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J Am Soc Nephrol 15:717-721, 2004
© 2004 American Society of Nephrology

CLINICAL SCIENCE

Prospective Study of TNF{alpha} Blockade with Infliximab in Anti-Neutrophil Cytoplasmic Antibody-Associated Systemic Vasculitis

Anthony Booth*, Lorraine Harper{dagger}, Tariq Hammad{ddagger}, Paul Bacon{dagger}, Megan Griffith§, Jeremy Levy{ddagger}, Caroline Savage{dagger}, Charles Pusey{ddagger} and David Jayne*

*Department of Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom; {dagger}Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom; {ddagger}Division of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; and §Department of Renal Medicine, St. Mary’s Hospital, London, United Kingdom.

Correspondence to Dr. A.D. Booth, Department of Renal Medicine, University of Cambridge, Box 110, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom. Phone: 44-1223-245151 ext. 3259; Fax: 44-1223-216893; E-mail: tonybooth1{at}yahoo.co.uk

ABSTRACT. Tumor necrosis factor {alpha} (TNF{alpha}) plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. TNF{alpha} blockade is a potential therapy for these disorders. Methods: An open-label, multi-center, prospective clinical trial in two subgroups was performed. Study I examined acute disease, either first presentation or relapse (Birmingham Vasculitis Activity Score [BVAS] >= 10; n = 16); study II examined persistent disease (BVAS >= 4; n = 16). Patients received infliximab (5 mg/kg) at 0, 2, 6, and 10 wk. Concomitant therapy in study I included prednisolone and cyclophosphamide. Study II patients continued their existing treatment regimens, with prednisolone tapered according to clinical status. Results: Mean age was 52.4 yr, 53% of the patients were female, and follow-up was 16.8 mo. Twenty-eight patients (88%) achieved remission (14 per study group). BVAS decreased from 12.3 (confidence interval [CI] = 10.5 to 14.0) at entry to 0.3 (CI = 0.2 to 0.9) at wk 14 (P < 0.001). C-reactive protein (mg/L) decreased from 29.4 (CI = 16.8 to 42.0) at entry to 7.0 (CI = 3.3 to 10.9) by wk 14 (P = 0.001). Mean prednisolone dose (mg/d) in study II decreased from 23.8 (CI = 15.0 to 32.5) at entry to 8.8 (CI = 5.9 to 11.7) at wk 14 (P = 0.002). There were two deaths and seven serious infections. Relapse occurred in five patients (three in study II) after a mean of 27 wk. Conclusion: TNF{alpha} blockade with infliximab was effective at inducing remission in 88% of patients with antibody-associated systemic vasculitis and permitted reduction in steroid doses. Severe infections were seen in 21% of patients, and despite continued infliximab, 20% of initial responders experienced disease flares. Infliximab is a promising new therapy for vasculitis both as a component of initial therapy and in the management of refractory disease. These results need confirmation in larger randomized trials.




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