Ulcerative Colitis: Improving Outcomes with a Targeted Formulation

This article was sponsored by Santarus, Inc.

The Burden of Ulcerative Colitis and Its Clinical Course

Ulcerative colitis (UC) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that affects the mucosal surface of the colon and rectum.^1,2 The inflammation associated with UC begins in the rectum, oftentimes extends proximally in a continuous manner, and is capable of damaging the entire length of the colon.^1,2 The reported incidence and prevalence rates of UC in North America range from 2.3 to 15.6 cases per 100,000 person-years and 37.5 to 246 cases per 100,000 people, respectively.³ While UC typically demonstrates a bimodal distribution with respect to age at onset, UC can present at any age, and there is a slight predominance in males versus females.^2,3

Although bloody diarrhea with or without mucus is the hallmark of UC, patients affected by the condition may also present with symptoms such as abdominal discomfort or pain, fecal urgency, and/or tenesmus.^2,4 While the onset of UC is often gradual, its clinical course is characterized by alternating periods of spontaneous remission and subsequent relapse, and the disease can progress over time.^1,2,4 The unchecked progression of UC can lead to further intestinal complications including bleeding, toxic or fulminant colitis, toxic megacolon, stricture, dysplasia or colorectal cancer, and colectomy. Extra-intestinal manifestations of UC may also occur, including involvement of the musculoskeletal, hepatobiliary, hematopoietic, and/or coagulation systems.^2,4

Best Practices for Diagnosis and Management of Ulcerative Colitis

UC is typically diagnosed through lower endoscopic studies (eg, colonoscopy) and histological evaluations. These studies and evaluations allow clinicians to determine the severity of inflammation and define the extent of disease, which provides valuable prognostic information and guides treatment strategies.⁴ UC is classified as mild, moderate, severe, or fulminant, as defined in the Table. The majority of patients have mild or moderate UC.^5-8

The goals of UC treatment are to induce and maintain remission and to suppress inflammation. To achieve these goals, clinicians have often enlisted the help of various oral, parenteral, and rectal pharmacologic agents, including aminosalicylates, glucocorticoids (GCs), immunosuppressants, and biologic agents that target tumor necrosis factor (TNF)-α.^1,2

Defining the Role of Glucocorticoids in Ulcerative Colitis

Systemic GCs are widely used for the treatment of mild, moderate, and severe active UC and acute flares of UC.^2,9 Systemic GCs have high glucocorticoid (cortisol-like) effects and are often associated with a broad range of adverse reactions that limit their use, such as hypertension, diabetes mellitus, peptic ulcer, glaucoma, and osteoporosis.^2,10 To help reduce the risk of complications due to GCs, the American Gastroenterological Association performance measures for IBD recommend that exposure to systemic GCs be limited, and that treatment be shifted to steroid-sparing agents.¹¹ Selecting an oral GC such as budesonide may be preferable because of its topical anti-inflammatory effects and reduced adverse reaction profile due to its extensive first-pass metabolism and low systemic bioavailability.^2,12 Furthermore, an orally administered topical GC with targeted drug delivery would potentially reduce systemic exposure, decrease toxicity, and improve efficacy.^9,13

UCERIS for Ulcerative Colitis

UCERIS (budesonide) extended release tablets is a unique formulation of budesonide, available by prescription only, that is indicated for the induction of remission in patients with active, mild-to-moderate UC, to be taken once daily in the morning by mouth, with or without food, for up to 8 weeks.¹⁴ Its unique formulation with multi-matrix technology (MMX) causes pH-dependent dissolution at a pH of 7 or greater, which allows the active drug, budesonide, to undergo a controlled and targeted release throughout the entire length of the colon while limiting systemic absorption.^2,14 As a result of the extensive first-pass metabolism (90%) and low systemic bioavailability and the controlled release of budesonide via MMX technology, systemic absorption of budesonide is limited, reducing the likelihood of systemic GC-related adverse reactions.^2,12,14 Controlled ileal release budesonide targets the ileum/ascending colon, dissolving at a pH greater than 5.5 (the approximate pH level of the duodenum), and is not indicated for the treatment of UC.¹⁵ The clinical effect of this information is unknown.

