Anais Brasileiros de Dermatologia 2025;100(2):260---271

Anais Brasileiros de
Dermatologia
www.anaisdedermatologia.org.br

ORIGINAL ARTICLE

Efficacy and safety of risankizumab versus

methotrexate in patients with moderate-to-severe
plaque psoriasis: results from IMMbrace, a randomized,
double-blind, phase 3 study with an open-label
extension period in Brazil夽
Tania F. Cestari a,∗ , Cacilda da Silva Souza b , Luna Azulay-Abulafia c ,
Ricardo Romiti d , André V.E. Carvalho e , Caio César Silva de Castro f ,
Sílvio Alencar Marques g , João Roberto Antonio h , Lincoln Fabrício i ,
Ahmed M. Soliman j , Tianshuang Wu j , Ranjeeta Sinvhal j ,
Vassilis Stakias j , Alexandra P. Song j , Jasmina Kalabic k , Naomi Martin j,l
,
Luiza Keiko Matsuka Oyafuso m

a
Department of Dermatology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS,
Brazil
b
Division of Dermatology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
c
Instituto de Dermatologia e Estética do Rio de Janeiro, Rio de Janeiro, Brazil
d
Department of Dermatology, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil
e
Department of Dermatology, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
f
Discipline of Dermatology, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil
g
Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual
Paulista, Botucatu, SP, Brazil
h
Discipline of Dermatology, Faculdade Estadual de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil
i
Dermaology Service, Hospital Universitário Evangélico Mackenzie de Curitiba, Curitiba, PR, Brazil
j
AbbVie Inc., North Chicago, Illinois, United States
k
AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany
l
In memoriam
m
Department of Dermatology, Faculdade de Medicina de ABC, São Paulo, SP, Brazil

夽 Study conducted at the Instituto de Dermatologia e Estética do Brasil, Rio de Janeiro, RJ, Brazil; Fundação Faculdade Regional de

Medicina de São Jose do Rio Preto, São Jose do Rio Preto, SP, Brazil; Hospital das Clinicas, Faculdade de Medicina de Ribeirão Preto ---,
Universidade de São Paulo, Ribeirão Preto, SP, Brazil; Hospital Moinhos de Vento, Porto Alegre, RS, Brazil; Hospital de Clinicas de Porto
Alegre, Porto Alegre, RS, Brazil; Hospital de Clinicas, Universidade Estadual de Campinas, Campinas, SP, Brazil; Unidade de Pesquisa Clinicia
da Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil; Faculdade de Medicina do ABC, Santo André, SP, Brazil; Hospital das Clinicas,
Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil; PUC Trials-Nucleo de Pesquisa Clínica da Escola de Medicina da
PUCPR, Curitiba, PR, Brazil; CETI --- Centro de Estudos em Terapias Inovadoras, Curitiba, PR, Brazil.
∗ Corresponding author.

E-mail: [email protected] (T.F. Cestari).

https://doi.org/10.1016/j.abd.2024.08.002
0365-0596/© 2024 Published by Elsevier España, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article
under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
 Anais Brasileiros de Dermatologia 2025;100(2):260---271

Received 6 June 2024; accepted 19 August 2024

Available online 7 December 2024

KEYWORDS
Abstract:
Methotrexate; Background: Psoriasis, a chronic, inflammatory skin disease, requires long-term therapy.
Psoriasis; Risankizumab is a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits
Risankizumab interleukin 23 by binding to its p19 subunit.
Objective: The authors assessed the efficacy and safety of risankizumab compared with
methotrexate in adults with moderate-to-severe plaque psoriasis.
Methods: IMMbrace was a phase 3, multicenter, randomized, double-blind, double-dummy,
active-controlled study. Patients received subcutaneous risankizumab 150 mg at weeks 0, 4,
and 16 plus oral placebo weekly, or oral methotrexate 5 mg weekly (with dose escalation up
to 25 mg based on response and tolerability) plus subcutaneous placebo at weeks 0, 4, and
16. Primary efficacy endpoints were the proportions of patients who achieved ≥ 90% improve-
ment in Psoriasis Area and Severity Index (PASI90) and static Physician’s Global Assessment of
clear/almost clear (sPGA 0/1) at week 28. Safety was also assessed.
Results: Among 98 patients randomized (risankizumab, n = 50; methotrexate, n = 48), 95 com-
pleted the double-blind period. At week 28, significantly higher proportions of patients treated
with risankizumab versus methotrexate achieved PASI90 (84.0% vs. 35.4%; p < 0.001); sPGA 0/1
was achieved by 90.0% and 64.6% of patients in the risankizumab and methotrexate groups
(p ≤ 0.001). Risankizumab efficacy was maintained throughout week 112. Adverse event rates
were similar in the two groups.
Study limitations: The sample size was small due to the difficulty of recruiting patients without
methotrexate use.
Conclusions: Risankizumab demonstrated superior efficacy over methotrexate at week 28; effi-
cacy was maintained, and no new safety findings were observed through week 112.
© 2024 Published by Elsevier España, S.L.U. on behalf of Sociedade Brasileira de Dermatologia.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/
by/4.0/).

