Benefits of tumor necrosis factor inhibitors for cardiovascular disease in ankylosing spondylitis.

Ankylosing spondylitis (AS) has been associated with an increased cardiovascular disease (CVD) risk, with current guidelines recommending multiple CVD-related risk assessment strategies. CVD risk prediction using a scoring model with lipids might be another promising alternative, for which ultrasound screening for subclinical atherosclerosis may be considered together with surrogate markers. Theoretically, tumor necrosis factor inhibitors (TNFi), which are known to inhibit endothelial activation and inflammation caused by the disease and underlying metabolic dysfunction, might prevent microvascular events. In this narrative review, we summarized the evidence of TNFi effects on CVD in AS. Although early case reports revealed that CVD occurred during TNFi treatment, more recent evidence shows that it could be successfully treated. Studies of TNFi on lipid changes and subclinical atherosclerosis have shown controversial results, possibly due to genetic predisposition, differences in affinity for membrane-bound TNF leading to insufficient inhibition of inflammation or primary failure response to TNFi, and not enough follow-up time to identify potential significance. Overall, patients vulnerable to CVD could benefit from long-term administration of TNFi when inflammation is under control. Besides healthy lifestyle modification, traditional CVD risk factors and metabolic syndrome-related diseases should be further assessed and treated if necessary.

Human papillomavirus symptomatic infection associated with increased risk of new-onset alopecia areata: A nationwide population-based cohort study.

BACKGROUND: We investigated the correlation between a history of human papillomavirus (HPV) infection and alopecia areata risk. METHODS: The study cohort comprised 30,001 patients with newly diagnosed HPV infection between 2000 and 2012; and with use of computer-generated randomly numbers, patients not had HPV infection were randomly selected as the comparison cohort. HPV infection cohort were matched to comparison individuals at a 1:1 ratio by age, gender and index year. All study individuals were followed up until they developed alopecia areata, withdraw from the insurance program, lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of alopecia areata with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted hazard ratio (aHR) of alopecia areata for HPV patients relative to controls was 2.55 (95% C.I. = 1.88-3.47) after adjusting sex, age and comorbidities. Subgroup analysis indicated that patients with HPV infections had a significantly greater risk of alopecia areata for both genders, all age subgroups, and those with mental disorder diseases. CONCLUSIONS: A history of HPV infection is associated with the development of subsequent alopecia areata in Taiwanese subjects.

Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial.

BACKGROUND: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. METHODS: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. FINDINGS: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. INTERPRETATION: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. FUNDING: Eli Lilly and Company.

Epigallocatechin gallate attenuates amyloid ß-induced inflammation and neurotoxicity in EOC 13.31 microglia.

Microglia are the primary immune cells that contribute to neuroinflammation by releasing various proinflammatory cytokines and neurotoxins in the brain. Microglia-mediated neuroinflammation is one of the key characteristics of Alzheimer's disease (AD). Therefore, inhibitory reagents that prevent microglial activation may be used as potential therapeutic agents for treating AD. Recently, many studies have been performed to determine the bioactivities of green tea polyphenol epigallocatechin-3-gallate (EGCG), an efficient antioxidant that prevents neuroinflammation. However, limited information is available on the effects of EGCG on microglia-mediated neuroinflammation. In this study, we investigated the inhibitory effects of EGCG on amyloid ß (Aß)-induced microglial activation and neurotoxicity. Our results indicated that EGCG significantly suppressed the expression of tumor necrosis factor α (TNFα), interleukin-1ß, interleukin-6, and inducible nitric oxide synthase (iNOS) in Aß-stimulated EOC 13.31 microglia. EGCG also restored the levels of intracellular antioxidants nuclear erythroid-2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thus inhibiting reactive oxygen species-induced nuclear factor-κB (NF-κB) activation after Aß treatment. Furthermore, EGCG effectively protected neuro-2a neuronal cells from Aß-mediated, microglia-induced cytotoxicity by inhibiting mitogen-activated protein kinase-dependent, Aß-induced release of TNFα. Taken together, our findings suggested that EGCG suppressed Aß-induced neuroinflammatory response of microglia and protected against indirect neurotoxicity. These results suggest that EGCG is a possible therapeutic agent for preventing Aß-induced inflammatory neurodegeneration.