Observational studyNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2026
No association between the wearing-off effect and α4-integrin receptor saturation in natalizumab treated patients with relapsing-remitting multiple sclerosis.
Observational study in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- The wearing-off effect with natalizumab: Back to the drawing board.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 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 α4-integrin 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 α4-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 α4-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 α4-integrin receptor saturation in any T-lymphocyte subset. Our findings suggest that WOE is not related to reduced α4-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.