Introduction Risankizumab, a humanized immunoglobulin G1 mon-

oclonal antibody that binds to the p19 subunit to
Psoriasis is a chronic, immune-mediated inflammatory skin specifically inhibit interleukin 23,8 has demonstrated supe-
disorder causing red, scaly plaques and is associated with rior clinical efficacy compared with placebo at week
reduced quality of life.1,2 The estimated prevalence in 169---11 and against other psoriasis treatments, includ-
Brazil ranges from 1.1%---1.5%, with the highest indica- ing ustekinumab,10 adalimumab,12 and secukinumab.13
tors in the South and Southeast regions.3 The management Risankizumab is approved in Brazil (September 2020) and
of moderate-to-severe psoriasis includes controlling the many other countries to treat adult patients with moderate-
disease activity while minimizing treatment-related side to-severe plaque psoriasis.14 However, to date, no clinical
effects. Methotrexate has been widely used as a sys- studies have compared risankizumab with traditional sys-
temic therapy and has been the standard of care for temic agents such as methotrexate. Here, the authors
psoriasis management in Brazil for decades; however, report results from the first phase 3b head-to-head trial
methotrexate is associated with various complications, comparing the clinical safety and efficacy of risankizumab
including gastrointestinal, hepatic, renal, and hematopoi- with methotrexate in adults with moderate-to-severe
etic abnormalities.4---6 A growing understanding of the plaque psoriasis following the approval of risankizumab in
disease pathogenesis has led to newer, target-specific bio- Brazil.
logic agents, including interleukin 23 antagonists.7

261
 T.F. Cestari, C.S. Souza, L. Azulay-Abulafia et al.

Figure 1 Study design. MTX, methotrexate; PASI90; ≥90% improvement in Psoriasis Area and Severity Index; PBO, Placebo; PO, by
mouth; q12 weeks, every 12-weeks; RZB, risankizumab; SC, subcutaneous; sPGA 0/1, static Physician’s Global Assessment of clear
or almost clear. a Oral MTX doses were also adjusted due to patient-reported symptoms, findings at physical examination, reported
adverse events, and/or changes in clinical laboratory profiles, as deemed appropriate by the study investigators. b Starting at week
8, patients who did not achieve PASI90 or Spga 0/1 had their MTX dose increased by 5 mg (up to 20 mg per week) through week 15.
c
Starting at week 16, patients who did not achieve PASI90 or sPGA 0/1 had their MTX dose increased by 5 mg (up to 25 g per week)
through week 27.

Methods double-dummy, active-controlled clinical trial that com-

pared the efficacy and safety of subcutaneous risankizumab
Patients with oral methotrexate in patients with moderate-to-severe
plaque psoriasis. The study was conducted at 11 sites
located in Brazil. The study design included a 30-day screen-
Eligible patients were adults aged ≥ 18 years with a ≥
ing period, a 28-week double-blind treatment period, and
6-month history of moderate-to-severe plaque psoriasis,
an 84-week open-label treatment period (Fig. 1). In the
defined as ≥ 10% body surface area involvement; Psoria-
double-blind period, patients were randomized 1:1 into two
sis Activity and Severity Index (PASI) of ≥ 12; and static
treatment groups to receive (in a double-dummy design)
Physician Global Assessment (sPGA) score of ≥ 3. Patients
either Risankizumab 150 mg as subcutaneous injections at
were candidates for treatment with methotrexate accord-
weeks 0, 4, and 16 plus placebo capsules by mouth weekly, or
ing to local labeling and were without clinically significant
methotrexate capsules by mouth once weekly plus placebo
findings on chest X-rays. Patients were ineligible to enroll
injections at weeks 0, 4, and 16 (Fig. 1). Methotrexate
if they had non-plaque forms of psoriasis (including gut-
dosing started at 5 mg and could be increased to 25 mg
tate, erythrodermic, or pustular); drug-induced psoriasis;
based on clinical response and tolerability. Investigators
evidence of chronic or relevant acute infections includ-
determined all methotrexate dosage adjustments (with-
ing HIV, viral hepatitis, and/or tuberculosis; an active or
holding, reducing, or increasing) based on patient-reported
suspected malignancy or history of malignancy within 5
symptoms, findings on physical examination, adverse events
years before screening; any other relevant medical condi-
(AEs), and/or changes in clinical laboratory profiles. From
tions (e.g., chronic alcohol or drug abuse, organ transplant,
week 28, patients continuing in the study received open-
abnormal clinical laboratory values, history of hypersensi-
label Risankizumab 150 mg every 12 weeks through week 100
tivity to a systemically administered biologic therapy); or
(Open-Label Extension [OLE] period). The last study visit was
active ongoing inflammatory diseases that might confound
at week 112; a follow-up telephone call occurred 20 weeks
study evaluations according to the investigator’s judgment.
after the final subcutaneous injection or 4 weeks after the
Women of childbearing potential and all men were required
final oral administration, whichever was later.
to use contraception during the study and for at least 20
The study was conducted in accordance with Good
weeks (for women) or 3 months (for men) after the last dose
Clinical Practice guidelines as defined by the Interna-
of methotrexate/methotrexate placebo.
tional Council for Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use guidelines, the Dec-
Study design and treatment laration of Helsinki, and all applicable guidelines and
regulations governing clinical study conduct; all patients
The IMMbrace study (ClinicalTrials.gov; NCT03219437) provided written informed consent. An independent ethics
was a phase 3b, multicenter, randomized, double-blind, committee/institutional review board ensured the study’s

262
 Anais Brasileiros de Dermatologia 2025;100(2):260---271

Figure 2 Patient disposition. MTX, Methotrexate; RZB, Risankizumab.

