Patients with mild to moderate extensive colitis should begin therapy with oral sulfasalazine in daily doses titrated up to 4-6 g/day, or an alternate aminosalicylate in doses up to 4.8 g/day. Oral steroids are generally reserved for patients who are refractory to oral aminosalicylates with or without topical therapy, or for patients whose symptoms are so troubling as to demand a “quick fix.” 6-Mercaptopurine (6-MP) or azathioprine are effective for patients who do not respond to oral prednisone but are not so acutely ill as to require intravenous therapy.

When inflammation extends proximal to the reach of topical therapy (i.e., middescending colon-splenic flexure) oral therapy is required, either solely or in combination with topical therapy (though this latter option has not been studied in randomized controlled trials). For clinically mild to moderate, but anatomically extensive disease, the first-line therapy traditionally has been sulfasalazine. Responses are dose related with up to 80% of patients who receive daily doses of 4-6 g manifesting complete clinical remission or significant clinical improvement within 4 weeks [11] [12] and approximately half achieving sigmoidoscopic remission [11] . However, the benefits of greater efficacy with the higher dose are offset by the increase in side effects. The advantages of sulfasalazine compared with the newer aminosalicylates are its longer track record and considerably lower cost. If it happens or is anticipated that these higher doses of sulfasalazine will not be well tolerated, then a 5-aminosalicylate should be used at doses of at least 2 g/day, titrating up to 4.8 g/day [14] .

The newer aminosalicylates–olsalazine [15] [16] [17] [18] , Eudagrit-S coated mesalamine [13] , and ethylcellulose-coated mesalamine [38] –are all superior to placebo and equivalent to sulfasalazine in acute therapy [9] [39] . As with sulfasalazine, therapeutic benefit is dose-related, with daily doses less than 2 g being ineffective [9] [13] [14] [38] . No significant differences in response rates have so far been demonstrated among any of the newer aminosalicylate preparations, but direct comparisons are limited by the large sample sizes that would be necessary to permit definitive conclusions [9] . Although controlled trials have not studied the combination of oral aminosalicylates with topical treatments, patients often note a more prompt resolution of rectal symptoms when a topical therapy is added. Order Brand Cialis

Oral prednisone demonstrates a dose-response effect between 20-60 mg/day [40] [41] [42] [43] , with 60 mg/day modestly more effective than 40 mg/day but at the expense of greater side effects [42] . No randomized trials have studied steroid taper schedules; most authorities [10] [43] recommend 40-60 mg/day until significant clinical improvement occurs and then a dose taper of 5-10 mg weekly until a daily dose of 20 mg is reached. At this point, tapering generally proceeds at 2.5 mg/wk [10] .

Controlled [44] [45] and uncontrolled trials [46] [47] of azathioprine in doses up to 1.5-2.5 mg/kg/day have demonstrated its effectiveness in patients who do not respond to, or cannot be weaned from steroids. Uncontrolled series have also demonstrated its value in achieving remission in patients refractory to high doses of oral steroids [46] [48] . In this capacity, its use is limited by its slow onset of action; up to 3-6 months of treatment is usually necessary to appreciate an optimal effect. As described below, azathioprine has been found effective in maintaining remission in a controlled drug withdrawal study [49] , whereas retrospective studies have demonstrated the value of 6-MP in maintaining long-term remission [50] .


So Many Advances in Medicine, So Many Yet to Come