Association of antimalarial drugs with decreased overall and cause specific mortality in systemic lupus erythematosus.

OBJECTIVE: To evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. METHODS: Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. RESULTS: We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. CONCLUSION: Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.

Cyclophosphamide could be a better choice than methotrexate as induction treatment for patients with more severe Takayasu's arteritis.

To assess the effectiveness of cyclophosphamide (CYC) versus methotrexate (MTX) for active Takayasu's arteritis (TA). The current study was based on a cohort of TA at Zhongshan Hospital, Fudan University. TA was diagnosed using the 1990 American College of Rheumatology criteria. Fifty-eight subjects receiving induction treatment with CYC (n = 46) or MTX (N = 12) were included in the analysis. Effectiveness and toxicity were assessed in all 58 cases. Clinical remission was defined as: Kerr score reduction to ≤ 1 and glucocorticoids (GC) treatment at a dose of ≤ 0.2 mg/kg/day (≤ 15 mg/day) at the end of the 6th month. At the baseline, the CYC group had higher Kerr scores (60.9% vs. 16.7% at ≥3, p = 0.044), higher ESR (55 ± 52 vs. 25 ± 22 mm/H, p = 0.048), ITAS_ESR (12.4 ± 1.7 vs. 9.1 ± 1.1 mg/L, p = 0.043). The 6-month clinical remission rate was 71.7% vs. 75% in the CYC and MTX group, respectively. In the CYC group, a significant decrease was observed in ESR (55 ± 52 vs. 25 ± 48 mm/H, p = 0.008), hs-CRP (27 ± 23 vs. 6.9 ± 6.6 mg/L, p = 0.007), ITAS (11.7 ± 2.2 vs. 7.0 ± 1.5, p = 0.048), and ITAS_ESR (7.1 ± 2.0 vs. 12.4 ± 1.7, p = 0.033). However, no significant reductions in these measures were demonstrated in the MTX group. Whole-body contrast enhanced magnetic resonance angiography (MRA) revealed significant radiologic improvement (wall enhancement scores: 4.2 ± 2.3 vs. 10.3 ± 3.8, p = 0.032) in the CYC group, but not in the MTX group. No severe adverse events occurred in any subject. Cyclophosphamide could be a better choice than methotrexate as induction treatment for patients with more severe Takayasu's arteritis.

Determination of Anticyclic Citrullinated Peptide Based on Biotin-Streptavidin-Amplified Time-Resolved Fluoroimmunoassay.

BACKGROUND: A rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) based on the biotin-streptavidin amplification system was developed for the determination of anticyclic citrullinated peptide (anti-CCP). METHODS: Europium-labeled streptavidin derivatives combined with europium and anhydride of diethylene triamine pentaacetic acid were used to label streptavidin, biotin was coupled with rabbit anti-human IgG to form a biotin-anti-human IgG bridge between streptavidin-europium and the anti-CCP antibody in the immunoassay. The anti-CCP assay was carried out by measuring the fluorescence of Eu(3+) -streptavidin at 615 nm. RESULTS: The presented method produced a wide linear range from 0.58 to 9,463 U/ml, while it was only 591.4-18.48 U/ml when using an ELISA kit, and featured a detection limit up to 0.5 U/ml for anti-CCP. The values determined by the biotin-streptavidin-TRFIA and ELISA correlated well (R(2) = 0.8927). The method was applied to determine anti-CCP in serum samples with satisfied recoveries of 96.45-104.63%. CONCLUSION: The assay results obtained by the present method showed that biotin-streptavidin-amplified TRFIA improve the traditional ELISA kit for anti-CCP detection. Therefore, it offers a better alternative immunoassay in rheumatoid arthritis management.

Detection of anti-cyclic citrullinated peptide using a time-resolved fluoroimmunoassay.

In an effort to enhance the linear range of anti-CCP we developed a new immunoassay based on time-resolved fluoroimmunoassay. The precision, sensitivity, specificity, and stability of the assay were evaluated ELISA set as control. The anti-CCP IgG TRFIA kit we established had a wider detectable range than commercial ELISA ones. With regard to intra- and inter-assay precision, the TRFIA kit was better than threee commercial ELISA ones. The mean recovery rate was 101.0%. The TRFIA we developed for anti-CCP IgG detection yielded a more sensitive and reliable method for RA diagnosis and large-scale screening programs as well.

