PowerPoint Presentation


Calcipotriene plus betamethasone dipropionate (0.005%/0.064%) foam 
and apremilast: matching-adjusted indirect comparison and 

US cost per responder analyses
Martin Erik Nyeland, PhD1, Lidia Becla, MSc1, Dharm S. Patel, PhD2, Karen A. Veverka, PhD2, Andrine R. Swensen, PhD2

1LEO Pharma A/S, Ballerup, Denmark; 2LEO Pharma Inc., Madison, New Jersey

Background

Results

Conclusions

Methodology

Acknowledgements

References

 New and effective topical treatments and systemic 
treatments with improved safety for the treatment of plaque 
psoriasis have blurred the distinction among treatment 
options, particularly for patients who may be considered for 
either topical treatment or non-biologic systemic treatment 
present with a broad range of symptoms and factors.

 Calcipotriene and betamethasone dipropionate 
0.005%/0.064%) foam is a fixed-combination, once-daily
topical treatment for adult patients with plaque psoriasis.1

 Apremilast is a twice-daily oral treatment for patients with 
moderate to severe plaque psoriasis who are candidates 
for phototherapy or systemic therapy.2

 Despite overlap in studied populations, head-to-head 
clinical trials and comparative analyses have not been 
conducted between Cal/BD foam and apremilast.

Study Design (Figure 1)
 Matching-adjusted indirect comparisons (MAICs) use 

individual patient data (IPD) from trials of one treatment to 
match baseline summary statistics reported from trials of 
another treatment to compare treatment outcomes across 
a balanced patient population.3

 Published clinical trials with sufficiently similar populations 
and outcomes to support indirect comparisons were 
identified for Cal/BD foam and apremilast. 

 Priority baseline variables for matching included disease 
severity (Psoriasis Area and Severity Index, PASI, or body 
surface area, BSA), quality of life, demographics, duration 
of psoriasis, body mass index, and history of topical 
treatment.

 MAIC analysis was conducted between Cal/BD foam and 
apremilast4 and associated economic evaluation through 
US cost per responder analysis.

Figure 1.  Methodology of MAIC analysis of Cal/BD foam and apremilast4

 Weighted analyses of response rate variables PGA and 
PASI 75 were conducted with IPD from pooled Cal/BD foam 
trials and aggregated results from the other treatment study 
using a logistic model and 95% confidence intervals (CIs)

 Sensitivity analyses were completed to investigate results 
by comparison to phase 3 PSO-ABLE Cal/BD trial data 
from Week 4 and Week 12.

Statistical Analysis

Exclusion Criteria for Comparator Trials:  

 Mean PASI or mean BSA ≥15 [suitability range 3-15] to ensure 
comparability between Cal/BD foam and apremilast study 
populations with moderate disease

 Combination therapy treatment approaches due to difficulty in 
isolating effect of one treatment

 No efficacy measures available limiting any comparative 
effectiveness comparisons

 No baseline demographics and/or disease characteristics 
available preventing adequate matching of study populations

 Time points of efficacy measures not specified limiting 
comparative efficacy comparisons

Inclusion Criteria for Comparator Trials:
 Apremilast had to be studied, over time either retrospectively or 

prospectively 
 Manuscript languages:  English, Danish, Swedish or Norwegian
 Apremilast investigated for plaque psoriasis

Comparator Trial Used in MAIC:

 Based on inclusion and exclusion criteria, and 
overlap of studied populations, only one study of 
apremilast (UNVEIL9) met the criteria and was
included in the MAIC analysis (Table 1)

 This analysis used matching-adjusted indirect 
comparison to balance study populations in terms of 
baseline characteristics in a comparative efficacy 
and cost per responder evaluation. 

 Results demonstrate that Cal/BD foam has higher 
PGA 0/1 and PASI-75 response rates and a lower cost 
per PASI-75 responder in the US than apremilast in 
adult patients with moderate plaque psoriasis.

Table 2.  sPGA 0/1 efficacy response rates calculated 
via MAIC between Cal/BD foam and apremilast.4

 After matching study populations, 52.7% of patients 
treated with Cal/BD foam achieved sPGA 0/1 at week 4 
vs. 30.4% treated with apremilast at week 16 (p<0.001).

Table 3. PASI75 efficacy response rates calculated via 
MAIC between Cal/BD foam and apremilast.4

Poster presented at the Fall Clinical Dermatology Conference, Las Vegas, Nevada, October 18-21th, 2018

Figure 2.  Average Cost Per PASI-75 Responder for Cal/BD foam 
and apremilast based on the MAIC analysis.

 In the US, cost per PASI-75 response Cal/BD foam is $3,770, and 
is lower than cost per response for apremilast ($66,671).

This study was sponsored by LEO Pharma.

Table 4. Economic evaluation of Cal/BD foam for 4 weeks and apremilast for 16 weeks for treatment of moderate 
plaque psoriasis through a cost per PASI-75 responder analysis.

Objective

Conduct a matching-adjusted indirect comparison (MAIC) 
analysis to compare individual patient data from available 
study populations for Cal/BD foam with aggregate patient 
characteristics and treatment outcomes from published 
efficacy assessments of apremilast in adult patients with 
moderate plaque psoriasis.

