Michael K. Racke, MD

Expert Perspective

Multiple Sclerosis: Biomarkers, Treatment, and Depression Management

Practice Community
Columbus, OH
Hospital and Institute Affiliations
Ohio State University Wexner Medical Center
Number of Patients Seen in a Week
Approximately 40-50 MS patients
Practice Niche
Multiple Sclerosis, Neuroimmunology


What are the clinical roles for molecular biomarkers in diagnosing and monitoring MS disease progression and treatment response?


In diagnosing MS, there are really no real molecular biomarkers. Magnetic resonance imaging has been very helpful and the presence of oligoclonal bands or elevated IgG index have been used for years to help in the diagnosis of multiple sclerosis. There are some tests that are under development. One test called the antibody gene signature has shown some predictive value in helping determine whether an initial CNS inflammatory event might go on to multiple sclerosis.

For monitoring disease progression, there has been use of things such as the presence of neurofilament in the CSF, but that has not gained use as a clinical tool that everyone could order and is still basically a research biomarker. Ocular coherence tomography (OCT) also is being used to measure disease progression in MS and in research studies has been used to evaluate the potential of treatments for their ability to be neuroprotective. Regarding treatment response, many use the MRI and if there are no new lesions, the clinician may feel that this is reflective of a good treatment response.

Other tests used in monitoring patients on therapy include things like neutralizing antibodies for patients on interferon-beta. The use of the anti-JCV-antibody titer has been helpful in guiding clinicians on risk of developing PML for patients considering natalizumab as a treatment. Varicella Zoster (VZV) antibody and tuberculosis (TB) immunity are also some times checked to assess risk for some of the newer immunosuppressive agents.


How have the newer immunomodulatory agents changed the standard of care? (What do we know about optimal combinations or sequencing of treatments?)


Perhaps the biggest change with the higher efficacy agents is the sense that rather than just reducing disease activity, we should try to prevent further disease activity. The concept of NEDA (no evidence of disease activity) has not only become a secondary outcome measure in clinical trials, but many clinicians are now checking brain kris with the idea of seeing whether the agent the patient is taking is suppressing MRI activity. Because these agents have more significant effects on the immune response, there does need to be additional vigilance to prevent complications such as progressive multifocal leukoencephalopathy (PML). Unfortunately, we know very little about sequencing of agents, particularly with regard to safety. There have been few trials, such as CARES MS II, where patients basically had to fail interferon-beta in order to enter the study.1 The CHORD trial is currently examining the effectiveness of ocrelizumab in patients who have failed a disease modifying therapy. The HALT MS trial was one of the few studies in which a treatment was tried in patients who had to have failed two treatments.2 Unfortunately, the question of the sequence of agents and particularly does an agent following a strong immunosuppressant have greater risks than if given to a treatment naïve patient, really has not been addressed in a systematic fashion.


How should depression be managed among people with MS?


The incidence of depression is much higher in MS patients than the general population. Because MS and treatment can cause symptoms of depression, reduced sleep, and other issues, management of depression is often very helpful in improving the quality of life in patients with multiple sclerosis. While this can often take the form of pharmacologic management with an antidepressant, exercise, behavioral therapy, and other techniques can also help MS patients with depression.


Giovannoni G, Cohen JA, Coles AJ, et al. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016;87(19):1985-1992. doi: 10.1212/WNL.0000000000003319

Nash RA, Hutton GH, Racke MK, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88:1-11. Doi: 10.1212/WNL.0000000000003660