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Ann Rheum Dis. 2007 April; 66(4): 564–565.
PMCID: PMC1856044

Infliximab in patients with systemic vasculitis that is difficult to treat: poor outcome and significant adverse effects

The traditional treatment of systemic vasculitides with long‐term oral cyclophosphamide (CPM) and high‐dose corticosteroids has given way to more conservative approaches with shorter induction with CPM, followed by maintenance treatment with azathioprine or methotrexate.1 Despite this, 30–50% of patients relapse by 12 months. Endothelial dysfunction and tumour necrosis factor (TNF) α play a major part in pathogenesis.2 Raised TNF levels are associated with vascular damage and correlate with disease activity.

We describe an open‐label uncontrolled prospective study of anti‐TNFα (infliximab), in the management of patients with systemic vasculitides who failed to maintain remission on conventional immunosuppressive treatment.

We prospectively recruited nine patients with systemic vasculitides: three with Wegener's granulomatosis, two with Behçet's disease, and one each with Churg Strauss vasculitis, adult onset still's disease, Henoch Schonlein purpura and relapsing polychondritis. All failed to respond to one or more immunosuppressives (cyclophosphamide, methotrexate, azathioprine or mycophenolate mofetil) and required >15 mg/day prednisolone (range 15–80 mg).

All patients were scheduled to receive five infusions of infliximab (5 mg/kg) over a period of 6 months. The study was approved by the Guy's and St Thomas' Hospital Research Ethics Committee, and informed consent was obtained from patients before entering the study.

The median age of the patients was 46 years (range 34–62 years) and disease duration was 6 years (range 3–8 years).3,4,5,6,7,8 Only five patients completed five infusions of infliximab; in four, infliximab was discontinued because of adverse effects (table 11).

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Table 1 Adverse effects/flares after infliximab infusions

We found no improvement in the median Birmingham Vasculitis Activity Score, Vascular Damage Index and SF‐36 scores. Four patients developed new autoantibodies (table 11),), which became negative 3 months after discontinuation of infliximab. Four patients required admission for a severe flare of symptoms and lupus‐like reaction, and rescue with methyl prednisolone (500 mg) pulses and intravenous immunoglobulins (table 11).). One patient with adult‐onset still's disease died after 6 months secondary to cardiac failure. Her inflammatory markers remained grossly abnormal throughout (table 11).). The relationship with the infliximab infusions was not clear, but a postmortem examination did not show coronary artery disease, thrombosis or valvular abnormality. The study was terminated prematurely on safety grounds, and relevant authorities were informed.

Previously, several reports have suggested that anti‐TNFα is effective in patients with systemic vasculitides.3,4 Booth et al5 described improvement in endothelial function after anti‐TNFα treatment in patients with systemic vasculitides. Our findings do not support previous observations that infliximab helps to achieve remission in patients with systemic vasculitides that is difficult to treat.

A recent study (Wegener's Granulomatosis Etanercept Trial) failed to show any additional advantage when etanercept was added to conventional treatment. Solid malignancies were noted in the etanercept arm, giving rise to serious safety concerns.6

In summary, the adverse effects and lack of benefit experienced in our series raises concerns about the role of anti‐TNFα in patients with systemic vasculitides. Other biological treatments such as B cell depletion7 and/or intravenous immunoglobulin in antineutrophil cytoplasmic antibodies associated vasculitides may be more fruitful.8


CPM - cyclophosphamide

TNF - tumour necrosis factor


Competing interests: None declared.


1. Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert J W, Dadoniene J. et al A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003. 34936–44.44 [PubMed]
2. Bacon P A. Endothelial cell dysfunction in systemic vasculitis: new developments and therapeutic prospects. Curr Opin Rheumatol 2005. 1749–55.55 [PubMed]
3. Lamprecht P, Voswinkel J, Lilienthal T, Nolle B, Heller M, Gross W L. et al Effectiveness of TNF‐alpha blockade with infliximab in refractory Wegener's granulomatosis. Rheumatology 2002. 411303–1307.1307 [PubMed]
4. Booth A, Harper L, Hammad T, Bacon P, Griffith M, Levy J. Prospective study of TNF alfa blockade with infliximab in anti‐neutrophil cytoplasmic antibody‐associated systemic vasculitis. J Am Soc Nephrol 2004. 15717–721.721 [PubMed]
5. Booth A D, Jayne D R, Kharabanda R K, McEniery C M, Mackenzie I S, Brown J. et al Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 2004. 1091718–1723.1723 [PubMed]
6. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005. 352351–361.361 [PubMed]
7. Keogh K A, Ytterberg S R, Fervenza F C, Carlson K A, Schroeder D R, Specks U. Rituximab for refractory Wegener's granulomatosis: report of a prospective, open‐label pilot trial. Am J Respir Crit Care Med 2006. 173180–187.187 [PMC free article] [PubMed]
8. Jayne D. What place for the new biologics in the treatment of necrotising vasculitis. Clin Exp Rheumatol 2006. 24S1–S5.S5 [PubMed]

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