2023 Meeting Magazine - 27

with shortened gastrointestinal transit times. Instruct patients to contact
their healthcare provider if medication residue is observed repeatedly.
Monitor patients clinically and consider alternative treatment if there is an
inadequate therapeutic response.
ADVERSE REACTIONS
The following clinically significant adverse reactions are described
elsewhere in the labeling:
* Serious Infections [see Warnings and Precautions]
* Mortality [see Warnings and Precautions]
* Malignancy and Lymphoproliferative Disorders [see Warnings and
Precautions]
* Major Adverse Cardiovascular Events [see Warnings and Precautions]
* Thrombosis [see Warnings and Precautions]
* Hypersensitivity Reactions [see Warnings and Precautions]
* Gastrointestinal Perforations [see Warnings and Precautions]
* Laboratory Abnormalities [see Warnings and Precautions]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug cannot be
directly compared to rates in the clinical trials of another drug and may not
reflect the rates observed in practice.
Adverse Reactions in Patients with Rheumatoid Arthritis
A total of 3833 patients with rheumatoid arthritis were treated with
upadacitinib in the Phase 3 clinical trials of whom 2806 were exposed for
at least one year.
Patients could advance or switch to RINVOQ 15 mg from placebo, or be
rescued to RINVOQ from active comparator or placebo from as early as
Week 12 depending on the trial design.
A total of 2630 patients received at least 1 dose of RINVOQ 15 mg, of whom
1860 were exposed for at least one year. In trials RA-I, RA-II, RA-III and
RA-V, 1213 patients received at least 1 dose of RINVOQ 15 mg, of which
986 patients were exposed for at least one year, and 1203 patients received
at least 1 dose of upadacitinib 30 mg, of which 946 were exposed for at
least one year.
Table 1: Adverse Reactions Reported in ≥ 1% of Rheumatoid
Arthritis Patients Treated with RINVOQ 15 mg in
Placebo-controlled Trials
Placebo
Adverse Reaction
Upper respiratory tract infection (URTI)*
Nausea
Cough
Pyrexia
N = 1042
(%)
9.5
2.2
1.0
RINVOQ
15 mg
N = 1035
(%)
13.5
3.5
2.2
1.2
*URTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal
pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral
upper respiratory tract infection
Other adverse reactions reported in less than 1% of patients in the RINVOQ
15 mg group and at a higher rate than in the placebo group through Week 12
included pneumonia, herpes zoster, herpes simplex (includes oral herpes),
and oral candidiasis.
Four integrated datasets are presented in the Specific Adverse Reaction
section:
Placebo-controlled Trials: Trials RA-III, RA-IV, and RA-V were integrated to
represent safety through 12/14 weeks for placebo (n=1042) and RINVOQ
15 mg (n=1035). Trials RA-III and RA-V were integrated to represent safety
through 12 weeks for placebo (n=390), RINVOQ 15 mg (n=385), and
upadacitinib 30 mg (n=384). Trial RA-IV did not include the 30 mg dose and,
therefore, safety data for upadacitinib 30 mg can only be compared with
placebo and RINVOQ 15 mg rates from pooling trials RA-III and RA-V.
MTX-controlled Trials: Trials RA-I and RA-II were integrated to represent
safety through 12/14 weeks for MTX (n=530), RINVOQ 15 mg (n=534), and
upadacitinib 30 mg (n=529).
12-Month Exposure Dataset: Trials RA-I, II, III, and V were integrated to
represent the long-term safety of RINVOQ 15 mg (n=1213) and upadacitinib
30 mg (n=1203).
Exposure adjusted incidence rates were adjusted by trial for all the adverse
events reported in this section.
