Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Tuberculosis
Additions and/or revisions underlined:
…
In clinical trials, 105 subjects with plaque psoriasis,
143 subjects with psoriatic arthritis, 43 subjects with ulcerative colitis,
and 36 subjects with Crohn’s disease with latent TB who were concurrently treated
with TREMFYA and appropriate TB prophylaxis did not develop active TB.
…
6
Adverse Reactions
6.1 Clinical
Trials Experience
Additions and/or revisions underlined:
Adverse
Reactions in Adults with Psoriatic Arthritis
TREMFYA
was studied in two placebo-controlled trials (PsA1 and PsA2) in adult
subjects with psoriatic arthritis (748 subjects on TREMFYA and 372 subjects on
placebo). Of the 748 subjects who received TREMFYA, 375 subjects received TREMFYA
100 mg at Week 0, Week 4, and every 8 weeks (q8w) thereafter and 373 subjects
received TREMFYA 100 mg every 4 weeks (q4w).
…
TREMFYA was additionally studied in a
placebo-controlled trial (PsA3) in 1054 subjects with psoriatic arthritis (668
subjects on TREMFYA and 386 subjects on placebo). Of the 668 subjects who
received TREMFYA, 388 subjects received TREMFYA 100 mg at Week 0, Week 4, and
q8w thereafter and 280 subjects received TREMFYA 100 mg q4w. The overall safety
profile observed in subjects with psoriatic arthritis treated with TREMFYA in
trial PsA3 is consistent with the safety profile observed in trials PsA1 and
PsA2.
Specific Adverse Reactions
In the 24-week placebo-controlled period in trials
PsA1, PsA2, and PsA3, elevated liver enzymes were reported more frequently in
the TREMFYA q4w (6.1%) group compared with the q8w group (4.8%) and to the
placebo group (2.8%). Through Week 24, all events were mild to moderate in
severity and none led to discontinuation of TREMFYA.
…
8
Use in Specific Populations
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 6418 subjects with plaque psoriasis,
psoriatic arthritis, ulcerative colitis, or Crohn’s disease exposed to TREMFYA,
a total of 489 subjects were 65 years or older, and 55 subjects
were 75 years or older.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.4 Hepatotoxicity
Additions and/or
revisions underlined:
…
In patients with plaque psoriasis or psoriatic
arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at
baseline, and periodically thereafter according to routine patient management.
…
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or
revisions underlined:
…
The safety of TREMFYA was studied in one placebo-
and active-controlled clinical trial (PsO5) that included 120 pediatric
subjects 6 years of age and older with moderate-to-severe plaque psoriasis [see
Clinical Studies (14.1)]. The safety profile observed in pediatric subjects
6 years of age and older treated with TREMFYA up to 52 weeks was consistent
with the safety profile observed in adult subjects with moderate-to-severe
plaque psoriasis.
…
8
Use in Specific Populations
8.1 Pregnancy
…
Risk
Summary
Available
data from literature, post-marketing reports, and ongoing pregnancy registry
with TREMFYA use in pregnant women are insufficient to establish a
drug-associated risk of major birth defects, miscarriage or other adverse
maternal or fetal outcomes. Monoclonal antibodies are actively transported
across the placenta (see Clinical
Considerations).
…
Additions
and/or revisions underlined:
8.4
Pediatric Use Plaque Psoriasis
The
safety and effectiveness of TREMFYA for the treatment of moderate-to-severe
plaque psoriasis have been established in pediatric patients 6 years
of age and older who are candidates for systemic therapy or phototherapy [see Adverse Reactions (6.1) and Clinical
Studies (14.1)].
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with plaque psoriasis who are younger than 6 years of age.
Psoriatic
Arthritis
The
safety and effectiveness of TREMFYA have been established for treatment of
active psoriatic arthritis in pediatric patients 6 years of age and older.
Use
of TREMFYA in this age group is supported by evidence from adequate and well
controlled trials of TREMFYA in adults with plaque psoriasis and psoriatic
arthritis, pharmacokinetic data from adult subjects with plaque psoriasis and
psoriatic arthritis and pediatric subjects with plaque psoriasis, and safety
data from a clinical trial in 120 subjects 6 to 17 years of age with plaque
psoriasis. The observed pre-dose (trough) concentrations are generally
comparable between adult subjects with plaque psoriasis, adult subjects with
psoriatic arthritis and pediatric subjects with plaque psoriasis, and the
systemic exposure is expected to be comparable between adult and pediatric
patients with psoriatic arthritis [see
Adverse Reactions (6.1), Clinical
Pharmacology (12.3), and Clinical
Studies (14.1, 14.2)].
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with psoriatic arthritis who are younger than 6 years of age.
Ulcerative
Colitis
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with ulcerative colitis.
Crohn’s
Disease
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with Crohn’s disease.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions
and/or revisions underlined:
…
TREMFYA may cause
serious side effects, including:
…
Liver problems. With the treatment
of Crohn’s disease or ulcerative colitis, your healthcare provider will do blood
tests to check your liver before and during treatment with TREMFYA. With the
treatment of plaque psoriasis or psoriatic arthritis, your healthcare provider
may do blood tests to check your liver before and as necessary during treatment
with TREMFYA. Your healthcare provider may stop treatment with TREMFYA if
you develop liver problems.
