• DOI:10.1212/WNL.53.3.457
• Corpus ID: 26126291

TNF neutralization in MS

@article{Bgw1999TNFNI,
  title={TNF neutralization in MS},
  author={Arnason Bgw. and G Jacobs and Matthew Hanlon and Brian Clay and Noronha Abc. and Anthony Auty and Bradley E. Davis and Avindra Nath and J-P. Bouchard and C Belanger and France Gosselin and Manon Thibault and Pierre Duquette and Pierre Bourgoin and R. Dubois and Marc P. Girard and George Cornell Ebers and Rice Gpa. and Margaret K. Vandervoort and Gordon S. Francis and Lauren Duncan and Yves Lapierre and Mark Steven Freedman and Suzanne N. Christie and Hyman H. Rabinovitch and David G. Patry and William F. Murphy and S. Peters and S{\'e}amus McGuiness and Thomas J. Murray and Virender Bhan and Charles E. Maxner and R. A. Van Dorpe and Jo{\"e}l J. -F. Oger and James Nelson and W. Morrison and N Bogle and Sarah Beall and G. Vorobeychick and Anita Hiltbrunner and Jason Bock and Werner Lesslauer and Li Dkb. and Donald W. Paty and Guojun Zhao and Grp Lmss. and Grp Ubcmsmria.},
  journal={Neurology},
  year={1999},
  volume={53},
  pages={457 - 457}
}

• Arnason Bgw., G. Jacobs, +44 authors Grp Ubcmsmria.
• Published 1 August 1999
• Medicine, Biology
• Neurology

Objective: A double-blind, placebo-controlled phase II study was conducted in 168 patients, most with relapsing-remitting MS, to evaluate whether lenercept would reduce new lesions on MRI. Background: Tumor necrosis factor (TNF) has been implicated in MS pathogenesis, has been identified in active MS lesions, is toxic to oligodendrocytes in vitro, and worsens the severity of experimental allergic encephalomyelitis (EAE) in animals. Lenercept, a recombinant TNF receptor p55 immunoglobulin fusion protein (sTNFR-IgG p55), protects against EAE. Methods: Patients received 10, 50, or 100 mg of lenercept or placebo IV every 4 weeks for up to 48 weeks. MRI scans and clinical evaluations were performed at screening, at baseline, and then every 4 weeks (immediately before dosing) through study week 24. Results: There were no significant differences between groups on any MRI study measure, but the number of lenercept-treated patients experiencing exacerbations was significantly increased compared with patients receiving placebo (p = 0.007) and their exacerbations occurred earlier (p = 0.006). Neurologic deficits tended to be more severe in the lenercept treatment groups, although this did not affect Expanded Disability Status Scale scores. Anti-lenercept antibodies were present in a substantial number of treated patients; serum lenercept trough concentrations were detectable in only a third. Adverse events that increased in frequency in treated patients included headache, nausea, abdominal pain, and hot flushes. Conclusions: Lenercept failed to be beneficial, but insight into the role of TNF in MS exacerbations was gained.