All treatments will have a beneficial effect, but also side effects. To choose the most optimal treatment both these has to be balanced. Randomized clinical trials will provide the basic evidences for each drug to be approved for each indication. Rituximab has proved to be beneficial for MS treatment, but no randomized clinical trial will be done for this indication. Instead COMBAT-MS will provide this data through a long-term observational study of the off-label use of rituximab in comparison with all other approved immunotherapies for MS.