Patients With Psoriasis Treated With Brodalumab: A Pooled Post Hoc Analysis of a Marker of Liver  
Inflammation in Individuals With Potential Indicators of Early Nonalcoholic Fatty Liver Disease

Ronald Prussick, MD1; Mark Lebwohl, MD2; Nadege Gunn, MD3; Susan Harris, MS4; Jason Vittitow, PhD4; Zeev Heimanson, PharmD4; Abby Jacobson, MS, PA-C5; Robert J. Israel, MD4
1George Washington University, Washington, DC; 2Mount Sinai Hospital, New York, NY; 3Austin Gastroenterology, Austin, TX; 4Salix Pharmaceuticals, Bridgewater, NJ; 5Ortho Dermatologics, Bridgewater, NJ

INTRODUCTION
• Nonalcoholic fatty liver disease (NAFLD) is a broad term that includes a range of liver diseases 

categorized via imaging or histology in patients with intrahepatic fat accumulation without 
substantial alcohol consumption (eg, nonalcoholic fatty liver; nonalcoholic steatohepatitis)1

 – NAFLD is intimately linked to metabolic syndrome and is commonly associated with 
comorbidities, such as diabetes mellitus, dyslipidemia, and obesity1,2

• Interestingly, patients with psoriasis are at increased risk for NAFLD compared with patients 
without psoriasis3,4

 – In one population-based cohort study, patients ≥55 years of age with psoriasis were 70% more 
likely to have NAFLD after adjusting for confounding risk factors (adjusted odds ratio, 1.7;  
95% confidence interval, 1.2–2.5)4

 – Published cohort data have suggested that the overall prevalence of NAFLD in adults with 
psoriasis approaches 50%5 to 60%6

• Although the relationship between psoriasis and NAFLD has not been fully elucidated, chronic low-
grade systemic inflammation plays a key role in psoriasis and NAFLD pathophysiologies7,8

• Current guidelines from the American Association for the Study of Liver Diseases do not 
recommend routine screening for NAFLD in high-risk groups in nonhepatology settings1

 – Therefore, the possible presence of NAFLD and potential harmful versus beneficial impact of 
psoriasis medications on the liver in patients with NAFLD should be carefully considered4

• Brodalumab is an anti–interleukin (IL)-17 receptor A monoclonal antibody indicated for moderate to 
severe plaque psoriasis in adults who have failed or lost response on other systemic therapies9

 – Binding to this receptor inhibits IL-17–mediated release of pro-inflammatory cytokines and 
chemokines

• Given the potential role chronic low-grade systemic inflammation may play in the relationship 
between psoriasis and NAFLD,7,8 a post hoc exploratory analysis was conducted to examine 
changes in C-reactive protein (CRP), a systemic marker of chronic inflammation,10 in patients with 
psoriasis and early indicators of NAFLD who were treated with brodalumab

OBJECTIVE
• Post hoc analysis to examine changes in CRP levels in patients with psoriasis with an aspartate 

aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio suggestive of liver fibrosis or who 
had decreases in liver test parameters while taking brodalumab in clinical trials

METHODS
• Exploratory analysis of data pooled from 4 randomized, double-blind, placebo-controlled trials11-13

• Included patients who received ≥1 dose of subcutaneous brodalumab 210 mg every 2 weeks, 
ustekinumab per the US indicated dosing regimen14 (in 2 trials13), or placebo

• Patients were subgrouped post hoc (ie, not prespecified outcomes) by various indicators to 
determine liver disease (eg, baseline AST/ALT ratio [≥0.9 suggestive of mild to more advanced 
fibrosis15,16] and maximum postbaseline AST and ALT grade decreases during treatment [based on 
common terminology criteria for adverse events])

• Findings were summarized using descriptive statistics (eg, mean and standard deviation)

RESULTS
• Overall, 1496 patients received ≥1 dose of brodalumab 210 mg every 2 weeks, 613 patients 

received ≥1 dose of ustekinumab, and 879 patients received ≥1 dose of placebo in the  
4 trials (Table 1)
 – 802 patients in the brodalumab group, 339 in the ustekinumab group, and 474 in the placebo 

group had an AST/ALT ratio ≥0.9

Table 1. Demographics and Baseline Characteristics (Overall Pooled Population)

Parameter

Brodalumab  
210 mg q2w  

(n=1496)
Ustekinumab 

(n=613)
Placebo 
(n=879)

