Yuan An

Low-dose interleukin-2 treatment selectively modulates CD4 + T cell subsets in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease characterized by altered balance of activity between effector and regulatory CD4+ T cells. The homeostasis of CD4+ T cell subsets is regulated by interleukin (IL)-2, and reduced production of IL-2 by T cells is observed in individuals with SLE. Here we report that treatment with low-dose recombinant human IL-2 selectively modulated the abundance of regulatory T (Treg) cells, follicular helper T (TFH) cells and IL-17-producing helper T (TH17) cells, but not TH1 or TH2 cells, accompanied by marked reductions of disease activity in patients with SLE.

Frequency and predictors of the lupus low disease activity state in a multi-national and multi-ethnic cohort

BackgroundSystemic lupus erythematosus (SLE) is a chronic heterogeneous disease with considerable burden from disease activity and damage. A novel clinical treatment target in the form of the lupus low disease activity state (LLDAS) has been recently reported, with retrospective validation showing that time spent in LLDAS translates to reduced damage accrual. The objectives of this study were to describe the frequency and identify the predictors of attaining LLDAS in a large multinational cohort of patients with SLE.MethodsData were collected at the recruitment visit in patients with SLE enrolled in a longitudinal study in nine countries. Data were analysed cross-sectionally against the recently published definition of LLDAS, and the frequency and characteristics associated with presence of LLDAS were determined. Stepwise multivariable logistic regression was used to determine predictors of LLDAS.ResultsOf the 1846 patients assessed, criteria for LLDAS were met by 44xa0%. Patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95xa0% CI 0.19–0.49, pu2009<u20090.001). Likewise, patients with a history of discoid rash (OR 0.66, 95xa0% CI 0.49–0.89, pu2009=u20090.006), renal disease (OR 0.60, 95xa0% CI 0.48–0.75, pu2009<u20090.001), elevated double stranded DNA (OR 0.65, 95xa0% CI 0.53–0.81, pu2009<u20090.001) or hypocomplementaemia (OR 0.52, 95xa0% CI 0.40–0.67, pu2009<u20090.001) were less likely to be in LLDAS. When countries were compared, higher national social wealth (OR 1.57, 95xa0% CI 1.25–1.98, pu2009<u20090.001) as measured by the gross domestic product per capita was positively associated with LLDAS, but ethnicity was not.ConclusionThe lupus low disease activity state is observed in less than half of patients with SLE at a single point in time. Disease duration and phenotype, and national social wealth, are predictive of LLDAS.

Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study

BackgroundSystemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). Recently, meeting a definition of a lupus low disease activity state (LLDAS), analogous to low disease activity in rheumatoid arthritis, was preliminarily validated as associated with protection from damage accrual. The LLDAS definition has not been previously evaluated for association with patient-reported outcomes. The objective of this study was to determine whether LLDAS is associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of patients with SLE.MethodsHR-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 the SLE disease activity index (SLEDAI-2xa0K), physician global assessment (PGA) and LLDAS.ResultsSignificant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level and damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (pu2009<u20090.001), a higher level of education (pu2009<u20090.001), younger age (pu2009<u20090.001) and shorter disease duration (pu2009<u20090.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (pu2009<u20090.001) was negatively associated with PCS, and cutaneous activity (pu2009=u20090.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (pu2009<u20090.001) and MCS (pu2009<u20090.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (pu2009<u20090.001), but not MCS scores.ConclusionsEthnicity, education, disease damage and specific organ involvement impacts HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.

Monoclonal gammopathy in rheumatic diseases

To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, Pu2009=u20090.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, Pu2009=u20090.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), Pu2009=u20090.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), Pu2009=u20090.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015–1.251), Pu2009=u20090.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011–1.242), Pu2009=u20090.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551–197.435), Pu2009=u20090.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.

AB0514 Efficacy and Safety of Tofacitinib in Chinese Patients with Active Rheumatoid Arthritis: Subgroup Analysis from a Phase 3 Study of Tofacitinib in Combination with Nonbiologic Disease-Modifying Antirheumatic Drugs

