Wise Young
04-16-2002, 08:43 PM
[S23.003] Natalizumab Treatment for Relapsing MS: Further Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Catherine Dalton, Paul O'Connor, George Rice, Omar Khan, J. Theodore Phillips, Gareth Barker, David MacManus, Katherine Miszkiel, David Miller, the International Natalizumab (Antegren™) MS Trial GroupÂ*London, United Kingdom; Toronto, Canada; London, ON, Canada; Detroit, MI; Dallas, TX
OBJECTIVE: To assess the effect of monthly IV administrations of natalizumab (3.0 or 6.0 mg/kg) vs placebo over a 6 month treatment period and for an additional 6 months following discontinuation of study treatment on brain lesion activity in patients with relapsing MS.
BACKGROUND: The cell adhesion molecule alpha4beta1 integrin, also known as VLA-4, is thought to play an important role in the trafficking of mononuclear cells into sites of inflammation. Through its interaction with vascular cell adhesion molecule-1 (VCAM-1), alpha4beta1 mediates migration of autoreactive lymphocytes into the brain leading to the inflammatory lesions of multiple sclerosis. Recently it has been demonstrated that monthly treatments with natalizumab, an alpha4-integrin antagonist in the class of selective adhesion molecule inhibitors (SAMIs), reduced the occurrence of new gadolinium enhancing MRI lesions and clinical relapses in patients with multiple sclerosis over the six month treatment period (Multiple Sclerosis 2001 (Abstract;7:S16.). The present report describes additional analyses performed during the six months of treatment and follow up.
DESIGN/METHODS: 213 patients with relapsing MS were randomized to receive either natalizumab at 3 or 6 mg/kg or placebo IV every 4 weeks for 6 months and were followed for an additional 6 months for safety. Inclusion criteria included relapsing disease with 2 relapses within the last 2 years, an EDSS of 2.0 to 6.5 and no concomitant disease modifying treatment. T1 gadolinium-enhanced and T2-weighted imaging were performed pretreatment, every 4 weeks during the 6 month treatment period and quarterly during the 6 month post-treatment safety follow-up.
RESULTS: At the six month time point, natalizumab treatment resulted in a statistically significant reduction in the number of new and enlarging T2 lesions, the number of new T1 hypointense lesions and the number of active scans, i.e. containing new enhancing lesions. During the six month follow-up period there were no significant differences in numbers of enhancing brain lesions or relapses between treatment groups. Natalizumab treatment appeared to be well tolerated.
CONCLUSIONS: During the six month treatment period, natalizumab suppressed new T1 gadolinium-enhanced, T2-weighted and T1 hypointense brain lesions as well as clinical relapses. Post treatment MRI and clinical activity resumed to a level similar to placebo. In view of these promising findings, Phase III trials are underway to evaluate the longer term effect on relapses and disability.
Supported By: Elan Pharmaceuticals Inc. and Biogen Inc.
Category - MS and Related Diseases
SubCategory - Clinical Trials
Catherine Dalton, Paul O'Connor, George Rice, Omar Khan, J. Theodore Phillips, Gareth Barker, David MacManus, Katherine Miszkiel, David Miller, the International Natalizumab (Antegren™) MS Trial GroupÂ*London, United Kingdom; Toronto, Canada; London, ON, Canada; Detroit, MI; Dallas, TX
OBJECTIVE: To assess the effect of monthly IV administrations of natalizumab (3.0 or 6.0 mg/kg) vs placebo over a 6 month treatment period and for an additional 6 months following discontinuation of study treatment on brain lesion activity in patients with relapsing MS.
BACKGROUND: The cell adhesion molecule alpha4beta1 integrin, also known as VLA-4, is thought to play an important role in the trafficking of mononuclear cells into sites of inflammation. Through its interaction with vascular cell adhesion molecule-1 (VCAM-1), alpha4beta1 mediates migration of autoreactive lymphocytes into the brain leading to the inflammatory lesions of multiple sclerosis. Recently it has been demonstrated that monthly treatments with natalizumab, an alpha4-integrin antagonist in the class of selective adhesion molecule inhibitors (SAMIs), reduced the occurrence of new gadolinium enhancing MRI lesions and clinical relapses in patients with multiple sclerosis over the six month treatment period (Multiple Sclerosis 2001 (Abstract;7:S16.). The present report describes additional analyses performed during the six months of treatment and follow up.
DESIGN/METHODS: 213 patients with relapsing MS were randomized to receive either natalizumab at 3 or 6 mg/kg or placebo IV every 4 weeks for 6 months and were followed for an additional 6 months for safety. Inclusion criteria included relapsing disease with 2 relapses within the last 2 years, an EDSS of 2.0 to 6.5 and no concomitant disease modifying treatment. T1 gadolinium-enhanced and T2-weighted imaging were performed pretreatment, every 4 weeks during the 6 month treatment period and quarterly during the 6 month post-treatment safety follow-up.
RESULTS: At the six month time point, natalizumab treatment resulted in a statistically significant reduction in the number of new and enlarging T2 lesions, the number of new T1 hypointense lesions and the number of active scans, i.e. containing new enhancing lesions. During the six month follow-up period there were no significant differences in numbers of enhancing brain lesions or relapses between treatment groups. Natalizumab treatment appeared to be well tolerated.
CONCLUSIONS: During the six month treatment period, natalizumab suppressed new T1 gadolinium-enhanced, T2-weighted and T1 hypointense brain lesions as well as clinical relapses. Post treatment MRI and clinical activity resumed to a level similar to placebo. In view of these promising findings, Phase III trials are underway to evaluate the longer term effect on relapses and disability.
Supported By: Elan Pharmaceuticals Inc. and Biogen Inc.
Category - MS and Related Diseases
SubCategory - Clinical Trials