CORE I & II: COlonic RElease Budesonide for the Induction of Remission for Mild-Moderate Ulcerative Colitis

  • Peter R. McNally, DO, MACG, MSRF
Keywords: KEY Words, Budesonide MMX, Uceris, Ulcerative Colitis, Corticosteroids, Colitis, CORE I, CORE II, Mayo Score, UCDAI, and ACG Ulcerative Colitis Guideline.

Abstract

Budesonide is a second generation corticosteroid with very high affinity for the cortisol receptor, and active first pass hepatic metabolism through the cytochrome p450-3CA4 pathway.1,2 With a 90% first pass hepatic metabolism of budesonide, systemic corticosteroid side effects are minimized, while targeted end organ release can maximize corticosteroid benefit.1,2 The use of targeted release forms of budesonide for allergic disorders of the nasopharynx, esophagus, and respiratory tract are now considered standard of care over oral corticosteroids.2,3,4,5 Budesonide MMX (multi-matrix system, Cosmo Pharmaceuticals SpA, Lainte, Italy) utilizes a unique pH dependent drug release process to deliver and release budesonide throughout the colon, see Figure 1.6 This pharmacology theoretically maximizes drug delivery to the colon and minimizes systemic corticosteroid side effects.6

In this edition of VHJOE, I will review the important findings of two Phase III pharmaceutical studies that confirm the efficacy of Budesonide MMX (Uceris* Santarus, Inc., now Salix Pharmaceuticals, Inc/Santarus Inc. all rights reserved, Raleigh, NC USA) for the treatment of mild-moderate ulcerative colitis (UC).

Author Biography

Peter R. McNally, DO, MACG, MSRF
Deputy Editor, VHJOE, Center of Human Simulation, Unversity of Colorado School of Medicine. Aurora, Colorado. Chief GI Evans Army Hospital, Colorado Springs, CO. Conflict of Interest: Advisory Boards: Salix, Gastroenterology & Endoscopy News, Roche, Astra-Zeneca, Takeda Consultant: Salix, Takeda, Astra-Zeneca Speaker’s List: Salix, Takeda, Astra-Zeneca, Wyeth, P&G, Roche, Novartis, UCB, Abbott Grants: Novartis, Astra-Zeneca, Given, Abbott, Salix, Roche Pharmaceutical Stocks: 0

References

References:

  1. Edsbacker S, Jonsson S, Lindberg C, Ryrfeldt A, Valén A. Metabolic pathways of the topical glucocorticoid budesonide in man. Drug Metab Dispos 1983; 11: 590-596.
  2. García-Martín E, Canto G, Agúndez JA. Metabolic considerations of drugs in the treatment of allergic diseases. Expert Opin Drug Metab Toxicol. 2013 Nov;9(11):1437-52.
  3. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids: new developments. Am J Respir Crit Care Med 1998;157:S1- S53.
  4. Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev. 2013 Dec 16;12:CD009019. doi: 10.1002/14651858.CD009019.pub2.
  5. Prieto R, Richter JE. Eosinophilic esophagitis in adults: an update on medical management. Curr Gastroenterol Rep. 2013 Jun;15(6):324. doi: 10.1007/s11894-013-0324-6.
  6. Varshosaz J, Emami J, Tavakoli N, Minaiyan M, Rahmani N, Dorkoosh F. Development and Evaluation of a Novel Pellet-Based Tablet System for Potential Colon Delivery of Budesonide. J Drug Deliv. 2012; 2012: 905191
  7. Sandborn WJ, Travis S, Moro L, Jones R, Gautille T, Bagin R, Huang M, Yeung P, Ballard ED.  Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012 Nov;143(5):1218-26
  8. Travis SPL, Danese S, Kupcinskas L, Alexeeva O, D’Haens G, Gibson PR, Moro L, Jones R, Ballard ED, Masure J, Rossini M, Sandborn WJ.  Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomized CORE II study.  Gut. 2014 Mar;63(3):433-41.
  1. Schroeder KW, Tremaine WJ, Ilstrup DM.  Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9.

  1. Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010 Mar;105(3):501-23.
  2. Travis, S, Danese E, Ballard D, Moro L, Jones RJ, et al. Safety analysis of budesonide MMX 6 mg used for the maintenance of remission in patients with ulcerative colitis: results from a Phase III, 12 month safety and extended use study. Gastroenterology. 2012;142(5):S566-7 (Su2080).
  3. Lichtenstein GA, Danese S, Ballard D, Moro L, Jones RJ, et al. Effect of budesonide MMX 6 mg on the Hypothalamic-Pituitary-Adrenal (HPA) axis in patients with ulcerative colitis: results from a phase III, 12 month safety and extended use study. Gastroenterology. 2012;142(5):S785 (Tu252).
  4. Travis S, Danese E, Ballard D, Moro L, Jones RJ, et al. Effect of long term Budesonide MMX use on bone mineral density in patients with ulcerative colitis: results from a phase III, 12 month safety and extended use study. Gastroenterology. 2012;142(5):S566-67 (Su2088).
Published
2014-06-11
Section
Literature Review