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). In the global Phase 3 ORAL Sync study (NCT00856544), tofacitinib improved disease activity in patients (pts) who had active RA despite treatment with nonbiologic disease-modifying antirheumatic drugs (DMARDs).1 Objectives To report a post-hoc analysis of efficacy and safety in a subgroup of Chinese pts. Methods ORAL Sync was a 1-year, double-blind, placebo-controlled, parallel-group study. Pts (N=795) with active RA were randomised 4:4:1:1 to oral tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg BID at 3 (nonresponders) or 6 (remaining pts) months. All pts remained on ≥1 background nonbiologic DMARD throughout. Co-primary efficacy endpoints were ACR20 response rate at Month 6 (M6), change from baseline in physical function (HAQ-DI) at M3, and proportion of pts achieving DAS28-4(ESR)<2.6 at M6. Efficacy and safety outcomes in the subgroup of pts from 20 centres in China vs the global study population are reported; post-hoc tests for statistical significance were performed. Results In total, 792 pts were treated (global population), including 216 Chinese pts. Baseline demographics were similar across treatment groups in the Chinese population (n=86 tofacitinib 5 mg BID; n=86 tofacitinib 10 mg BID; n=44 placebo; 85% female; mean age, 48 years). Both tofacitinib doses demonstrated significant improvements vs placebo in ACR20 response rate at M6 in Chinese pts (p≤0.0001). ACR20 response rates at M6 were numerically higher with tofacitinib in Chinese pts vs the global population (Table). Numerically more Chinese pts achieved DAS28-4(ESR)<2.6 with tofacitinib 5 and 10 mg BID vs placebo at M6, which was significant with the 10 mg BID dose (p=0.1803 and p=0.0120 with tofacitinib 5 and 10 mg BID, respectively; Table). Both tofacitinib doses also demonstrated significant improvements in HAQ-DI at M3 in Chinese pts; least squares (LS) mean difference (95% CI) vs placebo was -0.23 (-0.40, -0.05; p=0.0137) and -0.35 (-0.53, -0.17; p=0.0002) with tofacitinib 5 and 10 mg BID, respectively. Tofacitinib efficacy was generally sustained over 12 months. The most frequently reported adverse events (AEs) were upper respiratory tract infection, elevated aminotransferases, and leukopenia. Incidence of AEs, serious AEs (SAEs), AE discontinuations, serious infections and herpes zoster infections over M0–3 are reported in the Table. SAEs over M3–6 and after M6 were reported in 2 (1.2%) Chinese pt with tofacitinib 10 mg BID. Conclusions Tofacitinib, in combination with background DMARDs, significantly improved signs and symptoms and improved physical function vs placebo over 1 year in Chinese pts with active RA. Efficacy and safety findings in the Chinese subgroup were consistent with the global population. References Kremer J et al. Ann Intern Med 2013; 159: 253-261. Acknowledgements All aspects of this work were funded by Pfizer Inc. Editorial support, under the direction of the authors, was provided by Amanda Pedder of Complete Medical Communications, and funded by Pfizer Inc. Disclosure of Interest Y. An: None declared, Z. Li: None declared, Q. Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Tofacitinib with conventional synthetic disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis: Patient-reported outcomes from a Phase 3 randomized controlled trial

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assess the effect of tofacitinib + conventional synthetic disease‐modifying anti rheumatic drugs (csDMARDs) on patient‐reported outcomes in Chinese patients with RA and inadequate response to DMARDs.

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.

THU0215 Effects of tofacitinib on patient-reported outcomes in a phase 3 study of chinese patients with active rheumatoid arthritis and an inadequate response to dmards

Background Rheumatoid arthritis (RA) worsens patients health-related quality of life.1 Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of RA. Improvements in patient-reported outcomes (PROs) have been reported in the global population of Phase 3 tofacitinib trials.2 Objectives To explore the effect of tofacitinib administered with conventional synthetic DMARDs (csDMARDs) on PROs in Chinese patients with RA and an inadequate response to DMARDs. Methods This was a post-hoc analysis of data from Chinese patients in the 12 month, double-blind Phase 3 study ORAL Sync (NCT00856544), with patients randomised 4:4:1:1 to tofacitinib 5 mg BID, tofacitinib 10 mg BID, placebo (PBO)→tofacitinib 5 mg BID or PBO→tofacitinib 10 mg BID, with csDMARDs. Non-responders (defined as those who did not achieve a 20% improvement in both of the swollen or tender joint counts) receiving PBO advanced blindly to tofacitinib at Month 3; all remaining PBO patients advanced to tofacitinib at Month 6. Least squares mean changes from baseline were reported for Health Assessment Questionnaire-Disability Index (HAQ-DI), patient assessment of arthritis pain (VAS), patient global assessment of disease activity (PtGA), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale, Short Form-36 Health Survey (SF-36), EuroQol five dimensions questionnaire (EQ-5D), and Work Limitations Questionnaire (WLQ), using a mixed-effects model for repeated measures. All patients receiving ≥1 dose of study treatment with ≥1 post-baseline assessment were included. Results Overall 216 patients were included (n=86, tofacitinib 5 mg BID; n=86, tofacitinib 10 mg BID; n=22, PBO→tofacitinib 5 mg BID; n=22, PBO→tofacitinib 10 mg BID). There were no major differences in demographics or baseline characteristics between treatment groups. At Month 3, tofacitinib resulted in significantly greater changes in HAQ-DI (5 mg BID, p<0.05; 10 mg BID, p<0.001), PtGA (5 mg BID, p<0.05; 10 mg BID, p<0.001), Pain (5 mg BID, p<0.001; 10 mg BID, p<0.001) and SF-36 Physical Component Summary (PCS) scores (5 mg BID, p<0.05; 10 mg BID, p<0.001) vs PBO (Figure). Numeric improvements in FACIT-Fatigue, SF-36 Mental Component Summary (MCS) [Figure] and EQ-5D health state profile (utility scores) were observed at Month 3 with tofacitinib vs PBO. There were no improvements in WLQ observed at Month 3 with tofacitinib vs PBO. Improvements were generally maintained at 6 and 12 months (Figure). The proportion of patients achieving HAQ-DI improvement ≥0.22 from baseline at Month 3 was significantly higher with tofacitinib vs PBO (5 mg BID, p<0.05; 10 mg BID, p<0.05). Conclusions Tofacitinib 5 and 10 mg BID administered with csDMARDs significantly improved PROs including SF-36 PCS, PtGA, physical function and pain vs PBO. These improvements were maintained for up to 12 months in Chinese patients with RA. References Strand V, Khanna D. Clin Exp Rheumatol 2010; 28: S32-S40. Strand V et al. Arthritis Care Res (Hoboken) 2016. doi:10.1002/acr.23004. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by C Evans of CMC and was funded by Pfizer Inc. Disclosure of Interest Z. Li Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Y. An Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, G. Li Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Q. Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