ethical, scientific, and medical appropriateness before Safety

the study was conducted and approved all relevant Safety evaluations, including monitoring Treatment-
documentation. Emergent AEs (TEAEs), analyzing results from standard
laboratory tests, performing physical examinations, and
conducting vital sign measurements, were performed
Assessments throughout the study and findings were tabulated using
Medical Dictionary for Regulatory Activities system organ
Efficacy class and preferred terms (version 24.0).
The ranked primary efficacy endpoints were achievement
of ≥ 90% improvement from baseline in PASI (PASI90) and
sPGA of clear or almost clear (sPGA 0/1) at week 28. The Statistical analysis
ranked secondary efficacy endpoints (all assessed at week
28) were achievement of 100% improvement from baseline A sample size of 100 patients was needed to achieve more
in PASI (PASI100), sPGA of clear (sPGA0), ≥ 75% improve- than 95% power to detect the difference of 40% between
ment from baseline in PASI (PASI75), change from baseline risankizumab and methotrexate. Data were analyzed using
in European Quality of Life 5 Dimensions (EQ-5D-5L) index SAS statistical software version 9.4 (SAS Institute Inc.,
score, and achievement of a ≥ 0.1-point increase (Mini- Cary, NC, USA). All efficacy analyses were performed in
mal Clinically Important Difference [MCID]) from baseline in the intent-to-treat population, which included all random-
EQ-5D-5L index score. Using post hoc analyses, the authors ized patients. The ranked primary and secondary efficacy
evaluated change from baseline in EQ-5D-5L index score endpoints were analyzed in a hierarchical order using
and achievement of MCID from baseline in EQ-5D-5L index two-sided tests with a type 1 error of 0.05. Categorical
score among patients with a baseline EQ-5D-5L index score endpoints were analyzed using the Cochran-Mantel-Haenszel
≤ 0.9 at week 28. An additional endpoint was the pro- test stratified by the study center; missing data were
portion of patients achieving a Dermatology Life Quality imputed using non-responder imputation for the primary
Index score of 0 (DLQI 0 [no effect on patient’s life]) at analysis and non-responder imputation incorporating mul-
week 28. tiple imputations to handle missing data due to COVID-19

263
 T.F. Cestari, C.S. Souza, L. Azulay-Abulafia et al.

Table 1 Baseline demographics and characteristics.

Parameter RZB 150 mg MTX 5---25 mg

(n = 50) (n = 48)
Age, years, mean (SD) 48.3 (14.6) 48.2 (14.4)
Male, n (%) 35 (70.0) 32 (66.7)
Race, n (%)
White 46 (92.0) 38 (79.2)
Black 3 (6.0) 9 (18.8)
Multiplea 1 (2.0) 1 (2.1)
Hispanic or Latino, n (%) 46 (92.0) 45 (93.8)
BMI, kg/m2 , n (%)
< 25 6 (12.0) 7 (14.6)
25 to < 30 19 (38.0) 17 (35.4)
≥ 30 25 (50.0) 24 (50.0)
Duration of plaque psoriasis, years, mean (SD) 16.6 (13.2) 12.4 (10.5)
BSA affected by psoriasis, mean (SD) 30.2 (16.9) 34.3 (17.5)
Median (range) 25.0 (10.0---70.0) 29.5 (10.0---80.0)
PASI, mean (SD) 20.0 (7.9) 22.1 (7.4)
Median (range) 15.3 (12.1---41.4) 19.4 (13.5---46.0)
sPGA, n (%)
Moderate (score of 3) 43 (86.0) 39 (81.3)
Severe (score of 4) 7 (14.0) 9 (18.8)
EQ-5D-5L index score, mean (SD) 0.8 (0.2) 0.7 (0.3)
Median (range) 0.9 (0.1---1.0) 0.9 (-0.2---1.0)
DLQI, mean (SD) 12.3 (7.0) 13.1 (7.3)
Median (range) 12.0 (0---27.0) 13.5 (0---29.0)

BMI, Body Mass Index; BSA, Body Surface Area; DLQI, Dermatology Life Quality Index; EQ-5D-5L, European Quality of Life 5 Dimensions;
MTX, Methotrexate; PASI, Psoriasis Area and Severity Index; RZB, Risankizumab; sPGA, Static Physician’s Global Assessment.
a Any patients identifying as more than one race were categorized as multiple.

for the long-term analysis. Continuous endpoints were ana- were male. At baseline, patients had a mean PASI of 21.0
lyzed using a one-way analysis of covariance with treatment, and a mean EQ-5D-5L index score of 0.8%; 83.7% and
study site, and baseline value in the model; the last- 16.3% of patients had moderate and severe sPGA scores,
observation-carried-forward method was used to impute respectively.
missing data. Safety was analyzed in all patients random-
ized at baseline who received at least one dose of the study
drug. Efficacy

