title: Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command.
abstract: OBJECTIVE
  The therapies available today for multiple sclerosis (MS) reduce but do not fully control disease activity. The objective of this article is to review the definitions of and treatments for suboptimally controlled MS and highlight the challenges faced by clinicians to increase awareness of recognizing and managing patients with suboptimally controlled MS.
  
  
  METHODS
  Published literature describing treatment failure, treatment optimization paradigms or algorithms, clinical studies of therapies in patients with suboptimally controlled MS, or case reports of management of patients with suboptimally controlled MS were identified from searches of EMBASE and MEDLINE. This was supplemented with case reports and discussions from an expert panel meeting of MS specialists focused on the diagnosis and treatment of suboptimally controlled MS.
  
  
  RESULTS
  Several groups have created recommendations for evaluating suboptimal response to disease-modifying drugs (DMDs) in MS. Currently no robust evidence-based data exist to guide treatment decisions in patients who have suboptimal response to a particular therapy. In the absence of data, several treatment paradigms for suboptimally controlled MS have been proposed using a step therapy or platform therapy approach. Therapy modifications require consideration of disease- and patient-specific factors while accounting for the risk-benefit profile of the agent(s). Unapproved drugs and combination therapies should be reserved as agents of last resort because of the experimental nature of these treatments.
  
  
  CONCLUSIONS
  In the absence of evidence-based data, identifying and treating MS patients with suboptimal response to the available platform therapies remains challenging. Developing algorithms able to quantify breakthrough disease activity and suboptimal response to DMDs in individual MS patients remains an important target for the MS community. Consideration should be given for all reasons why a particular DMD may not be working for a given patient and for the use of an individualized step therapy.
authors.affiliation: University of Ottawa, Smyth Rd., Ottawa, ON, Canada K1H 8L6. mfreedman@ottawahospital.on.ca
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.forename: Bruce
authors.initials: B
authors.lastname: Cohen
authors.forename: Suhayl
authors.initials: S
authors.lastname: Dhib-Jalbut
authors.forename: Douglas
authors.initials: D
authors.lastname: Jeffery
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Reder
authors.forename: Magnhild
authors.initials: M
authors.lastname: Sandberg-Wollheim
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
mesh_terms: D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*