New hope for ulcerative colitis patients

Ulcerative colitis is a debilitating condition, but it doesn’t need to be a life sentence. Effective treatments exist1 but patient acceptance of those treatments may be the greatest barrier to inducing and maintaining remission.2

Pharmacological treatments, in particular aminosalicylate preparations, have been demonstrated effective in inducing and maintaining remission of the disease.¹ While non-compliance with demanding drug regimens has traditionally reduced the efficacy of these medicines, new once-daily, prolonged-release aminosalicylate formulations make treatment compliance much easier.²

They offer new hope for reducing symptoms and improving quality of life² for the considerable number of Australians affected by ulcerative colitis.³

UC background

Ulcerative colitis is one of several types of inflammatory bowel disease, characterised by chronic inflammation of the colonic mucosa.¹ It affects 16,000–33,000 Australians at any given time.³ The condition is diagnosed based on a combination of clinical symptoms and evidence from biopsy and endoscopic investigations. These are usually sufficient to identify ulcerative colitis. However, its features often mimic those of other diseases, particularly Crohn’s disease and infectious conditions, which should be considered in the differential diagnosis.¹

Dr Miles Sparrow, Consultant Gastroenterologist at the Alfred Hospital in Victoria, says that a thorough history-taking can help the diagnosis of ulcerative colitis.

“While Crohn’s can manifest with bloody diarrhoea this symptom will, more often than not, indicate ulcerative colitis.  Crohn’s is also more likely to present with pain and weight loss than ulcerative colitis,” Dr Sparrow said, but continued that “the gold standard for differentiating these two conditions is colonoscopy.”

Selecting and instituting treatment

Following diagnosis, the best course of management is decided based on the features and severity of the disease.¹ Most cases present at the mild–moderate stage,⁴ when common symptoms include rectal bleeding and faecal urgency.⁵ Aminosalicylate preparations containing the active moiety aminosalicylic acid (5-ASA, or mesalazine), have demonstrated the best efficacy with regard to inducing and maintaining remission of mild–moderate disease.¹

“All ulcerative colitis sufferers should be treated with aminosalicylates and most of these will achieve remission,” said Dr Sparrow.

In the management of mild–moderate ulcerative colitis, topical preparations applied to the rectum and absorbed in the colon, including gels, foams and enemas, have traditionally been considered the gold standard.⁶ However, due to patient dislike, oral preparations that require complex dosing schedules are usually used in favour of more effective topical preparations.²

Medication compliance

Despite good efficacy of oral and topical aminosalicylates² and the quality of life improvements known to accompany remission,⁶ medication non-compliance significantly reduces the effectiveness of pharmacotherapies in practice.² Compliance with topical preparations for rectal insertion is particularly problematic, despite these being the most effective form of treatment. Withdrawal from treatment once remission is achieved is also a considerable issue, as ongoing therapy is needed to maintain remmission.²

Estimates suggest that only 40% of patients are medication compliant, and non-compliance increases the risk of relapse by a factor of five.² This is a significant issue when taken in the context of evidence suggesting that relapse related to non-adherence may lead to increased colorectal cancer and dysplasia rates.⁸

Reasons for medication non-compliance

Achieving medication adherence in patients with chronic conditions that have long periods of remission, as in UC, is especially challenging.⁹ The young and the educated are particularly at risk of not maintaining adherence to their medication regimen⁹ due to psychological and dose administration issues.⁸ Patients cite difficulties associated with taking numerous tablets in multiple daily doses as a key reason for non-compliance, indicating that easier dosing schedules are an important factor in increasing medication compliance. In this context, prolonged-release aminosalicylate preparations that enable once-daily dosing schedules offer great promise in reducing the barriers to treatment compliance,² a position supported by Dr Sparrow.

“The potential for once-daily dosing with aminosalicylates is the biggest recent advance in optimising medication compliance in people with ulcerative colitis and has been shown to be as effective as multiple daily dose regimens,” he said, and added that “the once-daily formulations make it easier for patients to keep taking their medication once remission has been achieved and this helps to maintain remission.”

Prolonged-release tablets have an acid-resistant coating that prevents the release of active ingredients until the tablet reaches the lower gastrointestinal tract, reducing systemic side effects and increasing delivery to the affected sites.⁶

However, until the development and evaluation of multi-matrix system 5-ASAs, prolonged-release preparations had proven to be less effective than topical preparations. Multi-matrix system 5-ASA is an aminosalicylate preparation encapsulated in an acid-resistant coating which also incorporates lipophilic and hydrophilic excipients that promote the release of 5-ASA throughout the colon and are suitable for once-daily doses. It is the first prolonged-release formula to demonstrate comparable effectiveness to the current gold standard treatment, aminosalicylate enema.²

Effectiveness and cost-effectiveness

There is evidence that 5-ASAs with multi-matrix system coatings are a cost-effective method of treatment.⁷ A recent study assessed cost-effectiveness in the context of the United Kingdom National Health Service and considered quality adjusted life years (QALYs) in the cost-effectiveness assessment. Despite an overall increased cost to the health service of £8 per patient, multi-matrix system coated mesalazine was likely to produce cost savings in 62% of cases and be cost-effective in 74% of cases, when QALYs were taken into account.⁷ Dr Sparrow has observed a similar trend in Australia when these medications were used in a proactive management strategy.

“The benefits to patients in terms of improved quality of life, reduced absenteeism and decreased hospital visits are cost-effective when compared to the effects of poorly-controlled active disease,” he said.

New hope for ulcerative colitis patients

The promising initial evidence for new aminosalicylate preparations provide an easier, once-daily medication schedule compared to traditional preparations. For patients with ulcerative colitis, who have a high risk of medication non-compliance due to difficult dosing regimens, once-daily dosing should improve medication compliance, which is associated with a five-fold reduced risk of relapse.² The single most important factor in improving compliance in chronic asymptomatic conditions is the use of medications that allow the lowest daily dose frequency.¹⁰ Recent advances in delivery mechanisms for 5-ASA medications allow once-daily dosing and bring with them new hope for ulcerative colitis patients.

More information

References

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