Ustekinumabside effects

The following serious adverse reactions are discussed elsewhere in the label: Infections Malignancies Serious Hypersensitivity Reactions Posterior Reversible Encephalopathy Syndrome (PRES) Noninfectious Pneumonia Most common adverse reactions are: Psoriasis and Psoriatic Arthritis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue. Crohn's Disease in Adults induction (≥3%): vomiting. maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. Ulcerative Colitis in Adults induction (≥3%): nasopharyngitis. maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea. 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. Adult Subjects with Plaque Psoriasis The safety data reflect exposure to STELARA in 3117 adult subjects with plaque psoriasis, including 2414 exposed for at least 6 months, 1855 exposed for at least one year, 1653 exposed for at least two years, 1569 exposed for at least three years, 1482 exposed for at least four years and 838 exposed for at least five years. Table 8 summarizes the adverse reactions that occurred at a rate of at least 1% with higher rates in the STELARA groups during the placebo-controlled period of Ps STUDY 1 and Ps STUDY 2.

Table 8: Adverse Reactions, Reported by ≥1% of Subjects with Plaque Psoriasis and at Higher Rates in the STELARA Groups through Week 12 in Ps STUDY 1 and Ps STUDY 2 STELARA Placebo 45 mg 90 mg Subjects treated 665 664 666 Nasopharyngitis 51 (8%) 56 (8%) 49 (7%) Upper respiratory tract infection 30 (5%) 36 (5%) 28 (4%) Headache 23 (3%) 33 (5%) 32 (5%) Fatigue 14 (2%) 18 (3%) 17 (3%) Back pain 8 (1%) 9 (1%) 14 (2%) Dizziness 8 (1%) 8 (1%) 14 (2%) Pharyngolaryngeal pain 7 (1%) 9 (1%) 12 (2%) Pruritus 9 (1%) 10 (2%) 9 (1%) Injection site erythema 3 (<1%) 6 (1%) 13 (2%) Myalgia 4 (1%) 7 (1%) 8 (1%) Depression 3 (<1%) 8 (1%) 4 (1%) Adverse reactions that occurred at rates less than 1% in the controlled period of Ps STUDIES 1 and 2 through week 12 included: cellulitis, herpes zoster, diverticulitis, and certain injection site reactions (pain, swelling, pruritus, induration, hemorrhage, bruising, and irritation). One case of PRES occurred during clinical trials in adult subjects with plaque psoriasis. Infections In the placebo-controlled period of clinical trials of subjects with plaque psoriasis (average follow-up of 12.6 weeks for subjects receiving placebo and 13.4 weeks for STELARA-treated subjects), 27% of STELARA-treated subjects reported infections (1.39 per patient-years of follow-up) compared with 24% of subjects receiving placebo (1.21 per patient-years of follow-up). Serious infections occurred in 0.3% of STELARA-treated subjects (0.01 per patient-years of follow-up) and in 0.4% of subjects receiving placebo (0.02 per patient-years of follow-up). In the controlled and non-controlled portions of clinical trials in subjects with plaque psoriasis (median follow-up of 3.2 years), representing 8998 patient-years of exposure, 72.3% of STELARA-treated subjects reported infections (0.87 per patient-years of follow-up). Serious infections were reported in 2.8% of subjects (0.01 per patient-years of follow-up). Malignancies In the controlled and non-controlled portions of clinical trials in subjects with plaque psoriasis (median follow-up