ABSTRACT
Background: Natalizumab (NZB) is a disease-modifying treatment (DMT) used in persons with MS (PwMS) with an active relapsing course, either as a first-line, or after previous treatments. The principal biological effect of NZB is thought to be the blockade of the molecular interaction between β4β1-integrin (also known as very late antigen-4) expressed by mononuclear inflammatory cells, and vascular cell adhesion molecule-1 (CAM-1) expressed by cerebral vascular endothelial cells. NZB is a potent DMT which must be monitored with caution, its use being hampered by the risk of opportunistic infections, mostly progressive multifocal leukoencephalopathy (PML). Objectives: To document the efficacy and safety of NZB for the treatment of RRMS in a population of persons with MS (PwMS) followed in a regular MS Clinic setting. Methods: We report our single-centre experience over a period of 13 years: from JAN 2007 through the end of May 2020. All PwMS treated with NZB were included, regardless of the treatment duration. The retainment of patients in our MS Clinic is 95%. We use the iMed database, an international MS registry. . Results: We report on 230 PwMS, 159 women, 71 men treated with NZB since 2007, up to 30 April 2020. We had no PML case. We had 2 PML 'clinical alerts', but CSF search for JC virus (JCV) was negative. There was no rebound of activity, nor IRIS, after NZB cessation, as we usually quickly switch to an alternative DMT. Median age at MS onset: 26.3 years. Median age at NZB initiation: 35 years. Median disease duration before treatment: 8.07 years. First line use: 94. Previous BRACE DMT: 136. Risk factors: previous immuno-suppression: 7;NZB duration > 24 months: 112;JCV index > 1: 81. Median treatment duration: 23 months;still active: 71 including 7 after > 6 years. ARR at NZB onset: 1.5;during NZB: 0.27;current: 0.89. Median EDSS at NZB start: 3.0. Current median EDSS: 2.8. EDSS stable: 65, worsened: 58;improved: 60. MRI: stable: 133 (58%) ;improved: 5 (2%);worsened: 35 (25%). Conversion to SPMS: 48 (20%) 29 W, 19 M. Reasons for NZB cessation: planned: 27;pregnancy: 3;loss of efficacy: 39;increased JCV index: 62. No blood toxicity (CBC, ALT). We had 9 pregnancies: 4 planned interruptions;5 full term, with normal babies. Treatment after NZB cessation: 48 fingolimod, glatiramer: 17;ocrelizumab: 16;others: 29;none: 32 (no rebound observed). One patient had COVID 1 year after NZB: complete recovery;needed only nasal O2 during 3 day hospital admission. Conclusions: NZB, when used with caution, is an effective and safe MS DMT during the RRMS phase, even after extended disease and treatment durations. NZB is most effective to reduce relapse frequency, less effective against progression, as 20% of PwMS transited to the secondary progressive phase. Gender, disease duration, and age do not influence outcomes. We encountered no significant toxicity, in particular no PML. Clinical, JCV index measures, and MRI monitoring are paramount to maintain safety.