%)10 (83)28 (87)0.66AAV typeMPA, n (%) / GPA, n (%)6 (50) / 6 (50)26 (81) / 6 (19)0.06Newly diagnosed, n (%)6 (50)27 (84)0.045*ANCA positivity MPO, n (%) / PR3, n (%)11 (92) / 0 (0)30 (94) / 3 (9)1 / 0.55 negative, n (%)1 (8)1 (3)0.48CRP (mg/dl)3.34 ± 4.018.15 ± 6.860.03*eGFR (mL/min)55.8 ± 25.357.7 ± 24.70.93BVAS12.0 ± 8.014.8 ± 6.80.23Remission induction therapyCY, n (%) / RTX, n (%)5 (42) / 7 (58)16 (50) / 16 (50)0.74Maintenance therapy AZA, n (%)7 (58)14 (44)0.50 RTX, n (%)1 (8)6 (19)0.65 others, n (%)2 (17)3 (9)0.60 without IS, n (%)2 (17)9 (28)0.70The p-value was estimated using Fisher’s exact or Wilcoxson rank sum test. yo, years old; AAV, ANCA-associated vasculitis; MPA, microscopic polyangiitis; GPA, granulomatosis with polyangiitis; CY, cyclophosphamide; RTX, rituximab; AZA, azathioprine; IS, immunosuppressants. *pConclusion:There was no difference in remission rate between two groups. Severe infections were observed only in the ≥70 yo group. We suggest that younger AAV patients need attention to relapse after the remission because of lower relapse free survival in References:[1]Sada KE, et al. Arthritis Res Ther 2014; 16: R101.Figure 1.Relapse free survival Relapse free survival was calculated by Kaplan-Meier method and compared by log-rank test. *pDisclosure of Interests:None declared

Background:Recently, there are many reports from Japan about methotrexate associated lymphoproliferative disorder (MTX-LPD). We are investigating the predictive factor of spontaneous regression (SR) in MTX-LPD. On the other hand, FDG-PET/CT is used for diagnosis of LPD including malignant lymphoma. In addition, it was reported that imaging biomarkers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) could predict the prognosis of malignant tumor (1, 2). However, there is no report that these imaging biomarkers could predict the SR of MTX-LPD.Objectives:We investigate the usefulness of FDG-PET/CT for predictive factor of SR in MTX-LPD.Methods:We enrolled 24 RA patients who diagnosed MTX-LPD and performed FDG-PET/CT from 2005 to 2019. We divided these cases into spontaneous regression cases (SR group; 15 cases) and cases that treated with chemotherapy after MTX discontinuation (CTx group; 9 cases), and compared the difference as follow subjects between two groups; clinical data including histopathological findings, SUVmax to evaluate malignant tumor activity by FDG-PET/CT, MTV and TLG which refer to metabolically active volume of the tumor segmented FDG-PET/CT. In addition, we analyzed cut off levels, sensitivity and specificity using statistical software JMP.Results:Diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL) were 5 and 1 cases in SR group, and 1 and 5 cases in CTx group. In addition, MTV and TLG by FDG-PET/CT was significantly lower in SR group, although SUVmax is no difference between two groups (figure 1). Cut off levels of MTV and TLG were 103.12 ml (sensitivity; 88.9%, specificity; 86.7%) and 361.75 ml (sensitivity; 88.9%, specificity; 86.7%), respectively.Conclusion:We suggested that MTV and TLG were useful for predict of SR in MTX-LPD.References:[1]Chen HH, Chiu NT, Su WC. et al. Prognostic value of whole-body total lesion glycolysis at pretreatment FDG PET/CT in non-small cell lung cancer. Radiology. 2012 Aug;264(2):559-66.[2]Chu KP, Murphy JD, La TH. et al. Prognostic value of metabolic tumor volume and velocity in predicting head-and-neck cancer outcomes. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1521-7.Figure 1.Comparison of the level of MTV(a) and TLG (b).Disclosure of Interests:None declared

