Miaojia Zhang

Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate.

OBJECTIVE To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS In this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks. RESULTS After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T-614 therapy groups. Side effects in the T-614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T-614 groups. CONCLUSION Results indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.

Prognostic Indicators of Hospitalized Patients with Systemic Lupus Erythematosus: A Large Retrospective Multicenter Study in China

Objective. To investigate the mortality of hospitalized patients with systemic lupus erythematosus (SLE) and determine the influential factors associated with poor prognosis. Methods. Medical records of 1956 SLE inpatients from 15 hospitals during the period January 1, 1999, to December 31, 2009, were reviewed. All patients were followed up in January 2010. Potential factors associated with mortality were analyzed, comparing patients who were living with those who were deceased. The independency of those factors significantly related to death was determined by Cox regression analysis. Results. Male to female ratio was 1:15 in this cohort; median age at disease onset was 30 years. Hematologic (70.0%), mucocutaneous (68.2%), musculoskeletal (57.9%), and renal (48.7%) involvements were most often seen in these patients at time of admission. The overall mortality was 8.5% (n = 166), with infection (25.9%), renal failure (19.3%), and neuropsychiatric lupus (18.7%) the leading 3 causes of death. Independent predictors for mortality in this cohort of SLE patients were neuropsychiatric involvement [hazard ratio (HR) 2.19], anemia (HR 1.69), SLEDAI score > 8 at discharge (HR 1.64), increased serum creatinine (HR 1.57), low serum albumin (HR 1.56), cardiopulmonary involvement (HR 1.55), and patient untreated before admission (HR 1.48), whereas the use of antimalarial drugs (HR 0.62) and positive anti-Sm antibody (HR 0.60) were shown to be protective factors. Conclusion. SLE patients with delayed treatment and refractory disease have poorer prognosis. A high incidence of death would be expected if they have neuropsychiatric involvement, anemia, azotemia, or cardiopulmonary involvement. Combination therapy with antimalarial drugs may provide some benefit to patients with SLE.

Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus.

We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P < 0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P < 0.05). Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P < 0.05). Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

Primary Sjögren Syndrome in Han Chinese: Clinical and Immunological Characteristics of 483 Patients

AbstractThe epidemiological characteristics of Sjögren syndrome (SS) are significantly varied in different countries. We conducted the present study to survey the epidemiological characteristics of primary SS in China. We recruited 483 primary SS patients from 16 Chinese medical centers nationwide from January 2009 to November 2011 and assessed salivary and lacrimal gland dysfunction, organ involvement, and autoimmunity in these patients. The cohort included 456 women and 27 men (ratio, 17:1; mean age at onset, 42 ± 11 years; median age at diagnosis, 49 years; range, 41–56 years). Male patients showed a lower frequency of xerophthalmia (37.0% vs 60.7%) and a higher frequency of arthritis (40.7% vs 16.4%). Young-onset patients showed a higher frequency of low C3 levels (57.7% vs 36.3%) and pancytopenia (22.2% vs 8.8%). Patients with systemic involvement had a higher frequency of immunoglobulin A (IgA) (39.4% vs 22.5%) and immunoglobulin M (IgM) (12.4% vs 37.9%). Patients with pulmonary involvement had a higher parotid enlargement (21.4% vs 10.2%), purpura (12.1% vs 5.7%) and higher anti-La/SS-B (61.7% vs 41.8%), immunoglobulin G (IgG) (80.7% vs 64.6%) and IgA (48.9% vs 30.6%) levels. Patients with anti-Ro/SSA antibodies had more frequent exocrine gland symptoms and some extraglandular symptoms and immunological alterations. Compared with previous studies performed in other countries, SS patients in China showed particular clinical manifestation, systemic involvement, and immunological alterations.

