PowerPoint Presentation


Poster #18223 Long-term proactive management of psoriasis vulgaris with fixed-dose combination of calcipotriene 0.005% and betamethasone 
dipropionate 0.064% foam: results of a Phase III randomized controlled trial
Mark Lebwohl1, Jean-Philippe Lacour2, Monika Liljedahl3, Charles Lynde4,5, Marie Holst Mørch3, Diamant Thaçi6 and Richard B Warren7

1Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Department of Dermatology, University Hospital of Nice, Nice, France; 3LEO Pharma A/S, Ballerup, Denmark; 4Lynde Dermatology, Probity Medical Research, Markham, ON, Canada; 5Department of Medicine, University of Toronto, Toronto, 
ON, Canada; 6Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 7Dermatology Centre, Salford Royal NHS Foundation Trust and NIHR Biomedical Research Centre, University of Manchester, Manchester, UK

Materials and Methods

Introduction

Presented at AAD Annual Meeting 2020, Denver, Colorado, USA, March 20–24, 2020

 Eligible patients for this Phase III, multicentre trial received 
once-daily Cal/BD foam during the 4-week open-label lead-in 
phase (Figure 1). 
─ Patients with trunk and/or limb psoriasis, involving 

2–30% of body surface area (BSA); physician’s global 
assessment (PGA) of disease severity ≥’mild’; modified 
psoriasis area and severity index (m-PASI) ≥2.

 Patients achieving success at the end of the open-label 
lead-in phase (PGA score ‘clear’/‘almost clear’ [PGA <2] with 
≥2-grade improvement from baseline of the open-label 
lead-in phase) were randomized 1:1 to twice-weekly Cal/BD 
foam or vehicle foam for 52 weeks (Figure 1). 

Primary objective and endpoints

 To evaluate the efficacy of a twice-weekly proactive maintenance 
regimen with Cal/BD foam compared with reactive management 
with vehicle foam in the prevention of relapse in patients with 
psoriasis.
─ Time to first relapse (defined as a PGA score of at least ‘mild’ 

[PGA≥2]).

Time to first relapse

Remission
 Patients in the proactive group had 41 extra days in remission

compared to patients in the reactive group (p<0.001), over 1 year 
(95% CI, 29–53 days). 

Results
Patient population

 545 patients were randomized (safety analysis set [SAS]); 521 
achieved treatment success in the open-label lead-in phase 
(proactive n=256; reactive n=265 [full analysis set (FAS)]). 251 
(46.1%) patients completed the trial.

 Disease characteristics at randomization were similar between 
groups. Mean age of randomized patients was 52.2 years; 91% of 
patients were white and 68% male.

 82% of randomized patients in each treatment group had a PGA 
score of ‘moderate’ at baseline of the open-label lead-in phase.

Conclusions

 Proactive management with Cal/BD foam was superior in 
prolonging time to first relapse, reducing number of relapses and 
increasing days in remission versus vehicle-controlled reactive 
management. 

 The results of this trial are promising. They are the first to 
demonstrate that proactive management with fixed-dose Cal/BD 
foam could offer improved long-term control of psoriasis over 
conventional reactive treatment.

Secondary objective and endpoints

 To evaluate the long-term efficacy (up to 52 weeks) of proactive 
management twice weekly as maintenance therapy compared with
reactive management in patients with psoriasis.
─ Number of relapses.
─ Proportion of days in remission (PGA<2).

Safety objective

 Safety objectives, endpoints and data are presented in poster 
#12797.

Rate of relapse
 Rate of relapse over 1 year was reduced by 46% in the proactive 

group compared to the reactive group (95% CI, 37–54%; p<0.001).
 Predicted number of relapses in 1 year was 4.0 in the proactive 

group and 7.5 in the reactive group.

Safety results

 Proactive management was well tolerated over the 52-week trial 
period (data presented in poster #12797). 

References
1. Feldman, et al. Am Health Drugs Benefits. 2016:9;504‒513; 2. Armstrong, et al. JAMA Dermatol. 2013:149;1180‒1185; 3. 
Bonnekoh, et al. EMJ Dermatol. 2017:5;36‒43; 4. EMC. Enstilar Summary of Product Characteristics 2018; 5. FDA. Enstilar -
Prescribing Information 2019; 6. Paul, et al. J Eur Acad Dermatol Venereol. 2017:31;119‒126; 7. Koo, et al. J Dermatolog
Treat. 2016:27;120‒127

Acknowledgements
The authors thank the investigators and patients who participated in this trial. The authors would like to thank Lauren Whyte, 
PhD, a freelance Medical Writer contracted by Ashfield Healthcare Communications, part of UDG Healthcare plc, for medical 
writing support, funded by LEO Pharma in accordance with Good Publications Practice (GPP3) guidelines 
(http://www.ismpp.org/gpp3).

Disclosures
All authors met the ICMJE authorship criteria and had full access to the relevant data. Neither honoraria nor payments were 
made for authorship. ML, J-PL, DT, RBW, CL have consulted for, conducted studies funded by, or received honoraria for 
services provided to LEO Pharma; ML, MHM are employees of LEO Pharma. Fixed-dose combination calcipotriene (Cal) 
0.005%/betamethasone dipropionate (BD) 0.064% aerosol foam is approved for the treatment of psoriasis vulgaris (plaque 
psoriasis) for up to 4 weeks in adults (under the trade name Enstilar® in the US and Enstilar® or Enstilum® in the EU). 
Cal/BD foam is also approved in the US for adolescents 12–18 years.

