Immunological and clinical status 14 months after cessation of natalizumab therapy

Background: Natalizumab ( registered Tysabri) is a humanized recombinant monoclonal antibody against very late activation antigen-4 (VLA-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 magnetic resonance imaging (MRI) three months after discontinuation of therapy. Objective: The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunological parameters in peripheral blood and cerebrospinal fluid (CSF), as well as safety in MS patients after discontinuation of natalizumab therapy. Methods: This study is a serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were followed over 14 months. The annual relapse rate, neurological 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. The occurrence of clinical relapses was associated with high lymphocyte numbers in the CSF. Conclusions: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunological rebound phenomenon after discontinuation of natalizumab therapy.