ISPOR 18th Annual European Congress, 7–11 November, 2015, Milan, Italy
GLATIRAMER ACETATE 40 MG/ML THREE TIMES A WEEK FOR THE TREATMENT OF
RELAPSING FORMS OF MULTIPLE SCLEROSIS: POTENTIAL COST BENEFITS OF A REGIMEN
WITH INFREQUENT INJECTIONS WHICH MAY MINIMISE SWITCHING TO THE NEWLYINTRODUCED FIRST-LINE AND SECOND-LINE DISEASE MODIFYING THERAPIES
Garcia Bujalance L1, Kelly M2, Blackney M2, Zeidman R2, Skroumpelos A3, Bijedic Mitranic A1, Sanchez-de la Rosa R1, Plich A3
Teva Pharmaceuticals, Madrid, Spain, 2Covance Market Access, London, United Kingdom, 3Teva Pharmaceuticals Europe B.V, Amsterdam, Netherlands
1
INTRODUCTION
Initiation and monitoring costs (Table 2) were derived as follows:
►► Pre-treatment costs included tests recommended by individual SmPC with the assumption that all patients would require an initial neurology outpatient appointment to
conduct a baseline magnetic resonance image (MRI) scan6, 13–22.
►► Multiple sclerosis (MS), of which relapsing forms (RMS) are the most common1-3, imposes a considerable economic burden on healthcare systems4.
►► Glatiramer acetate (GA; COPAXONE ) 20 mg/ml once-daily has demonstrated long-term (over 20 years), real-world efficacy and safety for the treatment of RMS and
has low monitoring, testing and administration requirements5, 6.
®
►► Teva has developed GA 40 mg/ml three times a week to offer patients the same known efficacy and safety benefits of GA 20 mg/ml once-daily but with a less intense
treatment regimen.
►► Compared with GA 20 mg/ml once-daily, patients receiving GA 40 mg/ml three times a week require 60% fewer injections, experience significantly fewer injection-related
adverse events (IRAEs) and find the treatment experience to be significantly more convenient7.
►► As both the frequency of injection-related adverse events and treatment convenience influence treatment adherence8, 9, introduction of GA 40 mg/ml three times a week
may improve retention on GA-based treatment regimens compared with GA 20 mg/ml once-daily.
►► Improving GA-based treatment retention may generate cost savings for healthcare systems by reducing treatment switching from GA to other newly-introduced first-line,
and second-line, disease-modifying therapies (DMTs), which are not proven to be more efficacious or safer than GA, but are more costly and necessitate more frequent
treatment initiation and monitoring tests.
OBJECTIVE
►► Initiation and monitoring costs while on treatment were based on the frequency of testing required as reported in the SmPC6, 13–22, with the cost of testing charged as an
outpatient tariff26; for GA 20 mg/ml once-daily and 40 mg/ml three times a week, no monitoring requirements are reported in the SmPCs.
RESULTS
►► An estimated 5,084 people with MS received GA 20 mg/ml once-daily in Spain in 2014, corresponding to 12.1% of those receiving DMTs.
►► Assuming progressive switching from GA 20 mg/ml once-daily to newly-introduced first-line, and second-line, DMTs at an annual rate of 8%, and accounting for no change
in the distribution of the interferons and a population increase of 0.6% per year (Table 3), total additional expenditure on MS treatments was estimated at €2.60 billion
over five years (scenario 1; Figure 2).
►► Assuming progressive switching from GA 40 mg/ml three times a week to newly-introduced first-line, and second-line, DMTs at a reduced annual rate of 5% due to the
benefit of lower rates of IRAEs with improved treatment convenience (Table 3; a 38% reduction compared with GA 20 mg/ml once-daily), total additional expenditure on
MS treatments was estimated at €2.57 billion over five years (scenario 2; Figure 2).
►► In both scenarios, the majority (>95%) of the additional cost arose from the higher acquisition costs of the newly-introduced first-line DMTs (Figure 2).
►►
An economic model was developed to estimate the financial impact to the Spanish healthcare system of improved treatment retention with GA 40
mg/ml three times a week compared with GA 20 mg/ml once-daily.
►►
The model assessed the budget impact of switching patients from GA-based treatment regimens to newly-introduced first-line DMTs (terifluonimide
14 mg; dimethyl fumarate 240 mg) and second-line DMTs (natalizumab 300 mg; fingolimod 0.5 mg; alemtuzumab 10 mg/ml; Figure 1).
►► Overall, compared with GA 20 mg/ml once-daily, GA 40 mg/ml three times a week has the potential to reduce costs of switching by between €5.9 million and €7.2
million annually (Figure 3), with savings totalling €32.8 million over five years.
