2023 Meeting Magazine - 28

Placebo
Adverse Reaction
Fatigue
Neutropenia
Myalgia
Influenza like illness
N = 902
(%)
1
<1
1
1
RINVOQ
15 mg
N = 899
(%)
1
1
1
1
RINVOQ
30 mg
N = 906
(%)
2
2
2
2
* Includes: laryngitis, laryngitis viral, nasopharyngitis, oropharyngeal
pain, pharyngeal abscess, pharyngitis, pharyngitis streptococcal,
pharyngotonsillitis, respiratory tract infection, respiratory tract infection
viral, rhinitis, rhinolaryngitis, sinusitis, tonsillitis, tonsillitis bacterial,
upper respiratory tract infection, viral pharyngitis, viral upper respiratory
tract infection
** Includes: acne and dermatitis acneiform
*** Includes: genital herpes, genital herpes simplex, herpes dermatitis,
herpes ophthalmic, herpes simplex, nasal herpes, ophthalmic herpes
simplex, herpes virus infection, oral herpes
**** Includes anaphylactic reaction, anaphylactic shock, angioedema,
dermatitis exfoliative generalized, drug hypersensitivity, eyelid oedema,
face oedema, hypersensitivity, periorbital swelling, pharyngeal swelling,
swelling face, toxic skin eruption, type I hypersensitivity, urticaria
***** Includes abdominal pain and abdominal pain upper
****** Includes herpes zoster and varicella
Other adverse reactions reported in less than 1% of patients in the RINVOQ
15 mg and/or 30 mg group and at a higher rate than in the placebo group
through Week 16 included anemia, oral candidiasis, pneumonia, nonmelanoma
skin cancer, and the adverse event of retinal detachment.
The safety profile of RINVOQ through Week 52 was generally consistent with
the safety profile observed at Week 16.
Overall, the safety profile observed in patients with AD treated with
RINVOQ was similar to the safety profile in patients with RA. Other specific
adverse reactions that were reported in patients with AD included eczema
herpeticum/Kaposi's varicelliform eruption.
Eczema Herpeticum/Kaposi's Varicelliform Eruption
Placebo-controlled Period (16 weeks): Eczema herpeticum was reported
in 4 patients (1.6 per 100 patient-years) treated with placebo, 6 patients
(2.2 per 100 patient-years) treated with RINVOQ 15 mg and 7 patients
(2.6 per 100 patient-years) treated with RINVOQ 30 mg.
12-Month Exposure (Weeks 0 to 52): Eczema herpeticum was reported in
18 patients (1.6 per 100 patient-years) treated with RINVOQ 15 mg and 17
patients (1.5 per 100 patient-years) treated with RINVOQ 30 mg.
Adverse Reactions in Patients with Ulcerative Colitis
RINVOQ was studied up to 8 weeks in patients with moderately to severely
active ulcerative colitis in two randomized, double-blind, placebo-controlled
induction studies (UC-1, UC-2) and a randomized, double-blind, placebo
controlled, dose-finding study (UC-4; NCT02819635). Long term safety up
to 52-weeks was evaluated in patients who responded to induction therapy
in a randomized, double-blind, placebo-controlled maintenance study (UC-3)
and a long-term extension study.
In the two induction studies (UC-1, UC-2) and a dose finding study (UC-4),
1097 patients were enrolled of whom 719 patients received RINVOQ 45 mg
once daily.
In the maintenance study (UC-3), 746 patients were enrolled of whom 250
patients received RINVOQ 15 mg once daily and 251 patients received
RINVOQ 30 mg once daily.
Adverse reactions reported in ≥2% of patients in any treatment arm in the
induction and maintenance studies are shown in Tables 3 and 4, respectively.
