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Efficacy, safety, usability, and acceptability of
risankizumab 150 mg formulation administered
by prefilled syringe or by an autoinjector for
moderate to severe plaque psoriasis
Andrew Blauvelt, Kenneth B. Gordon, Patricia Lee, Jerry Bagel, Howard
Sofen, Benjamin Lockshin, Ahmed M. Soliman, Ziqian Geng, Tianyu Zhan,
Gabriela Alperovich & Linda Stein Gold
To cite this article: Andrew Blauvelt, Kenneth B. Gordon, Patricia Lee, Jerry Bagel, Howard Sofen,
Benjamin Lockshin, Ahmed M. Soliman, Ziqian Geng, Tianyu Zhan, Gabriela Alperovich & Linda
Stein Gold (2021): Efficacy, safety, usability, and acceptability of risankizumab 150 mg formulation
administered by prefilled syringe or by an autoinjector for moderate to severe plaque psoriasis,
Journal of Dermatological Treatment, DOI: 10.1080/09546634.2021.1914812
To link to this article: https://doi.org/10.1080/09546634.2021.1914812
© 2021 The Author(s). Published with
license by Taylor & Francis Group, LLC. View supplementary material
Published online: 05 May 2021. Submit your article to this journal
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ARTICLE
Efficacy, safety, usability, and acceptability of risankizumab 150 mg formulation
administered by prefilled syringe or by an autoinjector for moderate to severe
plaque psoriasis
Andrew Blauvelt
a
, Kenneth B. Gordon
b
, Patricia Lee
c
, Jerry Bagel
d
, Howard , Sofen
e
, Benjamin
Lockshin
f,g,h
, Ahmed M. Soliman
i
, Ziqian Geng
i
, Tianyu Zhan
i
, Gabriela Alperovich
j
and Linda Stein Gold
k
a
Oregon Medical Research Center, Portland, OR, USA;
b
Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA;
c
Center for Clinical Studies, Webster, TX, USA;
d
Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USA;
e
Department of
Medicine/Dermatology, UCLA School of Medicine, Los Angeles, CA, USA;
f
DermAssociates, Silver Spring, MD, USA;
g
Department of
Dermatology, Georgetown University, Washington, DC, USA;
h
Department of Dermatology, Johns Hopkins University, Baltimore, MD, USA;
i
AbbVie Inc., North Chicago, IL, USA;
j
AbbVie Inc., Madrid, Spain;
k
Henry Ford Health System, Detroit, MI, USA
ABSTRACT
Background: Risankizumab is approved for treatment of moderate to severe plaque psoriasis.
Availability of a patient-controlled single self-injection of risankizumab may improve adherence and
long-term management of psoriasis.
Objective: To investigate efficacy, safety, and usability of a new risankizumab 150mg/mL formulation
administered as a single subcutaneous injection via prefilled syringe (PFS) or autoinjector (AI).
Methods: Efficacy, safety, usability, and acceptability of risankizumab 150 mg/mL PFS or AI were inves-
tigated in adults with moderate to severe psoriasis in two phase 3 studies. Study 1 was a multicenter,
randomized, double-blinded, placebo-controlled study that investigated 150mg/mL risankizumab PFS;
study 2 was a multicenter, single-arm, open-label study that investigated 150 mg/mL risankizumab AI.
Results: At week 16, risankizumab 150 mg/mL demonstrated efficacy vs. placebo (Psoriasis Area and
Severity Index 90% improvement (PASI 90), 62.9% vs. 3.8%; static Physician Global Assessment
(sPGA) 0/1, 78.1% vs. 9.6%; both p<.001) in study 1; in study 2, PASI 90 and sPGA 0/1 were 66.7%,
and 81.5%, respectively. All patients successfully self-administered study treatments via PFS or AI.
Acceptability of self-injection was high in both studies. Efficacy and safety of risankizumab 150mg/mL
were comparable with results from previous risankizumab phase 3 studies using the 90 mg/mL
formulation.
Conclusions: The efficacy, safety, and usability of 150 mg/mL risankizumab delivered as a single PFS
or AI injection support use of this new formulation in patients with moderate to severe pla-
que psoriasis.
Clinical trials: NCT03875482 and NCT0387508
ARTICLE HISTORY
Received 23 March 2021
Accepted 6 April 2021
KEYWORDS
Risankizumab; psoriasis;
autoinjector; pre-
filled syringe
Introduction
Psoriasis is a chronic immune-mediated inflammatory disease
associated with comorbidities and reduced quality of life (1–4).
Due to its chronic nature, therapies that provide long-term
safety and efficacy are often needed to manage this disease (5).