Primary analysis
Results After 28 weeks of treatment, significantly higher propor-
tions of patients treated with risankizumab achieved the
Patients primary efficacy endpoints compared with patients treated
with methotrexate (Fig. 3). PASI90 was achieved by 84.0%
This study was conducted from July 2018 through November and 35.4% of patients in the risankizumab and methotrexate
2021. A total of 11 sites enrolled 104 patients in this study; groups at week 28 (p ≤ 0.001), and sPGA 0/1 was achieved
however, one study site was closed for non-compliance with in 90.0% and 64.6% of patients in the risankizumab and
the protocol, and all patients enrolled at this site were methotrexate groups (p ≤ 0.001). A significantly greater pro-
excluded from efficacy and safety analyses. Of 98 patients portion of patients receiving risankizumab also achieved
randomized to receive risankizumab (n = 50) or methotrex- secondary endpoints of PASI100, sPGA0, and PASI75 at
ate (n = 48) at compliant sites, 95 (96.9%) completed the week 28 compared with patients receiving methotrexate
double-blind period, and 92 (95.8%) completed the OLE (Fig. 4).
period (Fig. 2). Six patients discontinued the study, including Improvements in patient-reported outcomes measuring
four in the risankizumab group (two due to an AE and two health-related quality of life (HRQoL) were observed in
due to other reasons) and two in the methotrexate group both risankizumab and methotrexate groups. By week
(one due to an AE and one due to other reasons). Demo- 28 of treatment, changes in EQ-5D-5L index scores and
graphic and baseline disease characteristics were generally proportion of patients achieving the MCID in EQ-5D-5L
similar across treatment groups (Table 1). The mean (SD) index scores numerically increased from baseline in both
patient age was 48.2 (14.4) years and 68.4% of patients groups with no significant differences in outcomes between

264
 Anais Brasileiros de Dermatologia 2025;100(2):260---271

Figure 3 Primary clinical efficacy results. Highlighted data at week 28 denote primary efficacy endpoints. Non-responder impu-
tation was used through week 28; non-responder imputation incorporating multiple imputation for data missing due to COVID-19
was used after week 28. MTX, Methotrexate; PASI90, ≥ 90% improvement in Psoriasis Area and Severity Index; RZB, Risankizumab;
sPGA 0/1, static Physician’s Global Assessment of clear or almost clear. *p ≤ 0.05, **p ≤ 0.01, ***p < 0.001 versus MTX. a Response
rates at later timepoints (after week 40) may be partially impacted by a higher frequency of missing data in the RZB group versus
the MTX/RZB group.

patients treated with risankizumab versus methotrexate Long-term open-label extension analysis
(Fig. 5). Among patients with baseline EQ-5D-5L index PASI and sPGA responses were generally sustained through
scores ≤0.9, the least squares mean change from baseline week 112 among patients who continued risankizumab treat-
(95% CI) in EQ-5D-5L index score at week 28 was similar in ment in the OLE period; the numbers of patients with
both groups (0.16 [0.10, 0.23] with risankizumab and 0.17 missing data during the OLE period are shown in Supple-
[0.11, 0.23] with methotrexate). In the post hoc analysis mentary Table S1. Improvements in PASI and sPGA outcomes
evaluating patients with baseline EQ-5D-5L index scores were observed from weeks 28 to 112 among patients who
≤0.9, the authors observed that the proportion of patients were initially randomized to methotrexate in the double-
achieving the MCID in EQ-5D-5L index scores at week 28 was blind period and then switched to risankizumab in the OLE
numerically greater, but not significantly different, in the period. The EQ-5D-5L index score response rates generally
risankizumab group versus the methotrexate group (61.5% remained stable through 112 weeks of therapy, regardless of
vs. 54.5%). At week 28, a significantly greater propor- the treatment group. From weeks 28 to 112, DLQI 0 response
tion of patients achieved DLQI 0 in the risankizumab rates remained stable among patients receiving continuous
group versus patients in the methotrexate group risankizumab and increased among patients who switched
(Supplementary Fig. S1). from methotrexate to risankizumab.

265
 T.F. Cestari, C.S. Souza, L. Azulay-Abulafia et al.

Figure 4 Ranked secondary clinical efficacy results. Highlighted data at week 28 denote ranked secondary efficacy endpoints.
Non-responder imputation was used through week 28; non-responder imputation incorporating multiple imputation for data missing
due to COVID-19 was used after week 28. MTX, methotrexate; PASI75/100, ≥ 75%/ ≥ 100% improvement in Psoriasis Area and Severity
Index; RZB, risankizumab; sPGA0, static Physician’s Global Assessment of clear. *p ≤ 0.05, **p ≤ 0.01, ***p < 0.001 versus MTX.

266
 Anais Brasileiros de Dermatologia 2025;100(2):260---271

Figure 5 Ranked secondary quality-of-life efficacy results. Highlighted data at week 28 denote ranked secondary efficacy end-
points. MCID was defined as ≥0.1 increase in EQ-5D-5L from baseline. EQ-5D-5L, European Quality of Life 5 Dimensions; LS, least
squares; MCID, Minimal Clinically Important Difference; MTX, Methotrexate; RZB, Risankizumab. a Last-observation-carried-forward
imputation was used. b Non-responder imputation was used through week 28; non-responder imputation incorporating multiple
imputation for data missing due to COVID-19 was used after week 28.

