A C TApproximately half of patients with relapsing-remitting multiple sclerosis treated with natalizumab (NTZ) report transient symptom worsening -particularly fatigue -toward the end of the dosing interval.This phenomenon, commonly referred to as the wearing-off effect (WOE), has been hypothesized to result from a decrease in 4integrin receptor saturation on circulating leucocytes.However, existing evidence is inconsistent, considering either small samples studied or conflicting results derived from previous studies.Our study aimed to investigate the association between 4-integrin receptor saturation and the WOE in a large prospective cohort of NTZ treated patients.We conducted a prospective observational study collecting demographic and clinical data, including WOE assessment via a structured questionnaire, treatment interval data, and 4-integrin receptor saturation levels across T-lymphocyte subset.Among 117 participants, 57.3 % reported experiencing WOE.WOE was significantly associated with higher disability (EDSS score) and longer NTZ treatment duration.However, no significant correlation was found between WOE and 4-integrin receptor saturation in any T-lymphocyte subset.Our findings suggest that WOE is not related to reduced 4-integrin receptor saturation and thus does not reflect diminished pharmacodynamic efficacy of NTZ.These results provide reassurance regarding the continued therapeutic effect of NTZ in patients experiencing WOE.
Freeman et al. (Sun,) studied this question.