Furthermore, adherence to therapy is important for favorable
long-term treatment outcomes (6). More specifically, injectable
therapies that can be self-administered at home in a single
injection can improve adherence and ease the management of
disease (7,8).
Interleukin (IL)-23 inhibitors have demonstrated efficacy in
clinical trials in patients with moderate to severe plaque psoria-
sis (9–11). Risankizumab, a fully humanized monoclonal anti-
body that binds with high affinity to the human IL-23 p19
subunit (12), has demonstrated superior efficacy in phase 3
clinical trials when compared with placebo, secukinumab, usteki-
numab, or adalimumab for the treatment of patients with mod-
erate to severe plaque psoriasis (11,13–15). In the pivotal phase
3 clinical trials, the risankizumab 150-mg dose was administered
via two subcutaneous (SC) 75-mg injections of a 90-mg/mL for-
mulation delivered with a prefilled syringe (PFS).
To allow a more patient-controlled self-injection experience,
a new risankizumab formulation of 150 mg/mL that enables
administration of the 150-mg dose with one SC injection was
developed. A phase 1 pharmacokinetic (PK) study in healthy
subjects demonstrated that the 150 mg/mL PFS is bioequivalent
to the currently approved 90 mg/mL PFS, with comparable PK,
immunogenicity, and safety profile (16). In addition, the 150 mg/
mL autoinjector (AI) showed bioequivalent exposure and com-
parable immunogenicity to the risankizumab 150 mg/mL PFS
(16). Here, we report efficacy, safety, tolerability, and usability of
CONTACT Andrew Blauvelt ablauvelt@oregonmedicalresearch.com Oregon Medical Research Center, 9495 SW Locust St, Ste G, Portland, OR 97223, USA
Supplemental data for this article can be accessed here.
ß2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in
any way.
JOURNAL OF DERMATOLOGICAL TREATMENT
https://doi.org/10.1080/09546634.2021.1914812
the single injection formulation of risankizumab 150 mg/mL
administered via PFS or AI in adult patients with moderate to
severe plaque psoriasis in two phase 3 clinical studies.
Materials and methods
Study designs
Study 1 (NCT03875482) was a multicenter, randomized, double-
blinded, placebo-controlled, parallel-group study conducted at
38 sites in the United States, including Puerto Rico, that eval-
uated the efficacy and safety of risankizumab 150 mg/mL PFS in
patients with moderate to severe plaque psoriasis. The study
included a 30-day screening period, a treatment period with
study drug self-administered at weeks 0, 4, and 16, and a subse-
quent follow-up safety call at approximately 20 weeks after the
last dose of study drug; dosing on week 4 was self-administered
at home after a study visit (Supplemental Figure 1A). Patients
were randomized in a 2:1 ratio to risankizumab 150 mg
or placebo.
Study 2 (NCT03875508) was a multicenter, single-arm, open-
label study conducted at 24 sites in the United States that
evaluated usability, efficacy, safety, and tolerability of the risan-
kizumab 150 mg/mL AI in patients with moderate to severe pla-
que psoriasis. The study included a 30-day screening period; a
treatment period with study drug self-administered at weeks 0,
4, 16, and 28; and a subsequent follow-up safety call at approxi-
mately 20 weeks after the last dose of study drug. Dosing on
weeks 4 and 16 was self-administered at home after a study
visit (Supplemental Figure 1B).
All patients provided written informed consent, and the
study protocol was approved by an institutional review board or
independent ethics committee at each study site. Both studies
were conducted in accordance with applicable regulations and
the ethical principles of Good Clinical Practice as defined by the
International Conference on Harmonisation and Declaration
of Helsinki.
Participants
Adults (18 years old) from the United States, including Puerto
Rico, with a diagnosis of moderate to severe plaque psoriasis
for at least 6 months before the baseline visit were eligible for
the studies. Eligible patients met the following disease activity
criteria: 10% body surface area (BSA) psoriasis involvement,
static Physician Global Assessment (sPGA) score of 3, and
Psoriasis Area and Severity Index (PASI) 12. Patients were also
required to have laboratory values meeting the following criteria
during the screening period, prior to the first dose of study
drug: serum aspartate transaminase <2upper limit of normal
(ULN); serum alanine transaminase <2ULN; serum direct bili-
rubin 2.0 mg/dL (except for patients with isolated elevation of
indirect bilirubin relating to a confirmed diagnosis of Gilbert
syndrome); total white blood cell count >3000/lL; absolute
neutrophil count >1500/lL; platelet count >100,000/lL; and
hemoglobin >8 g/dL.