Specific Adverse Reactions
Infections
Placebo-controlled Trials: In RA-III, RA-IV, and RA-V, infections were
reported in 218 patients (95.7 per 100 patient-years) treated with
placebo and 284 patients (127.8 per 100 patient-years) treated with
RINVOQ 15 mg. In RA-III and RA-V, infections were reported in 99
patients (136.5 per 100 patient-years) treated with placebo, 118 patients
(164.5 per 100 patient-years) treated with RINVOQ 15 mg, and 126 patients
(180.3 per 100 patient-years) treated with upadacitinib 30 mg.
MTX-controlled Trials: Infections were reported in 127 patients
(119.5 per 100 patient-years) treated with MTX monotherapy, 104 patients
(91.8 per 100 patient-years) treated with RINVOQ 15 mg monotherapy, and
128 patients (115.1 per 100 patient-years) treated with upadacitinib 30 mg
monotherapy.
12-Month Exposure Dataset: Infections were reported in 615 patients
(83.8 per 100 patient-years) treated with RINVOQ 15 mg and 674 patients
(99.7 per 100 patient-years) treated with upadacitinib 30 mg.
Serious Infections
Placebo-controlled Trials: In RA-III, RA-IV, and RA-V, serious infections were
reported in 6 patients (2.3 per 100 patient-years) treated with placebo, and
12 patients (4.6 per 100 patient-years) treated with RINVOQ 15 mg. In RA-III
and RA-V, serious infections were reported in 1 patient (1.2 per 100 patientyears)
treated with placebo, 2 patients (2.3 per 100 patient-years) treated
with RINVOQ 15 mg, and 7 patients (8.2 per 100 patient-years) treated with
upadacitinib 30 mg.
MTX-controlled Trials: Serious infections were reported in 2 patients
(1.6 per 100 patient-years) treated with MTX monotherapy, 3 patients
(2.4 per 100 patient-years) treated with RINVOQ 15 mg monotherapy, and
8 patients (6.4 per 100 patient-years) treated with upadacitinib 30 mg
monotherapy.
12-Month Exposure Dataset: Serious infections were reported in 38 patients
(3.5 per 100 patient-years) treated with RINVOQ 15 mg and 59 patients
(5.6 per 100 patient-years) treated with upadacitinib 30 mg.
The most frequently reported serious infections were pneumonia and cellulitis.
Tuberculosis
Placebo-controlled Trials and MTX-controlled Trials: In the placebocontrolled
period, there were no active cases of tuberculosis reported
in the placebo, RINVOQ 15 mg, and upadacitinib 30 mg groups. In the
MTX-controlled period, there were no active cases of tuberculosis reported
in the MTX monotherapy, RINVOQ 15 mg monotherapy, and upadacitinib
30 mg monotherapy groups.
12-Month Exposure Dataset: Active tuberculosis was reported for 2 patients
treated with RINVOQ 15 mg and 1 patient treated with upadacitinib 30 mg.
Cases of extra-pulmonary tuberculosis were reported.
Opportunistic Infections (excluding tuberculosis)
Placebo-controlled Trials: In RA-III, RA-IV, and RA-V, opportunistic infections
were reported in 3 patients (1.2 per 100 patient-years) treated with placebo,
and 5 patients (1.9 per 100 patient-years) treated with RINVOQ 15 mg.
In RA-III and RA-V, opportunistic infections were reported in 1 patient
(1.2 per 100 patient-years) treated with placebo, 2 patients (2.3 per 100
patient-years) treated with RINVOQ 15 mg, and 6 patients (7.1 per 100
patient-years) treated with upadacitinib 30 mg.
MTX-controlled Trials: Opportunistic infections were reported in 1 patient
(0.8 per 100 patient-years) treated with MTX monotherapy, 0 patients
treated with RINVOQ 15 mg monotherapy, and 4 patients (3.2 per 100
patient-years) treated with upadacitinib 30 mg monotherapy.
12-Month Exposure Dataset: Opportunistic infections were reported in 7
patients (0.6 per 100 patient-years) treated with RINVOQ 15 mg and 15
patients (1.4 per 100 patient-years) treated with upadacitinib 30 mg.