…
What is TREMFYA?
TREMFYA
is a prescription medicine used to treat:
adults
and children 6 years of age and older who also weigh at least 88 pounds (40 kg)
with moderate-to- severe plaque psoriasis who may benefit from taking
injections or pills (systemic therapy) or phototherapy (treatment using
ultraviolet or UV light)
adults
and children 6 years of age and older who also weigh at least 88 pounds (40 kg)
with active psoriatic arthritis (PsA)
adults with moderately to severely active
ulcerative colitis
adults with moderately to severely active Crohn’s
disease
It
is not known if TREMFYA is safe and effective in children under 18 years of age
with ulcerative colitis or Crohn’s disease or in children under 6 years of
age with plaque psoriasis or psoriatic arthritis.
…
Before using
TREMFYA,
tell your healthcare provider about all
of your medical conditions, including if you:
…
have
recently received or are scheduled to receive an immunization (vaccine). You
should avoid receiving live vaccines during treatment with TREMFYA. Children
should be brought up to date with all vaccines before starting TREMFYA.
…
How should I use
TREMFYA?
…
Adults or children 6 years of age or older who also
weigh at least 88 pounds (40 kg) with plaque psoriasis or psoriatic
arthritis will receive TREMFYA as an injection under the skin (subcutaneous
injection).
Adults may self-inject with the TREMFYA prefilled pen,
prefilled syringe, or One-Press injector.
Adults
with ulcerative colitis or Crohn’s disease will receive their beginning
(induction) doses with TREMFYA through a vein in the arm (intravenous infusion)
in a healthcare facility by a healthcare provider or as injections under the
skin (subcutaneous injection). After completing the beginning (induction)
doses, patients will receive TREMFYA as an injection under the skin
(subcutaneous injection).
How will my child
receive TREMFYA?
See the detailed
“Instructions for Use” that comes with TREMFYA.
Children with plaque psoriasis or psoriatic arthritis
will receive
TREMFYA as an injection under the skin (subcutaneous injection).
Children should not self-inject using the TREMFYA
prefilled syringe, One-Press injector, or Prefilled pen. A healthcare provider
or caregiver should give children their injections.
Your child’s first dose will be given by a healthcare
provider. If your child’s healthcare provider decides that you or another adult
caregiver may give your child TREMFYA injections at home, you or the adult
caregiver should be shown the right way to give the injections by your
healthcare provider.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.4 Hepatotoxicity
Additions and/or revisions
underlined:
…
In patients with plaque psoriasis or psoriatic
arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at
baseline, and periodically thereafter according to routine patient management.
…
8
Use in Specific Populations
8.1 Pregnancy
Additions
and/or revisions underlined:
…
Risk
Summary
Available
data from literature, post-marketing reports, and ongoing pregnancy registry
with TREMFYA use in pregnant women are insufficient to establish a
drug-associated risk of major birth defects, miscarriage or other adverse
maternal or fetal outcomes. Monoclonal antibodies are actively transported
across the placenta (see Clinical
Considerations).
…
Additions
and/or revisions underlined:
8.4
Pediatric Use Plaque Psoriasis
The
safety and effectiveness of TREMFYA for the treatment of moderate-to-severe
plaque psoriasis have been established in pediatric patients 6 years of age and
older who are candidates for systemic therapy or phototherapy [see Adverse Reactions (6.1) and Clinical
Studies (14.1)].
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with plaque psoriasis who are younger than 6 years of age.
Psoriatic
Arthritis
The
safety and effectiveness of TREMFYA have been established for treatment of
active psoriatic arthritis in pediatric patients 6 years of age and older.
Use
of TREMFYA in this age group is supported by evidence from adequate and well
controlled trials of TREMFYA in adults with plaque psoriasis and psoriatic
arthritis, pharmacokinetic data from adult subjects with plaque psoriasis and
psoriatic arthritis and pediatric subjects with plaque psoriasis, and safety
data from a clinical trial in 120 subjects 6 to 17 years of age with plaque
psoriasis. The observed pre-dose (trough) concentrations are generally
comparable between adult subjects with plaque psoriasis, adult subjects with
psoriatic arthritis and pediatric subjects with plaque psoriasis, and the
systemic exposure is expected to be comparable between adult and pediatric
patients with psoriatic arthritis [see
Adverse Reactions (6.1), Clinical
Pharmacology (12.3), and Clinical
Studies (14.1, 14.2)].
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with psoriatic arthritis who are younger than 6 years of age.
Ulcerative
Colitis
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with ulcerative colitis.
Crohn’s
Disease
The
safety and effectiveness of TREMFYA have not been established in pediatric
patients with Crohn’s disease.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions
and/or revisions underlined:
…
TREMFYA
may cause serious side effects, including:
…
Liver
problems. With
the treatment of Crohn’s disease or ulcerative colitis, your healthcare
provider will do blood tests to check your liver before and during treatment
with TREMFYA. With the treatment of plaque psoriasis or psoriatic arthritis,
your healthcare provider may do blood tests to check your liver before and as
necessary during treatment with TREMFYA. Your healthcare provider may stop
treatment with TREMFYA if you develop liver problems.
…
What
is TREMFYA?
