2023 Meeting Magazine - 37

SKYRIZI®
(sky-RIZZ-ee) (risankizumab-rzaa) injection, for subcutaneous or intravenous use
150 mg/mL single-dose pen and prefilled syringe
600 mg/10 mL single-dose vial for intravenous infusion
180 mg/1.2 mL single-dose prefilled cartridge with on-body injector
360 mg/2.4 mL single-dose prefilled cartridge with on-body injector
PROFESSIONAL BRIEF SUMMARY
CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE
Plaque Psoriasis
SKYRIZI® is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates
for systemic therapy or phototherapy.
Psoriatic Arthritis
SKYRIZI is indicated for the treatment of active psoriatic arthritis in adults.
Crohn's Disease
SKYRIZI is indicated for the treatment of moderately to severely active Crohn's disease in adults.
CONTRAINDICATIONS
SKYRIZI is contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or
any of the excipients [see Warnings and Precautions].
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of SKYRIZI. If a
serious hypersensitivity reaction occurs, discontinue SKYRIZI and initiate appropriate therapy immediately
[see Adverse Reactions].
Infections
SKYRIZI may increase the risk of infections [see Adverse Reactions].
Treatment with SKYRIZI should not be initiated in patients with any clinically important active infection until the
infection resolves or is adequately treated.
In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior
to prescribing SKYRIZI. Instruct patients to seek medical advice if signs or symptoms of clinically important
infection occur. If a patient develops such an infection or is not responding to standard therapy, monitor the
patient closely and do not administer SKYRIZI until the infection resolves.
Tuberculosis
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI. Across the Phase 3
psoriasis clinical studies, of the 72 subjects with latent TB who were concurrently treated with SKYRIZI and
appropriate TB prophylaxis during the studies, none developed active TB during the mean follow-up of 61
weeks on SKYRIZI. Two subjects taking isoniazid for treatment of latent TB discontinued treatment due to liver
injury. Of the 31 subjects from the PsO-3 study with latent TB who did not receive prophylaxis during the study,
none developed active TB during the mean follow-up of 55 weeks on SKYRIZI. Consider anti-TB therapy prior to
initiating SKYRIZI in patients with a past history of latent or active TB in whom an adequate course of treatment
cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SKYRIZI treatment.
Do not administer SKYRIZI to patients with active TB.
Hepatotoxicity in Treatment of Crohn's Disease
A serious adverse reaction of drug-induced liver injury in conjunction with a rash that required hospitalization
was reported in a patient with Crohn's disease (ALT 54x ULN, AST 30x ULN, and total bilirubin 2.2x
ULN) following two 600 mg intravenous doses of SKYRIZI. The liver test abnormalities resolved following
administration of steroids. SKYRIZI was subsequently discontinued.
For the treatment of Crohn's disease, evaluate liver enzymes and bilirubin at baseline, and during induction at
least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.
Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause
of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt
treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek
immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.
Administration of Vaccines
Avoid use of live vaccines in patients treated with SKYRIZI. Medications that interact with the immune system
may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with
SKYRIZI, complete all age-appropriate vaccinations according to current immunization guidelines. No data are
available on the response to live or inactive vaccines.
ADVERSE REACTIONS
The following adverse reactions are discussed in other sections of labeling:
* Hypersensitivity Reactions [see Warnings and Precautions]
* Infections [see Warnings and Precautions]
* Tuberculosis [see Warnings and Precautions]
* Hepatotoxicity in Treatment of Crohn's Disease [see Warnings and Precautions]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse drug reaction rates observed in
the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may
not reflect the rates observed in practice.
Plaque Psoriasis
A total of 2234 subjects were treated with SKYRIZI in clinical development trials in plaque psoriasis. Of these,
1208 subjects with psoriasis were exposed to SKYRIZI for at least one year.
Data from placebo- and active-controlled trials were pooled to evaluate the safety of SKYRIZI for up to 16
weeks. In total, 1306 subjects were evaluated in the SKYRIZI 150 mg group.
Table 1 summarizes the adverse drug reactions that occurred at a rate of at least 1% and at a higher rate in
the SKYRIZI group than the placebo group during the 16-week controlled period of pooled clinical trials.
