Ocrelizumab VErsus Rituximab Off-Label at the Onset of Relapsing MS Disease

Phase 3 Active not recruiting 214 enrolled Haukeland University Hospital Helse Stavanger HF · collab Oslo University Hospital · collab St. Olavs Hospital · collab University Hospital of North Norway · collab University Hospital, Akershus · collab

RandomizedParallel-groupTriple-blindTreatment

Summary

This is a multicenter non-inferiority study, designed to establish non-inferiority of the study treatment rituximab compared with the comparator ocrelizumab for consecutively included patients (male or female) with active relapsing-remitting multiple sclerosis aged 18-60 years.

Timeline

Start: 2020-11-02
Primary completion: 2025-08-14
Completion: 2025-09-14

Outcome

Met primary endpoint

paper risk difference of -2.6 percentage points (95% confidence interval, -9.4 to 4.3), which met the prespecified noninferiority criterion. PMID 42384870 ↗

Publications

Torkildsen O, Brustad HK, Hogestol EA, Alstadhaug KB, Bhan A, Flemmen HO, Habbestad A, Hoglund RAA, LeBlanc M, Lopen P, Lorentzen AR, Morsund AH, Lossius A, Lundby R, Nygaard GO, Rod BE, Simonsen CS, Steffensen L, Torgauten H, Piehl F, Wergeland S, Myhr KM; OVERLORD-MS Investigators. Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis. N Engl J Med. 2026 Jul 2;395(1):44-53. doi: 10.1056/NEJMoa2600993.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Ocrelizumab	Monoclonal antibody	600 mg	Intravenous
Subject	Rituximab	Monoclonal antibody	500 mg	Intravenous