Two randomized, double-blind, placebo-controlled studies were conducted in a total of 899 adult patients with active, mild to moderate UC.¹⁴ The rigorous primary end point assessed combined clinical remission and mucosal healing.^12,13 With regard to efficacy, in a pooled analysis of data from 2 phase III trials, 3 times more patients who received budesonide MMX (9 mg) achieved clinical remission and mucosal healing versus placebo (18% and 6%, respectively).¹⁶ No clinically significant differences were observed with respect to the overall percentages of patients with any glucocorticoid-related effects between UCERIS (9 mg) and placebo after 8 weeks of treatment.¹⁴ In a 12-month safety study, the incidence of treatment-related adverse reactions was similar with UCERIS (6 mg) and placebo (21.0% and 21.3% respectively).¹⁷ The most common adverse reactions with UCERIS with an incidence of 2% or greater are headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, and constipation.¹⁴

UCERIS offers a convenient, orally administered, effective, locally acting corticosteroid option with targeted MMX technology for patients with mild to moderate UC, and is supported by a copay assistance program to increase patient accessibility.

References

• Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012;380:1606-1619.
• Sherlock ME, Seow CH, Steinhart AH, Griffiths AM. Oral budesonide for induction of remission in ulcerative colitis (review). Cochrane Database Syst Rev. 2011;10:1-44.
• Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126:1504-1517.
• Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365:1713-1725.
• Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2(4947):1041-1048.
• Rao SS, Holdsworth CD, Read NW. Symptoms and stool patterns in patients with ulcerative colitis. Gut. 1988;29(3):342-345.
• Langholz E, Munkholm P, Nielsen OH, Kreiner S, Binder V. Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987. Scand J Gastroenterol. 1991;26(12):1247-1256.
• 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;105(3):501-523.
• Patel NV, Patel JK, Shah SH, Patel JN. Central composite design for the formulation and optimization of a multi-unit potential colonic drug delivery system of budesonide for ulcerative colitis. Pharmazie. 2011;66:124-129.
• Schimmer BP, Funder JW. ACTH, adrenal steroids, and pharmacology of the adrenal cortex. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011. www.accessmedicine.com/content.aspx?aID=16674048. Accessed June 27, 2013.
• American Gastroenterological Association. Adult inflammatory bowel disease physician performance measures set. 2011.
• Travis SPL, Danese S, Kupcinskas L, et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study [published online February 22, 2013]. Gut.
• Sandborn WJ, Travis S, Moro L, et al. 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;143:1218-1226.
• Uceris [prescribing information]. San Diego, CA: Santaurus, Inc; 2013.
• Entocort EC [prescribing information]. Wilmington, DE: AstraZeneca; 2011.
• Data on file. Santarus, Inc.
• Sandborn WJ, Travis S, Bala N, et al. Induction of clinical and endoscopic remission of mild to moderately active ulcerative colitis with budesonide MMX^® 9 mg: analysis of pooled data from two phase 3 studies [abstract]. Am J Gastroenterol. 2011;106:S485.

INDICATIONS AND USAGE

UCERIS is a glucocorticosteroid indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis.

DOSAGE AND ADMINISTRATION

• The recommended dosage of UCERIS is one 9-mg tablet to be taken once daily in the morning with or without food for up to 8 weeks.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

UCERIS is contraindicated in patients with known hypersensitivity to budesonide or any of the ingredients of UCERIS.

WARNINGS AND PRECAUTIONS

• Hypercorticism and adrenal suppression: Since UCERIS is a glucocorticosteroid, general warnings concerning glucocorticoids should be followed.
• Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids with high systemic effects. Taper patients slowly from systemic corticosteroids if transferring to UCERIS.
• Immunosuppression: Potential worsening of infections (eg, existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.
• Increased systemic glucocorticoid susceptibility: Reduced liver function affects the elimination of glucocorticosteroids.
• Other glucocorticoid effects: Caution should be taken in patients with hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where glucocorticosteroids may have unwanted effects.

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥2%) are headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, and constipation.

DRUG INTERACTIONS

Avoid Cytochrome P450 3A4 inhibitors (eg, ketoconazole, grapefruit juice). May cause increased systemic corticosteroid effects.

USE IN SPECIFIC POPULATIONS

Hepatic impairment: Monitor patients for signs and/or symptoms of hypercorticism.

The Important Safety Information does not include all the information needed to use UCERIS safely and effectively. See Full Prescribing Information for additional information.

UCERIS is a registered trademark of Santarus, Inc.

MMX is a registered trademark of Cosmo Technologies, Ltd.

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