Fuzapladib in a randomized controlled multicenter masked study in dogs with presumptive acute onset pancreatitis

• Published in: Journal of veterinary internal medicine 2023-11, Vol.37 (6), p.2084-2092
• Main Authors: Steiner, Joerg M., Lainesse, Chantal, Noshiro, Yuya, Domen, Yumiko, Sedlacek, Heather, Bienhoff, Stephen E., Doucette, Kelly P., Bledsoe, David L., Shikama, Hiroshi
• Format: Article
• Language: English
• Subjects: Abdomen; Acute Disease; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Antiemetics; Antigens; C-Reactive Protein - analysis; canine acute onset pancreatitis; Cytokines; dog; Dog Diseases - drug therapy; Dogs; fuzapladib; Inflammation - veterinary; Inflammatory bowel disease; Laboratories; Leukocytes; LFA‐1 activation inhibitor; lipase; Neutrophils; Nonsteroidal anti-inflammatory drugs; Pancreas; Pancreatitis; Pancreatitis - drug therapy; Pancreatitis - veterinary; Pathophysiology; Tumor necrosis factor-TNF; Variance analysis; Veterinarians
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/jvim.16897

Background Currently, no specific treatment is available for acute onset pancreatitis (AP), and management relies on symptomatic and supportive standard of care (SOC). Fuzapladib is a novel leukocyte function‐associated antigen type‐1 (LFA‐1) activation inhibitor, blocking activation and subsequent adhesion and migration of neutrophils, potentially decreasing the risk of pancreatitis progression and systemic inflammation. Objective Evaluate the safety and clinical response of dogs with AP after 3 days of administration of fuzapladib. Animals Sixty‐one client‐owned dogs with presumptive AP. Methods Randomized, masked, and placebo controlled multicenter study. Sixty‐one dogs with AP were included for safety assessment, whereas 35 evaluable cases (fuzapladib, n = 16; placebo, n = 19) were included for clinical evaluation. Clinical improvement was assessed based on the change in the modified clinical activity index (MCAI) score on Day 3 compared to Day 0. Secondary variables included canine acute pancreatitis clinical severity index (CAPCSI) scores and serum concentrations of canine pancreatic lipase immunoreactivity, cytokines, and C‐reactive protein. Results Fuzapladib was well tolerated by all treated dogs. Mean change in MCAI scores was significantly higher in the fuzapladib‐treated (−7.75) than the placebo group (−5.68; P = .02, 95% confidence interval [CI] for the difference, −4.33, −0.35), suggesting clinical improvement in fuzapladib‐treated dogs. No significant difference was found in any of the secondary variables between groups. Conclusions and Clinical Relevance Administration of fuzapladib to dogs was safe, and a favorable response was detected in 2 clinical activity scores. Effects of fuzapladib on survival and duration of hospitalization were not studied.