Figure 1. Percentage of PASI 75, PASI 90, and PASI 100 responders receiving continuous tildrakizumab 100 mg (left) and 
200 mg (right) over time by baseline metabolic syndrome status in reSURFACE 1

MetS, metabolic syndrome; PASI, Psoriasis Area and Severity Index; TIL, tildrakizumab.

• In reSURFACE 2, the proportion of patients receiving tildrakizumab 100 mg who achieved PASI 75/90/100 were comparable 
between patients with vs without MetS at week 52 and remained comparable at weeks 100 and 148 (Figure 2)

Figure 2. Percentage of PASI 75, PASI 90 and PASI 100 responders receiving continuous tildrakizumab 100 mg (left) and 
200 mg (right) over time by baseline metabolic syndrome status in reSURFACE 2

MetS, metabolic syndrome; PASI, Psoriasis Area and Severity Index; TIL, tildrakizumab.

• In patients receiving tildrakizumab 200 mg in reSURFACE 2, those with MetS had numerically lower PASI 75 response rates at 
week 100 and week 148 relative to patients without MetS; PASI 90 and PASI 100 response rates at weeks 52, 100, and 148 were 
also lower in patients with MetS vs without MetS (Figure 2)

• At week 148, in both reSURFACE 1 (Figure 3) and reSURFACE 2 (Figure 4), overall PASI scores decreased from baseline 
 — In reSURFACE 1, the percentage decrease in median PASI scores in patients with vs without MetS was 89% vs 92% 

(tildrakizumab 100 mg) and 88% vs 91% (tildrakizumab 200 mg), respectively  
 — In reSURFACE 2, the percentage decrease in median PASI scores in patients with vs without MetS was 93% vs 96% 

(tildrakizumab 100 mg) and 84% vs 94% (tildrakizumab 200 mg), respectively 

Figure 3. Median absolute PASI scores over time in patients receiving A) tildrakizumab 100 mg and B) 
tildrakizumab 200 mg, stratified by metabolic syndrome status in reSURFACE 1

A)                     B)

MetS, metabolic syndrome; PASI, Psoriasis Area and Severity Index; TIL, tildrakizumab.

Figure 4. Median absolute PASI scores over time in patients receiving A) tildrakizumab 100 mg and B) 
tildrakizumab 200 mg, stratified by metabolic syndrome status in reSURFACE 2

A)                     B)

MetS, metabolic syndrome; PASI, Psoriasis Area and Severity Index; TIL, tildrakizumab.

CONCLUSIONS
• The efficacy of both tildrakizumab 100- and 200-mg doses was maintained over 148 weeks of the reSURFACE 1 and 2 

studies without evidence of reduced drug survival in patients with MetS and was comparable to that of patients without 
MetS

REFERENCES
1) Alberti KG, et al. Circulation. 2009;120(16):1640–5. 2) Fernandez-Armenteros JM, et al. J Eur Acad Dermatol Venereol. 2019;33(1):128–35. 3) Singh S, et al. PLoS One. 
2017;12(7):e0181039. 4) Langan SM, et al. J Invest Dermatol. 2012;132(3 Pt 1):556–62. 5) Talamonti M, et al. J Eur Acad Dermatol Venereol. 2018;32(10):1737–44. 6) Jacobi A, et 
al. Int J Dermatol. 2016;55(3):296–302. 7) Pinter A, et al. J Dermatolog Treat. 2019:1–7. 8) Reich K, et al. Lancet. 2017;390(10091):276–88. 9) National Institutes of Health. https://
www.nhlbi.nih.gov/files/docs/guidelines/atp3xsum.pdf; 2001 [accessed August 18, 2018]. 10) Lebwohl M. Presented at: AAD Annual Meeting 2019. 11) Leonardi C. Presented at: 
AAD Annual Meeting 2019. 12) Mehta N, et al. J Am Acad Dermatol. 2019;81(4 S1): AB131.

ACKNOWLEDGMENTS
We thank patients for their participation. The studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Analyses were funded 
by Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA. Editorial support was provided by Puneet Dang, PhD, of AlphaBioCom, LLC, and funded by Sun Pharmaceutical 
Industries, Inc.

