044 Safety and efficacy of anti-IL-17 (Secukinumab) for the treatment of pyoderma gangrenosum

Abstract

Pyoderma gangrenosum (PG) is a severe autoinflammatory disease causing relapsing, painful ulcers of the skin. Typically, wounds are surrounded by a highly inflammatory margin and any mechanical manipulation promotes further inflammation. Treatment of PG is difficult and requires potent anti-inflammatory agents, such as high-dose corticosteroids or cyclosporine. As neutrophil granulocytes dominate the inflammatory infiltrate in PG lesions, IL-17 might be a central regulator of PG pathogenesis. To test this hypothesis we performed an investigator initiated phase I-II pilot study evaluating the safety and efficacy of secukinumab for the treatment of PG (Eudra-CT 2015- 000762-65). In total seven patients were included. All patients received 300mg secukinumab every week from week 0 – 4, followed by 300mg every 4 weeks until week 16 (2 patients) or 300mg secukinumab every two weeks until week 32 (5 patients). Concomitant immunosuppressive treatment was not allowed. The primary endpoint was the change of 5 point scale physician’s global assessment (PGA) at week 16. Secondary endpoints included change of ulcer surface size, inflammatory serum parameters and dermatological life quality index (DLQI). Four patients received secukinumab treatment until week 16, whereas the other patients dropped out earlier due to worsening of PG. Mean PGA was 3.3 at baseline and 2.8 at week 16. All patients reported a reduction of pain during treatment. Three patients receiving secukinuamb every 2 weeks continued treatment until week 32. Of these, two had a marked decrease of ulcer size, inflammatory serum parameters and DLQI. No new safety signals were observed. Thus, treatment with secukinumab monotherapy resulted in improvement of PG in 2/7 patients (28%). Further studies are needed to test the potential of anti-IL-17 treatment in combination with conventional immunosuppressants.