Background: Ofatumumab (OMB) was approved as a self-injectable disease-modifying therapy (DMT) for relapsing multiple sclerosis (MS) in August 2020. This study aimed to examine treatment persistence and adherence of OMB to oral and platform self-injectable DMTs in a real-world setting. Methods: This was a retrospective cohort study using IQVIA Pharmetrics Plus (R) in adults diagnosed with MS and treated with OMB, oral DMTs, or platform self-injectable DMTs (index treatment) between August 2020 and November 2021. Patients had at least 12 months of continuous enrollment before the index date and 6 months of follow-up after the index date; the index date was defined as the date of the first pharmacy claim for an index treatment. Inverse probability of treatment weighting (IPTW) analysis was used to account for differences in baseline characteristics among patients initiating OMB versus oral DMTs and, separately, OMB versus platform self-injectable DMTs. Persistence was defined as the number of days from the index date until the earliest time of discontinuation (>60-day gap) or switch to a new DMT. Adherence was calculated based on proportion of days covered (PDC) with adherence defined as PDC >= 0.8. Persistence and adherence were compared between OMB versus oral DMTs and OMB versus platform self-injectable DMTs. Persistence was assessed via Kaplan-Meier analyses of the weighted sample, and log-rank tests were used to compare time to treatment discontinuation and treatment switch. The proportion of patients adherent at 6 and 12 months post index were compared using chi-square tests. Results: A total of 11,167 patients were identified with an incident claim of OMB, an oral DMT, or a platform selfinjectable DMT. After applying all inclusion and exclusion criteria and IPTW, two sets of study cohorts were created. For the oral DMT analysis, 577 patients treated with OMB and 2,468 patients treated with oral DMTs were identified. For the self-injectable DMT analysis, 574 patients treated with OMB and 578 patients treated with a platform self-injectable DMT were identified. At 6- and 12-month follow-up, the proportion of patients who were persistent on DMT was higher in the OMB cohort compared with the oral DMT cohort (6 months: 79.9% vs. 75.4 %, 12 months: 71.4% vs. 62.9 %; p < 0.05), as well as in the OMB cohort compared with the selfinjectable DMT cohort (6 months: 79.3% vs. 60.4 %, 12 months: 71.5% vs. 48.7 %; p < 0.0001). A similar proportion of patients were adherent to OMB versus oral DMTs at 6- and 12-months post index, whereas a higher proportion of patients treated with OMB versus platform self-injectable DMTs were adherent at 6-and 12-months post index. Conclusions: OMB showed better persistence and adherence compared with platform self-injectable DMTs, as well as better persistence compared with oral DMTs. This real-world analysis provides additional insights into OMB utilization among patients with MS in clinical practice and demonstrates that OMB is a valuable treatment option for these patients.