SummaryConcerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin (IL)‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I 2 statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10–4·63); anti‐IL‐17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09–11·09) or ustekinumab (OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.

Evidence of associations between co-trimoxazole-induced SJS/TEN and HLA alleles including HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01 were found in the study population. These findings may suggest that apart from the HLA molecules, other molecules involved in the molecular pathogenesis of these severe cutaneous adverse drug reactions may play an important role in the susceptibility of individuals to SJS/TEN caused by co-trimoxazole.

Slow acetylator status in the NAT2 genotype is a significant risk factor for DILI in Thai patients with TB. This evidence provides confirmatory data in support of the role of NAT2 in AT-DILI in the Thai population.

Background The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. Objectives To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. Methods Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis‐α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. Results We included 5468 biologic‐naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25–p75) follow‐up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16–3.21), 1.93 (1.05–3.34), 1.94 (1.09–3.32), 1.92 (0.93–3.45) and 1.43 (0.84–2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41–2.22); ustekinumab vs. adalimumab: 0.81 (0.30–2.17); etanercept vs. adalimumab: 0.81 (0.28–2.30)] and methotrexate against adalimumab [1.05 (0.34–3.28)]. Conclusions In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow‐up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.