Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity

Abstract

Intravenous immunoglobulin (IVIg) is a potential alternative treatment for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) with less toxicity than conventional immunosuppressive agents. This randomized, placebo-controlled trial aimed to investigate the efficacy of a single course of IVIg (total dose 2 g/kg) in previously-treated AASV with persistent disease activity in whom there was an intention to escalate therapy. Vasculitic activity was monitored by the Birmingham vasculitis activity score (BVAS), C-reactive protein (CRP) and ANCA levels. Treatment response was defined as a reduction in BVAS of more than 50% after 3 months, and there was an intention to keep doses of concurrent immunosuppressive drugs unchanged during this period; follow-up continued to 12 months. Seventeen patients were randomized to receive IVIg and 17 to receive placebo. Treatment responses were found in 14/17 and 6/17 of the IVIg and placebo groups, respectively (p=0.015, OR 8.56, 95%CI 1.74-42.2). Following infusion of trial medication, greater falls in CRP were seen at 2 weeks (p=0.02) and 1 month (p=0.04) in the IVIg group. No differences were observed between ANCA levels or cumulative exposure to immunosuppressive drugs, and after 3 months there were no differences in CRP levels or disease activity between the IVIg and placebo groups. Seventeen adverse effects occurred after IVIg and six after placebo: they were mostly mild, although reversible rises in serum creatinine occurred in four from the IVIg group. A single course of IVIg reduced disease activity in persistent AASV, but this effect was not maintained beyond 3 months; mild, reversible side-effects following IVIg were frequent. IVIg is an alternative treatment for AASV with persistent disease activity after standard therapy.

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

“…In a retrospective series of patients treated with MMF, a reduction in disease activity occurred in 86% (19 of 22); however, few achieved complete remission, and 47% experienced a relapse by 14 months, which required other therapies (25). In a placebo-controlled trial, 82% of patients (14 of 17) responded to IVIG therapy; however, the response was not maintained beyond 3 months (26). In a longterm followup of 71 patients treated with alemtuzumab, 85% responded; however, relapses occurred in 72% at a median of 9.2 months (27).…”

Therapeutic Effect of Anti–TNF-α Antibodies in an Experimental Model of Anti-Neutrophil Cytoplasm Antibody–Associated Systemic Vasculitis

“…This approach mirrors closely the scenario encountered in clinical practice, when patients present with established disease. In addition, we believed that it was critical to use an appropriate mouse IgG as a control, as the administration of IgG in itself has a therapeutic effect in vasculitis (34). Although not identical to human microscopic polyangiitis (rats with EAV develop little excretory renal insufficiency or involvement of organs other than kidney and lung), the EAV model shares many of the features of its human counterpart.…”

Diffuse alveolar hemorrhage

“…22 IVIG has been used in recurrent or persistent disease, but the response is often transient. 23 Following successful induction patients are on a maintenance regimen for at least 24 months or longer. Methotrexate weekly (10-20 mg) and azathioprine daily (2 mg/kg) are well studied treatment options.…”