Repository corticotropin injection attenuates collagen-induced arthritic joint structural damage and has enhanced effects in combination with etanercept.

Decker DA, Higgins P, Hayes K, Bollinger C, Becker P, Wright D

BMC musculoskeletal disorders31 Aug 2020Cited by 2 (Europe PMC)

PMID32867752PMCIDPMC7460755DOI10.1186/s12891-020-03609-3PepBankPUB-32867752

Summary

BackgroundMelanocortin 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).MethodsAfter 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 2-way 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.ResultsRCI 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.ConclusionsAs 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In rats with collagen-induced arthritis, Acthar Gel dose-dependently reduced ankle edema, inflammation, pannus formation, cartilage damage, bone resorption, and periosteal bone formation.
In plain wordsIn rats with arthritis, Acthar Gel dose-dependently reduced edema and reported joint damage measures compared with vehicle.
Peptide
ACTH (corticotropin)
Outcome
DecreaseHistopathologic joint outcomes and ankle edema
Study
ratn: not reported in source
Collagen-induced arthritis
Comparator
Vehicle
Outcome group
Bone and joint · Musculoskeletal
Studied dose
40, 160, or 400 U/kg twice daily · subcutaneous · days 13 through 19As given in this study (rat).
Source sentences
Summary
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.
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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).
Show in the study text Report a problemFND-3286775201
02AnimalAnimal study (in vivo)Efficacy outcome
In rats with collagen-induced arthritis, Acthar Gel alone significantly reduced radiographic bone damage.
In plain wordsIn rats with arthritis, Acthar Gel alone reduced radiographic bone damage compared with vehicle.
Peptide
ACTH (corticotropin)
Outcome
DecreaseRadiographic bone damage
Study
ratn: not reported in source
Collagen-induced arthritis
Comparator
Vehicle
Outcome group
Bone and joint · Musculoskeletal
Studied dose
40, 160, or 400 U/kg twice daily · subcutaneous · days 13 through 19As given in this study (rat).
Source sentences
Summary
Radiographic evidence of bone damage was significantly reduced in rats that received RCI alone or in combination with ETN.
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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).
Show in the study text Report a problemFND-3286775202

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Version history

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Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

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