Effectiveness of TNF-alpha blockade with infliximab in refractory Wegener's granulomatosis.

OBJECTIVE

To study the effect of the chimeric monoclonal anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in the induction of remission in six patients refractory to standard treatment with cyclophosphamide and corticosteroids. In four patients, other measures for treating refractory Wegener's granulomatosis (WG) that have been advocated previously, i.e. intensified cyclophosphamide therapy and additional intravenous immunoglobulin, were ineffective.

METHODS

Patients received infliximab (3 mg/kg in two patients and 5 mg/kg in four patients) with a 2-week interval after the first administration and 4-week intervals between infusions until remission, in addition to cyclophosphamide and corticosteroids. Vasculitis activity was assessed with the Birmingham Vasculitis Activity Score (BVAS). A standardized interdisciplinary approach was used for the follow-up of specific organ involvement.

RESULTS

Remission was induced in five patients and corticosteroid doses could be tapered. Acute-phase responses (e.g. C-reactive protein) normalized. Titres of c-ANCA (cytoplasmic pattern antineutrophil cytoplasmic antibodies) were no longer detectable. The BVAS was reduced to zero. The higher dose of infliximab (5 mg/kg) seemed more effective in inducing remission. One patient was withdrawn because of suspected systemic infection. Five patients remained in remission for 6-24 months of follow-up.

CONCLUSION

The data suggest that infliximab may provide an effective and more specific therapeutic option in the treatment of active WG refractory to standard treatment.