Malignancies
Placebo-controlled Trials: In RA-III, RA-IV, and RA-V, malignancies excluding
NMSC were reported in 1 patient (0.4 per 100 patient-years) treated with
placebo, and 1 patient (0.4 per 100 patient-years) treated with RINVOQ
15 mg. In RA-III and RA-V, malignancies excluding NMSC were reported in 0
patients treated with placebo, 1 patient (1.1 per 100 patient-years) treated
with RINVOQ 15 mg, and 3 patients (3.5 per 100 patient-years) treated with
upadacitinib 30 mg.
MTX-controlled Trials: Malignancies excluding NMSC were reported in
1 patient (0.8 per 100 patient-years) treated with MTX monotherapy,
3 patients (2.4 per 100 patient-years) treated with RINVOQ 15 mg
monotherapy, and 0 patients treated with upadacitinib 30 mg monotherapy.
12-Month Exposure Dataset: Malignancies excluding NMSC were reported in
13 patients (1.2 per 100 patient-years) treated with RINVOQ 15 mg and 14
patients (1.3 per 100 patient-years) treated with upadacitinib 30 mg.
Gastrointestinal Perforations
Placebo-controlled Trials: There were no gastrointestinal perforations
(based on medical review) reported in patients treated with placebo, RINVOQ
15 mg, and upadacitinib 30 mg.
MTX-controlled Trials: There were no cases of gastrointestinal perforations
reported in the MTX and RINVOQ 15 mg group through 12/14 weeks. Two
cases of gastrointestinal perforations were observed in the upadacitinib
30 mg group.
12-Month Exposure Dataset: Gastrointestinal perforations were reported
in 1 patient treated with RINVOQ 15 mg and 4 patients treated with
upadacitinib 30 mg.
Thrombosis
Placebo-controlled Trials: In RA-IV, venous thrombosis (pulmonary embolism
or deep vein thrombosis) was observed in 1 patient treated with placebo
and 1 patient treated with RINVOQ 15 mg. In RA-V, venous thrombosis
was observed in 1 patient treated with RINVOQ 15 mg. There were no
observed cases of venous thrombosis reported in RA-III. No cases of arterial
thrombosis were observed through 12/14 weeks.
MTX-controlled Trials: In RA-II, venous thrombosis was observed in 0
patients treated with MTX monotherapy, 1 patient treated with RINVOQ
15 mg monotherapy and 0 patients treated with upadacitinib 30 mg
monotherapy through Week 14. In RA-II, no cases of arterial thrombosis
were observed through 12/14 weeks. In RA-I, venous thrombosis was
observed in 1 patient treated with MTX, 0 patients treated with RINVOQ
15 mg and 1 patient treated with upadacitinib 30 mg through Week 24. In
RA-I, arterial thrombosis was observed in 1 patient treated with upadacitinib
30 mg through Week 24.
12-Month Exposure Dataset: Venous thrombosis events were reported in
5 patients (0.5 per 100 patient-years) treated with RINVOQ 15 mg and 4
patients (0.4 per 100 patient-years) treated with upadacitinib 30 mg. Arterial
thrombosis events were reported in 0 patients treated with RINVOQ 15 mg
and 2 patients (0.2 per 100 patient-years) treated with upadacitinib 30 mg.
Laboratory Abnormalities
Hepatic Transaminase Elevations
In placebo-controlled trials (RA-III, RA-IV, and RA-V) with background
DMARDs, for up to 12/14 weeks, alanine transaminase (ALT) and aspartate
transaminase (AST) elevations ≥ 3 x upper limit of normal (ULN) in at least
one measurement were observed in 2.1% and 1.5% of patients treated with
RINVOQ 15 mg, and in 1.5% and 0.7% of patients treated with placebo,
respectively. In RA-III and RA-V, ALT and AST elevations ≥ 3 x ULN in at least
one measurement were observed in 0.8% and 1.0% of patients treated with
RINVOQ 15 mg, 1.0% and 0% of patients treated with upadacitinib 30 mg
and in 1.3% and 1.0% of patients treated with placebo, respectively.