Funding
This study was funded by LEO Pharma.

 Topical therapies are considered first-line treatment for psoriasis,1
however maintaining long-term disease control is a challenge, with 
many patients untreated or undertreated.2 Current topical psoriasis 
treatment relies on a reactive approach to disease flares, as 
opposed to a more long-term proactive approach.3

 Data supporting the efficacy and safety of calcipotriene 0.005% and 
betamethasone dipropionate 0.064% (Cal/BD) foam approved as a 
reactive treatment are available from trials of 4- and 12-weeks 
duration in patients with psoriasis vulgaris (plaque psoriasis).4,5,6,7 

 Here, we report the efficacy of Cal/BD foam in long-term proactive 
management of psoriasis over 52 weeks (NCT02899962). Data 
from the open-label lead-in phase of this trial are presented in 
poster #16830.

Table 1. Time to first relapse

*Number of days from randomization until 50% of patients had experienced their first relapse.

Double-blind treatment during the maintenance phase

 ‘Proactive’ management was treatment with Cal/BD 
foam twice-weekly for 52 weeks when in remission.

 ‘Reactive’ management was treatment with vehicle foam 
twice-weekly for 52 weeks when in remission.

 Relapse: PGA≥2 [either previously treated and/or new skin area]). 
Flare medication (as separate flare bottles) was Cal/BD foam 
once-daily for 4 weeks for both the proactive and reactive 
management groups (Figure 1).

Figure 2. Patient disposition 
Entered open-label lead-in phase (n=650) Discontinued (n=105)

• Adverse event (n=2); Lost to follow-up (n=9); 
W ithdrawal by patient (n=11); Lack of efficacy (n=4); 
Patient did not achieve treatment success at end of 
open-label lead-in phase (n=68); Failed screening (n=1); 
Other (n=10)

Proactive management
(n=272 SAS [n=256 FAS])

Reactive management
(n=273 SAS [n=265 FAS])

Completed the trial (n=251 SAS [n=246 FAS])

Discontinued (n=141 SAS)
• Adverse event (n=2); Lost to follow-up (n=12); W ithdrawal by 

patient (n=30); Lack of efficacy (n=20); Patient did not achieve 
treatment success after open-label lead-in phase (n=3); Other 
(n=9); Patient not clear or almost clear (PGA<2) after 
treatment of relapse (n=65).

Discontinued (n=153 SAS)
• Adverse event (n=1); Death (n=1); Lost to follow-up (n=14); 

W ithdrawal by patient (n=36); Lack of efficacy (n=16); Patient 
did not achieve treatment success after open-label lead-in 
phase (n=2); Other (n=13); Patient not clear or almost clear 
(PGA<2) after treatment of relapse (n=70).

Experienced at least one relapse (n=210 FAS) Experienced at least one relapse (n=237 FAS)

Randomized into maintenance phase (n=545 SAS [n=521 FAS]) 

Randomized in error* 
(n=24 [16 proactive and 8 reactive])

Completed (n=5) Discontinued (n=19)

*excluded from FAS
The SAS included all patients exposed to Cal/BD foam or vehicle foam following randomization. The FAS included all randomized patients who had treatment success at randomization.

 43% reduction in risk of experiencing a first relapse for patients 
in the proactive group compared to reactive group (hazard ratio, 
0.57; 95% confidence interval [CI], 0.47–0.69; p<0.001).

Figure 3. Time to first relapse

Proactive 
(N=256)

Reactive 
(N=265)

Median time to first relapse* 56 days 30 days

Trial design and treatments
Figure 1. Trial design

Screening 
& washout 

(up to 
4 weeks)

Maintenance phase
Follow-
up for 

8 weeks

1
0

2
4

3
8

4
12

5
16

6
20

7
24

8
28

9
32

10
36

11
40

12
44

13
48

14
52

15
56

FU1
58

FU2
60

FU3
64Visit

Week

Cal/BD foam once 
daily for 4 weeks*

Relapse (PGA ≥2) 

1:1 RandomizationBaseline
End of maintenance 

phase

Follow-
up for 

rebound

Adults with 
plaque 

psoriasis

* Success following 4 weeks of once daily flare medication was defined as PGA<2 (‘clear [0]’ or ‘almost clear’ [1]) 
** Patients re-started the twice-weekly maintenance according to the original randomization scheme. 

PGA<2**
PGA ≥2 Withdrawn

Open-
label

lead-in 
phase

Cal/BD foam 
daily for 
4 weeks

Proactive management: Cal/BD foam twice weekly for 52 weeks

Reactive management: vehicle foam twice weekly for 52 weeks

1.0

0.8

0.6

0.4

0.2

0.0
1 28 56 84 112 140 168 196 224 252 280 308 336 364

Days after randomizationP
ro

ba
bi

lit
y 

of
 h

av
in

g 
no

t h
ad

 re
la

ps
e 

ye
t

Number of patients with no relapse yet

Proactive
Reactive

256
265

219
198

128
73

100
40

83
32

75
25

65
17

47
15

41
11

36
8

34
8

31
7

31
6

24
5

Patients who did not achieve PGA<2 after 4 weeks of once-daily flare medication following relapse were withdrawn 
from the trial.

Treatment group
Proactive
Reactive


	Slide Number 1