Sandborn and colleagues [1] state that their placebo-controlled trial showed that "transdermal nicotine at the highest tolerated dosage (22 mg/d) has a clinically significant therapeutic benefit in active ulcerative colitis after 4 weeks." How could they make this statement if only 39% of their patients improved clinically (compared with 9% of those who received placebo)? I do not consider a 30% response (39% –9%) in ulcerative colitis to be clinically meaningful, especially because 77% of patients who received nicotine patches had various side effects; in 13%, these effects were severe enough to discontinue use of the patches.

Also puzzling is the authors' statement that "these results are particularly striking given the fact that the study patients had chronically active ulcerative colitis that was resistant to first-line therapy." How could their patients be considered resistant to therapy if their study protocol mandated that no more than 20 mg of prednisone per day be given? Why exclude patients who received higher doses? Why not administer 40, 60, or 80 mg of prednisone; nine or twelve 5-aminosalicylic acid capsules; or 150 to 200 mg of 6-mercaptopurine or azathioprine before we call these patients "resistant to therapy"? Why use low-dose prednisone therapy as a litmus test of refractoriness to justify giving these patients "the highest tolerated dosage" of nicotine?

Any conclusion about the inadequacy of response to undertreatment or inappropriate therapy is inherently flawed and misleading. I believe that in a direct comparison with an adequate and appropriate therapy, nicotine patches would have proven significantly inferior in the treatment of ulcerative colitis and would have been associated with an unacceptably high rate of side effects.