Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson’s Disease: An Analysis of NET-PD LS1

Article type: Research Article

Authors: Hauser, Robert A.^{a; *} | Li, Ruosha^b | Pérez, Adriana^b | Ren, Xuehan^b | Weintraub, Dan^c | Elm, Jordan^d | Goudreau, John L.^e | Morgan, John C.^f | Fang, John Y.^g | Aminoff, Michael J.^h | Christine, Chadwick W.^h | Dhall, Rohitⁱ | Umeh, Chizoba C.^j | Boyd, James T.^k | Stover, Natividad^l | Leehey, Maureen^m | Zweig, Richard M.ⁿ | Nicholas, Anthony P.^o | Bodis-Wollner, Ivan^p | Willis, Allison^q | Kieburtz, Karl^r | Tilley, Barbara C.^b | for the NINDS NET-PD Investigators

Affiliations: [a] Departments of Neurology, Molecular Pharmacology and Physiology, University of South Florida, Parkinson’s Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa FL, USA | [b] Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA | [c] Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA | [d] Medical University of South Carolina, Department of Public Health Sciences, Charleston, SC, USA | [e] Department of Neurology, Michigan State University, East Lansing, MI, USA | [f] National Parkinson Foundation Center of Excellence, Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA | [g] Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA | [h] University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA | [i] The Parkinson’s Institute and Clinical Center, Sunnyvale, CA, USA | [j] Division of Movement Disorders, Brigham and Women’s Hospital, Boston, MA, USA | [k] Department of Neurological Sciences, University of Vermont, College of Medicine, Burlington, VT, USA | [l] Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA | [m] Department of Neurology, University of Colorado, School of Medicine, Aurora, CO, USA | [n] Department of Neurology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA | [o] Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA | [p] Departments of Neurology and Ophthalmology, Parkinson’s Disease and Related Disorders Clinic, Center of Excellence, State University of New York, Downstate Medical Center, Brooklyn, NY, USA | Department of Neurology, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA | University of Rochester, Center for Human Experimental Therapeutics, Rochester, NY, USA

Correspondence: [*] Correspondence to: Robert A. Hauser, MD, MBA, Departments of Neurology, Molecular Pharmacology and Physiology University of South Florida, Parkinson’s Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, 4001 E Fletcher Ave, Tampa FL, 33596 USA. Tel.: +813 396 0765; Fax: +813 905 9829; E-mail: [email protected].

Abstract: Background: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. Objective: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. Methods: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson’s Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually. Results: 1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was – 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002). Conclusions: Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.

Keywords: Parkinson’s disease, MAO-B inhibitor, rasagiline, selegiline, treatment, disease modification

DOI: 10.3233/JPD-160965

Journal: Journal of Parkinson's Disease, vol. 7, no. 1, pp. 117-127, 2017