Background:Apremilast, the small-molecule phosphodiesterase (PDE) -4 inhibitor, was approved for the treatment of recurrent oral ulcers associated with Behcet’s disease (BD) in Japan from September 2019, following the success of the phase 3 RELIEF study (1). However, the efficacy of apremilast on domains other than oral ulcers in BD patients is unclear. On the other hand, it has been reported that apremilast may decrease the production of proinflammatory cytokine and increase the production of anti-inflammatory mediators in psoriasis (PS) and psoriatic arthritis (PsA) (2).Objectives:To evaluate the effects and safty of apremilast on clinical symptoms and the changing of serum cytokine expression.Methods:BD patients who had treated with apremilast for active oral ulcers were included in the study. We investigated the improvement rate of oral and genital ulcers, skin lesions, arthritis. In addition, serum cytokines (IFN-γ, IL-10, IL-8, and TNF-α) before and after apremilast treatment were measured using a multiplex immunoassay (Luminex Assay, R&D Systems).Results:Fourteen patients (3 males and 11 females) were enrolled in this study. The mean age was 46.6 ± 13.0 years and the mean duration of disease was 10.2 ± 8.8 years. All patients had active oral ulcers, five had genital ulcers, six had skin lesions, and four had arthritis. Three months after the treatment with apremilast, oral ulcers improved in 13 patients (92.9%). The improvement rates of genital ulcers, skin lesions and arthritis were 60%, 25% and 25%, respectively. Changes in serum cytokines were different from those previously reported in PS. Adverse events were gastrointestinal symptoms such as nausea and diarrhea in 6 patients and sensorineural deafness in 1 patient. Medication was reduced in 2 patients, and discontinued in 1 patient due to nausea and diarrhea.Conclusion:Apremilast is useful not only for oral ulcers, but also for other lesions in BD patients. The effect of apremilast for other domain such as genital ulcers, skin lesions, arthritis was not comparable to that of active oral ulcers. Additionally, BD may have different cytokine profile from PS and PsA.References:[1]Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of Apremilast for Oral Ulcers in Behcet’s Syndrome. N Engl J Med. 2019;381(20):1918-28[2]Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83(12):1583-1590Disclosure of Interests:None declared

Background:Previous reports showed that connective tissue disease (CTD) have a high risk for adverse pregnancy outcomes (APOs) such as preterm birth, light-for-date, or preeclampsia1). It was revealed that these APOs were associated with high disease activity or treatment agents, particularly in glucocorticoid2). Some patients, who have no or insufficient preconception care and became unplanned pregnant, exacerbate the underlying disease, and lead to disappointing pregnancy outcomes. Therefore, preconception care and planning for pregnancy is very important to control disease activities and manage the appropriate treatment agents, including glucocorticoid, immunosuppressants, biologics, hydroxychloroquine, and anticoagulants3).Objectives:We investigate whether the presence or absence of preconception care before pregnancy affects clinical disease course and pregnancy outcomes.Methods:We examined 200 CTD women who delivered their newborns in our institution from March 2006 to January 2021. We analyzed the association between preconception care and the clinical course of underlying diseases during pregnancy or pregnancy outcomes.Results:Of all 200 cases, 133 (55.9%) cases had preconception care in our institution, while the others had no or insufficient preconception care. We showed the comparison of treatment agents and pregnancy outcomes between the cases with and without preconception care in Table 1. There was no significant difference in the rate of glucocorticoid use and the mean prednisolone dose during pregnancy between these two groups. However, the rate of increased dose of glucocorticoid or pulse therapy was significantly higher in the cases without preconception care. As for pregnancy outcomes, there was no significant