The real-world effectiveness and safety of off-label rituximab in a large cohort of Middle Eastern multiple sclerosis patients

Rituximab (RTX) is increasingly used off-label for the treatment of multiple sclerosis (MS), yet real-world evidence from Middle Eastern populations remains limited. This multicenter, retrospective observational study evaluated the effectiveness and safety of RTX using data from the MENACTRIMS registry across seven Middle Eastern countries (Iraq, Kuwait, Lebanon, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates). A total of 774 MS patients were included: 482 with relapsing-remitting MS (RRMS) and 292 with active secondary progressive MS (aSPMS). Patients received intravenous RTX at doses of 500 mg or 1000 mg every 6–12 months. The cohort was predominantly female (72.1%), with a mean age of 39.6 years and a mean disease duration of 11.9 years from symptom onset. RTX treatment was associated with a significant reduction in annualized relapse rate (ARR), decreasing from 1.65 to 0.08 in RRMS and from 2.03 to 0.02 in aSPMS (p < 0.001). Expanded Disability Status Scale (EDSS) scores remained stable in RRMS but increased by 1.0 point in aSPMS (p < 0.001). MRI activity was suppressed in most RRMS patients, with 89.1% showing no new or enlarging lesions, whereas only 8.1% of aSPMS patients demonstrated similar stability. NEDA-3 was achieved in 47.3% of RRMS patients. A total of 491 adverse events were reported, predominantly mild infusion-related reactions (92.5%). Overall, off-label RTX demonstrated substantial real-world effectiveness and a favorable safety profile in Middle Eastern MS patients, particularly in RRMS.