TREMFYA
is a prescription medicine used to treat:
adults
and children 6 years of age and older who also weigh at least 88 pounds (40 kg)
with moderate-to- severe plaque psoriasis who may benefit from taking
injections or pills (systemic therapy) or phototherapy (treatment using
ultraviolet or UV light)
adults and children 6 years of age and older who also
weigh at least 88 pounds (40 kg) with active psoriatic arthritis (PsA)
adults with moderately to severely active
ulcerative colitis
adults with moderately to severely active
Crohn’s disease
It
is not known if TREMFYA is safe and effective in children under 18 years of age
with ulcerative colitis or Crohn’s disease or in children under 6 years of
age with plaque psoriasis or psoriatic arthritis.
…
Before using
TREMFYA,
tell your healthcare provider about all
of your medical conditions, including if you:
…
have
recently received or are scheduled to receive an immunization (vaccine). You
should avoid receiving live vaccines during treatment with TREMFYA. Children
should be brought up to date with all vaccines before starting TREMFYA.
…
How should I use
TREMFYA?
…
Adults or children 6 years of age or older who also
weigh at least 88 pounds (40 kg) with plaque psoriasis or psoriatic
arthritis will receive TREMFYA as an injection under the skin (subcutaneous
injection).
Adults may self-inject with the TREMFYA prefilled pen,
prefilled syringe, or One-Press injector.
Adults
with ulcerative colitis or Crohn’s disease will receive their beginning
(induction) doses with TREMFYA through a vein in the arm (intravenous infusion)
in a healthcare facility by a healthcare provider or as injections under the
skin (subcutaneous injection). After completing the beginning (induction)
doses, patients will receive TREMFYA as an injection under the skin
(subcutaneous injection).
How will my child
receive TREMFYA?
See the detailed
“Instructions for Use” that comes with TREMFYA.
Children with plaque psoriasis or psoriatic arthritis
will receive
TREMFYA as an injection under the skin (subcutaneous injection).
Children should not self-inject using the TREMFYA
prefilled syringe, One-Press injector, or Prefilled pen. A healthcare provider
or caregiver should give children their injections.
Your child’s first dose will be given by a healthcare
provider. If your child’s healthcare provider decides that you or another adult
caregiver may give your child TREMFYA injections at home, you or the adult
caregiver should be shown the right way to give the injections by your
healthcare provider.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Infections
Additions and/or
revisions underlined:
TREMFYA may increase the risk of infection [see Adverse Reactions (6.1)].
In placebo-controlled clinical trials of
up to 48 weeks in subjects with ulcerative colitis and Crohn’s disease,
serious infections occurred in less than or equal to 2% of subjects who
received TREMFYA. In the 16-week placebo-controlled trials in subjects with
plaque psoriasis, the rate of serious infections for the TREMFYA group and the
placebo group was less than or equal to 0.2%. A similar rate of serious
infections was seen in placebo-controlled trials in subjects with psoriatic
arthritis. The overall rates of infections were similar between subjects in
the TREMFYA groups and subjects in the placebo groups in clinical trials for
all indicated populations [see Adverse
Reactions (6.1)].
. . .
6
Adverse Reactions
6.1 Clinical
Trials Experience
Extensive changes;
please refer to label for complete information
8
Use in Specific Populations
8.5 Geriatric Use
Additions and/or
revisions underlined:
Of the 5723 subjects with plaque psoriasis,
psoriatic arthritis, ulcerative colitis, or Crohn’s disease exposed to TREMFYA,
a total of 313 subjects were 65 years or older, and 32 subjects
were 75 years or older.
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or
revisions underlined:
.
. .
Ulcerative
Colitis and Crohn’s Disease Subcutaneous Induction Dosing Instructions (400 mg
Subcutaneous dose)
If
patients are to receive the 400 mg subcutaneous induction dosage for ulcerative
colitis or Crohn’s disease, instruct patients or caregivers to administer
two 200 mg prefilled pens or prefilled syringes to achieve the full 400 mg dose
[see Medication Guide and Instructions
for Use].
.
. .
MEDICATION GUIDE
Additions and/or
revisions underlined:
.
. .
The most common
side effects of TREMFYA include:
. . .
. . .
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2
Infections
Additions
and/or revisions underlined:
TREMFYA
may increase the risk of infection. In clinical trials in subjects with plaque
psoriasis,infections occurred in 23%
of subjects in the TREMFYA group versus 21% of subjects in the placebo group
through 16 weeks of treatment. Upper respiratory tract infections,
gastroenteritis, tinea infections, and herpes simplex infections occurred more
frequently in the TREMFYA group than in the placebo group [see Adverse
Reactions (6.1)]. The rate of serious infections for the TREMFYA group and
the placebo group was less than or equal to 0.2%. A similar risk of infection
was seen in placebo-controlled trials in subjects with psoriatic arthritis,
ulcerative colitis, and Crohn’s disease. Treatment with TREMFYA should
not be initiated in patients with any clinically important active infection
until the infection resolves or is adequately treated.
. . .
