Patient Characteristics, Diagnostic Delays, Treatment Patterns, Treatment Outcomes, Comorbidities, and Treatment Costs of Acromegaly in China: A Nationwide Study.

Purpose: Acromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China. Methods: This is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform. Results: In total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were <1 year. The most common first-line therapy was surgery with a transsphenoidal (76.1%) or transcranial approach (3.2%). Somatostatin analogues or dopamine agonists were administered in 20.5% of the patients as first-line therapies and in 41.7% as adjuvant therapies. Radiotherapy was performed in 32.1% of patients, 99.3% of whom received radiotherapy as an adjuvant therapy. After a median 5-year follow-up, 46.2% achieved biochemical control. Comorbidities were reported in 88.2% of the patients at follow-up; memory deterioration and thyroid nodules were the most common. Controlled patients had greater improvements in symptoms and comorbidities during follow-up than uncontrolled patients. The annual per-capita cost-of-treatment was $11013 in 2018, with medical treatments being the largest contributor (67%). Medical insurance covered 47.2% of all treatment costs. Conclusion: This study provides the first comprehensive description of real-world acromegaly data in China, serving as a basis for future population-based studies.

Opicapone and Levodopa-Carbidopa Intestinal Gel Infusion: The Way Forward Towards Cost Savings for Healthcare Systems?

Combined catechol-O-methyl-transferase-inhibition and Levodopa-Carbidopa intestinal gel (LCIG) infusion has the potential to reduce LCIG daily dose and the costs of this therapy. In this retrospective analysis, we report on Parkinson's disease (PD) patients on LCIG with concomitant Opicapone. In 11 patients, the introduction of Opicapone led to LCIG daily dose being reduced by 24.8% (p = 0.05) without any significant worsening of dyskinesia. Three patients withdrew from Opicapone due to side effects or inefficacy. LCIG daily dose reduction could lead to cost savings of £142,820.63/year in the United Kingdom while maintaining clinical care.

An Economic Analysis of Bromocriptine Versus Trans-Sphenoidal Surgery for the Treatment of Prolactinoma.

Prolactinomas account for ∼40% of all pituitary adenomas and are important causes of infertility and gonadal dysfunction. In general, most prolactinomas are treated medically with dopaminergic agonists, while surgery is reserved for patients intolerant or nonresponsive to these medications. The aim of this study was to carry out a comparative analysis of the cost-effectiveness of medical therapy with bromocriptine and surgical therapy with trans-sphenoidal surgery. A Markov model was developed based on retrospective data from 126 patients with prolactinoma treated in our hospital between October 2008 and May 2009, and from data published previously. For patients with microadenoma, the cost of medical treatment was estimated to be ¥20,555, while the cost of surgery was calculated to be ¥22,527. For patients with macroadenoma, the cost of therapy with bromocriptine was ¥31,461 in males and ¥27,178 in females, while the cost of surgery was ¥42,357 in males and ¥44,094 in females. Sensitivity analyses (carried our using variations in patient age, bromocriptine therapeutic dose, bromocriptine maintenance dose, and the success rate of bromocriptine withdrawal) indicated that our model showed good stability, although our results were most heavily influenced by variations in the bromocriptine maintenance dose. It is concluded that, from an economic viewpoint, medical therapy with bromocriptine should be the first-line treatment option for patients with prolactinoma, irrespective of whether this is a microadenoma or macroadenoma.

Multi-modal management of acromegaly: a value perspective.

PURPOSE: The Acromegaly Consensus Group recently released updated guidelines for medical management of acromegaly patients. We subjected these guidelines to a cost analysis. METHODS: We conducted a cost analysis of the recommendations based on published efficacy rates as well as publicly available cost data. The results were compared to findings from a previously reported comparative effectiveness analysis of acromegaly treatments. Using decision tree software, two models were created based on the Acromegaly Consensus Group's recommendations and the comparative effectiveness analysis. The decision tree for the Consensus Group's recommendations was subjected to multi-way tornado analysis to identify variables that most impacted the value analysis of the decision tree. RESULTS: The value analysis confirmed the Consensus Group's recommendations of somatostatin analogs as first line therapy for medical management. Our model also demonstrated significant value in using dopamine agonist agents as upfront therapy as well. Sensitivity analysis identified the cost of somatostatin analogs and growth hormone receptor antagonists as having the most significant impact on the cost effectiveness of medical therapies. CONCLUSION: Our analysis confirmed the value of surgery as first-line therapy for patients with surgically accessible lesions. Surgery provides the greatest value for management of patients with acromegaly. However, in accordance with the Acromegaly Consensus Group's recent recommendations, somatostatin analogs provide the greatest value and should be used as first-line therapy for patients who cannot be managed surgically. At present, the substantial cost is the most significant negative factor in the value of medical therapies for acromegaly.

Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.

OBJECTIVE: To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. METHODS: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. RESULTS: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. CONCLUSION: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.

Health care resource utilization and costs associated with restless legs syndrome among managed care enrollees treated with dopamine agonists.

PURPOSE: This study assessed the direct economic burden of restless legs syndrome (RLS) among patients treated with dopamine agonists (DAs) using a large United States managed care database. DESIGN: Retrospective database analysis. METHODOLOGY: Patients were required to have > or =1 prescriptions for a DA (i.e., pergolide, pramipexole, ropinirole) between 1/1/2005 and 12/31/2007 (date of first DA, or "index"); continuous enrollment for > or =6 months before and > or =12 months after index; > or =1 diagnosis of RLS, before and after index; and no diagnosis of Parkinson's disease. Study measures included annual all-cause and RLS-related costs by care setting (hospitalizations, emergency room, office, pharmacy, other, total) and treatment-pattern events (discontinuations, switches, adjunctive treatments, titrations). PRINCIPAL FINDINGS: A total of 7,796 patients met the inclusion criteria. About 70% of patients received ropinirole, and 30% received pramipexole at index. Approximately 91% had >1 RLS-related office visits, and patients filled an average of 6.5 RLS-related prescriptions (DAs, gabapentin, carbidopa/levodopa) during the 1-year follow-up period. Mean (SD) all-cause health care costs were $11,485 ($21,362) per patient, mostly due to multiple medical conditions occurring with RLS. RLS-related costs were 6.7% of total all-cause costs (mean [SD] $774 [$1,504]), consisting of office visits (16%), pharmacy (63%), and other costs (20%). Approximately 58% had a treatment-pattern event suggesting a dopamine-related side effect. Opioids were the most commonly used adjunctive therapy (13% of patients). CONCLUSION: We found relatively low costs associated with RLS treatment. These findings should encourage expanding the coverage of treatment to reduce the suffering and costs associated with RLS.

Trends in resource utilization for Parkinson's disease in Germany.

OBJECTIVE: The prevalence of Parkinson's disease (PD) and costs of healthcare resources for this disease have been increasing in recent years. The objective was to determine the trends in the resource utilization for PD in Germany. METHODS AND PATIENTS: We compared resource utilization in two cohorts of PD patients recruited in 2000 (n=145) and 2004 (n=133) from two clinical departments, two office-based neurologists and several general practitioners. Direct and indirect costs were assessed based on a patient diary and structured personal interviews. Clinical status was classified in Hoehn and Yahr (HY) stages. Cost-driving factors were determined using multivariate regression analysis. RESULTS: In 2004, total annual costs for PD ranged from EUR 18,660 for HY I-II to EUR 31,660 for HY II-V. As compared to costs in 2000, total costs increased in 2004 by 25-31%. Drug costs increased by 14-20% during this time. The largest increase in direct costs was observed in the early disease (HY I-II), primarily due to rising costs for inpatient care and drugs. Motor complications, age, HY stage and study year were independent cost-driving factors. CONCLUSION: The resource utilization in PD increased rapidly over the four year study period. Increasing consumption of healthcare resources due to medical progress is a major factor of rising costs. Future studies should attend more to trends in the utilization of healthcare resources and identify factors which could slow down the expanding costs of healthcare.

Cost effectiveness of rasagiline and pramipexole as treatment strategies in early Parkinson's disease in the UK setting: an economic Markov model evaluation.