Safety ate to risankizumab, the safety profile of risankizumab

remained consistent, and TEAE rates were stable with long-
During the double-blind period, the proportion of patients term risankizumab treatment. Rates of TEAEs of safety
with TEAEs was slightly higher in the methotrexate treat- interest were generally low in both groups, and there
ment group (83.3%) than in the risankizumab group (77.6%; were no serious hypersensitivity reactions. In the group
Table 2). However, TEAE profiles were generally similar receiving continuous risankizumab, one adjudicated major
between treatment groups, and the rates of serious AEs, adverse cardiovascular event in a patient with multiple
severe AEs, and TEAEs of safety interest were generally low cardiovascular risk factors was reported. All fungal infec-
in both groups, with no meaningful differences between the tions were related to skin or vaginal Candida. Among
methotrexate and risankizumab groups. Rates of serious AEs patients who received continuous risankizumab, pancreatic
were < 5% in the risankizumab group, and none of the serious cancer was reported for one patient who was a former
AEs in either group were deemed related to the study drug smoker. Overall, the mean changes from baseline in labora-
by the investigator. The most frequently reported TEAEs (≥ tory parameters were generally small among patients who
5% of patients) in the risankizumab group were headache, switched from methotrexate to risankizumab and patients
diarrhea, arthralgia, and anxiety. The most frequently who continued risankizumab treatment; laboratory val-
reported TEAEs (≥5% of patients) in the methotrexate group ues remained within normal ranges throughout the OLE
were nausea, headache, influenza, and increased alanine period.
aminotransferase levels. No patients discontinued the study
due to TEAEs in the risankizumab group. There were no
cases of tuberculosis, malignancy, serious hypersensitiv- Discussion
ity, or adjudicated major adverse cardiovascular events
in either group. Though numerically higher transaminase In this phase 3 study, risankizumab demonstrated supe-
elevations compared with baseline were observed with riority over methotrexate in the proportion of patients
methotrexate (alanine transaminase, 8.0 U/L; aspartate achieving PASI90 and sPGA0/1. The response rates for
aminotransferase, 5.0 U/L) versus risankizumab (≤ 1.1 U/L PASI90 and achievement of sPGA0/1 were consistent with
change in aspartate aminotransferase or alanine transam- those reported for the pivotal global studies in psoriasis
inase), mean levels remained within the normal range for for risankizumab.10 Further, significant improvements were
both groups. shown with risankizumab treatment in the ranked secondary
In the long-term extension period, TEAE rates remained efficacy endpoints, including total skin clearance (sPGA0
similar among patients who continued with open-label and PASI100). Efficacy was maintained through week 112
risankizumab or switched from methotrexate to open-label for patients who initially received risankizumab, and out-
risankizumab (Table 3). Incidence of serious AEs, TEAEs comes improved through week 112 for patients who started
leading to discontinuation, and TEAEs of safety interest on methotrexate and then switched to risankizumab at week
remained low. After patients switched from methotrex- 28.

267
 T.F. Cestari, C.S. Souza, L. Azulay-Abulafia et al.

Table 2 Overview of treatment-emergent adverse events (primary analysis double-blind period: weeks 0---28).

Parameter Double-blind period

RZB 150 mg MTX 5---25 mg

(n = 49) (n = 48)
n (%) n (%)
Any TEAE 38 (77.6) 40 (83.3)
Serious TEAE 2 (4.1) 4 (8.3)
TEAE leading to discontinuation of study drug 0 2 (4.2)a
Most common TEAEs (≥ 5% of patients)
Headache 9 (18.4) 5 (10.4)
Nausea 2 (4.1) 9 (18.8)
Influenza 2 (4.1) 5 (10.4)
Diarrhea 5 (10.2) 3 (6.3)
Nasopharyngitis 2 (4.1) 4 (8.3)
Alanine aminotransferase increased 2 (4.1) 4 (8.3)
Abdominal pain 0 4 (8.3)
Arthralgia 3 (6.1) 1 (2.1)
Back pain 3 (6.1) 2 (4.2)
Dizziness 3 (6.1) 0
Anxiety 3 (6.1) 0
Skin exfoliation 3 (6.1) 0
Pyrexia 0 4 (8.3)
TEAEs of safety interest
Adjudicated MACE 0 0
Adjudicated anaphylaxis 0 0
Serious infections 0 1 (2.1)
Opportunistic infections 0 0
Active TB 0 0
Malignant tumors 0 0
Serious hypersensitivity 0 0
Hepatic events 4 (8.2) 5 (10.4)
Deaths 0 1 (2.1)b

MACE, Major Adverse Cardiovascular Events; MTX, Methotrexate; RZB, Risankizumab; TB, Tuberculosis; TEAE, Treatment-Emergent
Adverse Events.
a Two patients discontinued study treatment due to TEAEs assessed by the investigator as possibly related to study drug (one due to

abdominal pain and appendicitis and one due to urinary tract infection, abdominal pain, and vomiting).
b One death in the MTX group was due to serious infections of appendicitis, peritonitis, and abdominal sepsis, none of which were

considered possibly related to the study drug.

Improvements in HRQoL are important in assessing the tools like the DLQI, Psoriasis Symptom Scale, and 36-Item
overall benefits of new therapies. In this study, EQ-5D- Short Form Health Survey).9---12,15
5L index score changes and MCID response rates were Risankizumab was well tolerated, and no new safety con-
not different between the risankizumab and methotrexate cerns were identified. The TEAEs of anxiety and dizziness
groups. Notably, EQ-5D-5L is a short, generic, non-disease- (reported for three patients each in the risankizumab arm
specific measure of health status and can be less sensitive during the double-blind period) were not identified as com-
to improvements in HRQoL experienced by people with mon adverse events in an integrated analysis of the safety
psoriasis when their symptoms improve. Nearly twice as of risankizumab in patients with psoriasis across 17 global
many patients treated with risankizumab versus methotrex- clinical trials.16 The safety profile of risankizumab observed
ate achieved the exploratory endpoint of DLQI 0 at week through 112 weeks of therapy was consistent with the safety
28. DLQI0 responses were maintained through 112 weeks profile of long-term risankizumab treatment in patients with
of therapy for patients who continued risankizumab treat- psoriasis.
ment, and outcomes improved through week 112 for patients A limitation of this study is the small sample size due to
who switched from methotrexate to risankizumab at week the difficulty of recruiting patients with moderate-to-severe
28. Results from previous studies have also shown that psoriasis who have not previously used methotrexate.
patients treated with risankizumab experience significant Methotrexate has been widely used as a first-line treat-
and clinically meaningful improvements in their HRQoL when ment for psoriasis in Brazil. The most recently published
assessed by more comprehensive and/or disease-specific Brazilian guideline for moderate-to-severe psoriasis (2019)
HRQoL instruments and patient-reported outcomes (e.g., suggests that biologics should be reserved for patients with

