Comparison of the efficacy of the tumour necrosis factor   blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis

Hochberg, Marc C.; Tracy, J. Kathleen; Hawkins-Holt, M; Flores, R H

doi:10.1136/ard.62.suppl_2.ii13

Cited by 130 publications

(96 citation statements)

References 21 publications

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“…In fact, when comparing the results of the study by Tugwell et al (CSA added to preexisting MTX treatment in a step-up design) (11) with those of the study by Gerards et al (CSA monotherapy compared with CSA plus MTX in a parallel design) (31), the clinical response to CSA monotherapy and to CSA step-up treatment were virtually identical (Table 1). Rheumatologists (in contrast to other subspecialists, such as oncologists) tend to avoid comparing arms from different trials and miss important information that is possible to obtain relatively objectively (32). Thus, with all the limitations of such between-trials comparisons, the data reviewed above imply that the combination of these agents may not be superior to monotherapy.…”

Section: Study Design Issuesmentioning

confidence: 99%

Superior efficacy of combination therapy for rheumatoid arthritis: Fact or fiction?

Smolen

Aletaha

Keystone

2005

Arthritis & Rheumatism

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Section: Study Design Issuesmentioning

confidence: 99%

Superior efficacy of combination therapy for rheumatoid arthritis: Fact or fiction?

Smolen

Aletaha

Keystone

2005

Arthritis & Rheumatism

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“…1A). In contrast, S4B6 slightly inhibited BrdU incorporation by CD4 ϩ T cells and had no significant effect on the Foxp3 ϩ subpopulation of CD4 ϩ T cells (regulatory T cells (Tregs) 3 ; Fig. 1B).…”

Section: S4b6 Selectively Increases Cd8 ϩ T Cell Proliferation In Vivomentioning

confidence: 99%

“…This did not seem to be accomplished by decreasing urinary excretion of IL-2, because S4B6 administration actually increased the IL-2 content of urine excreted during the 24 h subsequent to IL-2 injection. We 3 Abbreviations used in this paper: Treg, regulatory T cell; FcRn, neonatal Fc receptor.…”

Section: S4b6 Promotes Il-2 Agonist Effects By Increasing Il-2 Half-lifementioning

confidence: 99%

Cutting Edge: Mechanism of Enhancement of In Vivo Cytokine Effects by Anti-Cytokine Monoclonal Antibodies

Phelan

Orekov

Finkelman

2008

The Journal of Immunology

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Inhibitory anti-cytokine mAbs are used to treat cytokine-mediated disorders. Recently, however, S4B6, an anti-IL-2 mAb that blocks IL-2 binding to IL-2Rα, a receptor component that enhances affinity but is not required for signaling, was shown to enhance IL-2 agonist effects in vivo. We evaluated how S4B6 enhances IL-2 effects and whether a similar mechanism allows mAbs to IL-4 to enhance IL-4 effects. Induction of T cell proliferation by IL-2/S4B6 complexes did not require complex dissociation and was IL-2Rα independent. S4B6 increased IL-2 agonist effects by increasing in vivo half-life, not by focusing IL-2 onto cells through Fc receptors. In contrast to IL-2/S4B6 complexes, anti-IL-4 mAb enhancement of in vivo IL-4 effects required IL-4/anti-IL-4 mAb complex dissociation. Thus, agonist effects observed with high doses of anti-IL-2 mAb are most likely only applicable for mAbs that maintain cytokine half-life without blocking binding to receptor signaling components.

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“…Second, infliximab (Remicade, Centocor, Horsham, PA) is a chimeric IgG1 mAb that binds and inhibits soluble as well as membrane-bound TNF-␣. The efficacy of both treatments in patients with rheumatoid arthritis seems to be comparable (36), but in patients with Crohn's disease, etanercept, in contrast to infliximab, seems not to be effective (37). The role of adalimumab (Humira, Abbott, Chicago, IL), a novel, fully human TNF-␣-inhibiting mAb (38) that has been shown to be effective in rheumatoid arthritis and Crohn's disease when the response to etanercept or infliximab is lost (39,40), in the treatment of ANCA-associated vasculitis remains to be established.…”

Section: Tnf-␣ Inhibition: Human Studiesmentioning

confidence: 96%

TNF-α Bioactivity-Inhibiting Therapy in ANCA-Associated Vasculitis

Huugen

Tervaert

Heeringa

2006

Clinical Journal of the American Society of Nephrology

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Wegener's granulomatosis, microscopic polyangiitis, idiopathic necrotizing crescentic glomerulonephritis, and Churg-Strauss syndrome are associated with the presence of ANCA with specificity for myeloperoxidase or proteinase 3. Current therapy consists mainly of corticosteroids and cyclophosphamide, but because this treatment regimen is associated with considerable morbidity, other treatment modalities remain desirable. There is compelling evidence that TNF-␣ plays an important role in the pathogenesis of ANCA-associated vasculitis. Consequently, inhibition of TNF-␣ bioactivity potentially results in attenuation of disease. This review discusses whether TNF-␣ bioactivity-inhibiting drugs are useful in the treatment of ANCAassociated vasculitis. The results of in vitro and in vivo experiments, as well as clinical studies, are evaluated. Although the importance of TNF-␣ during lesion development is evident, clinical trials that use TNF-␣ blockers in patients with ANCAassociated vasculitis give mixed results. Importantly, in a large-scale, randomized trial, treatment with etanercept was found not to be effective and resulted in an excess of treatment-related morbidity. It remains to be investigated whether inhibition of TNF-␣ bioactivity is effective in a subgroup of patients.

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Comparison of the efficacy of the tumour necrosis factor blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis

Cited by 130 publications

References 21 publications

Superior efficacy of combination therapy for rheumatoid arthritis: Fact or fiction?

Superior efficacy of combination therapy for rheumatoid arthritis: Fact or fiction?

Cutting Edge: Mechanism of Enhancement of In Vivo Cytokine Effects by Anti-Cytokine Monoclonal Antibodies

TNF-α Bioactivity-Inhibiting Therapy in ANCA-Associated Vasculitis

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