Observational Studies of MS Disease Course & Therapy

Overview

Observational studies harnessed from real-world data in clinical practice have valuable implications in decision-making and can answer clinically relevant questions that have broad applicability. Clinical trial data, while valuable from a regulatory standpoint for approval of new medications, have more limited applications in the clinical setting. At Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, we are using our large patient experience to better understand the effectiveness, safety, and patient experience with different treatment strategies in clinical practice. These studies leverage data from routine care that are not constrained by rigid clinical trials and are thus more generalizable and applicable to healthcare providers and patients living with multiple sclerosis (MS).

Some of these pragmatic observational studies use propensity score (PS) analysis to compare the safety and effectiveness of disease modifying therapies (DMTs) using real-world experiences. PS methods reduce the impact of confounding and certain biases that are inherent in observational studies, thereby approximating a randomized study design for determining treatment effect differences. Our investigators also use PS analysis to investigate MRI stability as a treatment target in MS and the long-term benefit of DMTs using the Knowledge Program, a Cleveland Clinic-developed database that collects longitudinal patient- and clinician-reported outcomes electronically.

We also harness observational data to describe the influence of various comorbidities on MS disease activity, analyze patient reported outcomes in patients transitioning from relapsing-remitting to secondary progressive MS, study the real-world experience of patients using technology-enabled neuroperformance testing, and describe the Mellen Center experience in DMT discontinuation to better understand disease and patient reported outcomes in older individuals living with MS. Altogether, through structured collection and analysis of clinical data, we are able to leverage real-world outcomes to answer clinically relevant questions and inform decision-making in routine practice.

Contact Information

Carrie M. Hersh, DO, MSc
hershc@ccf.org

Research Focus Areas

Clinical trials of MS disease therapies and therapeutic strategies (Cohen)
Clinical trials of MS symptomatic therapies (Bethoux)
Clinical trials of neuroprotective and restorative therapies for MS (Cohen, Fox, Planchon Pope)
Observational studies of MS disease course and therapy (Hersh, Conway, Hua, Ontaneda)
Technology-enabled data collection to integrate patient care and clinical research (Bermel, Weber)
Advanced imaging techniques to detect and quantify MS-related CNS pathology (Ontaneda, Fox)
Tissue acquisition program to elucidate MS pathology and imaging-pathology correlations (Ontaneda)
Development and validation of self-reported measures of health status and quality of life (Miller)
Decision-making and risk stratification with MS therapies (Fox, Ontaneda)
Pediatric MS – disease characteristics and treatment MS (Rensel)
Access to health care (Miller)
Behavioral medicine research (Sullivan)

Funding

Devon Conway, MD, MSc has a funded collaboration with Novartis to describe disease modifying therapy adherence and the transition from relapsing-remitting MS to secondary progressive MS in patients treated with fingolimod.

Le Hua, MD receives research support from the Eric and Sheila Samson Foundation.

Daniel Ontaneda MD, MSc has completed a funded research project with Novartis examining the comparison on first line and second line use of fingolimod in clinical practice.

Daniel Ontaneda MD, MSc has a funded research project with Genentech to examine the early tolerability and efficacy of ocrelizumab in clinical practice.

Carrie Hersh has received biostatistical support from the Cleveland Clinic Neurological Institute Center for Outcomes Research and Evaluation (NICORE).

Publications

Early tolerability and safety of fingolimod in clinical practice J Neurol Sci 2012;323:167-72. Ontaneda D, Hara-Cleaver C, Rudick RA, Cohen J, Bermel R.

Experience with fingolimod in clinical practice. Hersh, CM, Hara-Cleaver, C, Rudick, RA, Cohen, JA, Bermel, RA, Ontaneda, D. Int J Neurosci. 2015; 125(9):678-85.

Comparative efficacy and discontinuation of dimethyl fumarate and fingolimod in clinical practice at 12-month follow-up. Hersh, CM, Love, TE, Cohn, S, Hara-Cleaver, C, Bermel, RA, Fox, RJ, Cohen, JA, Ontaneda, D. Mult Scler Relat Disord. 2016; 10:44-52.

