TREMFYA
Generic: GUSELKUMAB
Basic Information
Manufacturer
Janssen Biotech, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
1e6dc9ae-1c4c-42d9-87aa-c315ecc51b56
Indications & Usage
1 INDICATIONS AND USAGE TREMFYA is an interleukin-23 antagonist indicated for the treatment of: adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.
( 1.1 ) adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis.
( 1.2 ) adults with moderately to severely active ulcerative colitis.
( 1.3 ) adults with moderately to severely active Crohn's disease.
( 1.4 ) 1.1 Plaque Psoriasis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.
1.2 Psoriatic Arthritis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis.
1.3 Ulcerative Colitis TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.
1.4 Crohn's Disease TREMFYA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.
( 1.1 ) adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis.
( 1.2 ) adults with moderately to severely active ulcerative colitis.
( 1.3 ) adults with moderately to severely active Crohn's disease.
( 1.4 ) 1.1 Plaque Psoriasis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.
1.2 Psoriatic Arthritis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis.
1.3 Ulcerative Colitis TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.
1.4 Crohn's Disease TREMFYA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.
Adverse Reactions
6 ADVERSE REACTIONS 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) ] Most common adverse reactions associated with TREMFYA are: Plaque Psoriasis and Psoriatic Arthritis (≥1%): upper respiratory infections, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.
( 6.1 ) Ulcerative Colitis (≥3%) : injection site reactions, arthralgia, upper respiratory tract infections, headache, gastroenteritis, fatigue, pyrexia, and rash.
( 6.1 ) Crohn's Disease (≥3%) : respiratory tract infections, abdominal pain, injection site reactions, headache, fatigue, arthralgia, diarrhea, and gastroenteritis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc.
at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 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 Adults with Plaque Psoriasis In clinical trials, a total of 1823 adult subjects with moderate-to-severe plaque psoriasis received TREMFYA.
Of these, 1393 subjects were exposed to TREMFYA for at least 6 months and 728 subjects were exposed for at least 1 year.
Data from two placebo- and active-controlled trials (PsO1 and PsO2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 8 weeks).
Weeks 0 to 16: In the 16-week placebo-controlled period of the pooled clinical trials (PsO1 and PsO2), adverse events occurred in 49% of subjects in the TREMFYA group compared to 47% of subjects in the placebo group and 49% of subjects in the U.S.
licensed adalimumab group.
Serious adverse events occurred in 1.9% of subjects in the TREMFYA group (6.3 events per 100 patient-years of follow-up) compared to 1.4% of subjects in the placebo group (4.7 events per 100 patient-years of follow-up), and in 2.6% of subjects in U.S.
licensed adalimumab group (9.9 events per 100 patient-years of follow-up).
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TREMFYA group than in the placebo group during the 16-week placebo-controlled period.
Table 1: Adverse Reactions Occurring in ≥1% of Adult Subjects with Moderate-to-Severe Plaque Psoriasis through Week 16 in Trials PsO1 and PsO2 TREMFYA Subjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter 100 mg N=823 n (%) Adalimumab U.S.
licensed adalimumab N=196 n (%) Placebo N=422 n (%) Upper respiratory infections Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI.
118 (14.3) 21 (10.7) 54 (12.8) Headache Headache includes headache and tension headache.
38 (4.6) 2 (1.0) 14 (3.3) Injection site reactions Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria.
37 (4.5) 15 (7.7) 12 (2.8) Arthralgia 22 (2.7) 4 (2.0) 9 (2.1) Diarrhea 13 (1.6) 3 (1.5) 4 (0.9) Gastroenteritis Gastroenteritis includes gastroenteritis and viral gastroenteritis.
11 (1.3) 4 (2.0) 4 (0.9) Tinea infections Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections.
9 (1.1) 0 0 Herpes simplex infections Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex.
9 (1.1) 0 2 (0.5) Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA group and at a higher rate than in the placebo group through Week 16 in trials PsO1 and PsO2 were migraine, candida infections, and urticaria.
Specific Adverse Reactions Infections Infections occurred in 23% of subjects in the TREMFYA group compared to 21% of subjects in the placebo group through 16 weeks of treatment.
The most common (≥ 1%) infections that occurred more frequently in the TREMFYA group than in the placebo group were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of TREMFYA.
The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%.
Elevated Liver Enzymes Elevated liver enzymes were reported more frequently in the TREMFYA group (2.6%) than in the placebo group (1.9%).
