title: Canakinumab in adults with steroid-refractory pyoderma gangrenosum.
abstract: BACKGROUND
  Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.|Department of Immunology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: A G A
authors.initials: AG
authors.lastname: Kolios
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: J-T
authors.initials: JT
authors.lastname: Maul
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Meier
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Kerl
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität Mönchen, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.affiliation: Departments of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hertl
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Röcken
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität Mönchen, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ring
authors.affiliation: Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Facchiano
authors.affiliation: Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Mondino
authors.affiliation: Department of Dermatology, Bern University Hospital, Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Yawalkar
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Contassot
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: A A
authors.initials: AA
authors.lastname: Navarini
authors.affiliation: Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland.
authors.forename: L E
authors.initials: LE
authors.lastname: French
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines / Q000378:metabolism; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D017511:Pyoderma Gangrenosum / Q000188:drug therapy* / Q000378:metabolism; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D003879:Dermatologic Agents; D013256:Steroids; C541220:canakinumab