Zhenbin Li

Societal Costs of Rheumatoid Arthritis in China: A Hospital-Based Cross-Sectional Study

To estimate the annual direct and indirect costs of rheumatoid arthritis (RA) in China and identify the predictors for cost of illness.

Antibodies to α-fodrin derived peptide in Sjögren’s syndrome

Sjogren’s syndrome (SS) is a chronic autoimmune disorder of unknown cause. Haneji et al identified a 120 kDa fragment of the ubiquitous cytoskeletal protein α-fodrin as an autoantigen in an NFS/sld mouse model of human SS.1 More recently, the sensitivity and specificity of α-fodrin antibodies in SS in several studies suggested that it might be of value in the diagnosis of SS.1–3 In the present study, a conserved motif, rather than the whole protein, in α-fodrin was used as antigenic peptide to define further the role of anti-α-fodrin antibodies in SS. This is the first study so far to evaluate the prevalence of anti-α-fodrin peptide antibodies (α-FPA) in a cohort of Chinese patients with SS. Serum samples from 89 patients with SS (85 female, 4 male; 74 with primary SS (pSS) and 15 with …

Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study

Cyclophosphamide (CYC) has long been considered a gold standard in inducing renal remission and preventing renal flares for patients with systemic lupus erythematosus (SLE). However, the rational use of CYC has not reached a consensus, such as the timing and length of treatment, the route of administration, and the ideal dosage. The objective of this study was to assess the efficacy and safety of short-interval lower-dose (SILD) intravenous (IV) CYC in the treatment of SLE. A total of 225 patients with lupus nephritis were randomly assigned to a 1-year trial, either the SILD group (12 fortnightly pulses at a fixed dose of 400 mg followed by 6 monthly pulses) or high-dose (HD) group (6 monthly pulses followed by two quarterly pulses at a dose of 0.5~1.0 g/m2). At 6 months of treatment, 28 % (30/107) of patients in the SILD group reached a complete remission (CR), and 51.4 % (55/107) were in partial remission (PR), as compared with 32.7 % (35/107) and 45.8 % (49/107) in the HD group, respectively. Serum albumin, 24-h urinary protein, and the scores of disease activity were significantly improved in both groups at 6 months and maintained at the end of clinical trial. However, the SILD group showed much less menstrual disturbances (11.5 %), gastrointestinal adverse effects (5.3 %), and leukopenia (9.7 %) than the HD group (28.6, 26.8, and 19.8 %, respectively) at the end of clinical trial. The efficacy of the short-interval lower-dose (SILD) IV CYC regimen in the treatment of lupus nephritis is equivalent to that of the high-dose (HD) regimen, whereas the incidence of adverse events is much lower in the SILD group.

Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China

This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients’ social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.

AB0525 Safety and Efficiency of Low-Dose Interleukin-2 Treatment in Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nuclear self-antigens, production of pathogenic autoantibodies and damage to multiple organs. While corticosteroids and immunosuppressive agents have improved the outcome of patients, there remains a significant unmet need for safe and more effective treatments. Low-dose Interleukin-2 (IL-2) therapy has recently been shown effective to treat autoimmune disease. Objectives To assess the safety and efficacy of low-dose IL-2 therapy in active SLE. Methods We conducted a clinical trail on active SLE patients (NCT02084238). A total of 40 patients were enrolled. Patients with SLE Disease Activity Index (SLEDAI) scores ≥8 received three courses of low dose recombinant human IL-2 (1 million IU every second day for 2 weeks followed by a 2-week hiatus). The primary end point was the response rate at week 10. Both the safety and efficiency of IL-2 therapy were evaluated. Results Total 36 patients (36/40, 90%) achieved an SLE Responder Index (SRI) improvement at week 6. No patients demonstrated high grad adverse events; mild injection-site reaction was observed in 5 patients (5/40, 12.5%). Better response was seen in patients with skin involvement (erythema, photo sensibility, Rdynolds, vasculitis), hematologic abnormities (leukopenia, Thrombocytopenia and anemia) and disease-related fever. Patients showed the improvement of major laboratory indicators, including reduced anti-dsDNA autoantibody titres and 24-hour proteinuria, and increased levels of the complement proteins C3 and C4. Immunological analysis showed significant increase of Treg cells and decrease of effector helper T cells after the therapy. Conclusions Our results showed that low-dose IL-2 therapy in active SLE were safe and achieved satisfactory efficacy with increasing Treg and decreasing effector helper T cells. References Jing He, Louis M. Tsai, Yew Ann Leong, Xin Hu, Cindy S. Ma, Nina Chevalier, Xiaolin Sun, Kirsten Vandenberg, Steve Rockman, Yan Ding, Lei Zhu, Wei Wei, Changqi Wang, Alexander Karnowski, Gabrielle T. Belz, Joanna R. Ghali, Matthew C. Cook, D. Sean Riminton, André Veillette, Pamela L. Schwartzberg, Fabienne Mackay, Robert Brink, Stuart G. Tangye, Carola G. Vinuesa, Charles R. Mackay, Zhanguo Li,* and Di Yu,* Circulating Precursor CCR7loPD-1hi CXCR5+ CD4+ T Cells Indicate Tfh Cell Activity and Promote Antibody Responses upon Antigen Reexposure. Immunity, 2013, 39(4),770-781 Disclosure of Interest None declared

