Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel

BACKGROUND: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. OBJECTIVE: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. METHODS: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. RESULTS: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. CONCLUSION: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time

Application of the '5-2-1' screening criteria in advanced Parkinson's disease : interim analysis of DUOGLOBE

Aim: A Delphi expert consensus panel proposed that fulfilling ≥1 of the '5-2-1 criteria' (≥five-times daily oral levodopa use, ≥two daily hours with 'Off' symptoms or ≥one daily hour with troublesome dyskinesia) suggests advanced Parkinson's disease (PD). Patients & methods: DUOdopa/Duopa in Patients with Advanced PD - a GLobal OBservational Study Evaluating Long-Term Effectiveness (DUOGLOBE) - is a single-arm, postmarketing, observational, long-term effectiveness study of levodopa-carbidopa intestinal gel (LCIG) for advanced PD. Results: This 6-month interim analysis (n = 139) affirms that most (98%) enrolled patients fulfill ≥1 of the 5-2-1 criteria. These patients responded favorably to LCIG treatment. Safety was consistent with other LCIG studies. Conclusion: In advanced PD patients, the 5-2-1 criteria generally aligns with clinician assessment. Clinical Trial Registration: NCT02611713 (ClinicalTrials.gov)

DUOGLOBE: One‐Year Outcomes in a Real‐World Study of Levodopa Carbidopa Intestinal Gel for Parkinson's Disease

Background:Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for improvingmotor and some non-motor symptoms (NMS) in patients with advanced Parkinson’s disease (PD). Prospectivelong-term data in routine clinical practice are limited.ObjectiveObjective:Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real-worldroutine clinical practice.MethodsMethods:Duodopa/Duopa in patients with advanced Parkinson’s disease—a global observational studyevaluating long-term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational,observational study of LCIG-naïve patients treated as part of routine clinical practice; 3 years of follow-up areplanned. The primary outcome is the change in patient-reportedofftime. Other assessments include theUnified Dyskinesia Rating Scale (UDysRS), Non-Motor Symptoms Scale (NMSS), Parkinson’s Disease Sleep scale(PDSS-2), Epworth Sleepiness Scale (ESS), health-related quality of life (HR-QoL), caregiver burden, and seriousadverse events (SAEs). Outcomes from baseline to month (M) 12 are presented.ResultsResults:In this 12-month follow-up, patients (N=195) had baseline characteristics similar to other LCIG studies.Significant improvements (mean change to M12) were observed inofftime ( 3.9 3.6 hr/day,P< 0.001),dyskinesia assessed using the UDysRS ( 9.6 22.5,P< 0.001), NMSS ( 23.1 41.4,P< 0.001), sleep andsleepiness symptoms on the PDSS-2 ( 6.5 12.2,P< 0.001) and ESS ( 1.0 5.7,P< 0.05), HR-QoL ( 9.0 21.6,P< 0.001), and caregiver burden ( 1.9 6.7,P=0.008). Overall, 40.5% (n=79) of patients experienced SAEs;fall (n=6; 3.1%) and urinary tract infection (n=6; 3.1%) were SAEs reported in≥3% of patients.ConclusionsConclusions:These 12-month outcome data show sustained, long-term improvements and support the real-world effectiveness of LCIG in patients with advanced PD. Safety was consistent with previous studies

Levodopa Carbidopa Intestinal Gel in Advanced Parkinson’s Disease: DUOGLOBE Final 3-Year Results

Background: Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson’s disease (aPD). Objective: To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson’s Disease – a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713). Methods: DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care. The primary endpoint was change in patient-reported “Off” time to Month 36. Safety was assessed by monitoring serious adverse events (SAEs). Results: Significant improvements in “Off” time were maintained over 3 years (mean [SD]: –3.3 hours [3.7]; p < 0.001). There were significant improvements to Month 36 in total scores of the Unified Dyskinesia Rating Scale (–5.9 [23.7]; p = 0.044), Non-Motor Symptoms Scale (–14.3 [40.5]; p = 0.002), Parkinson’s Disease Sleep Scale-2 (–5.8 [12.9]; p < 0.001), and Epworth Sleepiness Scale (–1.8 [6.0]; p = 0.008). Health-related quality of life and caregiver burden significantly improved through Months 24 and 30, respectively (Month 24, 8-item Parkinson’s Disease Questionnaire Summary Index, –6.0 [22.5]; p = 0.006; Month 30, Modified Caregiver Strain Index, –2.3 [7.6]; p = 0.026). Safety was consistent with the well-established LCIG profile (SAEs: 54.9% of patients; discontinuations: 54.4%; discontinuations due to an adverse event: 27.2%). Of 106 study discontinuations, 32 patients (30.2%) continued LCIG outside the study. Conclusion: DUOGLOBE demonstrates real-world, long-term, reductions in motor and non-motor symptoms in patients with aPD treated with LCIG

Application of the †5-2-1' screening criteria in advanced Parkinson's disease:Interim analysis of DUOGLOBE

Aim: A Delphi expert consensus panel proposed that fulfilling ≥1 of the ‘5-2-1 criteria’ (≥five-times daily oral levodopa use, ≥two daily hours with ‘Off’ symptoms or ≥one daily hour with troublesome dyskinesia) suggests advanced Parkinson’s disease (PD). Patients & methods: DUOdopa/Duopa in Patients with Advanced PD – a GLobal OBservational Study Evaluating Long-Term Effectiveness (DUOGLOBE) – is a single-arm, postmarketing, observational, long-term effectiveness study of levodopa–carbidopa intestinal gel (LCIG) for advanced PD. Results: This 6-month interim analysis (n = 139) affirms that most (98%) enrolled patients fulfill ≥1 of the 5-2-1 criteria. These patients responded favorably to LCIG treatment. Safety was consistent with other LCIG studies. Conclusion: In advanced PD patients, the 5-2-1 criteria generally aligns with clinician assessment