In MTX-controlled trials, for up to 12/14 weeks, ALT and AST elevations
≥ 3 x ULN in at least one measurement were observed in 0.8% and 0.4% of
patients treated with RINVOQ 15 mg,
1.7% and 1.3% of patients treated with upadacitinib 30 mg and in 1.9% and
0.9% of patients treated with MTX, respectively.
Lipid Elevations
Upadacitinib treatment was associated with dose-related increases in
total cholesterol, triglycerides and LDL cholesterol. Upadacitinib was also
associated with increases in HDL cholesterol. Elevations in LDL and HDL
cholesterol peaked by Week 8 and remained stable thereafter. In controlled
trials, for up to 12/14 weeks, changes from baseline in lipid parameters in
patients treated with RINVOQ 15 mg and upadacitinib 30 mg, respectively,
are summarized below:
* Mean LDL cholesterol increased by 14.81 mg/dL and 17.17 mg/dL.
* Mean HDL cholesterol increased by 8.16 mg/dL and 9.01 mg/dL.
* The mean LDL/HDL ratio remained stable.
* Mean triglycerides increased by 13.55 mg/dL and 14.44 mg/dL.
Creatine Phosphokinase Elevations
In placebo-controlled trials (RA-III, RA-IV, and RA-V) with background
DMARDs, for up to 12/14 weeks, dose-related increases in creatine
phosphokinase (CPK) values were observed. CPK elevations > 5 x ULN were
reported in 1.0%, and 0.3% of patients over 12/14 weeks in the RINVOQ
15 mg and placebo groups, respectively. Most elevations >5 x ULN were
transient and did not require treatment discontinuation. In RA-III and RA-V,
CPK elevations > 5 x ULN were observed in 0.3% of patients treated with
placebo, 1.6% of patients treated with RINVOQ 15 mg, and none in patients
treated with upadacitinib 30 mg.
Neutropenia
In placebo-controlled trials (RA-III, RA-IV, and RA-V) with background
DMARDs, for up to 12/14 weeks, dose-related decreases in neutrophil
counts, below 1000 cells/mm3 in at least one measurement occurred in
1.1% and <0.1% of patients in the RINVOQ 15 mg and placebo groups,
respectively. In RA-III and RA-V, decreases in neutrophil counts below
1000 cells/mm3 in at least one measurement occurred in 0.3% of patients
treated with placebo, 1.3% of patients treated with RINVOQ 15 mg, and
2.4% of patients treated with upadacitinib 30 mg. In clinical trials, treatment
was interrupted in response to ANC less than 1000 cells/mm3.
Lymphopenia
In placebo-controlled trials (RA-III, RA-IV, and RA-V) with background
DMARDs, for up to 12/14 weeks, dose-related decreases in lymphocyte
counts below 500 cells/mm3 in at least one measurement occurred in 0.9%
and 0.7% of patients in the RINVOQ 15 mg and placebo groups, respectively.
In RA-III and RA-V, decreases in lymphocyte counts below 500 cells/mm3
in at least one measurement occurred in 0.5% of patients treated with
placebo, 0.5% of patients treated with RINVOQ 15 mg, and 2.4% of patients
treated with upadacitinib 30 mg.
Anemia
In placebo-controlled trials (RA-III, RA-IV, and RA-V) with background
DMARDs, for up to 12/14 weeks, hemoglobin decreases below 8 g/dL in at
least one measurement occurred in <0.1% of patients in both the RINVOQ
15 mg and placebo groups. In RA-III and RA-V, hemoglobin decreases below
8 g/dL in at least one measurement were observed in 0.3% of patients
treated with placebo, and none in patients treated with RINVOQ 15 mg and
upadacitinib 30 mg.
