Canakinumab in adults with steroid-refractory pyoderma gangrenosum

A. G A Kolios, J. T. Maul, B. Meier, K. Kerl, C. Traidl-Hoffmann, M. Hertl, D. Zillikens, M. Röcken, J. Ring, A. Facchiano, C. Mondino, N. Yawalkar, E. Contassot, A. A. Navarini, L. E. French

Research output: Contribution to journalArticlepeer-review

Abstract

Background Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. Objectives To determine whether canakinumab is an effective and safe treatment in PG. Methods Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels. Results Interleukin (IL)-1β and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other. Conclusions Our data indicate that IL-1β plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

Original languageEnglish
Pages (from-to)1216-1223
Number of pages8
JournalBritish Journal of Dermatology
Volume173
Issue number5
DOIs
Publication statusPublished - Nov 1 2015

ASJC Scopus subject areas

  • Dermatology

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