Get access

Increased expression of IL-17A and limited involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised controlled trial

Authors


  • Conflicts of interest

    • Dr Bissonnette has been an Investigator, Advisory Board Member, Consultant and/or Speaker and has received grants and/or honoraria from Abbott, Amgen, Novartis, Janssen, Pfizer, Tribute, Eli Lilly, Merck, Astellas and Incyte.
    • Dr Nigen has been an Investigator, Advisory Board Member and/or Consultant and has received grants and/or honoraria from Abbott, Amgen, Novartis, Janssen, Pfizer, Tribute, Eli Lilly, Merck and Astellas.
    • Dr Langley has been an Investigator, Scientific Advisory Board Member and/or Speaker and has received grants and/or honoraria from Amgen, Janssen, Abbott, Biogen-Idec, Centocor/Schering-Plough, EMD Serono, MedImmune, Astellas, Boehringer-Ingelheim, Pfizer, Celgene, Eli Lilly, Genentech and Novartis.
    • Dr Lynde has been an Investigator, Advisory Board Member, Consultant and/or Speaker and has received grants and/or honoraria from Abbott, Amgen, Astellas, Janssen, Eli Lilly, Novartis and/or Pfizer.
    • Dr Tan has been an Investigator, Advisory Board Member and/or Speaker and has received grants and/or honoraria from Abbott, Astellas, Amgen, Celgene, Johnson and Johnson, and Leo.
    • Dr Fuentes-Duculan has been supported in part by grant #8 UL1 TR000043 from the National Center for Research Resources, National Institutes of Health.
    • Dr Krueger has been a consultant and has received grants and honoraria from Centocor/Janssen, Pfizer, Boehringer-Ingleheim, Merck, Eli Lilly, Novartis, Leo and Amgen.
  • Funding sources

    • Research funded and medication provided by Janssen Inc. Canada. They were involved in study design but not in data collection, manuscript preparation or publication decisions.

Abstract

Background

Palmo-plantar pustular psoriasis (PPPP) and palmo-plantar pustulosis (PPP) are chronic skin diseases with significant impact on quality of life.

Objectives

The purpose of this study was to study the efficacy of ustekinumab in PPPP and PPP and gain more knowledge on the pathophysiology and the role of the interleukin-23 (IL-23) signalling pathway in these diseases.

Methods

Thirty-three patients with either PPPP (20) or PPP (13) and seven volunteers with normal palmo-plantar skin were recruited. Patients with PPP or PPPP were randomised (1 : 1) to receive either an anti IL-12/IL-23 antibody (ustekinumab 45 mg) or placebo at day 0 and week 4 with subsequent placebo cross-over to ustekinumab at week 16. The primary endpoint was the proportion of patients randomized to ustekinumab achieving a 50% improvement in the Palmo-Plantar Pustular Area and Severity Index (PPPASI-50) as compared to placebo. Skin biopsies of the palms and soles of normal subjects and patients with PPP or PPPP were performed and analysed by RT-PCR and immunohistochemistry.

Results

There was no statistically significant difference in the proportion of patients randomised to ustekinumab as compared to those randomised to placebo achieving PPPASI-50 at week 16 for patients with PPPP (10%, 20%; P = 1.000) or PPP (20%, 37.5%; P = 1.000) respectively. Compared to normal subjects an 89-fold increase in IL-17A expression was found in palms/soles of patients with PPPP (P = 0.006) and a 190-fold increase for patients with PPP (P = 0.051). There were no statistically significant changes in cytokine expression at week 16 in the palms and soles of patients with PPP or PPPP.

Conclusion

Taken together these results suggest that ustekinumab at a dose of 45 mg has limited efficacy in PPPP and PPP. IL-17A may have a more important role than IL-23 in patients with PPPP and PPP. Conclusions are limited by the small sample size of this study.

Ancillary