Table 3: Adverse Reactions Reported in ≥2% of Patients with
Ulcerative Colitis Treated with RINVOQ 45 mg in PlaceboControlled
Induction Studies (UC-1, UC-2 and UC-4)
Placebo
Adverse Reaction
Upper respiratory tract infection*
Acne*
Increased blood creatine
phosphokinase
Neutropenia*
Rash*
Elevated liver enzymes**
Lymphopenia*
Folliculitis
Herpes simplex*
* Composed of several similar terms
** Elevated liver enzymes composed of elevated ALT, AST, GGT, ALP,
liver transaminases, hepatic enzymes, bilirubin, drug-induced liver injury
and cholestasis.
Other adverse reactions reported in less than 2% of patients in the RINVOQ
45 mg group and at a higher rate than in the placebo group through Week 8
included herpes zoster and pneumonia.
Table 4: Adverse Reactions Reported in ≥2% of Patients with
Ulcerative Colitis Treated with RINVOQ 15 mg or 30 mg in the
Placebo-Controlled Maintenance Study (UC-3)1
RINVOQ
Adverse Reaction
Placebo
Upper respiratory tract
infection*
Increased blood creatine
phosphokinase
Neutropenia*
Elevated liver enzymes**
Rash*
N = 245
(%)
18
2
2
1
4
15 mg Once
Daily
N = 250
(%)
16
6
3
6
5
RINVOQ
30 mg Once
Daily
N = 251
(%)
20
8
6
4
5
N = 378
(%)
7
1
1
<1
1
2
1
1
<1
RINVOQ
45 mg Once Daily
N = 719
(%)
9
6
5
5
4
3
3
2
2
Herpes zoster
Folliculitis
Hypercholesterolemia*
Influenza
Herpes simplex*
Lymphopenia*
Hyperlipidemia*
RINVOQ
Adverse Reaction
Placebo
N = 245
(%)
2
1
1
1
2
* Composed of several similar terms
** Elevated liver enzymes composed of elevated ALT, AST, GGT, ALP,
liver transaminases, hepatic enzymes, bilirubin, drug-induced liver injury,
and cholestasis.
The adverse reaction of non-melanoma skin cancer was reported in 1% of
patients in the RINVOQ 30 mg group and none of the patients in the RINVOQ
15 mg or placebo group through Week 52.
The safety profile of RINVOQ in the long-term extension study was similar
to the safety profile observed in the placebo-controlled induction and
maintenance periods.
Overall, the safety profile observed in patients with ulcerative colitis treated
with RINVOQ was generally similar to the safety profile in patients with RA
and AD.
Specific Adverse Reactions
Serious Infections
Induction Studies: In UC-1, UC-2, and UC-4, serious infections were reported
in 5 patients (8.4 per 100 patient-years) treated with placebo and 9 patients
(8.4 per 100 patient-years) treated with RINVOQ 45 mg through 8 weeks.
Placebo-controlled Maintenance Study: In UC-3, serious infections were
reported in 8 patients (6.3 per 100 patient-years) treated with placebo,
8 patients (4.5 per 100 patient-years) treated with RINVOQ 15 mg, and 6
patients (3.1 per 100 patient-years) treated with RINVOQ 30 mg through
52 weeks.
Laboratory Abnormalities
Hepatic Transaminase Elevations
In studies UC-1, UC-2, and UC-4, elevations of ALT to ≥ 3 x ULN in at
least one measurement were observed in 1.5% of patients treated with
RINVOQ 45 mg, and 0% of patients treated with placebo for 8 weeks. AST
elevations to ≥ 3 x ULN occurred in 1.5% of patients treated with RINVOQ
45 mg, and 0.3% of patients treated with placebo. Elevations of ALT to
≥ 5 x ULN occurred in 0.4% of patients treated with RINVOQ 45 mg and 0%
of patients treated with placebo.
In UC-3, elevations of ALT to ≥ 3 x ULN in at least one measurement were
observed in 4% of patients treated with RINVOQ 30 mg, 2% of patients
treated with RINVOQ 15 mg, and 0.8% of patients treated with placebo for
52 weeks. Elevations of AST to ≥ 3 x ULN in at least one measurement were
observed in 2% of patients treated with RINVOQ 30 mg, 1.6% of patients
treated with RINVOQ 15 mg and 0.4% of patients treated with placebo.
Elevations of ALT to ≥ 5 x ULN were observed in 0.8% of patients treated
with 30 mg, 0.4% of patients treated with 15 mg, and 0.4% of patients
treated with placebo.
Overall, laboratory abnormalities observed in patients with ulcerative colitis
treated with RINVOQ were similar to those described in patients with RA.
Adverse Reactions in Patients with Crohn's Disease
RINVOQ was studied up to 12 weeks in patients with moderately to severely
active CD in two randomized, double-blind, placebo-controlled induction
studies (CD-1, CD-2). Long term safety up to 52 weeks was evaluated in
patients who responded to induction therapy in a randomized, double-blind,
placebo-controlled maintenance study (CD-3), with additional data provided
from a long-term extension (LTE) period.
In the two induction studies (CD-1, CD-2), 1021 patients were enrolled, of
whom 674 patients received RINVOQ 45 mg once daily during the placebocontrolled
period.
In the maintenance study (CD-3), 673 patients were enrolled, of whom
221 patients received RINVOQ 15 mg once daily and 229 patients received
RINVOQ 30 mg once daily during the randomized, placebo-controlled period.
Overall, the safety profile observed in patients with Crohn's disease treated
with RINVOQ was consistent with the known safety profile for RINVOQ in
other indications.
Adverse reactions reported in ≥2% of patients treated with RINVOQ and at
a higher rate than placebo in the induction and maintenance studies are
shown in Tables 5 and 6, respectively.
Table 5: Adverse Reactions Reported in ≥2% of Patients with Crohn's
Disease Treated with RINVOQ 45 mg in Placebo-Controlled
Induction Studies (CD-1 and CD-2)
Placebo
Adverse Reaction
Upper respiratory tract infection*
Anemia*
Acne*
Pyrexia
Increased blood creatine
phosphokinase
Influenza
Herpes simplex*
Leukopenia*
Neutropenia*
Herpes zoster
* Composed of several similar terms
N = 347
(%)
8
6
2
3
1
1
1
1
<1
RINVOQ
45 mg Once Daily
N = 674
(%)
13
7
6
4
3
3
3
2
2
2
15 mg Once
Daily
N = 250
(%)
4
2
2
3
2
3
2
RINVOQ
30 mg Once
Daily
N = 251
(%)
4
4
4
3
3
2
2
1 Patients who were responders to 8 weeks induction therapy with RINVOQ
45 mg once daily
Adverse reactions reported in less than 2% of patients in the RINVOQ
45 mg group and at a higher rate than in the placebo group through Week
12 included folliculitis, hypercholesterolemia, bronchitis, pneumonia, oral
candidiasis, and hyperlipidemia.
Table 6: Adverse Reactions Reported in ≥2% of Patients with Crohn's
Disease Treated with RINVOQ 15 mg or 30 mg in the PlaceboControlled
Maintenance Study (CD-3)1
RINVOQ
Placebo
Adverse Reaction
Upper respiratory tract
infection*
Pyrexia
Herpes zoster*
Headache*
Acne*
Gastroenteritis*
Fatigue
Increased blood creatine
phosphokinase
Elevated liver enzymes2
Leukopenia*
Neutropenia*
Bronchitis*
Pneumonia*
Cough
N = 223
(%)
11
2
2
1
3
2
2
1
<1
<1
<1
1
2
15 mg Once
Daily
N = 221
(%)
14
3
3
3
2
3
3
2
2
1
1
1
4
3
RINVOQ
30 mg Once
Daily
N = 229
(%)
12
7
5
5
5
3
3
3
3
2
2
2
1
1
1 Patients who were responders to 12 weeks induction therapy with
RINVOQ 45 mg once daily.
2 Elevated liver enzymes includes alanine aminotransferase increased,
aspartate aminotransferase increased, blood alkaline phosphatase
increased, transaminases increased, blood bilirubin increased.
* Composed of several similar terms
Adverse reactions reported in less than 2% of patients in the RINVOQ 15 mg
or 30 mg group and at a higher rate than in the placebo group through Week
52 included hyperlipidemia, oral candidiasis, and hypercholesterolemia.
