Natalizumab extended-interval dosing in a real-life context: efficacy study

ABSTRACT

Introduction: Natalizumab (NTZ) is a widely used second-line treatment for multiple sclerosis (MS), administered with a fourweeks infusion interval. Extending the interval between two infusions could reduce the economic costs of this therapy, the incidence of rare side effects such as progressive multifocal leukoencephalopathy and improve the patients' quality of life with less frequent day-hospitalizations. Aim(s) At the Fondation Rothschild Hospital in Paris, for sanitary reasons during COVID-19 lockdown, patients were systematically switched to a 6-weeks NTZ extended-interval dosing (EID) from April 2020 to the present day. In this monocentric retrospective study, we aimed at evaluating the clinical and radiological efficacy of NTZ EID compared to the 4 weeks standard-interval dosing (SID) in adult patients with active MS. Method(s) We screened the local pharmacy database for NTZ administration and included all adult patients diagnosed with MS and treated with NTZ for at least 6 months with a SID, before being treated with an EID for at least 12 months. Data about disease activity, treatments received, MRI and clinical data were retrospectively collected from the local French MS observatory (OFSEP) database. The primary outcomes were the incidence of MS attacks, new MRI lesions or the presence of gadoliniumenhancing lesions during NTZ SID or EID. Result(s) A total of 49 patients were included for final analysis. 21 (42.9%) were male, with a median MS duration from the first symptom to NTZ introduction of 60 [30, 110] months. Patients were treated for a median time of 34.6 [15.1, 72.4] months by a SID, followed by a median time of 18.6 [14.7, 20.6] months by an EID. The mean EDSS before EID was 2.0 [1.5, 3.0] and 1.5 [0.0, 2.8] during EID. During natalizumab SID, one patient (2%) presented a new MS attack, 5/45 patients (11%) had new MRI lesions, with gadolinium enhanced lesions in 1/45 (2%) patient. This did not differ significantly during natalizumab EID where no MS attack were observed (p = 1), new MRI lesions were present in 1/41 (2%) patient and no gadolinium-enhancing lesion was found. Patients were followed for a median time of 130 [78, 205] months in total. Conclusion(s) We did not observe more clinical attacks or MRI activity signs when extending the interval between NTZ infusions from 4 to 6 weeks. Data from randomized controlled trials are needed to allow better consideration of side-effects and safety.