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BackgroundAlthough proliferative (class III or IV) lupus nephritis (LN) is the most common finding in the classification of LN, pure membranous (class V) or mesangial (class I or II) LN can occur as a form of LN. Even though non-proliferative LN (class I, II, or V) is a less severe form with good outcomes, data on long-term renal prognosis are limited.ObjectivesThis study investigated the long-term outcomes and prognostic factors in non-proliferative LN.MethodsWe retrospectively reviewed the medical records of patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V or II+IV by kidney biopsy between 1997 and 2021 at a tertiary referral center. Clinical and laboratory data were compared between patients with and without poor renal outcomes. Poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 or death due to renal cause. Univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the factors associated with poor renal outcomes.ResultsWe included 71 patients with non-proliferative LN (4: class I; 17: class II; 48: class V, 17; 2: class II+V). Median follow-up duration was 103 months (interquartile range 27–185) and the overall rate of poor renal outcomes at last follow-up was 29% (21/71), including end-stage renal disease (n=2) and renal death (n=1).Univariate analysis indicated that older age (HR 1.05; 95% CI: 1.00–1.09), low eGFR (HR 0.97; 95% CI: 0.95–0.99) and failure to reach complete remission at 6 months (HR 0.332; 95% CI: 0.12–0.92) were significantly associated with poor renal outcomes. Multivariate analysis revealed that low eGFR at 6 months (HR 0.97; 95% CI: 0.95–0.99) was significantly associated with poor renal outcomes.Figure 1.Renal outcomes at last follow upeGFR, estimated glomerular filtration rate (ml/min/1.73m2)Table 1.Univariate and multivariate Cox proportional hazard regression analyses of the factor associated with poor renal outcomesParameterUnivariate analysisMultivariate analysisHR95% CIp valueHR95% CIp valueClinical features Age1.0461.003-1.0910.0361.0020.960-1.0470.921 Sex1.6540.375-7.2980.506 SLEDAI1.0360.965-1.1120.327 Extra renal SLEDAI1.0380.971-1.110.272Renal profiles eGFR at LN diagnosis0.9930.976-1.0110.456 Proteinuria at LN diagnosis1.0001.000-1.0000.444 > 1g/24 hours0.6690.243-1.8410.437 > 3g/24 hours0.6240.229-1.6990.356 eGFR at 6M0.9670.948-0.9860.0010.9680.948-0.9880.002 eGFR at 12M0.9640.947-0.9810.000 Complete remission at 6M0.3320.119-0.9240.0350.5530.179-1.7070.303 Complete remission at 12M0.6670.232-1.9140.451 Transformation1.2460.423-0.7010.692Laboratory data Anti-dsDNA1.0010.999-1.0030.196 C31.0201.000-1.0410.051 C41.0270.969-1.0890.367 Albumin1.1800.661-2.1090.576ClassificationaClass I0.8020.102-6.3030.834Class II1.2980.412-4.0880.656Class V0.8870.308-2.5570.824Class II+V0.0480.000-16850.837Medicationsb ACEi/ARB1.6520.603-4.5280.329 Hydroxychloroquine1.3260.414-4.2420.635 Corticosteroid1.1860.154-9.1080.870 CNI2.4390.464-12.8240.292 MMF3.7880.959-14.9650.057 AZA0.5890.133-2.6110.486a LN classifications were based on the International Society of Pathology/Renal Pathology Society (ISN/RPS) classification.b Medications maintained at least one year since Lupus Nephritis diagnosis.HR, hazard ratio; 95% CI, 95% confidence interval; SLEDAI, systemic lupus erythematosus disease activity index; eGFR, estimated glomerular filtration rate; LN, lupus nephritis; anti-dsDNA, anti-double strand DNA; C3/C4; complement 3/4; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CNI, carcineurin inhibitor; MMF, mycophenolate mofetil; AZA, azathioprine.ConclusionPoor renal outcomes occurred in approximately 30% of patients with non-proliferative LN (class I, II or V) after long-term follow-up.Our findings suggest that more active management may be needed for non-proliferative LN, particularly in patients with low eGFR at 6 months.Disclosure of InterestsNone declared