Table 1. Adverse Drug Reactions Occurring in ≥ 1% of Subjects on SKYRIZI through Week 16
Adverse Drug Reactions
SKYRIZI
N = 1306
n (%)
Upper respiratory infectionsa
Headacheb
Fatiguec
Injection site reactionsd
Tinea infectionse
170 (13.0)
46 (3.5)
33 (2.5)
19 (1.5)
15 (1.1)
Placebo
N = 300
n (%)
29 (9.7)
6 (2.0)
3 (1.0)
3 (1.0)
1 (0.3)
a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis,
nasopharyngitis, pharyngitis (including viral), tonsillitis
b Includes: headache, tension headache, sinus headache, cervicogenic headache
c Includes: fatigue, asthenia
d Includes: injection site bruising, erythema, extravasation, hematoma, hemorrhage, infection, inflammation,
irritation, pain, pruritus, reaction, swelling, warmth
e Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, tinea infection,
onychomycosis
Adverse drug reactions that occurred in < 1% but > 0.1% of subjects in the SKYRIZI group and at a higher rate
than in the placebo group through Week 16 were folliculitis and urticaria.
Specific Adverse Drug Reactions
Infections
In the first 16 weeks, infections occurred in 22.1% of the SKYRIZI group (90.8 events per 100 subjectyears)
compared with 14.7% of the placebo group (56.5 events per 100 subject-years) and did not lead to
discontinuation of SKYRIZI. The rates of serious infections for the SKYRIZI group and the placebo group were
≤0.4%. Serious infections in the SKYRIZI group included cellulitis, osteomyelitis, sepsis, and herpes zoster.
In Studies PsO-1 and PsO-2, through Week 52, the rate of infections (73.9 events per 100 subject-years) was
similar to the rate observed during the first 16 weeks of treatment.
Safety Through Week 52
Through Week 52, no new adverse reactions were identified, and the rates of the adverse reactions were
similar to those observed during the first 16 weeks of treatment. During this period, serious infections that led
to study discontinuation included pneumonia.
Psoriatic Arthritis
The overall safety profile observed in subjects with psoriatic arthritis treated with SKYRIZI is generally
consistent with the safety profile in subjects with plaque psoriasis. Additionally, in the Phase 3 placebocontrolled
trials the incidence of hepatic events was higher in the SKYRIZI group (5.4%, 16.7 events per 100
patient years) compared to the placebo group (3.9%, 12.6 events per 100 patient years). Of these, the most
common events that were reported more frequently in both the placebo group and the SKYRIZI group were ALT
increased (placebo: n=12 (1.7%); SKYRIZI: n=16 (2.3%)), AST increased (placebo: n=9 (1.3%); SKYRIZI: n=13
(1.8%)), and GGT increased (placebo: n=5 (0.7%); SKYRIZI: n=8 (1.1%)). There were no serious hepatic events
reported. The incidence of hypersensitivity reactions was higher in the SKYRIZI group (n=16, 2.3%) compared
to the placebo group (n=9, 1.3%). In the Phase 3 placebo-controlled trials, hypersensitivity reactions reported
at a higher rate in the SKYRIZI group included rash (placebo: n=4 (0.6%); SKYRIZI: n=5 (0.7%), allergic rhinitis
(placebo: n=1 (0.1%); SKYRIZI: n=2 (0.3%), and facial swelling (placebo: n=0 (0.0%); SKYRIZI n=1 (0.1%).
One case of anaphylaxis was reported in a subject who received SKYRIZI in the Phase 2 clinical trial.
Upper respiratory infectionsb
Headachec
Arthralgia
Crohn's Disease
SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active Crohn's disease in two
randomized, double-blind, placebo-controlled induction studies (CD-1, CD-2) and a randomized, doubleblind,
placebo-controlled, dose-finding study (CD-4; NCT02031276). Long-term safety up to 52 weeks was
evaluated in subjects who responded to induction therapy in a randomized, double-blind, placebo-controlled
maintenance study (CD-3).
In the two induction studies (CD-1, CD-2) and the dose finding study (CD-4), 620 subjects received the SKYRIZI
intravenous induction regimen at Weeks 0, 4 and 8. In the maintenance study (CD-3), 297 subjects who
achieved clinical response, defined as a reduction in CDAI of at least 100 points from baseline after 12 weeks
of induction treatment with intravenous SKYRIZI in studies CD-1 and CD-2, received a maintenance regimen
of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every 8 weeks thereafter for up to an
additional 52 weeks.
