This study showed that the two drugs are similar in maintaining remission after induction in the AAVs. However, perhaps surprisingly, the hypothesis that MTX would be a safer alternative was not proven. Why might this be the case? One possibility is that the target dose of MTX (25 mg per week) was higher than doses commonly used in RA and other inflammatory arthritides. In addition, significant numbers of patients had renal disease. That the presence of renal disease may have influenced the frequency of ADEs is suggested by findings in the NORAN trial (Nonrenal Wegener’s Granulomatosis Treated Alternatively with Methotrexate) in which ADEs led to discontinuation of the drug in only 8% of patients.5 In the present study, there was no association between the frequency and severity of ADEs and renal impairment in the MTX group, but numbers were relatively small.
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Explore This IssueApril 2009
I see both good and bad news in the outcome of this study. Both AZA and MTX are effective as maintenance medications in patients with AAV achieving remission, so the clinician has options and might tailor maintenance therapy to the individual. However, both agents have a significant failure rate as measured by late relapses and significant ADEs. Clearly, more refined treatment regimens—both induction and maintenance—are required. Based on extensive experience using MTX relatively safely for RA and other arthritic diseases, I think that many clinicians, including myself, may still consider MTX the preferred agent for maintenance in individuals with more limited forms of AAV—for example, in patients with no renal disease or other high-risk disease features and for whom lower doses of MTX might be adequate.
- Haubitz M, Schellong S, Gobel U, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement. Arthritis Rheum. 1998;41:1835-1844.
- Guillerin L, Cordier JF, Lhote F, et al. A prospective, multi-center, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of Wegener’s granulomatosis. Arthritis Rheum. 1997;40:2187-2198.
- Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutophil cytoplasmic antibodies. N Engl J Med. 2003; 349:36-44.
- Langford C, Talar-Williams C, Barron KS, Sneller MC. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener’s granulomatosis: extended follow-up and rate of relapse. Am J Med. 2003;114:463-469.
- deGroot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005; 52:2461-2469.