Migraine Burden and Costs: A Nationwide Population-Based Controled Cohort Study Using The French EGB Database

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by exploring ‘first-time’ claims in the database defined as not having an MS related claim in the previous two years. Prevalence was estimated based on the number of individuals having an MS claim within the concerning year.  Results: Average prevalence of MS in the Netherlands over 9 years was 88 per 100,000 inhabitants (males 48, 127 females). This is comparable with previously reported prevalence in the literature. The average incidence was 9 per 100,000; somewhat higher than reported in previous studies. Yearly per patient medication costs were highest in the year after the first MS claim and then decreased about 15% in the two years after. Mean hospital costs were 30% higher in the year of the first MS claims than in the three years after. Drug and hospitalization costs remained higher than before the first MS claim.  Conclusions: Dutch incidence and prevalence estimates based on claims data seem consistent with previous estimates over time. Patients’ drug and hospital costs increased strongly in the year after an MS diagnosis and then decrease again, but stay higher than before diagnosis. PND14 Incidence and Prevalence of Epilepsy in Germany Groth A1, Borghs S2, Gille P3, Joeres L3, Wilke T4 HWM GmbH, Wismar, Germany, 2UCB Pharma, Slough, Germany, 3UCB Pharma GmbH, Monheim, Germany, 4IPAM, Wismar, Germany

1Ingress-Health

Objectives: Epilepsy is one of the most frequent neurological diseases. No current precise data about the epidemiology of epilepsy and focal epilepsy (FE) in Germany are available. The aim of this contribution is to quantify age-/gender-specific prevalence and incidence of epilepsy in Germany, in 2013.  Methods: The analysis based on claims-data of 2.7 million members of a regional German statutory health insurance fund. Patients were classified as epilepsy prevalent if they had received at least one inpatient and/or confirmed outpatient diagnosis of epilepsy (ICD10-Code G40.-) in the observation year 2013. Patients were considered to have incident epilepsy in 2013 if they had not received any antiepileptic medication and any epilepsy diagnosis 6 months before the first observed epilepsy diagnosis in 2013. Additionally, FE prevalence/incidence (ICD10-Code G40.0/G40.1/G40.2) was analysed separately. In a sensitivity analysis, patients were classified as prevalent/incident only if they received at least one prescription of an antiepileptic medication in 2013 in addition to the epilepsy diagnosis. Prevalence/incidence was reported as age- and genderadjusted numbers, based on German population age/gender structure.  Results: Prevalence was estimated to be 1.998% for epilepsy and 0.703% for FE. Among prevalent patients, 50.9%/49.1% were male/female for epilepsy, respectively 50.1%/49.9% for FE. The sensitivity analysis resulted in a prevalence of 1.426% (0.599% in FE). Epilepsy incidence in our sample was 4.860 cases/1,000 person-years in men (1.366 cases in FE) and 3.781 cases/1,000 person-years in women (1.175 cases in FE). Based on the more conservative epilepsy definition, incidence was 1.439 cases/1,000 person-years and 0.656 cases/1,000 person-years in FE.  Conclusions: Using this claims data source, the prevalence and incidence was found to be higher in Germany than reported in previous studies. Therefore, the resulting healthcare burden of epilepsy is expected to be larger than previously estimated. PND15 The Prevalence and Treatment Status of Different Multiple Sclerosis Phenotypes in a Italian Reference Center Cortesi PA1, Cozzolino P1, Cesana G1, Capra R2, Mantovani LG1 of Milano-Bicocca, Monza, Italy, 2Multiple Sclerosis Center, Spedali Civili of Brescia, Brescia, Italy 1University

