Ulcerative colitis remission therapy

Treatment of acute episodes of ulcerative colitis is dictated by the severity and extent of disease, and first-line therapy of mild to moderate disease involves oral or topical aminosalicylate derivatives. Topical suppositories and enemas are preferred for active distal UC (left-sided disease and proctitis), as they deliver mesalamine directly to the site of inflammation. Topical mesalamine is superior to both topical corticosteroids and oral aminosalicylates for inducing remission in active mild to moderate UC.1,33,34 Enemas are appropriate for patients with... 

Maintenance of remission of ulcerative colitis may be achieved with oral or topical aminosalicylates. Mesalamine suppositories 1 g daily may prevent relapse in up to 90% of patients with proctitis.1 Mesalamine enemas are appropriate for left-sided disease and may often be dosed three times weekly. Oral mesalamine at lower doses (e.g., 1.6 g per day) may be combined with topical therapies to maintain remission. Topical or oral corticosteroids are not effective for maintaining remission of distal UC and should be avoided. 

Ulcerative colitis In the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis for the prolongation of the remission period between acute attacks of ulcerative colitis (refer to the sulfasalazine monograph in the Gl chapter). 

Sulfasalazine treatment results in an 85% remission rate in mild to moderate ulcerative colitis. Termination of therapy leads to an 80% relapse within the next year. In Crohn s disease, sulfasalazine acts primarily on involved colonic mucosa, although remission of ileal disease also has been reported. The National Cooperative Crohn s Disease Study found sulfasalazine to be better in the treatment of colonic disease, while corticosteroids were judged better in the treatment of small bowel disease. Since sulfasalazine does not prevent relapse of Crohn s disease once remission is achieved, maintenance therapy is not characteristically used. 

Adjunctive treatment of ulcerative colitis Rectal 100 mg at bedtime for 21 nights or until clinical and proctologic remission occurs (may require 2-3 mo of therapy). Rectal (Cortifoam) 1 applicator 1-2 times a day for 2-3 wk, then every second day until therapy ends. Topical Apply sparingly 2-4 times a day. 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

ASA drugs induce and maintain remission in ulcerative colitis and are considered to be the first-line agents for treatment of mild to moderate active ulcerative colitis. Their efficacy in Crohn s disease is unproven, although many clinicians use 5-ASA agents as first-line therapy for mild to moderate disease involving the colon or distal ileum. 

Azathioprine and 6-MP are important agents in the induction and maintenance of remission of ulcerative colitis and Crohn s disease. Although the optimal dose is uncertain, most patients with normal thiopurine-S-methyltransferase (TPMT) activity (see below) are treated with 6-MP, 1-1.5 mg/kg/d, or azathioprine, 2-2.5 mg/kg/d. After 3-6 months of treatment, 50-60% of patients with active disease achieve remission. These agents help maintain remission in up to 80% of patients. Among patients who depend on long-term glucocorticoid therapy to control active disease, purine analogs allow dose reduction or elimination of steroids in the majority. 

Infliximab is approved for the treatment of patients with moderate to severe ulcerative colitis who have had inadequate response to mesalamine or corticosteroids. After induction therapy of 5-10 mg/wk at 0, 2, and 6 weeks, 70% of patients have a clinical response and one third achieve a clinical remission. With continued maintenance infusions every 8 weeks, approximately 50% of patients have continued clinical response. 

Pulsed glucocorticoid therapy for moderately severe ulcerative colitis, given on an out-patient basis, can induce remission more quickly than conventional oral glucocorticoid therapy (421). There were no serious adverse effects in 11 patients given pulsed glucocorticoids or in eight treated conventionally. The two regimens were equally efficacious. 

Steroids do not have a role in the maintenance of remission with ulcerative cohtis because they are ineffective. Steroids should he gradually withdrawn after remission is induced (over 3 to 4 weeks). If they are continued, the patient will he exposed to steroid side effects without likelihood of benefits. Azathioprine is effective in preventing relapse of ulcerative colitis for periods exceeding 4 years. However, 3 to 6 months may be required for beneficial effect. For patients who initially respond to infliximab, continued administration of 5 mg/kg every 8 weeks as maintenance therapy is an alternative for steroid dependent patients. 

Ciclosporin may induce remission in some patients with severe ulcerative colitis unresponsive to corticosteroid. The drug is given in a dose of 2-4 mg/kg i.v. until remission is attained. Renal function should be monitored closely as ciclosporin is nephrotoxic (see p. 620). For maintenance therapy azathioprine (see below) is often substituted. Ciclosporin use only delays surgery for many patients after 1 year 50% will have relapsed and undergone colectomy. 