BackgroundThe systemic lupus erythematosus (SLE) disease activity in patients with lupus nephritis (LN) generally declines after the initiation of renal replacement therapy (RRT); this is known as the “burn out” phenomenon that possibly occurs due to the suppression of cellular and humoral immunity in the end-stage renal disease (ESRD) state and elimination of disease pathogenic factor by dialysis [1-4]. However, several studies showed that SLE flares could occur even during RRT [5-8]. Nevertheless, the details of disease flares of SLE in patients under dialysis have not been studied yet.ObjectivesThis study aimed to investigate the clinical features, risk factors, and treatment details of SLE patients experiencing disease flare under RRT.MethodsThe medical records of SLE patients who received dialysis at two tertiary referral hospitals in Seoul and Ulsan, South Korea were reviewed. All patients in this study were either clinically or histologically diagnosed with LNResultsOf a total of 121 patients with SLE on dialysis, 96 (79.3%) were on hemodialysis (HD) and 25 (20.6%) were on peritoneal dialysis (PD). During a median follow-up of 45 months (IQR, 23–120) after the initiation of dialysis, 32 (26.4%) patients experienced SLE flare (HD, n = 25; PD, n = 7). The most common features of SLE flare were hematologic (40.6%) and constitutional manifestations (40.6%). Treatments for disease flares were based on corticosteroids, and 11 (34.3%) patients required additional immunosuppressants including cyclophosphamide and mycophenolate mofetil. There was no case of severe adverse events related to medication. non-renal SLE Disease Activity Index (SLEDAI) score before dialysis initiation (HR 1.235; 95% CI, 1.122–1.359; P = 0.001) was a significant risk factor for disease flare during dialysis.Table 1.Multivariable analysis of factors associated with SLE flare under dialysisHazard ratio95% CIP-valueNon-renal SLEDAI at the initiation of dialysis1.2351.122–1.3590.001Hematologic manifestation prior to dialysis1.2560.690–2.8260.150Cumulative amount of steroid during 1 year prior to the initiation of dialysis1.0400.995–1.0870.086Dialysis modality: hemodialysis0.7660.262–2.2430.630ConclusionMore than one-quarter of SLE patients experienced disease flare during dialysis, which most commonly had hematologic manifestations. Continued follow-up and appropriate treatments including immunosuppressants should be considered for patients with SLE under dialysis.References[1]Coplon NS, Diskin CJ, Petersen J, Swenson RS. The Long-Term Clinical Course of Systemic Lupus Erythematosus in End-Stage Renal Disease. New England Journal of Medicine 1983;308:186-90.[2]Lee P-T, Fang H-C, Chen C-L, Chiou Y-H, Chou K-J, Chung H-M. Poor prognosis of end-stage renal disease in systemic lupus erythematosus: a cohort of Chinese patients. Lupus 2003;12:827-32.[3]Pahl MV, Gollapudi S, Sepassi L, Gollapudi P, Elahimehr R, Vaziri ND. Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression. Nephrology Dialysis Transplantation 2010;25:205-12.[4]Ribeiro FM, Fabris CL, Bendet I, Lugon JR. Survival of lupus patients on dialysis: a Brazilian cohort. Rheumatology 2013;52:494-500.[5]Okano K, Yumura W, Nitta K et al. Analysis of Lupus Activity in End-Stage Renal Disease Treated by Hemodialysis. Internal Medicine 2001;40:598-602.[6]Barrera-Vargas A, Quintanar-Martínez M, Merayo-Chalico J, Alcocer-Varela J, Gómez-Martín D. Risk factors for systemic lupus erythematosus flares in patients with end-stage renal disease: a case–control study. Rheumatology 2015:kev349.[7]Cucchiari D, Graziani G, Ponticelli C. The dialysis scenario in patients with systemic lupus erythematosus. Nephrology Dialysis Transplantation 2014;29:1507-13.[8]Kang S-H, Chung B-H, Choi S-R et al. Comparison of Clinical Outcomes by Different Renal Replacement Therapy in Patients with End-Stage Renal Disease Secondary to Lupus Nephritis. The Korean Journal of Internal Medicine 2011;26:60.Disclosure of InterestsNone declared