difference in the live birth rate. On the other hand, the gestational weeks at delivery were significantly shorter, and the rate of preterm birth was higher in the cases without preconception care. In addition, the rate of the hospitalization of neonatal intensive care unit (NICU) was also significantly higher in the cases without preconception care.Conclusion:We revealed that preconception care before pregnancy reduced the need for intensified treatment such as increasing dose of glucocorticoid or pulse therapy. The rate of preterm birth and NICU hospitalization was also shown to decrease. Therefore, it is important for our rheumatologists to provide an appropriate preconception care for CTD women of childbearing age and to make a plan for pregnancy.References:[1]Tsuda S, Sameshima A, Sekine M, Kawaguchi H, Fujita D, Makino, et al. Mod Rheumatol 2019:24;1-10.[2]Clowse ME, Magder LS, Petri M. J Rheumaotol 2011;38:1012-1016.[3]Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. Arthritis Care Res 2020;72:461-488.Table 1.Comparison of treatment agents and pregnancy outcomes between the cases with and without preconception carePreconception care (+) (n=113)Preconception care (-) (n=89)P valueTreatment agents during pregnancy Glucocorticoid use (n (%))64 (56.6)50 (56.2)1.00 Mean glucocorticoid dose (mg/day)6.3±3.98.4±6.10.09 Dose-up of glucocorticoid (n (%))11 (9.7)26 (29.2) Glucocorticoid pulse therapy (n (%))0 (0)8 (9.0)0.01* Immunosuppressant (n (%))14 (12.5)4 (4.5)0.08 Hydroxychloroquine (n %))7 (6.2)6 (6.7)1.00 Anticoagulant therapy (n (%))21 (18.8)16 (17.8)1.00Pregnancy outcome Spontaneous abortion (n (%))8 (7.1)6 (6.7)1.00 Live birth (n (%))100 (88.5)78 (87.6)1.00 Gestational weeks at delivery (week)38.7±1.437.3±3.50.01* Birth weight of newborn (gram)2888.8±453.72678.4±732.60.25 Adverse pregnancy outcomes (n (%))26 (26.0)28 (35.0)0.20 Preterm birth (n (%))5 (5.0)19 (23.8) Light-for-date (n (%))10 (10.0)9 (11.3)0.81 Hypertensive disorder (n (%))5 (5.0)8 (10.0)0.25 NICU management (n (%))13 (13.0)24 (30.0)Disclosure of Interests:None declared

Background:In systemic lupus erythematosus(SLE), a higher frequency of atherosclerotic lesions is associated with a poor life prognosis (1). Hydroxychloroquine (HCQ) has been reported to improve the prognosis of life and dyslipidemia in SLE (2), and the mechanism has been unclear.Objectives:To determine the effect of HCQ treatment on serum cytokines associated with atherosclerosis in SLE.Methods:SLE patients who received additional HCQ and maintained low disease activity between January 2016 and September 2020 were included in this study. Disease activity was assessed by SLEDAI, CLASI and LLDAS, and serum complement titers, anti-ds-DNA antibodies, serum insulin and serum cytokines (adiponectin, resistin and leptin) were analyzed before and after HCQ treatment.Results:Fifty-four patients (3 males, 51 females, mean age 41.9±12.8 years) were included (Table 1). Thirty-two patients achieved LLDAS at baseline. Serum adiponectin and insulin levels were significantly increased after 3 months of HCQ treatment compared to baseline, and serum resistin levels were significantly lower (Figure 1). Patients with a history of renal disease had greater degree of changes in serum adiponectin and resistin levels. Among SLE patients who did not achieve LLDAS at baseline, those who still did not achieve LLDAS after 3 months had significantly lower serum leptin levels before HCQ treatment than those who achieved it after 3 months.The change of serum resistin levels correlated with those of serum S100A8 levels (r=0.5, p=0.0001).Conclusion:Additional HCQ treatment in SLE patients improves lipid abnormalities. HCQ may improve prognosis by controlling disease activity in SLE and reducing risk factors for atherosclerosis.References:[1]Gregory Katz, et al. Systemic Lupus Erythematosus and Increased Prevalence of Atherosclerotic Cardiovascular Disease in Hospitalized Patients. Mayo Clin Proc. 2019; 94:1436-1443.