Lisa M. Bloudek

Review and Meta-Analysis of Biomarkers and Diagnostic Imaging in Alzheimer's Disease

Mild Alzheimers disease (AD) is often difficult to differentiate from mild cognitive impairment (MCI) or non-AD dementias. A multitude of diagnostic biomarkers and advanced imaging strategies have been developed to aid in the diagnosis and management of AD. We sought to review and analyze the published evidence on key test characteristics of major diagnostic strategies to formulate best estimates of sensitivity (SN) and specificity (SP). A systematic review was undertaken to locate and abstract all studies of biomarkers or diagnostic imaging for AD published in English from January 1990 to March 2010 that provided estimates of SN and SP. Meta-analysis was performed using a bivariate mixed-effects binary regression model. We calculated -SN, SP, and area under the receiver operating curves (AUROC), with confidence and prediction contours. Of 1,840 unique studies identified, 119 presented primary data sufficient for analysis. SN and SP were calculated against non-demented controls, non-AD dementias with and without MCI, if available. Compared to non-demented controls, FDG-PET demonstrated the highest AUROC (0.96), with 90% SN (95%CI 84% to 94%), and 89% SP (95% CI 81% to 94%). FDG-PET also was most accurate in discriminating AD from demented controls (including MCI) with AUROC 0.91, and 92% SN (95%CI 84% to 96%) and 78% SP (95% CI 69% to 85%). For discrimination of AD from non-AD dementias (excluding MCI), CSF Ptau, and SPECT produced identical AUROC (0.86). Diagnostic strategies for AD show wide variation in test characteristics and some show promise for use in clinical practice.

Patterns of Use and Reasons for Discontinuation of Prophylactic Medications for Episodic Migraine and Chronic Migraine: Results From the Second International Burden of Migraine Study (IBMS‐II)

Our objective was to characterize patterns of preventive medication use in persons with episodic migraine (EM) and chronic migraine (CM).

Adherence with migraine prophylaxis in clinical practice.

Objective:  To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice.

The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK

Abstract Background: Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK. Methods: A state-transition (Markov) model was developed comparing onabotulinumtoxinA to placebo. Efficacy data and utility values were taken from the pooled Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trials program (n = 1384). Estimates of resource utilisation were taken from the International Burden of Migraine Study (IBMS), and stopping rules were informed by published medical guidelines and clinical data. This study estimated 2-year discounted costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective. Results: At 2 years, treatment with onabotulinumtoxinA was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with onabotulinumtoxinA reduced headache days by an estimated 38 days per year at a cost of £18 per headache day avoided. Sensitivity analysis showed that utility values had the greatest influence on model results. The ICER remained cost-effective at a willingness to pay threshold of £20,000–£30,000/QALY in the majority of scenario analyses as well as in probabilistic sensitivity analysis, where onabotulinumtoxinA was cost-effective on 96% of occasions at a threshold of £20,000/QALY and 98% of occasions at £30,000/QALY. Conclusion: OnabotulinumtoxinA has been shown to reduce the frequency of headaches in patients with chronic migraine and can be considered a cost-effective use of resources in the UK National Health Service. The uncertainties in the model relate to the extrapolation of clinical data beyond the 56-week trial.

Headache-related health resource utilisation in chronic and episodic migraine across six countries

Objective To describe headache-related health resource usage in chronic and episodic migraine across six countries. Methods A web-based questionnaire eliciting data on several topics, including health resource usage, was administered to panellists with migraine from the USA, Canada, UK, Germany, France and Australia. Respondents were grouped into episodic and chronic migraine, based on reported headache phenotype and headache-day frequency. ORs were calculated, comparing usage in each country to that in the US, controlling for chronic versus episodic migraine and other factors. Results Relative to the USA, the odds of visiting a provider for headache during the preceding 3 months were significantly higher in all countries, except Germany. Respondents in France were more likely to report having a provider they typically visited for headache-related care. The odds of visiting the emergency department for headache were significantly lower in France, the UK and Germany, and hospitalisation for headache was significantly more frequent in Canada and Australia. Respondents from all countries, except Canada, were more likely to report currently using a prescription-acute treatment, and those from France were more likely to report trying more than three acute treatments. Preventive treatment use did not differ significantly. Conclusions Headache-related resource usage differed significantly between the USA and other countries. US respondents were generally less likely to report recent provider visits and use of prescription-acute treatments. They were more likely to report emergency department visits than in European countries, but less likely to report hospitalisation than in Canada and Australia.

Treatment Persistence and Switching in Triptan Users: A Systematic Literature Review

To conduct a systematic review to evaluate persistence to and switching of triptan therapy for the acute treatment of migraine.

Estimating the Economic Impact of Adding Panobinostat to a U.S. Formulary for Relapsed and/or Refractory Multiple Myeloma: A Budget Impact and Cost-Benefit Model

BACKGROUND Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course. OBJECTIVE To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model. METHODS Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs. RESULTS In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost <

CDR State Transition Probabilities in Alzheimer's Disease with and without Cholinesterase Inhibitor Intervention in an Observational Cohort

0.01 per member per month. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment. CONCLUSIONS Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money. DISCLOSURES Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speakers bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

Real-world economic impact of onabotulinumtoxina in patients with chronic migraine

Cholinesterase inhibitors and memantine are medications used in the treatment of Alzheimers disease (AD). These agents have been shown to reduce the rate of AD progression in randomized trials. The objective of this study is to evaluate the association between treatment with cholinesterase inhibitors or memantine and the probability of transitioning to a more severe Clinical Dementia Rating (CDR) state. Analysis was limited to possible or probable AD patients from NACC-UDS with three or more observations, baseline CDR score of 0.5 or 1, and without reported use AD drugs at enrollment. Use of an AD drug at any observation after baseline was classified as treatment. Odds of CDR stage were calculated by multinomial logistic regression controlling for baseline age, baseline MMSE score, education, marital status, race, gender, place of residence, and time since last measure. The resulting coefficients from logistic regression were used to calculate transitional probabilities. A total of 1,114 patients were included. No differences were observed in the probability of transitioning to more severe CDR states based on treatment, but treated patients had lower odds of death, OR 0.49 (95% CI 0.31 to 0.79) compared to untreated. Ultimately, this study failed to detect a difference in the probability of progressing to a more severe AD state as a result of treatment in an observational cohort of AD patients, but is limited by non-randomized treatment selection and small dataset. The NACC-UDS dataset is ongoing and this analysis may be improved if repeated when more data is available.

Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS)

Compared to episodic migraine, chronic migraine (CM) is associated with greater disability, worse quality of life, and higher costs related to healthcare resource use (HRU). OnabotulinumtoxinA can be used effectively for headache prophylaxis in CM patients with CM, but the effect of treatment on HRU is unknown.