title: Failed, interrupted and inconclusive trials on relapsing multiple sclerosis treatment: update 2010-2015.
abstract: The treatment of multiple sclerosis (MS) remains challenging despite the great efforts made in the development of novel therapies. Driven by the growing knowledge of the immunopathogenesis of the disease, a plethora of new pharmacological agents have been developed and tested in clinical trials. However, the therapeutic advantages and positive clinical trials of some of these agents are outweighed by studies of promising agents that either failed due to negative or inconclusive results or had to be withdrawn because of serious unexpected adverse events. Most failed clinical trials did not lack a well-considered pathophysiological rationale, but concepts from experimental models were proven wrong in humans. Lessons learned from these discrepancies help to optimize future study design and, potentially more importantly, provide further insight into the immunopathogenesis of MS. Here, we summarize trials on MS treatments since 2010 that failed or were interrupted, identifying potential underlying reasons for failure or inconclusiveness.
authors.affiliation: a Department of Neurology , University of Muenster , Muenster , Germany.|b Institute for Translational Neurology , University of Muenster , Muenster , Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Pfeuffer
authors.affiliation: a Department of Neurology , University of Muenster , Muenster , Germany.|b Institute for Translational Neurology , University of Muenster , Muenster , Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.affiliation: c Department of Neurology , University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: a Department of Neurology , University of Muenster , Muenster , Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: a Department of Neurology , University of Muenster , Muenster , Germany.|b Institute for Translational Neurology , University of Muenster , Muenster , Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D012008:Recurrence; D012107:Research Design
chemical_list: D007166:Immunosuppressive Agents
keywords: Clinical trials; MS; drug development; failure; interruption; novel therapies; treatment