BackgroundThere is still controversy about the efficacy of COVID-19 vaccination and its extent in lowering immunogenicity of Rheumatoid Arthritis (RA) patients. The guideline in whether immunosuppressive agents need to be discontinued before the vaccination is continuously updated because it is considered to lower immunogenicity. Furthermore, there is great discussion on the effectiveness of the COVID-19 booster vaccine and interest in antibody generation in different types of vaccine, as in South Korea there are many patients who were prescribed the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine.ObjectivesThus, we investigated the differences of antibody production between patients who received only two doses of ChAdOx1-S nCoV-19 and those who received the mRNA booster vaccine. Also, antibody production under different types of immunosuppressive agents was analyzed.MethodsFrom October 14, 2021 to January 21, 2022 at a tertiary referral center, two patient groups diagnosed with RA were studied prospectively; one group that completed 1st and 2nd doses of ChAdOx1-S nCoV-19 vaccine, second group that completed mRNA booster vaccine as well as two doses of ChAdOx1-S nCoV-19 vaccine. SARS-CoV-2 antibody testing on the semiquantitative anti-SARS-CoV-2 S enzyme immunoassay was done, and differences in antibody titers were analyzed in patients who received different immunosuppressive agents such as csDMARD, TNF inhibitor, JAK inhibitor, Tocilizumab, Abatacept and Corticosteroid. Statistical analysis with a multivariate logistic regression model was performed.ResultsIn a total of 261 patients, 153 patients had completed two doses of ChAdOx1-S nCoV-19, 108 patients had completed third mRNA booster vaccine. Anti-SARS-CoV-2 RBD antibody positive rate (titer>0.8U/mL) was 97%(149/153) and 99%(107/108) respectively, and only 5 patients showed negative result. In the aspect of high antibody titer(>250U/mL), which is the upper limit of the RBD antibody immunoassay, the result showed rate of 31% (47/153) in the non-booster group and 94%(102/108) in the booster group respectively.Among the different immunosuppressive agents and other clinical aspects, multivariate analysis revealed that corticosteroid use (OR 0.91; 95% CI: 0.86-0.98), older age(OR 4.33; 95% CI: 1.34-13.91), and male gender(OR 0.35; 95% CI 0.16-0.75) were significantly associated with low rate of high antibody titer.Furthermore, out of 14 patients who underwent antibody test twice before and after the mRNA booster vaccine, other than four patients who already showed high titer of >250U/mL before the mRNA booster vaccine, 10 patients showed an increase in titer after the booster vaccine and 7 patients were acquired high titer of >250U/mL.Figure 1.Anti-SARS-CoV RBD antibody titer of two groupsTable 1.Analysis of immunosuppressive agents and other clinical aspects for high antibody titer(>250U/mL) after two doses of ChAdOx1-S nCoV-19Univariate analysisMultivariate analysisParameterOR95% CIp valueOR95% CIp valueClinical features Age0.9170.860-0.9780.0080.9170.857-0.9810.012 Sex3.6741.206-11.1910.0224.3301.348-13.9120.014 DAS 281.1440.670-1.9500.622 Duration0.9300.830-1.0430.214Medications csDMARD1.2730.639-2.5331.273 TNF inhibitor2.2110.795-6.1450.128 JAK inhibitor0.6650.275-1.6070.365 Abatacept0.3680.038-3.6020.391 Tocilizumab1.2640.438-3.6480.665 Corticosteroid0.4720.235-0.9490.0350.3490.163-0.7480.007Medication dose Methotrexate0.9930.919-1.0720.855 Corticosteroid0.8490.719-1.0030.054ConclusionAnti-SARS-CoV-2 RBD antibody positive rate was 97% or more regardless of the mRNA booster vaccination. However, patients who received the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine showed high antibody titer (>250U/mL) three times more than those who did not receive the booster shot.Our findings also showed that corticosteroid use, old age, and male gender is significantly associated with low rate of acquiring high antibody titer.Disclosure of InterestsNone declared

BackgroundMacrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to be secondary hemophagocytic lymphohistiocytosis (HLH) in patients with rheumatic disease.ObjectivesThe aim of study was to evaluate the clinical manifestations and outcomes in patients with MAS with rheumatic disease.MethodsWe performed a retrospective study of 20 adult patients who were diagnosed with MAS from 2012 to 2020. MAS was classified according to the HLH-2004 criteria. Patients’ information, including clinical features, laboratory findings, and treatment regimens, was collected, and the overall survival rate was estimated by the Kaplan–Meier method.ResultsTwenty patients (18 women, 35.6 ± 18.3 years) who met the HLH-2004 criteria also fulfilled the 2016 EULAR/ACR/PRINTO classification criteria for MAS, and HScore was higher than 169 (median, 238.5). Fourteen patients with systemic lupus erythematosus and 6 patients with adult-onset Still’s disease were included. All patients were treated initially with corticosteroids, and 16 patients required additional immunosuppressants. The overall survival at 3 and 6 months was 75.2% and 64.3%. In survivors, renal impairment was less common (23.1% versus 42.9%, p = 0.007), the levels of AST (202.0 versus 72.0 IU/L, p = 0.006) and LDH (1144.0 versus 343.0IU/L, p = 0.001), and platelet count (90.0 versus 46.0 × 109/L, p = 0.016) were higher in compared to non-survivors. Nine patients had opportunistic infections, five of whom died during admission.ConclusionThe mortality of patients with MAS remains high. Renal impairment, levels of AST and LDH, and platelet count might be associated with prognosis.Table 1.Treatments and management characteristics of patients with MASNo.Age/sexDiseaseDisease duration (months)1st Treatment (corticosteroids)2nd Treatment3rd TreatmentCombined infectionAlive/dead119/FSLE11 mg/kgIVIG + PPTCZ, RTXBacteremiaDead220/MSLE01 mg/kg---Alive320/FAOSD11 mg/kgVP16--Alive422/FSLE1100 mgIVIG + PP-PneumoniaDead522/FAOSD0500 mgIVIG--Alive623/FSLE1821 mg/kg---Alive723/FSLE411 mg/kg---Alive830/FSLE1461 mg/kgIVIGCsA-Alive932/FSLE1271 mg/kgIVIG + PPCsA, TCZPneumoniaAlive1035/FAOSD01 mg/kgCsA-Viral infectionAlive1137/FSLE651 mg/kgCsA, VP16-BacteremiaAlive1238/FSLE01 mg/kgIVIG + PPRTX-Dead1340/FAOSD00.5 mg/kgCsA--Alive1443/FSLE601 mg/kgIVIG + PPTCZ, RTX, CsA,PCP,DeadVP16, IFXViral infection1549/FSLE01 mg/kgCYC-BacteremiaAlive1651/FAOSD01 mg/kg---Alive1757/FSLE01 mg/kgIVIG + PPCsA, VP16Fungal infectionDead1861/FSLE21 mg/kgIVIG + PPTCZ-Dead1968/FSLE21 mg/kgIVIG + PPCsAFungal infectionAlive2070/MAOSD01 mg/kgIVIG + PPCsA, VP16Fungal infectionDeadSLE: Systemic lupus erythematosus, IVIG: Intravenous immunoglobulin, PP: Plasmapheresis, TCZ: Tocilizumab, RTX: Rituximab, AOSD: Adult-onset still’s disease, VP16: Etoposide, PCP: Pneumocystis pneumonia, CsA: Cyclosporin, IFX: Infliximab, MCTD: Mixed connective tissue disease.Disclosure of InterestsNone declared

BackgroundPatients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus erythematosus (SLE). We sought to examine the clinical characteristics of patients with primary ITP who later developed SLE, and identified the risk factors for the development of SLE.ObjectivesWe retrospectively examined patients who were diagnosed with primary ITP at a tertiary hospital between August 2001 and November 2019. We compared the clinical characteristics according to the development of SLE. Logistic regression analysis was performed to identify the factors associated with the development of SLE.MethodsOf 130 patients with primary ITP, 10 (7.7%) were later diagnosed with SLE during follow-up (median, 30 months [IQR, 15.5–105]). The presence of skin bleeding, organ bleeding, lymphopenia, anemia, and positive antinuclear