Adverse reactions reported in > 3% of subjects in induction studies and at a higher rate than placebo are
shown in Table 2.
Table 2. Adverse Drug Reactions Reported in > 3% of Subjects with Crohn's Disease Treated with
SKYRIZI in Placebo-Controlled 12-Week Induction Studies
SKYRIZI
Adverse Drug Reactions
600 mg Intravenous
Infusiona
N = 620
n (%)
66 (10.6)
41 (6.6)
31 (5.0)
Placebo
N = 432
n (%)
40 (9.3)
24 (5.6)
19 (4.4)
a SKYRIZI 600 mg as an intravenous infusion at Week 0, Week 4, and Week 8.
b Includes: influenza like illness, nasopharyngitis, influenza, pharyngitis, upper respiratory tract infection,
viral upper respiratory tract infection, COVID-19, nasal congestion, respiratory tract infection viral, viral
pharyngitis, tonsillitis, upper respiratory tract inflammation
c Includes: headache, tension headache
Adverse reactions reported in >3% of subjects in the maintenance study and at a higher rate than placebo are
shown in Table 3.
Table 3. Adverse Reactions Reported in >3% of Subjects with Crohn's Disease Treated with SKYRIZIa
in Placebo-Controlled 52-Week Maintenance Study (CD-3)
SKYRIZI
Adverse Drug Reactions
Arthralgia
Abdominal painb
Injection site reactionsc,d
Anemia
Pyrexia
Back pain
Arthropathy
Urinary tract infection
180 mg Subcutaneous
Injection
N = 155
n (%)
13 (8.4)
9 (5.8)
7 (4.5)
7 (4.5)
4 (2.6)
3 (1.9)
1 (0.6)
1 (0.6)
SKYRIZI
360 mg Subcutaneous
Injection
N = 142
n (%)
13 (9.2)
12 (8.5)
8 (5.6)
7 (4.9)
7 (4.9)
6 (4.2)
5 (3.5)
5 (3.5)
Placebo
N = 143
n (%)
12 (8.4)
6 (4.2)
4 (2.8)
6 (4.2)
4 (2.8)
3 (2.1)
2 (1.4)
4 (2.8)
a SKYRIZI 180 mg or 360 mg at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks
b Includes: abdominal pain, abdominal pain upper, abdominal pain lower
c Includes: injection site rash, injection site erythema, injection site swelling, injection site urticaria, injection
site warmth, injection site pain, injection site hypersensitivity, injection site reaction
d Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are
counted only once per subject for the rate calculations.
Specific Adverse Drug Reactions
Infections
In the maintenance study (CD-3) through Week 52, the rate of infections was 32.3% (50.2 events per 100
subject-years) in subjects who received SKYRIZI 180 mg and 36.6% (60.8 events per 100 subject-years) in
subjects who received SKYRIZI 360 mg compared to 36.4% (60.3 events per 100 subject-years) in subjects
who received placebo after SKYRIZI induction. The rate of serious infections was 2.6% (2.7 events per 100
subject-years) in subjects who received SKYRIZI 180 mg and 5.6% (7.4 events per 100 subject-years) in
subjects who received SKYRIZI 360 mg compared to 2.1% (2.4 events per 100 subject-years) in subjects who
received placebo after SKYRIZI induction.
Lipid Elevations
Elevations in lipid parameters (total cholesterol and low-density lipoprotein cholesterol [LDL-C]) were first
assessed at 4 weeks following initiation of SKYRIZI in the induction trials (CD-1, CD-2). Increases from
baseline and increases relative to placebo were observed at Week 4 and remained stable to Week 12.
Following SKYRIZI induction, mean total cholesterol increased by 9.4 mg/dL from baseline to a mean absolute
value of 175.1 mg/dL at Week 12. Similarly, mean LDL-C increased by 6.6 mg/dL from baseline to a mean
absolute value of 92.6 mg/dL at Week 12. Mean LDL-C increased by 3.1 mg/dL from baseline to a mean
absolute value of 99.0 mg/dL at Week 52 with SKYRIZI 180 mg maintenance treatment and by 2.3 mg/dL from
baseline to a mean absolute value of 102.2 mg/dL at Week 52 with SKYRIZI 360 mg maintenance treatment.