5.3
Tuberculosis
Additions and/or
revisions underlined:
Evaluate patients for
tuberculosis (TB) infection prior to initiating TREMFYA treatment. Do not
administer TREMFYA to patients with active TB infection. Initiate treatment
of latent TB prior to administering TREMFYA. Consider anti-TB therapy prior to
initiating TREMFYA in patients with a past history of latent or active TB in
whom an adequate course of treatment cannot be confirmed. Monitor all
patients for signs and symptoms of active TB during and after TREMFYA
treatment.
In clinical trials, 105
subjects with plaque psoriasis, 71 subjects with psoriatic arthritis, 31
subjects with ulcerative colitis, and 36 subjects with Crohn’s disease with
latent TB who were concurrently treated with TREMFYA, and appropriate TB
prophylaxis did not develop active TB. In clinical trials of TREMFYA in
subjects with Crohn’s disease, active TB was reported in 2 subjects during
treatment with TREMFYA [see Adverse
Reactions (6.1)].
Newly
added subsection:
5.4
Hepatotoxicity
A serious adverse reaction
of drug-induced liver injury was reported in a clinical trial subject with
Crohn’s disease following three doses of a higher than the recommended
induction regimen. This subject had peak alanine aminotransferase (ALT) of 18x
the upper limit of normal (ULN), aspartate aminotransferase (AST) of 11x ULN,
and total bilirubin of 2.4x ULN. TREMFYA was subsequently discontinued, and the
liver test abnormalities resolved following administration of corticosteroids.
In patients with Crohn’s
disease or ulcerative colitis, evaluate liver enzymes and bilirubin at
baseline, for at least 16 weeks of treatment, and periodically thereafter
according to routine patient management.
Consider other treatment
options in patients with evidence of acute liver disease or 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.
6
Adverse Reactions
Additions
and/or revisions underlined:
The following adverse
reactions are discussed in greater detail in other sections of labeling:
- Hypersensitivity
Reactions [see Contraindications (4) and Warnings and Precautions (5.1)]
- Infections [see
Warnings and Precautions (5.2)]
- Tuberculosis
[see Warnings and Precautions (5.3)]
- Hepatotoxicity
[see Warnings and Precautions (5.4)]
6.1
Clinical Trials Experience
Additions
and/or revisions underlined:
.
. .
Crohn’s
Disease
TREMFYA
was studied in four clinical trials in subjects with moderately to severely
active Crohn’s disease [see Clinical Studies (14.4)]. In two randomized,
double-blind, placebo-controlled trials (CD1, CD2) and one randomized,
double-blind, dose-ranging trial (CD4, NCT03466411); subjects received
intravenous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended
subcutaneous TREMFYA dosing regimens for a total duration of up to 48 weeks. In
a randomized, double-blind, placebo-controlled trial (CD3); subjects received
subcutaneous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended
subcutaneous TREMFYA dosing regimens for a total duration of up to 48 weeks.
Trials
CD1, CD2, and CD4
In
CD1, CD2, and CD4; 1349 subjects were enrolled, of whom 649 were randomized to
intravenous TREMFYA 200 mg at Weeks 0, 4, and 8 followed by either subcutaneous
TREMFYA 100 mg every 8 weeks (with the first dose given at Week 16) for up to
an additional 32 weeks (from Week 16 through Week 48) or subcutaneous TREMFYA
200 mg every 4 weeks (with the first dose given at Week 12) for up to an
additional 36 weeks (from Week 12 through Week 48); and 211 subjects were
randomized to receive placebo.
Through
Week 12 in CD1, CD2, and CD4; headache (including headache, migraine, and sinus
headache) was reported in greater than or equal to 3% of subjects treated with
intravenous TREMFYA and at a greater rate than placebo (3.4% TREMFYA-treated
subjects vs. 1.9% placebo-treated subjects). In TREMFYA-treated subjects in
CD2, one case of active extrapulmonary TB was reported between Weeks 12-48 and
one case of active pulmonary TB was reported after Week 48. Both subjects had
negative baseline screenings and resided in TB-endemic regions [see Warnings
and Precautions (5.3)]. In general, the safety profile in subjects treated
with subcutaneous TREMFYA from Week 12 up to Week 48 in these trials was
generally similar to that reported with intravenous TREMFYA through Week 12.
Trial
CD3
In
CD3, 347 subjects were enrolled, of whom 230 subjects were randomized to
receive TREMFYA. Randomization was 1:1:1 to subcutaneous TREMFYA 400 mg at
Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks (with
the first dose given at Week 16) for up to an additional 32 weeks (from Week 16
through Week 48); subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by
subcutaneous TREMFYA 200 mg every 4 weeks (with the first dose given at Week
12) for up to an additional 36 weeks (from Week 12 through Week 48); or
placebo.
Adverse
reactions reported in CD3 through Week 48 in greater than or equal to 3% of
subjects treated with either subcutaneous
TREMFYA dosing regimen and at a higher rate than placebo are shown in Table 3.
Table 3: Adverse Reactions Occurring in greater
than or equal to 3% of Subjects with Crohn’s Disease Treated with Either Recommended
Subcutaneous TREMFYA Regimen through Week 48 in CD3
Newly added table, please refer to label for
complete information
Specific Adverse Reactions
Elevated
Liver Enzymes
Through Week 12 in CD1, CD2, and CD4; ALT greater than or equal to 5x ULN
was reported in 2/645 (0.3%) subjects treated with intravenous TREMFYA 200 mg
at Weeks 0, 4, and 8 and 0/211 subjects treated with placebo. These elevations occurred
without concomitant elevations in total bilirubin.