DISCLOSURES
MGL is an employee of Mount Sinai, which receives research funds from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly and Co., Incyte, Janssen/
Johnson & Johnson, Kadmon, LEO Pharmaceuticals, MedImmune, Novartis, Pfizer, SciDerm, UCB, Ortho Dermatologics, and ViDac; and is a consultant for Allergan, Almirall, 
Arcutis, Avotres, BirchBioMed, Boehringer Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Dermavant, Encore, Inozyme, LEO Pharmaceuticals, Meiji, Menlo, 
Mitsubishi Pharma, Neuroderm, Pfizer, Promius/Dr. Reddy, Theravance Biopharma, and Verrica. NNM is a full-time employee of the US government and has received support in 
the form of grants to the NIH from AbbVie, Celgene, Janssen, and Novartis. ABG has current consulting/advisory board agreements with AbbVie; Allergan; Avotres Therapeutics; 
Beiersdorf; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Dermira; Eli Lilly and Co.; Incyte; Janssen; LEO Pharmaceuticals; Novartis; Reddy Labs; Sun Pharmaceutical 
Industries, Inc.; UCB; Valeant; and XBiotech; and has received research/educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, and XBiotech. AMM 
is an employee of Sun Pharmaceutical Industries, Inc.; and has individual shares in Johnson & Johnson, and as part of retirement account/mutual funds. JP is an employee 
of Sun Pharmaceutical Industries, Inc.; and has served as statistical consultant for Sun Pharmaceutical Industries, Inc.; and Kyowa Kirin Pharmaceutical Development. SJR is 
an employee of Sun Pharmaceutical Industries, Inc. MAM has received grants and/or honoraria as a consultant, investigator, and/or speaker for AbbVie, Abbott Labs, Amgen, 
Anacor, Boehringer Ingelheim, Celgene, Eli Lilly and Co., Janssen, LEO Pharmaceuticals, Merck, Novartis, Sienna, and UCB; and has been on an advisory board for AbbVie, 
Amgen, Boehringer Ingelheim, Eli Lilly and Co., Janssen, LEO Pharmaceuticals, and Sienna.

INTRODUCTION
• Metabolic syndrome (MetS) is a combination of common cardiometabolic abnormalities 

associated with an increased risk of cardiovascular disease and diabetes1 and has higher 
prevalence in patients with moderate to severe psoriasis compared with the overall 
population2-4

• In patients with psoriasis treated with anti-tumor necrosis factor or anti–interleukin (IL)-17 
agents, MetS may reduce the absolute Psoriasis Area and Severity Index (PASI) response 
and long-term drug survival5-7

• Tildrakizumab—a high-affinity, humanized, immunoglobulin G1κ, anti–IL-23p19 
monoclonal antibody—is approved in the US, Europe, and Australia for treatment of 
moderate to severe plaque psoriasis 

 — The efficacy of tildrakizumab was demonstrated in 2 phase 3 clinical studies, 
reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754)8 

 — Treatment with tildrakizumab significantly increased the proportion of patients with 
≥75%, ≥90%, and 100% improvement in PASI scores (PASI 75, PASI 90, and PASI 
100, respectively) and Physician’s Global Assessment 0/1 response rates compared 
with placebo8

• Previously, we evaluated tildrakizumab efficacy in patients meeting National Cholesterol 
Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria9 for MetS (including 
diminished high-density lipoprotein cholesterol and elevated blood pressure, body mass 
index [BMI], triglycerides, and glucose) after 1 year of treatment

 — MetS has a minimal effect on tildrakizumab efficacy10 and safety11 and there are no 
increases in cardiac events or worsening of diabetes in patients with MetS following 1 
year of tildrakizumab treatment12

OBJECTIVE
• To update the efficacy of tildrakizumab in psoriasis patients with vs without MetS with up 

to 3 years (148 weeks) of follow-up in reSURFACE 1 and reSURFACE 2

METHODS
Study design
• This post hoc analysis of the reSURFACE 1 and reSURFACE 2 phase 3, double-blind, 

randomized controlled studies included patients aged ≥18 years with moderate to severe 
chronic plaque psoriasis; full trial designs were published previously8

