Background/Purpose:

Repository corticotropin injection (RCI: H.P. Acthar® gel) contains a purified porcine pituitary ACTH-analogue, and is an FDA-approved treatment for short-term adjunctive therapy of acute episode or exacerbation in rheumatic disorders.  It has been suggested that ACTH modulates the immune response via binding to melanocortin receptors (MC1R to MC5R).  These receptors are expressed on a number of cells including immune cells and bone cells, and have been shown to modulate several immune responses. This study was designed to investigate the effects of RCI treatment compared to prednisolone with regard to arthritis disease attenuation and bone protection.

Methods:

Rat adjuvant-induced arthritis (AIA) model was used to determine efficacy in the subacute inflammation setting. Disease was induced by an injection of a lipoidal amine in Freund’s complete adjuvant (FCA) on day 0. The AIA rats were treated with either vehicle, prednisolone (5 mg/kg) or RCI (40, 160, 400 IU/kg) every other day by subcutaneous injection beginning on the day of disease induction and continuing for 15 days (8 total doses). Disease progression was monitored on days 7-14 by measuring both paw diameter and body weight. Inflammation and bone damage were evaluated histologically at the end of the study.

Results:

Treatment with RCI showed significant and dose responsive inhibition of disease induction as determined by evaluation of ankle diameter (area under the curve (AUC) inhibition of 44%, 74%, 94% for 40 IU/kg, 160 IU/kg and 400 IU/kg, respectively) whereas prednisolone reduced swelling by 33%.  Microscopic examination of the ankle joints showed that RCI significantly inhibited total histopathology sum score by 64% and 85% at 160 IU/kg and 400 IU/kg, respectively, while treatment with prednisolone resulted in 33% inhibition, which was not significantly different from the controls.  Furthermore, RCI inhibited inflammation-related bone resorption and reduced the number of osteoclasts in the inflamed joint.  Interestingly, prednisolone significantly reduced the number of osteoclasts but did not show a significant benefit on joint damage as evaluated by bone resorption and cartilage damage.

Conclusion:

RCI treatment significantly inhibited the development of disease in rat AIA, whereas prednisolone treatment alone only showed a minor benefit.  Furthermore, there was a significant reduction in the number of osteoclasts following RCI treatment.  These findings support the use of RCI for treatment of rheumatoid arthritis and suggest a potential bone sparing effect.