Introduction

Calcipotriene plus betamethasone dipropionate (0.005%/0.064%) foam vs 
halobetasol propionate and tazarotene (0.01%/0.045%) lotion: matching-adjusted 

indirect comparison & US cost-per-responder analysis
Jashin J. Wu, MD1, Jes B. Hansen, PhD2, Dharm S. Patel, PhD2, Nanna Nyholm Jensen, MSc2, Karen A. Veverka, PhD2, Andrine R. Swensen, MS, PhD2

1Dermatology Research and Education Foundation, Irvine, CA 2LEO Pharma, Ballerup, DK & Madison, NJ

Acknowledgements

References

 Fixed-combination topical treatments for plaque psoriasis 
provide treatment advantages via a dual mechanism of 
action.  The combination of active pharmaceutical 
ingredients (API), skin penetration, bioavailability of APIs, 
and formulation can impact clinical efficacy. 

 Additionally, adherence is impacted by length of therapy 
and vehicle acceptability. In the absence of head-to-head 
trials, a comparison of relative effectiveness between fixed-
combination topical treatments is pertinent.

 Calcipotriene and betamethasone dipropionate 
(0.005%/0.064%, Cal/BD) foam is a fixed-combination, 
once-daily topical treatment of plaque psoriasis in patients 
12 years of age and older.1

 Halobetasol propionate and tazarotene (0.01%/0.045%, 
HP/TAZ) lotion is a fixed-combination, once-daily topical 
treatment of plaque psoriasis in adults.2

Study Design
 MAIC 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

 Baseline characteristics for matching were selected based 
on clinical input and by forward selection using a logistic 
model, with the relevant end point (ie, treatment success) as 
the dependent variable and selection entry criteria, p<0.2. 

 Available baseline variables for matching included disease 
severity (PGA, BSA), quality of life, demographics, duration 
of psoriasis, body mass index, and history of topical 
treatment (Table 1).

 MAIC analysis was conducted between Cal/BD foam and 
HP/TAZ lotion, number-needed-to-treat (NNT) was 
conducted between active treatment and respective 
vehicle, and associated pharmacoeconomic evaluation 
through US incremental cost per responder analysis (ICPR).

Figure 1.  Methodology of MAIC analysis of Cal/BD foam and HP/TAZ lotion 

 This analysis used an anchored MAIC to balance baseline 
characteristics of study populations in an indirect, 
comparative effectiveness evaluation of two fixed-
combination topical treatments for plaque psoriasis. 

 Evaluation demonstrates that Cal/BD foam treatment has 
statistically greater difference in PGA 0/1 response rates, a 
lower cost per PGA 0/1 responder, and quicker treatment 
response than HP/TAZ lotion in adult patients with 
moderate-to-severe plaque psoriasis.

Table 2.  Anchored MAIC evaluating PGA ‘treatment success’ response rates and 
NNT for Cal/BD foam and HP/TAZ lotion.  

 After reweighting of 
patients and anchoring to 
vehicle effect, significantly 
more Cal/BD foam patients 
demonstrated greater 
difference in treatment 
success relative to vehicle 
after 4 weeks than did 
HP/TAZ lotion patients after 
8 weeks (51.4% vs 30.7%; 
treatment difference=20.7%; 
P<.001) (Table 2)

 The number needed to 
treat (NNT) relative to 
vehicle with Cal/BD foam 
was also less than HP/TAZ 
lotion (1.9 vs 3.3). 

Poster presented at the 17th Annual Winter Clinical Dermatology Conference - Hawaii® Puako, HI, January 17-22nd, 2020

Figure 2.  Average Cost Per PGA Responder for Cal/BD foam and 
HP/TAZ lotion based on the anchored MAIC analysis.

This study was sponsored by LEO Pharma.

Table 3. Economic evaluation of Cal/BD foam for 4 weeks and HP/TAZ lotion for 8 weeks for treatment of moderate 
plaque psoriasis through a cost per PGA ‘treatment success’ responder analysis.

Conduct an anchored matching-adjusted indirect 
comparison (MAIC) and incremental cost per responder (ICPR) 
analysis using individual patient data from Cal/BD foam 
studies and aggregate patient characteristics and outcomes 
from published efficacy assessments of HP/TAZ lotion in adult 
patients with moderate-to-severe plaque psoriasis. 