Objectives: More information are needed on the prevalence of different Multiple Sclerosis (MS) phenotypes and their treatment management. This study assessed the prevalence and the treatment management of the main different MS phenotypes: relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS).  Methods: Patients covered by Lombardy Healthcare System with a diagnosis of MS in the period 2004-2010 were identified through regional healthcare administrative databases. Data extracted from these databases were linked with clinical information collected by a major MS center located in Lombardy. Combing the clinical and administrative data we assessed the prevalence of the different MS phenotypes at the last observed year (2010), stratifying the patients for their diseases severity, assessed with the Expanded Disability Status Scale (EDSS), and their treatment status (first DMTs, second DMTs, no DMTs).  Results: The study identified 831 patients with MS at 2010. The prevalence of RRMS was 79.3%, while SPMS was reported in 13.7% and PPMS in 7.0% of patients. PPMS reported the highest mean age (58.5 years), followed by SPMS (56.3 years) and RRMS (41.4 years). An EDSS lower than 7 was reported by 98.8% of RRMS, 59.6% of PPMS and 50.9% of SPMS; while an EDSS lower than 3 was reported by 70.0% of RRMS, 3.5% of PPMS and 0.9% of SPMS. The RRMS reported the high prevalence of patients treated with DMTs (63.9%), followed by SPMS (34.2%) and PPMS (1.7%). Within the RRMS treated patients, 82 patients (19.5%) were previously treated with another DMTs.  Conclusions: Our study provide data on the prevalence of the different MS phenotypes, the EDSS distribution and the treatment status in a reference MS center in Italy. This information are of primary interest to estimate the target population of new DMTs that are approaching the market and to assess their possible budget impact.

NEUROLOGICAL DISORDERS – Cost Studies PND16 Budget Impact Analysis for Daclizumab Beta In Relapsing Remitting Multiple Sclerosis In Italy Demma F1, Casamassima G2, Cocco E3, Di Turi R4, Paolicelli D5, Fantaccini S2, Santoni L2, Furneri G1 1EBMA Consulting SRL, Melegnano, Italy, 2Biogen, Milan, Italy, 3University of Cagliari, Cagliari, Italy, 4Local Health Unit of Rome 3, Rome, Italy, 5University of Bari, Bari, Italy

Objectives: Daclizumab beta is a humanized monoclonal antibody recently approved for the treatment of adults with relapsing forms of multiple sclerosis (MS). The objective of this budget impact analysis is to estimate the economic consequences of the introduction and use of daclizumab beta in Italy, for the treatment of patients with relapsing remitting MS (RRMS), eligible to second line therapies.  Methods: The analysis evaluates the economic impact of the first three years of daclizumab commercialization, from the perspective of the Italian National Healthcare Service (NHS). Direct healthcare costs (drugs, administration, monitoring, relapse and adverse event management) were calculated comparing two scenarios: i) current scenario, where second line treatments (fingolimod, natalizumab, alemtuzumab), currently available in Italy, are used to treat RRMS patients, ii) alternative scenario, where daclizumab beta is introduced as an alternative. Target population was estimated in 9,950, 11,480 and 13,080 patients at years 1, 2 and 3 respectively, based on Italian prevalence, incidence and market data. Impact of relapses was estimated using results from recently published mixed treatment comparison. Unit costs were based on national prices, tariffs, and published literature (in euros 2017). One-way sensitivity analysis was conducted.  Results: According to negotiated price and reimbursement conditions, the introduction and use of daclizumab beta would decrease total costs, compared to the current scenario. In the current scenario, estimated costs were approximately 170.2, 196.4 and 223.8 million euros in years 1, 2, and 3 respectively. In the alternative scenario estimated costs were approximately 168.9, 192.4 and 217.9 million euros. The cumulative budget impact over three years was a saving of approximately 11.2 million euros for the Italian NHS. All scenarios tested in sensitivity analysis were favorable to the alternative scenario.  Conclusions: The adoption of daclizumab beta for the treatment of RRMS patients eligible to second line therapies is economically favorable (budgetsaving) for the Italian NHS. PND17 Budget Impact Analysis of Oral Glycopyrronium Bromide (Sialanar™) For The Symptomatic Treatment of Severe Sialorrhoea (DROOLING) In The UK Setting Langham S1, Wright A1, Shaw H2, Bryson S2, O’Leary S3 1Maverex Ltd, Manchester, UK, 2Proveca Ltd, Manchester, UK, 3ValueAxis Ltd, Manchester, UK

