Three-country analysis of costs (UK, Spain and Portugal) and PASI 75 response for combination of calcipotriol and betamethasone dispropionate vs. non-biologic systemic therapies in patients with psoriasis.

1. 1. Goff KL, Karimkhani C, Boyers LN, Weinstock MA, Lott JP, Hay RJ, et al. The global burden of psoriatic skin disease. The British journal
of dermatology. 2015;172(6):1665-8.
2. Baker C, Mack A, Cooper A, Fischer G, Shumack S, Sidhu S, et al. Treatment goals for moderate to severe psoriasis: An Australian
consensus. Australasian Journal of Dermatology 2013;54(2):148–54
3. Lambert J, Hol CW, Vink J. Real-life effectiveness of once-daily calcipotriol and betamethasone dipropionate gel vs. ointment
formulations in psoriasis vulgaris: 4- and 12-week interim results from the PRO-long study. Journal of the European Academy of
Dermatology and Venereology : JEADV. 2014;28(12):1723-31.
4. Lambert J, Hol CW, Vink J. Real-life effectiveness of once-daily calcipotriol and betamethasone dipropionate gel vs. ointment
formulations in psoriasis vulgaris: final analysis of the 52-week PRO-long study. Journal of the European Academy of Dermatology and
Venereology : JEADV. 2015;29(12):2349-55.
5. Mason AR, Mason J, Cork M, Dooley G, Hancock H. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev.
2013(3):CD005028.
6. Menter A, Gold LS, Bukhalo M, Grekin S, Kempers S, Boyce BM, et al. Calcipotriene plus betamethasone dipropionate topical
suspension for the treatment of mild to moderate psoriasis vulgaris on the body: a randomized, double-blind, vehicle-controlled trial.
Journal of drugs in dermatology : JDD. 2013;12(1):92-8.
7. Paul C., Stein Gold L., Cambazard F., Kalb R.E., Lowson D., Bang B., et al. Calcipotriol plus betamethasone dipropionate aerosol foam
provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO‐ABLE study. Journal of the European
Academy of Dermatology and Venereology. 2017;31(1):119-26.
8. Koo J, Tyring S, Werschler WP, Bruce S, Olesen M, Villumsen J, et al. Superior efficacy of calcipotriene and betamethasone
dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris--A randomized phase II study. The Journal of
dermatological treatment. 2016;27(2):120-7.
9. Leonardi C, Bagel J, Yamauchi P, Pariser D, Xu Z, Olesen M, et al. Efficacy and Safety of Calcipotriene Plus Betamethasone
Dipropionate Aerosol Foam in Patients With Psoriasis Vulgaris--a Randomized Phase III Study (PSO-FAST). Journal of drugs in
dermatology : JDD. 2015;14(12):1468-77.
10.Lebwohl M, Tyring S, Bukhalo M, Alonso-Llamazares J, Olesen M, Lowson D, et al. Fixed Combination Aerosol Foam Calcipotriene
0.005% (Cal) Plus Betamethasone Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for Psoriasis
Vulgaris: A Randomized, Double-blind, Multicenter, Three-arm, Phase 2 Study. The Journal of Clinical and Aesthetic Dermatology.
2016;9(2):34-41.
11.Bewley A, Shear NH, Calzavara-Pinton P, Hansen JB, Nyeland ME, Signorovitch J. Calcipotriol plus betamethasone dipropionate
aerosol foam versus apremilast, methotrexate, acitretin, or fumaric acid esters: a matching-adjusted indirect comparison. Abstract
submitted to EADV conference; Paris.2018.
12.Bewley A, Shear NH, Calzavara-Pinton P, Hansen JB, Nyeland ME, Signorovitch J. Calcipotriol Plus Betamethasone Dipropionate
Aerosol Foam Versus Apremilast, Methotrexate, Acitretin, or Fumaric Acid Esters: A Matching-Adjusted Indirect Comparison. 2018.
