Abstract
Objective:
To compare the risk of developing uveitis in patients initiating anti-tumor necrosis factor (anti-TNF) agents (adalimumab, etanercept, and infliximab) for ankylosing spondylitis ...(AS).
Methods:
Anti-TNF-naive patients with a diagnosis of AS and without a history of uveitis (N = 2115) who subsequently initiated anti-TNF therapy for AS were identified in a large claims database (2005 to 2011). A multivariate Cox proportional-hazards model was used to compare the risk of uveitis in patients who received etanercept or infliximab vs adalimumab.
Results:
The median number of days to the first occurrence of uveitis after initiation of anti-TNF was 191. Among the three anti-TNF groups, the median time to event of uveitis was longest in patients taking adalimumab (243 days), followed by etanercept (182 days) and infliximab (144 days). The incidence rate for uveitis over 1 year was lowest for patients who received adalimumab (2.4%, N = 717), highest for patients who received etanercept (4.5%, N = 1087), and intermediate for patients who received infliximab (3.2%, N = 311). The risk of uveitis was 1.9 times higher in patients receiving etanercept compared with those taking adalimumab (hazard ratio HR: 1.91, 95% confidence interval CI: 1.1 to 3.31). For patients taking infliximab, the risk of uveitis was not statistically significantly different (HR: 1.35, 95% CI: 0.62 to 2.95) compared to adalimumab.
Conclusion:
The results indicated that initial adalimumab therapy is associated with a significantly lower risk of developing uveitis compared to initial etanercept therapy in patients diagnosed with AS and no prior history of uveitis; however, the risk was not different between adalimumab and infliximab. Limitations to consider when interpreting this conclusion include that disease-level clinical data, such as disease duration, were not available for inclusion in the model and that risk of uveitis beyond 1 year was not evaluated.
Background and Aims
Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end‐stage renal disease (ESRD). Previously available ...direct‐acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes.
Methods
EXPEDITION‐5 is a phase 3 study to evaluate efficacy and safety of the fixed‐dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experience. The primary efficacy endpoint was percentage of patients with sustained virologic response at 12 weeks post‐treatment (SVR12).
Results
Among the 101 patients enrolled in the study, 24% had predialysis CKD and 76% were on dialysis. Eighty‐four patients were treated with G/P for 8 weeks, 13 patients for 12 weeks and four patients for 16 weeks. Fifty‐five per cent of patients had genotype 1, 27% had genotype 2, 15% had genotype 3 and 4% had genotype 4, and none had genotype 5 or 6 infection. The SVR12 rate was 97% (98/101, 95% confidence interval, 91.6‐99.0). No patients experienced virologic failure. Adverse events (AEs) reported in at least 5% of the patients were pruritus, bronchitis, hypertension and generalized pruritus. Serious AEs were reported in 12% of patients; none related to study drug.
Conclusions
G/P treatment yielded high SVR12 rates irrespective of the presence of stage 3b, 4 or 5 CKD. No safety signals were detected.
Clinicaltrials.gov identifier
This Phase 3 clinical trial was funded by AbbVie and registered with clinicaltrials.gov as NCT03069365 (EXPEDITION‐5).
Introduction
Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients ...with advanced Parkinson’s disease (PD) when other treatments have not given satisfactory results. Reduction in ‘off’-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on ‘off’-time.
Methods
Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and ‘off’-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: ‘off’-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson’s Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes.
Results
Twenty-seven studies were included in this review. The improvement in ‘off’-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. ‘Off’-time was reduced from baseline to end of follow-up by 38–84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of ‘off’-time demonstrated mean relative reductions of 47–82% at 3–6 months and up to 83% reduction at 3–5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device.
Conclusion
In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing ‘off’-time.
Infographic
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Video Abstract
Plain Language Summary
By synthesising publications from scientific journals, this article shows that levodopa/carbidopa intestinal gel (LCIG; also known as carbidopa/levodopa enteral suspension or the tradenames Duodopa® and Duopa®) may have benefits for patients with advanced Parkinson’s disease that last for 12 months or more. Pills taken by mouth for Parkinson’s disease often do not work as well after a few years. This means the symptoms of Parkinson’s disease, such as shaking or slow movements, etc., re-emerge despite medication (known as ‘off’-time). To reduce the amount of ‘off’-time, people with advancing Parkinson’s disease may switch from pills to other types of treatments, for example, those that use devices to deliver the drug into the body, such as LCIG. LCIG has been available for many years and is known to help patients by reducing ‘off’-time. Despite this, less is known about how long the benefits of LCIG last. By summarising all information available on the long-term use of LCIG, this report shows that when patients have been taking LCIG for at least 12 months, they have 2–4 h less ‘off’-time each day than they did before starting the LCIG treatment. This effect is maintained for 3–5 years after starting LCIG treatment. There were no unexpected side effects with long-term use of LCIG. The time not spent in ‘off’ may allow people with advanced Parkinson’s to increase their independence in daily activities.