• Tildrakizumab 100 or 200 mg was administered at week 0, week 4, and every 12 weeks 
thereafter up to week 220/244 (reSURFACE 1/2) 

 — Additional patients in reSURFACE 2 received etanercept twice weekly to week 12 and 
once weekly to week 28

Table 1. Clinical definition of metabolic syndrome at baseline
Risk factor Defining level
BMIa >30 kg/m2

Triglycerides ≥150 mg/dL
HDL cholesterol
   Men
   Women

<40 mg/dL
<50 mg/dL

Blood pressure ≥130/≥85 mm Hg
Fasting glucose ≥110 mg/dL

aDiagnosis of metabolic syndrome was made when ≥3 risk factors were present. BMI was used as a surrogate for waist circumference.
BMI, body mass index; HDL, high-density lipoprotein.

Evaluations and assessments
• At baseline, metabolic syndrome was defined as the presence of ≥3 risk factors per the 

NCEP-ATP III criteria (Table 1)9 
• Data were collected from patients who continuously received tildrakizumab 100 or 200 mg
• Efficacy of tildrakizumab, stratified by MetS status, was determined by the proportion of 

patients achieving PASI 75/90/100 in each visit, and absolute and percent changes in 
median PASI scores from baseline to week 148 

• Missing data were imputed as nonresponse for PASI response rates and using last 
observation carried forward methodology for PASI scores

Tildrakizumab efficacy by metabolic syndrome status in psoriasis: Post hoc analysis of 3-year data from the phase 3 reSURFACE 1 and reSURFACE 2 studies
Mark G Lebwohl,1 Nehal N Mehta,2 Alice B Gottlieb,3 Alan M Mendelsohn,4 Jeff Parno,4 Stephen J Rozzo,4 M Alan Menter5
1Department of Dermatology, Mount Sinai Hospital, New York, NY, USA; 2National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA; 3Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA; 5Division of Dermatology, Baylor Scott & White, and Texas A&M College of Medicine, Dallas, TX, USA

RESULTS
• Of patients who continuously received tildrakizumab 100 (n = 124) and 200 mg (n = 147), 26 (21%) and 34 (23%), respectively had 

MetS in reSURFACE 1 
• In reSURFACE 2, 44 (21%) and 30 (19%) patients continuously receiving tildrakizumab 100 (n = 214) and 200 mg (n = 160), 

respectively, had MetS
• Baseline demographic and disease characteristics were similar between groups; patients with MetS had numerically higher mean 

baseline weight, BMI, and prevalence of cardiovascular disease and diabetes mellitus vs patients with no MetS (Table 2) 

Table 2. Patient demographics and disease characteristics by trial, treatment group and metabolic syndrome status

reSURFACE 1 reSURFACE 2

TIL 100 mg TIL 200 mg TIL 100 mg TIL 200 mg

Without 
MetS

(n = 98)

With
MetS

(n = 26)

Without 
MetS

(n = 113)

With
MetS

(n = 34)

Without 
MetS

(n = 170)

With
MetS

(n = 44)

Without 
MetS

(n = 130)

With
MetS

(n = 30)

Age, y 46.1 ± 14.0 49.1 ± 12.7 46.2 ± 13.5 50.7 ± 11.0 43.2 ± 13.2 45.9 ± 12.7 44.6 ± 13.2 48.7 ± 12.4

Sex, male, n (%) 65 (66.3) 18 (69.2) 80 (70.8) 19 (55.9) 120 (70.6) 34 (77.3) 82 (63.1) 23 (76.7)

Race, White, n (%) 64 (65.3) 21 (80.8) 67 (59.3) 27 (79.4) 156 (91.8) 41 (93.2) 118 (90.8) 29 (96.7)

Weight at baseline, kg 80.8 ± 18.1 106.0 ± 29.6 81.7 ± 17.5 112.0 ± 32.2 82.6 ± 17.0 106.9 ± 21.7 82.0 ± 17.8 108.2 ± 17.6