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is
highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody
(including neutralizing antibody) positivity in an assay may be influenced by several factors including assay
methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence
of antibodies in other studies or to other products, including other risankizumab products, may be misleading.
Plaque Psoriasis
By Week 52, approximately 24% (263/1079) of subjects treated with SKYRIZI at the recommended dose
developed antibodies to risankizumab-rzaa. Of the subjects who developed antibodies to risankizumabrzaa,
approximately 57% (14% of all subjects treated with SKYRIZI) had antibodies that were classified as
neutralizing. Higher antibody titers in approximately 1% of subjects treated with SKYRIZI were associated with
lower risankizumab-rzaa concentrations and reduced clinical response.
Psoriatic Arthritis
By Week 28, approximately 12.1% (79/652) of subjects treated with SKYRIZI at the recommended dose
developed antibodies to risankizumab-rzaa. None of the subjects who developed antibodies to risankizumabrzaa
had antibodies that were classified as neutralizing. Antibodies to risankizumab-rzaa were not associated
with changes in clinical response for psoriatic arthritis. A higher proportion of subjects with anti-drug
antibodies experienced hypersensitivity reactions (6.3% (5/79)) and injection site reactions (2.5% (2/79))
compared to subjects without anti-drug antibodies (3.8% (22/574) with hypersensitivity reactions and
0.7% (4/574) with injection site reactions). None of these hypersensitivity and injection site reactions led to
discontinuation of risankizumab-rzaa.
Crohn's Disease
By Week 64, antibodies to risankizumab-rzaa developed in approximately 3.4% (2/58) of subjects treated with
SKYRIZI induction followed by 360 mg maintenance regimen. No subjects (0/57) treated with SKYRIZI induction
followed by 180 mg maintenance regimen developed antibodies to risankizumab-rzaa. None of the subjects
who developed antibodies to risankizumab-rzaa had antibodies that were classified as neutralizing.
Postmarketing Experience
The following adverse reactions have been reported during post-approval of SKYRIZI. Because these reactions
are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to SKYRIZI exposure:
* Skin and subcutaneous tissue disorders: eczema and rash
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while
treated with SKYRIZI. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting
http://glowpregnancyregistry.com.
Risk Summary
Available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient
to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal
outcomes. Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported
across the placenta, and SKYRIZI may cause immunosuppression in the in utero-exposed infant. There are
adverse pregnancy outcomes in women with inflammatory bowel disease (see Clinical Considerations).
In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeys were
administered subcutaneous doses of 5 or 50 mg/kg risankizumab-rzaa once weekly during the period of
organogenesis up to parturition. Increased fetal/infant loss was noted in pregnant monkeys at the 50 mg/kg
dose (see Data). The 50 mg/kg dose in pregnant monkeys resulted in approximately 10 times the exposure
(AUC) in humans administered the 600 mg induction regimen and 39 times the exposure (AUC) to the
360 mg maintenance doses, respectively. No risankizumab-rzaa-related effects on functional or immunological
development were observed in infant monkeys from birth through 6 months of age. The clinical significance of
these findings for humans is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk
of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population,
the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is
2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-associated maternal and embryo/fetal risk
Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease
is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before
37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.
Fetal/Neonatal adverse reactions
Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks
during the third trimester. Because risankizumab may interfere with immune response to infections, risks and
benefits should be considered prior to administering live vaccines to infants exposed to SKYRIZI in utero. There
are insufficient data regarding infant serum levels of risankizumab at birth and the duration of persistence of
risankizumab in infant serum after birth. Although a specific timeframe to delay live virus immunizations in
infants exposed in utero is unknown, a minimum of 5 months after birth should be considered because of the
half-life of the product.
Data
Animal Data
An enhanced pre- and post-natal developmental toxicity study was conducted in cynomolgus monkeys.