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
Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with ...advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool.
Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts’ clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value).
The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient ICC 0.843; Fleiss weighted kappa ƙweighted 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01).
MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.
•There is no consensus objective criteria for identifying and managing advancing PD.•MANAGE-PD is a clinician tool to manage patients with PD with suboptimal PD control.•MANAGE-PD demonstrated robust validity and clinical value.•Clinical use of MANAGE-PD may complement clinician treatment decision-making.•MANAGE-PD may facilitate timely identification and management of PD symptoms.
Introduction
Patients with advanced Parkinson’s disease (PD) may require device-aided therapies (DAT) for adequate symptom control. However, long-term, real-world efficacy and safety data are ...limited. This study aims to describe real-world, long-term treatment persistence for patients with PD treated with levodopa-carbidopa intestinal gel (LCIG). The study also aims to describe patient profiles, treatment discontinuation rates, co-medication patterns, monotherapy rates, and rates of healthcare visits and their associated costs for patients receiving all forms of DAT (deep brain stimulation DBS, continuous subcutaneous apomorphine infusion CSAI, or LCIG).
Methods
In this retrospective analysis of the Israeli Maccabi Healthcare Services database, adult patients with PD were analyzed in three cohorts, based on DAT (DBS, CSAI, or LCIG). The primary endpoint was LCIG treatment persistence 12 months after initiation.
Results
This analysis included 161 DAT-treated patients (LCIG,
n
= 62; DBS,
n
= 76; CSAI,
n
= 23). Among those who discontinued, the mean time to discontinuation was 86.4 months for LCIG and 42.4 months for CSAI (
p
= 0.046). Twelve months after initiation, 14.3% LCIG, 10.7% DBS, and 5.9% CSAI patients were not receiving any additional anti-parkinsonian therapy. At the last recorded visit, 28.6% LCIG, 13.3% DBS, and 5.9% CSAI patients received DAT as monotherapy. During the first 12 months after initiation, 45.2% LCIG, 65.2% CSAI, and 1.3% DBS patients had no reported hospitalization days. Annual healthcare visit costs decreased following LCIG initiation (US$9491 vs. $8146) and increased following DBS ($4113 vs. $7677) and CSAI ($6378 vs. $8277).
Conclusion
DAT are well maintained in patients with advanced PD. These retrospective data suggest that patients receiving LCIG may have higher long-term persistence rates compared with patients receiving CSAI. A subgroup of patients was treated with DAT as monotherapy without additional oral anti-parkinsonian therapy, with LCIG showing the highest rates.
OFF Episodes occur in people with Parkinson's disease when their medication wears off, and motor and/or non-motor symptoms emerge. Existing measures used to assess OFF Episodes focus on the time ...spent in OFF Episodes through diaries or by identifying symptoms, but they are limited in their ability to capture the severity and functional impact of OFF episodes. The aim of this study was to develop and validate a new instrument, called “OFFELIA,” that measures the impact of OFF episodes on the quality of life of individuals with Parkinson's disease.
Participants completed a cross-sectional questionnaire, “Impact and Communication on OFF Periods,” while enrolled in the online clinical study Fox Insights. The data collected was used to develop OFFELIA. Psychometric testing was performed on 18 candidate items using classical, exploratory factor analysis, and item response theory methods.
569 individuals with Parkinson's disease completed the questionnaire. All items were retained for the final measure, with 17 items aggregated into two multi-item scales (functioning and psychological well-being) and one item reported separately as it did not function well with the other items (employment). Known group comparisons based on average duration, frequency and unpredictability of OFF episodes indicated that OFFELIA subscales were more sensitive than existing generic and condition-specific measures.
Initial evidence supports the validity of OFFELIA, a new instrument that assesses the impact of OFF periods on daily life. This instrument can be used in assessing clinical therapeutic strategies targeting OFF episodes in Parkinson's disease.
•OFFELIA is a new patient-reported outcome measure for Parkinson's Disease.•OFFELIA assesses off episodes' impact on quality of life in people with Parkinson's.•Evidence supports validity and reliability of OFFELIA.•OFFELIA aids clinicians assessing treatment's effect on off episodes.•OFFELIA measures impact of interventions on off episodes in trials.
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.
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