Patients with a history of erythrodermic psoriasis, generalized
or localized pustular psoriasis, medication-induced or medica-
tion-exacerbated psoriasis, or new onset guttate psoriasis, active
skin disease other than psoriasis that could interfere with the
assessment of psoriasis, chronic infections, or documented
active or suspected malignancy or history of any malignancy
within the last 5 years (except for successfully treated non-mel-
anoma skin cancer or localized carcinoma in situ of the cervix)
were excluded from the studies. In addition, patients with previ-
ous exposure to risankizumab or concomitant use of systemic
non-biologic or biologic therapy for psoriasis, topical psoriasis
treatment, and phototherapy were also excluded.
Efficacy endpoints
Key efficacy endpoints (co-primary endpoints in study 1) were
the proportion of patients achieving PASI 90 (defined as at least
90% improvement from baseline in PASI) at week 16, and pro-
portion of patients achieving sPGA of clear (0) or almost clear
(1) at week 16. Additional endpoints (ranked secondary end-
points in study 1) were proportion of patients achieving PASI
100 (defined as 100% improvement from baseline in PASI) at
week 16 and proportion of patients achieving sPGA 0 at week
16; percent change from baseline in PASI at all visits was
also assessed.
Usability and acceptability experience
In study 1, usability of the PFS for self-injection was assessed as
the proportion of patients with an observer rating of successful
patient self-administration, defined as any patients who success-
fully completed the sequence of three critical steps (‘select cor-
rect injection site’,‘remove the needle cover’, and ‘slowly push
plunger all the way in until all the liquid is injected and syringe
is empty’) without errors to administer study drug, and meas-
ured at baseline and at week 16 by an observer at the study
site. In study 2, usability of the AI for self-injection was assessed
as the proportion of patients with an observer rating of success-
ful self-administration, defined as any patients who successfully
completed the sequence of 4 critical steps (‘chose an appropri-
ate injection site’,‘removed cap from AI’,‘activated the injec-
tion’, and ‘performed a complete injection’) without errors in
the administration of study drug via AI, and measured at base-
line and at week 28 by an observer at the study site. In add-
ition, potential hazards assessed by the observer based on a
pre-defined possible use-related hazards checklist for self-admin-
istration with PFS or AI were measured at baseline and at week
16 (study 1) or at week 28 (study 2).
Patient rating of acceptability of their experience with the
PFS or AI using the Self-Injection Assessment Questionnaire
(SIAQ) was assessed at study visits in both studies. SIAQ meas-
ures overall patient experience with SC self-injection and
includes two parts: the PRE module completed by the patient
immediately before baseline self-injection and the POST module
completed by the patient 20–40 min after each self-injection at
all visits with study drug dosing. The PRE module included three
domains: ‘feelings about injections’,‘self-confidence’, and
‘satisfaction with self-injection’. The POST module included six
domains: ‘feelings about injections’,‘self-image’,‘self-confi-
dence’,‘injection-site pain’, and ‘reactions during and after the
injection’,‘ease of use’, and ‘satisfaction with self-injection’(17).
Patients rated each item of the SIAQ, with ratings that varied
from ‘not at all’to ‘extremely’; these ratings were later trans-
formed to scores ranging from 0 (worst experience) to 10 (best
experience) (Supplemental Table 1). Transformed scores were
averaged to compute a domain score. Higher domain scores
indicated higher acceptability by patients to use the PFS or AI.
2 A. BLAUVELT ET AL.
Safety
Safety evaluations included adverse event (AE) monitoring,
physical examinations, vital sign measurements, and clinical
laboratory testing (hematology and chemistry). Treatment-
emergent AEs were defined as any event with an onset that is
after the first dose of study drug and with an onset date within
20 weeks (140 days) after the last dose of study drug.
(A)
(B)
Study 1
Disconnued study: 20 (38.5%)
-Lack of efficacy: 11 (21.2%)
-Withdrew consent: 6 (11.5%)
-Lost to follow-up: 2 (3.8%)
-Adverse event: 1 (1.9%)
Completed study
n=32 (61.5%)
Completed study
n=92 (87.6%)
Disconnued study: 13 (12.4%)
-Lost to follow up: 8 (7.6%)
-Withdrew consent: 5 (4.8%)
Risankizumab 150 mg/mL PFS
n=105
Randomized and Treated with Risankizumab 150 mg/mL
PFS
N=157
Placebo
n=52
Disconnued study drug: 17 (32.7%)
-Lack of efficacy: 8 (15.4%)
-Withdrew consent: 6 (11.5%)
-Lost to follow-up: 2 (3.8%)
-Adverse event: 1 (1.9%)
Disconnued study drug: 11 (10.5%)
-Lost to follow up: 6 (5.7%)
-Withdrew consent: 4 (3.8%)
-Lack of efficacy: 1 (1.0%)
Risankizumab 150 mg/mL PFS
n=105
Randomized and treated with Risankizumab 150 m/mL PFS
N=157
Placebo
n=52
Figure 1. Patient disposition and study drug discontinuation in (A) study 1 and (B) study 2. AI: autoinjector; PFS: prefilled syringe.