Objectives: Oral glycopyrronium bromide 400 micrograms/ml (Sialanar™) is indicated for the symptomatic treatment of severe sialorrhoea (drooling) in children and young people with chronic neurological disorders. It is the only licensed medication in Europe and has been launched in the UK. The market had previously been dominated by use of unlicensed products or preparations made by specials manufacturers or pharmacists. It is not possible, using routinely collected data, to assess use of unlicensed products for this indication, therefore we carried out an evaluation of budget impact utilising real world evidence to validate assumptions around input parameters.  Methods: A budget impact model was developed for the UK setting using local epidemiological and cost data from multiple published and unpublished sources. It was assumed that licensed oral glycopyrronium bromide 400 micrograms/ml would displace unlicensed products. Data on use of unlicensed products were derived from a sample of patients receiving treatment for sialorrhoea identified in a UK observational database (Clinical Practice Research Datalink). Annual net budget impact over 5 years, from the perspective of the UK National Health Service, was estimated.  Results: The budget impact of the newly licensed oral glycopyrronium bromide over 5 years was estimated to be cost saving, even under assumptions of increasing prescription rates over time. Certain displacement scenarios (e.g. areas with a high prescription rate of the tablet form of an unlicensed product) resulted in substantial cost savings.  Conclusions: The introduction of oral glycopyrronium bromide 400 micrograms/ml may lead to substantial cost savings for the UK healthcare service. Use of real world evidence to understand clinical practice and treatment decisions is critical to validate assumptions around input parameters when estimating the budget impact of introducing a newly licensed product into a previously unlicensed market. This allows national and local decision makers to make informed decisions on use for their patient population. PND18 Migraine Burden and Costs: A Nationwide Population-Based Controled Cohort Study Using The French EGB Database Aly S1, Emery C2, Fagnani F3, Gourmelen J4, Mahieu N5, Leiba G1, Allaf B1, Chouette I1, Levy P6, Donnet A7 1Novartis Pharma, Rueil-Malmaison, France, 2Cemka, Bourg La Reine, France, 3CEMKA-EVAL, Bourg la Reine, France, 4UMS 011 - Inserm - UVSQ, Villejuif, France, 5Novartis, Rueil Malmaison, France, 6Université Paris-Dauphine, Paris, France, 7CHU Timone, Marseille, France

Objectives: To describe and analyze the burden, healthcare resource use and costs of adult patients using acute migraine treatments in France, with a comparison to a matched control group.  Methods: Analysis was based on the EGB (“Echantillon Généraliste de Bénéficiaires”) database, a 1/97 random sample of the French healthcare insurance database linked with the hospital discharge database (PMSI). Adult patients with at least one delivery of any specific migraine acute treatment (triptans or ergots derivatives) in 2014 were selected. A control group matched on age, gender and geographic area was identified (3 controls per case). Treatment overusers were defined as a consumption of > 20 DDD (triptans) or > 10 DDD (ergots), per month for at least 3 consecutive months. The cost analysis was performed in a societal perspective by comparing healthcare costs between cases and controls.  Results: 8 639 patients using acute migraine treatments (mean age: 44.6 years; 78.7% of women) were selected representing a crude prevalence rate of 1.8%. Most frequent prescribers of triptans were GPs (86.6%). Only 6.9% of patients consulted a neurologist. 3.4% of patients were considered triptan overusers and 11.7% ergots overusers. 9.6% of patients had severe depression compared to 5.5% in controls and 20.8% of patients used antidepressant agents compared to 11% in controls. 19.5% of patients had at least one episode of sick leaves. In 2014, the mean annual per capita healthcare costs was 2463€  in patients, 4005€  in triptans/ergots overusers and 2182€  in controls. The