Of the 21 subjects who were reported to have elevated liver enzymes in the TREMFYA group, all events except one were mild to moderate in severity and none of the events led to discontinuation of TREMFYA.
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.
Adverse Reactions in Pediatric Subjects with Plaque Psoriasis 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.
Adverse Reactions in Adults with Psoriatic Arthritis TREMFYA was studied in two placebo-controlled trials 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 thereafter and 373 subjects received TREMFYA 100 mg every 4 weeks.
The overall safety profile observed in adult subjects with psoriatic arthritis treated with TREMFYA is generally consistent with the safety profile in adult 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.
A similar risk of infection and serious infections was seen in placebo-controlled trials in subjects with psoriatic arthritis as in subjects with plaque psoriasis.
Adverse Reactions in Adults with Ulcerative Colitis TREMFYA was studied up to 12 weeks in adult subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction trial (UC1) and a randomized, double-blind, placebo-controlled, induction dose-finding trial (UC3; NCT04033445).
Long-term safety up to 44 weeks was evaluated in subjects who responded to induction therapy in trials UC1 or UC3 in a randomized, double-blind, placebo-controlled maintenance trial (UC2).
In a randomized, double-blind, placebo-controlled trial (UC4), 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 24 weeks [see Clinical Studies (14.3) ] .
Trials UC1, UC2 and UC3 In the induction trials (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 ≥30% and ≥2 points from baseline with either a ≥1 decrease from baseline in rectal bleeding subscore (RBS) or RBS of 0 or 1.
In the maintenance trial (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 trial UC2) or TREMFYA 200 mg every 4 weeks (with the first dose given at Week 0 of trial UC2), by subcutaneous (SC) injection for up to an additional 44 weeks.
Respiratory tract infections occurred in ≥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 trials (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 ≥3% of subjects treated with TREMFYA and at a higher rate than placebo through Week 44 in the maintenance trial (UC2) are shown in Table 2.
Table 2: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Ulcerative Colitis through Week 44 in Trial UC2 TREMFYA Subjects receiving TREMFYA 100 mg at Week 16 and every 8 weeks thereafter or TREMFYA 200 mg at Week 12 and every 4 weeks thereafter.
100 mg Subcutaneous Injection N=186 n (%) TREMFYA 200 mg Subcutaneous Injection N=190 n (%) Placebo N=192 n (%) Injection site reactions Injection site reactions include administration site pain, injection site hematoma, injection site hemorrhage, injection site hypersensitivity, injection site erythema, injection site pain, injection site pruritus, injection site rash, injection site reaction, and injection site urticaria.
2 (1.1) 17 (8.9) TREMFYA 200 mg was administered as two 100 mg injections.
2 (1) Arthralgia 8 (4.3) 15 (7.9) 13 (6.8) Upper respiratory tract infection 6 (3.2) 13 (6.8) 8 (4.2) Trial UC4 In trial UC4, 418 subjects were enrolled, of whom 279 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 8 weeks (from Week 16 through Week 24); 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 12 weeks (from Week 12 through Week 24); or placebo.
Adverse reactions reported in trial UC4 through Week 24 in ≥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 ≥3% of Adult Subjects with Moderately to Severely Active Ulcerative Colitis through Week 24 in Trial UC4 TREMFYA 400 mg/100 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 100 mg as a subcutaneous injection at Week 16 and every 8 weeks thereafter.
N=139 n (%) TREMFYA 400 mg/200 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter.
N=140 n (%) Placebo N=139 n (%) Arthralgia 11 (7.9) 7 (5.0) 3 (2.2) Upper respiratory tract infections Upper respiratory tract infections include upper respiratory tract infection and viral upper respiratory tract infection.
11 (7.9) 5 (3.6) 9 (6.5) Injection site reactions Injection site reactions include injection site erythema, injection site swelling, injection site pain, injection site paresthesia, injection site edema, injection site bruising, injection site induration, injection site pruritus, application site edema, application site erythema, and application site pain.
7 (5.0) 9 (6.4) 4 (2.9) Headache Headache includes headache, migraine, and sinus headache.
8 (5.8) 7 (5.0) 3 (2.2) Gastroenteritis 4 (2.9) 3 (2.1) 0 Fatigue 2 (1.4) 4 (2.9) 1 (0.7) Pyrexia 1 (0.7) 4 (2.9) 2 (1.4) Rash Rash includes rash and rash pruritic.