Age, y, mean (SD)
Range

45.0 (12.9)
18–75

45.1 (13.1)
18–75

44.6 (12.9)
18–86*

Male, n (%) 1037 (69.3) 417 (68.0) 607 (69.1)

Race, white, n (%) 1351 (90.3) 551 (89.9) 799 (90.9)

Psoriasis duration, y, mean (SD) 18.6 (12.3) 18.5 (12.2) 18.5 (12.0)

PASI score, mean (SD)
Range

20.2 (8.0)
12–72

20.0 (8.4)
12–60

20.0 (8.2)
12–66

*2 patients were >75 years of age. 
PASI = Psoriasis Area Severity Index; q2w = every 2 weeks; SD = standard deviation.

• For the subgroup of patients with a baseline AST/ALT ratio of ≥0.9 to <1.4, a larger mean numeric 
decrease from baseline in CRP level was observed for patients treated with brodalumab and 
ustekinumab compared with placebo after 12 weeks of treatment (Table 2; Figure 1)

Table 2. CRP Levels in Patients Subgrouped by Baseline AST/ALT Ratio

Assessment
Brodalumab  
210 mg q2w Ustekinumab Placebo

Baseline AST/ALT ratio of ≥0.9 to <1.4

Baseline CRP level, mg/L
Mean (SD)

n=607
6.4 (11.8)

n=264
4.9 (5.4)

n=361
5.7 (9.2)

Week 12 CRP level, mg/L
Mean (SD)

n=599
5.2 (10.9)

n=259
4.2 (5.3)

n=343
5.3 (12.7)

Change from baseline at Week 12 CRP level, mg/L
Mean (SD)

n=587 
-1.2 (13.1)

n=255 
-0.7 (5.4)

n=341 
-0.3 (11.7)

Baseline AST/ALT ratio ≥1.4

Baseline CRP level, mg/L
Mean (SD)

n=178
6.6 (12.6)

n=69
5.6 (9.8)

n=109
6.2 (11.9)

Week 12 CRP level, mg/L
Mean (SD)

n=176
4.6 (9.1)

n=64
4.1 (9.6)

n=103
6.5 (9.6)

Change from baseline at Week 12 CRP level, mg/L
Mean (SD)

n=174 
-2.0 (11.6)

n=63 
-1.7 (7.4)

n=102 
+0.2 (11.8)

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CRP = C-reactive protein; q2w = every 2 weeks; SD = standard deviation.

• Similarly, for patients with an AST/ALT ratio of ≥1.4, a larger mean numeric decrease from baseline 
in CRP level was observed for patients treated with brodalumab or ustekinumab compared with 
placebo after 12 weeks of treatment (Table 2; Figure 1)

Figure 1. Change From Baseline in CRP Levels at Week 12, by Baseline Liver 
Function Parameter AST/ALT Ratio

0.5

0

-0.5

-1

-1.5

-2

-2.5

Baseline AST/ALT Ratio ≥0.9 to <1.4 Baseline AST/ALT Ratio ≥1.4 

C
h

a
n

g
e

 F
ro

m
 B

a
s
e

lin
e

 
in

 C
R

P
 L

e
ve

l (
m

g
/L

) 

Brodalumab Ustekinumab Placebo

-1.2

-2.0

-0.7

-1.7

-0.3

0.2

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CRP = C-reactive protein.

• During 12 weeks of treatment, a larger numeric decrease from baseline in CRP levels was 
observed in patients with any decrease in AST grade, ALT grade, or both in brodalumab and 
ustekinumab groups versus placebo (Table 3; Figure 2)

Table 3. CRP Levels in Patients With Any Decrease in AST Grade, ALT Grade, or 
Both During 12 Months of Treatment

Assessment
Brodalumab 
210 mg q2w Ustekinumab Placebo

Patients with any AST decrease

Baseline CRP level, mg/L
Mean (SD)

n=62
6.7 (8.6)

n=20
2.6 (2.3)

n=26
6.4 (9.9)

Week 12 CRP level, mg/L
Mean (SD)

n=58
4.1 (5.5)

n=19
1.6 (1.9)

n=25
7.3 (13.1)

Change from baseline at Week 12 CRP level, mg/L
Mean (SD)

n=57 
-2.2 (6.0)

n=19 
-0.8 (2.1)

n=25 
+1.2 (13.6)

