Research from JAMA Dermatology — Immunosuppressive Level and Other Risk Factors for Basal Cell Carcinoma and Squamous Cell Carcinoma in Heart Transplant Recipients

Background The phase 3 reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti–interleukin‐23p19 monoclonal antibody tildrakizumab for psoriasis treatment are complete. Objectives We present 5‐year pooled data from reSURFACE 1 and reSURFACE 2. Methods reSURFACE 1 and reSURFACE 2 were double‐blind, randomised, controlled studies with optional long‐term extensions. Adults with moderate‐to‐severe chronic plaque psoriasis were randomised 2:2:1 to tildrakizumab 100 (TIL100) or 200 mg (TIL200) or placebo at weeks 0 and 4, and every 12 weeks thereafter (reSURFACE 2 included an etanercept arm). Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in tildrakizumab responders (≥75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and etanercept partial responders and nonresponders (PASI <75 response) switched to TIL200 at week 28. Safety was assessed from adverse events (AEs) in all patients as‐treated. Results Efficacy analyses included 329 and 227 week 28 responders to TIL100 and TIL200, respectively, and 121 etanercept partial responders/nonresponders switched to TIL200 at week 28. Of TIL100 or TIL200 responders and etanercept partial responders/nonresponders entering the extensions, 235/302, 176/213, and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5%, and 81·3%, respectively, achieved PASI 75 response. Exposure‐adjusted rates of serious AEs were 6·3 and 6·0 patients with events/100 patient‐years of TIL100 and TIL200, respectively. Conclusions Tildrakizumab treatment provided sustained disease control over 5 years in week 28 tildrakizumab responders and etanercept partial responders/nonresponders, with a reassuring safety profile.

Management of psoriasis in elderly patients can be challenging, because of the impairment of immune system efficiency and the presence of co...

A convincing deal of evidence supports the fact that severe psoriasis is associated with cardiovascular diseases. However, the precise underlying mechanisms linking psoriasis and cardiovascular diseases are not well defined. Psoriasis shares common pathophysiologic mechanisms with atherosclerosis and cardiovascular (CV) risk factors. In particular, polymorphism in the IL-23R and IL-23 genes, as well as other genes involved in lipid and fatty-acid metabolism, renin–angiotensin system and endothelial function, have been described in patients with psoriasis and with cardiovascular risk factors. Moreover, systemic inflammation in patients with psoriasis, including elevated serum proinflammatory cytokines (e.g., TNF-α, IL-17, and IL-23) may contribute to an increased risk of atherosclerosis, hypertension, alteration of serum lipid composition, and insulin resistance. The nonlinear and intricate interplay among various factors, impacting the molecular pathways in different cell types, probably contributes to the development of psoriasis and cardiovascular disease (CVD). Future research should, therefore, aim to fully unravel shared and differential molecular pathways underpinning the association between psoriasis and CVD.

Background: The genetics of syndromic hidradenitis suppurativa (HS), an immune-mediated condition associated with systemic comorbidities such as inflammatory bowel diseases and arthritis, has not been completely elucidated. Objective: To describe clinical features and genetic signature of patients with the main syndromic HS forms, i.e., PASH, PAPASH, and PASH/SAPHO overlapping. Methods: Whole-exome sequencing (WES) approach was performed in ten patients with syndromic HS. Results: Three clinical settings have been identified based on presence/absence of gut and joint inflammation. Four PASH patients who had also gut inflammation showed three different variants in NOD2 gene, two variants in OTULIN, and a variant in GJB2, respectively. Three PAPASH and three PASH/SAPHO overlapping patients who had also joint inflammation showed two different variants in NCSTN, one in WDR1 and PSTPIP1, and two variants in NLRC4, one of whom was present in a patient with a mixed phenotype characterized by gut and joint inflammation. Limitations: Limited number of patients that can be counterbalanced by the rarity of syndromic HS. Conclusion: Syndromic HS can be considered as a polygenic autoinflammatory condition; currently WES is a diagnostic tool allowing more accurate genotype-phenotype correlation.