Background
Caring for a partner or family member with Parkinson’s disease (PD) negatively affects the caregiver’s own physical and emotional well-being, especially those caring for people with ...advanced PD (APD). This study was designed to examine the impact of APD on caregiver perceived burden, quality of life (QoL), and health status.
Methods
Dyads of people with PD and their primary caregivers were identified from the Adelphi Parkinson’s Disease Specific Program (DSP™) using real-world data from the United States, Japan and five European countries. Questionnaires were used to capture measures of clinical burden (people with PD) and caregiver burden (caregivers).
Results
Data from 721 patient-caregiver dyads in seven countries were captured. Caregivers had a mean age 62.6 years, 71.6% were female, and 70.4% were a spouse. Caregivers for people with APD had a greater perceived burden, were more likely to take medication and had lower caregiver treatment satisfaction than those caring for people with early or intermediate PD; similar findings were observed for caregivers of people with intermediate versus early PD. Caregivers for people with intermediate PD were also less likely to be employed than those with early PD (25.3% vs 42.4%) and spent more time caring (6.6 vs 3.2 h/day).
Conclusions
This real-world study demonstrates that caregivers of people with APD experience a greater burden than those caring for people with early PD. This highlights the importance of including caregiver-centric measures in future studies, and emphasizes the need for implementing treatments that reduce caregiver burden in APD.
Trial registration:
N/A.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Background
Parkinson’s disease is a progressive neurodegenerative disease, which significantly impacts patients’ quality of life and is associated with high treatment and direct healthcare costs. In ...England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson’s disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory.
Objective
We aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson’s disease in England, using real-world data.
Methods
A Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson’s disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted.
Results
Total costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG.
Conclusions
The base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England.
Background
Parkinson’s disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of ...the disease leads to a gradual deterioration in patients’ quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers.
Objective
We aimed to quantify the incremental economic burden of Parkinson’s disease by disease severity in a real-world setting across differing geographic regions.
Methods
Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson’s Disease Specific Program™, conducted in the USA, five European countries, and Japan.
Results
A total of 563 neurologists provided data for 5299 individuals with Parkinson’s disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs.
Conclusions
People with Parkinson’s disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson’s disease and their caregivers, whilst also substantially impacting societal costs.
Introduction
Complex polypharmacy regimens to manage persistent motor fluctuations result in significant pill burden for patients with advanced Parkinson’s disease (APD). This study evaluated the ...effectiveness of carbidopa/levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on reducing pill burden in APD patients.
Methods
We utilized 100% Medicare fee-for-service claims from 2014 to 2018 linked to CLES Patient Support Program (PSP) data. CLES initiators (CLES-I) were propensity matched 1:1 with patients enrolled in PSP who did not initiate treatment (CLES-NI) (
N
= 188) or undergo DBS, and 1:3 with patients who received DBS (
N
= 204,
N
= 612). Average daily pill burden and levodopa equivalent daily dosage (LEDD) were measured at baseline, 0–6 months and 7–12 months follow-up.
Results
CLES-I and CLES-NI had higher pill burden than DBS patients at baseline. However, at 6 months post-treatment, CLES-I had significantly fewer pills/day than CLES-NI (4.7 versus 11.4,
p
< 0.05) and DBS (4.8 versus 7.4,
p
< 0.05). A significant reduction in pill burden was observed at 0–6 months (46.3%) and 7–12 months (68.3%) follow-up for CLES-I (
p
< 0.001) versus increased burden for CLES-NI (+10.5%,
p
< 0.05 and +8.2%,
p
> 0.05) and insignificant reductions for DBS (−3.9% and −6.1%,
p
> 0.05). Mean adjusted pill burden showed 57.3% fewer pills at 0–6 months and 74.1% at 7–12 months among CLES-I compared with CLES-NI, and 49.6% and 70.1% reduction compared with DBS. CLES-I showed a decrease in LEDD at 7–12 months compared with baseline (935 to 237 mg) and to CLES-NI (237 mg versus 1112 mg) and DBS patients (236 mg versus 594 mg).
Conclusion
CLES led to a significant reduction in pill burden and oral LEDD compared with CLES-NI and DBS patients. Pill burden reduction could be considered a treatment goal for patients with APD challenged by complex polypharmacy regimens that interfere with activities of daily living and quality of life.
Graphical Abstract
Plain Language Summary
Management of uncontrollable motor movements in patients with advanced Parkinson’s disease rely on oral levodopa-based treatments. Non-motor symptoms such as depression and anxiety are managed with additional oral medications. Over time, higher and more frequent dosing of oral medications is required, resulting in complex medication regimens that impact quality of life and adherence.
A real-world study of 10,752 Parkinson’s disease patients between 2014 and 2018 evaluated the effectiveness of two device-aided therapies to reduce pill burden, carbidopa/levodopa enteral suspension and deep brain stimulation. Carbidopa/levodopa suspension treatment involves continuous delivery of levodopa to the intestines through a surgical port attached to a portable pump. Brain stimulation involves surgery to attach metal wires to the brain to send electrical pulses via an implanted stimulator.
As Parkinson’s disease predominately affects the elderly, we compared Medicare patients on carbidopa/levodopa suspension to a matched control group receiving no suspension and to those receiving brain stimulation. Average pill burden/day was measured prior to receiving a device-aided treatment (baseline) and at 0–6 months and 7–12 months post-treatment (follow-up).
The top graph shows that by 6-months post-treatment, patients on carbidopa/levodopa suspension required fewer pills than those without suspension (4.7 versus 11.4), with further pill reduction at 12 months (3.5 versus 11.1). The bottom graph shows that by 6 months, patients on carbidopa/levodopa suspension required fewer pills than patients treated with brain stimulation (4.8 versus 7.4), with further reduction at 12 months (3.6 versus 7.0). The reduction in oral pill burden suggests that the carbidopa/levodopa suspension may present an opportunity to simplify treatment regimens.
•In APD, fluctuations between patients’ motor states develop as disease progresses.•Evidence on long-term impact of CLES on motor fluctuations across the day is limited.•CLES was associated with ...fewer motor fluctuations and increased symptom control.•Patients taking CLES had faster onset to good ON time after waking.•CLES may improve patients’ quality of life by reducing unpredictable OFF periods.
Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson’s disease patients across 54 weeks. Evidence on CLES’s long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.
We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients’ motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states’ durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD).
Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58–65 min; wk54: 60–78 min; all P < 0.0001) and reductions in OFF (wk4: 50–61 min; wk54: 56–68 min; all P < 0.0001). At weeks 4 and 54, patients’ motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001).
CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.
Introduction
In advanced Parkinson’s disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of ...carbidopa–levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden.
Methods
A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS.
Results
The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: −5.62,
p
< 0.0001; ∆DBS: −1.48,
p
= 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: −4.14,
p
< 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively,
p
= 0.0123).
Conclusions
Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS.
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