Remission assessment of rheumatoid arthritis in daily practice in China: a cross-sectional observational study

The objective of this study is to evaluate the remission rate and describe the current use of medication in a large cohort of rheumatoid arthritis (RA) patients under routine clinical care in China. RA patients were recruited from 40 large teaching hospitals nationwide in China. Data regarding RA disease activity, medication treatment, and adverse events were recorded using a standardized clinical data questionnaire. RA remission was evaluated by the 28 Joint Disease Activity Score DAS28-ESR Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria. A total of 1945 patients with RA were included in the study. The proportions of patients who fulfilled the DAS28-ESR, CDAI, SDAI, and ACR/EULAR remission criteria were 10.90%, 6.17%, 5.04% , and 1.75%, respectively. Most patients had taken at least one disease-modifying anti-rheumatic drug (DMARD), and the most common prescriptions included leflunomide (LEF) and methotrexate (MTX). DMARD combined with botanics were the most common and dominant strategy for RA management (29.16%). Overall, 433 patients (22.27%) had at least one adverse event. Gastrointestinal adverse events (41.27%) were the most frequently reported events. The incidence of side effects in patients using biologics DMARDs (bDMARDs) was significantly lower than that in those taking MTX, LEF, or sulfasalazine (SSZ). The remission rate of RA disease activity, as assessed in Chinese clinical practice, was very low. Adverse effects of the medicine occurred in approximately one in five RA patients, with bDMARDs were demonstrated to be the medication with the lowest side effects.

68 Identifying clinical and epidemiological risk factors associated with thrombosis and pregnancy morbidity in a large cohort of chinese aps patients

Background and aims The evaluation of thrombotic and pregnancy risks associated with antiphospholipid antibodies (aPLs) in individual patients is challenging. Our objective was to identify potential clinical and epidemiological predictors of thrombosis and pregnancy morbidities in a large Chinese antiphospholipid syndrome (APS) cohort. Methods This cohort included 177 consecutive APS patients and 146 asymptomatic aPLs control patients who attended the rheumatology clinic at People’s Hospital of Beijing University Health Science Centre. All APS patients fulfilled the 2006 revised criteria APS. All control patients had at least one persistent positive aPLs without any other criteria APS manifestations. When assessing risk factors associated with pregnancy morbidities, only reproductive age (age <45) female controls were used. Chi-squared or Fisher’s exact test univariate analysis and multivariable logistic regression analyses were used to assess association between different clinical and epidemiological risk factors and clinical manifestations. Results Of the 177 APS patients, 134 (75.7%) were women with a mean age of 43. 5 (S.D. 16). When comparing to controls, risk factors associated with thromboembolic events included: Raynaud’s phenomenon (odds ratio (OR)=2.371, 95% Confidence interval (CI) 1.039–5.637, p=0.0462), hypertension (OR=1.829, 95% CI 1.114–3.05, p=0.022), and smoking (OR=3.941, 95% CI 1.816–8.799, p=0.0004). Age, hyperlipidemia, diabetes, hypocomplementemia, and thrombocytopenia did not demonstrate significant association with thrombosis. None of the analysed clinical characteristics showed significant association with pregnancy morbidities. A high frequency of thrombocytopenia and hypocomplementemia were observed in both APS patients and control patients with persistent +aPLs. Conclusions Smoking, Raynaud’s phenomenon, and hypertension are potential predictors of thromboembolic events in +aPLs Chinese patients.

33 Association of the lupus low disease activity state (lldas) with health related quality of life

Background and Aims Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). The Lupus Low Disease Activity State (LLDAS) definition has not been previously evaluated for association with patient reported outcomes. The objective of this study was to determine whether LLDAS was associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of SLE patients. Methods HR-QoL was measured using the Medical Outcomes Study 36-item Short Form Health Survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using SLE disease activity index (SLEDAI-2K), physician global assessment (PGA) and LLDAS. Results Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level, damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p<0.001), a higher level of education (p<0.001), younger age (p<0.001) and shorter disease duration (p<0.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (p<0.001) was negatively associated with PCS, and cutaneous activity (p=0.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (p<0.001) and MCS (p<0.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (p<0.001), but not MCS scores. Conclusions Ethnicity, education, disease damage, and specific organ involvement impacts on HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.

