Canakinumab Might Be Effective for Pyoderma Gangrenosum
Jeffrey P. Callen, MD reviewing Kolios AGA et al. Br J Dermatol 2015 Oct 16.
IL-1β antagonists could serve as therapeutic agents for this inflammatory condition.
Pyoderma gangrenosum (PG), a rare inflammatory ulceration of the skin, has an unknown pathogenesis, but a variety of inflammatory mediators seem to drive the observed neutrophilic infiltrate. Increased interleukin (IL)-1β levels have been demonstrated in patients with PG as part of an autoinflammatory syndrome. The biologic canakinumab targets IL-1β and is approved for use in cryopyrin-associated autoinflammatory syndromes. It has demonstrated effectiveness in single cases of PG-associated syndromic autoinflammatory disorders.
These investigators performed an open-label study of five patients with refractory nonsyndromic PG not associated with systemic disease. All patients were resistant to systemic corticosteroids and at least one additional agent. Although the protocol called for pre- and posttreatment biopsies, only four patients had pretreatment biopsies, and none allowed posttreatment biopsy. Canakinumab 150 mg was given subcutaneously at study onset, week 2, and week 8. The second and third administrations depended upon a physician global assessment of partial response; the third administration could be at 300 mg. Cytokine analysis occurred only at treatment onset but demonstrated high levels of IL-1α, IL-1β, IL-6, IL-8, and IL-36α in PG lesions.
Four patients responded to canakinumab; three had complete response. The nonresponding patient initially had a very small, superficially ulcerated lesion within a surgical scar, which worsened during the study to a more characteristic lesion. Two patients had typical PG lesions with a reasonably rapid response to therapy. Minor fatigue was observed in one patient; one developed scrotal ulcers resulting in hospitalization, which was considered a serious adverse reaction.
Citation(s):
Kolios AGA et al. Canakinumab in adults with steroid-refractory pyoderma gangrenosum. Br J Dermatol 2015 Oct 16; 173:1216.