of 3.2 years, representing 8998 patient-years of exposure), 1.7% of STELARA-treated subjects reported malignancies excluding non-melanoma skin cancers (0.60 per hundred patient-years of follow-up). Non-melanoma skin cancer was reported in 1.5% of STELARA-treated subjects (0.52 per hundred patient-years of follow-up). The most frequently observed malignancies other than non-melanoma skin cancer during the clinical trials were: prostate, melanoma, colorectal and breast. Malignancies other than non-melanoma skin cancer in STELARA-treated subjects during the controlled and uncontrolled portions of trials were similar in type and number to what would be expected in the general U.S. population according to the 1969–2004 SEER database (adjusted for age, gender and race). Pediatric Subjects with Plaque Psoriasis The safety of STELARA was assessed in two trials of pediatric subjects with moderate to severe plaque psoriasis. Ps STUDY 3 evaluated safety for up to 60 weeks in 110 pediatric subjects 12 to 17 years old. Ps STUDY 4 evaluated safety for up to 56 weeks in 44 pediatric subjects 6 to 11 years old. The safety profile in pediatric subjects was similar to the safety profile from trials in adults with plaque psoriasis. Psoriatic Arthritis The safety of STELARA was assessed in 927 subjects in two randomized, double-blind, placebo-controlled trials in adults with active psoriatic arthritis (PsA). The overall safety profile of STELARA in subjects with PsA was consistent with the safety profile seen in clinical trials in adult subjects with plaque psoriasis. A higher incidence of arthralgia, nausea, and dental infections was observed in STELARA-treated subjects when compared with placebo-treated subjects (3% vs. 1% for arthralgia and 3% vs. 1% for nausea; 1% vs. 0.6% for dental infections) in the placebo-controlled portions of the PsA clinical trials. Adult Subjects with Crohn's Disease The safety of STELARA was assessed in 1407 subjects with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] greater than or equal to 220 and less than or equal to 450) in three randomized, double-blind, placebo-controlled, parallel-group, multicenter trials. These 1407 subjects included 40 subjects who received a prior investigational intravenous ustekinumab formulation but were not included in the efficacy analyses. In trials CD-1 and CD-2 there were 470 subjects who received STELARA 6 mg/kg as a weight-based single intravenous induction dose and 466 who received placebo. Subjects who were responders in either trial CD-1 or CD-2 were randomized to receive a subcutaneous maintenance regimen of either 90 mg STELARA every 8 weeks, or placebo for 44 weeks in trial CD-3. Subjects in these 3 trials may have received other concomitant therapies including aminosalicylates, immunomodulatory agents [azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate (MTX)], oral corticosteroids (prednisone or budesonide), and/or antibiotics for their Crohn's disease. The overall safety profile of STELARA was consistent with the safety profile seen in the clinical trials in adult subjects with plaque psoriasis and psoriatic arthritis. Common adverse reactions in trials CD-1 and CD-2 and in trial CD-3 are listed in Tables 9 and 10, respectively.

