Natalizumab Immunogenicity in Multiple Sclerosis: Evaluating Antibody Development and Clinical Outcomes in an Iraqi Cohort

Background: Natalizumab is an effective disease-modifying drug for multiple sclerosis (MS); nevertheless, the formation of anti-natalizumab antibodies (ANA) may reduce therapeutic effectiveness. Objective: To determine the prevalence of ANA, as well as the association between ANA and disease activity and clinical outcome. Methods: This cross-sectional research included 80 MS patients. Demographics and clinical profile, anti-natalizumab antibodies, and JCV status were all evaluated. Disease activity was determined using the Expanded Disability Status Scale (EDSS) and active/inactive disease categorization. To identify predictors of ANA development, correlation and multivariable logistic regression analyses were performed. Results: ANA were detected in 25 individuals (31.25%, 95% CI: 21.4–42.3%). 86% of participants showed ANA during the first 18 months of therapy, with a median time of 14.5 months (IQR: 8.2-22.1 months). Active disease was reported in 33(41.2%) of the 80 participants. There was no significant relationship between ANA levels and disease activity (p=0.927). The mean EDSS scores didn't differ between groups (ANA-positive: 3.70 vs. ANA-negative: 3.96; p=0.576). The ANA-positive cohorts showed reduced EDSS progression (1.58) compared to those with ANA-negative (2.03), although this difference was not statistically significant (p=0.517). Conclusions: Anti-natalizumab antibodies were prevalent in MS patients, although their existence had no meaningful correlation with clinical outcome. There was no link between disease activity and antibody production.