Accepted for publication in JEADV.
13.Strober B, Bagel J, Lebwohl M, Stein Gold L, Jackson JM, Chen R, et al. Efficacy and Safety of Apremilast in Patients With Moderate
Plaque Psoriasis With Lower BSA: Week 16 Results from the UNVEIL Study. Journal of drugs in dermatology : JDD. 2017;16(8):801-8.
14.Cabello Zurita C, Grau Pérez M, Hernández Fernández CP, González Quesada A, Valerón Almazán P, Vilar Alejo J, et al. Effectiveness
and safety of Methotrexate in psoriasis: an eight-year experience with 218 patients. Journal of Dermatological Treatment.
2017;28(5):401-5.
15.Chiricozzi A, Panduri S, Dini V, Tonini A, Gualtieri B, Romanelli M. Optimizing acitretin use in patients with plaque psoriasis.
Dermatologic therapy. 2017;30(2).
16.Inzinger M, Weger W, Heschl B, Salmhofer W, Quehenberger F, Wolf P. Methotrexate vs. fumaric acid esters in moderate-to-severe
chronic plaque psoriasis: data registry report on the efficacy under daily life conditions. Journal of the European Academy of
Dermatology and Venereology. 2013;27(7):861-6.
17.UK drug costs: BNF online (accessed March 2018)
18.Spain drug costs: https://www.mscbs.gob.es/profesionales/nomenclator.do
19.Portugal drug costs: Diário da República, 1.ª série — N.º 132 — 11 de julho de 2017
20.NHS reference costs (https://improvement.nhs.uk/resources/reference-costs/ )
21.PSSRU unit costs of health and social care (https://www.pssru.ac.uk/project-pages/unit-costs/unit-costs-2017/)
22.NICE Psoriasis guideline (https://www.nice.org.uk/guidance/cg153)
23.https://www.fraternidad.com/sites/default/files/2016-07/FM-DOCUM-152_4119_Tarifa%20Servicios%20Sanitarios%202016.pdf,
24.http://www.ffis.es/investigacion/precios_pruebas.php
25.https://www.comb.cat/Upload/Documents/4635.PDF
26.Carretero G et al. Guidelines on the Use of Methotrexate in Psoriasis. Actas Dermosifiliogr. 2010;101(7):600-613
27.Carretero G et al. Guidelines for the Use of Acitretin in Psoriasis. Actas Dermosifiliogr. 2013;104(7):598-616
28.Royal National Hospital for Rheumatic Diseases. DMARD monitoring guidelines – Reviewed 23.01.15. Published at
http://www.rnhrd.nhs.uk/our-services/for-clinicians [accessed in 19/04/2018]
29.Ormerod et al. British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology. British Journal of
Dermatology 2010; 162: pp952–963.
30.Malta RF. Terapêutica sistémica clássica (não-biológica) na psoríase: metoxato acitretina e ciclosporina. Faculdade de Medicina da
Universidade de Coimbra. Published at http://hdl.handle.net/10316/43401 [accessed on 19/04/2018]
PSS16r
Cost per responder analysis of calcipotriol plus betamethasone
dipropionate aerosol foam versus non-biologic systemic therapy in
the treatment of moderate-to-severe plaque psoriasis
Becla L1, Carrascosa JM2, Antunes JF3, Bewley AP4, Delgado Perala M5, Charrua MF6 7, Treloggen JR1, Sawyer LM8, Cornic L8
1LEO Pharma A/S, Ballerup, Denmark, 2Hospital Universitari Germans Trias i Pujol, Barcelona, Spain, 3Centro Hospitalar Lisboa Norte, EPE - Hospital de Santa Maria, Lisbon, Portugal, 4Barts Health NHS Trust, Leytonstone,
United Kingdom, 5LEO Pharma, Barcelona, Spain, 6LEO Pharma, Lisbon, Portugal, 7LEO Pharma UK/IRE, Hurley, United Kingdom, 8Symmetron Limited, Elstree, United Kingdom
BACKGROUND
Psoriasis is a chronic, immune-mediated inflammatory condition that affects 1.5% to 3% of the world’s
population (1). Treatment of psoriasis aims to reduce the severity of skin signs and symptoms. Topical
therapies are usually considered as the first-line option in mild or moderate psoriasis while phototherapies or
oral systemic therapies are generally offered for more severe disease or after failure of topical therapy (2).