Table 9: Common Adverse Reactions Through Week 8 in Trials CD-1 and CD-2 occurring in ≥3% of STELARA-Treated Subjects and Higher Than Subjects Receiving Placebo Placebo STELARA 6 mg/kg Single Intravenous Induction Dose N=466 N=470 Vomiting 3% 4% Other less common adverse reactions reported in subjects in trials CD-1 and CD-2 included asthenia (1% vs 0.4%), acne (1% vs 0.4%), and pruritus (2% vs 0.4%).

Table 10: Common Adverse Reactions Through Week 44 in Trial CD-3 occurring in ≥3% of STELARA-Treated Subjects and Higher Than Subjects Receiving Placebo Placebo STELARA 90 mg Subcutaneous Maintenance Dose Every 8 Weeks N=133 N=131 Nasopharyngitis 8% 11% Injection site erythema 0 5% Vulvovaginal candidiasis/mycotic infection 1% 5% Bronchitis 3% 5% Pruritus 2% 4% Urinary tract infection 2% 4% Sinusitis 2% 3% Infections In subjects with Crohn's disease, serious or other clinically significant infections included anal abscess, gastroenteritis, and pneumonia. In addition, listeria meningitis and ophthalmic herpes zoster were reported in one subject each. Malignancies With up to one year of treatment in the Crohn's disease clinical trials, 0.2% of STELARA-treated subjects (0.36 events per hundred patient-years) and 0.2% of placebo-treated subjects (0.58 events per hundred patient-years) developed non-melanoma skin cancer. Malignancies other than non-melanoma skin cancers occurred in 0.2% of STELARA-treated subjects (0.27 events per hundred patient-years) and in none of the placebo-treated subjects. Hypersensitivity Reactions Including Anaphylaxis In CD trials, two subjects reported hypersensitivity reactions following STELARA administration. One subject experienced signs and symptoms consistent with anaphylaxis (tightness of the throat, shortness of breath, and flushing) after a single subcutaneous administration (0.1% of subjects receiving subcutaneous STELARA). In addition, one subject experienced signs and symptoms consistent with or related to a hypersensitivity reaction (chest discomfort, flushing, urticaria, and increased body temperature) after the initial intravenous STELARA dose (0.08% of subjects receiving intravenous STELARA). These subjects were treated with oral antihistamines or corticosteroids and in both cases symptoms resolved within an hour. Pediatric Subjects 2 Years of Age and Older with Crohn's Disease The safety of STELARA has been studied in 101 pediatric subjects (2 to 17 years of age) with moderately to severely active Crohn's disease and 48 subjects received the recommended maintenance dosage. In general, adverse reactions reported in the clinical trial of pediatric subjects with Crohn's disease were similar to those reported in adult subjects with Crohn's disease in Studies CD-1, CD-2, and CD-3. Other adverse reactions reported in at least 10% of pediatric subjects were upper respiratory tract infection (13% during induction and 17% during maintenance), COVID-19 (17% during maintenance), and headache (10% during maintenance). One pediatric subject discontinued treatment with STELARA after developing anaphylactic shock within the first two minutes of initiation of the first intravenous infusion and was stabilized with medical intervention. Ulcerative Colitis The safety of STELARA was evaluated in two randomized, double-blind, placebo-controlled clinical trials (UC-1 [IV induction] and UC-2 [SC maintenance]) in 960 adult subjects with moderately to severely active ulcerative colitis. The overall safety profile of STELARA in subjects with ulcerative colitis was consistent with the safety profile seen across all approved indications. Adverse reactions reported in at least 3% of STELARA-treated subjects and at a higher rate than placebo were: Induction (UC-1): nasopharyngitis (7% vs 4%). Maintenance (UC-2): nasopharyngitis (24% vs 20%), headache (10% vs 4%), abdominal pain (7% vs 3%), influenza (6% vs 5%), fever (5% vs. 4%), diarrhea (4% vs 1%), sinusitis (4% vs 1%), fatigue (4% vs 2%), and nausea (3% vs 2%). Infections In subjects with ulcerative colitis, serious or other clinically significant infections included gastroenteritis and pneumonia. In addition, listeriosis and ophthalmic herpes zoster were reported in one subject each. Malignancies With up to one year of treatment in the ulcerative colitis clinical trials, 0.4% of STELARA-treated subjects (0.48 events per hundred patient-years) and 0.0% of subjects receiving placebo (0.00 events per hundred patient-years) developed non-melanoma skin cancer. Malignancies other than non-melanoma skin cancers occurred in 0.5% of STELARA-treated subjects (0.64 events per hundred patient-years) and 0.2% of subjects receiving placebo (0.40 events per hundred patient-years).

6.2 Postmarketing

Experience The following adverse reactions have been reported during post-approval use of STELARA. 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 STELARA exposure.

Immune system disorders: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, dyspnea, rash, urticaria), including a fatal case that presented with chest tightness and dyspnea during infusion of the first dose. Some cases of serious hypersensitivity reactions have been reported in patients with a history of alpha-gal syndrome, allergy to mammalian meat or meat products, or anti-alpha-gal IgE. In most of these cases the reactions occurred at the time of initial administration.

Infections and infestations: Lower respiratory tract infection (including opportunistic fungal infections and tuberculosis).

Neurological disorders: Posterior Reversible Encephalopathy Syndrome (PRES). Respiratory, thoracic, and mediastinal disorders: Interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia.

Skin reactions: Pustular psoriasis, erythrodermic psoriasis, hypersensitivity vasculitis.