Prolonged treatment of refractory Wegener's granulomatosis with 15-deoxyspergualin: an open study in seven patients

Abstract

In patients with refractory Wegener's granulomatosis, prolonged treatment with DSG seems safe and successful.

Rituximab for Refractory Wegener's Granulomatosis

“…Refractory disease was defined as meeting the first three criteria while receiving a maximally tolerated dose of cyclophosphamide or having contraindications for the repeated use of cyclophosphamide for treatment of the severe disease flare (history of documented cytopenias or hemorrhagic cystitis that prompted discontinuation of cyclophosphamide in the past, or malignancies other than nonmelanoma skin cancers within the last 5 yr). This definition of refractory disease is consistent with the definition used by the European Vasculitis Study Group and allows for comparability of trial results with those of other reports (37,38). In addition, patients had to be 18 yr or older, able to provide informed consent, and have an absolute white blood count of 1,000/l or greater, and premenopausal women had to use an acceptable method of birth control for the duration of the trial.…”

“…For the domain of Physical Functioning, the change from baseline to 1 yr was found to be significantly correlated with the BVAS/ WG score at enrollment (Spearman rank correlation, r ϭ ϩ0.73, p ϭ 0.026). (38). In all cases, data are presented as means Ϯ SD.…”

In vivoeffects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis

“…Nevertheless, it is believed that ANCA production is, at least partly, T celldependent. Because DSG treatment decreases ANCA titre, as we have shown previously [3,4], this could indicate that activation of autoreactive T cells is also impaired by DSG, either directly or by influencing antigen presentation. However, direct proof for this assumption has to be established.…”

“…The activity of disease was evaluated according to clinical and radiological parameters and assessed according to the Birmingham Vasculitis Activity Score (BVAS). The clinical outcome of the patients has been described previously [4].…”

“…Therefore, new treatment strategies are warranted, particularly in frequent relapsing or refractory patients and in those suffering from side effects of cyclophosphamide. Previously we have reported that treatment with the immunosuppressive drug 15-deoxyspergualin is successful in patients with refractory WG [3] and may also have beneficial effects during long-term treatment [4]. 15 laterosporus.…”