Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis

The DanNORMS study is a phase 3, non-inferiority clinical trial examining whether treatment of active multiple sclerosis with rituximab is non-inferior to ocrelizumab regarding efficacy and safety.

Inclusion Criteria: * MS diagnosis and definition of disease course according to the 2017 McDonald criteria * Expanded disability status scale (EDSS) ≤6.5 * Fulfilling criteria for active MS: * Treatment naïve relapsing remitting multiple sclerosis (RRMS) patients (never treated, or no DMT the previous 2 years): 1. ▪≥2 relapse previous 12 months OR 2. 1 relapse previous 12 months with severe residual symptoms and EDSS ≥ 3.0 OR 3. 1 relapse previous 12 months AND ≥9 T2 lesions on brain and/or spinal cord MRI AND * 1 contrast-enhancing lesion or ≥1 new or enlarging T2 lesion on brain and/or spinal cord MRI previous 12 month * Previously treated RRMS patients: 1. ≥1 relapse previous 12 months OR 2. ≥1 contrast-enhancing lesion or ≥2 new/enlarging T2 lesions on brain and/or spinal cord MRI previous 12 months * Progressive MS patients: 1. ≥1 relapse previous 12 months OR 2. ≥1 contrast-enhancing lesion previous 12 months or ≥1 new/enlarging T2 lesions on brain and/or spinal cord MRI previous 12 months or ≥2 new or enlarging T2 lesion on brain and/or spinal cord MRI previous 24 months OR 3. Increased levels of neurofilament light chain (NFL) in serum or cerebrospinal fluid (CSF) in sample collected previous 12 months. Progressive MS patients not fulfilling the clinical/MRI criteria for active disease, may qualify for inclusion in the study if: (A) CSF NFL level (measured with NF-Light® ELISA assay from Uman Diagnostics or Simoa): * 18 to 40 years \>560 ng/l * 41 to 60 years \>890 ng/l * 61 to 65 years \>1850 ng/l or (B) Serum NFL level (measured with Simoa™ NF-light® Advantage Kit) o Increased sNFL based on individual age-determined cut-off: \>4.19 × 1.029\^age ng/L OR o Increased sNFL based age-partitioned cut-offs: * 18 to 20 years \>7.4 ng/L * 21 to 30 years \>9.9 ng/L * 31 to 40 years \>13.1 ng/L * 41 to 50 years \>17.5 ng/L * 51 to 60 years \>23.3 ng/L * 61 to 65 years \>30.9 ng/L * Signed written informed consent Exclusion Criteria: * Pregnancy or breast feeding * Lack of effective contraception for women of child-bearing potential (effective contraception include oral contraception, intrauterine devices and other forms of contraception with failure rate \