Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries.

BACKGROUND: The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5-2-1 screening criteria. METHODS: Data were drawn from the Adelphi Parkinson's Disease Specific Program (DSP™), a multi-country point-in-time survey (2017-2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5-2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) "off" symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5-2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. RESULTS: From the analytic sample (n = 4714), 33% of patients met the 5-2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5-2-1 positive. Concordance between clinician judgment and 5-2-1 screening criteria was > 75%. 5-2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5-2-1-negative group, 5-2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5-2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5-2-1-positive patients also had significantly lower quality of life and worse caregiver burden. CONCLUSIONS: 5-2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5-2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.

Motor and nonmotor symptoms in patients treated with 24-hour daily levodopa-carbidopa intestinal gel infusion: Analysis of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS).

INTRODUCTION: Patients with advanced Parkinson's disease (APD) commonly experience motor and nonmotor symptoms (NMS) associated with functional limitations and decreased quality of life. We compared motor and nonmotor outcomes in patients with APD receiving 24- versus 16-h levodopa-carbidopa intestinal gel (LCIG). METHODS: Data from COSMOS, a large, real-world, retrospective and cross-sectional, observational study on LCIG and comedication in APD were obtained from medical records and a single patient visit for patients receiving 24- and 16-h LCIG infusion. Changes from baseline were evaluated for motor symptoms, NMS, and clinical characteristics. Safety was also assessed. RESULTS: Data for 401 patients were included in this subanalysis. At the patient visit there were 35 patients on 24-h LCIG and 366 on 16-h LCIG. "Off" time and dyskinesia (duration and severity) were reduced in both groups. In both LCIG treatment groups, prevalence of most symptoms was reduced. There were significant differences in the change from baseline in severity and frequency of freezing of gait with 24-h LCIG versus 16-h LCIG (p = 0.011 and p = 0.038), severity of urinary symptoms (p = 0.006), and frequency of cognitive impairment (p = 0.014) with 24-h LCIG versus 16-h LCIG. Adverse events were similar for both treatment groups and considered tolerable. CONCLUSIONS: LCIG 24-h infusion may be a useful treatment option, when clinically justified, for select patients with APD. CLINICAL TRIAL NUMBER: NCT03362879.

Characteristics of advanced Parkinson's disease patients seen in movement disorder clinics - Australian results from the cross-sectional OBSERVE study.

OBJECTIVES: To evaluate the proportion of Parkinson's disease (PD) patients identified as having advanced Parkinson's disease (APD) according to physician's judgement in Australia. METHODS: This cross-sectional, non-interventional observational study was performed in movement disorder clinics from 18 countries. Results from Australia are presented. Participants included consecutive adults with PD attending routine clinical visits, or inpatients, who could speak English. The primary outcome was the proportion of patients diagnosed with APD via physician judgement. RESULTS: 100 patients were recruited in Australia: 61.0% (95% CI 51.4-70.6%) diagnosed with APD by physician judgement. Patients were 66.6 ±â€¯8.5 years, 65% were male, were living at home (97%), and diagnosed with PD for median 10.7 years (0-30.5 years). Motor fluctuations were present in 68%. For those with APD, referral was predominantly to enable access to device assisted therapies (DAT) (49%), while for non-APD, referral was largely for diagnostic purposes (41%). Patients had a median follow-up at the movement disorder clinic of 4.8 years for those with APD, or 3.6 years for non-APD. While 62% were eligible for DAT, only two-thirds of these received them. The most commonly used DAT was deep brain stimulation (64.3%). There was fair agreement between physician's judgement and the APD criteria by Delphi method (Cohen's kappa) 0.325 (95% CI 0.150-0.500) in the Australian subset. CONCLUSIONS: The definition of APD requires refinement in order to facilitate greater agreement among movement disorder specialists. A third of APD patients eligible for DAT remain untreated. Better referral and education of patients with APD is needed.