Table 1.  Identification of Cal/BD foam and HP/TAZ lotion trials for MAIC analysis

 Incremental cost per responder analysis was based on the FDA Prescribing Information1,2 and anchored MAIC 
analysis using US Wholesale Acquisition Cost (WAC) drug pricing from June 2019 (Analysource®).

 Cost per treatment period was calculated by multiplying the per gram drug WAC with the average consumption of 
study drug over treatment period of 4 weeks and 8 weeks, respectively, assuming equal weekly consumption rates.  

 The estimated incremental cost per responder (ICPR) was calculated by multiplying the NNT by the overall drug 
costs throughout the treatment period and corresponds to the additional cost to achieve 1 additional responder 
for each of the treatments vs vehicle (Table 3).

 The incremental cost per PGA 0/1 responder relative to vehicle for Cal/BD foam was $3988 and is 37% lower 
compared with HP/TAZ lotion ($6294) (Figure 2). 

 Observed (e.g. patient randomization) and unobserved (e.g. 
vehicle) cross-trial differences may not be accounted for in 
the analysis 

 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 June 2019.

 Time to response difference between Cal/BD foam (4 
weeks)1 and HP/TAZ lotion (8 weeks)2.

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

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

 Additional head-to-head research should be conducted to 
confirm these comparative effectiveness findings. 

1. Enstilar® Foam [package insert]. Madison, NJ: LEO Pharma Inc. July 2019 
2. DUOBRII™ Lotion [package insert]. Bridgewater, NJ: Bausch Health Americas, Inc. 

April 2019 
3. Signorovitch, JE, Sikirica V, Erder MH, et al. Value in Health. 2012;12:940-947.
4. Leonardi C et al. J Drugs Dermatol. 2015;14(12):1468-1477; 
5. Paul C et al. J Eur Acad Dermatol Venereol. 2017;31(1):119-126; 
6. Koo J et al. J Dermatol Treat. 2016;27(2);120-127; 
7. Sugarman JL et al. J Drugs Dermatol. 31 Jul 2018, 17(8):855-861
8. Analysource®, DMD America; accessed June 2019)

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

Objective

Methods

Results

Limitations

Conclusions

Disclosures
JJW has been an advisor with/without funding from LEO Pharma 
Inc. JBH, DSP, NNJ, KAV, and ARS are employees of LEO Pharma.

Potential Matching Variables Pooled Cal/BD foam Studies Pooled HP/TAZ lotion Studies

Study design Three multicenter, randomized, double-blind, controlled studies4-6
Two multicenter, randomized, double-blind, vehicle-controlled 

Phase 3 studies7
Dosing QD (4 weeks) QD (8 weeks)
Treatment Cal/BD foam Foam vehicle All HP/TAZ lotion Lotion vehicle All
N 649 199 848 276 142 418
Mean age (SD), y 52.0 (13.9) 48.0 (14.0) 51.0 (14.0) 50.0 (14.2) 51.0 (13.2) 50.3 (13.8)
Male, n (%) 417 (64.3) 108 (54.3) 525 (61.9) 175 (63.4) 97 (68.3) 272 (65.1)
White/Caucasian, n (%) 577 (88.9) 180 (90.5) 757 (89.3) 232 (84.1) 126 (88.7) 358 (85.6)
Mean BMI (SD), kg/m2 31.3 (7.3) 31.2 (7.9) 31.2 (7.4) - - -
Mean BSA (SD), % 7.4 (6.3) 7.9 (6.8) 7.5 (6.4) 6.0 (2.9) 5.7 (2.5) 5.9 (2.8)
Mean duration of psoriasis 
(SD), y

17.1 (14.0) 15.8 (12.5) 16.8 (13.7) NR NR NR

Mean PASI (SD) score 7.2 (4.6) 7.5 (5.5) 7.3 (4.8) NR NR NR
IGA, n (%)
Mild
Moderate
Severe

126 (19.4)
465 (71.6)
58 (8.9)

38 (19.1)
140 (70.4)
21 (10.6)

164 (19.3)
605 (71.3)
79 (9.3)

-
237 (85.9)
39 (14.1)

-
119 (83.9)
23 (16.2)

-
356 (85.2)
62 (14.8)

Study Selection
 Published clinical trials with sufficiently similar populations 

and outcomes to support indirect comparisons were 
identified for Cal/BD foam and HP/TAZ lotion (Figure 1). 