[Clinical features and prognosis of patients with lupus nephritis].

OBJECTIVE: To explore the clinical features and prognosis of patients with lupus nephritis (LN) in a large multicenter lupus cohort of Jiangsu Province. METHODS: Medical records of 2 078 systemic lupus erythematosus (SLE) inpatients from 15 hospitals at the first admission from 1999 to 2012 were reviewed and classified into two groups with LN or without. The clinical features between two groups were compared with Mann-Whitney U or Chi-square test and potentially associated factors tested by Cox regression. RESULTS: A total of 883 (42.5%) hospitalized lupus patients were diagnosed as LN. And the median age at disease onset of LN patients was lower than that of those without LN [(30 ± 11) vs (32 ± 12) years, P < 0.01]. Cardiopulmonary involvement, neuropsychiatric disorder, gastrointestinal dysfunction, hematologic disease, ophthalmopathy, SLEDAI score > 9 at admission and SLE disease activity index (SLEDAI) score > 9 at discharge were more often seen in patients with LN compared to those without LN (31.5%, 7.9%, 13.9%, 69.0%, 1.5%, 77.4%, 29.8% vs 18.8%, 5.1%, 6.8%, 63.1%, 0.3%, 43.1%, 8.1%, all P < 0.01). The mortality rates at 1 or 5 years after first admission were both significantly higher in LN patients than those without LN (7.2%, 15.0% vs 3.1%, 6.3%, P < 0.01). Independent predictors for mortality in patients with LN were neuropsychiatric involvement[hazard ratio (HR) 2.46], SLEDAI score > 9 at discharge (HR 2.34), increased serum creatinine (HR 2.21) and elevated alanine aminotransferase and (or) aspartate transaminase (HR 2.09) whereas glucocorticosteroid therapy (HR 0.18) was a protective factor. CONCLUSION: LN is one common complication of SLE patients during an early stage. And LN patients are more prone to present other vital organ involvement, higher disease activity and worse treatment outcomes. When accompanied with neuropsychiatric involvement, increased serum creatinine or elevated transaminase, worse prognosis is expected. Glucocorticosteroid treatment may offer some benefits.

A hypersensitive biotin-avidin-TRFIA for quantitative detection of ANA-Ig(GAM) and its clinical application.

We demonstrate herein a novel time-resolved fluoroimmunoassay (TRFIA) with high sensitivity and wide range for quantitative detection of ANA-Ig(GAM) antibodies using a biotin-avidin amplification system. The immunoassay was conducted by following procedures for a typical sandwich immunoreactions with cell nucleus form Hela and the Eu(3+)-labeled biotin combined with biotinylated mouse anti-human Ig(GAM) served as the solid nuclear antigen for ANA and the tracer, respectively. The sensitivity, specificity, and stability of the kit were evaluated and comparison with the classical enzyme-linked immunosorbent assay (ELISA) kit was also made. The average intra-assay and interassay CVs detected by the established ANA-Ig(GAM) biotin-avidin-TRFIA were 4.21% and 6.34%, respectively. The lower detection limit was 2.24 U/mL, and the mean recovery rate was 100.74%. The good measurable range of the established biotin-avidin-TRFIA was within 1.95-64,000 U/mL, while it was only within 32.5-4000 U/mL using an ELISA kit. The values determined by the biotin-avidin-TRFIA and ELISA correlated well (R2 = 0.989). The positive rate of healthy volunteers and patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary biliary cirrhosis (PBC), Sjögren's syndrome (SS), scleroderma, and mixed connective tissue disease (MCTD) was 0, 100%, 18.5%, 100%, 37.9%, 90.9%, and 92%, respectively. We conclude that the biotin-avidin-TRFIA we developed gives promise for greater sensitivity and accurate detection for ANA-Ig(GAM) in diagnosing and monitoring autoimmune disorders.

Comparison of Contributors to Mortality Differences in SLE Patients with Different Initial Disease Activity: A Larger Multicenter Cohort Study.

