A major problem physicians and patients face when deciding on the treatment of rare diseases such as pemphigus and bullous pemphigoid is deciding on the best course to take. The decision is difficult as it is best made on the basis of objective evidence that the selected treatment works, and that evidence is sparse. The best objective evidence that a treatment is effective is to conduct a randomized trial, in which two or more treatments are compared head-to-head. Unfortunately, as bullous diseases are rare (which is a good thing), very few randomized trials have been conducted.
But there is another problem, which is rarely appreciated. It is that even when a randomized trial is conducted, the conclusions may not be clear. The problem is illustrated by a recent randomized trial in which the effectiveness of mycophenolate mofetil (CellCept) was compared to that of azathioprine (Imuran) for the treatment of bullous pemphigoid. All patients were also treated with systemic steroids. The physicians need to be commended on conducting the trial – it is one of the very few randomized trial in this disease. Their conclusion was that mycophenolate mofetil was preferable to azathioprine because it was similarly effective but less toxic.
However, the opposite conclusion can be drawn from the same data that azathioprine is more effective and overall just as safe as mycophenolate mofetil. The time to induce complete remissions, the cumulative dose of steroids used, and the duration of remission were all better in patients treated with azathioprine than in those treated with mycophenolate mofetil. The average time to induce complete remission was 50% shorter, the time to induce remission in 100% of patients was 3 times less, the cumulative dose of steroids used was 15% less, and the duration of remissions was 30% longer in patients treated with azathioprine (n=38) that in those treated with mycophenolate (n=35). While these differences were not statistically significant, because the number of patients was small, the trend points to azathioprine as the more effective drug.
The authors also concluded mycophenolate mofetil was a safer drug because it was associated with fewer liver toxic effects. However, infections were more common in patients treated with mycophenolate and the overall number of serious side effects (grades 3 and 4) was similar in both groups; i.e. 11 serious adverse events in patients treated with azathioprine compared to 13 in those treated with mycophenolate mofetil.
What to make of these different interpretations of the same data That even the results of randomized trials need to be interpreted carefully. In this trial, where the same data can be interpreted differently, there probably was little difference in the efficacy or safety of azathioprine and mycophenolate mofetil as adjuvant therapies for the treatment of bullous pemphigoid. A more fundamental question is whether either of these drugs provides a benefit over the use of only systemic steroids in the treatment of this disease. A randomized trial is needed to answer this question.