 Comparative studies were excluded for the following 
reasons: the sample size included fewer than 40 patients 
(this exclusion was stipulated to preserve adequate 
statistical power); treatment efficacy was not measured, or 
time points of efficacy measurements were not specified; 
baseline characteristics were not reported; and the mean 
baseline Psoriasis Area and Severity Index (PASI) or body 
surface area (BSA) were greater than 15.

Pooled Data

Treatment
Cal/BD foam (+vehicle)4-6 HP/TAZ lotion 

(+vehicle)7Before re-weighting After re-weighting
Effective sample size, n 649 (+199) 586 276 (+142)
Baseline PGA, %
Moderate
Severe

71.3%
9.3%

85.2%
14.8%

85.2%
14.8%

BSA 7.5% 5.9% 5.9%
Male, n (%) ​​ 61.9% 65.1% 65.1%
White/Caucasian at baseline, % 89.3% 85.6% 85.6%
Active
PGA Treatment success rate (95% CI)

48.5% 
(41.2%, 55.9%)

55.7% 
(52.3%, 59.1%)

40.6% 
(34.8%, 46.4%)

Vehicle
PGA Treatment success rate (95% CI)

5.0% 
(4.4%, 5.7%)

4.3% 
(3.5%, 5.1%)

9.9% 
(5.0%, 14.8%)

Active - Vehicle
Difference in PGA success rates 
(95% CI)

43.5% 
(36.5%, 50.5%)

51.4% 
(47.6%, 55.2%)

30.7% 
(23.1%, 38.3%)

Anchored MAIC
Difference in PGA success rates 
between Cal/BD foam & HP/TAZ lotion
(95% CI; P-value)

20.7%
(12.2%, 29.1%; P<.001)

Number needed to treat (NNT) relative to 
vehicle - Cal/BD foam vs HP/TAZ lotion 1.9 vs 3.3

PGA, physicians’ global assessment; BSA, body surface area; MAIC, matching adjusted indirect comparison

No 
units/pack

Grams per 
unit

Unit cost per 
pack (WAC)

[$]8
Cost per gram

Treatment
period

[weeks]

Quantity 
used per 
treatment 

period 

Anchored 
MAIC: PGA 
0/1 (4 vs. 8 

weeks)

ICPR per 
PGA 0/1 

responder 
[$]

Cal/BD Foam 1 60 gm $1050 $17.50 4 117.1 gm* 51.4% $3988

HP/TAZ Lotion 1 100 gm $825 $8.25 8 234.2 gm** 30.7% $6294

Data Source Prescribing Information
Prescribing 
Information

Analysource® (3rd party 
provider of US pricing

information; June 2019)

Analysource® (3rd 
party provider of US 
pricing information; 

June 2019)

Anchored MAIC 
(Pooled data from 
3 Cal/BD studies; 
2 HP/TAZ studies) 

*Pooled 
consumption from 3 

Cal/BD studies
**Assumes equal 

weekly consumption 
to Cal/BD (Data NR)

Anchored MAIC 
(Pooled data from 3 
Cal/BD studies; 2 
HP/TAZ studies) 

Cost-per-responder

 Define inclusion and 
exclusion criteria

 Define search terms 
to identify 
comparator studies in 
the literature

Literature search for 
HP/TAZ lotion 

comparator studies

 Cal/BD foam 
randomized 
controlled trials

 Pooled analysis (3 
trials) of Cal/BD foam 
randomized 
controlled trials

Identify Cal/BD 
foam trials available 
with IPD for analysis

 Identify comparator trials 
to perform indirect 
efficacy comparison

 Identify matching 
variable priorities 
between comparator 
aggregate data and IPD 
for Cal/BD foam

MAIC Inputs: Cal/BD 
foam vs HP/TAZ 

lotion

 Indirect effectiveness 
comparison (PGA) 
between treatment 
options before and 
after re-weighting of 
matching variables

MAIC Analysis 
Output

 $-

 $1,000

 $2,000

 $3,000

 $4,000

 $5,000

 $6,000

 $7,000

 $8,000

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$3988

$6294

Δ 37%

Cal/BD foam HP/TAZ lotion


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