Comparative efficacy and discontinuation of dimethyl fumarate and fingolimod in clinical practice at 24-month follow-up. Hersh, CM, Love, TE, Bandyopadhyay, A, Cohn, S, Hara-Cleaver, C, Bermel, RA, Fox, RJ, Cohen, JA, Ontaneda, D. Mult Scler J Exp Transl Clin. 2017 Aug 24;3(3):2055217317715485. doi: 10.1177/2055217317715485. eCollection 2017 Jul-Sep.

Influence of Hypertension, Diabetes, Hyperlipidemia, and Obstructive Lung Disease on Multiple Sclerosis Disease Course. Conway, DS, Thompson, NR, Cohen, JA. Mult Scler. 2017; 23(2): 277-285.

Lack of Magnetic Resonance Imaging Lesion Activity as a Treatment Target in Multiple Sclerosis: An Evaluation Using Electronically Collected Outcomes. Conway DS, Thompson, NR, Cohen JA. Mult Scler Relat Disord. 2016; 9: 129-134.

Long Term Benefit of Multiple Sclerosis Treatment: An Investigation Using a Novel Data Collection Technique. Conway DS, Miller DM, O’Brien RG, Cohen JA. Mult Scler J. 2012; 18(11): 1617-24.

Discontinuation and comparative effectiveness of dimethyl fumarate and fingolimod in two centers. Vollmer, B, Ontaneda D, Bandyopadhyay, A, Cohn, S, Nair, K, Sillau, S, Bermel, R, Corboy, J, Fox, RJ, Vollmer, T, Cohen, JA, Alvarez, A, Hersh, CM. Neurol Clin Pract. 2018; 8(4):292-301. doi: 1212/CPJ.0000000000000487.

Harnessing real-world data to inform treatment decisions in multiple sclerosis. Hersh, CM and Marrie, RA. Neurology. 2019; 93(7):285-286. doi: 1212/WNL.0000000000007934.

Comparative discontinuation, effectiveness, and switching practices of dimethyl fumarate and fingolimod at 36-month follow-up. Vollmer, B, Ontaneda, D, Harris, H, Nair, K, Bermel, R, Corboy, J, Fox, RJ, Vollmer, T, Cohen, JA, Alvarez, A, Hersh, CM. J Neurol Sci. 2019; 407:116498. doi:10.1016/j.jns.2019.116498.

Prognostic Factors of Disability in Relapsing Remitting Multiple Sclerosis. Briggs FBS, Thompson NR, Conway DS. Mult Scler Relat Disord. 2019 May; 30: 9-16.

Comprehensive Assessments in Clinic Using Technology-Enabled Neuroperformance Testing, Patient Reported Outcomes, and Quantitative MRI. Baldassari, LE, Nakamura, K, Moss, BP, Macaron, G, Li, H, Weber, M, Jones, SE, Rao SM, Miller, D, Conway, DS, Bermel, R, Cohen, JA, Ontaneda, D, McGinley M. Mult Scler Relat Disord. 2019; 38:101525. Doi: 10.1016/j.msard.2019.101525.

Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60.Hua, LH, Fan, TH, Conway, D, Thompson, N, Kinzy, TG. Mult Scler. 2019; 25(5):699-708. doi: 10.1177/1352458518765656.

Changes in patient-reported outcomes between continuers and discontinuers of disease modifying therapy in patients with multiple sclerosis over age 60. Hua, LH, Harris, H, Conway, D, Thompson, NR. Mult Scler Relat Disord. 2019 May;30:252-256. doi: 10.1016/j.msard.2019.02.028.

Members Collaborators

Cleveland Clinic

External Relationships and Collaborations

Enrique Alvarez, MD, PhD, Rocky Mountain Multiple Sclerosis Center at University of Colorado