Conference Coverage

MS Treatment Decisions Based on Milestones That Matter

Disability trajectories in MS may not be adequately captured by EDSS and MRI.


PARIS—Tracking disease impact in patients with multiple sclerosis (MS) by predictable loss of economically important milestones trajectory, beyond what can be documented by EDSS, MRI, or apparent or reported relapse, can be accomplished by use of objective multidomain cognitive testing, according to a report presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Such a strategy can provide patient-centric information such as predicting likely loss of economically impactful abilities that are not completely dependent upon EDSS nor currently obtained in the course of traditional MS care or clinical trials. “This objective approach might provide a pathway towards actionable change by objectively monitoring disease progression in a way that EDSS and MRI are unable and that will likely impact therapy choice as well as timing of disease-modifying treatment change,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, on behalf of his coauthors. “This approach can be incorporated into routine care and also can be utilized to easily and quantitatively track examiner independent multidomain cognitive impact longitudinally in a patient-centric manner in people with MS to perhaps improve care outcomes and reduce economic costs that accompany such increased disease burden.”

Mark Gudesblatt, MD

MS, which is usually characterized by relapses and progression, is traditionally measured by relapse rate reduction, changes in EDSS, and MRI findings. “EDSS change is primarily driven by physical findings or walking impairment, neither of which accounts for cognitive impact or reserve or accumulation of cognitive impairment,” Dr. Gudesblatt said. Cognitive impairment, he added, is not typically quantified or tracked in patients with MS in routine care or clinical trials. EDSS is also insensitive to the degree or types of cognitive impairment. Cognitive impairment, Dr. Gudesblatt and colleagues posit, impacts economically important abilities (eg, employment, ability to drive, and freedom from falls for both simple and complex daily activities) that are not addressed by traditional metrics.

Another layer of complexity is treatment choice. There are multiple available disease-modifying therapies of varied routes, dosing frequency, and efficacy. This makes individual treatment choice and timing of disease-modifying therapy change problematic. “A patient-centric objective analysis of disease trajectory and loss of economically important milestones relating to predictive loss of ability can supplement and perhaps improve alternative approaches to guide treatment choice, change, and timing,” Dr. Gudesblatt said.

An objective, quantitative, patient-centric, and granular EDSS-independent approach of likely disability trajectory might improve decision making regarding disease-modifying therapy choice and timing of change, offer a path to compare outcome measures across clinical trials, and possibly provide an opportunity to preempt the appearance of important disabilities that result in significantly increased cost of care and reduced quality of life. “Objective comprehensive analytics documenting unseen disease impact and change offer unique opportunities to improve care,” Dr. Gudesblatt said.

Toward this end, Dr. Gudesblatt and colleagues conducted a cross-sectional review of a prospective digital MS registry obtained in the course of routine care utilizing standardized computerized cognitive testing (NeuroTrax) to evaluate the relationship of cognitive impairment to disability. Cognitive impairment was defined as number of cognitive domains impaired (CDI) more than one standard deviation from age/education normal. Disability domains assessed were unemployment, loss of driving, and freedom from falls. Patients with an EDSS of less than 6 were included in the study cohort (ie, no one was included who was disabled to the point of requiring a cane to ambulate).

The researchers found that increasing accumulated number of CDI in patients with MS and an EDSS less than 6 is associated with likely progressive loss of:

  • Employment (n = 543, CDI-0 = 61%, CDI-1 = 50%, CDI-2 = 43%, CDI-3 = 32%)
  • Driving (n = 115, CDI-0 = 100%, CDI-1 = 66%, CDI-2 = 53%, CDI-3 = 21%)
  • Freedom from falls (n = 159) for simple daily activities (CDI-0 = 77%, CDI-1 = 65%, CDI-2 = 37%, CDI-3 = 39%) and reduced freedom from falls for complex daily activities (CDI-0 = 72%, CDI-1 = 58%, CDI-2 = 36%, CDI-3 = 33%).

Increased risk of falls and reduced likelihood of employment and driving all represent significant impact on quality of life and result in increased economic burden and long-term costs of the disease, Dr. Gudesblatt and colleagues said.