4 (2.9) 1 (0.7) 1 (0.7) Specific Adverse Reactions Infections In the 44-week trial (UC2), serious infections occurred in 0.8% of subjects treated with TREMFYA versus 0% of subjects in the placebo group.
In the 24-week trial (UC4), serious infections occurred in 1.8% of subjects treated with TREMFYA versus 0.7% of subjects in the placebo group.
Adverse Reactions in Adults with Crohn's Disease TREMFYA was studied in four clinical trials in adult 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 trials 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 trials CD1, CD2, and CD4; headache (including headache, migraine, and sinus headache) was reported in ≥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 trial 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 trial 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 trial CD3 through Week 48 in ≥3% of subjects treated with either subcutaneous TREMFYA dosing regimen and at a higher rate than placebo are shown in Table 4.
Table 4: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Crohn's Disease Treated with Either Recommended Subcutaneous TREMFYA Regimen through Week 48 in Trial CD3 TREMFYA 400 mg/100 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 100 mg as a subcutaneous injection at Week 16 and every 8 weeks thereafter.
TREMFYA 400 mg/200 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter.
Placebo N=115 n (%) N=115 n (%) N=117 n (%) Respiratory tract infections Respiratory tract infections include bronchitis, COVID-19, H1N1 influenza, influenza, influenza like illness, nasopharyngitis, pneumonia, respiratory tract infection, tonsillitis, upper respiratory tract infection, and viral upper respiratory tract infection.
44 (38.3) 35 (30.4) 30 (25.6) Abdominal pain Abdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper.
14 (12.2) 16 (13.9) 8 (6.8) Injection site reactions Injection site reactions includes application site hypersensitivity, application site pruritus, injection site edema, injection site erythema, injection site hemorrhage, injection site mass, injection site rash, injection site reaction, and injection site swelling.
5 (4.3) 4 (3.5) 0 Fatigue 3 (2.6) 4 (3.5) 0 Headache Headache includes headache and tension headache.
7 (6.1) 9 (7.8) 5 (4.3) Arthralgia 6 (5.2) 5 (4.3) 4 (3.4) Diarrhea 6 (5.2) 4 (3.5) 3 (2.6) Gastroenteritis 4 (3.5) 2 (1.7) 1 (0.9) Specific Adverse Reactions Infections In the 48-week clinical trial in subjects with Crohn’s disease (CD3), serious infections occurred in 1.5% of subjects treated with TREMFYA versus 0% of subjects in the placebo group.
Elevated Liver Enzymes Through Week 12 in CD1, CD2, and CD4; ALT ≥5× 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 ≥5× 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.
6.2 Postmarketing Experience 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 [see Warnings and Precautions (5.1) ] Skin and subcutaneous tissue disorders: Rash [see Warnings and Precautions (5.1) ]
( 6.1 ) Ulcerative Colitis (≥3%) : injection site reactions, arthralgia, upper respiratory tract infections, headache, gastroenteritis, fatigue, pyrexia, and rash.
( 6.1 ) Crohn's Disease (≥3%) : respiratory tract infections, abdominal pain, injection site reactions, headache, fatigue, arthralgia, diarrhea, and gastroenteritis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc.
at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 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 Adults with Plaque Psoriasis In clinical trials, a total of 1823 adult subjects with moderate-to-severe plaque psoriasis received TREMFYA.
Of these, 1393 subjects were exposed to TREMFYA for at least 6 months and 728 subjects were exposed for at least 1 year.
Data from two placebo- and active-controlled trials (PsO1 and PsO2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 8 weeks).
Weeks 0 to 16: In the 16-week placebo-controlled period of the pooled clinical trials (PsO1 and PsO2), adverse events occurred in 49% of subjects in the TREMFYA group compared to 47% of subjects in the placebo group and 49% of subjects in the U.S.
licensed adalimumab group.
Serious adverse events occurred in 1.9% of subjects in the TREMFYA group (6.3 events per 100 patient-years of follow-up) compared to 1.4% of subjects in the placebo group (4.7 events per 100 patient-years of follow-up), and in 2.6% of subjects in U.S.
licensed adalimumab group (9.9 events per 100 patient-years of follow-up).
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TREMFYA group than in the placebo group during the 16-week placebo-controlled period.