[2]Laura Durcan, et al. Longitudinal Evaluation of Lipoprotein Parameters in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy. J Rheumatol. 2016; 43: 745–750.Table 1.Characteristics of SLE patients enrolled in this studyCharacteristicsn=54, no.(%)Female, no(%)51(94)Age, years, mean±SD41.9±12.8Disease duration, years, mean±SD15.1±11.1Past involvementRenal involvement23 (43)NPSLE5 (9)ComplicationAPS10 (19)Dyslipidemia2 (4)Diabetes 1 (2)Concomitant immunosuppressive treatmentsPrednisone No.(%)46 (85) Median Dosage, mg/day (range)5.0 (1-10)Disease activitySLENA-SLEDAI score3.9±2.0 Current skin involvement30 (56) anti-dsDNA positive, no(%)21 (39)low complement, no(%)29 (54)Anti-dsDNA positive means anti ds-DNA titer increases over 12 IU/mlLow complement means any of C3, C4 and CH50 decreases to less 68mg/dl, less 12mg/dl, 30U/ml.APS: Anti-phospholipid antibody syndrome, NPSLE: neuropsychiatric SLE,Disclosure of Interests:None declared

Background:Rituximab(RTX) and Cyclophosphamide(CY) has been indicated for ANCA-associated vasculitis(AAV) as remission induction therapy. However, older age and renal disfunction were independent predictor of treatment related adverse effects in remission induction with CY in recent reports1). Japanese AAV patients are characterized by the predominance of elderly, and the study about comparison of efficacy and safety between RTX and CY in elderly Japanese AAV patients are limited.Objectives:To compare the efficacy and safety between RTX versus CY as remission induction therapy in Japanese AAV patients.Methods:We analyzed 40 cases (20 cases received RTX and 20 cases received CY) who received remission induction therapy in our hospital between January 2016 and August 2019. Clinical and laboratory variables at diagnosis, rates of complete remission(CR) at 6 months, defined as Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone 7.5 mg/day, AAV relapse at 12 months, and adverse effects were investigated.Results:Of 40 patients, mean age was 73.5±9.6 years (6 males and 34 females). Diagnosis of MPA and GPA were 30 cases and 10 cases, respectively. 37 cases (93%) were positive for MPO-ANCA. Treatment regimen was determined by attending physician. Baseline characteristic of each group (RTX group and CY group) are shown in Table1. Baseline charactor, disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. At 6 months, there was no difference of remission rate between two groups (RTX: CY = 62%: 44%, p=0.35) (Figure 1). However, mean PSL dosage at 3 months was significantly lower in RTX group (10.0±4.6mg/day) as compared to CY group (15.8±9.5mg/day; p=0.025) (Figure 2). At 12 months, 1 case in CY group and no case in RTX group had relapse. Adverse effects through 12 months are shown in Table 2. 8 infections (30%) in CY group and 7 infections (35%) occurred in RTX group (p=0.64), respectively. 1 case in RTX group had died due to renal failure.Table 1.Comparison of clinical characteristics at baseline between RTX and CY groups.RTX(n=20)CY(n=20)p valueDeath, n (%)1 (5)0 (0)0.50Infections, n (%)7 (35)8 (30)0.46Serious (grade 3), n (%)4 (15)3 (10)0.50Malignancy, n (%)1 (5)0 (0)0.50VTE, n (%)1 (5)0 (0)0.50AMI, n (%)1 (5)0 (0)0.50Leukopenia, n (%)3 (15)3 (10)0.70Necrosis of femoral head, n (%)0 (0)1 (5)0.50Mediastinal emphysema0 (0)1 (5)0.50VTE: venous thrombotic emboli, AMI: acute myocardial infarctionConclusion:We indicated that PSL was tapered more rapidly in RTX group, although there was no difference of remission rate at 6 months and infection at 12 months between RTX and CY therapy. Therefore, remission induction therapy with RTX might be more safety for elderly Japanese AAV patients.References:[1]Little MA, Nightingale P, Verburgh CA, Hauser T, et al. Ann Rheum Dis 2010; 69:1036–1043.Table 