BMI, kg/m2 27.9 ± 6.0 35.6 ± 8.5 28.3 ± 5.8 38.5 ± 8.3 27.5 ± 5.3a 35.6 ± 6.1 27.3 ± 5.3 37.6 ± 9.8

Body surface area, % 29.4 ± 16.7 32.2 ± 16.6 32.6 ± 19.5 30.1 ± 19.4 34.1 ± 18.4 30.3 ± 18.9 31.4 ± 17.2 27.6 ± 12.9

Disease duration, y 17.2 ± 12.6 16.2 ± 12.3 16.6 ± 11.5 16.7 ± 12.9 16.1 ± 10.6 15.2 ± 11.2 18.0 ± 13.5 20.1 ± 14.8

Baseline PASI score 19.9 ± 7.1 20.5 ± 7.1 21.5 ± 9.3 20.6 ± 9.7 19.6 ± 6.9 20.8 ± 8.8 19.5 ± 7.2 19.2 ± 6.3

Baseline PGA score 3.3 ± 0.6 3.4 ± 0.6 3.4 ± 0.6 3.5 ± 0.6 3.3 ± 0.5 3.4 ± 0.6 3.3 ± 0.6b 3.4 ± 0.6

CV disorders, n (%) 14 (14.3) 17 (65.4) 31 (27.4) 16 (47.1) 29 (17.1) 17 (38.6) 27 (20.8) 16 (53.3)

Diabetes, n (%) 8 (8.2) 8 (30.8) 11 (9.7) 8 (23.5) 5 (2.9) 7 (15.9) 11 (8.5) 7 (23.3)

Psoriatic arthritis, n (%) 16 (16.3) 5 (19.2) 19 (16.8) 9 (26.5) 24 (14.1) 11 (25.0) 17 (13.1) 4 (13.3)

Response to >1 traditional 
systemic medicine, n (%)c 22 (44.9) 5 (71.4) 40 (65.6) 8 (57.1) 111 (65.3) 24 (54.6) 80 (61.5) 17 (56.7)

Prior exposure to biologic 
therapy for psoriasis, n (%) 16 (16.3) 8 (30.8) 20 (17.7) 7 (20.6) 23 (13.5) 5 (11.4) 17 (13.1) 7 (23.3)

Data provided as mean ± standard deviation unless otherwise indicated.
an = 169; bn = 129; cData not available for the missing patients in each group. 
BMI, body mass index; CV, cardiovascular; MetS, metabolic syndrome; PASI, Psoriasis Area and Severity Index; PGA, Physician’s Global Assessment; TIL, tildrakizumab.

• In reSURFACE 1, a total of 2 patients with MetS (both receiving tildrakizumab 100 mg [7.7%]) and 17 patients without MetS (n = 11 
[11.2%] receiving tildrakizumab 100 mg and n = 6 [5.4%] receiving tildrakizumab 200 mg) did not complete the study through week 148 

• In reSURFACE 2, 12 patients with MetS (n = 7 [15.9%] receiving tildrakizumab 100 and n = 5 [16.6%] receiving tildrakizumab 200 
mg) and 37 patients without MetS (n = 21 [12.6%] receiving tildrakizumab 100 mg and n = 16 [12.4%] receiving tildrakizumab 200 
mg) did not complete the study through week 148

 — The most frequent reason for discontinuation was withdrawal by patient
 — Two patients with MetS receiving tildrakizumab 200 mg withdrew due to an adverse event in reSURFACE 2

• In reSURFACE 1, the proportion of patients receiving tildrakizumab 100 mg and 200 mg who achieved PASI 75/90/100 were 
comparable between patients with vs without MetS at week 52 and remained comparable at weeks 100 and 148 (Figure 1)

Week

Without MetS (n = 170) With MetS (n = 44)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480
0

5

10

15

20

25

PA
S

I, 
M

ed
ia

n 
(Q

1,
 Q

3)

TIL 100 mg

0

5

10

15

20

25

PA
S

I, 
M

ed
ia

n 
(Q

1,
 Q

3)

TIL 200 mg

Week

Without MetS (n = 130) With MetS (n = 30)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480