Through Week 48 in CD3, ALT greater than or equal to 5x ULN was reported in
0/115 subjects treated with subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8
followed by subcutaneous TREMFYA 100 mg every 8 weeks; 2/115 (1.7%) subjects
treated with subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by
subcutaneous TREMFYA 200 mg every 4 weeks; and 0/117 subjects treated with
placebo. These elevations occurred without concomitant elevations in total
bilirubin.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
. . .
Risk Summary
. . .
In a combined embryofetal development and pre- and
post-natal development study, no adverse developmental effects were observed in
infants born to pregnant monkeys after subcutaneous administration of
guselkumab during organogenesis through parturition at doses up to 18 times the
exposure (AUC) in humans administered 200 mg intravenously and 16 times
the exposure (AUC) to the 400 mg dose given subcutaneously. Neonatal
deaths in monkeys were observed at 4 to 18 times the exposure (AUC) in humans
administered 200 mg intravenously and 4 to 16 times the exposure
(AUC) to the 400 mg dose given subcutaneously (see Data). The
clinical significance of these nonclinical findings is unknown.
. . .
Fetal/Neonatal
Adverse Reactions
Transport of endogenous IgG antibodies across the
placenta increases as pregnancy progresses, and peaks during the third
trimester. Therefore, it is expected that TREMFYA administered will be present
in infants exposed in utero during the third trimester. The potential
clinical impact of guselkumab exposure in infants exposed in utero should
be considered.
Data
Animal Data
In a combined embryofetal development and pre- and
post-natal development study, pregnant cynomolgus monkeys were administered
weekly subcutaneous doses of guselkumab from the beginning of organogenesis to
parturition at a dose (50 mg/kg) resulting in exposures (AUC) 18 times the
exposure in humans administered 200 mg intravenously and 16 times the
human exposure at 400 mg given subcutaneously. Neonatal deaths occurred
in the offspring of one control monkey, three monkeys administered guselkumab
at 10 mg/kg/week (4 times the exposure (AUC) in humans administered 200 mg
intravenously or 400 mg given subcutaneously) and three monkeys
administered guselkumab at 50 mg/kg/week (18 times the exposure (AUC) in humans
administered 200 mg intravenously and 16 times the exposure (AUC)
following a 400 mg subcutaneous dose).
. . .
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 5392 subjects with plaque psoriasis,
psoriatic arthritis, ulcerative colitis, or Crohn’s disease exposed to
TREMFYA, a total of 285 subjects were 65 years or older, and 28
subjects were 75 years or older. Clinical studies of TREMFYA, within each
indication, did not include sufficient numbers of subjects 65 years of age and
older to determine whether they respond differently from younger adult
subjects.
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
What
is the most important information I should know about TREMFYA?
TREMFYA
may cause serious side effects, including:
. . .
- Liver
problems. With the treatment of Crohn’s disease or ulcerative colitis, your
healthcare provider will do blood tests to check your liver before and during
treatment with TREMFYA. Your healthcare provider may stop treatment with
TREMFYA if you develop liver problems. Tell your healthcare provider right away
if you notice any of the following symptoms:
- unexplained rash
- vomiting
- tiredness (fatigue)
- yellowing of the skin or the whites of your eyes
- nausea
- stomach pain (abdominal)
- loss of appetite
- dark urine
. . .
What
is TREMFYA?
TREMFYA is a prescription medicine used to treat
adults:
. . .
- with
moderately to severely active Crohn’s disease
. . .
How
should I use TREMFYA?
.
. .
- Adults with ulcerative colitis will receive their beginning
(induction) doses with TREMFYA through a vein in the arm (intravenous
infusion) in a healthcare facility by a healthcare provider. After completing
the beginning (induction) doses, patients will receive TREMFYA as an
injection under the skin (subcutaneous injection).
- Adults with Crohn’s disease
will receive their beginning (induction) doses with TREMFYA through a vein in
the arm (intravenous infusion) in a healthcare facility by a healthcare
provider or as injections under the skin (subcutaneous injection). After
completing the beginning (induction) doses, patients will receive TREMFYA as an
injection under the skin (subcutaneous injection).
. . .
The most common
side effects of TREMFYA include:
. . .
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
. . .
Tuberculosis
Advise patients to contact their healthcare
provider if they experience symptoms suggestive of TB (e.g., unexplained fever,
cough, or difficulty breathing) [see Warnings and Precautions (5.3)].
Hepatotoxicity
Inform patients that TREMFYA may cause liver
injury. 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 (5.4)].
. . .
Crohn’s Disease Subcutaneous Induction Dosing
Instructions (400 mg Subcutaneous dose)
If patients are to receive the 400 mg subcutaneous
induction dosage for Crohn’s disease, instruct patients or caregivers to
administer two 200 mg prefilled pens or prefilled syringes to achieve the full
400 mg dose [see Medication Guide and Instructions for Use].
Instruction on Injection Technique
Instruct patients or caregivers to perform the
first self-injection under the supervision and guidance of a qualified
healthcare professional for proper training in subcutaneous injection technique,
including injection of the full dose [see Medication Guide and
Instructions for Use].
