Changes in lipid levels and incidence of cardiovascular events following tofacitinib treatment in patients with psoriatic arthritis: a pooled analysis acrossphase III and long‐term extension studies

Objective: The risk of cardiovascular disease (CVD) is higher in patients with psoriatic arthritis (PsA) compared to the general population. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Because tofacitinib increases circulating lipid levels in some patients, we evaluated CVD risk factors and major adverse cardiovascular events (MACE) in patients with active PsA receiving tofacitinib 5 or 10 mg twice daily plus conventional synthetic disease‐modifying antirheumatic drugs. Methods: Data were pooled from 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond]) and 1 ongoing long‐term extension (Open‐Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance], data cutoff January 2017; database not locked). Outcomes included fasting lipid levels, blood pressure, hypertension‐related adverse events (AEs; including hypertension, high blood pressure, and increased blood pressure), and MACE. Results: Overall, 783 tofacitinib‐treated patients were included. Percentage increases from baseline in low‐density lipoprotein cholesterol (LDL‐c) and high‐density lipoprotein cholesterol (HDL‐c) levels ranged from 9% to 14% for tofacitinib 5 mg and 10 mg at 3 and 6 months; no meaningful changes in LDL‐c:HDL‐c or total cholesterol:HDL‐c ratios were observed. Blood pressure remained stable for 24 months. Fifty‐eight patients (7.4%) had hypertension‐related AEs; none were fatal (incidence rate [IR] per 100 patient‐years 4.81 [95% confidence interval (95% CI) 3.65–6.22]). Five patients (0.6%) had MACE (IR 0.24 [95% CI 0.05–0.70]); 2 were fatal. Conclusion: Serum lipid level increases at month 3 following tofacitinib treatment in PsA were consistent with observations in rheumatoid arthritis and psoriasis. The IR of hypertension‐related AEs and MACE was low; long‐term follow‐up is ongoing

Introduction to skin aging

YesCutaneous science has seen considerable development in the last 25 years, in part due to the -Omics revolution, and the appreciation that this organ is hardwired into the body’s key neuroimmuno- endocrine axes. Moreover, there is greater appreciation of how stratification of skin disorders will permit more targeted and more effective treatments. Against this has been how the remarkable extension in the average human life-span, though in the West at least, this parallels worrying increases in lifestyle-associated conditions like diabetes, skin cancer etc. These demographic trends bring greater urgency to finding clinical solutions for numerous age-related deficits in skin function caused by extrinsic and intrinsic factors. Mechanisms for aging skin include the actions of reactive oxygen species (ROS), mtDNA mutations, and telomere shortening, as well as hormonal changes. We have also significantly improved our understanding of how to harness the skin’s considerable regenerative capacity e.g., via its remarkable investment of stem cell subpopulations. In this way we hope to develop new strategies to selectively target the skin’s capacity to undergo optimal wound repair and regeneration. Here, the unsung hero of the skin regenerative power may be the humble hair follicle, replete with its compliment of epithelial, mesenchymal, neural and other stem cells. This review introduces the topic of human skin aging, with a focus on how maintenance of function in this complex multi-cell type organ is key for retaining quality of life into old age