Repository corticotropin injection attenuates collagen-induced arthritic joint structural damage and has enhanced effect
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(2020) 21:586
RESEARCH ARTICLE
Open Access
Repository corticotropin injection attenuates collagen-induced arthritic joint structural damage and has enhanced effects in combination with etanercept Dima A. Decker1, Paul Higgins1, Kyle Hayes2, Chris Bollinger2, Patrice Becker1 and Dale Wright2*
Abstract Background: Melanocortin receptor (MCR) agonists have anti-inflammatory and immunomodulatory properties mediated by receptors expressed on cells relevant to arthritis. Repository corticotropin injection (RCI; Acthar® Gel), an MCR agonist preparation, is approved as adjunctive therapy for rheumatoid arthritis (RA), but its mechanism of action in RA is unclear. This study explored the efficacy of RCI as monotherapy or adjunctive therapy with etanercept (ETN) in an established animal model of collagen-induced arthritis (CIA). Methods: After induction of CIA, rats (n = 10 per group) were randomized to receive subcutaneous RCI (40, 160, or 400 U/kg twice daily) alone or in combination with ETN (10 mg/kg 3 times daily), ETN alone, or vehicle (on days 13 through 19). Inflammation was assessed via changes in paw edema. Bone damage was determined by microfocal computed tomography histopathology, and immunohistochemistry. Statistical analyses were performed using a 2way analysis of variance (ANOVA) followed by the Newman-Keuls, Dunn’s, or Dunnett’s multiple comparisons test or a 1-way ANOVA followed by the Dunnett’s or Holm-Sidak multiple comparisons test. Results: RCI administration resulted in dose-dependent decreases in ankle edema and histopathologic measures of inflammation, pannus formation, cartilage damage, bone resorption, and periosteal bone formation. RCI and ETN showed combined benefits on all parameters measured. Radiographic evidence of bone damage was significantly reduced in rats that received RCI alone or in combination with ETN. This reduction in bone density loss correlated with decreases in the number of CD68-positive macrophages and cathepsin K–positive osteoclasts within the lesions. Conclusions: As monotherapy or adjunctive therapy with ETN, RCI attenuated CIA-induced joint structural damage in rats. These data support the clinical efficacy of RCI as adjunctive therapy for patients with RA. Keywords: Rheumatoid arthritis, Melanocortin receptor agonist, Repository corticotropin injection, Bone loss, Etanercept, Osteoclast
* Correspondence: [email protected] 2 Mallinckrodt Pharmaceuticals, 675 McDonnell Blvd, Bedminster, NJ 63042, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indi
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