Potential matching
variable (priority) Pooled data

5-8 UNVEIL9

Treatment Cal/BD foam Apremilast

Study design Randomized, double-blind 
controlled study Phase IV randomized study

Dosing QD 30 mg BID

N 749​ 148

Sex, male (%) 470 (62.8%)​ 74 (50.0%)

mean Age (SD) 51.4 (14.1)​ 48.6 (15.4)

mean BMI (SD) 31.2 (7.2)​ 30.5 (7.4)

mean BSA (SD) 7.3 (6.1)​ 7.2 (1.6)

Years of psoriasis (SD) 16.8 (14.0)​ 17.5 (13.9)

mean PASI (SD) 7.3 (4.6)​ 8.2 (4.0)

mean DLQI (SD) - 11.0 (6.5)

BSA X PGA (SD) 21.9 (20.5)​ 21.8 (5.3)

Prev. topical treatment, yes 637 (85.1%) 122 (82.4%)

Prev. syst treatment, yes 233 (31.1%) -

Table 1.  Identification of Cal/BD foam and apremilast trials 
for MAIC analysis4

Pooled data5-8 UNVEIL9

Treatment Cal/BD foam Apremilast

Before re-weighting After reweighting

Effective sample 
size, n 748 640 148

BMI 31.2 30.5 30.5

PASI 7.3 8.2 8.2

Previous topical 
treatment 85.1% 82.4% 82.4%

PGA 0/1 
responder, % 

(95% CI)

56.4% 
(51.9%; 60.9%)

52.7% 
(44.9%; 60.4%)

30.4% 
(23.6%; 38.2%)

P-value (t-test) p<0.001

Pooled data5-8 UNVEIL9

Treatment Cal/BD foam Apremilast

Before re-weighting After reweighting

Effective sample 
size, n 748 651 148

Age 51.3 48.6 48.6

BMI 31.2 30.5 30.5

Previous topical 
treatment 85.1% 82.4% 82.4%

PASI-75 
responder, % 

(95% CI)

51.4% 
(51.2%, 51.5%)

51.1% 
(50.5%, 51.7%)

21.6% 
(15.8%, 28.9%)

P-value (t-test) p<0.001

 After matching study populations, 51.1% of patients 
treated with Cal/BD foam achieved PASI-75 at week 4 
vs. 21.6% treated with apremilast at week 16 (p<0.001).

PASI 75 Treatment period[weeks]
Consumption per 
treatment period Pack cost

# Units
per Pack Unit Unit per pack Price per Unit 

Cal/BD foam 51.1% 4 117.1 g* $987.09
$1974.18

1
2

60 g
60 g x 2

60-120 g $16.45 per g

Apremilast 21.6% 16 6570 mg** $1012.5 -
3939.71

27-60 10-30 mg
690-

1800 mg
$2.19 per mg

Data Source MAIC 
(Table 2) 

Approved FDA 
indication

*4 pooled Cal/BD 
studies

**FDA indication

Analysource®, accessed April 2018 
(third party provider of WAC pricing data)

 Cost per responder analysis was conducted based on the regimens approved by the FDA using US drug pricing.
o Apremilast dosing per treatment - 6570 mg over 16 weeks2
o Cal/BD foam dosing per treatment - average consumption data in 4 phase II/III trials5-8; 117.1 g over 4 weeks

 Cost per treatment period was calculated by multiplying the drug WAC per unit dose (mg or g, respectively) with total 
dosing (apremilast) or average consumption (Cal/BD foam) over treatment period.

 Cost per PASI-75 Responder was calculated by multiplying cost per treatment period by proportion of patients achieving 
PASI-75, as calculated in the MAIC analysis4.

Limitations
 Comparative safety analyses and associated economic impact 

were not conducted.

 WAC prices do not reflect manufacturer rebates, are not reflective 
of actual spend, and are dated for April 2018.

 Time to response difference between Cal/BD foam (4 weeks) and 
apremilast (16 weeks) precluded use of the same treatment time 
horizon.

 Analyses based on clinical trials may not be generalizable to the 
real world.

 Imbalance in sample size exists due to applicable publications on 
comparator, and may not be fully addressed by methodology.

 Additional head-to-head research should be conducted to confirm 
the comparative efficacy findings. 

1. Enstilar® Foam [package insert]. Madison, NJ: LEO Pharma Inc. 

2. Otezla® tablets [package insert]. Summit, NJ: Celgene Corporation. 

3. Signorovitch,JE, Sikirica V, Erder MH, et al. Value in Health. 2012;12:940-947.

4. Bewley AA, et al. Eur Acad Dermatol Venereol Annual Congress 2018. P1927. 

5. Paul C et al. J Eur Acad Dermatol Venereol. 2017;31(1):119-126

6. Leonardi C et al. J Drugs Dermatol. 2015;14(12):1468-1477

7. Lebwohl M, et al. J Am Acad Dermatol. 2015; 72 (5 Suppl 1): AB222

8. Koo J et al. J Dermatol Treat. 2016;27(2);120-127

9. Strober B, et al. J Drugs Dermatol. 2017;16(8):801-808.

BMI, body mass index; BSA, body surface area;  PASI, psoriasis area and severity index; DLQI, 
dermatology life quality index; PGA, physician’s global assessment; QD, once daily; BID, twice daily


	Slide Number 1