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

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 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. 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.

SUBMITTER: Decker DA

PROVIDER: S-EPMC7460755 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Decker Dima A DA Higgins Paul P Hayes Kyle K Bollinger Chris C Becker Patrice P Wright Dale D

BMC musculoskeletal disorders 20200831 1

<h4>Background</h4>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 o ...[more]

PMID: 32867752

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Project description:BACKGROUND:Repository corticotropin injection (RCI) has regulatory approval for many indications, including symptomatic sarcoidosis. This large case series of patients with advanced symptomatic sarcoidosis treated with RCI describes patient characteristics, RCI utilization patterns, concomitant therapies, and physicians' assessments of treatment response. METHODS:Patients ⩾18 years with symptomatic sarcoidosis, treated with RCI in the previous 36 months, who had completed a course of RCI or received RCI for ⩾6 months at the time of data collection were included. RESULTS:The study included 302 patients (mean age, 51 years; 52%, women) with a mean 4.8 years since initial diagnosis of sarcoidosis. Most patients (76%) had extrapulmonary involvement, primarily in the skin (28%), joints (25%), heart (22%), and eyes (22%); 34% had multiple (⩾2) organ involvement. The mean duration of RCI treatment was 32.5 weeks, with 61.6% of patients continuing RCI therapy for ⩾6 months. The RCI utilization pattern indicated an individualized approach to therapy, with a higher starting dose associated with a shorter duration of therapy compared with a lower starting dose. The percentage of patients who used corticosteroids decreased from 61.3% during the 3 months before initiation of RCI to 12.9% 3 months after RCI therapy; the mean daily dose of corticosteroid decreased from 18.2 mg to 9.9 mg. The proportion of patients given <10 mg/day of prednisone increased from 21% before RCI use to 47% 3 months after RCI use. According to physicians' assessments of change in patients' health status after RCI therapy, overall status improved in 95% of patients, overall symptoms in 73%, lung function in 38%, and inflammation in 33%. CONCLUSIONS:The findings suggest that RCI is a viable treatment option for patients with advanced symptomatic sarcoidosis and provide insights on patient characteristics and practice patterns to help clinicians determine appropriate use. The reviews of this paper are available via the supplemental material section.

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

Publications

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

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