Adrenomedullin Therapy in Patients with Refractory Ulcerative Colitis: A Case Series

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Abstract
Background and Aims Adrenomedullin (AM) is a multifunctional biologically active peptide that has an ameliorative effect against inflammatory bowel disease in several experimental models. We reported the first case where AM infusion dramatically improved symptoms and colonoscopy findings in patients with refractory ulcerative colitis (UC). To confirm the reproducibility of the efficacy and safety of AM infusion, this pilot study evaluated the clinical feasibility of intravenous administration of AM in patients with refractory UC. Methods Seven patients with active refractory UC participated and received intravenous infusion of AM (1.5 pmol/kg/min) for 8 h daily for 14 days, and their Disease Activity Index (DAI) were evaluated before and 2 and 12 weeks after beginning AM administration. Results DAI were improved in all patients after AM administration. Within 2 weeks, marked declines in DAI (≥3 points and ≥30 %) were observed in six patients (85.7 %), while a more modest decline was observed in one patient (14.3 %). Overall mean DAI improved from 9.3 ± 0.6 at baseline to 4.6 ± 0.8 at 2 weeks, and then to 1.2 ± 0.5 at 12 weeks. Endoscopic examination revealed substantial amelioration of ulcers, with mucosal healing and scarring. Four patients remained in clinical remission 12 months after AM treatment. AM administration produced significant increases in plasma AM concentrations (approximately 2.5-fold) that had a mild effect on blood pressure and heart rate, but with no serious adverse effects. Conclusion AM is a potentially useful agent that acts via a novel mechanism to safely induce mucosal healing and clinical remission in patients with refractory UC.
Funding Information
  • Health and Labor Science Research Grants for Translational Research from the Ministry of Health, Labor and Welfare, Japan
  • Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS), Japan
  • Specific Research Grant from the Uehara Memorial Foundation, Japan
  • Grant-in-Aid for Vascular Biology Innovation from the Japan Foundation for Applied Enzymology, Japan

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