Proper Sharps Disposal Instructions
Counsel patients and caregivers on the proper
technique of needle and syringe disposal. Instruct patients to dispose
needles and syringes in a puncture-resistant container. Advise patients and
caregivers not to reuse needles or syringes.
Administration Instructions
Instruct patients that if they forget to administer
a dose of TREMFYA, then they should administer TREMFYA as soon as
they remember. Instruct patients to administer the next dose at the regular
scheduled time.
. . .
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Infections
Additions and/or
revisions underlined:
… The rate of
serious infections for the TREMFYA group and the placebo group was less than or
equal to 0.2%. A similar risk of infection was seen in placebo-controlled
trials in subjects with psoriatic arthritis and ulcerative colitis.
Treatment with TREMFYA should not be initiated in patients with any clinically
important active infection until the infection resolves or is adequately
treated.
…
5.3 Pre-treatment Evaluation for Tuberculosis
Additions and/or
revisions underlined:
![]()
Evaluate patients for tuberculosis (TB) infection prior to initiating
treatment with TREMFYA. Initiate treatment of latent TB prior to administering
TREMFYA. In clinical trials, 105 subjects with plaque psoriasis, 71 subjects
with psoriatic arthritis, and 31 subjects with ulcerative colitis with
latent TB who were concurrently treated with TREMFYA and appropriate TB
prophylaxis did not develop active TB. Monitor patients for signs and symptoms
of active TB during and after TREMFYA treatment.
…
5.4 Immunizations
![]()
Additions
and/or revisions underlined:
Avoid use of live vaccines in patients treated with
TREMFYA. Medications that interact with the immune system may increase the risk
of infection following administration of live vaccines. Prior to initiating therapy with TREMFYA, complete all
age-appropriate vaccinations according to current immunization guidelines. No
data are available on the response to live or inactive vaccines.
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
…
Ulcerative Colitis
TREMFYA was studied up to 12 weeks in subjects with
moderately to severely active ulcerative colitis in a randomized, double-blind,
placebo-controlled induction study (UC1) and a randomized, double-blind,
placebo controlled, induction dose-finding study (UC3; NCT04033445). Long-term
safety up to 44 weeks was evaluated in subjects who responded to induction
therapy in a randomized, double-blind, placebo-controlled maintenance study
(UC2) [see Clinical Studies (14.3)].
In the induction studies (UC1 and UC3), 522 subjects
received at least one dose of the TREMFYA intravenous induction regimen (i.e.,
200 mg at Week 0, Week 4, and Week 8). Clinical response was defined as a
decrease in modified Mayo score (mMS) of greater than or equal to 30% and
greater than or equal to 2 points from baseline with either a greater than or
equal to 1 decrease from baseline in rectal bleeding subscore (RBS) or RBS of 0
or 1. In the maintenance study (UC2), subjects who achieved clinical response
after 12 weeks of TREMFYA intravenous induction treatment were randomized and
received either TREMFYA 100 mg every 8 weeks (with the first dose given at Week
4 of UC2) or TREMFYA 200 mg every 4 weeks (with the first dose given at Week 0
of UC2), by subcutaneous (SC) injection for up to an additional 44 weeks.
Respiratory tract infections occurred in greater
than or equal to 2% of subjects treated with TREMFYA and at a higher rate than
placebo (8.8% TREMFYA-treated subjects vs. 7.3% placebo-treated subjects)
through Week 12 in the induction studies (UC1 and UC3). Respiratory tract
infections included COVID-19, influenza, nasopharyngitis, respiratory tract
infection, upper respiratory tract infection, and viral respiratory tract
infection.
Adverse reactions that occurred in greater than or
equal to 3% of subjects treated with TREMFYA and at a higher rate than placebo
through Week 44 in the maintenance study (UC2) are shown in Table 2.
Please refer to label to view Table 2.
…
8
Use in Specific Populations
8.5 Geriatric Use
Additions
and/or revisions underlined:
Of
the 4303 subjects with plaque psoriasis, psoriatic arthritis, or
ulcerative colitis exposed to TREMFYA, a total of 240 subjects were
65 years or older, and 23 subjects were 75 years or older. Clinical
studies of TREMFYA, within each indication, 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 guselkumab were
observed based on age
[see Clinical Pharmacology (12.3)].
8.1 Pregnancy
Additions and/or revisions underlined:
Pregnancy
Exposure Registry
There
is a pregnancy registry that monitors pregnancy outcomes in women exposed to
TREMFYA during pregnancy. Patients should be encouraged to enroll in the
registry by visiting www.mothertobaby.org/ongoing- study/tremfya-guselkumab,
by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu.
Risk
Summary
Available
data
from literature, post-marketing reports, and ongoing pregnancy registry with
TREMFYA use in pregnant women are insufficient to establish a
drug-associated risk of major birth defects, miscarriage or other adverse
maternal or fetal outcomes. Human IgG antibodies are known to cross the
placental barrier; therefore, TREMFYA may be transmitted from the mother to the
developing fetus.
