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Background/objectives We aimed to determine how low-efficacy disease modifying therapies (leDMTs) and high-efficacy DMTs (heDMTs) compare with respect to reduction in brain atrophy in patients with relapsing remitting multiple sclerosis (RRMS).Methods We searched the EMBASE, MEDLINE and COCHRANE databases between 1995–2022 for RCTs in RRMS reporting on brain atrophy. We performed meta-analyses to compare the mean percentage brain volume change (PBVC)/parenchymal fraction between leDMTs and heDMTs and placebo/control at 12 months and 24 months. We also directly compared leDMTs and heDMTs at 12 months and 24 months.Results 29 studies were included in the meta-analysis with a total of 28,069 patients. No statistically significant difference in the mean PBVC/parenchymal fraction was seen at 12 months between leDMTs and placebo/control (Cohen’s d=0.04, 95% CI -0.08 – 0.17, P=0.48) or with heDMTs and placebo/control (Cohen’s d=0.07, 95% CI -0.06–0.20, P=0.30). A statistically significant reduction in mean PBVC/parenchymal fraction was seen at 24 months with leDMTs (Cohen’s d=0.28, 95% CI 0.15–0.41, P=0.00) and heDMTs (Cohen’s d=0.16, 95% CI 0.16 – 0.29, P=0.00) compared to placebo. No significant difference in the mean PBVC/parenchymal fraction was seen between leDMTs and heDMTs up to 12 months (Cohen’s d=0.06, 95% CI -0.12–0.25, P=0.51) or up to 24 months (Cohen’s d=0.13, 95% CI -0.05- 0.32, P=0.16).Conclusion Our analysis suggests that leDMTs and heDMTs require at least 24 months to demonstrate a significant reduction on brain atrophy. Therefore, to adequately assess brain atrophy trials with longer follow-up are required or alternative methods to assess progression are required.