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extrapolated nationwide annual direct cost attributable to migraine treated by acute treatments was estimated at 242M€  in 2014.  Conclusions: Migraine generates a significant burden in patients with an increase of depression and anxiety. Drug abuse is associated with greater burden and healthcare related costs. Due to high prevalence (20%), costs related to migraine consist of a significant societal burden. PND19 Impact of Ocrelizumab Vs. Interferon Beta-1a In Delaying The Deterioration Of Patients’ Daily Functions and Associated Costs In Relapsing-Remitting Multiple Sclerosis Yang H1, Duchesneau ED1, Guerin A2, Ma E3, Thomas NP3 1Analysis Group, Inc., Boston, MA, USA, 2Analysis Group, Inc., Montreal, QC, Canada, 3Genentech, Inc., South San Francisco, CA, USA

Objectives: Ocrelizumab has better efficacy in delaying disease progression than subcutaneous interferon beta-1a (SC IFN-β -1a) among patients with relapse-remitting multiple sclerosis (RRMS). This study compared ocrelizumab vs. SC IFN-β -1a in terms of progression over Extended Disability Status Scale (EDSS) states and associated costs.  Methods: A Markov cohort model was developed to compare ocrelizumab vs. SC IFN-β -1a for the treatment of RRMS over 20-years time horizon, from a US payer perspective. Patients entered the model initiating treatment and distributing across EDSS states as observed at the baseline of two Phase III randomized controlled trials comparing ocrelizumab vs. SC IFN-β -1a (OPERA I and II). Patients could transition between 21 health states: EDSS 0-9 in RRMS, EDSS 0-9 in secondary-progressive multiple sclerosis (SPMS), and death. Efficacy of ocrelizumab and SC IFN-β -1a were from OPERA I and II. Data from the literature were used to inform other inputs. The model estimated the distribution of patients across EDSS states and cumulative treatment and EDSS state costs (2016 USD).  Results: At the end of 20 years, a higher proportion of patients receiving ocrelizumab vs. SC IFN-β -1a were able to maintain full daily activities (EDSS< 5: 20.7% vs. 15.5%) and to walk without a walking aid (EDSS< 6: 23.8% vs. 18.1%). Patients receiving ocrelizumab vs. SC IFN-β -1a were predicted to spend more time in EDSS states capable of full daily activities (9.67 vs. 8.52 years) and in states capable of walking without aid (10.93 vs. 9.76 years) over the 20 years period. The treatment costs ($455,501 vs. $556,003) and EDSS state costs ($204,986 vs. $229,652) were also lower for ocrelizumab vs. SC IFN-β -1a.  Conclusions: Ocrelizumab, compared to SC IFN-β -1a, is associated with delayed deterioration in RRMS patients’ ability to conduct full daily activities and to walk without aid in RRMS, which also translated to lower EDSS state costs. PND20 The Economic Burden of Different Multiple Sclerosis Phenotypes Cozzolino P1, Cortesi PA1, Cesana G1, Capra R2, Mantovani LG1 1University of Milano-Bicocca, Monza, Italy, 2Multiple Sclerosis Center, Spedali Civili of Brescia, Brescia, Italy

