Liver-related long-term outcomes of thiazolidinedione use in persons with type 2 diabetes.

BACKGROUND & AIMS: Studies have described prominent histologic improvement in patients with nonalcoholic steatohepatitis (NASH) using thiazolidinedione (TZD); however, these were all short term with moderate sample size, no liver-related long-term outcomes could be noted. METHODS: This retrospective cohort study enrolled patients with newly diagnosed type 2 diabetes mellitus (T2DM) from Taiwan's National Health Insurance Research Database between 1 January 2000 and 31 December 2013. We matched TZD users and nonusers at a 1:1 ratio through propensity score matching. This study included 5095 paired TZD users and nonusers. Cox proportional hazard models were used to compare the risks of cirrhosis, hepatic decompensation, hepatic failure and all-cause mortality between TZD users and nonusers. The Kaplan-Meier method was used to compare the cumulative incidence of these main outcomes. RESULTS: The incidence rates of cirrhosis, hepatic decompensation, hepatic failure and all-cause mortality during follow-up were 0.77 vs 1.95, 1.43 vs 1.75, 0.36 vs 0.70, and 4.89 vs 3.78 per 1000 person-years between TZD users and nonusers. The adjusted hazard ratios of cirrhosis, hepatic decompensation, hepatic failure and all-cause mortality were 0.39 (95% confidence interval [CI]: 0.21-0.72), 0.86 (95% CI: 0.52-1.44), 0.46 (95% CI: 0.18-1.17) and 1.18 (95% CI: 0.87-1.61) respectively. CONCLUSIONS: Our study demonstrated that TZD use could significantly lower the risk of cirrhosis. In clinical settings, TZD use might be able to improve liver-related long-term outcomes.

Rheumatic diseases are associated with a higher risk of dementia: A nation-wide, population-based, case-control study.

AIM: Previous research demonstrated the possible relevance of dementia and rheumatic diseases. This population-based study aims to investigate the association of rheumatic diseases and dementia. METHODS: The data of this case-control study was extracted from the Taiwan National Health Insurance Research Database. Diagnosis of dementia and rheumatic diseases mentioned in this study were retrieved by the International Classification of Diseases-9 code. We recruited cases (n = 10 180) with dementia and controls (n = 61 080) during 2000-2010, by matching on age, gender and index date with a match ratio 1 : 6. The Chi-square test was used to calculate the baseline characteristics of the cases and controls for categorical variables such as age and gender. Simple conditional and multivariable conditional logistic regression models were used to estimate crude and adjusted odds ratios. RESULTS: Statistical significance was observed in Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and osteoarthritis (OA) among females (P < 0.05 for SS and SLE; P < 0.01 for OA), and in SS, psoriatic arthritis (PsA) and OA among males (P < 0.01 for SS; P < 0.05 for PsA and OA). Further, we also demonstrated a significant difference in SLE and OA among the younger group (age = 40-64) (P < 0.01 for SLE and OA), and in SS and OA among the older group (age â‰§ 65) (P < 0.01 for SS and OA). CONCLUSION: In this population-based case-control study, we found that patients with rheumatoid arthritis, SS, SLE, PsA and OA are significantly associated with a higher risk of dementia than those without rheumatic diseases. We hypothesized that inflammation and medications are two possible mechanisms.

Efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis: 52-week pooled results from two phase 3 studies.