In
a combined embryofetal development and pre- and post-natal development study,
no adverse
developmental effects were observed in infants born to pregnant monkeys after
subcutaneous administration of guselkumab during organogenesis through
parturition at doses up to 18 times the exposure (AUC) in humans
administered 200 mg intravenously and 32 times the exposure (AUC) to the 200 mg
dose given subcutaneously. Neonatal deaths in monkeys were
observed at 4 to 18 times the exposure (AUC) in humans administered 200 mg
intravenously and 7 to 32 times the exposure (AUC) to the 200 mg dose given
subcutaneously (see Data). The
clinical significance of these nonclinical findings is unknown.
…
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 (IBD) is associated with increased disease activity.
Adverse pregnancy outcomes include preterm delivery (before 37 weeks
gestation), low birth weight (less than 2500 g) infants, and small for
gestational age at birth.
Data
Animal Data
In a combined embryofetal development and pre- and
post-natal development study, pregnant cynomolgus monkeys were administered
weekly subcutaneous doses of guselkumab from the beginning of organogenesis to
parturition at a dose (50 mg/kg) resulting in exposures (AUC) 18 times the
exposure in humans administered 200 mg intravenously and 32 times the human
exposure at 200 mg given subcutaneously. Neonatal deaths occurred in the
offspring of one control monkey, three monkeys administered guselkumab at 10
mg/kg/week (4 times the exposure (AUC) in humans administered 200
mg intravenously and 7 times the exposure (AUC) at 200 mg given
subcutaneously) and three monkeys administered guselkumab at 50 mg/kg/week
(18 times the exposure (AUC) in humans administered 200 mg intravenously and
32 times the exposure (AUC) following a 200 mg subcutaneous dose). The
clinical significance of these findings is unknown. No guselkumab-related
effects on functional or immunological development were observed in the infants
from birth through 6 months of age.
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
There are no data on the presence of guselkumab in
human milk, the effects on the breastfed infant, or the effects on milk
production. Guselkumab was not detected in the milk of lactating cynomolgus
monkeys. Endogenous maternal IgG and monoclonal antibodies are transferred
into human milk. The effects of local gastrointestinal exposure and the extent
of systemic exposure in the breastfed infant to guselkumab are unknown. The
developmental and health benefits of breastfeeding should be considered along
with the mother's clinical need for TREMFYA and any potential adverse effects
on the breastfed infant from TREMFYA or from the underlying maternal condition.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or revisions underlined:
…
Immunizations
Advise patients treated with TREMFYA to avoid use of
live vaccines [see Warnings and
Precautions (5.4)].
Instruction on Injection Technique
Instruct patients or caregivers to perform the first
self-injection under the supervision and guidance of a qualified healthcare
professional for proper training in subcutaneous injection technique. Instruct
patients who are self-administering to inject the full dose of TREMFYA/TREMFYA
PEN [see Medication Guide and
Instructions for Use].
…
Remind patients if they forget to take their dose of
TREMFYA/TREMFYA PEN to inject their dose as soon as they remember. They
should then take their next dose at the appropriate scheduled time.
Pregnancy
Advise patients that there is a pregnancy registry
that monitors pregnancy outcomes in patients exposed to TREMFYA during
pregnancy [see Use in Specific
Populations (8.1)].
MEDICATION GUIDE
Additions
and/or revisions underlined:
…
What is TREMFYA?
TREMFYA
is a prescription medicine used to treat adults:
…
with moderately to severely active ulcerative colitis
…
Before using
TREMFYA,
tell your healthcare provider about all
of your medical conditions, including if you:
…
are
pregnant or plan to become pregnant. It is not known if TREMFYA can harm your
unborn baby.
Pregnancy Registry: If you become
pregnant during treatment with TREMFYA, talk to your healthcare provider about
registering in the pregnancy exposure registry for TREMFYA. You can enroll in
this registry by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling
1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu. The purpose of
this registry is to collect information about the safety of TREMFYA during
pregnancy.
…
How
should I use TREMFYA/TREMFYA PEN?
See
the detailed “Instructions for Use” that comes with TREMFYA/TREMFYA PEN
for information on how to prepare and inject a dose of TREMFYA, and how to
properly throw away (dispose of) the used TREMFYA prefilled syringe, One-Press injector
or prefilled pen (TREMFYA PEN).
…
Adults with plaque psoriasis or psoriatic arthritis
will receive TREMFYA as an injection under the skin (subcutaneous injection).
Adults with ulcerative colitis will receive their
starter doses with TREMFYA through a vein in the arm (intravenous infusion) in
a healthcare facility by a healthcare provider. After completing the starter
doses, patients will receive TREMFYA as an injection under the skin
(subcutaneous injection).
…
How should I store
TREMFYA?
Store TREMFYA in the refrigerator between 36°F to 46°F
(2°C to 8°C).
Keep TREMFYA in the original carton to protect it from
light until time of use.
TREMFYA is not made with natural rubber latex.
Do not freeze TREMFYA.
Do not shake TREMFYA.
Keep TREMFYA and
all medicines out of the reach of children.