2.Adverse effects through 12 months. % = patients with 1 effectsRTX(n=20)CY(n=20)p valueAge, year72.3 ± 11.074.8 ± 8.010.55female, n (%)16 (80)18 (90)0.33AAV type0.14 MPA, n (%)13 (65)17 (85) GPA, n (%)7 (35)3 (15)Newly diagnosis, n (%)7 (35)4 (20)0.24ANCA positivity MPO, n (%)20 (100)17 (85)0.12 PR3, n (%)1 (5)2 (10)0.50 negative, n (%)0 (0)2 (10)0.24 eGFR (mL/min)55.0 ± 29.558.1 ± 21.50.45Organ involvement General, n (%)14 (70)19 (95)0.046* Cutaneous, n (%)1 (5)3 (15)0.30 Eyes, n (%)4 (20)1 (5)0.17 ENT, n (%)5 (25)5 (25)1.00 Pulmonary, n (%)14 (70)15 (75)0.50 Renal, n (%)14 (70)13 (65)0.50 Neurologic, n (%)8 (40)4 (20)0.15BVAS13.8 ± 6.614.1 ± 7.60.73RTX: Rituximab, CY: Cyclophosphamide, ANCA: antineutrophil cytoplasmic autoantibody, AAV: ANCA-associated vasculitis, GPA: granulomatosis with polyangiitis, MPA: microscopic polyangiitis, ENT: Ear, Nose, and Throat, BVAS Birmingham Vasculitis Activity Score, * p Disclosure of Interests:None declared

Background:Lymphoproliferative disorders (LPD) that develop in rheumatoid arthritis (RA) patients treated with MTX (MTX-LPD) is one of the important complications for RA patients. We have previously epidemiologically demonstrated an association between MTX and the development of LPD in RA patients1). MTX-LPD has varied pathologies including various clinical symptom and histological finding. Therefore, we need more information about MTX-LPD. In addition, it is one of the characteristics for MTX-LPD that spontaneous regression (SR) after MTX discontinuation. However, the mechanism of SR is not clarified.Objectives:We collect the information such as clinical symptom and histological finding of MTX-LPD with RA patients, and clarify the clinical features of MTX-LPD. In addition, we investigated the difference between SR cases and cases that treated with chemotherapy after MTX discontinuation (CTx cases).Methods:We enrolled 90 MTX-LPD patients from Kagawa Prefecture, Japan between June 2005 and December 2019. Patients were diagnosed according to American College of Rheumatology (ACR) 1987 classification criteria or ACR/European League Against Rheumatism (EULAR) 2010 classification criteria, and treated with disease modifying antirheumatic drugs (DMARDs) including MTX. We collected as follow information; age, gender, duration of RA, laboratory data (lymphocyte counts and sIL-2R) and treatment of MTX-LPD. In addition, we divided 16 MTX-LPD cases diagnosed histological into two groups (SR:CTx group; n=10:6), and analyzed the histological findings (CD4, CD8, CD163 and CD47) using the staining in immunohistochemistry (IHC) between the two groups. Each positive cell analyzed using virtual viewer soft ImageScope.Results:Characteristics of 90 MTX-LPD patients are as follow; mean age 66.5±11.2 years,63 female, duration of RA 18.5±19.4 years. 65 patients (72.2%) were spontaneously improved by discontinuing MTX. 58 patients (64.4%) were proven MTX-LPD histologically. In these patients, diffuse large B-cell lymphoma (DLBCL) was the most frequent histological type of MTX-LPD (56.9%). Infiltration of CD8 positive lymphocyte in the lesion was significant less in the SR cases than in the CTx cases (Figure 1). However, CD4, CD163 and CD47 positive cells had no significant difference between two groups.Figure 1.CD8 positive lymphocytes in the specimen of lesion using the staining in immunohistochemistry (IHC) between SR and CTxgroup.Conclusion:We revealed clinical features of MTX-LPD with RA patients. In addition, CD8 positive lymphocytes are involved in tumor immunity. In this study, we suggested that the extent of CD8 positive lymphocyte infiltration may predict SR of MTX-LPD. Further study is necessary on revealing the mechanism of SR in MTX-LPD.References:[1]Kameda T. et al. Arthritis Care Res (Hoboken). 2014 Sep;66(9):1302-9.