Abstract
Natalizumab effectively prevents disease activity in relapsing-remitting multiple sclerosis by binding α4 integrin and inhibiting leukocyte migration to the central nervous system. We recently reported an association between low natalizumab receptor occupancy and subjective wearing-off symptoms at the end of the 4-week dosing interval. Here, we aimed to evaluate the short-term risk of disease activity in a 1-year prospective follow-up of the same patient cohort (n = 40). We found that all patients available for follow-up after one year (n = 35) fulfilled the criteria for no evidence of disease activity (NEDA). Thus, wearing-off symptoms were not associated with increased short-term risk of disease activity. Longer follow-up in a larger patient cohort is required to establish whether therapeutic efficacy is maintained in patients with wearing-off symptoms.
Highlights
Natalizumab (Tysabri®, Biogen) administered intravenously at a standard dose of 300 mg every 4 weeks efficiently reduces disease activity in relapsing-remitting multiple sclerosis (RRMS) [1]
Natalizumab receptor occupancy (RO) refers to the proportion of α4 integrins occupied by natalizumab on single cells, and has been suggested as a biomarker to monitor therapeutic efficacy and possibly patient-tailor therapy [2]
Serum collected at inclusion and after one year was stored at −80 °C and Neurofilament light chain (NF-L) was quantified with a single-molecule array (Simoa) assay (Quanterix)
Summary
Natalizumab (Tysabri®, Biogen) administered intravenously at a standard dose of 300 mg every 4 weeks efficiently reduces disease activity in relapsing-remitting multiple sclerosis (RRMS) [1]. Neurofilament light chain (NF-L) is another emerging biomarker for disease activity and neuroaxonal damage in RRMS, and is reported to return to levels of healthy individuals following initiation of natalizumab therapy [3]. 50% of patients treated with natalizumab report a feeling of the effect “wearing off” towards the end of the 4-week dosing interval, and that subjective symptoms, most commonly fatigue, increase during the last week of the dosing interval and improve shortly after receiving the infusion [4,5,6]. The underlying mechanisms of this phenomenon are unknown, but we recently found that patients who regularly reported wearing-off symptoms at the end of dosing intervals had lower natalizumab RO than those reporting such symptoms occasionally or never [6]. We aimed to investigate if the patients who regularly reported wearing-off symptoms had increased risk of disease activity during a 1-year follow-up
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