88.7% Of Ulcerative Colitis Patients In Remission Remained Relapse-Free At 12 Months With Once Daily Mezavant(R) XL (MMX Mesalazine)

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Clinical Trials / Drug Trials;  Irritable-Bowel Syndrome
Article Date: 10 Oct 2008 - 4:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

Shire Limited, the global specialty biopharmaceutical company, announces that data published in Gut show that 64.4% of patients with mild to moderate ulcerative colitis (UC) who achieved clinical and endoscopic remission maintained this at 12 months when given two mesalazine 1200mg gastro-resistant, prolonged release tablets (Mezavant XL) once a day as a maintenance therapy. [1] In this study, remission was calculated using a modified Ulcerative Colitis Disease Activity Index (UC-DAI) score ≤1, with a score of 0 for rectal bleeding and stool frequency, a combined physicians global assessment (PGA) and a sigmoidoscopy score ≤1 with a sigmoidoscopy score reduction of 1 point or more from baseline.

Furthermore, at month 12, 88.7% (n=171) of patients remained relapse-free with Mezavant XL 2.4g/d once daily.1 In this study relapse was defined as a requirement for alternative treatment for UC (including surgery or an increase in the dose of MMX mesalazine above 2.4g/day).

Patients with active, mild to moderate UC who achieved clinical and endoscopic remission during induction treatment in two 8-week randomised, Phase III, double-blind, placebo-controlled trials were enrolled in this open-label, 12-month long-term study. Patients received Mezavant XL as a maintenance therapy 2.4g once daily or 1.2g twice daily.*

"This study shows that high clinical and endoscopic remission rates can be maintained via once-daily dosing with MMX mesalazine," said Professor Michael Kamm, St Vincent's Hospital, Melbourne, Australia, who led the study while at St Mark's Hospital, London, UK. "Maintenance treatment for UC should be as convenient as possible to increase the chance of patients complying. A once-daily treatment could therefore be beneficial since simplifying drug regimens may help compliance with prescribed medications and thereby improve symptom control in our patients."

* Mezavant XL is not licensed for twice daily use.

http://www.shire.com

Many currently available UC treatments require tablets to be taken in divided doses throughout the day which can make taking the medication challenging. In fact, a recent study confirms that over 60% of patients were noncompliant with their current therapy, citing tablet burden and inconvenience associated with the medication as key reasons. [2]
Most people with mild or moderate UC are treated with aminosalicylates first. [3] This class of drugs, including mesalazine and sulfasalazine, contain 5-aminosalicyclic acid (5-ASA) to help control inflammation in the large intestine. Mezavant XL is the only 5-ASA tablet licensed for once daily dosing. [4]

Mezavant XL, with novel MMX (MULTI MATRIX SYSTEM®) drug delivery technology, is designed to provide a prolonged release of mesalazine throughout the colon. [5] Available as a single strength tablet, containing mesalazine 1200mg, Mezavant XL is to be taken in a once daily dose of two to four tablets. Mezavant XL is indicated both for the induction of clinical and endoscopic remission in patients with mild to moderate, active UC; and for maintenance of remission. [6] Mezavant XL may be used in cases where mesalazine is an appropriate choice of treatment and offers the potential advantage of once-daily administration.

In 2006 it was estimated that over 118,000 patients in the UK were suffering with UC, [7] a type of inflammatory bowel disease (IBD) that produces inflammation and ulcers along the inside of the large intestine, also called the bowel or colon.8 The ulcers and inflammation can interfere with the normal functioning of the bowel, often causing cramping, diarrhoea, bleeding, fatigue, weight loss and frequent bowel movements. [8] UC is a chronic condition that has periods of remission and relapse, although most patients will have a normal life span.8

Non-compliance with 5-ASA therapy (defined as refilling <80% of prescribed medication)9 has been shown to be associated with a >5-fold increase in the risk of recurrence of UC. [9] Compliance is lower among male and unmarried patients and those taking multiple concomitant medications. [10]

About Shire Limited

Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit and hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.

For further information on Shire, please visit: http://www.shire.com

Shire has in-licensed the exclusive rights from Giuliani S.p.A. to develop and commercialise MMX mesalazine in the US, Canada, Europe (excluding Italy) and the Pacific Rim. Shire markets or plans to market this product as Mezavant XL in the UK and Ireland, Mezavant LP in France, Mezavant in Canada and certain other European Union countries, as well as Lialda in the United States.

Giuliani S.p.A. retains the development and commercialisation rights in Italy, (where it will receive a duplicate licence), and in South and Central America. Cosmo S.p.A., Milan developed the MMX (MULTI MATRIX SYSTEM) technology and their wholly-owned subsidiary, Cosmo Technologies Limited, owns the trademark, MMX (MULTI MATRIX SYSTEM).

Prescribing Information
(Please refer to full Summary of Product Characteristics [SPC] before prescribing)

Mezavant® XL 1200mg, gastro-resistant, prolonged release tablets.

Presentation: Mesalazine provided as 1200mg gastro-resistant, prolonged release tablets. Uses: For the induction of clinical and endoscopic remission in patients with mild to moderate, active ulcerative colitis. For maintenance of remission.

