In addition to the clinical trials, there is emerging data from open label real-world observational studies on the safety and efficacy of CLES. Outcomes evaluates in these studies include motor symptoms, non-motor symptoms, QoL, ADL amongst others. A meta-analysis approach allows for pooling data across multiple studies to comprehensively evaluate the impact of drug on relevant patient-centric outcomes.
Published trials and observational studies examining the efficacy of CLES were identified from EMBASE, MEDLINE, Derwent Drug File, and BIOSIS Previews up to September 7, 2017. Outcomes of interest for this analysis include: (i) QoL (PDQ-8, PDQ-39, EQ-5D VAS, EQ-5D), and ADL (UPDRS-II)The pooled mean change from baseline (CFB) with 95% confidence interval (CI) was estimated for each 3-month interval up to 24 months by a random-effects model. Heterogeneity was evaluated using I2 and Q-statistic.
A total of 27 studies (4 clinical trials and 23 observational studies) evaluating a total of 1,562 patients with advanced PD were included in this analysis. All outcomes of interest showed statistically significant improvement within 1–3 months of starting CLES. Improvement in PD-related QoL was sustained up to a period of 2 years after CLES initiation [For PDQ-39: CFB10–12months = −8.6(−6.58,−10.62); CFB22–24months = −7.74(−3.07,−12.40). Improvement in ADL was sustained up to a period of 2 years after CLES initiation [For UPDRS-IIOFF: CFB10–12months = −5.36(−2.03,−8.70); CFB 22–24months = −3.88(−2.42,−5.34)]. Results were robust to the exclusion of studies driving heterogeneity.
CLES leads to improvement in QoL and ADL measures in APD patients that are consistent across a broad range of studies and persist for up to 2 years. Future analyses will evaluate correlation with other outcomes.
David Standaert, Vardhaman Patel, Sonya Snedecor, Sandeep Thakkar, Yash J. Jalundhwala, Pavnit Kukreja, David Kratochvil, Yanjun Bao, Rajesh Pahwa