Induction, maintenance therapies for ulcerative colitis compared

Combined oral and rectal mesalazine therapy and high-dose mesalazine are superior to standard-dose mesalazine for induction of remission, but not for maintenance of remission, in patients with mildly to moderately active left-sided or extensive ulcerative colitis, a review found.

Researchers conducted a systematic review to assess the comparative efficacy and tolerability of induction and maintenance therapies of ulcerative colitis among adults. Randomized controlled trials were included if patients were treated with oral sulfasalazine, diazo-bonded 5-aminosalicylates (5-ASAs), mesalazine (low dose, <2 g/d; standard dose, 2 to 3 g/d; high dose, >3 g/d), controlled ileal-release budesonide, or budesonide multimatrix, alone or in combination with rectal 5-ASA therapy, and if the treatments were compared with each other or placebo for induction or maintenance of clinical remission.

Results were published Aug. 16 by The Lancet Gastroenterology & Hepatology.

Eligible studies included 75 randomized trials with 12,215 patients. Based on 48 induction randomized trials (8,020 participants), combined oral and rectal 5-ASAs and high-dose mesalazine were ranked highest for induction of remission. Both interventions were superior to standard-dose mesalazine for failure to induce remission (odds ratios, 0.41 [95% CI, 0.22 to 0.77] and 0.78 [95% CI, 0.66 to 0.93], respectively). Twenty-eight randomized trials involving 4,218 participants compared six active interventions for maintenance of remission and found that all six were superior to placebo. However, combined oral and rectal 5-ASAs and high-dose mesalazine were not superior to standard-dose mesalazine, the authors wrote.

The findings can directly inform treatment guidelines, the authors continued. Patients with mild ulcerative colitis are likely to achieve remission with standard-dose mesalazine or a diazo-bonded 5-ASA. Certain patients, particularly those with more moderately active disease or those who live in areas where high-unit dose forms of mesalazine are available at a low cost, could reasonably use high-dose oral mesalazine to induce remission. Patients with extensive colitis could add a rectal 5-ASA to standard-dose or high-dose oral mesalazine, and patients with suboptimal response to oral therapy could add a rectal dose in four to six weeks.

For maintenance, standard-dose mesalazine and a diazo-bonded 5-ASA might be preferred options, the authors said. They added that cautious de-escalation of therapy to standard doses should be considered in patients who required high-dose mesalazine for induction of remission after six to 12 months.

Budesonide multimatrix might be considered as monotherapy or in addition to 5-ASA therapy in patients with moderately active disease, either initially or in the case of suboptimal response to optimized 5-ASA therapy, the review found. The review also found that budesonide multimatrix, 9 mg, can safely and effectively induce remission in patients with mild to moderate ulcerative colitis but is not more effective than an optimized 5-ASA. In addition, because it has inferior tolerability and cannot be used for long-term maintenance, it might not be an appropriate first-line medication, the authors cautioned. However, budesonide multimatrix has been suggested to have a small benefit in patients with persistent mild to moderate ulcerative colitis when added to a 5-ASA and may be an appropriate alternative to oral prednisone because it is better tolerated.

“Optimisation of 5-ASA is often an underused approach in the management of patients with mild to moderate ulcerative colitis; at the same time, 5-ASA-based therapy is often relied on too heavily, with failure to recognise patients who might be at high risk of colectomy and might therefore benefit from early escalation to immunosuppressive therapy,” the authors wrote. “By informing comparative efficacy of different 5-ASA-based treatment strategies and a quantitative assessment of success of these therapies, we believe our findings can inform clinical practice and treatment guidelines.”