Natalizumab wearing-off symptoms: effect of extend interval dosing during Sars-CoV-2 pandemic

Abstract

Background Many patients treated with Natalizumab experience wearing-off symptoms (WoS) towards the end of the administration cycle. During the pandemic we advised and asked patients undergoing treatment with Natalizumab if they wanted to be shifted from a standard interval dosing (StID of 4 weeks) to an extended interval dosing (ExID of 5-6 weeks), regardless of their JCV index. Our main objective was to study prevalence and incidence of WoS when ExID was adopted. Methods We enrolled 86 patients, from May 2020 to January 2021, evaluated at baseline and during a 6 months follow-up with a survey focused on WoS, Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS) and MRI. Results Among the 86 patients, 32 (37.2%) reported WoS. Most common one was fatigue (93.7%). Mean EDSS was higher in the group reporting WoS (3.8 WoS vs 3.1 non-WoS, p < 0.05). Sphincterial function was the EDSS item that significantly differed between the WoS group and the non-WoS group (1.4 WoS vs 0.6 non-WoS, p < 0.001). WoS correlate with the FSS scale (p < 0.001). Conclusion Adopting an extended interval dosing does not result in significantly different occurrence of WoS between the ExID and the StID populations, in our cohort of patients. Interestingly, there is a strong correlation between WoS and a higher EDSS and FSS. Safety and efficacy of Natalizumab with ExID are relatively preserved in our study. KeywordsFatigue • Multiple sclerosis • Natalizumab wearing-off symptoms (WoS) • End of dosing interval symptoms (EDIs) • Extended interval dosing (ExID)

Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience

“…Few other studies have evaluated the impact of BMI on various aspects of natalizumab therapy. The well-known wearing-off effect, particularly evident in the use of an EID, is influenced by BMI [ 29 , 30 ]. Other authors have hypothesized that a lower alpha integrin saturation in subjects with higher BMI could underlie the reduction in the efficacy of therapy [ 5 ].…”