antibody (ANA) titer (> 1:160) were more common among patients who later developed SLE than did those who did not develop SLE. Multivariate analysis showed that young age (< 40 years; odds ratio [OR], 8.359 [95% confidence interval (CI), 1.230–56.793]; p = 0.033), organ bleeding (OR, 18.349 [95% CI, 2.771–121.517]; p = 0.003), and ANA positivity (>1:160; OR, 7.692 [95% CI, 1.482–39.910]; p = 0.015) were significantly associated with the development of SLE.ResultsYoung age (< 40 years), organ bleeding, and ANA positivity (> 1:160) were risk factors for the development of SLE in patients with primary ITP.ConclusionThese results suggest that continued follow-up for the detection of SLE development is needed for patients with ITP, particularly those with young age, ANA positivity, or organ bleeding.References[1]Zhu, Fang-Xiao, et al. “Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a population-based cohort study.” Annals of the rheumatic diseases 79.6 (2020): 793-799.Table 1.Factors associated with the development of SLE in patients with primary ITPUnivariateMultivariateOR95% CIP valueOR95% CIP valueYoung agea5.4441.332–22.2500.0188.3591.230–56.7930.033Female4.3330.530–35.4220.17BMI0.8730.717–1.0700.20Skin bleeding8.4191.034–68.5330.046Mucosa bleeding1.2500.247–6.3300.79Organ bleeding14.8643.633–60.815< 0.00118.3492.771–121.5170.003Platelet counts0.9110.828–1.0020.06ANA positivityb16.5003.984–68.341< 0.0017.6921.482–39.9100.015Neutropeniac2.1110.229–19.4990.51Lymphopeniad4.8461.189–19.7590.028Anemiae10.1182.044–50.0910.005SLE: systemic lupus erythematosus, ITP: immune thrombocytopenia, BMI: body mass index, ANA: antinuclear antibody, OR: odds ratio, CI: confidence interval.aYoung age = age < 40 yearsbANA positivity ≥ 1:160cNeutropenia = Absolute neutrophil count < 1500 μLdLymphopenia = Absolute lymphocyte count < 1500 μLeAnemia = Hemoglobin < 12 g/dLDisclosure of InterestsNone declared

Background Ankylosing spondylitis (AS) is a chronic inflammatory arthritis characterized by bony overgrowth. It has been suggested that erosive bone destruction, followed by repair with ossification, leads to new bone formation. However, little is known about the molecular mechanisms underlying proliferative bone formation in AS. Previously, we have reported that IL-32 could affect bone physiology via osteoclast activation. Objectives To investigate the role of IL-32 on osteoblast differentiation and its association with new bone formation in AS. Methods The concentration and expression levels of IL-32 and TNF-α were evaluated in the synovial fluid and tissue from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA) by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. To address whether IL-32 affects bone formation in vivo , we examined osteoblast differentiation from calvarial cells of IL-32 transgenic (Tg) mice and also the bone volume in these mice. To elucidate the mechanism of IL-32 effect on osteoblastogenesis, osteoblast regulators including DKK1, BMPRII, BMP2 and LRP5 were assayed in the IL-32 Tg mice. To determine the role of IL-32 in the interaction of osteoblasts and osteoclasts, the expression of RANKL and OPG was measured with or without IL-32 treatment in human primary osteoblasts. Results The levels of IL-32 were significantly higher in the synovial fluid of AS patients compared with RA or OA patients. In addition, the expression of IL-32 in AS synovia was increased compared to that in RA or OA synovia. The differentiation of osteoblasts from calvarial cells was more robust and rapid in IL-32 Tg mice than in wild-type mice. Micro-CT analysis further revealed that IL-32 Tg mice, particularly males, have a higher bone volume than wild-type mice. The levels of DKK-1, a negative regulator of Wnt signaling, were decreased in IL-32 Tg mice during osteoblast differentiation. In addition, after IL-32 stimulation, DKK-1 expression was significantly decreased in osteoblast precursor cells from mice and also in human osteoblasts. Furthermore, the expression of RANKL, but not OPG, was enhanced by the stimulation with IL-32, leading to a higher expression ratio of RANKL to OPG. Conclusions These results indicate that IL-32 is significantly highly expressed in AS and may enhance osteoblast differentiation via its inhibitory effects on DKK-1. Therefore, IL-32 might have a role in osteoproliferation and is a potential biomarker to predict new bone formation in AS. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2857

