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Published online before print November 5, 2008, doi:10.1212/01.wnl.0000327341.89587.76)
Accepted June 9, 2008 Immunologic and clinical status 14 months after cessation of natalizumab therapyO. Stüve MD, PhD*,
From the Neurology Section (O.S.), VA North Texas Health Care System, Medical Service, Dallas; Departments of Neurology (O.S., P.D.C., E.M.F., G.M.R., M.P.S., E.M.C., N.L.M.), Immunology (O.S., E.M.C., N.L.M.), Ophthalmology (E.M.F.), and Clinical Sciences (S.Z.), University of Texas Southwestern Medical Center at Dallas; Department of Neurology (O.S., G.v.G., S.C.), Heinrich Heine University Düsseldorf, Germany; Multiple Sclerosis Center at Texas Neurology (J.T.P.), Dallas; Departments of Clinical and Experimental Immunology (J.W.C.T.) and Neurology (M.D.B.), University Hospital Maastricht, The Netherlands; Department of Neuroinflammation (D.M., D.H.M.), Institute of Neurology, Queen Square, London, UK; Institute of Neuroradiology (E.W.R.), Department of Medical Radiology, University Hospital Basel, Switzerland; Biogen-Idec (R.K.), Cambridge, MA; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technische Universität München, Germany; and Department of Neurology (M.K.R.), The Ohio State University Medical Center, Columbus. * To whom correspondence should be addressed. E-mail: olaf.stuve{at}utsouthwestern.edu.
Objective: Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy. Methods: This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored. Results: With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed. Conclusion: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.
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