Systemic therapies or phototherapies are often associated with greater costs to the healthcare system and
potentially more serious side effects than topical treatments.
A fixed-dose combination of calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD)
has been shown to have an improved safety profile and to be more effective than monotherapy for the
treatment of plaque psoriasis (3-6). An aerosol foam has been developed for the established fixed-dose
combination of calcipotriol (Cal, 50 μg/g) and betamethasone dipropionate (BD, 0.5 mg/g) (hereafter
“Cal/BD foam”), and it has demonstrated significantly improved efficacy with comparable safety profile in 4
studies of the Cal/BD foam clinical trial program, compared to Cal/BD gel formulation (7) and Cal/BD
ointment (8), compared to foam vehicle (9), and Cal or BD aerosol foams alone (10).
In a recently presented matching-adjusted indirect comparison (MAIC) analysis, Cal/BD foam has
demonstrated greater efficacy compared to apremilast [APR], methotrexate [MTX], or acitretin [AC] and
comparable efficacy to fumaric acid esters [FAE] in patients with moderate to severe psoriasis who could be
considered eligible for either topical or non-biologic systemic treatments (11).
OBJECTIVE
To compare the cost and efficacy of Cal/BD foam, used according to label, versus non-biologic systemic
therapies in patients with psoriasis who could be considered for either topical or non-biologic systemic
treatment.
For this comparison, the cost per PASI 75 responder (defined as a 75% reduction in Psoriasis Area and
Severity Index score) was calculated for Cal/BD foam versus approved comparators in the UK (MTX, APR,
AC, FAE), Spain (MTX, APR, AC) and Portugal (MTX, AC). Ciclosporin was not included in the analysis due
to a lack of published studies in the relevant patient population.
METHODS
Efficacy
Efficacy was derived from a study using a MAIC approach which matched the characteristics of patient
populations from four 4-week Cal/BD foam trials (based on pooled individual patient-level data) with those
from 12-week efficacy studies for each of MTX, AC, or FAE and a 16-week efficacy study of APR (11,12).
Published clinical trials and observational studies were included to support indirect comparisons.
Comparator studies for which methods, populations, and outcomes aligned with the Cal/BD foam trials were
identified based on a comprehensive literature review of 3,090 screened publications. Baseline variables for
matching included PASI score, age, body mass index, and percentage with previous topical treatment and
were selected based on clinical input and by responder analysis (11,12).
A series of pairwise MAIC analyses were conducted using the pooled results of 4 RCTs evaluating the
efficacy of Cal/BD foam (7-10). Individual patient data were matched with summary findings from the
UNVEIL study for APR (13) and from observational cohort analyses for MTX (14), AC (15) and FAE (16).
The results of each pairwise comparison using the 4-week efficacy data from a pooled analysis of 4 Cal/BD
foam RCTs were considered in the base case analysis. Additionally, the results of the MAICs using the 12-
week Cal/BD foam efficacy from the PSO-ABLE study (7) were explored in a sensitivity analysis. The results
of both MAIC analyses are presented in Table 1.
Costs & Health care resource use
The Cal/BD foam dose modelled (117.1 g) was calculated from a weighted average of doses observed in the
RCTs included in the pooled analysis. In a sensitivity analysis, the mean dose received at 12 weeks in the
PSO-ABLE study (236.4 g) was used. Systemic therapy doses were determined according to the label or
clinical practice and calculated for the treatment duration.
