Pharmacokinetics and Clinical Efficacy of Cyclosporine Treatment of Dogs with Steroid‐Refractory Inflammatory Bowel Disease

Abstract

The usual treatment of dogs with inflammatory bowel disease (IBD) consists of administration of immunosuppressive doses of steroids. However, some dogs are refractory to steroid treatment and pose a significant challenge to the veterinarian. Because cyclosporine A (cyA) has been shown to be effective in steroid-resistant IBD in humans, the purpose of this study was to investigate the pharmacokinetics and clinical efficacy of PO cyA treatment in dogs with steroid-refractory IBD (n = 14). All dogs were treated with cyA 5 mg/kg PO q24h for a period of 10 weeks. A clinical activity score was assigned to assess severity of clinical signs before and after treatment. The total number of infiltrating lymphocytes and T cells in duodenal biopsies were assessed before and after treatment in 9 dogs. In addition, serum concentration of cyA was measured in 8 dogs over a 24-hour period. Pharmacokinetic profiles in dogs with IBD were similar to those of healthy dogs. Improvement of clinical signs was observed in 12 of 14 dogs with IBD. Median clinical activity score after treatment with cyA was significantly reduced from a median score of 9 to a median score of 5 (P = 0.001). T cell numbers in duodenal biopsies were significantly decreased after treatment from a median +/- 95% range in the villous region of 28 (19-30) cells/10,000 microm2 before versus 7 (0-10)/10,000 microm2 after treatment, P = 0.01; and from a median +/- 95% range number in the crypt region of 15 (6-23) cells/10,000 microm2 before versus 4 (0-9)/10,000 microm2 after treatment, P = 0.02, implying T cell lysis as a possible mechanism of action. In conclusion, based on this small study, cyA appears to be an effective alternative drug in dogs with IBD that are refractory to immunosuppressive doses of steroids.

Cyclosporine A Inhibits the mRNA Expressions of IL-2, IL-4 and IFN-.GAMMA., but not TNF-.ALPHA., in Canine Mononuclear Cells

“…TNF-α is a proinflammatory cytokine and considered to be an important effector molecule in the pathogenesis of IBD and immune-mediated polyarthritis [13,27]. Although a previous clinical study reported that CsA appeared to be effective in dogs with IBD that were refractory to steroids [1], the results of the present study indicate that CsA should be used with care for the treatment of TNF-α-mediated diseases. TNF-α is known to cause nausea and vomiting via brain cell targets [6].…”

Analytical validation of a quantitative reverse transcriptase polymerase chain reaction assay for evaluation of T-cell targeted immunosuppressive therapy in the dog

“…A poor correlation between cyclosporine blood concentrations and clinical response has been demonstrated with both canine atopy and inflammatory bowel disease (Allenspach et al, 2006; Steffan et al, 2004). Cyclosporine dosing in veterinary cases is therefore often empirically adjusted based solely on clinical response.…”

Idiopathic Eosinophilic Masses of the Gastrointestinal Tract in Dogs

“…The optimal treatment remains to be determined, and additional medical therapies, such as cyclosporine, azothiaprine, sulfasalazine, or cromolyn, might be of benefit in select cases. 25 As with inflammatory bowel disease, specific histopathologic characterization of IEGM is challenging and some variations in the findings are expected. However, suggested criteria include the presence of a mass containing moderate to severe eosinophilic inflammation, often transmural in surgical biopsies, with fibrosis as a consistent feature.…”