268
 Anais Brasileiros de Dermatologia 2025;100(2):260---271

Table 3 Overview of treatment-emergent adverse events (long-term analysis: weeks 28---112).

Events Open-label extension perioda

RZB/RZB MTX/RZB All RZB

n = 49 n = 46 n = 95
PYs = 83.4 PYs = 81.1 PYs = 190.9
E/100 PYs E/100 PYs E/100 PYs
Any TEAE 144 (172.7) 172 (212.1) 451 (236.2)
Serious TEAE 3 (3.6) 9 (11.1) 17 (8.9)
TEAE leading to discontinuation of study drug 2 (2.4) 0 2 (1.0)
Most common TEAEs (≥ 5 E/100 PY)
Headache 4 (4.8) 7 (8.6) 23 (12.0)
COVID-19 3 (3.6) 9 (11.1) 12 (6.3)
Hypertension 3 (3.6) 8 (9.9) 12 (6.3)
Anxiety 5 (6.0) 4 (4.9) 12 (6.3)
Nasopharyngitis 7 (8.4) 2 (2.5) 11 (5.8)
Blood creatine phosphokinase increased 5 (6.0) 4 (4.9) 9 (4.7)
Upper respiratory tract infection 1 (1.2) 7 (8.6) 10 (5.2)
Pain in extremity 0 6 (7.4) 8 (4.2)
Nephrolithiasis 5 (6.0) 1 (1.2) 7 (3.7)
Hypertensive crisis 0 5 (6.2) 6 (3.1)
Rhinitis 5 (6.0) 0 5 (2.6)
TEAEs of safety interest
Adjudicated MACE 1 (1.2)b 0 1 (0.5)b
Serious infections 0 6 (7.4) 6 (3.1)
Opportunistic infections excluding TB and herpes zoster 0 0 0
Active TB 0 0 0
Malignant tumors excluding NMSC 1 (1.2) 0 1 (0.5)
NMSC 0 1 (1.2) 1 (0.5)
Hepatic events 5 (6.0) 3 (3.7) 12 (6.3)
Serious hypersensitivity 0 0 0
Deaths 0 0 0

E, Events; MACE, Major Adverse Cardiovascular Events; MTX, Methotrexate; NMSC, Non-Melanoma Skin Cancer; PYs, Patient-Years; RZB,
Risankizumab; TB, Tuberculosis; TEAE, Treatment-Emergent Adverse Events.
a Safety includes data from weeks 28---112 (open-label extension period), including those patients who started on RZB 150 mg or MTX

5---25 mg at randomization and continued with or switched to open-label RZB 150 mg after week 28.
b A serious myocardial infarction event occurred in a 55-year-old male with a medical history of arterial hypertension, diabetes,

hyperlipidemia, obesity, and a history of smoking; the event was assessed as having no reasonable possibility of a relationship to the
study drug.

no response to treatment, contraindications for using a spe- methotrexate to risankizumab in the long-term OLE period.
cific drug, or intolerance to at least one systemic drug or The safety profile of risankizumab was consistent with the
phototherapy.17 Physicians’ reluctance to choose a biologic safety profile reported in the other risankizumab studies in
as first-line therapy may be connected to access restric- psoriasis. Overall, these results confirm risankizumab as a
tions associated with cost or partly due to the lack of data viable treatment option in patients with moderate-to-severe
from clinical studies that compare traditional methotrex- plaque psoriasis.
ate therapy with biologics. The present results support that
risankizumab provides greater efficacy than methotrexate
in patients with moderate-to-severe plaque psoriasis, with Data availability statement
no additional safety risks.
AbbVie is committed to responsible data sharing regarding
the clinical trials the authors sponsor. This includes access
Conclusions to anonymized individual and trial-level data (analysis data
sets), as well as other information (e.g., protocols, clinical
Risankizumab demonstrated significant improvements in study reports, or analysis plans), as long as the trials are
psoriasis symptoms and superior efficacy compared with not part of an ongoing or planned regulatory submission.
methotrexate at week 28. Further, the effectiveness of This includes requests for clinical trial data for unlicensed
risankizumab was maintained over time through week 112, products and indications.
demonstrating that durability and improvements in effi- These clinical trial data can be requested by any qualified
cacy were demonstrated in patients who switched from researchers who engage in rigorous, independent, scientific

