A G A Kolios1,2, J-T Maul1, B Meier1, K Kerl1, C Traidl-Hoffmann3, M Hertl4, D Zillikens5, M Röcken6, J Ring3, A Facchiano7, C Mondino8, N Yawalkar9, E Contassot1, A A Navarini1, L E French1. 1. Department of Dermatology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland. 2. Department of Immunology, Zürich University Hospital, Gloriastraße 31, 8091, Zürich, Switzerland. 3. Department of Dermatology and Allergy Biederstein, Technische Universität Mönchen, Munich, Germany. 4. Departments of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany. 5. Department of Dermatology, University of Lübeck, Lübeck, Germany. 6. Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany. 7. Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Rome, Italy. 8. Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland. 9. Department of Dermatology, Bern University Hospital, Bern, Switzerland.
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.
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.