Anakinra for recalcitrant pyoderma gangrenosum

Abstract

Pyoderma gangrenosum (PG) is an autoinflammatory neutrophilic dermatosis characterized by rapidly enlarging, painful ulcers. Anakinra is a recombinant interleukin (IL)-1 receptor antagonist that blocks the activity of IL-1a and IL-1b by competitively inhibiting IL-1 binding to the IL-1 type 1 receptor. We present a series of two patients with recalcitrant PG, who had limited therapeutic options and multiple comorbidities and multiple previous treatment failures, who obtained 100% healing with anakinra. Compared with conventional first-line therapies for PG, the safety profile of anakinra may be preferable for patients with multiple comorbidities. Further research is needed to assess the safety and efficacy of anakinra for PG.

Targeted therapy with ixekizumab in pyoderma gangrenosum: A case series and a literature overview

“… 9 In addition, IL-1 antagonists may be effective in treating recalcitrant PG. 1 O’Connor et al 10 reported 100% healing with anakinra, an IL-1 receptor antagonist that blocks the activity of IL-1α and IL-1β, in 2 patients with multiple comorbidities.…”

Inflammatory skin diseases and wounds

“…Corticosteroids can be combined with immunosuppressive or immunomodulating drugs such as colchicine, dapsone, minocycline, apremilast, thalidomide, methotrexate, mycophenolate mofetil, cyclophosphamide, azathioprine, tacrolimus and high‐dose intravenous immunoglobulins 51 . There is increasing evidence of the very good efficacy of different biologics, including anti‐TNF‐α drugs such as infliximab, 52 adalimumab, 53 etanercept, 54 anti‐IL‐12/23: ustekinumab, 55 anti‐IL‐1: anakinra, 56 canakinumab 57 or small molecules like JAK/STAT inhibitors: tofacitinib 58 . A valid treatment approach for severe courses of PG may be an initial combination of systemic drugs and then maintenance of remission with a less toxic regimen of local therapeutics after disease activity is under control.…”

Comorbidities present in hidradenitis suppurativa

“…IL‐1 directed treatment with Anakinra and Bermekimab, reached HiSCR in approximately 60%–80% of HS patients in randomized controlled trials 23,24 . Case report data has also demonstrated the successful treatment of both PG and PAPA syndrome with IL‐1 blockade 25,26 22,27 …”

“…23,24 Case report data has also demonstrated the successful treatment of both PG and PAPA syndrome with IL-1 blockade. 25,26 Use of TNF-α directed therapies (Adalimumab, Infliximab) have also been efficacious in the management of acne, HS, and PG, given overexpression of TNF-α in the lesional skin of both HS and PG. 22,27 IL-17 also plays a critical role alongside IL-1 and TNF-α, in the creation of metalloproteinases by neutrophils which results in extracellular matrix destruction and in further production of inflammatory chemokines.…”