269
 T.F. Cestari, C.S. Souza, L. Azulay-Abulafia et al.

research, and will be provided following review and approval manuscript critical review; preparation and writing of the
of a research proposal, statistical analysis plan, and exe- manuscript.
cution of a data sharing agreement. Data requests can be Tianshuang Wu: Approval of the final version of the
submitted at any time after approval in the US and Europe manuscript; data collection, analysis, and interpretation;
and after acceptance of this manuscript for publication. The manuscript critical review; preparation and writing of the
data will be accessible for 12 months, with possible exten- manuscript; statistical analysis; study conception and plan-
sions considered. For more information on the process or to ning.
submit a request, visit the following link: https://vivli.org/ Ranjeeta Sinvhal: Approval of the final version of the
ourmember/abbvie/, then select ‘‘Home’’. manuscript; data collection, analysis, and interpretation;
manuscript critical review; preparation and writing of the
Financial support manuscript; study conception and planning.
Vassilis Stakias: Approval of the final version of the
manuscript; data collection, analysis, and interpretation;
AbbVie funded this study and participated in the study
manuscript critical review; preparation and writing of the
design, research, analysis, data collection, interpretation of
manuscript.
data, reviewing, and approval of the publication. All authors
Alexandra P. Song: Approval of the final version of the
had access to relevant data and participated in the draft-
manuscript; data collection, analysis, and interpretation;
ing, review, and approval of this publication. No honoraria
manuscript critical review; preparation and writing of the
or payments were made for authorship. Medical writing sup-
manuscript.
port was provided by Melissa Julyanti, PharmD, of JB Ashtin,
Jasmina Kalabic: Approval of the final version of the
and funded by AbbVie.
manuscript; data collection, analysis, and interpretation;
manuscript critical review; preparation and writing of the
Author’s contribution manuscript.
Naomi Martin: Approval of the final version of the
Tania F. Cestari: Approval of the final version of the manuscript; data collection, analysis, and interpretation;
manuscript; data collection, analysis, and interpretation; manuscript critical review; preparation and writing of the
manuscript critical review; preparation and writing of the manuscript.
manuscript. Luiza Keiko Matsuka Oyafuso: approval of the final version
Cacilda da Silva Souza: Approval of the final version of of the manuscript; data collection, analysis, and interpreta-
the manuscript; data collection, analysis, and interpreta- tion; manuscript critical review; preparation and writing of
tion; manuscript critical review; preparation and writing of the manuscript.
the manuscript.
Luna Azulay-Abulafia: Approval of the final version of the
manuscript; data collection, analysis, and interpretation; Conflicts of interest
manuscript critical review; preparation and writing of the
manuscript. Dr. Cestari has served as a speaker, consultant,
Ricardo Romiti: Approval of the final version of the and/or investigator for AbbVie, Janssen-Cilag, La
manuscript; data collection, analysis, and interpretation; Roche-Posay, LEO Pharma, Novartis, Pierre-Fabre, and
manuscript critical review; preparation and writing of the Vichy.
manuscript. Dr. da Silva Souza has served as a consultant and/or inves-
André V.E. Carvalho: Approval of the final version of the tigator for AbbVie, Boehringer Ingelheim, Janssen-Cilag, LEO
manuscript; data collection, analysis, and interpretation; Pharma, and Novartis.
manuscript critical review; preparation and writing of the Dr. Azulay-Abulafia has served as a consultant and/or
manuscript. investigator for AbbVie, Janssen-Cilag, LEO Pharma, Lilly,
Caio César Silva de Castro: Approval of the final version Novartis, and Pfizer.
of the manuscript; data collection, analysis, and interpreta- Dr. Romiti has served as a consultant, speaker, and/or
tion; manuscript critical review; preparation and writing of investigator for AbbVie, Bioderma, Boehringer Ingelheim,
the manuscript. Galderma, Janssen-Cilag, LEO Pharma, Lilly, Novartis, Pfizer,
Silvio Alencar Marques: Approval of the final version of and UCB.
the manuscript; data collection, analysis, and interpreta- Dr. Carvalho has served as a consultant, speaker, and/or
tion; manuscript critical review; preparation and writing of investigator for AbbVie, AMGEN, Boehringer Ingelheim, GSK,
the manuscript. Janssen-Cilag, LEO Pharma, Lilly, and Novartis.
João Roberto Antonio: Approval of the final version of Dr. de Castro has served as a consultant, speaker, and/or
the manuscript; data collection, analysis, and interpreta- investigator for AbbVie, Janssen, Novartis, and Pfizer.
tion; manuscript critical review; preparation and writing of Dr. Marques has served as a local investigator and
the manuscript. received grants/research funding from Janssen.
Lincoln Fabrício: Approval of the final version of the Dr. Antonio has served as a speaker and principal inves-
manuscript; data collection, analysis, and interpretation; tigator for AbbVie, Janssen, and Novartis.
manuscript critical review; preparation and writing of the Dr. Fabrício has served as a speaker for Abbott, AbbVie,
manuscript. Bayer, Bioderma, Biolab, Boticário, Galderma, Hypermar-
Ahmed M. Soliman: Approval of the final version of the cas, Isdin, Janssen, La Roche-Posay, LEO Pharma, Pfizer,
manuscript; data collection, analysis, and interpretation; and Stiefel/GSK, and has received sponsorship for scientific