The total dose received over the treatment duration was calculated and a cost per mg was applied to
calculate the total drug cost. Total drug and administration and monitoring costs were calculated over a 4-
week period for Cal/BD foam, 12-week for MTX, AC and FAE and 16-week for APR (see Table 2). In a
conservative scenario analysis, these costs were calculated over a 4-week period for all drugs.
A payer perspective was considered for the analysis. Drug costs as well as administration and monitoring
costs (general practitioner visits, specialist visits and monitoring tests) were considered for each country
according to local databases and clinical guidelines.
MTX APR AC FAE Source
Systemic therapy 33.5% 21.6% 31.7% 47.0% Bewley 2018 (11)
Cal/BD foam (pooled analysis)
50.8%
(P < 0.001)
51.1%
(P < 0.001)
50.9%
(P = 0.009)
42.4%
(P = 0.451)
Bewley 2018 (11)
Cal/BD foam
(PSO-ABLE 12 weeks)*
59.8%
(P < 0.001)
60.4%
(P < 0.001)
77.5%
(P < 0.001)
58.5%
(P = 0.11)
Bewley 2018 (12)
Table 1. Proportion of PASI 75 responders with Cal/BD foam vs non-biologic systemic therapies - results of the
MAIC using a pooled analysis of 4 Cal/BD foam RCTs at 4 weeks and 12-week data from PSO-ABLE (11,12)
Notes: P values are for Cal/BD foam vs systemic therapy; *MAIC analysis using the 12-week Cal/BD foam efficacy data from PSO-ABLE study
(7) used in sensitivity analysis. Abbreviations: AC: acitretin; APR: apremilast; Cal/BD: calcipotriol and betamethasone dipropionate; FAE:
fumaric acid ester; MTX: methotrexate.
Treatment
Total dose per
treatment period
UK (GBP) Spain (EUR) Portugal (EUR)
Drug costs†
Adm. &
monitoring
costs‡
Drug costs†
Admin. &
monitoring
costs‡
Drug costs†
Admin. &
monitoring
costs‡
Cal/BD foam 117.1 g 77.44 33.50 69.85 107.45 89.27 34.10
MTX oral 202.5 mg* 7.62 423.42 4.12 291.25 6.97 178.28
MTX injection 202.5 mg* NA NA 147.58 291.25 279.27 178.28
APR 6.57 g 1,882.03 100.54 3,265.36 131.82 NA NA
AC 3.15 g 101.51 411.17 75.60 237.16 154.54 136.54
FAE 34.02 g 667.80 317.56 NA NA NA NA
Table 3. Drug and healthcare resource use costs in the UK, Spain and Portugal
Notes: *The dose is achieved through a titration period starting with 7.5 mg at week 1, 10 mg at week 2 and 3, 15 mg at week 4, 5, 6, 20 mg
from week 7 to 10 and 25 mg from week 11 onwards (Source: SmPC and national external experts in dermatology and poster co-authors);
† Drug cost references (17-19), shown using List & Drug Tariff prices for UK, wholesale purchase prices for Spain, and pharmacy selling prices
for Portugal; ‡ Admin and monitoring cost references: UK (20-22), Spain (23-27), Portugal (28-30).
Abbreviations: AC: acitretin; Adm.: administration; APR: apremilast; Cal/BD: calcipotriol and betamethasone dipropionate; FAE: fumaric acid
ester; MTX: methotrexate; NA: not applicable.
SCENARIO ANALYSES
The primary analysis compared data consistent with the recommended treatment period (i.e. 4-week Cal/BD
foam efficacy vs 12 or 16-week efficacy for the non-biologic systemic therapies). To test the robustness of the
results to alternative assumptions, 2 additional scenarios were explored:
1. 12-week efficacy and costs of Cal/BD foam from the PSO-ABLE study were compared with 12 or 16-
week efficacy and costs for the systemic therapies.
2. 12 or 16-week efficacy rates for the systemic therapies were conservatively combined with 4-week
costs for all systemic comparators.