SAT0282 Frequency and Predictors of Attainment of The Lupus Low Disease Activity State (LLDAS) in A Cross Sectional Study of Sle Patients in The Asia Pacific

Background Systemic lupus erythematosus (SLE) is a heterogeneous disease characterised by fluctuating disease activity. A low disease activity endpoint, the Lupus Low Disease Activity State (LLDAS), was recently reported and retrospective validation showed that time spent in LLDAS translated into reduced damage accrual (Franklyn, Ann Rheum Dis, 2015). A large prospective study to validate LLDAS in a multiethnic cohort of lupus patients from the Asia Pacific Region is underway. Objectives To describe the frequency and identify the predictors of fulfilling criteria for LLDAS in baseline visit data from a large multinational multiethnic cohort of patients with SLE in nine Asia Pacific countries. Methods Prospectively collected baseline visit data from 1846 SLE patients enrolled in a longitudinal study were analysed cross sectionally against the recently published definition of LLDAS, and patient characteristics associated with LLDAS attainment determined. Results LLDAS criteria were met by 44% of patients at a single baseline visit. Stepwise multivariable logistic regression revealed that patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95% CI 0.19–0.49, p<0.001). Likewise, discoid rash (OR 0.66, 95% CI 0.49–0.89, p=0.006), renal disease (OR 0.60, 95% CI 0.48–0.75, p<0.001), elevated double stranded DNA (OR 0.65, 95% CI 0.53–0.81, p<0.001) or hypocomplementaemia (OR 0.52, 95% CI 0.40–0.67, p<0.001) were negatively associated with LLDAS attainment. Significant differences in LLDAS attainment between countries were observed, and higher national social wealth as measured by the Gross Domestic Product per capita was positively associated with LLDAS (OR 1.57, 95% CI 1.25–1.98, p<0.001). Conclusions Low disease activity was observed in less than half of SLE patients at a single point in time. Disease duration and phenotype, as well as national social wealth, were predictive of LLDAS attainment. Disclosure of Interest None declared

AB0373 Treatment of primary sjogren’s syndrome-associated lung disease: a prospective study

Background Pulmonary involvement is common in primary Sjögren’s syndrome (pSS), which seriously affects the prognosis and survival rate. However, the treatment of those patients has hardly been explored before. Most studies were specifically designed to evaluate sicca features. Objectives To analyze efficacy and safety of corticosteroid therapy combined with hydroxychloroquine (HCQ) or intravenous cyclophosphamide (CTX) in pSS-associated lung disease. Methods A total of 15 patients were recruited in the prospective study. Among them, 7 patients took oral prednisone combined with HCQ and 8 patients received oral prednisone combined with intravenous CTX. Prednisone was prescribed initially at a dosage of 30-40mg/day, and was tapered to 7.5mg/d within 4 months. This dosage of prednisone was maintained or tapered for the rest of the follow up as appropriate. HCQ was administered at a dosage of 200mg, twice a day. CTX was administered intravenously at an initial dosage of 400mg, every 2 weeks for 6 months, and then tapered to 400mg every 4 weeks. Results Fourteen patients receiving oral prednisone combined with HCQ or intravenous CTX were followed up for 11.57±4.91 months. One patient from CTX group withdrew from the study for stopping DMARDs to have surgery. Six of 7 patients (85.71%) were female of both groups. The mean age was 55.57±14.52 and 55.43±14.33 years old for HCQ group and CTX group, with median disease duration 120 and 180months, respectively. During the follow up, there was evidence of improvement in HRCT for most of the patients, and no obvious deterioration of PFT was observed. One patient in HCQ group presented hypoleukemia, which was ameliorated after reducing to 100mg, twice a day. Two patients had pneumonia and one had herpes zoster virus (HZV) infection in CTX group. No life-threatening side effect was observed in both groups. Conclusions Corticosteroid therapy combined with hydroxychloroquine or intravenous cyclophosphamide is administered with a favorable response seen in the majority of patients. This should be further confirmed in a large cohort. References Ramos-Casals M, Tzioufas AG, Stone JH, Siso A, Bosch X. Treatment of primary Sjogren syndrome: a systematic review. JAMA. 2010; 304: 452-60. Shi JH, Liu HR, Xu WB, et al. Pulmonary Manifestations of Sjogren’s Syndrome. Respiration. 2009; 78: 377-86. Disclosure of Interest None Declared