Objectives: Poor specific information on economic burden of Multiple Sclerosis (MS) phenotypes are available. This study assessed the costs associated to the main MS phenotypes: relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS).  Methods: Patients covered by Lombardy Healthcare System with a diagnosis of MS in the period 2004-2010 were identified through regional healthcare administrative databases. Data extracted from these databases were linked with clinical information collected by a major MS center in Lombardy, and for each patient we identified the MS phenotype and diseases severity assessed with the Expanded Disability Status Scale (EDSS). We identified drug prescriptions, hospitalizations, outpatient visits and diagnostic tests provided to patients for their MS during the years after the identification. We estimated the health care resources consumption and the mean annual cost per capita stratified by EDSS level and MS phenotype.  Results: The study identified 871 patients with a mean age of 37.9 years. At start of observation, 83.9% reported RRMS, 8.5% SPMS and 7.2% PPMS. More than 8% of RRMS developed SPMS during observational period. RRMS reported the highest annual cost per patient with a mean of €  7,136 in patients with EDSS level 0-3, € 9,820 with EDSS level 4-6 and € 11,569 with EDSS level 7-9. The PPMS patients reported the lower annual mean cost per patient (€  2,261 EDSS 0-3, € 3,920 EDSS 4-6, and € 8,290 EDSS 7-9). The higher cost of RRMS patients was mainly due to the use of disease modifying therapies (DMTs), with a low impact associated to relapse cost (€ 405 per relapse). The RRMS patients treated with DMTs reported a treatment switch rate of 12.1 per 100 person-years.  Conclusions: Costs were highly correlated with disease severity and MS phenotype. These data can help health care decision-maker to better assess the burden of MS pheotypes and the possible impact of DMTs. PND21 The Direct Cost of Patients With Multiple Sclerosis In France Detournay B1, Cousin M1, Gourmelen J2, Bitoun L3, Pau D3, Cozzone D3, Tehard B3 011 - Inserm - UVSQ, Villejuif, France, 3Roche, Boulogne-Billancourt, France

1Cemka-Eval, Bourg-la-Reine, France, 2UMS

Objectives: To estimate the direct healthcare cost of patients with multiple sclerosis (MS) in France in 2014.  Methods: Using data from the EGB database, a 1/97th random sample of the major French national health insurance system covering about 59 million individuals, we identified adults MS patients considering either long standing condition status (ICD-10 code: G35)/ hospital stays referencing MS as main or related diagnosis/ at least one reimbursement of an MS-specific drug over the 2007-2014 period. The global direct healthcare cost of patients with MS was estimated in a collective perspective. An incremental matched-control approach was then used to estimate the direct burden of MS.  Results: Overall 940 patients with MS were identified on January 1st, 2014. On average they were 50.9 (± 13.7) years old. 71.4% of patients were female. The sum of all 2014 health care expenditure for these patients was estimated to 12,225€  (±12,704€ ). Nearly all patients (91.7%) were visited at least once during the year by a GP and 38.9% a neurologist. Overall, 44.3% of patients have received at least one delivery of a primary therapy for MS in 2014 mostly beta-interferons and assimilated (28.8%). 22.1% of patients beneficiated of technical aids for their disabilities and 46.9% of patients were treated by a

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physiotherapist. Finally, 6.2% of patients were hospitalized for MS (average duration of 3.6 days). Comparing MS patients to a matched control group resulted in estimating the excess direct cost attributable to MS to 9,659€  (±6,059€ ) in 2014 (average annual growth rate: 3.9% over 2012-2014). Main cost drivers were pharmaceuticals (49%), hospital care (22.9%), nursing care (7.8%), medical devices (6.5%) and physiotherapy care (6%).  Conclusions: The direct burden of MS was evaluated to 965 € million in 2014 in France mainly due to disease-modifying therapies. Such burden highlights the importance of developing cost-effective drugs. PND22 Evaluating The Real-Life Daily-Cost of Treatment With Antiepileptic Drugs In France: A Study Based on The Combination Of French National Health Insurance Public Database, and The EMR LPD Private Database Troubat A, Bodaghi C, Ansolabehere X, Gibon N, Verschelde S QuintilesIMS, Paris La Défense, France