Table 3. Current vs revised patient distributions for GA-based treatments based on annual switching rates of 8% (scenario 1; GA 20 mg/ml once-daily) and 5%
(scenario 2; GA 40 mg/ml three times a week)
Scenario
Current, % (n)
Figure 1. Model structure
Scenario 1
People with MS
Switching from GA 20 mg/ml once-daily
to other DMTs* at an annual rate of 8%
Scenario 2
Switching from GA 40 mg/ml once-daily
to other DMTs* at an annual rate of 5%
Medicine costs
Net spending
and budget impact
Year 2
Year 3
Year 4
Year 5
GA 20 mg/ml once-daily
(scenario 1)
12.1
(5,084)
11.1
(4,664)
10.2
(4,312)
9.4
(3,997)
8.6
(3,679)
7.9
(3,400)
GA 40 mg/ml three times a week
(scenario 2)
12.1
(5,084)
11.5
(4,832)
10.9
(4,608)
10.4
(4,423)
9.9
(4,235)
9.4
(4,046)
Administration, testing
and monitoring costs
Figure 2. Net spending over five years
*Alemtuzumab 10 mg/ml, dimethyl fumarate 240 mg, fingolimod 0.5 mg, natalizumab 300 mg and teriflunomide 14 mg.
3,000,000
METHODS
2,604,509
2,571,694
2,500,000
Model specifications
2,000,000
Table 1. Model specifications
Country
Net spending
(€; millions)
Spain
Time horizon
1,500,000
0
Note: Interferon-based therapies were also included in the model, however their distribution
was assumed to remain the same throughout the model time horizon in both scenarios.
0.0
2014 Euros (where available)
GA 20 mg/ml
once-daily
(Scenario 1)
GA 40 mg/ml
three times a week
(Scenario 2)
Year 1
Year 2
Year 3
Year 4
Year 5
-7.2
-7.0
25.8
32.8
-1.0
Population
-2.0
The eligible population was the estimated number of individuals with MS in Spain, based on:
-3.0
Net budget impact
(€; millions)
►► The total Spanish population reported as of mid-2014 – 46,820,08410.
►► The prevalence of MS per 100,000 Spanish individuals – 90 – which was derived from a cross-sectional study reporting the prevalence of MS over a 17-year period in
Osona, Catalonia, Spain11. It was assumed this value is representative of the total Spanish population.
-4.0
-5.0
-6.0
Medicine costs
-5.9
-6.2
-6.5
-7.0
►► Medicine costs (cost per pack) for all DMTs, except GA, were sourced from the Spanish General Council of Pharmacists database12.
-8.0
►► The cost per pack of GA-based medicines was based on confidential prices agreed with the Spanish Ministry of Health.
►► D
osing information (number of packs used per year) were taken from the Summary of Product Characteristics (SmPC) documentation for each
medicine6, 13–22.
Cumulative total
(€; millions)*
►► A
s alemtuzumab is only administered during the first two years of treatment, the number of packs (vials) used per year was calculated according to the recommended adult
daily dose, as reported in the SmPC21, taking account of the five-year model time horizon.
5.9
12.1
18.6
*Values subject to rounding.
Administration and additional care costs
CONCLUSIONS
Table 2. Administration and additional care costs
Administration costs (€)
Year 1
Medicines
Figure 3. Budget impact over five years
Prevalence-based
Costs
Administration
500,000
GA 20 mg/ml once-daily (scenario 1)
GA 40 mg/ml three times a week (scenario 2)
Teriflunomide 14 mg
Dimethyl fumarate 240 mg
Fingolimod 0.5 mg
Alemtuzumab 10 mg/ml
Natalizumab 300 mg
Eligible population
Initiation and monitoring
1,000,000
Five years
Comparators
Medicine
Year 1
*In each year, the current scenario also takes account of the population increase. The distribution of the interferons is assumed to be unchanged throughout the model time horizon, with patients
switching from GA-based treatments being distributed among the newly-introduced first-line, and second-line, DMTs evenly (distributions of all other DMTs in the current scenario: interferon beta1a (Avonex®) = 14.3%; interferon beta-1a (Rebif®) = 14.9%; interferon beta-1b (Betaferon®) = 5.2%; interferon beta-1b (Extavia®) = 5.2%; teriflunomide 14 mg = 6.2%; dimethyl fumarate 240 mg =
6.8%; fingolimod 0.5 mg = 11.1%; alemtuzumab 10 mg/ml = 1.5%; natalizumab 300 mg = 6.0%; not receiving DMTs = 16.7%).
Medicine costs
Administration, testing
and monitoring costs
Revised, % (n)*
►►
Initiation and monitoring costs (€)
Per subsequent year
Pre-treatment
Year 1
Per subsequent year
The tolerability and treatment convenience benefits of GA 40 mg/ml three times a week, compared with GA 20 mg/ml once-daily, may improve
patient retention on GA-based treatment regimens and reduce switching to the newly-introduced first-line, and second-line, DMTs; this may generate
considerable cost savings for healthcare systems.