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

SAT0252 Long-Term Survival Analysis and Prognostic Outcome Factors in Idiopathic Inflammatory Myopathy

Background Idiopathic inflammatory myopathy is a group of systemic connective tissue diseases, including dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). PM/DM are characterized by chronic muscle inflammation and can affect other internal organs. Survival rate and prognostic factors of PM/DM vary widely. The 5-year survival rates for PM/DM range from 60% to 95%. Additionally, the long-term outcome of a large group of Chinese patients with PM/DM is absent. Although Interstitial lung disease (ILD) and coexistent cancer were indicated to be predictors of mortality, few studies conducted multivariate regression analysis to provide independent prognostic factors, as well as the calculation of Standardized Mortality Ratio for PM/DM patients. Objectives To analyze the survival rate, cause of death and the prognostic outcome factors in idiopathic inflammatory myopathy (IIM). Methods A total of 201 IIM patients treated in Peking University Peoples Hospital from January 1996 to September 2013 were included. Medical records were abstracted for clinical, laboratory and therapeutic data. Results The follow-up time of 201 IIM patients, including 121 with DM, 33 with PM and 47 with CADM, ranged from one to 492 months, and 56 cases were lost to follow up. Overall cumulative survival rate was 93.0%, 87.0%, 86.0% and 84.0% at 1, 3, 5 and 10 years respectively from the disease onset. The rates were similar in DM, PM and CADM. During the follow-up period, 26 (19.3%) patients died, among which 21 cases died within 3 years from the onset. Respiratory failure associated with ILD was the main cause of death, followed by cardiac involvement and coexistent malignancy. Rapidly progressive ILD, myalgia, fever, abnormal ECG, normal CKMB, lymphopenia and hypoalbuminemia, elevated LDH and CEA were associated with mortality (P<0.05). In multivariate Cox regression analysis, elevated CEA was the significant predictor of poor outcome. Therapy with glucocorticoids combined with immunosuppressants for more than one year was negatively correlated with mortality, as well as methylprednisolone pulse therapy for patients with rapidly progressive ILD. Intravenous cyclophosphamide therapy was associated with a better survival than MTX. Conclusions The ten-year survival rate shows no statistically significant difference among DM, PM and CADM. The survival rate of patients with rapidly progressive ILD is significantly lower than patients with chronic or without ILD. Elevated CEA acts as the independent risk factor for poor prognosis. Glucocorticoids combined with immunosuppressants for more than one year is associated with high survival rate. Intravenous cyclophosphamide therapy is associated with a better survival than MTX. References Sultan SM, Ioannou Y, Moss K, Isenberg DA. Outcome in patients with idiopathic inflammatory myositis: morbidity and mortality. Rheumatology. 2002;41(1):22–6. Schiopu E, Phillips K, MacDonald PM, Crofford LJ, Somers EC. Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine. Arthritis research & therapy. 2012;14(1):R22. Danko K, Ponyi A, Constantin T, Borgulya G, Szegedi G. Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features: a longitudinal study of 162 cases. Medicine. 2004;83(1):35–42. Disclosure of Interest None declared