Biologic and small-molecule medications in the management of pyoderma gangrenosum

Abstract

Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disorder characterized by neutrophil dysfunction. There are currently no FDA-approved drugs for the treatment of this disease, and treatment has typically relied on traditional immunosuppressive medications such as prednisone or cyclosporine. The efficacy of biologics in the treatment of other pro-inflammatory conditions such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease is well-documented in the literature. Therefore, the use of biologic medications for the treatment of rarer inflammatory skin conditions, such as PG, is a compelling topic for investigation. Biologic and small-molecule therapies allow physicians to target specific pro-inflammatory mediators that underlie PG pathogenesis. This review provides an update on the use of biologic and small-molecule medications for the treatment of PG and summarizes the latest data on the clinical efficacy and pharmacology of these treatments.

Recent advances in managing and understanding pyoderma gangrenosum

“…This is also evident in PG’s association with other disorders related to neutrophilic dysfunction, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), seronegative arthritis, hematologic disorders, and malignancies such as acute myeloid leukemia (AML) 4, 7 . Interleukin-6 (IL-6), a pro-inflammatory cytokine that plays a role in activation and accumulation of neutrophils, has been found to be elevated in PG lesions 8 . Interestingly, some studies have shown PG lesions to be related to defects in adhesion and function of neutrophils, suggesting a multifactorial pathogenesis 7 .…”

“…No TNFα antagonist has been proven to be more efficacious than others in the treatment of PG. Their use has been associated with a decrease in C-reactive protein (CRP), IL-1, IL-6, and immune cell adhesion markers 8 .…”

“…The literature surrounding adalimumab is composed of case reports and small case series; in some of these, it was added to or replaced current therapy because of treatment failure. The majority of the literature showed either complete resolution or partial improvement 8 . However, the sample size was small and evidence is limited 4 .…”

“…Etanercept functions as a decoy receptor for TNFα and has activity against TNFβ. Data are limited to case reports and small case series, the majority of which showed clinical improvement or complete resolution 8 . However, etanercept is less efficacious than other TNF antagonists in the treatment of coexisting IBD 4, 6 .…”

“…Another novel TNFα inhibitor is certolizumab pegol. Future studies are needed to further evaluate the use of Golimumab and Certrolizumab Pegol PG 8, 44 .…”