Table 1: Adverse Reactions Occurring in ≥1% of Adult Subjects with Moderate-to-Severe Plaque Psoriasis through Week 16 in Trials PsO1 and PsO2 TREMFYA Subjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter 100 mg N=823 n (%) Adalimumab U.S.
licensed adalimumab N=196 n (%) Placebo N=422 n (%) Upper respiratory infections Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI.
118 (14.3) 21 (10.7) 54 (12.8) Headache Headache includes headache and tension headache.
38 (4.6) 2 (1.0) 14 (3.3) Injection site reactions Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria.
37 (4.5) 15 (7.7) 12 (2.8) Arthralgia 22 (2.7) 4 (2.0) 9 (2.1) Diarrhea 13 (1.6) 3 (1.5) 4 (0.9) Gastroenteritis Gastroenteritis includes gastroenteritis and viral gastroenteritis.
11 (1.3) 4 (2.0) 4 (0.9) Tinea infections Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections.
9 (1.1) 0 0 Herpes simplex infections Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex.
9 (1.1) 0 2 (0.5) Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA group and at a higher rate than in the placebo group through Week 16 in trials PsO1 and PsO2 were migraine, candida infections, and urticaria.
Specific Adverse Reactions Infections Infections occurred in 23% of subjects in the TREMFYA group compared to 21% of subjects in the placebo group through 16 weeks of treatment.
The most common (≥ 1%) infections that occurred more frequently in the TREMFYA group than in the placebo group were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of TREMFYA.
The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%.
Elevated Liver Enzymes Elevated liver enzymes were reported more frequently in the TREMFYA group (2.6%) than in the placebo group (1.9%).
Of the 21 subjects who were reported to have elevated liver enzymes in the TREMFYA group, all events except one were mild to moderate in severity and none of the events led to discontinuation of TREMFYA.
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.
Adverse Reactions in Pediatric Subjects with Plaque Psoriasis 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.
Adverse Reactions in Adults with Psoriatic Arthritis TREMFYA was studied in two placebo-controlled trials 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 thereafter and 373 subjects received TREMFYA 100 mg every 4 weeks.
The overall safety profile observed in adult subjects with psoriatic arthritis treated with TREMFYA is generally consistent with the safety profile in adult 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.
A similar risk of infection and serious infections was seen in placebo-controlled trials in subjects with psoriatic arthritis as in subjects with plaque psoriasis.
Adverse Reactions in Adults with Ulcerative Colitis TREMFYA was studied up to 12 weeks in adult subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction trial (UC1) and a randomized, double-blind, placebo-controlled, induction dose-finding trial (UC3; NCT04033445).
Long-term safety up to 44 weeks was evaluated in subjects who responded to induction therapy in trials UC1 or UC3 in a randomized, double-blind, placebo-controlled maintenance trial (UC2).
In a randomized, double-blind, placebo-controlled trial (UC4), 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 24 weeks [see Clinical Studies (14.3) ] .
Trials UC1, UC2 and UC3 In the induction trials (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 ≥30% and ≥2 points from baseline with either a ≥1 decrease from baseline in rectal bleeding subscore (RBS) or RBS of 0 or 1.
In the maintenance trial (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 trial UC2) or TREMFYA 200 mg every 4 weeks (with the first dose given at Week 0 of trial UC2), by subcutaneous (SC) injection for up to an additional 44 weeks.
Respiratory tract infections occurred in ≥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 trials (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 ≥3% of subjects treated with TREMFYA and at a higher rate than placebo through Week 44 in the maintenance trial (UC2) are shown in Table 2.
Table 2: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Ulcerative Colitis through Week 44 in Trial UC2 TREMFYA Subjects receiving TREMFYA 100 mg at Week 16 and every 8 weeks thereafter or TREMFYA 200 mg at Week 12 and every 4 weeks thereafter.
100 mg Subcutaneous Injection N=186 n (%) TREMFYA 200 mg Subcutaneous Injection N=190 n (%) Placebo N=192 n (%) Injection site reactions Injection site reactions include administration site pain, injection site hematoma, injection site hemorrhage, injection site hypersensitivity, injection site erythema, injection site pain, injection site pruritus, injection site rash, injection site reaction, and injection site urticaria.
2 (1.1) 17 (8.9) TREMFYA 200 mg was administered as two 100 mg injections.
