The British journal of dermatology
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Randomized Controlled Trial
Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials.
Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. ⋯ Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.
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Observational Study
MicroRNA-145-5p regulates fibrotic features of recessive dystrophic epidermolysis bullosa skin fibroblasts.
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder caused by mutations in the COL7A1 gene encoding type VII collagen, a cutaneous basement membrane component essential for epidermal-dermal adhesion. Hallmarks of the disease are unremitting blistering and chronic wounds with severe inflammation and fibrosis. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression also implicated in fibrotic processes. However, the role of miRNAs in RDEB fibrosis is almost unexplored. ⋯ Our results highlight the profibrotic role of miR-145-5p and its regulatory networks in RDEB, shedding light on novel disease pathomechanisms and targets for future therapeutic approaches. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB) is a highly disabling genetic skin disease caused by mutations in the collagen VII gene and characterized by unremitting blistering and defective wound healing, leading to inflammation and fibrosis. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression in health and disease, and their deregulation has been implicated in fibrotic skin conditions. To date, only miR-29 has been associated with injury-driven fibrosis in RDEB. What does this study add? In patients with RDEB, miR-145-5p is overexpressed in RDEB skin fibroblasts (RDEBFs), where it plays a profibrotic role, as its inhibition reduces RDEBF fibrotic traits (contraction, proliferation and migration). miR-145-5p inhibition in RDEBFs determines the reduction of contractile markers α-smooth muscle actin and transgelin through upregulation of Krüppel-like factor 4, a transcriptional repressor of contractile proteins, and downregulation of Jagged1 (JAG1), an inducer of fibrosis. What is the translational message? Our findings expand the knowledge on miRNA-driven pathomechanisms implicated in RDEB fibrosis. miR-145-5p and its targets (e.g. JAG1) could represent relevant molecules for the development of novel therapeutic strategies to counteract fibrosis progression in patients with RDEB.