GA 40 mg/ml three times a week
78.81
0.00
229.38
64.46
64.46
GA 20 mg/ml once-daily
78.81
0.00
229.38
64.46
64.46
ACKNOWLEDGEMENTS
Interferon beta (1a and 1b)
78.81
0.00
319.27
179.51
179.51
►► The authors would like to thank Shaista Nisar and Damian Kosinski (Covance Market Access) for editorial and design support, respectively.
Terifluonimide 14 mg
0.00
0.00
319.20
1,070.25
498.30
Dimethyl fumarate 240 mg
0.00
0.00
292.93
255.11
191.56
REFERENCES
172.16
0.00
344.14
484.29
244.10
Fingolimod 0.5 mg
Alemtuzumab 10 mg/ml*
Natalizumab 300 mg
1,308.12
2,009.02
200.34*
2,009.02
357.10
365.42
984.50
298.15
984.50
298.15
*As alemtuzumab is only administered in the first two years, costs represent the total second year costs for administration of alemtuzumab averaged over the remaining four years of the five-year
model time horizon.
Administration costs (Table 2) were derived as follows:
►► The cost of administering GA-based regimens was based on the assumption that three hours of nurse time would be required to teach people with MS how to self-administer
injections, with the cost per nurse hour reported by an analysis of clinical decision making strategies in Spain23; it is assumed that administration costs would only be
incurred in the first year of treatment.
►► It was conservatively assumed that oral treatments would not incur any administration costs.
1
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Fox RJ, et al. Cleve Clin J Med. 2006;73(1):91–102.
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Confavreux C, Vukusic S. Brain. 2006;129(Pt 3):606–16.
21. LEMTRADA™ (alemtuzumab). Summary of Product Characteristics. Genzyme Therapeutics Ltd, Mar
2014.
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Oleen-Burkey M, et al. Patient. 2012;5(1):57–69.
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Boster AL, et al. Expert Rev Neurother. 2015;15(6):575–86.
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Glanz BI, et al. Int J MS Care. 2014;16(2):68–75.
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Beer K, et al. BMC Neurol. 2011;11:144.
10. Spanish Office for National Statistics, January 2014-based Statistical Bulletin. 2014. Available at:
http://www.ine.es/jaxi/tabla.do. Accessed: Nov 2014.
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duodenal no complicada. Tesis doctoral. UPV. (Referido a: Osakidetza).
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día. Versión 2002. Catálogos SIE. Generalitat Valenciana. Conselleria de Sanitat, Valencia.
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Generalitat de Catalunya nº 4932.
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botplusweb.portalfarma.com/. Accessed: Nov 2014.
13.COPAXONE® (glatiramer acetate) 40 mg/ml solution for injection, pre-filled syringe. Summary of
Product Characteristics. Teva Pharmaceuticals Ltd, Jan 2015.
14.AVONEX® (interferon beta-1a). Summary of Product Characteristics. Biogen Idec Ltd, Dec 2014.
►► Administration costs for alemtuzumab were based on yearly infusion requirements, costed according to the catalogue of diagnostic and therapeutic procedures for
Spain24, and additional medicine requirements (e.g. methylprednisolone and aciclovir 200 mg) as specified in the SmPC21, costed according Spanish General Council of
Pharmacists database prices12.
15.BETAFERON® (recombinant interferon beta-1b). Summary of Product Characteristics. Bayer Pharma
AG, Sept 2014.
►► Administration costs for fingolimod were based on initial continuous electrocardiogram (ECG) and blood pressure monitoring requirements with the cost per nurse hour
reported by an analysis of clinical decision making strategies in Spain and the cost of two ECGs as reported by data from the Spanish of Department of Health23, 25.
17.REBIF® (interferon beta-1a). Summary of Product Characteristics. Merck Serono Europe Ltd, Sept
2014.
►► The cost of administering natalizumab was based on yearly infusion requirements, as reported by the catalogue of diagnostic and therapeutic procedures for
Spain24.
22.TYSABRI® (natalizumab). Summary of Product Characteristics. Biogen Idec Ltd, Apr 2014.
16.EXTAVIA® (recombinant interferon beta-1b). Summary of Product Characteristics. Novartis Europharm
Ltd, Oct 2014.
18.AUBAGIO® (teriflunomide). Summary of Product Characteristics. Sanofi-Aventis groupe, Nov 2014.
19.TECFIDERA® (dimethyl fumarate). Summary of Product Characteristics. Biogen Idec Ltd, Aug 2014.
Europe