Failed or inconclusive multiple sclerosis (MS) trials are invaluable to our understanding of the pathophysiology and treatment of MS.

Trial failure present in relapsing–remitting study populations unveiled, among other things, the complexity of B-cell involvement in MS pathophysiology, that higher selectivity can probably imply lower efficacy, and that current animal models are useful tools but are not able to completely mimic the complexity of human disease.

Trial failures in patient populations with progressive forms of MS indicate that the best placement of future trials is in the early and more active phases of the progressive disease. Careful selection of study duration and outcome parameters, with a focus on longer follow-up periods and shorter tract-based pathway functions might be critical to a successful outcome.