To explore the etiology of risk factors and quantify the mortality differences in systemic lupus erythematosus (SLE) patients with different initial disease activity. The Jiangsu Lupus database was established by collecting medical records from first-hospitalized SLE patients during 1999-2009 from 26 centers in Jiangsu province, China, and their survival status every five years. The initial SLEDAI scores [high (>12) vs. low-moderate (≤12)] differences in mortality attributable to risk factors were quantified using population attributable fraction (PAF), relative attributable risk (RAR) and adjusted relative risk (ARR). Among 2446 SLE patients, 83 and 176 deaths were observed in the low-moderate and high activity groups, with mortality rates of 7.7 and 14.0 per 1000 person years, respectively. Anemia was the leading contributor to mortality, with PAFs of 40.4 and 37.5 in the low-moderate and high activity groups, respectively, and explained 23.2% of the mortality differences with an ARR of 1.66 between the two groups. Cardiopulmonary involvement caused the highest PAFs in the low-moderate (20.5%) and high activity (13.6%) groups, explaining 18.3% of the mortality differences. The combination of anemia and cardiopulmonary involvement had the highest RAR, causing 39.8% of the mortality differences (ARR = 1.52) between the two groups. In addition, hypoalbuminemia and a decrease in the creatinine clearance rate accounted for 20-30% of deaths and explained 10-20% of the mortality differences between the two groups, while antimalarial drug nonuse accounted for about 35% of deaths and explained 3.6% of the mortality differences. Anemia, cardiopulmonary involvement and hypoalbuminemia may cause substantial mortality differences across disease activity states, suggesting additional strategies beyond disease activity assessment to monitor SLE outcomes.

Low dosage use of cyclophosphamide improves the survival of patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the effect of cyclophosphamide (CYC) on organ involvement and SLE patients' overall and cause-specific mortality. METHODS: Information about CYC prescription was taken from the Jiangsu Lupus database, which was set up to collect medical records from SLE patients since their first admission during 1999-2009 in Jiangsu province, China. Follow-up studies were carried out in 2010 and 2015 to check the survival status of the patients. Cox regression models were used to estimate the hazard ratio (HR) and 95% CI. Kaplan-Meier model was used to assess the effect of CYC on mortality between organ involvement and non-involvement. RESULTS: There were 221 deaths observed out of 2446 SLE patients. CYC users decreased overall mortality of SLE (8.4%) with adjusted HR (95% CI) of 0.74 (0.56-0.97), as compared to non-users. A decrease in overall mortality of SLE was found in the low dosage (< 600 mg) of CYC users, with adjusted HR (95% CI) of 0.54 (0.36-0.81). The protection of CYC on mortality of SLE was further observed in subgroups, such as female; SLEDAI score ≥ 15 group; and those with neuropsychiatric, renal, and hematological involvements, and low serum C3. In addition, CYC could eliminate the differences in mortality between organ involvement and non-involvement, including renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological involvement, but not for mucocutaneous and musculoskeletal involvement. CONCLUSION: Low dosage use of CYC decreased the risk of overall mortality of SLE. CYC might improve the survival of SLE patients with renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological involvements. Key Points • Cyclophosphamide decreases overall mortality of SLE patients. • Decreased mortality is mainly observed from low dosage use of cyclophosphamide. • Cyclophosphamide improves the survival of SLE patients when major systems such as renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological are involved.

Clinical and laboratorial outcome of different age-onset systemic lupus erythematosus patients in Jiangsu, China: a multicentre retrospective study.