JOURNAL OF DERMATOLOGICAL TREATMENT 3
Statistical analysis
In study 1, the intent-to-treat (ITT) population included all
randomized patients; patients were analyzed according to treat-
ment as randomized. The safety analysis population consisted of
all patients who received at least one dose of study drug;
patients were analyzed according to the first dose of study drug
(risankizumab or placebo) received. In study 2, the ITT popula-
tion, which included all patients who received at least one dose
of study drug, was analyzed for efficacy, usability, and safety.
In study 1, overall type-I error was controlled by simultan-
eously testing co-primary endpoints, followed by the ranked
secondary endpoints, in a hierarchical order. Comparison of the
primary and secondary efficacy endpoints were made between
the risankizumab and the placebo treatment groups using the
Chi-square test. In study 2, no statistical tests were performed.
For analysis of both studies, categorical efficacy variables
were analyzed using non-responder imputation (NRI) to handle
missing data; mixed-effect model repeat measurements
(MMRMs) of additional efficacy endpoints was used for continu-
ous variables. As-observed and modified NRI (mNRI) were con-
ducted as sensitivity analyses for efficacy endpoints (co-primary
and ranked secondary efficacy endpoints in study 1) for the two
studies. For mNRI, a patient was considered as a non-responder
for the visit if the patient did not have an evaluation and dis-
continued study drug due to lack of efficacy or due to an AE of
worsening of psoriasis during the visit window. Other missing
values were excluded from this sensitivity analysis. Usability
endpoints were analyzed as-observed cases for both studies. Of
note, the NRI approach was coupled with multiple imputation
to mitigate the impact of missing data due to COVID-19 for key
efficacy endpoints in study 2.
Sample size
Study 1 was designed to enroll approximately 150 patients.
Assuming the response rates at week 16 to be 74% for the
risankizumab arm and 3% for the placebo arm for PASI 90, and
85% for the risankizumab arm and 7% for the placebo arm for
sPGA 0/1, the study provided more than 95% power for each of
the two co-primary efficacy endpoints (an overall power of
more than 90%).
Study 2 was designed to enroll approximately 100 patients
receiving risankizumab. Assuming the point estimate is 90% for
the proportion of patients with an observer rating of successful
self-administration at week 28, the current sample size of 100
patients provided a 95% confidence interval of ±5.9% around a
point estimate. In addition, assuming comparable response rates
as the phase 3 pivotal studies, with the sample size of 100, the
PASI 90 rate at week 16 was estimated with a 95% confidence
interval of ±8.6%, when the point estimate is 74%; and the
sPGA 0/1 rate at week 16 was estimated with a 95% confidence
interval of ±7.0%, when the point estimate is 85%.
Results
Patient disposition and baseline characteristics
In study 1, a total of 157 patients were randomized to risankizu-
mab 150 mg/mL PFS (n¼105) or placebo (n¼52) and received
treatment. Of these, 124 completed the study (risankizumab,
n¼92 (87.6%); placebo, n¼32 (61.5%)). The most common pri-
mary reasons for study discontinuation were lack of efficacy (11
patients (7.0%); risankizumab, n¼0; placebo, n¼11), withdrawal
of consent (11 patients (7.0%); risankizumab, n¼5; placebo
n¼6), and lost to follow-up (10 patients (6.4%); risankizumab,
n¼8; placebo n¼2). In study 2, 108 patients were enrolled to
the study and received risankizumab 150 mg/mL formulation via
AI; of these, 96 (88.9%) completed the study. The most common
reason for discontinuation was lost to follow-up (eight patients
(7.4%); Figure 1).
Baseline demographic and disease characteristics, such as
duration of psoriasis, baseline PASI, BSA involvement, and prior
treatment with biologic therapy, were similar in the two treat-
ment arms in study 1 and also when comparing study 1 with
study 2 (Table 1).
Efficacy
Significantly greater proportions of patients receiving risankizu-
mab 150 mg/mL PFS met the co-primary endpoints of PASI 90
(62.9%) and sPGA 0/1 (78.1%) at week 16 vs. placebo (3.8% and
9.6%, respectively; both p<.001, NRI analysis) in study 1.
Similarly, significantly greater proportions of patients receiving
risankizumab 150 mg/mL PFS achieved PASI 100 (38.1%) and
sPGA 0 (39.0%) at week 16 vs. placebo (1.9% and 1.9%, respect-
ively; both p<.001, NRI analysis, Figure 2). The sensitivity ana-
lysis supported these results (PASI 90 was 67.3% and sPGA 0/1
was 83.7% for mNRI and as-observed case analyses in the risan-
kizumab arm).