Objectives: To evaluate the real-life daily-cost of treatment with antiepileptic drugs, delivered in retail pharmacies in France.  Methods: Two sources of data were extracted and combined for the purpose of this study. On the one hand, private EMR Longitudinal Patient Data were used to assess the daily dose of antiepileptics prescribed in real life to patients above fifteen. Besides, as GPs and neurologists have an important role in epilepsy management, both of their prescriptions data were used in this analysis. On the other hand, French health insurance Medic’AM public data were used to assess the actual price per milligram of antiepileptic drugs delivered and reimbursed in real life. The study focused on the ten main oral antiepileptic drugs of the N03 EphMRA class marketed in France, both generic or brandname products, and immediate or extended-release formulations. The data sources were analysed based on the same definitions in terms of period, prescriber profile, analysed products and formulations.  Results: The combination of these two reallife insights lead to the estimation of the daily dose with a price per milligram, and the assessment of a daily cost of treatment in real life for each drug. Crossing the two databases between October 2015 and September 2016 showed that among the ten main antiepileptics, the daily cost of treatment ranged from 0,17€  to 3,79€  per day. Medic’AM data also gave access to the substitution ratio between generic and brand-name drugs. It showed that generic drugs accounted for 66% of the amount reimbursed by the French national health insurance.  Conclusions: This analysis shows that combining private data on ambulatory drugs prescriptions and public data on their reimbursement enables the calculation of a real-life daily-cost. PND23 Cost Analysis of Several Treatment Sequences Used for The Treatment of Relapsing-Remitting Multiple Sclerosis In Portugal: The Case for Cladribine Tablets Silverio N, Goncalves A, Fonseca A Merck SA, Alges, Portugal

Objectives: To evaluate the impact of the introduction of Cladribine Tablets in the long term costs of several therapeutic sequences used for the treatment of relapsing-remitting multiple sclerosis in Portugal.  Methods: An Excel based model was developed to permit the comparison for a single patient of the cost of alternative sequences of treatment, over a 1 to 6 year horizon. Time on treatment for each therapy was determined assuming switch at time of relapse. Data on probability of relapse over time was obtained from published long-term studies following RCTs, namely, FREEDOMS and TRANSFORMS for Fingolimod, ENCORE for DMF, and CLARITY and CLARITY EXT for Cladribine Tablets. Solely drug purchasing costs were included and these were obtained from national official sources. Initial treatments could occur with Cladribine tablets, Fingolimod or DMF, while second line could be done with Fingolimod or Natalizumab (as normal in Portugal). For studies with data shorter than 6 years, final observation was carried forward to year 6.  Results: When all treatment options are compared initial treatment with DMF followed by Natalizumab seems the least expensive option in the short to mid-term (2 to 4 years), however when treatment horizon is expanded up to 6 years, Cladribine followed by Natalizumab becomes a better option (79.676 €  vs 82.847 €  for DMFNatalizumab). Regarding Fingolimod, in the first 3 years Fingolimod is cheaper than Cladribine, however beyond the 3rd year Cladribine followed by either Natalizumab or Fingolimod is always cost-saving when compared with Fingolimod followed by Natalizumab (67.270 €  for Cladribine-Natalizumab vs 73.810 €  for FingolimodNatalizumab, over 4 years), with the gap between the costs of the two sequences increasing over time.  Conclusions: Used according with its label and over a 4 to 6 years horizon, Cladribine tablets can be the best financial option for the treatment of patients with multiple sclerosis in Portugal. PND24 Costs and Benefits of Implementing Non-Invasive Prenatal Testing For Trisomy 21 (T21) Based on Cell Free DNA (CFDNA) Sequencing In Maternal Plasma In France Druais S, Sambuc C, Cohen-Akenine A, Delaveyne R, Cognet M, Rumeau-Pichon C, Scemama O The French National Authority for Health (HAS), Saint-Denis, France

Objectives: To estimate the costs and benefits of implementing cfDNA for T21 in prenatal screening to support recommendations on its use in France.  Methods: A model was developed to simulate outcomes (detected foetal T21s, miscarriages avoided, false and true negatives, screening withdrawals and test failures) and costs of using standard first trimester T21 screening in France, compared to screening strategies that include cfDNA with different T21 risk thresholds (i.e. 1/250, 1/1000 and 1/2500). The time horizon used for the model was less than one year. Methodological choices were based on HAS guidelines, a systematic literature review of health economics studies, and expert consultation. Data was derived from national datasets and completed with international studies, where needed. Sensitivity analyses and validation against international study results were