Current Status of Tumor Necrosis Factor Inhibition Strategies in the Treatment of Vasculitis

Stone, John H.

doi:10.1159/000072991

Cited by 7 publications

(7 citation statements)

References 59 publications

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“…Remission was induced in five patients and corticosteroid doses could be tapered. The soluble TNF-a receptor etanercept was shown to be safe and effective in patients receiving conventional treatment for WG [29]. Enrollment for a randomized trial, the Wegener's Granulomatosis Etanercept Trial (WGET), was completed in 2002.…”

Section: Newer Immunosuppressive Therapiesmentioning

confidence: 99%

Cyclophosphamide treatment in systemic necrotizing vasculitis and lupus nephritis. How long? How much?

Beimler

Andrássy

2004

Pediatr Nephrol

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The gold standard for inducing remission in systemic necrotizing vasculitis (SNV) and severe lupus nephritis is (and remains) the combination of cyclophosphamide and glucocorticoids. Long-term treatment with cyclophosphamide is limited because of toxicity. Recent prospective studies in antineutrophil cytoplasmic antibody (ANCA)-associated SNV revealed that after achievement of clinical remission (usually within 3-4 months after starting cyclophosphamide) cyclophosphamide can be replaced by azathioprine with no increase in relapse rates if treatment is continued for at least 1 year. Methotrexate is inferior to cyclophosphamide because of increased relapse rates-particularly in those with renal involvement-during follow-up. An ongoing study comparing mycophenolate mofetil (MMF) with azathioprine will clarify whether MMF is as successful as azathioprine or even better. The concomitant use of tumor necrosis factor (TNF)-alpha blockers increases the efficacy of immunosuppression. TNF-alpha blockers may be added if SNV is refractory to standard immunosuppressive therapy. However, with this addition to therapy, systemic infections are more frequent. In patients with severe lupus nephritis (WHO IV) the efficacy of combined i.v. therapy with cyclophosphamide and glucocorticoids was shown by NIH trials. This NIH regimen competes with the EURO-Lupus nephritis schedule with a lower dose of i.v. cyclophosphamide followed by maintenance therapy with azathioprine. Long-term follow-up is, however, still lacking in the EURO-Lupus trial. Ongoing prospective studies will reveal whether cyclophosphamide may be substituted by MMF from the very beginning or whether MMF is superior to azathioprine during maintenance therapy of lupus nephritis.

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Section: Newer Immunosuppressive Therapiesmentioning

confidence: 99%

Cyclophosphamide treatment in systemic necrotizing vasculitis and lupus nephritis. How long? How much?

Beimler

Andrássy

2004

Pediatr Nephrol

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“…Booth et al [10] also reported improvement in endothelial dysfunction in systemic vasculitis treated with infliximab. Cantini et al [15] also demonstrated benefit in four patients with active giant cell arteritis treated with infliximab, and at the present time there is a multicentre trial (USA and Europe) ongoing [81]. An open-label trial of anti-TNF therapy in difficult-to-treat Takayasu arteritis has recently been reported [39] in which infliximab was used in some patients and etanercept in others; the results showed an improvement in 14 of 15 patients and sustained remission in 10 of 15.…”

Section: New Immunomodulatory Strategies and Biologic Agentsmentioning

confidence: 84%

Vasculitis treatment – new therapeutic approaches

Dillon¹

2006

Eur J Pediatr

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In childhood, vasculitis carries with it a not inconsequential morbidity and mortality. Current therapy is usually effective in inducing remission, but there is a penalty in terms of significant and serious side effects as well as concerns about long-term maintenance regimens. Additionally, some patients are recalcitrant to treatment and options have, hitherto, been limited in relation to alternative therapy. In view of this, novel therapeutic approaches are being explored that include the better use of long-established agents as well as the utilization of newer immunosuppressive and immunomodulatory strategies. Blockade of circulating mediators and surface receptors as well as lymphocyte depletion and immunoablation are being introduced predominantly in adults but increasingly also in children. With greater understanding of the pathogenetic mechanisms involved in the disease processes it is becoming possible to utilize much more focussed therapy for these serious and life-threatening disorders with, hopefully, a decrease in long-term morbidity and mortality as well as a diminution of drug-induced adverse effects.

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“…We read with interest the article 'Current status of tumor necrosis factor inhibition strategies in the treatment of vasculitis' by Stone [1]. He refers to his own study on the use etanercept in addition to conventional treatment in patients with persistently active or new flares of Wegener's granulomatosis (WG) and to our study on the treatment of 6 patients with refractory WG with infliximab [2].…”

Section: Dear Sirmentioning

confidence: 99%

“…He refers to his own study on the use etanercept in addition to conventional treatment in patients with persistently active or new flares of Wegener's granulomatosis (WG) and to our study on the treatment of 6 patients with refractory WG with infliximab [2]. Since patients continued to receive immunosuppressive agents in addition to the TNF-· blocking agents, Stone [1] is cautious to draw any premature conclusions with regard to the efficacy of etanercept or infliximab in persistently active or refractory disease and calls for further studies.…”

Section: Dear Sirmentioning

confidence: 99%

“…However, 1 patient died of P. carinii pneumonia in another study, where infliximab was given in addition to standard treatment in non-refractory WG to test the efficacy of TNF-· for the induction of remission, corticoid-sparing effects, and evaluate subsequent maintenance of remission [8]. This trial was not unsimilar to the approach of the Wegener's Granulomatosis Etanercept Trial (WGET) of the eight US centers in which etanercept is given in addition to standard therapy in non-refractory patients in order to test the efficacy of etanercept on the maintenance of remission [1]. Against this background, we currently do not favor the use of infliximab or etanercept in situations other than refractory WG.…”

Section: Dear Sirmentioning

confidence: 99%

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