These results were also consistent with risankizumab 150 mg/
mL AI in study 2 in which 66.7% (72/108) of patients achieved
PASI 90, 81.5% (88/108) achieved sPGA 0/1, 46.3% (50/108)
achieved PASI 100, and 47.2% (51/108) achieved sPGA 0 at
week 16 (NRI analysis, Figure 2). Compared with the NRI analy-
ses, the proportions of patients achieving PASI 90 and sPGA 0/1
were numerically similar or higher for mNRI and as-observed
case analyses (67.9% and 83.0%, respectively). Of note, 84.4% of
patients achieved PASI 90 and 90.9% of patients achieved sPGA
clear or almost clear at week 28 in study 2 (NRI analysis,
Supplemental Figure 2). The percentage change from baseline
in PASI for studies 1 and 2 is shown in Table 2.
Table 1. Patient demographics and baseline disease characteristics in study 1
and 2.
Study 1 Study 2
Characteristic
Risankizumab
150 mg/mL PFS
(n¼105)
Placebo
(n¼52)
Risankizumab
150 mg/mL AI
(N¼108)
Age, years, mean (SD) 49.3 (15.1) 48.8 (15.5) 49.2 (14.3)
Male, n(%) 59 (56.2) 28 (53.8) 66 (61.1)
Race, White, n(%) 87 (82.9) 44 (84.6) 95 (88.0)
Weight, kg, mean (SD) 96.9 (28.9) 91.7 (23.5) 93.3 (26.4)
BMI, kg/m
2
, mean (SD) 33.3 (8.7) 31.6 (7.4) 32.0 (8.7)
Disease duration, years,
mean (SD)
20.9 (13.8) 15.8 (11.8) 16.9 (13.1)
PASI, mean (SD) 21.5 (9.6) 21.1 (10.3) 19.8 (7.2)
sPGA, n(%)
Score 3 86 (81.9) 46 (88.5) 88 (81.5)
Score 4 19 (18.1) 6 (11.5) 20 (18.5)
BSA involvement, %, mean (SD) 28.3 (16.4) 28.2 (18.5) 25.5 (17.5)
Psoriatic arthritis, n(%) 26 (24.8) 11 (21.2) 19 (17.6)
Prior biologic therapy, n(%) 47 (44.8) 23 (44.2) 48 (44.4)
AI: autoinjector; BMI: body mass index; PASI: Psoriasis Area Severity Index; PFS:
prefilled syringe; SD: standard deviation; sPGA: static physician global assess-
ment; BSA: body surface area.
4 A. BLAUVELT ET AL.
Usability and acceptability
In study 1, all patients in the risankizumab and placebo groups
successfully self-administered study treatments, defined as suc-
cessfully completing all three critical steps in the instructions for
use at baseline and week 16. Similarly, in study 2, all patients
successfully self-administered study treatments, defined as suc-
cessfully completing all four critical steps in the instructions for
use at baseline and week 28. In study 1, two observed use haz-
ards were reported in the placebo and risankizumab groups at
baseline (one each, delayed administration due to needle cover
removal difficulties); no observed use hazards were reported at
week 16. No reported use hazards were observed at baseline
and at week 28 in study 2 (Supplemental Table 2).
Mean domain scores for acceptability of self-injection experi-
ence were high at baseline (PRE module) and numerically higher
at week 16 (POST module) for both the risankizumab and pla-
cebo groups for PFS in study 1. Similar results were seen for
risankizumab AI in study 2, comparing PRE module and week 28
(POST module).
Domains with shared questions for the PRE and POST mod-
ules are reported in Figure 3. In the risankizumab groups in
studies 1 and 2, the mean scores for ‘feelings about injection’
domain were 8.4 and 8.1, for the baseline PRE module and 8.8
and 8.8 for the POST module at week 16 (study 1) or week 28
(study 2); for ‘self-confidence’domain the mean scores were 7.5
and 7.7 for PRE module and 8.2 and 8.4 for POST module at
week 16 (study 1) or week 28 (study 2); and for ‘satisfaction
with self-injection’domain the mean scores were 7.1 and 7.0 for
PRE module and 8.7 and 9.2 for POST module at week 16 (study
1) or week 28 (study 2). Similar results were observed in the pla-
cebo group in study 1. POST module mean SIAQ scores were
high at baseline and remained high or improved over time
among all patients in both studies.