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) have various organ involvements including pulmonary hypertension (PH), digital ulcers (DU), and interstitial lung disease (ILD). On the other hand, Nailfold capillary (NFC) abnormalities (enlarged/giant capillaries, fresh or old hemorrhages, avascular areas, ramified/bushy capillaries) detected by capillaroscopy are included in ACR/EULAR classification criteria for SSc as one of important findings. In addition, many studies have reported the relationship between NFC abnormalities and organ involvements (DU, PH) [1][2]. However, there are a few reports about the relationship between NFC abnormalities and ILD.Objectives:We clarify the association with NFC abnormalities and ILD in SSc patients.Methods:We enrolled SSc patients without PH from January 2016 to December 2019 in our institution. SSc patients were diagnosed according to EULAR classification criteria in 2013. ILD was detected by chest CT scans. We assessed severity of ILD with pulmonary function tests (PFT). Abnormal PFT was defined as vital capacity (%VC) or diffusion capacity (DLCO) < 70%. NFC abnormalities were detected with “OptiPiX capillaroscopy Clinic 1.7.x” and the number of capillaries was measured per 1mm in 2nd to 5th fingers of both hand. We defined enlarged and giant capillaries as >30 µm and >50 µm, respectively.Results:We enrolled 59 SSc patients (54 females, 5 males). Mean age is 65.0 ± 8.0 years. Thirty-one patients (52.5%) were complicated with ILD. Mean capillary counts are 6.6/mm. The number of patients with each NFC abnormalities (enlarged capillaries, giant capillaries, microhemorrhages, ramified, avascular areas) are 42, 32, 48, 38, and 33 cases, respectively. Two cases did not have NFC abnormalities. SSc patients with giant capillaries had fewer ILD complications (p Conclusion:We investigated the relationship between NFC abnormalities and ILD conplications in SSc patients. NFC abnormalities are associated with ILD complicacion and severity of ILD. It was suggested that no giant capillary in SSc patients may predict ILD complication. Moreover, no enlarged capillary may predict the severe ILD.References:[1]Valeria Riccieri et al. Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study. Rheumatology, Volume 52, Issue 8, 1 August 2013, Pages 1525–1528[2]Maurizio Cutolo et al. Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study. Arthritis Rheumatol. 2016 Oct; 68(10): 2527–2539.Disclosure of Interests:None declared

Background:HCQ for SLE in Japan has been administered in many cases after approval. Therefore, the effect of additional administration of HCQ on low disease activity of SLE was considered to be clearer.Objectives:To clarify the effect of HCQ treatment on the control of disease activity in SLE patients.Methods:All SLE patients with low disease activity (LDA) enrolled in this study started additional HCQ treatment from January 2016. All patients with LDA enrolled in this study started HCQ treatment and had been receiving oral HCQ continuously for at least 3 months without using other immunosuppressive treatments or glucocorticoids. Disease activity was evaluated by SLEDAI, CLASI, and LLDAS, and serum complement values, anti-DNA antibodies, and pro-inflammatory cytokines were analyzed as immunological biomarkers before and after HCQ treatment.Results:52 of 100 patients were enrolled in this study (M:F; 4:48, average age; 40.6±13.4). 24 lupus nephritis patients were in sustained remission. 