BACKGROUND: Levodopa is the most effective treatment for the symptoms of Parkinson's disease (PD). However, after an initial period of benefit, several limitations become apparent, including motor complications such as dyskinesia. Dyskinesia can severely affect patients' quality of life and increases healthcare resource use. Thus, delaying the need for levodopa, and therefore the onset of levodopa-induced dyskinesia, is important. OBJECTIVE: The aim of this study was to compare the cost effectiveness, from a UK healthcare payer perspective, of two antiparkinsonian treatment strategies in early PD: first-line monotherapy with rasagiline, a novel monoamine oxidase B inhibitor; and the non-ergoline dopamine receptor agonist pramipexole. METHODS: An economic Markov model was developed as a pragmatic tool to derive comparative information on the effectiveness, utility and costs of these two strategies over a 5-year period. Model input data were obtained from the TEMPO study for rasagiline and from a study by the Parkinson Study Group for pramipexole. Effectiveness outcomes were time to levodopa and time to levodopa-induced dyskinesia. Cost and quality-adjusted life-year (QALY) data were derived from published sources. RESULTS: Rasagiline was the dominant strategy. Compared with pramipexole, use of the rasagiline strategy was estimated to reduce costs by 18% per patient over 5 years and was associated with an additional 10% delay in dyskinesia onset (0.41 years; 95% CI 0.27, 0.55). This strategy was also found to prolong the time to levodopa initiation by 25% through a gain of 0.83 levodopa-free years (95% CI 0.56, 1.1). In addition, use of the rasagiline strategy was found to generate a 5% gain in QALYs over 5 years compared with the pramipexole strategy (3.7 +/- 0.02 vs 3.51 +/- 0.03). Sensitivity analyses confirmed that the model was robust. CONCLUSIONS: Rasagiline represents a cost-effective alternative to pramipexole in the treatment of early PD in the UK.

[Socioeconomic relevance of the idiopathic restless legs syndrome (RLS) in Germany: cost-of-illness study]. / Sozioökonomische Bedeutung des idiopathischen Restless-Legs-Syndroms (RLS) für Deutschland: Krankheitskostenanalyse.

BACKGROUND AND PURPOSE: 1.3% of German adults suffer from clinically relevant restless legs syndrome (RLS). A cost-of-illness study was conducted to evaluate the costs for diagnosis and therapy of the idiopathic RLS. METHODS: A clinical pathway based on expert guidelines was developed. The costs for the 1st year of treatment in idiopathic RLS were calculated with the Markov Model. Relevant published clinical study data were used for the model as well as questioning of physicians. RESULTS: Costs per patient with approved drug treatment are 989.80 Euro for sickness funds and 1,285.26 Euro from the societal perspective. Drug costs are the main cost components for sickness funds and the society with 69% and 61%, respectively. Less than half of the patients continue an L-dopa therapy longer than 1 year. About one quarter of all RLS patients need off-label therapy after the 1st year of treatment. CONCLUSION: The costs for a guideline-oriented therapy for all patients with clinically relevant RLS in Germany are about 1,135 billion Euro, representing 0.5% of all health-related costs in Germany. Further controlled clinical trials are required to provide evidence for the efficacy of different treatment options including drugs without an approval for RLS and long-term use. Health services research is required for cost-utility analysis, to evaluate the costs of inadequate treatment, and to obtain additional information to improve the resource allocation in RLS treatment.

Cost-effectiveness of licensed treatment options for restless legs syndrome in the UK and Sweden.

OBJECTIVE: To estimate the cost-effectiveness of pramipexole versus no treatment and ropinirole in moderate to very severe idiopathic restless legs syndrome (RLS) in the UK and Sweden. METHODS: A Markov model was developed using clinical trial data for pramipexole and ropinirole. Model health states were based on the International RLS Study Group Rating Scale (IRLS) scores. Health states were: no (IRLS 0), mild (IRLS 1-14), moderate (IRLS 15-24), severe (IRLS 25-34), very severe RLS (IRLS 35-40) and death. Patients entered the model with an IRLS score > 15 matching the trial inclusion criteria of the pramipexole trials. Resource use and utilities were based on trial data, literature, a patient survey and a panel of physicians from the UK and Sweden in the absence of published information. A healthcare sector perspective was taken for the UK and a societal perspective for Sweden using 2004-2005 unit costs. The base case analysis took a 1-year timeframe. RESULTS: In the UK the incremental cost per quality-adjusted life year (QALY) for pramipexole was 3349 pounds sterling versus no treatment and a cost-saving of 92 pounds sterling against ropinirole. In Sweden, pramipexole produced cost-savings of Swedish Krona (SEK) 2381 (176 pounds sterling) versus no treatment and SEK 3564 (264 pounds sterling) against ropinirole. QALY gains in both countries were 0.095 versus no treatment and 0.007 versus ropinirole. Results compare well with UK cost-effectiveness thresholds of 20,000 pounds sterling/30,000 pounds sterling per QALY and are cost-saving for Sweden. One-way and probabilistic sensitivity analyses showed results to be robust. CONCLUSIONS: Pramipexole is cost-effective compared to no treatment and ropinirole for patients with moderate to very severe RLS.