Dosage and administration: Oral. Tablets to be taken once daily (o.d.). Tablets must not be crushed or chewed and should be taken with food. Adults/Elderly: For induction of remission: 2.4 to 4.8g (two to four tablets) should be taken once daily. The highest dose of 4.8g/day is recommended for patients not responding to lower doses of mesalazine. When using the highest dose (4.8g/day), the effect of the treatment should be evaluated at 8 weeks. For maintenance of remission: 2.4g (two tablets) should be taken once daily. Children: Not recommended.

Contraindications: History of hypersensitivity to salicylates (including mesalazine) or any of the excipients of Mezavant XL. Severe renal impairment (GFR <30ml/min/1.73m2) and/or severe hepatic impairment. Special Warnings and Precautions: Use with caution in patients with confirmed mild to moderate renal impairment. All patients should have an evaluation of renal function prior to initiation of therapy and at least twice a year. If there is suspicion of blood dyscrasia, treatment should be terminated. If acute intolerance syndrome is suspected, prompt withdrawal of mesalazine is required. Caution should be used in prescribing to patients with hepatic impairment, patients with chronic lung function impairment, especially asthma (due to risk of hypersensitivity reactions), patients allergic to sulphasalazine, or patients with conditions predisposing to myo- or pericarditis. Organic or functional obstruction in the upper gastrointestinal tract may delay onset of action. See SPC for full details on warning and precautions. Interactions: Caution is recommended with concomitant use of known nephrotoxic agents including non-steroidal anti-inflammatory drugs (NSAIDS). Mesalazine inhibits thiopurine methyltransferase and caution is recommended for concurrent use of mesalazine with azathioprine or 6-mercaptopurine. Administration with coumarin type anticoagulants could result in decreased anticoagulant activity. Pregnancy and Lactation: Only use during pregnancy when clearly indicated, using caution with high doses. Caution should be exercised if using mesalazine whilst breastfeeding. Undesirable Effects: Approximately 14% subjects experienced treatment emergent adverse drug reactions in clinical trials with Mezavant XL, the majority being transient and mild or moderate in severity. Events reported as common (>1% and <10%) were flatulence, nausea or headache. Uncommon events (>0.1% and <1%) to Mezavant XL were: decreased platelet count, dizziness, somnolence, tremor, ear pain, tachycardia, hypertension, hypotension, pharyngolaryngeal pain, abdominal distension, abdominal pain, colitis, diarrhoea, dyspepsia, pancreatitis, rectal polyp, vomiting, increased alanine aminotransferase, abnormal liver function test, acne, alopecia, prurigo, pruritis, rash, urticaria, arthralgia, back pain, asthenia, face oedema, fatigue, pyrexia. Mesalazine has also been associated with the following; agranulocytosis, aplastic anaemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, neuropathy, myocarditis, pericarditis, allergic alveolitis, bronchospasm, cholelithiasis, hepatitis, angioedema, systemic-lupus erythematosus-like syndrome, myalgia, interstitial nephritis, nephrotic syndrome. Overdose: Conventional therapy for salicylate toxicity may be of benefit. Hypoglycaemia, fluid and electrolyte imbalance should be corrected and adequate renal function maintained.

Basic NHS price: £62.44 Legal category: POM. Marketing Authorisation number: PL 08081/0040. Marketing Authorisation holder: Shire Pharmaceuticals Contracts Limited, Hampshire International Business Park, Chineham, Basingstoke, Hampshire, RG24 8EP, UK. Date of revision: June 2008.

Further information is available from: Shire Pharmaceuticals Limited, Hampshire International Business Park, Chineham, Basingstoke, Hampshire, RG24 8EP, UK. Tel: 01256 894000.

MEZAVANT is a trademark of Shire LLC in the UK

Adverse events should be reported. Reporting forms and information can be found at http://www.yellowcard.gov.uk. Adverse events should also be reported to Shire Pharmaceuticals Ltd on 01256 894000.

References

[1] Kamm MA, Lichtenstein GR, Sandborn WJ et al. Gut 2008;57:893-902.

[2] Loftus EC Jr. A practical perspective on ulcerative colitis: patients' needs from aminosalicylate therapies. Inflamm Bowel Dis 2006;12:1107-1113.

[3] Travis SPL, Strange EF, Lemann M et al. European evidence-based Consensus on the diagnosis and management of ulcerative colitis: current management. J Crohn's Colitis 2008;2:24-62

[4] MIMS September 2008

[5] Lichtenstein GR, Kamm MA, Boddu P et al. Clin Gastroenterol Hepatol 2007;5(1):95-102

[6] Mezavant XL. Summary of Product Characteristics

[7] European Federation of Crohn's & Ulcerative Colitis Associations (EFCCA) newsletter, No 26, May 2007

[8] Clark ML. Gastrointestinal disease. In: Kumar P, Clarke C, editors. Kumar & Clarke Clinical Medicine (5th edition) London: Elsevier 2002; chapter 6, p253-334

[9] Kane SV et al. Medication nonadherence and the outcomes of patients with quiescent ulcerative colitis. Am J Med 2003;114:39-43

[10] Kane SV et al. Prevalence of nonadherence with maintenance mesalamine in quiescent ulcerative colitis. Am J Gastroenterol 2001;96:2929-33

Shire Limited