Repository corticotropin injection (H.P. Acthar® Gel) attenuates established collagen-induced arthritis when used alone or as adjuvant therapy with etanercept (Enbrel®) (THER5P.902)

Abstract Melanocortins have anti-inflammatory and immunomodulatory properties mediated by receptors expressed on cells relevant to the pathophysiology of immune-mediated arthritis. Repository corticotropin, a melanocortin preparation, is approved as adjunctive therapy for rheumatoid arthritis (RA), but its mechanism of action in RA has not been determined. We therefore explored the efficacy of corticotropin when used alone or as adjunct therapy with etanercept in a rat collagen-induced arthritis (CIA) model. Corticotropin (160 or 400 U/kg) administered after disease onset significantly attenuated CIA-related changes in ankle diameter and paw weight compared to vehicle treatment (p ≤ 0.05). Corticotropin (400 U/kg) also significantly reduced clinical (4.15 ± 0.38 vs 5.65 ± 0.21, p ≤ 0.01) and summed ankle histopathology (9.90 ± 0.88 vs 15.20 ± 0.85, p ≤ 0.0001) scores below those in vehicle treated rats. Overall efficacy of corticotropin and etanercept used alone in established CIA were comparable, however corticotropin in combination with etanercept synergistically attenuated anti-collagen antibodies and both clinical and histopathologic measures of CIA vs etanercept alone (p ≤ 0.05). In addition, corticotropin administered with etanercept significantly attenuated CIA-induced decreased average bone density, whereas neither drug alone was efficacious (p ≤ 0.05). These data support the potential clinical efficacy of repository corticotropin as an adjunctive therapy for patients with RA.