Objective: To compare off-time and QoL changes among APD patients taking LCIG, DBS, CSAI, and BMT at 6 months after therapy initiation.

Background: Advanced Parkinson’s disease (APD) patients often experience troublesome off time and worsening quality of life (QoL) despite best medical therapy (BMT). [1] Device-aided therapies such as levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) can improve off periods and reduce QoL burden. [2-4] Yet their comparative effectiveness is unclear.

Method: We conducted a systematic review and network meta-analysis by searching Medline, Embase, and the Cochrane Library (Jan 2003-Sep 2019). We included studies with 20+ PD patients, treated with any of the 4 therapies, and evaluated off time or QoL improvements at 6 months after initiation. Off time was assessed by dairy or Unified Parkinson’s Disease Rating Scale part IV item 39. QoL was measured by Parkinson’s Disease Questionnaire (PDQ-39/PDQ-8). Published results and original data were combined as available. We incorporated single-arm studies by unanchored matching-adjusted indirect comparison [5] and pooled all studies by Bayesian network meta-analysis. Therapies were compared and ranked based on improvements in off time and QoL and their 95% credible intervals (CI) from Bayesian iterations.

Results: 21 studies fulfilled inclusion criteria with a total of 2,063 patients. All device-aided therapies demonstrated greater improvements in off time and QoL compared with BMT at 6 months (p<0.05) [Fig.1]. Compared with CSAI, LCIG and DBS demonstrated significantly higher improvements in off time (LCIG: ∆1.35 hr/day; DBS ∆1.45 hr/day; p<0.05) and PD-related QoL (LCIG: ∆4.22; DBS: ∆3.63, p<0.05) [Fig.2]. There was no significant difference in off time and QoL between LCIG and DBS. Based on 135,000 Bayesian iterations, LCIG ranked highest (70% of iterations) for QoL improvement [Fig.3] and DBS ranked highest (58% of iterations) for off time reduction [Fig.4].

Conclusion: LCIG and DBS were associated with superior improvement in off time and PD-related QoL compared with CSAI and BMT at 6 months. Comprehensive evaluation of APD patients’ clinical status and preference is warranted to ensure optimal symptom control and maximize QoL.

References: 1. Timpka J, Nitu B, Datieva V, Odin P, Antonini A (2017) Device-Aided Treatment Strategies in Advanced Parkinson’s Disease. Int Rev Neurobiol 132, 453-474. 2. Olanow, C Warren et al. “Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study.” The Lancet. Neurology vol. 13,2 (2014): 141-9. doi:10.1016/S1474-4422(13)70293-X 3. Katzenschlager, R., Poewe, W., Rascol, O., Trenkwalder, C., Deuschl, G., Chaudhuri, K. R., Henriksen, T., van Laar, T., Spivey, K., Vel, S., Staines, H., & Lees, A. (2018). Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet. Neurology, 17(9), 749–759. 4. Weaver, F. M., Follett, K., Stern, M., Hur, K., Harris, C., Marks, W. J., Jr, Rothlind, J., Sagher, O., Reda, D., Moy, C. S., Pahwa, R., Burchiel, K., Hogarth, P., Lai, E. C., Duda, J. E., Holloway, K., Samii, A., Horn, S., Bronstein, J., Stoner, G., … CSP 468 Study Group (2009). Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA, 301(1), 63–73. 5.Phillipo D, Ades A, Dias S, Palmer S, Abrams K and Welton N. Methods for population-adjusted indirect comparisons in health technology appraisal (2018). Medical Decision Making. 38(2): 200-211.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-device-aided-therapies-on-qol-and-off-time-improvement-in-advanced-parkinsons-disease-patients-comparative-effectiveness-results-from-a-bayesian-network-meta-analysis/