Background Use of complementary and alternative medicine (CAM) is not uncommon in patients with rheumatoid arthritis (RA), but patient characteristics and the factors influencing and predicting its use is not well known. Objectives We aimed to assess the characteristics and outcomes of CAM in patients with RA and to analyze the predicting factor for its use. Methods A total of 5,360 RA patients from the KORONA (Korean Observational Study Network for Arthritis) prospective multicenter cohort were assessed for use of CAM and characteristics including age, sex, disease duration, delay in diagnosis, family history, comorbidities, socioeconomic status, fatigue, sleep, pain, exercise, smoking, HAQ, EQ-5D, DAS28, medication, radiographic damage, surgery, and adverse events. Multiple logistic regression was used to analyze the predicting factors for CAM use. Results Of the 5,360 patients, 2,468 (46.0%) patients responded that they have used CAM. Acupuncture was most common (73.3%) followed by herbal medicine (60.4%), moxibustion (30.7%), bee venom (19.1%), others (7.7%), and placenta injection (3.9%). Female used CAM significantly more and CAM users were significantly younger at onset (p Conclusions Patients with higher disease activity and lower health-related quality of life and higher functional disability used CAM significantly more frequently. Acknowledgements This study is supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Disclosure of Interest None Declared

Background The importance of tight control is supported by solid clinical evidence. While treating RA with the aim of achieving remission or a low disease activity-as determined by disease activity score employing 28 joints count (DAS28) or the simplified and the clinical disease activity index (SDAI, CDAI) -is reasonable and important, this approach is not widely accepted in the clinical situation. Objectives To identify the effects of tight control of rheumatoid arthritis (RA) on various disease outcomes in a large observational study. Methods We selected 1900 RA patients with a baseline DAS28-ESR of more than 3.2 and who had 1 year of follow-up data. The patients were divided into two groups: (1) disease-modifying antirheumatic drugs (DMARDs)-changed group (patients who changed the types or amounts of their DMARDs) and (2) DMARDs-unchanged group (patients who maintained their DMARDs). We measured various disease outcomes, including the Health Assessment Questionnaire–Disability Index (HAQ-DI), DAS28-ESR, C-reactive protein (CRP), ESR, and global health assessments by both physicians and patients. The t -test was used to identify the effects of tight control of RA on various disease outcomes. Results Patients in the DMARDs-changed group were younger, had a shorter disease duration, used less leflunomide, used more biologic agents. At baseline, they had higher DAS28-ESR (4.62±0.96 in DMARDs-changed group versus 4.42±0.90 in DMARDs-unchanged group, p p =0.006), CRP (–0.39±1.71 versus –0.11±1.37 mg/dl, p =0.001), and the global health assessment by a physician (–11.21±24.18 versus –8.10±19.20, p =0.002). Image/graph Conclusions Immediate changes in DMARDs according to disease activity can improve disease outcomes, especially DAS28-ESR, CRP, and the global health assessment by a physician. Disclosure of Interest None Declared