2 (1) Arthralgia 8 (4.3) 15 (7.9) 13 (6.8) Upper respiratory tract infection 6 (3.2) 13 (6.8) 8 (4.2) Trial UC4 In trial UC4, 418 subjects were enrolled, of whom 279 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 8 weeks (from Week 16 through Week 24); 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 12 weeks (from Week 12 through Week 24); or placebo.
Adverse reactions reported in trial UC4 through Week 24 in ≥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 ≥3% of Adult Subjects with Moderately to Severely Active Ulcerative Colitis through Week 24 in Trial UC4 TREMFYA 400 mg/100 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 100 mg as a subcutaneous injection at Week 16 and every 8 weeks thereafter.
N=139 n (%) TREMFYA 400 mg/200 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter.
N=140 n (%) Placebo N=139 n (%) Arthralgia 11 (7.9) 7 (5.0) 3 (2.2) Upper respiratory tract infections Upper respiratory tract infections include upper respiratory tract infection and viral upper respiratory tract infection.
11 (7.9) 5 (3.6) 9 (6.5) Injection site reactions Injection site reactions include injection site erythema, injection site swelling, injection site pain, injection site paresthesia, injection site edema, injection site bruising, injection site induration, injection site pruritus, application site edema, application site erythema, and application site pain.
7 (5.0) 9 (6.4) 4 (2.9) Headache Headache includes headache, migraine, and sinus headache.
8 (5.8) 7 (5.0) 3 (2.2) Gastroenteritis 4 (2.9) 3 (2.1) 0 Fatigue 2 (1.4) 4 (2.9) 1 (0.7) Pyrexia 1 (0.7) 4 (2.9) 2 (1.4) Rash Rash includes rash and rash pruritic.
4 (2.9) 1 (0.7) 1 (0.7) Specific Adverse Reactions Infections In the 44-week trial (UC2), serious infections occurred in 0.8% of subjects treated with TREMFYA versus 0% of subjects in the placebo group.
In the 24-week trial (UC4), serious infections occurred in 1.8% of subjects treated with TREMFYA versus 0.7% of subjects in the placebo group.
Adverse Reactions in Adults with Crohn's Disease TREMFYA was studied in four clinical trials in adult 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 trials 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 trials CD1, CD2, and CD4; headache (including headache, migraine, and sinus headache) was reported in ≥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 trial 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 trial 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 trial CD3 through Week 48 in ≥3% of subjects treated with either subcutaneous TREMFYA dosing regimen and at a higher rate than placebo are shown in Table 4.
Table 4: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Crohn's Disease Treated with Either Recommended Subcutaneous TREMFYA Regimen through Week 48 in Trial CD3 TREMFYA 400 mg/100 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 100 mg as a subcutaneous injection at Week 16 and every 8 weeks thereafter.
TREMFYA 400 mg/200 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter.
Placebo N=115 n (%) N=115 n (%) N=117 n (%) Respiratory tract infections Respiratory tract infections include bronchitis, COVID-19, H1N1 influenza, influenza, influenza like illness, nasopharyngitis, pneumonia, respiratory tract infection, tonsillitis, upper respiratory tract infection, and viral upper respiratory tract infection.
44 (38.3) 35 (30.4) 30 (25.6) Abdominal pain Abdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper.
14 (12.2) 16 (13.9) 8 (6.8) Injection site reactions Injection site reactions includes application site hypersensitivity, application site pruritus, injection site edema, injection site erythema, injection site hemorrhage, injection site mass, injection site rash, injection site reaction, and injection site swelling.
5 (4.3) 4 (3.5) 0 Fatigue 3 (2.6) 4 (3.5) 0 Headache Headache includes headache and tension headache.
7 (6.1) 9 (7.8) 5 (4.3) Arthralgia 6 (5.2) 5 (4.3) 4 (3.4) Diarrhea 6 (5.2) 4 (3.5) 3 (2.6) Gastroenteritis 4 (3.5) 2 (1.7) 1 (0.9) Specific Adverse Reactions Infections In the 48-week clinical trial in subjects with Crohn’s disease (CD3), serious infections occurred in 1.5% of subjects treated with TREMFYA versus 0% of subjects in the placebo group.
Elevated Liver Enzymes Through Week 12 in CD1, CD2, and CD4; ALT ≥5× 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 ≥5× 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.
6.2 Postmarketing Experience 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 [see Warnings and Precautions (5.1) ] Skin and subcutaneous tissue disorders: Rash [see Warnings and Precautions (5.1) ]