Pregnant cynomolgus monkeys were administered weekly subcutaneous doses of risankizumab-rzaa of
5 or 50 mg/kg from gestation day 20 to parturition, and the cynomolgus monkeys (mother and infants)
were monitored for 6 months after delivery. No maternal toxicity was noted in this study. There were no
treatment-related effects on growth and development, malformations, developmental immunotoxicology,
or neurobehavioral development. However, a dose-dependent increase in fetal/infant loss was noted in
the risankizumab-rzaa-treated groups (32% and 43% in the 5 mg/kg and 50 mg/kg groups, respectively)
compared with the vehicle control group (19%). The increased fetal/infant loss in the 50 mg/kg group was
considered to be related to risankizumab-rzaa treatment. The no observed adverse effect level (NOAEL) for
maternal toxicity was identified as 50 mg/kg and the NOAEL for developmental toxicity was identified as
5 mg/kg. On an exposure (AUC) basis, the 5 mg/kg dose in pregnant monkeys resulted in approximately
1.24 times the exposure in humans administered the 600 mg induction regimen and 5 times the exposure
in humans administered the 360 mg maintenance doses, respectively. In the infants, mean serum
concentrations increased in a dose-dependent manner and were approximately 17%-86% of the respective
maternal concentrations. Following delivery, most adult female cynomolgus monkeys and all infants from the
risankizumab-rzaa-treated groups had measurable serum concentrations of risankizumab-rzaa up to 91 days
postpartum. Serum concentrations were below detectable levels at 180 days postpartum.
Lactation
Risk Summary
There are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or
the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred in human
milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to
risankizumab-rzaa are unknown. The developmental and health benefits of breastfeeding should be considered
along with the mother's clinical need for SKYRIZI and any potential adverse effects on the breastfed infant from
SKYRIZI or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of SKYRIZI have not been established in pediatric patients.
Geriatric Use
Of the 2234 subjects with plaque psoriasis exposed to SKYRIZI, 243 subjects were 65 years or older and 24
subjects were 75 years or older. No overall differences in SKYRIZI exposure, safety, or effectiveness were
observed between older and younger subjects who received SKYRIZI. However, the number of subjects aged
65 years and older was not sufficient to determine whether they respond differently from younger subjects.
Clinical studies of SKYRIZI for the treatment of Crohn's disease did not include sufficient numbers of subjects
65 years of age and older to determine whether they respond differently from younger adult subjects.
No clinically meaningful differences in the pharmacokinetics of risankizumab-rzaa were observed in geriatric
subjects compared to younger adult subjects with Crohn's disease.
PATIENT COUNSELING INFORMATION
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and
Instructions for Use).
Hypersensitivity Reactions
Advise patients to discontinue SKYRIZI and seek immediate medical attention if they experience any symptoms
of serious hypersensitivity reactions [see Warnings and Precautions].
Infections
Inform patients that SKYRIZI may lower the ability of their immune system to fight infections. Instruct patients
of the importance of communicating any history of infections to the healthcare provider and contacting their
healthcare provider if they develop any symptoms of an infection [see Warnings and Precautions].
Hepatotoxicity in Treatment of Crohn's Disease
Inform patients that SKYRIZI may cause liver injury, especially during the initial 12 weeks of treatment. Instruct
patients to seek immediate medical attention if they experience symptoms suggestive of liver dysfunction.
(e.g., unexplained rash, nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine)
[see Warnings and Precautions].
Administration of Vaccines
Advise patients that vaccination with live vaccines is not recommended during SKYRIZI treatment and
immediately prior to or after SKYRIZI treatment. Medications that interact with the immune system may
increase the risk of infection following administration of live vaccines. Instruct patients to inform the healthcare
practitioner that they are taking SKYRIZI prior to a potential vaccination [see Warnings and Precautions].
Administration Instruction
Instruct patients or caregivers to perform the first self-injected dose under the supervision and guidance of a
qualified healthcare professional for training in preparation and administration of SKYRIZI, including choosing
anatomical sites for administration, and proper subcutaneous injection technique.
If using SKYRIZI 75 mg/0.83 mL, instruct patients or caregivers to administer two 75 mg single-dose syringes
to achieve the full 150 mg dose of SKYRIZI.
Instruct patients or caregivers in the technique of pen or syringe disposal.
Pregnancy
Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to
SKYRIZI during pregnancy [see Use in Specific Populations].
Manufactured by:
AbbVie Inc.
North Chicago, IL 60064, USA
US License Number 1889
SKYRIZI® is a registered trademark of AbbVie Biotechnology Ltd.
© 2019-2022 AbbVie Inc.
Ref: 20072970 Revised: September, 2022
LAB-8091 MASTER
US-SKZR-230005

http://www.SkyriziHCP.com/rheumatology http://www.glowpregnancyregistry.com

2023 Meeting Magazine

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