The safety profile of RINVOQ in the long-term extension study was similar
to the safety profile observed in the placebo-controlled induction and
maintenance periods.
Specific Adverse Reactions
Serious Infections
Induction Studies: In CD-1 and CD-2, serious infections were reported in
6 patients (8 per 100 patient-years) treated with placebo and 13 patients
(9 per 100 patient-years) treated with RINVOQ 45 mg through 12 weeks of
the placebo-controlled period.
Maintenance Study/LTE: In the long-term placebo-controlled period,
serious infections were reported in 10 patients (7 per 100 patient-years)
treated with placebo, 7 patients (4 per 100 patient-years) treated with
RINVOQ 15 mg, and 13 patients (6 per 100 patient-years) treated with
RINVOQ 30 mg.
Gastrointestinal Perforations
Induction Studies: During the induction studies in all patients treated with
RINVOQ 45 mg (N=938), gastrointestinal perforation was reported in 4
patients (2 per 100 patient-years). In the placebo-controlled induction
period, in CD-1 and CD-2, gastrointestinal perforation was reported in no
patients treated with placebo (N=347) and 1 patient (1 per 100 patientyears)
treated with RINVOQ 45 mg (N=674) through 12 weeks.
Maintenance Study/LTE: In the long-term placebo-controlled period,
gastrointestinal perforation was reported in 1 patient (1 per 100 patientyears)
treated with placebo, 1 patient (<1 per 100 patient-years) treated
with RINVOQ 15 mg, and 1 patient (<1 per 100 patient-years) treated with
RINVOQ 30 mg.
Patients who received placebo or RINVOQ 15 mg for maintenance therapy
and lost response were treated with rescue RINVOQ 30 mg (N=336). Among
these patients, gastrointestinal perforation was reported in 3 patients
(1 per 100 patient-years) through long-term treatment.
Adverse Reactions in Patients with Ankylosing Spondylitis
A total of 596 patients with ankylosing spondylitis were treated with RINVOQ
15 mg in the two clinical trials representing 577.3 patient-years of exposure,
of whom 220 were exposed to RINVOQ 15 mg for at least one year.
Overall, the safety profile observed in patients with active ankylosing
spondylitis treated with RINVOQ 15 mg was consistent with the safety
profile observed in patients with rheumatoid arthritis and psoriatic arthritis.
During the 14-week placebo-controlled period in Trial AS-I, the frequency of
headache was 5.4% with RINVOQ 15 mg and 2.1% with placebo. During the
14-week placebo-controlled period in Trial AS-II, the frequency of headache
was 3.3% with RINVOQ 15 mg and 1.4% with placebo.
Adverse Reactions in Patients with Non-radiographic Axial Spondyloarthritis
A total of 187 patients with non-radiographic axial spondyloarthritis were
treated with RINVOQ 15 mg in the clinical trial representing 116.6 patientyears
of exposure, of whom 31 were exposed to RINVOQ 15 mg for at least
one year.
Overall, the safety profile observed in patients with active non-radiographic
axial spondyloarthritis treated with RINVOQ 15 mg was consistent with
the safety profile observed in patients with rheumatoid arthritis, psoriatic
arthritis, and ankylosing spondylitis.
DRUG INTERACTIONS
Strong CYP3A4 Inhibitors
Upadacitinib exposure is increased when RINVOQ is co-administered with
a strong CYP3A4 inhibitor (such as ketoconazole, clarithromycin, and
grapefruit), which may increase the risk of RINVOQ adverse reactions.
Monitor patients with rheumatoid arthritis, psoriatic arthritis, ankylosing
spondylitis and non-radiographic axial spondylarthritis closely for adverse
reactions when co-administering RINVOQ 15 mg once daily with strong
CYP3A4 inhibitors. Food or drink containing grapefruit should be avoided
during treatment with RINVOQ.
For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once
daily with strong CYP3A4 inhibitors is not recommended.
https://www.rinvoqhcp.com/
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