What I Do…
For patients who receive cyclophosphamide for remission-induction, I follow the standard recommendation to switch to azathioprine or methotrexate between Months 3 and 6, continue maintenance to complete 18 months of treatment, then taper off the maintenance drug—in most patients. In the absence of data comparing 18-month to four-year strategies, I think the available data (e.g., see reference 9) suggest that the rate of first relapse accelerates or is unchanged after discontinuation of the maintenance drug at Month 18, rather than approaching a plateau as one would expect if patients with a tendency to relapse “declare themselves” early. Thus, for patients in whom a relapse might be devastating (e.g., due to tenuous renal function or poor tolerance of glucocorticoids), continuing maintenance therapy indefinitely is reasonable. It is also appropriate for patient preference to play a large role in decision making on this issue.
However, I prefer to use rituximab for remission-induction therapy in most ANCA-positive patients, and particularly those who have previously received cyclophosphamide.4 Since there cannot yet be a strong guideline for maintenance therapy in this setting, I interpret the observational data as follows. For a patient with a first episode of AAV associated with anti-MPO antibodies, I do not use any subsequent maintenance drug (other than prednisone, see below). For a patient with a severe relapse, particularly if it occurs on a maintenance drug, I continue rituximab, either 1,000 mg every four months or 1,000 mg twice every six months indefinitely; however, since the community’s experience with such a strategy only extends for three to four years, I am sure that the prospect of discontinuing therapy will arise among patients who do well for several years. For a patient with a first episode of AAV associated with anti-PR3 antibodies, I usually recommend a second course of rituximab six months after the first, then watchful waiting. Although I do not routinely start azathioprine or methotrexate for maintenance four to 12 months after an initial course of rituximab, I expect that some colleagues do.
I also continue prednisone 5 mg/day for a year in most patients, regardless of their induction regimen or ANCA specificity. I stress that expert opinion varies widely on this issue. It is again appropriate to involve the patient in the decision making in light of the uncertainties. Parenthetically, many patients, particularly those with GPA and upper-airway disease, require low or moderate doses of prednisone and other immune-suppressive drugs to keep inflammation in check on a chronic basis; this issue is distinct from “remission maintenance” as I have discussed it.