AIM: To evaluate efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis (AS) via a pooled subgroup analysis from two phase 3 studies, MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375). METHODS: In MEASURE 1, patients were randomized to intravenous secukinumab 10 mg/kg or placebo at baseline, Weeks 2 and 4, followed by subcutaneous (s.c.) secukinumab 150 mg, 75 mg or placebo every 4 weeks (q4w) at Week 8. In MEASURE 2, patients were randomized to s.c. secukinumab 150 mg, 75 mg or placebo at baseline, Weeks 1, 2 and 3, and q4w starting at Week 4. Efficacy outcomes were SpondyloArthritis International Society (ASAS) 20/40, high-sensitivity C-reactive protein (hsCRP), ASAS5/6, Bath Ankylosing Spondylitis Disease Activity Index, Short Form-36 physical component summary, AS quality of life (QoL), ASAS partial remission, and Ankylosing Spondylitis Disease Activity Score - CRP at Weeks 16 and 52. Due to lack of efficacy, the secukinumab 75 mg dose in MEASURE 2 was excluded from this pooled Asian subgroup analysis. Safety analysis included patients who received ≥ 1 dose of study treatment. RESULTS: Of 517 patients enrolled into the MEASURE studies, 69 (13.3%) were Asians: 46 in pooled secukinumab and 23 in placebo. At Week 16, ASAS20/40 responses in Asian patients were 69.6%/43.5% with pooled secukinumab versus 26.1%/17.4% with placebo, which were comparable with rates reported in the overall study population. Secukinumab improved predefined efficacy endpoints at Week 16, with responses sustained through Week 52. Secukinumab was well tolerated in Asian patients, with a safety profile consistent with that reported in the overall study population. CONCLUSION: Secukinumab improved signs and symptoms, physical function, and disease-specific QoL in Asian patients with active AS.

Identification of RGS1 as a candidate biomarker for undifferentiated spondylarthritis by genome-wide expression profiling and real-time polymerase chain reaction.

OBJECTIVE: To compare gene expression profiles between ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) patients with inflammatory low back pain. METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with AS, patients with uSpA, and healthy subjects were screened using genome-wide microarrays, followed by validation by real-time polymerase chain reaction (PCR). RESULTS: Microarray profiling and real-time PCR assays showed only minor differences between AS patients and healthy subjects. In contrast, 20 genes were strikingly more highly expressed in uSpA patients. Regulator of G protein signaling 1 (RGS1) was identified as the most useful biomarker for distinguishing uSpA patients, and to a lesser extent AS patients, from control subjects (P = 2.3 x 10(-7) and 6.7 x 10(-3), respectively). These findings were verified in an independent cohort that also included patients with rheumatoid arthritis and patients with mechanical low back pain. The receiver operating characteristic area under the curve values in the first and second cohorts of uSpA patients were 0.99 and 0.93, respectively (P = 1 x 10(-4)). To evaluate the possible derivation of RGS1, we cultured a monocyte-derived cell line with a panel of cytokines and chemokines. RGS1 was significantly induced either by tumor necrosis factor alpha (TNFalpha) or by interleukin-17 (IL-17). CONCLUSION: Our findings indicate that uSpA PBMCs carry strikingly more highly expressed genes compared with PBMCs from AS patients or healthy subjects, and that TNFalpha- and IL-17-inducible RGS1 is a potential biomarker for uSpA, and to a lesser extent for AS, with inflammatory low back pain.

Serum reactivity against Borrelia burgdorferi OspA in patients with rheumatoid arthritis.

Lyme arthritis and rheumatoid arthritis share common clinical features and synovial histology. It is unclear whether they also share similar pathogenesis. Previous studies have shown that the severity and duration of Lyme arthritis correlate directly with serum concentrations of antibody against outer surface protein A (OspA) of the causative pathogen Borrelia burgdorferi. We tested the sera of 68 subjects with rheumatoid arthritis, 147 subjects with other autoimmune diseases, and 44 healthy subjects who had never had Lyme disease, as well as sera of 16 patients who had Lyme disease, for reactivity against the B. burgdorferi OspA protein. The sera of about a quarter of the rheumatoid arthritis patients and a 10th of the autoimmune disease and Lyme disease patients reacted against OspA antigen. Of 50 rheumatoid arthritis patients who could be evaluated for disease severity, a 28-joint count disease activity score of >2.6 was noted for 11 of 15 (73%) patients whose sera reacted against OspA antigen and 13 of 35 (37%; P < 0.05) whose sera were nonreactive. Serum reactivity against OspA antigen is associated with the pathogenesis of rheumatoid arthritis.