270
 Anais Brasileiros de Dermatologia 2025;100(2):260---271

events from Abbott, AbbVie, Bayer, Bioderma, Galderma, 9. Blauvelt A, Leonardi CL, Gooderham M, Papp KA, Philipp S, Wu
Isdin, Janssen, La Roche-Posay, LEO Pharma, MSD, Novartis, JJ, et al. Efficacy and safety of continuous risankizumab therapy
and Pfizer. He has participated in advisory boards for Bayer, vs treatment withdrawal in patients with moderate to severe
Janssen, La Roche-Posay, LEO Pharma, and MSD. plaque psoriasis: a phase 3 randomized clinical trial. JAMA Der-
Dr. Soliman, Dr. Wu, Dr. Sinvhal, Dr. Stakias, Dr. Song, and matol. 2020;156:649---58.
10. Gordon KB, Strober B, Lebwohl M, Augustin M, Blauvelt
Dr. Kalabic are employees of AbbVie and may hold AbbVie
A, Poulin Y, et al. Efficacy and safety of risankizumab in
stock, stock options, and/or patents. moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-
Dr. Martin is a former employee of AbbVie. 2): results from two double-blind, randomised, placebo-
Dr. Oyafuso has served as a consultant and/or investigator controlled and ustekinumab-controlled phase 3 trials. Lancet.
for AbbVie, Janssen-Cilag, and Novartis. 2018;392:650---61.
11. Ohtsuki M, Fujita H, Watanabe M, Suzaki K, Flack M, Huang X,
et al. Efficacy and safety of risankizumab in Japanese patients
Acknowledgments
with moderate to severe plaque psoriasis: results from the Sus-
taIMM phase 2/3 trial. J Dermatol. 2019;46:686---94.
AbbVie and the authors thank all the trial investigators and 12. Reich K, Gooderham M, Thaçi D, Crowley JJ, Ryan C, Krueger
the patients who participated in this clinical trial. Medical JG, et al. Risankizumab compared with adalimumab in patients
writing support was provided by Melissa Julyanti, PharmD, with moderate-to-severe plaque psoriasis (IMMvent): a ran-
of JB Ashtin, and funded by AbbVie. domised, double-blind, active-comparator-controlled phase 3
trial. Lancet. 2019;394:576---86.
13. Warren RB, Blauvelt A, Poulin Y, Beeck S, Kelly M, Wu T, et al.
Appendix A. Supplementary data Efficacy and safety of risankizumab vs. secukinumab in patients
with moderate-to-severe plaque psoriasis (IMMerge): results
Supplementary material related to this article can be from a phase III, randomized, open-label, efficacy-assessor-
found, in the online version, at doi:https://doi.org/10. blinded clinical trial. Br J Dermatol. 2021;184:50---9.
1016/j.abd.2024.08.002. 14. National Committee for Health Technology Incorporation
into the Brazilian Public Health System (CONITEC). In:
Risankizumab for the treatment of adult patients with
References moderate to severe plaque psoriasis. Brazil: National
Committee for Health Technology Incorporation into
1. DiBonaventura M, Carvalho AVE, Souza CDS, Squiassi HB, Fer- the Brazilian Public Health System (CONITEC). Brazilian
reira CN. The association between psoriasis and health-related Ministry of Health; 2020 [cited 2022 Oct 24]. Available
quality of life, work productivity, and healthcare resource use from: https://www.gov.br/conitec/pt-br/midias/consultas/
in Brazil. An Bras Dermatol. 2018;93:197---204. relatorios/en2020/20210607 report 534 risankizumab for the
2. Griffiths CE, Barker JN. Pathogenesis and clinical features of treatment of.pdf/view
psoriasis. Lancet. 2007;370:263---71. 15. Thaçi D, Soliman AM, Eyerich K, Pinter A, Sebastian
3. Romiti R, Amone M, Menter A, Miot HA. Prevalence of psoriasis in M, Unnebrink K, et al. Patient-reported outcomes with
Brazil - a geographical survey. Int J Dermatol. 2017;56:e167---8. risankizumab versus fumaric acid esters in systemic therapy-
4. Duarte GV, Porto-Silva L, de Oliveira MFP. Epidemiology naïve patients with moderate to severe plaque psoriasis:
and treatment of psoriasis: a Brazilian perspective. Psoriasis a phase 3 clinical trial. J Eur Acad Dermatol Venereol.
(Auckl). 2015;5:55---64. 2021;35:1686---91.
5. Haustein UF, Rytter M. Methotrexate in psoriasis: 26 years’ expe- 16. Gordon KB, Lebwohl M, Papp KA, Bachelez H, Wu JJ, Langley
rience with low-dose long-term treatment. J Eur Acad Dermatol RG, et al. Long-term safety of risankizumab from 17 clinical
Venereol. 2000;14:382---8. trials in patients with moderate-to-severe plaque psoriasis. Br
6. Romiti R, Carvalho AVE, Duarte GV. Brazilian Consensus on Pso- J Dermatol. 2022;186:466---75.
riasis 2020 and Treatment Algorithm of the Brazilian Society of 17. Arnone M, Takahashi MDF, Carvalho AVE, Bernardo WM, Bressan
Dermatology. An Bras Dermatol. 2021;96:778---81. AL, Ramos AMC, et al. Diagnostic and therapeutic guidelines
7. Puig L. The role of IL 23 in the treatment of psoriasis. Expert for plaque psoriasis - Brazilian Society of Dermatology. An Bras
Rev Clin Immunol. 2017;13:525---34. Dermatol. 2019;94:76---107.
8. Skyrizi (risankizumab-rzaa). In: Prescribing information.
AbbVie Inc; 2022 [cited 2023 Jan 30]. Available from:
https://www.rxabbvie.com/pdf/skyrizi pi.pdf

271