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Background A 39-amino-acid peptide of the natural form of adrenocorticotropic hormone (ACTH) was designed to provide a prolonged release after administration by intramuscular or subcutaneous injection. It is FDA-approved as adjunctive therapy for psoriatic arthritis for short-term administration. Clinical data on the safety of ACTH in psoriatic arthritis is limited.Objective To assess the safety data for the use of ACTH in psoriatic arthritis and compare it with the safety data for corticosteroids.Methods We conducted a systematic review of the literature pertaining to the safety of ACTH versus corticosteroids in psoriatic arthritis. We queried the PubMed database for studies evaluating (i) ACTH and Acthar in psoriatic arthritis using the search terms “psoriatic arthritis” and “ACTH” or “acthar” or “adrenocorticotropic hormone” and (ii) ACTH and Acthar in RA or psoriatic arthritis using the terms “rheumatoid arthritis” or “psoriatic arthritis” and “ACTH” or “acthar” or “adrenocorticotropic hormone.” We placed no time limits on either search. From the search results, we selected studies that emphasize safety data. Due to limited psoriatic arthritis-related data, we included data related to rheumatoid arthritis (RA).Results The current body of knowledge surrounding the safety of ACTH in psoriatic arthritis is limited. Twenty studies met our inclusion criteria, 14 of which directly compared ACTH to corticosteroids in either psoriatic arthritis or RA. Of these, five studies reported comparable safety between the two, four studies reported more adverse events with ACTH, two studies reported more adverse events with corticosteroids, and three studies were inconclusive.Conclusion There is no clear evidence that ACTH is safer than corticosteroids for psoriatic arthritis.