Ulcerative Colitis: Achieving and Maintaining Remission

Hannah R. Howell, PharmD

Disclosures

US Pharmacist. 2008;33(12):30-38. 

In This Article

Other Medical Therapy

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are immunomodulators, and their activity results from an unknown mechanism of their active metabolites, 6-thioguanine nucleotides. Neither is used to induce remission, as their onset of activity is about three months. AZA or 6-MP is recommended for maintaining remission in patients who frequently relapse while on adequate doses of 5-ASA or who are intolerant to 5-ASA treatment.[3] They may also be used to lower or discontinue CCS therapy in patients with chronic, active UC who are dependent on CCSs.[23]

There have been conflicting data regarding the efficacy of AZA and 6-MP in maintaining remission of UC. A recent Cochrane review identified six randomized, controlled trials of at least one year's duration that compared AZA or 6-MP to placebo, sulfasalazine, or oral 5-ASA. AZA and 6-MP were superior to placebo in maintaining remission, but conclusions could not be drawn from the active comparator studies. The review concluded that in light of safer and more established maintenance therapy with 5-ASA, AZA or 6-MP could only be recommended in patients requiring repeated courses of CCSs.[27]

For long-term therapy, a large, multicenter study found that treatment with AZA or 6-MP reduced the incidence of active flares and steroid requirements in the first four years of treatment. Continuation beyond four years led to a further reduction in steroid use and improvement in disease activity.[28] Patients in complete remission for many years may be able to discontinue AZA or 6-MP, but continuing therapy may be beneficial in most patients.

Cyclosporine is an immunosuppressant that works by blocking lymphocyte activation. It can be used as a rescue therapy for patients with severe, refractory UC. High doses can be effective in achieving remission in up to 80% of hospitalized patients who have been unresponsive to CCSs.[29]

Cyclosporine alone is not effective for maintaining remission, but coadministration with AZA or 6-MP for a few months effectively maintains remission in the majority of patients who initially responded to IV cyclosporine.[29]

Infliximab is a chimeric monoclonal antibody directed against the proinflammatory cytokine tumor necrosis factor. It has been used to treat Crohn's disease for many years, and now is being used for patients with active UC who have not responded to conventional therapies.[30]

While earlier studies have reported conflicting results, the more recent randomized controlled ACT1 and ACT2 trials have established the efficacy of infliximab for inducing and maintaining remission for outpatients with moderate to severe UC for up to one year. Almost 25% of infliximab-treated patients were completely off steroids and in clinical remission at the end of the study compared to less than 10% of controls. In addition, the study showed that patients treated with infliximab were less likely to have mucosal damage, which may be significant since normal mucosa has been associated with a reduction in the risk of colorectal cancer.[31]

Although methotrexate and antibiotics like metronidazole may play a role in the treatment of Crohn's disease, there is not enough evidence to support the use of either in UC. Antibiotics should only be used if there is a known or suspected infection or immediately before surgery.[3]

Antidiarrheals or antispasmodics may help with mild diarrhea and abdominal cramping as long as obstruction and colonic dilation are not suspected. Routine opioids should be avoided due to the risk of addiction and the potential for inducing toxic megacolon. Patients who receive frequent CCSs should receive calcium and vitamin D supplementation, as well as bisphosphonates, due to the risk of osteoporosis.[26]

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