Ulcerative Colitis Blog

In response to my last blog on steroid use in UC, a comment was posted regarding options for patients who experience recurrent symptoms while reducing steroid doses.

As a brief overview, patients with UC on steroid therapy fall into 1 of 3 categories:
1) Steroid responsive - Approximately 50-55% of UC patients enter into prolonged disease remission with steroids and are able to transition to stable maintenance therapies.
2) Steroid dependent - This group encompasses about 25-30% of patients who experience remission of disease with high steroid doses, but then have recurrent symptoms as the steroids are titrated to lower doses or within 6 months of finishing the first steroid course.
3) Steroid refractory - A smaller proportion of patients (15-25%) have severe colitis that fails to respond to the highest acceptable dosages of oral steroids.

The comment posted raises the question about alternative therapies for patients who have developed steroid dependent UC. A few notes on this topic:

5-ASA Medications (ie; mesalamine, balsalazide)
Based on current scientific literature, the use of oral 5-ASA medications, either alone or in combination with other therapies, has not been shown to have a significant beneficial effect in steroid-dependent UC. There is little data regarding the use of topical 5-ASA medications (enema/suppository) in limited rectal disease for steroid-dependent UC.

As such, if a patient experiences rectal bleeding from a limited segment of disease in the rectum while tapering steroids, a trial of topical therapy could be considered. This would not be of value for patients with more extensive disease.

Thiopurines (ie; azathioprine, 6-mercaptopurine)
Thiopurines are commonly used in steroid-dependent UC in an effort to maintain remission as steroids are tapered. Since they have shown success as steroid-sparing agents, their use has gained wide acceptance in clinical practice. In order to be effective, however, they should be administered at optimal doses of 2-3mg/kg body weight for azathioprine and 1-1.5mg/kg body weight for 6-mercaptopurine. In patients who have persistent symptoms despite a routine dosage of medication, levels of the drug can be measured in the blood to see if it is being metabolized effectively. If the levels are low, the medication dose may need to be increased to fully treat the inflammation.

Methotrexate
Current guidelines do not advocate the use of methotrexate in steroid-dependent UC; however, this is mostly based upon the fact that there is a paucity of well-designed studies investigating this drug in steroid-dependent UC. There is limited evidence that higher doses of oral methotrexate or the injectable formulation may benefit a subset of steroid-dependent UC patients who are intolerant of or fail treatment with thiopurines. The use of this medication may warrant further study for this indication.

Infliximab
Infliximab received FDA approval for the treatment of moderate-severe active UC in the last year or so. At least one study specifically examining its utility in steroid-dependent patients has suggested it is potentially beneficial. Infliximab is typically administered as a dose of 5mg/kg at 0, 2, and 6 weeks, then once every 8 weeks. In patients who have an inadequate or waning response, the dose of the medication can be increased to 10mg/kg and/or the dosing interval can be shortened to every 4-6 weeks. The efficacy of adalimumab in UC is under investigation.

Experimental therapies
Some medical centers offer experimental therapies for patients who are failing the currently accepted medical regimens. Before exploring such therapies, patients and physicians should have a thorough discussion about the state of the patient's overall health status, realistic expectations for the future, and risks vs. benefits.

Surgery
The goal of any treatment is to restore a patient's physical health and wellbeing. For patients who have exhausted all possible medications, surgery may be the only tenable option to give a patient his or her quality of life back. While the prospect of surgery is understandably daunting and procedures are not without the possibility of complications, surgical management eliminates the future risk of colon cancer and has the potential to restore quality of life. Any UC patient considering surgery should discuss with his/her doctor referral to a colorectal surgeon who is specifically experienced in the surgical management of IBD patients. More on issues surrounding surgery will be discussed in future blogs.