Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson’s Disease: A Systematic Review and Bayesian Network Meta-analysis

Abstract

Introduction Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson’s disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. Methods A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson’s Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson’s Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. Results A total of 22 studies fulfilled the inclusion criteria ( n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5–70.9 years, duration of PD was 9.1–15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT ( p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. Conclusions This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-022-00963-9.

Effective Management of “OFF” Episodes in Parkinson’s Disease: Emerging Treatment Strategies and Unmet Clinical Needs

“…A network meta-analysis done by Antonini et al demonstrated that DBS and LCIG had greater improvements in OFF time than CSAI with DBS resulting in greatest OFF time reduction. 121 The change in OFF time was −1.45 hours/day for DBS and −1.35 hours/day for LCIG. 121 However, LCIG had the highest ranking in QoL improvement.…”

“… 121 The change in OFF time was −1.45 hours/day for DBS and −1.35 hours/day for LCIG. 121 However, LCIG had the highest ranking in QoL improvement. 121 Marsilli et al also found DBS and LCIG to be superior to CSAI and BMT in improving motor function, however at the expense of higher lifetime costs (CSAI had the lowest lifetime costs and LCIG had the highest).…”

“… 121 However, LCIG had the highest ranking in QoL improvement. 121 Marsilli et al also found DBS and LCIG to be superior to CSAI and BMT in improving motor function, however at the expense of higher lifetime costs (CSAI had the lowest lifetime costs and LCIG had the highest). 122 An advantage of CSAI is that no surgical procedure is required, however it is not available in all countries.…”

Levodopa–carbidopa intestinal gel in advanced Parkinson’s disease: long-term results from COSMOS

“…Likewise, a randomized, crossover design comparator study found that patients generally preferred infusion therapy with LCIG versus oral administration with levodopa ( n = 24) [ 32 ]. Indeed, meta-analyses have found significant improvements in off-time and quality of life or comparable benefits with LCIG versus deep brain stimulation, continuous subcutaneous apomorphine infusion, and best medical treatment [ 33 – 35 ], and similar cost between LCIG and standard of care [ 36 ].…”

Quality of Life in Patients With Parkinson’s Disease: A Cross-Sectional Study

“…Several factors influence the QOL in patients with parkinsonism. A study reported a decrease in the QOL of patients with PD, which was observed in both physical and psychological parameters [ 10 , 11 ].…”