Studies on clinical features of systemic lupus erythematosus among different age-onset patients are lacking in China. This multicentre study aimed to systemically compare clinical manifestations, comorbidities, organ involvement, and laboratory findings among 797 Chinese juvenile-onset, adult-onset, and late-onset SLE (JSLE, ASLE, and LSLE) patients. They were classified into JSLE, ASLE, and LSLE groups if first diagnosed at < 18, 18-50, and > 50 years old, respectively. Chi-square test and analysis of variance were employed for categorical and continuous variables respectively. In younger-onset patients, the SLE Disease Activity Index 2000 score was significantly higher (JSLE vs. ASLE vs. LSLE = 17.43 ± 9.139 vs. 16.34 ± 8.163 vs. 14.08 ± 6.474, p = 0.031). Mucocutaneous symptoms (79.5% vs. 73.4% vs. 62.0%, p = 0.042), especially malar rash (76.1% vs. 66.1% vs. 53.5%, p = 0.011) occurred more frequently, and proteinuria rate was higher (54.5% vs. 56.3% vs. 36.6%, p = 0.007). In later-onset patients, cardiopulmonary involvement increased (11.4% vs. 24.3% vs. 29.6%, p = 0.012). In ASLE, hypoalbuminemia rate elevated (46.6% vs. 59.9% vs. 47.9%, p = 0.015). Our study demonstrated in a Chinese population that JSLE may be more active and suffer mucocutaneous disorders, while LSLE tended to suffer cardiopulmonary involvement at-onset. These findings may help identify treatment priorities when facing different age-onset SLE patients.

Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort.

OBJECTIVES: To analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index (SLEDAI). METHODS: A total of 1069 adult systemic lupus erythematosus (SLE) patients who were hospitalized for the first time in 26 hospitals in Jiangsu Province from 1999 to 2009 were retrospectively analyzed. SLEDAI decrease ≥ 4 during hospitalization was identified as IDA. Relative factors of IDA were assessed by univariate and multivariate logistic regression. RESULTS: A total of 783 (73.2%) adult SLE patients showed IDA after the first hospitalization, while the remaining patients (n = 286) were in the non-IDA group. The IDA group had higher SLEDAI at admission; fewer patients had SLICC/ACR damage index (SDI) ≥ 1, comorbidities at admission, especially Sjögren's syndrome, abnormal serum creatinine, and glomerular filtration rate. More patients had mucocutaneous and musculoskeletal involvements, leukopenia, increased C-reactive protein, anti-dsDNA antibody positive, and hypocomplementemia at admission and were treated with methotrexate and leflunomide during hospitalization. After multivariate logistic regression analysis, SDI ≥ 1 (P = 0.005) and combined with Sjögren's syndrome (P < 0.001) at admission had negative association with IDA. Musculoskeletal involvement (P < 0.001), anti-dsDNA antibody positive (P = 0.012), hypocomplementemia (P = 0.001), and use of leflunomide (P = 0.030) were significantly related with IDA. CONCLUSION: Organ damage or comorbidities at admission were adverse to SLE improvement. Anti-dsDNA antibody positive, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment had positive association with IDA of SLE. Key Points • Organ damage or comorbidities at admission were negatively correlated with SLE improvement. • Anti-dsDNA antibody positivity, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment were positively associated with SLE improvement.

Development and Verify of Survival Analysis Models for Chinese Patients With Systemic Lupus Erythematosus.

Background: The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status. Methods: In this study, based on 1999-2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients' survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression. Results: The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment. Conclusions: The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Creatinine clearance rate predicts prognosis of patients with systemic lupus erythematosus: a large retrospective cohort study.

OBJECTIVE: To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). METHODS: We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59-3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02-3.19) and 6.84 (3.05-15.36). CONCLUSIONS: A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival. Key points • Decreasing creatinine clearance rate (Ccr) was positively associated with an overall mortality of SLE patients, with a dose-response relationship. • Moreover, decreasing Ccr was associated with elevated mortality primarily due to infection and renal failure.

The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

Efficacy and safety of leflunomide treatment in Takayasu arteritis: Case series from the East China cohort.

