Long-term single-centre experience with natalizumab

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.