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.