[Medical treatment of Parkinson's disease]. / Medikamentöse Therapie des Morbus Parkinson.

Our understanding of Parkinson's disease (PD) has evolved. Parkinson's disease is no longer regarded a pure motor disorder, but a complex disease with motor as well as non-motor symptoms, the latter having a major impact on the quality of life of the patient as well as the caregiver. After a few years of suffering from PD, complications of therapy add invariably to the burden of the disease. Many of these complications are not volunteered by the patient or the caregiver, either due to their embarrassing nature or due to lack of insight of their causal relationship with PD or the treatment of PD. However, proper treatment of PD has to address the non-motor symptoms and the complications of therapy as well.

Ropinirole, a non-ergoline dopamine agonist.

Dopamine agonists have become indispensable in the treatment of Parkinson's disease. In every-day practice, however, the decision to select the best compound for an individual patient is rendered difficult because of the large number of substances available on the market. This review article provides a closer look at the experimental and clinical studies with ropinirole published so far. Ropinirole is a non-ergoline dopamine agonist which has been proven to be effective in both, monotherapy and combination therapy of idiopathic Parkinson's disease. In addition to ameliorating bradykinesia, rigor, and tremor, ropinirole facilitates the daily life and improves depressive moods of patients with Parkinson's disease. The long-term complications of levodopa are avoided, and problems commonly associated with levodopa treatment are reduced. Ropinirole appears to have a neuroprotective effect. In addition to Parkinson's disease, ropinirole has also been used successfully in the treatment of restless legs syndrome.

[Cost-effect estimation of dopamine agonist (mirapex) application in patients with Parkinson's disease]. / Farmakoékonomicheskiaia tsenka primeneniia agonista dofaminovykh retseptorov (mirapeksa) u patsientov s bolezn'iu Parkinsona.

Parkinson's disease is a neurodegenerative disorder with a growing social significance. Currently, dopamine agonists are considered as first-line medication used before levodopa treatment. High cost of dopamine agonists makes it necessary to estimate their cost efficacy by means of pharmacoeconomical studies. We studied efficacy of mirapex evaluated by UPDRS and PDQ-39 scores before and after 1-year treatment in 44 patients with Parkinson's disease: 18 patients non-pretreated with levodopa and 26 patients pretreated with levodopa. Treatment cost was estimated separately for two patients groups with subsequent cost-effectiveness analysis. Early use of mirapex as a dopamine agonist for patients non-treated with levodopa seems to be beneficial from clinical well as from pharmacieconomical points of view.

[Cost analysis in Italy of various strategies for the treatment of Parkinson disease in the advanced phase]. / Analisi dei costi, in Italia, di diverse strategie per il trattamento della malattia di Parkinson in fase avanzata.

OBJECTIVE: To perform a comparative economic evaluation of therapies--L-dopa drugs, subcutaneous infusion of apomorphine and surgical intervention of Deep Brain Stimulation (DBS)--for the treatment of advanced Parkinson's disease (APD) and to verify the level of assistance guaranteed in Italy to patients affected by APD. METHODS: Literature review and Delphi Panel to collect data about the efficacy of the therapies for the treatment of APD and the use of healthcare resources for such therapies. Field survey to investigate financing mechanisms of the therapeutical alternatives in the Italian regions; cost-analysis over five years (NHS perspective); cost-analysis (hospital perspective) for the initial administration of therapeutic alternatives. RESULTS: Literature review shows that the reduction of the "off-periods" is 62% for Apomorphine and 80-90% for DBS compared to traditional therapy. The 5-years economic analysis from the NHS perspective shows that the cost of a patients with APD is [symbol: see text] 58.065 if treated with traditional therapy, [symbol: see text] 36.423 (including infusional pump and the drug) with subcutaneous apomorphine and respectively [symbol: see text] 56.489 and [symbol: see text] 41.379 (depending on reimbursement of electrodes and neurostimulator on top of the DRG tariff) with DBS. The field survey, highlighted that Regions which currently reimburse the infusion pump for apomorphine and the electrodes and neurostimulator for DBS--on top of the DRG tariff--are a very limited number. CONCLUSIONS: Apomorphine and DBS in the treatment of APD show higher efficacy and lower costs compared to traditional therapy.

[Analysis of direct costs in therapy of Parkinson disease]. / Analyse der direkten Kosten in der Parkinson-Therapie.

The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.