Responses to individual POST module items are summarized
in Supplemental Table 3. The majority of patients achieved the
highest two response categories in all of the POST module
Figure 2. Proportion of patients achieving PASI 90, PASI 100, sPGA 0/1, and sPGA 0 at week 16 with risankizumab and placebo (study 1) and OL risankizumab
(study 2). NRI analysis. AI: autoinjector; NRI: non-responder imputation; OL: open-label; PASI: Psoriasis Area Severity Index; PFS: prefilled syringe; sPGA: static physi-
cian’s global assessment.
Table 2. Percentage change from baseline in PASI over time.
Study 1 Study 2
LS mean
Risankizumab
150 mg/mL PFS
(n ¼105)
Placebo
(n ¼52)
Risankizumab
150 mg/mL AI
(N ¼108)
Week 4 –50.6(n¼101) –14.5 (n¼50) –61.6 (n¼107)
Week 16 –89.4(n¼98) –29.4 (n¼43) –89.3 (n¼106)
Week 28 –––95.5 (n¼100)
AI: autoinjector; LS: least squares; MRMMs: mixed-effect model repeat meas-
urements; PASI: Psoriasis Area Severity Index; PFS: prefilled syringe.
MMRM analysis.
p<.001 for placebo vs. risankizumab.
JOURNAL OF DERMATOLOGICAL TREATMENT 5
individual SIAQ questions. ‘Satisfaction with self-injection’
domain represented by the question ‘overall, how satisfied are
you with current way of taking your medication?’showed the
greatest increase in patients responding in the top two catego-
ries (i.e. satisfied and very satisfied) in the risankizumab groups,
increasing from 64.5% of patients in study 1 and 57.0% of
patients in study 2 in the PRE module at baseline to 93.0% with
the PFS (study 1) and to 97.6% with the AI (study 2) in the last
POST module assessment (week 16 for study 1 and week 28 for
study 2).
Safety
Adverse events for studies 1 and 2 are reported in Table 3.In
study 1, the occurrence of treatment-emergent AEs (21.0% vs.
21.2%), serious AEs (1.0% vs. 0%), and infections (5.7% vs. 5.8%)
was similar between risankizumab 150 mg/mL and placebo PFS
groups, respectively. The most common AEs in the risankizumab
group were nausea (4 (3.8%)) and nasal congestion (3 (2.9%)).
All other AEs were reported in <2% patients in the risankizu-
mab group. One mild injection site reaction was reported in the
risankizumab 150 mg/mL PFS group. A serious treatment-emer-
gent AE was reported in one patient (grade 3 acute pancreatitis,
in a patient with a medical history of chronic pancreatitis, con-
sidered not related to study drug). In study 2, AEs were
observed in 43.5% of patients, serious AEs in 5.6% of patients,
infections in 27.8%, and serious infections in 1.9% of patients
receiving risankizumab 150 mg/mL AI. Most AEs were mild or
moderate and not related to study drug. The most common AEs
were nasopharyngitis (8 (7.4%)), upper respiratory tract infection
(6 (5.6%)), and gastroenteritis (4 (3.7%)); all other AEs occurred
in <3% of patients. Seven serious treatment-emergent AEs were
Figure 3. Mean SIAQ baseline PRE module domain scores and week 16 POST module domain scores and SIAQ POST module domain scores over time with risan-
kizumab and placebo (study 1) and OL risankizumab (study 2). Observed case analysis. AI: autoinjector; BL: baseline; OL: open-label; PFS: prefilled syringe; SIAQ:
Self-Injection Assessment Questionnaire.
6 A. BLAUVELT ET AL.
reported in six patients; appendicitis and prostatitis occurring in
the same patient, and pyelonephritis, pyrexia, thermal burn,
lumbar spinal stenosis, and atrial fibrillation.
No deaths, malignancies, serious hypersensitivity reactions,
active tuberculosis, or adjudicated major adverse cardiovascular
events were observed in either study. There were two AEs of
COVID-19: one in each study; both were non-serious.
Discussion
The two reported clinical studies were conducted to demon-
strate efficacy and safety as well as to evaluate usability and
acceptability of self-administration of risankizumab 150 mg/mL
formulation delivered either via PFS or AI in patients with mod-
erate to severe plaque psoriasis. The placebo-controlled study
using the PFS (study 1) met the efficacy endpoints with signifi-
cant improvements in PASI and sPGA observed with risankizu-
mab 150 mg/mL PFS vs. placebo as early as week 4, with these
benefits continuing to improve over time. A similar improve-
ment was observed for risankizumab 150 mg/mL AI in the open-
label study (study 2). Efficacy results for both studies were con-
sistent with the week 16 results observed in the pivotal clinical
studies investigating risankizumab in adult patients with moder-
ate to severe plaque psoriasis administered as two SC 75-mg
injections of a 90 mg/mL formulation delivered via
PFS (11,13–15).