Patients with any ALT decrease

Baseline CRP level, mg/L
Mean (SD)

n=61
6.4 (7.8)

n=25
9.3 (34.6)

n=30
5.5 (9.6)

Week 12 CRP level, mg/L
Mean (SD)

n=58
4.7 (6.4)

n=22
5.0 (15.2)

n=31
5.5 (8.6)

Change from baseline at Week 12 CRP level, mg/L
Mean (SD)

n=58 
-1.6 (6.0)

n=22 
-5.2 (21.8)

n=30 
+0.1 (5.6)

Patients with both AST and ALT decrease

Baseline CRP level, mg/L
Mean (SD)

n=23
6.7 (9.0)

n=9
2.1 (1.9)

n=6
3.4 (3.3)

Week 12 CRP level, mg/L
Mean (SD)

n=22
3.3 (5.0)

n=9
1.0 (1.1)

n=6
3.1 (3.5)

Change from baseline at Week 12 CRP level, mg/L
Mean (SD)

n=22 
-3.4 (6.6)

n=9 
-1.1 (1.5)

n=6 
-0.4 (2.7)

ALT = alanine aminotransferase; AST = aspartate aminotransferase CRP = C-reactive protein; q2w = every 2 weeks; SD = standard deviation.

Figure 2. Change From Baseline in CRP Levels in Patients With Decreases in ALT 
and/or AST After 12 Weeks of Treatment

C
h

a
n

g
e

 F
ro

m
 B

a
s
e

lin
e

 in
C

R
P

 L
e

ve
l (

m
g

/L
) 

2

1

0

-1

-2

-3

-4

-5

-6

Any Decrease in AST Any Decrease in ALT Decrease in AST and ALT

Brodalumab Ustekinumab Placebo

-2.2
-1.6

1.2

-5.2

-3.4

-1.1
-0.4

0.1

-0.8

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CRP = C-reactive protein.

CONCLUSIONS
• The post hoc observation of a decrease in CRP levels in patients subgrouped by AST and ALT 

suggests that brodalumab may have activity in reducing liver inflammation and early indicators 
of NAFLD; further research is warranted

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ACKNOWLEDGMENTS: The studies were sponsored by Amgen/AstraZeneca and post hoc analyses were supported 
by Ortho Dermatologics. Technical editorial and medical writing support were provided under the direction of the authors  
by Mary Beth Moncrief, PhD, Synchrony Medical Communications, LLC, West Chester, PA. Funding for this support was 
provided by Ortho Dermatologics.

DISCLOSURES: RP reports serving on the speakers’ bureau for AbbVie Inc., Celgene Corp., Janssen Pharmaceuticals, 
Inc., and Pfizer Inc.; serving as a consultant for Immunotec Inc.; and receiving research funding from Celgene Corp. 
and Novartis AG. ML reports being an employee of Mount Sinai, which receives research funds from AbbVie Inc., 
Bausch Health Companies Inc., Boehringer Ingelheim GmbH, Celgene Corp., Eli Lilly and Company, Incyte Corp., 
Janssen Pharmaceuticals, Inc./Johnson & Johnson, LEO Pharma Inc., MedImmune, Novartis AG, Pfizer Inc., SCIderm 
GmbH, UCB, Inc., and Vidac Pharma; and serving as a consultant for Allergan plc, Aqua Pharmaceuticals, Arcutis 
Pharmaceuticals, Boehringer Ingelheim GmbH, LEO Pharma Inc., Menlo Therapeutics, Promius Pharma, LLC, and 
Verrica Pharmaceuticals. NG reports serving as a consultant for AbbVie Inc., Dova Pharmaceuticals, Gilead Sciences, 
Inc., Intercept Pharmaceuticals, Inc., and Salix Pharmaceuticals; and participating in research sponsored by Axcella 
Health Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, CymaBay Therapeutics, Genfit, Gilead Sciences, 
Inc., HighTide Therapeutics Inc., Luminist, Madrigal Pharmaceuticals, Inc., NGM Biopharmaceuticals, Inc., Novo 
Nordisk, Pfizer Inc., Progenity, Inc., and Second Genome, Inc. SH, JV, ZH, and RJI report being employees of Salix 
Pharmaceuticals or its affiliates. AJ reports being an employee of Ortho Dermatologics.

2019 Fall Clinical Dermatology Conference (FCDC) • October 17–20, 2019 • Las Vegas, NV