Prognosis for Hospitalized Patients with Systemic Lupus Erythematosus in China: 5-Year Update of the Jiangsu Cohort

Objective To identify early signs associated with poor prognosis in Chinese patients with systemic lupus erythematosus (SLE) through a large population-based follow-up study. Methods Medical records of > 2,500 SLE patients that first hospitalized between 1999–2009 were collected from 26 centers across Jiangsu province, China, and entered into a database. These patients were followed-up for 5 to 15 years, and those remained contact and had known survival status in 2015 were assessed for the association of factors presented at the initial hospitalization with mortality at two time points (≤1year and > 1year). The independency of mortality factors was evaluated using multivariate Cox regression analysis. Results Among 1,372 patients we assessed, 92.3% were women and 17.2% were deceased in 2015. The main causes of death were infection (30.1%), neuropsychiatric impairment (14.8%), renal failure (14.4%) and cardiopulmonary involvement (8.5%). Hazard ratios (HR) of independent predictors for mortality (≤1year and > 1year, respectively) included hospital presentation of neuropsychiatric involvement (2.03 and 1.91), cardiopulmonary involvement (1.94 and 1.61) and increased serum creatinine (2.52 and 2.58). Patients older than 45 years and with disease durations more than 2 years at admission had unfavorable short-term outcome (HR 1.76 and 1.79), while the presence of anti-dsDNA and anti-Sm antibodies indicated diverse prognosis after 1 year (HR 1.60 and 0.45). Treatment with cyclophosphamide was beneficial for patient’s first-year outcome (HR 0.50), and anti-malarial drugs significantly reduced the risk of mortality over different time points (HR 0.48 and 0.54). SLEDAI score, proteinuria or hypocomplementemia was not independently associated with the outcome in this cohort. Conclusion SLE patients presented with vital organ damages rather than active disease at initial hospitalization are likely to have a poor outcome, especially for those with neuropsychiatric, cardiopulmonary involvements and renal insufficiency. Early and effective intervention with the use of anti-malarial drugs may decrease mortality.

Safety of infliximab therapy in rheumatoid arthritis patients with previous exposure to hepatitis B virus

To evaluate the safety of tumor necrosis factor‐α (TNF‐α) monoclonal antibody (infliximab) therapy in patients with rheumatoid arthritis (RA) and previous exposure to hepatitis B virus (HBV) who had normal liver function.

Chinese SLE Treatment and Research Group (CSTAR) registry:VIII. Influence of socioeconomic and geographical variables on disease phenotype and activity in Chinese patients with SLE.

The aim of this study was to estimate the influence of socioeconomic and geographical variables on disease phenotype and activity of systemic lupus erythematosus (SLE) in a Chinese population.

AB0415 High expression of gitr in serum and labial salivary glands from patients with primary sjögren’s syndrome

Objectives Glucocorticoid-induced TNFR-related (GITR) is a gene coding for a member of the TNF receptor superfamily. After activated by its ligand GITRL, GITR could influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases included rheumatoid arthritis and autoimmune thyroid disease. We previously reported that serum GITRL levels are increased in SLE patients compared with healthy controls (HC)[1]. Here, we tested the levels of GITR and GITRL in serum and labial salivary glands from patients with primary Sjögren’s syndrome (SS), and investigated correlation of their expression levels with clinical and laboratory variables. Methods Serum GITR and GITRL levels in 30 primary SS patients and 30 healthy controls were measured by ELISA. Patients were assessed for clinical and laboratory variables. GITR and GITRL levels in labial salivary glands were detected by immunohistochemistry. Results Primary SS patients had significantly increased serum levels of soluble GITR and GITRL compared with controls [GITR:(5.65±3.43) ng/ml vs. (0.33±0.24) ng/ml, p<0.001; GITRL:(10.90±7.60)ng/ml vs. (0.36±0.28)ng/ml, p<0.001)]. Serum GITR and GITRL levels were positively correlated with IgG and ESR. More lymphocytes infiltration could be detected in SS patients compared to HC by Immunohistochemical analyses. Moreover, the expression levels of GITR in lymphocytic foci of the labial salivary glands from SS patients are higher than those in HC. However, GITRL expression was failed to be detected both in SS patient and HC. Conclusions High serum GITR and GITRL levels in SS patients were associated disease activity variables included IgG and ESR, and the expression of GITR was increased along with more lymphocytes infiltration in labial salivary glands, suggesting an important role of GITR and GITRL in the pathogenesis of primary SS pathogenesis. References Lei Gu, Lingxiao Xu, et al. Correlation of Circulating Glucocorticoid-Induced TNFR-Related Protein Ligand Levels with Disease Activity in Patients with Systemic Lupus Erythematosus. Clin. Dev. Immunol.2012,2012:265868 Disclosure of Interest None Declared