Preventing Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis—Reply

In Reply: Dr Arnaud and colleagues raise the concern that treatment with mycophenolate mofetil may be more effective if mycophenolic acid levels were monitored. In keeping with the current standard of care for treatment with mycophenolate mofetil, our trial protocol did not include mycophenolic acid level monitoring.

Although further research using mycophenolic acid level–driven dosing would be of interest, our recommendation that mycophenolate mofetil not be used as first-line therapy is unlikely to change. The addition of level-driven monitoring would have had to prevent 26 relapses in the mycophenolate mofetil group in our trial to be shown superior to azathioprine (a reduction from 55% to 21% of patients with relapse). Such a large additional treatment effect simply from mycophenolic acid level–driven dosing is improbable. Even if mycophenolic acid level monitoring improved the efficacy of mycophenolate mofetil, it is associated with higher mycophenolic acid exposure and toxicity. Further, marginal improvements in efficacy with mycophenolic acid level monitoring are unlikely to offset the additional costs and complexities in treatment that it would entail, making it a less appealing approach for both patients and health care systems.