Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis

4区 · 医学

Article

作者: Lago, Nestor ; Strusberg, Ingrid ; Klimovsky, Ezequiel ; Federico, Andrea ; Lazaro, Maria Alicia ; Citera, Gustavo ; de los Ángeles Correa, Maria ; Velasco Zamora, Jorge ; Gonzalez, Eliseo ; Cordeiro, Lucas ; Mysler, Eduardo ; Spindler, Alberto ; Siri, Daniel ; Venarotti, Horacio ; Pardo Hidalgo, Rodolfo ; Tate, Patricio ; Scheines, Eduardo

Background:

Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept.

Methods:

This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%.

Results:

In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, −1.2%; 95% confidence interval, −10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32.

Conclusions:

Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.

2006-12-01·Experimental eye research3区 · 医学

Inhibition of TNF-α reduces laser-induced choroidal neovascularization

3区 · 医学

Article

作者: Philipp S. Müther ; Norbert Kociok ; Antonia M. Joussen ; Xuan Shi ; Susanne Dell ; Irina Semkova

To investigate the role of the TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in a mouse model. Four separate laser burns were applied to induce ruptures of Bruch's membrane and subsequent choroidal neovascularization in C57BL/6J mice. TNF-alpha protein expression was semiquantitatively assessed by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment. To investigate the effect of TNF-alpha inhibition on CNV formation, animals were treated for 7 days via intraperitonealy implanted osmotic pumps either 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept), a chimeric monoclonal antibody (infliximab), or a purified rat anti-mouse/rat TNF monoclonal antibody (TNF-mAb), respectively. Fluorescein angiography, flat-mount preparations, and histopathology were performed at day 7, 10, or 14 after laser treatment. Western blotting demonstrated that TNF-alpha expression was 4.57-fold higher in the choroid and RPE one week after laser injury compared to control mice without laser. When evaluated one and two weeks after laser injury, etanercept and infliximab given from the 3rd day before laser-damage significantly reduced CNV size and pathological fluorescein leakage compared to the control group after laser treatment only. The inhibitory effect of the monoclonal TNF-alpha antibody on CNV formation was evident two weeks after photocoagulation but not after one week. Only etanercept administered 3 days after laser injury still reduced significantly the development of CNV lesions. Histopathology confirmed that CNV lesions in treated mice were smaller in size compared to the control animals without TNF inhibitor treatment. In conclusion, anti-TNF-alpha treatment with different inhibitors reduces both the size and the leakage of laser-induced CNV. These results suggest the involvement of TNF-alpha in the development of laser-induced CNV and its potential use as a therapeutic agent in the age-related macular degeneration.

2005-09-01·Annals of the rheumatic diseases

A major subset of patients with ankylosing spondylitis followed up in tertiary clinical care require anti-tumour necrosis factor biological treatments according to the current guidelines

Letter

作者: Direskeneli, H ; Temel, M ; Atagündüz, P

Therapeutic options for severe ankylosing spondylitis (AS) have been limited to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and to some traditional disease modifying drugs (DMARDs) such as sulfasalazine and methotrexate. In view of open label and controlled trials of treatment with a monoclonal chimeric tumour necrosis factor (TNF) α antibody (infliximab), and with recombinant human TNF receptor (etanercept), the need for more effective second line treatments in AS seems to be met.1–4 In this study we aimed at determining the proportion of patients with active AS, despite treatment with NSAIDs and second line treatments (sulfasalazine, methotrexate), using current guidelines for anti-TNF treatment in a tertiary clinical care. Study patients were selected according to the Modified New York criteria. ASAS and SPARTAN guidelines for biological treatments of AS were …

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