RESULTS
The base case results for the cost per PASI 75 responder using pooled MAIC analysis are presented in
Figure 1 for UK, Spain and Portugal. The higher or comparable efficacy of Cal/BD foam, combined with its
lower total costs, gives it the lowest cost per PASI 75 response among comparators in each country.
CONCLUSIONS
Cal/BD foam generated more responders than APR, AC and MTX and a comparable proportion of
responders to FAE at a lower cost and was associated with the lowest cost per PASI-75 response when
compared to available non-biologic systemic therapies in the UK, Spain and Portugal.
The main drivers of overall costs varied by treatment, with drug costs making up the majority of total costs
for Cal/BD foam, APR and FAE and specialist visit and monitoring costs making up the majority for MTX and
AC.
The main limitation of this study is the comparison across different timepoints, though these are in line with
the label usage for each therapy. Sensitivity analyses were performed to assess the robustness of the
conclusions to more conservative assumptions regarding treatment duration, efficacy and costs. Results
were consistent with the base case analysis.
The MAIC underpinning the efficacy was based on a comparison of non-randomised treatment groups, the
results of which may be confounded by unknown or unobserved differences between patient populations.
Only a head-to-head RCT can avoid such unobserved confounding.
This analysis demonstrated that compared to non-biologic systemic therapies, Cal/BD foam is likely to be a
cost-effective option for the treatment of patients with plaque psoriasis who would be considered eligible for
either topical or non-biologic systemic treatments in the UK, Spain and Portugal.
Figure 1. Cost per PASI 75 responder for Cal/BD foam compared to non-biologic systemic therapies,
by country
Scenario analysis results were consistent with results of the base case analysis:
1. Where the responder rate and mean dosage for Cal/BD foam at week 12 from the PSO-ABLE study
was used, both the costs and proportion of responders increased relative to the base case; however,
the cost per responder for Cal/BD foam remained significantly lower than for the comparator non-
biologic systemic therapies.
2. When the analysis considered only 4 weeks of resource use for all comparators, the total costs for
non-biologic systemic therapies decreased substantially; however, Cal/BD foam treatment was still
less costly overall and remained the treatment with the lowest cost per PASI 75 responder.
REFERENCES
UK (£)
NOTES: Apremilast cost-per-responder bars exceed scale, value is indicated on top of bar. Analyses carried out versus comparators recommended for use in each country, as reflected in
graphic. Cost-per-responder for Cal/BD foam varies due to differences in the individual MAIC analyses carried out per pairwise comparison. Abbreviations: Cal/BD: calcipotriol and
betamethasone dipropionate; MTX, methotrexate; NA: comparison not applicable as comparator not recommended for use in country.
243
553
1,366
242
918
0
500
1,000
1,500
2,000
2,500
3,000
Cal/BD
foam vs
MTX
MTX oral MTX
injection
Cal/BD
foam vs
Acitretin
Acitretin Cal/BD
foam vs
Apremilast
Apremilast Cal/BD
foam vs
Fumaric acid
Fumaric
acid
218
1,287
218
1,617
217 262
2,097
0
500
1,000
1,500
2,000
2,500
3,000
Cal/BD
foam vs
MTX
MTX oral MTX
injection
Cal/BD
foam vs
Acitretin
Acitretin Cal/BD
foam vs
Apremilast
Apremilast Cal/BD
foam vs
Fumaric acid
Fumaric
acid
NA
NA NA
9,179
349
882
1,310
348
987
347
0
500
1,000
1,500
2,000
2,500
3,000
Cal/BD
foam vs
MTX
MTX oral MTX
injection
Cal/BD
foam vs
Acitretin
Acitretin Cal/BD
foam vs
Apremilast
Apremilast Cal/BD
foam vs
Fumaric acid
Fumaric
acid
15,728
NA
Portugal (
Spain (
This study was funded by LEO Pharma A/S. The authors received graphic design
support in the preparation of this poster provided by Jana Tillotson.