Refractory Wegener's granulomatosis responds to tumor necrosis factor blockade

Wegener's granulomatosis is a systemic necrotising vasculitis of small vessels that leads to severe impairment of affected organ systems. Conventional treatment is based on immunosuppression with a combination of steroids, cyclophosphamide, azathioprine or methotrexate over a prolonged time course. Early recurrence or disease refractory to therapy often results in a fatal outcome. As in other inflammatory disorders, tumor necrosis factor (TNF) plays an early and crucial role in progression of disease activity. We report on a patient with severe orbital Wegener's granulomatosis who developed acute renal failure despite intense conventional immunosuppression with cyclophosphamide and steroids. To stop vasculitic activity, by disrupting the autoimmune inflammatory cascade, a TNF-blocking antibody (Infliximab) was administered six times in a six-month period at 3 mg/kg body weight. Conventional immunosuppressive therapy with steroids and cyclophosphamide was continued, the latter being changed to azathioprine after three months. The first infusion of TNF antibody induced improvement of renal function, which continued throughout the course of therapy. The modification of diet in renal disease-glomerular filtration rate (MDRD-GFR) increased from 15.3 ml/min/1.73 m2 before the start of TNF-blockade to 55.5 ml/min/1.73 m2 after six months of therapy. Serum creatinine levels, proteinuria and cANCA titer decreased concomitantly. Clinical remission of Wegener's granulomatosis was induced without any major adverse events. A slight flare of orbital inflammation was successfully treated with an increased dose of azathioprine. Thus, in this case of refractory Wegener's granulomatosis TNF-blockade by monoclonal chimeric TNF-antibody (Infliximab) served as an effective tool to rescue kidney function and induce clinical remission.