Week

With MetS (n = 26)Without MetS (n = 98)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480
0

5

10

15

20

25

PA
S

I, 
M

ed
ia

n 
(Q

1,
 Q

3)

TIL 100 mg

Week

Without MetS (n = 113) With MetS (n = 34)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480

0

5

10

15

20

25

PA
S

I, 
M

ed
ia

n 
(Q

1,
 Q

3)

TIL 200 mg

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

86%

85%
76%

65%

71%

69%

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

76%

76%

81%

68%

74%

71%

0

20

40

60

80

100

Week

P
A

S
I9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

62%

50%

50%

38%

51%

42%

0

20

40

60

80

100

Week

P
A

S
I 9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

55%

47%

59%

41%

55%

47%

0

20

40

60

80

100

Week

P
A

S
I 1

00
r e

s p
on

de
rs

,%

Without MetS (n = 98) With MetS (n = 26)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

31%

31%
22%

27%

23%

27%

0

20

40

60

80

100

Week

P
A

S
I1

00
r e

s p
on

de
rs

,%

Without MetS (n = 113) With MetS (n = 34)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

35%

21%

31%

21%

27%

24%

TIL 100 mg TIL 200 mg

PASI 75

PASI 90

PASI 100

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

, %

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

86%

85%
76%

65%

71%

69%

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

76%

76%

81%

68%

74%

71%

0

20

40

60

80

100

Week

P
A

S
I9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

62%

50%

50%

38%

51%

42%

0

20

40

60

80

100

Week

P
A

S
I 9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

55%

47%

59%

41%

55%

47%

0

20

40

60

80

100

Week

P
A

S
I 1

00
r e

s p
on

de
rs

,%

Without MetS (n = 98) With MetS (n = 26)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

31%

31%
22%

27%

23%

27%

0

20

40

60

80

100

Week

P
A

S
I1

00
r e

s p
on

de
rs

,%

Without MetS (n = 113) With MetS (n = 34)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

35%

21%

31%

21%

27%

24%

TIL 100 mg TIL 200 mg

PASI 75

PASI 90

PASI 100

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,
%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

94%

86%

88%

77%

79%

73%

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,
%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

87%

87%

85%

73%

81%

63%

0

20

40

60

80

100

Week

P
A

S
I9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

79%

68%

66%

52%

60%

57%

0

20

40

60

80

100

Week

P
A

S
I 9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

66%

53%

68%

53%

58%

43%

0

20

40

60

80

100

Week

P
A

S
I 1

00
r e

s p
on

d
er

s ,
%

Without MetS (n = 170) With MetS (n = 44)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

38%

32% 29%

30%

32%

34%

0

20

40

60

80

100

Week

P
A

S
I 1

00
r e

s p
on

d
er

s ,
%

Without MetS (n = 130) With MetS (n = 30)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

36%

23%

38%

20%

32%

23%

TIL 100 mg TIL 200 mg

PASI 75

PASI 90

PASI 100

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,
%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

94%

86%

88%

77%

79%

73%

0

20

40

60

80

100

Week

P
A

S
I 7

5
r e

s p
on

de
rs

,
%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

87%

87%

85%

73%

81%

63%

0

20

40

60

80

100

Week

P
A

S
I9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

79%

68%

66%

52%

60%

57%

0

20

40

60

80

100

Week

P
A

S
I 9

0
r e

s p
on

de
rs

,%

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

66%

53%

68%

53%

58%

43%

0

20

40

60

80

100

Week

P
A

S
I 1

00
r e

s p
on

d
er

s ,
%

Without MetS (n = 170) With MetS (n = 44)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

38%

32% 29%

30%

32%

34%

0

20

40

60

80

100

Week

P
A

S
I 1

00
r e

s p
on

d
er

s ,
%

Without MetS (n = 130) With MetS (n = 30)

4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148

36%

23%

38%

20%

32%

23%

TIL 100 mg TIL 200 mg

PASI 75

PASI 90

PASI 100

Presented at Fall Clinical Dermatology Conference for PAs & NPs 2020, April 3–5, Orlando, FL, USA