The goals of therapy for ulcerative colitis are to induce remission of the gastrointestinal inflammatory process, to relieve symptoms, and to maintain remission. The two most... 

Although steroids are effective in achieving remission of ulcerative colitis through their anti-inflammatory properties, they do not change the underlying disease process. In comparison with sulfasalazine or other aminosalicylates, corticosteroids seem to have a faster onset of action and induce remission in 2 to 4 weeks. Parenteral corticosteroids are indicated for severe ulcerative colitis. Once a response is achieved, IV corticosteroids should be converted to oral therapy. However, if there is no response from IV corticosteroids within 72 hours, surgery may be indicated. 

Placebo therapy in the treatment of ulcerative colitis has consistently shown a measurable benefit. Ilnyckyj et al. reviewed the literature to determine the extent of placebo response in the treatment of acute ulcerative colitis.Analysis of all double-blind, placebo-controlled trials of patients with active ulcerative colitis by multiple reviewers ensured appropriate data extraction and a series of analysis were conducted on the various elinical, endoscopic, and histological endpoints. Remission (10%) occurred less frequently than response (30%) with placebo therapy. Number of patient visits appeared to be related to placebo response (clinical, endoscopic, and histologic) but not remission. Therefore, the authors concluded that conditioned response with active intervention may have a significant effect in placebo response. 

Parenteral nutrition is an important component of the treatment of severe Crohn s disease or ulcerative colitis. The use of parenteral nutrition allows complete bowel rest in patients with severe ulcerative cohtis, which may alter the need for proctocolectomy. Parenteral nutrition has also been valuable in Crohn s disease, because remission may be achieved with parenteral nutrition in about 50% of patients. In some patients, the disease may worsen when parenteral nutrition is stopped. Patients with enterocutaneous fistulas of various etiologies benefit from parenteral nutrition. Parenteral nutrition may also be valuable in children or adolescents with growth retardation associated with Crohn s disease, but surgery is often necessary with severe disease. Finally, when possible, home parenteral nutrition should be used for patients requiring long-term therapy, particularly those with short gut as a consequence of surgical resection. 

Steroids have a place in the treatment of moderate to severe ulcerative colitis that is unresponsive to maximal doses of oral and topical mesalamine derivatives. Oral steroids (usually up to 1 mg/kg per day of prednisone equivalent) may be used for patients who do not have an adequate response to sulfasalazine or mesalamine. Overall, steroids and sulfasalazine appear to be equally efficacious however, the response to steroids may be evident sooner. Oral steroids should not be used as initial therapy for mild to moderate ulcerative colitis, mainly because of the known risks of steroid use. If steroids are used to attain remission, tapered drug withdrawal should be accomplished to minimize long-term steroid exposure. 

Rectally administered steroids or mesalamine can be used as initial therapy for patients with ulcerative proctitis or distal colitis. Rectal agents are also beneficial for treatment of tenesmus. With these agents, local actions are believed to be responsible for drug effects. Rectal steroids are effective in the treatment of active, distal ulcerative colitis. However, rectal mesalamine is more effective than rectal steroids for inducing remission. ... 

D Albasio G, Pacini F, Camarri E, et al. Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis A randomized double-blind study. Am J Gastroenterol 1997 92 1143-1147. 

Topical preparations of mesalamine suspended in a wax matrix suppository (rowasa) or in a suspension enema (canasa) are effective in active proctitis and distal ulcerative colitis, respectively. They appear to be superior to topical hydrocortisone in this setting, with response rates of 75-90%. Mesalamine enemas (4 g/60 mL) should be used at bedtime and retained for at least 8 hours the suppository (500 mg) should be used two to three times a day with the objective of retaining it for at least 3 hours. Response to local therapy with mesalamine may occur within 3-21 days however, the usual course of therapy is from 3-6 weeks. Once remission has occurred, lower doses are used for maintenance. 

Immunologic A 64-year-old woman developed persistent fever with mucositis and submandibular phlegm, not responsive to antibiotics. She was on therapy with mesalazine for ulcerative colitis, which was currently in remission, and levothyroxine for hypothyroidism. Laboratory tests showed leukopenia with severe neutropenia, and blood culture positive for multi-resistant Streptococcus oralis. The syndrome was managed with antibiotics and filgrastim. The latter drug yielded a scarce benefit, with a modest neutrophil count recovery, which was lost after its discontinuation. Mesalazine was then discontinued, and the patient had a complete and stable normalisation of her neutrophil count within the following 20 days [86 ]. 

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