29 patients (56%) achieved LLDAS and 3 patients (6%) achieved clinical remission (CR) before HCQ administration.Of the 20 patients (38%) who did not achieve LLDAS before HCQ administration, the LLDAS achievement rates at 3, 6, and 12 months after additional HCQ were 47%, 59%, and 81% (including 12.5% of CR achievement rates), respectively.Serum levels of MRP8, MRP14, TNF-α, IL-6, VEGF-A, IL-1ra, MIP-1a and IL-2 decreased significantly 3 months after additional HCQ treatment. In addition, serum levels of MRP8, MRP14, TNF-α, IL-6 and IL-2 also decreased significantly 3 months after additional HCQ treatment despite achieving LLDAS or CR. The expressions of IFN-α didn’t decrease significantly in 9 cases that could be detected.The magnitude of the changes in serum MRP8, MRP14, IL-8 and Il-1ra levels in patients with a history of LN was significantly higher than in those without a history of LN. The magnitude of the reduction in serum MCP-1 levels in patients not achieving LLDAS with a history of LN was significantly higher than in those without a history of LN(p=0.046).The change of CLASI activity score was correlated with the change in serum levels of MRP14 and MCP-1 with univariate analysis (MRP14: r=-0.41, p=0.017, MCP-1: r=-0.58, p=0.0006). The change of serum C3 levels had a negative correlation with MCP-1(r=-0.33, p=0.022).The magnitude of the change in serum levels of MRP14, TNF-α, IL-8, MCP-1, MIP-1a and IL-1ra in patients achieving LLDAS were correlated with the change of CLASI activity score with univariate analysis (MRP14: r=-0.49, p=0.041, TNFα: r=0.74, p=0.0038, IL-1ra: r=0.66, p=0.038, MIP-1a: r=0.63, p=0.037, Figure 1). Moreover, the change of serum C3 and C4 levels in them had a negative correlation with the change of serum MCP-1 levels (Figure 2).Figure 1.Correlation between change of CLASI activity scores and serum MCP-1 levels in SLE patients with LLDAS (IL-8: r=0.77,p=,0.0007, MCP-1: r=0.80,p=,0.0001).Figure 2.Correlation between change of serum C3 and C4 levels and serum MCP-1 levels in SLE patients with LLDAS (C3: r=-0.40, p=0.028, C4: r=-0.37, p=0.047).Conclusion:Additional administration of HCQ is useful for cytokine control even in LLDAS-achieved cases, and particularly contributes to the improvement of skin lesion.In addition, regulation of IL-8 and MCP-1 is important for control of renal lesions of SLE, and more control of the activity of SLEThe effect of HCQ on IL-8 and MCP-1 is related to the control of renal lesions in SLE, so that disease activity of more SLE patients might be more controlled disease activity.References:[1]R Wakiya, et al. Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus. Lupus. 2019;28:826-833Disclosure of Interests:None declared

Background:Recently, several type of biologics such as TNF inhibitors, IL-17 inhibitors, IL-12/23 (p40) inhibitors and IL-23 (p19) inhibitors are approved for PsA. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2015 Treatment Recommendation suggests the treat-to-target strategy for PsA1), however, this recommendation does not indicate how to determine which biologics to use. Recent reports revealed that IL-17 inhibitors were as effective as TNF inhibitors2). On the other hand, based on the Tight Control of Psoriatic Arthritis (TICOPA) study, present treatment strategies for PsA aim to reach on minimal disease activity (MDA)3).Objectives:We investigate the effectiveness of IL-17 inhibitors focusing on MDA achievement which were administered for the Psoriatic Arthritis (PsA) patients in our institution.Methods:We examined 46 patients whom were diagnosed and treated in our institution. We analyzed DAS28-CRP as the evaluation of arthritis and Minimal Disease Activity (MDA) achievement as that of overall disease activity.Results:Biologics were administered in 30 cases (65.2%) of all 46 cases. In 30 cases, 19 cases (63.3%) initiated TNF inhibitors (TNFi) and 7 cases (23.3%) were IL-17 inhibitors (naïve group). In 9 cases, TNFi were switched into Il-17 inhibitors (switch group), 7 cases continued TNFi (TNFi group). Patients characteristics in the cases which could collect the data were shown in Table 1. As for arthritis, DAS28-CRP has significantly improved at fourth weeks in naïve and TNFi group. In switch group, DAS28-CRP has not demonstrated significant improvement, however, IL-17 inhibitors