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The Clinical Approach to Patients with Vasculitis 171

[50]. It is not known whether tumor necrosis factor (TNF) biological blocking agents have an
additive effect on malignancy, however all such patients who developed malignancy received
cyclophosphamide prior to the TNF-blocker etanercept. Premature ovarian failure occurs in
30% to 50% of premenopausal women following cyclophosphamide therapy that is
cumulative and more pronounced with increasing age at administration. Accordingly, women
with GPA so treated with daily oral cyclophosphamide for up to 6 months had significant loss
of ovarian reserve as measured by the anti-Müllerian hormone level [51]. The approval of
rituximab for AAV which does not carry the risk of ovarian failure affords a therapeutic
alternative to cyclophosphamide. The administration of gonadotropin-releasing hormone
(GRH) analog ten days prior to an intravenous bolus of cyclophosphamide appears to
preserve fertility [52]. Cryopreservation techniques to preserve ovarian tissue and stimulate
oocytes can be offered to child-bearing women before treatment of cyclophosphamide [53].
Other immunosuppressive medications used in the therapy of vasculitides such as
methotrexate and mycophenolate mofetil, with well-documented teratogenic potential, should
be discontinued several months prior to conception. When necessary, azathioprine and
corticosteroids can be safely administered during pregnancy to control disease activity
although the safety of biologic agents during pregnancy is largely unknown. There is limited
transmission of rituximab across the placenta. One patient who received rituximab during her
first trimester of pregnancy for GPA sustained no adverse effects on fetal development [54].

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[4] Poulton, C. J., Nachman, P., Hu, Y., et al. Pathways to renal biopsy and diagnosis
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[5] Grayson, P. C., Cutherbertson, D., Carette, S., et al. New features of disease after
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[6] Pagnoux, C., Seror, R., Henegar, C., et al. Clinical features and outcomes in 348
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[7] De Vita, S., Quartuccio, L., Isola, M., et al. A randomized controlled trial of rituximab
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