OBJECTIVE: To evaluate the efficacy and safety of leflunomide (LEF) as induction treatment in a series of Takayasu arteritis (TA) patients based on a Chinese cohort. METHOD: Fifty-six patients from the East China TA cohort treated with LEF for at least 3 months were enrolled in this study, including the naïve LEF treatment patients (n = 41) and the cyclophosphamide (CYC)-resistant LEF treatment patients (n = 15). Data in clinical features, NIH score and angiography were collected. Response to treatment was assessed by rates of complete remission (CR) and partial remission (PR) and response rate (RR) after 6 and 12 months of treatment. RESULTS: The total CR rate and RR were 67.86% and 83.93% after 6 months, and 55.36% and 69.64% after 12 months, respectively. ESR and CRP levels and NIH scores decreased significantly after 12 months of LEF treatment (P < 0.05). Patients of CYC-resistant switched to LEF and reached the CR of 60.00% (9/15) and RR of 86.67% (13/15) after 6 months, and 73.33% (11/15) and 80.00% (12/15) after 12 months, respectively, with decrease in NIH scores (all P < 0.05). After following up for 14.44 ± 6.86 months, 48 patients (85.71%) continued LEF treatment with good tolerance. One patient died from progression of TA after 2 months, 2 patients relapsed, and 3 patients with side effects were switched to other immunosuppressive agents. CONCLUSIONS: LEF led to a quick induction and sustained remission of TA, especially in refractory cases, and therefore, should be considered as an alternative treatment for TA.

Analysis of predictive factors for treatment resistance and disease relapse in Takayasu's arteritis.

The objective of the study was to investigate the long-term treatment effects and predictive factors for treatment response and disease relapse for Takayasu's arteritis (TA). Eighty-one patients were recruited from the Department of Rheumatology, Zhongshan Hospital, Fudan University, between January 2009 and January 2015. The follow-up duration ranged from 6 to 36 months. Patients were divided into three groups: clinical remission (CR; n = 59); treatment-resistant (TR; n = 11); and disease relapse (DR; n = 11). Signs/symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging items were recorded at baseline and at each visit. Kerr's criteria, physician's global assessment, and Indian Takayasu Clinical Activity Score (ITAS2010) were used to evaluate disease activity. Incipient disease was more common in CR patients compared with DR cases (69.49 vs. 36.36%, p = 0.05). Fewer patients aged < 40 years were in the CR group in comparison with the DR group (57.63 vs. 90.91%, p = 0.04). In TR patients, high CRP levels (63.74 vs. 23.73%, p = 0.01) and aortic arch involvement (70.00 vs. 24.14%, p < 0.01) were more common in comparison with CR cases. Patients with high CRP levels (> 25 mg/L) (OR = 1.61, p = 0.03) carried a higher risk for treatment resistance. Age > 40 years (OR = - 2.82, p = 0.03), incipient disease (OR = - 2.47, p = 0.01), and treatment with cyclophosphamide (OR = - 2.07, p = 0.03) and hydroxychloroquine (OR = - 1.91, p = 0.05) could prevent disease relapse. Patients with high CRP levels carry a high risk of treatment resistance. In patients with incipient disease, aged > 40 years, treatment with cyclophosphamide and hydroxychloroquine protects against disease relapse.

Genetic predictors of efficacy and toxicity of iguratimod in patients with rheumatoid arthritis.

Iguratimod (IGU) is a novel disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). Like other DMARDs, IGU exhibited significant differences in effectiveness and safety. AIM: The aim of this study was to identify genetic predictorsof efficacyand toxicity of IGU in patients with RA. MATERIALS & METHODS: Seven SNPs from IGU-metabolizing genes were genotyped in 272 IGU-treated patients with RA. Results: ABCG2 rs2231142 A allele conferred a higher response to IGU, while NAT2 rs1495742 G carriersconferred a lower response to IGU. CYP2C19*2 rs4244285 A carriers had higher risk for IGU-induced toxicity compared to the GG carriers. CONCLUSION: Our study suggests that the polymorphisms of ABCG2 (rs2231142), NAT2 (rs1495741)and CYP2C19*2 (rs4244285) may help to predict thetherapeutic effectiveness and toxicity of IGU in patients with RA.

Smoking quantity determines disease activity and function in Chinese patients with ankylosing spondylitis.

The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

Clinical patterns and characteristics of ankylosing spondylitis in China.

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P < 0.05). The clinical patterns of our AS patients were similar to those in other studies in non-Chinese cohort: (1) the age at onset was 29.2 (11.4) years, which was older than found in other studies; (2) men were more likely be HLA-B27 carriers than women; and (3) AAU was less common in Chinese patients.