…
What are the
ingredients in TREMFYA? Active ingredient: guselkumab
Inactive
ingredients: Single-dose
prefilled syringe, single-dose One-Press patient-controlled injector,
single-dose prefilled pen for subcutaneous use: L-histidine,
L-histidine monohydrochloride monohydrate, polysorbate 80, sucrose and water
for injection. Single-dose vial for intravenous infusion: EDTA disodium
dihydrate, L-histidine, L-histidine monohydrochloride monohydrate,
L-methionine, polysorbate 80, sucrose and water for injection.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Hypersensitivity Reactions
(Additions and/or revisions
underlined)
Serious hypersensitivity reactions, including
anaphylaxis, have been reported with postmarket use of TREMFYA. Some
cases required hospitalization. If a serious hypersensitivity reaction occurs,
discontinue TREMFYA and initiate appropriate therapy.
5.2 Infections
(Additions and/or revisions
underlined)
TREMFYA may increase the risk of infection. In clinical
trials in subjects with plaque psoriasis, infections occurred in 23% of
subjects in the TREMFYA group versus 21% of subjects in the placebo group
through 16 weeks of treatment. Upper respiratory tract infections,
gastroenteritis, tinea infections, and herpes simplex infections occurred more
frequently in the TREMFYA group than in the placebo group. The rate of serious
infections for the TREMFYA group and the placebo group was less than or equal
to 0.2%. A similar risk of infection was seen in placebo-controlled trials
in subjects with psoriatic arthritis. Treatment with TREMFYA 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
TREMFYA. Instruct patients to seek medical help if signs or symptoms of
clinically important chronic or acute infection occur. If a patient develops a
clinically important or serious infection or is not responding to standard
therapy, monitor the patient closely and discontinue TREMFYA until the
infection resolves.
5.3 Pre-treatment Evaluation for
Tuberculosis
(Additions and/or revisions
underlined)
Evaluate patients for tuberculosis (TB) infection prior to
initiating treatment with TREMFYA. Initiate treatment of latent TB prior to
administering TREMFYA. In clinical trials, 105 subjects with plaque
psoriasis and 71 subjects with psoriatic arthritis with latent TB who were
concurrently treated with TREMFYA and appropriate TB prophylaxis did not
develop active TB. Monitor patients for signs and symptoms
of active TB during and after TREMFYA treatment.
6
Adverse Reactions
6.1 Clinical Trials Experience
(Additions and/or revisions
underlined; VOYAGE 1 and VOYAGE 2 replaced with PsO1 and PsO2 throughout labeling)
Safety through Week
48
Through Week 48, no new adverse reactions were identified
with TREMFYA use and the frequency of the adverse reactions was similar to the
safety profile observed during the first
16 weeks of treatment.
Psoriatic Arthritis
TREMFYA was studied in two placebo-controlled trials in
subjects with psoriatic arthritis (748 subjects on TREMFYA and 372 subjects on
placebo). Of the 748 subjects who received TREMFYA, 375 subjects received
TREMFYA 100 mg at Week 0, Week 4, and every 8 weeks thereafter and 373 subjects
received TREMFYA 100 mg every 4 weeks. The overall safety profile observed in
subjects with psoriatic arthritis treated with TREMFYA is generally consistent
with the safety profile in subjects with plaque psoriasis with the addition of
bronchitis and neutrophil count decreased. In the 24-week placebo-controlled
period, combined across the two studies, bronchitis occurred in 1.6% of
subjects in the TREMFYA q8w group and 2.9% of subjects in the TREMFYA q4w group
compared to 1.1% of subjects in the placebo group. Neutrophil count decreased
occurred in 0.3% of subjects in the TREMFYA q8w and 1.6% of subjects in the
TREMFYA q4w group compared to 0% of subjects in the placebo group. The majority
of events of neutrophil count decreased were mild, transient, not associated
with infection and did not lead to discontinuation.
6.2 Immunogenicity
(Additions and/or
revisions underlined)
As with all therapeutic proteins, there is the potential
for immunogenicity with TREMFYA. 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 incidence of antibodies to
guselkumab across indications or with the incidences of antibodies to
other products may be misleading.
Psoriatic Arthritis
Up to Week 24, 2% (n=15) of subjects treated with
TREMFYA developed antidrug antibodies. Of these subjects, 1 had antibodies that
were classified as neutralizing antibodies. Overall, the small number of
subjects who were positive for antibodies to guselkumab limits definitive
conclusion of the effect of immunogenicity on the pharmacokinetics, efficacy
and safety of guselkumab.
6.3 Postmarketing Experience
(Additions and/or
revisions underlined)
The following adverse reactions have been reported during
post-approval of TREMFYA. 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 TREMFYA exposure.
Immune system
disorders: Hypersensitivity, including anaphylaxis
Skin and
subcutaneous tissue disorders: Rash
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or
revisions underlined)
Pregnancy Exposure Registry
There is a pregnancy registry that monitors pregnancy
outcomes in women exposed to TREMFYA during pregnancy. Patients should be
encouraged to enroll by calling 1-877-311- 8972.
8.4 Geriatric Use
(Additions and/or
revisions underlined)
Of the
3406 subjects with plaque psoriasis
or
psoriatic arthritis exposed to TREMFYA, a total of
185 subjects were
65 years or older, and
13 subjects were 75 years or older. No overall
differences in safety or effectiveness were observed between older and younger
subjects who received TREMFYA. However, the number of subjects aged 65 years
and older was not sufficient to determine whether they respond differently from younger subjects.
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