Adverse Reactions in Patients with Psoriatic Arthritis
A total of 1827 patients with psoriatic arthritis were treated with
upadacitinib in clinical trials representing 1639.2 patient-years of exposure,
of whom 722 were exposed to upadacitinib for at least one year. In the two
Phase 3 trials, 907 patients received at least 1 dose of RINVOQ 15 mg, of
whom 359 were exposed for at least one year.
Two placebo-controlled trials were integrated (640 patients on RINVOQ
15 mg once daily and 635 patients on placebo) to evaluate the safety
of RINVOQ 15 mg in comparison to placebo for up to 24 weeks after
treatment initiation.
Overall, the safety profile observed in patients with active psoriatic arthritis
treated with RINVOQ 15 mg was consistent with the safety profile observed
in patients with rheumatoid arthritis. During the 24-week placebo-controlled
period, the frequencies of herpes zoster and herpes simplex were ≥1%
(1.1% and 1.4%, respectively) with RINVOQ 15 mg and 0.8% and 1.3%,
respectively with placebo. A higher incidence of acne and bronchitis was
also observed in patients treated with RINVOQ 15 mg (1.3% and 3.9%,
respectively) compared to placebo (0.3% and 2.7%, respectively).
Adverse Reactions in Patients with Atopic Dermatitis
Three Phase 3 (AD-1, AD-2, and AD-3) and one Phase 2b (AD-4)
randomized, double-blind, placebo-controlled, multicenter trials evaluated
the safety of RINVOQ in patients with moderate-to-severe atopic dermatitis.
The majority of patients were White (68%) and male (57%). The mean age
was 34 years (ranged from 12 to 75 years) and 13% of the patients were
12 to less than 18 years. In these 4 trials, 2612 patients were treated with
RINVOQ 15 mg or 30 mg orally once daily, with or without concomitant
topical corticosteroids (TCS).
In the Phase 3 clinical trials (AD-1, AD-2, and AD-3), a total of 1239 patients
received RINVOQ 15 mg, of whom 791 were exposed for at least one year
and 1246 patients received RINVOQ 30 mg, of whom 826 were exposed for
at least one year.
Trials AD-1, AD-2, and AD-4 compared the safety of RINVOQ monotherapy
to placebo through Week 16. Trial AD-3 compared the safety of RINVOQ +
TCS to placebo + TCS through Week 16.
Weeks 0 to 16 (Trials AD-1 to AD-4)
In RINVOQ trials with and without TCS (Trials AD-1, 2, 3 and 4) through
Week 16, the proportion of patients who discontinued treatment because
of adverse reactions in the RINVOQ 15 mg, 30 mg and placebo groups
were 2.3%, 2.9% and 3.8%, respectively. Table 2 summarizes the adverse
reactions that occurred at a rate of at least 1% in the RINVOQ 15 mg or
30 mg groups during the first 16 weeks of treatment.
Table 2: Adverse Reactions Reported in ≥ 1% of Patients with Atopic
Dermatitis Treated with RINVOQ 15 mg or 30 mg
Placebo
Adverse Reaction
Upper respiratory tract infection
(URTI)*
Acne**
Herpes simplex***
Headache
Increased blood creatine
phosphokinase
Cough
Hypersensitivity****
Folliculitis
Nausea
Abdominal pain*****
Pyrexia
Increased Weight
Herpes zoster******
Influenza
RINVOQ
15 mg
N = 902
(%)
17
2
2
4
2
1
2
1
1
1
1
1
1
<1
N = 899
(%)
23
10
4
6
5
3
2
2
3
3
2
2
2
2
RINVOQ
30 mg
N = 906
(%)
25
16
8
6
6
3
3
3
3
2
2
2
2
2
https://www.rinvoqhcp.com/
2023 Meeting Magazine

Table of Contents for the Digital Edition of 2023 Meeting Magazine
