• No evidence of disease activity (NEDA) in subgroups [ Time Frame: 4 years ]
  The proportion of patients maintaining NEDA-3 comparing the previous rituximab arm with the previous DMF arm from the RIFUND trial
• Time to first relapse [ Time Frame: 3 yeas ]
  Time to first relapse for the two dose arms
• Freedom of new or enlarged lesions on MRI [ Time Frame: 3 years ]
  Proportion of patients in each dosing arm without new/enlarging T2 lesions
• Development of brain atrophy [ Time Frame: 3 years ]
  Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume
• Development of confirmed sustained disability [ Time Frame: 3 years ]
  Proportion of patient with confirmed progression in EDSS according to pre-specified criteria
• Mean progression of disability [ Time Frame: 3 years ]
  The mean change in EDSS over the trial period in the two dosing arms
• Neurodegeneration [ Time Frame: 3 years ]
  The mean change of s-NFL concentration between the two dosing arms
• Dose persistence [ Time Frame: 3 years ]
  Time to discontinuation of dosing regimen allocation
• Development of hypogammaglobulinaemia [ Time Frame: 3 years ]
  The occurrence of hypogammaglobulinaemia in the two dosing arms
• Development of neutropenia [ Time Frame: 3 years ]
  The occurrence of neutropenia in the two dosing arms
• Development of infections [ Time Frame: 3 years ]
  The occurrence of infections in the two dosing arms

• Health economy [ Time Frame: 3 years ]
  Estimation of societal costs per year to supply the two dosing arms
• Treatment Satisfaction Questionnaire [ Time Frame: 3 years ]
  Validated scale that evaluate the degree of treatment satisfaction through 10 5- or 7 grade likert-scale questions

This is a prospective randomized phase 3 study comparing two dosing regimens of Rituximab in long-term treatment of MS. Primary endpoint is no evidence of disease activity (NEDA) in a non-inferiority analysis between 12-months dosing interval of 500 mg rituximab with 6-months dosing interval. The endpoint is a compound of being free from release, new or enlarging MRI lesions and sustained progression of disability measured by EDSS.

Each patient will have one treating physician responsible for all ongoing medical questions and decisions regarding continuation in the study and one examining physician performing the blinded Expanded Disability Status Scale examination and assessments of exacerbations. The coordinating nurse will administer the study-related tests and administer the rituximab infusions. MRI investigations will be performed blinded for the dosing arm allocation.

Randomization will be performed via a randomization module in the national Swedish MS registry. The patients will be randomized in a 1:1 ratio and receive their treatments in accordance with clinical practice. Thus, the study will mimic the real-life situation in which the treatments will be administered. This will lead to a high degree of validity in relation to expected outcome in clinical practice.

• Active Comparator: 6-month dosing interval
  This arm is receiving standard dose rituximab 500 mg every 6 months
  Intervention: Drug: Rituximab
• Experimental: 12-month dosing interval
  This arm is receiving the comparator dose rituximab 500 mg every 12 months
  Intervention: Drug: Rituximab

Inclusion criteria:

• Diagnosis of Relapsing Remitting MS according to the 2017 revised McDonald criteria OR one demyelinating episode in conjunction with at least one asymptomatic high intensity T2 lesion with size and location compatible with MS
• The patient has completed the RIFUND-MS trial and is treated with either of the study medications rituximab or DMF at the last visit of the RIFUND trial OR has been treated with rituximab with a dose regimen of 500 - 1000 mg followed by 500 mg every 6 months for up to two years as part of clinical practice
• Age 20 - 52 years (inclusive)
• EDSS 0 - 5,5 (inclusive)
• The patient is willing and able to give written informed consent, according to the judgement of the investigator.
• In fertile females, willing to comply with effective contraceptive methods. These include birth control pills, surgical sterilization of patient or partner or intrauterine device. Non-fertile women is defined as more than 12 months of amenorrhea without an alternative medical cause or, in case of ambiguities, an FSH level in the postmenopausal range.

Exclusion criteria:

• Diagnosis of Progressive MS
• Previous treatment with any "second-line" immunomodulatory drug, eg natalizumab, alemtuzumab, fingolimod, or other long-acting immunosuppressive agents.
• Pregnant or lactating women s-HCG will be tested on all women at screening, before each study-related infu-sion and in any situation where there is a reason to suspect pregnancy during the trial, e.g delayed menstrual period more than five days above expected time.
• Patients having contraindication for or otherwise not compliant with MRI investigations
• Simultaneous treatment with other immunosuppressive drugs
• Active, severe infections Signs of infections are assessed before inclusion and each study-related infusion through clinical examination and further evaluated by laboratory and other relevant investigations in case of suspected ongoing infection. Hepatitis serology (HBsAg and anti-HBc) will be evaluated before treatment onset if not tested within the previous three years.
• Severe cardiac disorder, e.g signs of congestive heart failure or coronary artery disease. This will be evaluated through clinical assessment before inclusion.
• Vaccination within 4 weeks of first dose of study medication.
• Documented allergy or intolerance to the IP
• Severe psychiatric condition