All patients successfully self-administered the study treat-
ments as demonstrated by performing the critical steps pre-
determined in both studies in the instructions for use, and by
showing high compliance with the remaining defined steps.
Nearly, all patients had no use hazards with either the PFS (with
the exception of two patients who had difficulty removing the
needle cover at the baseline visit) or AI in the two studies and
were able to administer the full volume of the injection.
These studies collected patient-reported assessments of their
perceptions about and experiences with PFS and AI through use
of the SIAQ. SIAQ is a reliable and valid tool that is used in
many clinical studies to evaluate the patient experience and
acceptability of self-injection (18–23). The results of the current
studies demonstrated that patients generally found both PFS
and AI to be easy to use. Patient confidence and satisfaction
with self-injection of risankizumab was high from baseline
through week 16 (for study 1) or week 28 (for study 2). Patient
acceptability of self-injection of risankizumab 150 mg/mL formu-
lation was rated high for the three common domains of the PRE
and POST modules of SIAQ (feelings about self-injections, self-
confidence, and satisfaction with self-injection) at baseline and
at the final assessments, and for all the remaining POST mod-
ules. This demonstrates that self-injection was acceptable to
patients before they administered the self-injection, and
remained highly acceptable, and in some cases, even improved
up to weeks 16 and 28. When the questions of the domains
were analyzed individually, ‘satisfaction with self-injection’was
the domain where the proportion of patients either ‘satisfied’or
‘very satisfied’increased the most between the PRE module and
POST module at the last assessment, indicating that the patient
experience might have an impact on improved adherence
to treatment.
No new safety findings were observed, and the risankizumab
150 mg/mL safety profile was consistent with risankizumab
phase 3 studies using risankizumab 90 mg/mL PFS (11,13–15).
No deaths, malignancies, serious hypersensitivity reactions,
active tuberculosis, or adjudicated major adverse cardiovascular
events were observed in either study. Only two patients discon-
tinued the study drug due to COVID-19 logistical restrictions,
and there were only two AEs of COVID-19 reported.
There were some limitations to this analysis. The two clinical
studies were relatively small and conducted in a single country
(the United States, including Puerto Rico), and did not have a
similar study design. The placebo-controlled study (study 1) was
not followed by an open-label extension, so the use of placebo,
even when the randomization was 2:1, might have contributed
to higher rates of discontinuation. Study 2 had an open-label
design. The higher proportion of treatment-emergent AEs in
study 2 might be partly explained by the longer study duration
in comparison with study 1. However, it is important to note
that the proportion of patients with treatment-emergent AEs in
both studies was similar or even lower than in phase 3 clinical
studies (11,14,15). The occurrence of the COVID-19 pandemic
when the two studies were ending had some impact on study
discontinuations or missing assessments. Nevertheless, it did not
affect the studies outcome or the interpretation of the results or
overall conclusions.
In summary, superiority of risankizumab 150 mg/mL PFS vs.
placebo was demonstrated in all co-primary and ranked second-
ary efficacy endpoints. The efficacy and safety profile of the
risankizumab 150 mg/mL AI was consistent with the 150 mg/mL
PFS, and with the 90 mg/mL formulation used in the pivotal
phase 3 clinical studies. Usability and positive patient acceptabil-
ity of the PFS and the AI as shown here support the use of
these devices in patients with moderate to severe pla-
que psoriasis.
Acknowledgements
AbbVie and the authors thank the patients who participated in
the trials and all trial investigators for their contributions.
Medical writing support was provided by Maria Hovenden, PhD,
Table 3. Treatment-emergent adverse events in study 1 and 2.
Study 1 Study 2
n(%)
Risankizumab
150 mg/mL PFS
(n ¼105)
Placebo
(n ¼52)
Risankizumab
150 mg/mL AI
(N ¼108)
Any AE 22 (21.0) 11 (21.2) 47 (43.5)
Serious AE
a
1 (1.0) 0 6 (5.6)
Severe AE (grade 3 or 4) 1 (1.0) 0 8 (7.4)
AEs possibly related to study drug 6 (5.7) 2 (3.8) 16 (14.8)
AEs leading to discontinuation 0 1 (1.9) 1 (0.9)
Adjudicated MACE 0 0 0
Infections 6 (5.7) 3 (5.8) 30 (27.8)
Serious infections
b
0 0 2 (1.9)
Active tuberculosis 0 0 0
Malignancies 0 0 0
Malignancies excluding NMSC 0 0 0
Serious hypersensitivity 0 0 0
Injection site reaction 1 (1.0) 0 0
Deaths 0 0 0
AE: adverse event; AI: autoinjector; MACE: major adverse cardiac event; NMSC:
non-melanoma skin cancer; PFS: prefilled syringe.
a
In study 1, one patient experienced one serious AE of acute pancreatitis; in
study 2, six patients experienced seven serious AEs: appendicitis and prosta-
titis occurring in the same patient, and pyelonephritis, pyrexia, thermal burn,
lumbar spinal stenosis, and atrial fibrillation.
b
Two patients experienced serious infections: appendicitis (n¼1) and pyelo-
nephritis (n¼1).
