Impact of Disease Duration in Effectiveness of Treatment with Levodopa-Carbidopa Intestinal Gel and Factors Leading to Discontinuation

Article type: Research Article

Authors: Regidor, Ignacio^{a; *} | Santos-García, Diego^b | Catalán, Mar;ıa José^c | Puente, Vıctor ^d | Valldeoriola, Francesc^e | Grandas, Francisco^f | Mir, Pablo^{g; h} | Parra, Juan Carlosⁱ | Arbelo, José Matías^j

Affiliations: [a] Functional Neurosurgery Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain | [b] Department of Internal Medicine, Neurology Section, Hospital Arquitecto Marcide, Complejo Hospitalario Universitario de Ferrol (CHUF), A Coruña, Spain | [c] Department of Neurology, Movement Disorders Unit, Hospital Clínico San Carlos, Madrid, Spain | [d] Department of Neurology, Movement Disorders Unit, Parc de salut Mar, Institut Hospital del Mar d’investigacions Mèdicas, Universitat Autònoma de Barcelona, Barcelona, Spain | [e] Department of Neurology, Movement Disorders Unit, Hospital Clínic, Barcelona, Spain | [f] Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Spain | [g] Department of Neurology, Movement Disorders Unit, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain | [h] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain | [i] AbbVie Spain S.L.U., Madrid, Spain | [j] Department of Neurology, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain

Correspondence: [*] Correspondence to: Ignacio Regidor, MD, PhD, Unidad de Neurocirugía Funcional; Hospital Universitario Ramón y Cajal, Carretera Colmenar km 9,100; 28034 Madrid, Spain. Fax: +34 91 3368037; E-mail: [email protected].

Abstract: Background:Levodopa-carbidopa intestinal gel (LCIG) is effective in the treatment of advanced Parkinson’s disease (PD). However, the patients’ profile that might benefit from treatment with LCIG has not been characterized. Objective:This retrospective study explored the influence of disease duration (DD) on the effectiveness of LCIG and identified factors associated with treatment discontinuation in a cohort of advanced PD patients. Methods:Patients initiating LCIG therapy between Jan-2006 and Dec-2011 in 18 Spanish centers were included. Effectiveness in treating motor symptoms (MSs), non-motor symptoms (NMSs), and adverse events (AEs) occurrence was compared in DD≥10 or <10 years and LCIG continuation/discontinuation groups. Factors associated with LCIG discontinuation were evaluated using univariate and multivariate analyses. Results:Overall, 177 PD patients were included (52.5% male; mean age 70.6±8.4 years; mean LCIG duration 35.6±18.6 months). Patients with DD≥10 years (n = 125) experienced less reduction in “off” time (–29%) than those with DD <10 years (–38%; n = 51; p = 0.021), and reported more severe AEs (32.8% vs. 17.6%; p = 0.043). DD did not significantly influence changes in NMSs or discontinuation rates. Fifty-four patients discontinued LCIG therapy, factors associated with discontinuation were higher percentages of waking day in the “off” state (OR, 1.028; 95% CI, 1.002–1.055; p = 0.0360) and in the “on” state with troublesome dyskinesia (OR, 1.032; 95% CI, 1.002–1.064; p = 0.0376) at baseline. Conclusions:Advanced PD patients with DD <10 years might benefit more from treatment with LCIG than patients with a longer DD. Although MSs severity at baseline was statistically associated with LCIG discontinuation, the probability was very low with little clinical significance.

Keywords: Parkinson’s disease, levodopa-carbidopa intestinal gel, non-motor symptoms, global clinical impression

DOI: 10.3233/JPD-181324

Journal: Journal of Parkinson's Disease, vol. 9, no. 1, pp. 173-182, 2019