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MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS

From the Institute of Neurology (D.H.M., D.S., K.T.F., D.G.M., G.J.B., T.A.Y, G.G.), University College London, UK; St. Michael's Hospital (P.W.O.), Toronto, Ontario, Canada; Multiple Sclerosis Center at Texas Neurology (J.T.P.), Dallas, TX; VU Medical Centre (C.H.P.), Free University Hospital, Amsterdam, the Netherlands; University Hospital Basel (L.K.), Switzerland; St. Vincent's University Hospital (M.H.), Dublin, Ireland; Neurological Department (E.H.), General Teaching Hospital, Prague, Czech Republic; Mellen Center (R.R.), Department of Biomedical Engineering (E.F.), Cleveland Clinic, OH; Mt. Sinai School of Medicine (F.D.L.), New York, NY; Silesian Medical University (A.W.), Katowice, Poland; and Biogen Idec, Inc. (F.L., M.A.P., A.W.S.), Cambridge, MA.

Address correspondence and reprint requests to Prof. David H. Miller, Department of Neuroinflammation, Institute of Neurology, Queen Square, London WC1N 3BG d.miller{at}ion.ucl.ac.uk

Background: In a 2-year, placebo-controlled trial (the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] study), involving 942 patients with relapsing multiple sclerosis (MS), natalizumab significantly reduced the relapse rate by 68% and progression of sustained disability by 42% vs placebo. We report the effect of natalizumab on MRI measures from the AFFIRM study.

Methods: The number and volume of gadolinium (Gd)-enhancing, new or enlarging T2-hyperintense, and new T1-hypointense lesions and brain parenchymal fraction were measured from annual scans obtained at baseline, 1 year, and 2 years.

Results: Compared with placebo, natalizumab produced a 92% decrease in Gd-enhancing lesions (means 2.4 vs 0.2; p < 0.001), an 83% decrease in new or enlarging T2-hyperintense lesions (means 11.0 vs 1.9; p < 0.001), and a 76% decrease in new T1-hypointense lesions (means 4.6 vs 1.1; p < 0.001) over 2 years. Median T2-hyperintense lesion volume increased by 8.8% in the placebo group and decreased by 9.4% in the natalizumab group (p < 0.001); median T1-hypointense lesion volume decreased by 1.5% in the placebo group and decreased by 23.5% in the natalizumab group (p < 0.001). Brain atrophy was greater in year 1 and less in year 2 in natalizumab-treated patients.

Conclusion: Natalizumab has a sustained effect in preventing the formation of new lesions in patients with relapsing multiple sclerosis.

Supplemental data at www.neurology.org

Received June 1, 2006. Accepted in final form December 19, 2006.

Disclosures: The AFFIRM study was sponsored by Biogen Idec and Elan Pharmaceuticals. Profs. Miller, Hutchinson, and Giovannoni report having received grants (>$10,000) from Biogen Idec for other research or activities not reported in this article as well as honoraria (<$10,000) from Biogen Idec during the course of this study. Prof. Polman reports having received grants (>$10,000) from Biogen Idec for other research or activities not reported in this article and honoraria (<$10,000) from Biogen Idec during the course of this study and has given expert testimony related to the subject of this article. Prof. Kappos reports having received grants (>$10,000) from Biogen Idec for other research or activities not reported in this article. Dr. Fisher reports having received research funding (>$10,000) for other research not reported in this article. Dr. O'Connor, Dr. Barker, and Prof. Havrdova report having received honoraria (<$10,000) from Biogen Idec during the course of this study. Dr. Phillips reports having received grant support (<$10,000) from Biogen Idec for other research/activities not reported in this article and honoraria from Biogen Idec (<$10,000) during the course of this study. Dr. Lublin reports having received honoraria (>$10,000) from Biogen Idec during the course of this study. Dr. Rudick reports having received research funding (>$10,000) for research not reported in this article and honoraria (<$10,000) from Biogen Idec during the course of this study. Ms. Lynn, Dr. Panzara, and Dr. Sandrock have equity interests (>$10,000) and are employees of Biogen Idec. Drs. Soon, Fernando, MacManus, Yousry, and Wajgt report no conflicts of interest.

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