BACKGROUND: Extended interval dosing (EID) of natalizumab (NTZ) every 6 weeks may reduce adverse events while maintaining efficacy. This study compared the effectiveness and safety of EID versus standard interval dosing (SID) in relapsing-remitting multiple sclerosis (RRMS) patients, focusing on treatment adherence and its impact on clinical and radiological outcomes. METHODS: This retrospective study involved 80 patients with RRMS from seven clinics: 52 received SID (300 mg every 4 weeks), and 28 received EID (300 mg every 6 weeks). Clinical and radiological disease activity, treatment adherence, and adverse events were assessed. RESULTS: The SID and EID groups differed significantly in sex distribution (78.8% female in SID vs. 46.4% in EID, p = 0.007), but median age was similar (32 vs. 36 years, p = 0.209). Clinical and radiological worsening rates were similar between the groups, with no significant differences (combined worsening: 9.6% in the SID group vs. 17.9% in the EID group, p = 0.308
radiological worsening: 5.8% in the SID group vs. 7.1% in the EID group, p = 1.00
clinical worsening: 9.6% in the SID group vs. 10.7% in the EID group, p = 1.00). Adherence rates were comparable across both dosing regimens, and no significant differences were observed in terms of treatment discontinuation. No progressive multifocal leukoencephalopathy cases were reported. CONCLUSION: Both SID and EID provide comparable efficacy and safety profiles, with similar adherence rates. Despite the observed sex distribution imbalance, additional analyses confirmed no significant sex- or group-related differences in baseline disability or clinical worsening, strengthening the interpretation that EID preserves efficacy. Findings should still be interpreted with caution due to the study's retrospective nature and limited sample size.