Diamant Thaçi

Introduction. Despite the availability of effective biologic therapies for psoriasis, there is no gold-standard treatment for nonpustular palmoplantar psoriasis (ppPsO). Methods. G-PLUS, a phase IIIb, double-blind, placebo-controlled, multicentre clinical trial, randomised adults with moderate-to-severe nonpustular ppPsO and limited plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥3 but <10) to guselkumab (an interleukin-23p19 blocker) or placebo. Placebo participants were crossed over to receive guselkumab at week (Wk) 16. The primary efficacy endpoint was the proportion of participants achieving palmoplantar PASI (ppPASI) 75 response at Wk16; clinical, biomarker, and quality-of-life endpoints were assessed through Wk48 and safety through Wk56. Results. At Wk16, ppPASI75 response was achieved by 35.9% of the guselkumab participants compared with 28.2% in the placebo group, resulting in a 7.7% difference in response rates (95% confidence interval: −11.5 and 24.7), which was not statistically significant ( p = 0.533 ). More pronounced numerical improvements favouring guselkumab were observed for more stringent efficacy endpoints, such as Wk16 palmoplantar Investigator’s Global Assessment (ppIGA) 0/1 response (guselkumab 34.6% vs. placebo 15.4%). Through Wk48, further improvements were observed in ppPASI75 response (55.1% and 64.1%) and ppIGA 0/1 response (42.3% and 48.7%) for the guselkumab and placebo-crossover groups, respectively. Dermatology Life Quality Index responses showed comparable trends at both timepoints. Safety and pharmacodynamic findings were consistent with the established profile for guselkumab. Serum biomarker levels were significantly reduced with guselkumab and correlated with the baseline PASI score but not the ppPASI score. Conclusion. Although the primary endpoint was not met, analysis of stringent secondary endpoints and post hoc analyses showed numerical improvements favouring guselkumab at Wk16. There were no new safety signals. Further studies are warranted to better understand the impact of guselkumab treatment in patients with ppPsO. This trial is registered with NCT03998683.

Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases.