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Canakinumab in adults with steroid-refractory pyoderma gangrenosum
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4517566
Author(s)
Kolios, A. G. A.; Maul, J.-T.; Meier, B.; Kerl, K.; Traidl-Hoffmann, C.; Hertl, M.; Zillikens, D.; Röcken, M.; Ring, J.; Facchiano, A.; Mondino, C.; Yawalkar, N.; Contassot, E.; Navarini, A. A.; French, L. E.
Canakinumab in adults with steroid-refractory pyoderma gangrenosum
Journal
The British Journal of Dermatology
Volume
173
Number
5
Pages / Article-Number
1216-23
Mesh terms
Administration, Cutaneous; Adult; Aged; Antibodies, Monoclonal, administration & dosage; Cytokines, metabolism; Dermatologic Agents, administration & dosage; Drug Administration Schedule; Drug Resistance; Humans; Middle Aged; Prospective Studies; Pyoderma Gangrenosum, drug therapy, metabolism; Steroids, therapeutic use; Treatment Outcome; Young Adult
Abstract
Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids.; To determine whether canakinumab is an effective and safe treatment in PG.; 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.; 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.; Our data indicate that IL-1β plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.
