How Important is Onset of Action in Ulcerative Colitis Therapy?

Pharmacotherapy is the cornerstone of management in ulcerative colitis. However, controversy remains over optimal medical strategies. Specifically, differences in the onset of action of various drug therapies are thought to influence the achievement and maintenance of remission of disease, yet this is poorly characterised.

There is a wide range of recent data concerning aminosalicylates, with much debate as to the relative merits of the various formulations and delivery systems. Meta-analyses confirm the efficacy of aminosalicylates for the induction and maintenance of remission and suggest that the newer agents are comparable in efficacy to sulfasalazine. Among aminosalicylates, data from clinical trials reveal that the onset of action is earlier with balsalazide than mesalazine. Although the efficacy of the newer 5-aminosalicylate agents is no greater than that of sulfasalazine, they have better adverse effect profiles. Factors such as tolerability and adherence appear more important than onset of action in long-term maintenance.

Corticosteroids have long been used in the treatment of ulcerative colitis, yet there is a paucity of data regarding this. They have a rapid onset of action but considerable systemic adverse effects. Therefore, corticosteroids are reserved for disease that fails to respond to other agents or for primary therapy in patients with severe disease, although there is no universal acceptance of a threshold at which to initiate corticosteroid treatment.

Rectal preparations of both aminosalicylates and corticosteroids have been developed in an attempt to exert a more rapid and direct onset of action while minimising adverse systemic effects. In clinical trials, topical preparations of both aminosalicylates and corticosteroids are effective in inducing remission. However, patient acceptability and proximal extent of disease dictate selection of a topical agent more than concern with rate of onset.

A wide range of immunomodulators have been investigated in patients with steroid-refractory ulcerative colitis. The thioguanine derivatives are the most widely used but have a limited evidence base to support this use with controlled trials providing equivocal results regarding efficacy in severe ulcerative colitis. In addition, the thioguanine derivatives have a protracted onset of action and a considerable serious adverse effect profile. Calcineurin inhibitors and methotrexate have a more rapid onset of action than the thiopurines but have even less data to support their widespread use. They are widely regarded as salvage therapy and further data are required. Regarding biological agents, infliximab revolutionised the treatment of Crohn’s disease, yet results in ulcerative colitis have been disappointing. Further trials are ongoing with great anticipation for more favourable data.

The practical clinical implications of any differences between the agents depend on patient satisfaction with various therapies. Noncompliance is a major concern in maintenance therapy and is probably associated with relapse. Dose administration schedules and acceptability of therapy appear to be important factors in adherence. Overall, it is not clear that onset of action has a major influence on patient adherence and addressing issues of compliance may have more direct clinical impact.