were effective for the cases to which they were initiated for arthritis. As for MDA, 71% and 78% have also achieved MDA at twentieth weeks in both naïve and switch groups. In the TNFi group, 67% have not achieved MDA at twentieth weeks because of no improvement of rash (Figure 1). In switch group, all cases to which IL-17 inhibitors were initiated for either arthritis or rash have achieved MDA, however, 40% of cases which were introduced for both arthritis and rash have not achieved MDA.Table 1.Comparison of clinical characteristics at baseline in 3 groups.Il-17 naïve group (n=7)IL-17 switch group (n=9)TNF group (n=7)p valueAge, year60.7 ± 18.953.8 ± 15.450.7 ± 13.6N.SDisease duration, year20.3 ± 25.817.4 ± 9.59.9 ± 12.4N.SMale, n (%)3 (43)6 (67)5 (71)N.SMTX, n (%)2 (29)4 (44)5 (71)N.SCRP(mg/dl)0.41 ± 0.501.87 ± 3.131.07 ± 1.77N.SSwollen joint count6.7 ± 7.33.6 ± 4.26.2 ± 6.9N.STender joint count6.6 ± 7.02.2 ± 2.66.9 ± 9.0N.SPatient pain VAS55.7 ± 22.347.1 ± 34.935.4 ± 13.6N.SBSA (%)12.5± 17.37.7 ± 14.87.4 ± 7.2N.SBiologics, nSecukinumab: 2Ixekizumab: 5secukinumab: 3Ixekizumab: 5Brodalumab: 1Infliximab: 3Adalimumab:3Etanercept:1TNF: Tumor Necrosis Factor, MTX: Methotrexate, VAS: visual analog scale, BSA: body surface area, N.S: not significantConclusion:In our study, IL-17 inhibitors could bring high rate of MDA achievement for both naïve and switch from TNFi. We suggest that TNFi should be switched into IL-17 inhibitors rapidly in the case of ineffective for TNFi.References:[1]Coates LC, Kavanaugh A, Mease PJ, et al. Arthritis Rheumatol. 2016;68:1060-71.[2]Miyagawa I, Nakayamada S, Tanaka Y. Curr Rheumatol Rep. 2019 20;21:21.[3]Coates LC, Moverley AR, McParland L, et al. Lancet. 2015 19;386:2489-98.Disclosure of Interests:None declared

Background:Pulmonary hypertension associated with connective tissue disease (CTD-PH) has complicated pathology including immune abnormalities, cardiac and pulmonary lesions. Therefore, it is difficult for rheumatologist to manage CTD-PH. We hesitate to use immunosuppressants in addition to pulmonary vasodilators to treat CTD-PH. Although there is a report that the cytokine such as Interleukin (IL)-6, IL-17 and IL-21 are involved in the development of PH1), changes in the hemodynamics of theses cytokines with treatment are not clear.Objectives:We investigate serum cytokine profile and clinical appearance in CTD-PH, and clarify the relationship between change in cytokines and hemodynamics before and after treatment.Methods:14 cases of CTD-PH (8 cases in Scleroderma; SSc-PH group, 4 cases in Mixed connective tissue disease; MCTD-PH group, 2 cases in Systemic lupus erythematosus; SLE-PH group), 6 cases in Other-PH group, and 2 cases of SSc without PH as controls were included. The following clinical data were collected: age, gender, underlying disease, complication of interstitial lung disease, treatment (immunosuppressant and pulmonary vasodilator). Serum samples in pre- and post-capillary before and after treatment were collected during cardiac catheterization examination. Serum cytokines (MCP-1, IL-6, IL-17 and IL-21) of these samples were measured by ELISA (ABCAM, UK).Results:Serum MCP-1, IL-6, and IL-21 levels were higher in SSc-PH group than in the other groups. Conversely, serum IL-17 levels tended to be higher in non-SSc group compared to SSc-PH group. Additionally, serum MCP-1 levels in SSc-PH group decreased in post-capillary as compared to pre-capillary. Furthermore, patients with decreased serum IL-17 and IL-21 levels before and after treatment showed improved pulmonary hemodynamics.Conclusion:SSc-PH had a different cytokine profile compared with non-SSc-PH. We suggested that the serum IL-17 and IL-21 levels effect the hemodynamics in CTD-PH.References:[1]Hashimoto-Kataoka T. et al. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2677-86.Disclosure of Interests:None declared