Oral mesalazine for ulcerative colitis and Crohn disease

• On 1 October and 1 December 2019, changes were made to oral mesalazine medicines listed on the PBS General Schedule
  Changes apply to restriction levels and clinical criteria for all oral mesalazine medicines for ulcerative colitis and Crohn disease.
• The PBAC considered a literature review, sponsor feedback, utilisation analysis and DUSC reports
  It concluded that over 50% of mesalazine use is first-line and outside the PBS restrictions, which include sulfasalazine intolerance.
• Tolerance and safety issues for sulfasalazine are likely driving the greater use of mesalazine
  Evidence demonstrates no efficacy differences between mesalazine and sulfasalazine, but mesalazine has improved tolerance and reduced likelihood of adverse events.
• PBS restriction levels were decreased to allow mesalazine use in the same circumstances as sulfasalazine
  The PBAC also recommended removing the clinical criteria, but only with a concurrent price reduction, to ensure cost-effectiveness.

On 1 October and 1 December 2019, changes were made to the listings of all oral mesalazine medicines on the PBS General Schedule (Section 85) for the treatment of either ulcerative colitis alone or ulcerative colitis/Crohn disease.^1,2 In the previous listings, the restriction levels were Authority Required (Streamlined) and included the clinical criteria of hypersensitivity to a sulfonamide or intolerance to sulfasalazine.³

In the new listings, the restriction levels have been decreased to Restricted Benefit and the clinical criteria have been removed for all PBS-listed oral mesalazine medicines (Table 1).^1,2

See the PBS website for complete details for each item.

At the March 2019 PBAC meeting, the PBAC considered a literature review, feedback from sponsors and utilisation analysis of oral 5-aminosalicylic acids (5-ASA) medicines (balsalazide, mesalazine, olsalazine and sulfasalazine).⁴ which are anti-inflammatory immunosuppressants prescribed for inflammatory bowel disease.⁵ It also considered reports from the Drug Utilisation Sub-Committee (DUSC) on ulcerative colitis and 5-ASA medicines.⁴

The PBAC found that a high proportion of patients (over 50%) are being prescribed mesalazine as first-line treatment, despite the PBS restrictions of hypersensitivity to a sulfonamide or intolerance to sulfasalazine, and that the daily dose of mesalazine had increased since it was initially PBS-listed. The PBAC concluded that subsidised use of oral mesalazine was no longer cost-effective.⁴

The DUSC reports found that tolerance and safety issues for sulfasalazine were likely driving the greater use of mesalazine.⁶ A Cochrane review of 5-ASAs demonstrated no differences in efficacy between mesalazine and sulfasalazine, but improved tolerance and a reduced likelihood of adverse events with mesalazine.⁷

The PBAC also considered that oral mesalazine may be used preferentially over sulfasalazine due to improved tolerance, reduced monitoring requirements (less frequent renal and liver function testing, and no need for complete blood counts⁵) and a lower pill burden.⁴

The PBAC advised it was willing to decrease the restriction levels to allow oral mesalazine to be used in the same circumstances as sulfasalazine. It also recommended the removal of the clinical criteria regarding documented hypersensitivity reaction to a sulfonamide, and patient intolerance to sulfasalazine, but required a price reduction from manufacturers to ensure cost-effectiveness of oral mesalazine.⁴

The different brands of mesalazine that are available are not interchangeable. This is due to differences in formulation (eg, controlled release, enteric coating) and release properties.⁵

In addition to adverse effects related to 5-ASAs in general, neuropathy is a rare adverse effect that may occur with the use of mesalazine.⁵

Patients may be checked for low treatment adherence to sulfasalazine due to the large pill burden and switched to mesalazine where appropriate as an alternative treatment option.⁶

Patients should be advised that mesalazine tablets or granules should be swallowed whole, not chewed or crushed.⁵