Current Medical Therapy

Alastair Makin, Manchester

Powerpoint File

The medical management of ulcerative colitis (UC) utilises a small number of tried and tested treatments but a number of new developments may increase the non-surgical options. Medical management is best considered in two ways – treatment of the acute episode and maintenance of remission.

TREATMENT OF AN ACUTE ATTACK

Aminosalicylates produce a response in approximately 60% of patients with moderately active UC but are not as effective as steroids. The response rate is dose related and studies have demonstrated the role of daily doses up to 4.8g to induce remission. Newer preparations of 5-ASA appear to be better tolerated and may be slightly more effective than sulphasalazine but are considerably more expensive.

Corticosteroids provide rapid and effective symptom relief. Hydrocortisone and prednisolone produce a similar response but the intravenous route is more effective in resistant cases. There is no evidence to confirm an optimal dose or duration of treatment but steroids should be weaned as quickly as possible to avoid toxicity. Topical steroids are as effective as oral or intravenous preparations for left-sided or distal disease.

The purine analogues, azathioprine and 6-mercaptopurine, have a slow onset of action which limits their use in the acute attack although there is evidence that initial treatment with intravenous azathioprine may accelerate the onset of action. Azathioprine and steroids are an effective combination in refractory colitis that allows a more rapid reduction of the steroid dose.

Intravenous cyclosporin is increasingly used as a salvage therapy in severe active and refractory colitis. Cyclosporin may defer surgery in up to 80% of these cases and produce a long-term remission rate of almost 50% when used in conjunction with long-term immunosuppression.

Infliximab may have a role in the acute attack but controlled evidence is lacking and a randomised clinical trial is needed. There is also interesting preliminary data suggesting that treatment with porcine whipworm ova may induce and maintain remission in steroid resistant or dependent disease.

MAINTENANCE OF REMISSION

Corticosteroids have no role in long-term maintenance because of their toxicity. 5-ASA preparations are the treatment of choice but doses of more than 2g/day are usually required. Remission is more likely when 5-ASA therapy is initiated along with steroids during the acute attack and when treatment is continued for at least 6 months. Balsalazide may have a role as a salvage therapy when other preparations have either failed or not been tolerated. It has been suggested recently that a combination of oral and topical 5-ASA preparations is more effective than treatment with either preparation alone. A recent study indicates that variable dosing with a 5-ASA determined by the patient may be a more effective method of maintaining remission.

Azathioprine and 6-mercaptopurine are the only other drugs with a proven role in maintenance. There are concerns concerning these drugs long-term use but it is suggested that treatment up to 2 years is safe. However, relapse rates are higher if the drug is discontinued within 4 years of initiation and this maybe the optimum duration of treatment.