JOURNAL OF DERMATOLOGICAL TREATMENT 7
Jennifer Venzie, PhD, and Janet Matsuura, PhD, of ICON (North
Wales, PA). All authors had access to relevant data and partici-
pated in the drafting, review, and approval of this publication.
No honoraria or payments were made for authorship.
Disclosure statement
Andrew Blauvelt has served as a scientific adviser and/or clinical
study investigator for AbbVie, Aligos, Almirall, Amgen, Arcutis,
Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb,
Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma,
Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi
Genzyme, Sun Pharma, and UCB Pharma. Kenneth B. Gordon
has received honoraria and/or research support from AbbVie,
Amgen, Arcutis, Arena Pharma, Bristol Myers Squibb, Dermavant,
Dermira, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma,
Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB. Patricia
Lee does not have any conflicts of interest, but her spouse is a
speaker for AbbVie. Jerry Bagel has received research funds pay-
able to Psoriasis Treatment Center from AbbVie, Amgen, Arcutis
Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb,
Celgene Corporation, Corrona LLC, Dermavant Sciences Ltd,
Dermira, UCB, Eli Lilly and Company, Glenmark Pharmaceuticals
Ltd, Janssen Biotech, Kadmon Corporation, Leo Pharma, Lycera
Corp, Menlo Therapeutics, Novartis, Pfizer, Regeneron
Pharmaceuticals, Sun Pharma, Taro Pharmaceutical Industries
Ltd, and Ortho Dermatologics; consultant fees from AbbVie,
Amgen, Celgene Corporation, Bristol-Myers Squibb, Eli Lilly and
Company, Janssen Biotech, Novartis, Sun Pharmaceutical
Industries Ltd, UCB; and fees for speaking from AbbVie, Celgene
Corporation, Eli Lilly, Janssen Biotech, and Novartis. Howard
Sofen has served as a scientific adviser and/or clinical study
investigator for AbbVie, Boehringer Ingelheim, Bristol Myers
Squibb, Dermavant, Eli Lilly, Incyte, Janssen, Leo, Novartis, Pfizer,
Sanofi Genzyme, Sun Pharma, and UCB. Benjamin Lockshin has
served as a speaker, consultant and/or clinical study investigator
for AbbVie, Bristol Myers Squibb, Celgene, Corrona registry, Eli
Lilly, Incyte, Novartis, Regeneron, Sanofi Genzyme, Sun Pharma,
and UCB. Ahmed M. Soliman, Ziqian Geng, Tianyu Zhan, and
Gabriela Alperovich are employees of AbbVie Inc. and may hold
stock or stock options. Linda Stein Gold has served as a scien-
tific adviser, speaker and/or clinical study investigator for
AbbVie, Almirall, Arcutis, Bristol Myers Squibb, Dermavant, Eli
Lilly and Company, Galderma, Incyte, Leo, Novartis, Ortho Derm,
Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and
UCB Pharma.
Funding
This work was supported by AbbVie. AbbVie participated in the
study design, research, analysis, data collection, interpretation of
data, reviewing, and approval of the publication.
ORCID
Andrew Blauvelt http://orcid.org/0000-0002-2633-985X
Howard http://orcid.org/0000-0001-7789-6915
Tianyu Zhan http://orcid.org/0000-0002-8572-4539
Linda Stein Gold http://orcid.org/0000-0002-2758-1605
Data availability statement
AbbVie is committed to responsible data sharing regarding the
clinical trials we sponsor. This includes access to anonymized,
individual, and trial-level data (analysis data sets), as well as
other information (e.g. protocols and Clinical Study Reports), as
long as the trials are not part of an ongoing or planned regula-
tory submission. This includes requests for clinical trial data for
unlicensed products and indications. These clinical trial data can
be requested by any qualified researchers who engage in rigor-
ous, independent scientific research, and will be provided fol-
lowing review and approval of a research proposal and
Statistical Analysis Plan (SAP) and execution of a Data Sharing
Agreement (DSA). Data requests can be submitted at any time
and the data will be accessible for 12 months, with possible
extensions considered. For more information on the process, or
to submit a request, visit the following link: https://www.abbvie.
com/our-science/clinical-trials/clinical-trials-data-and-information-
sharing/data-and-information-sharing-with-qualified-research-
ers.html.
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