The following information comes from DailyMed, an FDA label information provider.
The following serious adverse reactions of Stelara (ustekinumab) are discussed in greater detail in other sections:
- Psoriasis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue.
- Crohn’s Disease, induction (≥3%): vomiting.
- Crohn’s Disease, maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis.
- Ulcerative colitis, induction (≥3%): nasopharyngitis.
- Ulcerative colitis, maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea.
The following serious adverse reactions are discussed elsewhere in the label:
- Hypersensitivity Reactions
- Reversible Posterior Leukoencephalopathy Syndrome
- Herpes zoster
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 psoriasis subjects, 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 4 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the STELARA® groups than the placebo group during the placebo-controlled period of Ps STUDY 1 and Ps STUDY 2.
|Placebo||45 mg||90 mg|
|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%)|
|Diarrhea||12 (2%)||13 (2%)||13 (2%)|
|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 RPLS occurred during clinical studies.
In the placebo-controlled period of clinical studies of psoriasis subjects (average follow-up of 12.6 weeks for placebo-treated subjects and 13.4 weeks for STELARA®-treated subjects), 27% of STELARA®-treated subjects reported infections (1.39 per subject-year of follow-up) compared with 24% of placebo-treated subjects (1.21 per subject-year of follow-up). Serious infections occurred in 0.3% of STELARA®-treated subjects (0.01 per subject-year of follow-up) and in 0.4% of placebo-treated subjects (0.02 per subject-year of follow-up).
In the controlled and non-controlled portions of psoriasis clinical studies (median follow-up of 3.2 years), representing 8998 subject-years of exposure, 72.3% of STELARA®-treated subjects reported infections (0.87 per subject-years of follow-up). Serious infections were reported in 2.8% of subjects (0.01 per subject-years of follow-up).
In the controlled and non-controlled portions of psoriasis clinical studies (median follow-up of 3.2 years, representing 8998 subject-years of exposure), 1.7% of STELARA®-treated subjects reported malignancies excluding non-melanoma skin cancers (0.60 per hundred subject-years of follow-up). Non-melanoma skin cancer was reported in 1.5% of STELARA®-treated subjects (0.52 per hundred subject-years of follow-up). The most frequently observed malignancies other than non-melanoma skin cancer during the clinical studies were: prostate, melanoma, colorectal, and breast. Malignancies other than non-melanoma skin cancer in STELARA®-treated patients during the controlled and uncontrolled portions of studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender and race).1
Adolescent Subjects with Plaque Psoriasis
The safety of STELARA® was assessed in a study of 110 subjects 12 to 17 years of age with moderate to severe plaque psoriasis. The safety profile in these subjects through Week 60 was similar to the safety profile from studies in adults with plaque psoriasis.
The safety of STELARA® was assessed in 927 patients in two randomized, double-blind, placebo-controlled studies in adult patients with active psoriatic arthritis (PsA). The overall safety profile of STELARA® in patients with PsA was consistent with the safety profile seen in adult psoriasis clinical studies. A higher incidence of arthralgia, nausea, and dental infections was observed in STELARA®-treated patients when compared with placebo-treated patients (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 studies.
The safety of STELARA® was assessed in 1407 patients 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 studies. These 1407 patients included 40 patients who received a prior investigational intravenous ustekinumab formulation but were not included in the efficacy analyses. In Studies CD-1 and CD-2, there were 470 patients who received STELARA® 6 mg/kg as a weight-based single intravenous induction dose and 466 who received a placebo. Patients who were responders in either Study 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 Study CD-3. Patients in these 3 studies may have received other concomitant therapies including aminosalicylates, immunomodulatory agents [azathioprine (AZA), 6-mercaptopurine (6-MP), 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 adult psoriasis and psoriatic arthritis clinical studies. Common adverse reactions in Studies CD-1 and CD-2 and in Study CD-3 are listed in Tables 5 and 6, respectively.
6 mg/kg single intravenous induction dose
Other less common adverse reactions reported in patients in Studies CD-1 and CD-2 included asthenia (1% vs 0.4%), acne (1% vs 0.4%), and pruritus (2% vs 0.4%).
90 mg subcutaneous maintenance dose every 8 weeks
|Injection site erythema||0||5%|
|Vulvovaginal candidiasis/mycotic infection||1%||5%|
|Urinary tract infection||2%||4%|
In patients 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 patient each.
With up to one year of treatment in the Crohn’s disease clinical studies, 0.2% of STELARA®-treated patients (0.36 events per hundred patient-years) and 0.2% of placebo-treated patients (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 patients (0.27 events per hundred patient-years) and in none of the placebo-treated patients.
Hypersensitivity Reactions Including Anaphylaxis
In CD studies, two patients reported hypersensitivity reactions following STELARA® administration. One patient experienced signs and symptoms consistent with anaphylaxis (tightness of the throat, shortness of breath, and flushing) after a single subcutaneous administration (0.1% of patients receiving subcutaneous STELARA®). In addition, one patient 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 patients receiving intravenous STELARA®). These patients were treated with oral antihistamines or corticosteroids and in both cases symptoms resolved within an hour.
The safety of STELARA® was evaluated in two randomized, double-blind, placebo-controlled clinical studies (UC-1 [IV induction] and UC-2 [SC maintenance]) in 960 adult patients with moderately to severely active ulcerative colitis. The overall safety profile of STELARA® in patients with ulcerative colitis was consistent with the safety profile seen across all approved indications. Adverse reactions reported in at least 3% of STELARA®-treated patients 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%).
In patients with ulcerative colitis, serious or other clinically significant infections included gastroenteritis and pneumonia. In addition, listeriosis and ophthalmic herpes zoster were reported in one patient each.
With up to one year of treatment in the ulcerative colitis clinical studies, 0.4% of STELARA®-treated patients (0.48 events per hundred patient-years) and 0.0% of placebo-treated patients (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 patients (0.64 events per hundred patient-years) and 0.2% of placebo-treated patients (0.40 events per hundred patient-years).
As with all therapeutic proteins, there is potential for immunogenicity. 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 the incidence of antibodies to ustekinumab in the studies described below with the incidence of antibodies to other products may be misleading.
Approximately 6 to 12.4% of subjects treated with STELARA® in psoriasis and psoriatic arthritis clinical studies developed antibodies to ustekinumab, which were generally low-titer. In psoriasis clinical studies, antibodies to ustekinumab were associated with reduced or undetectable serum ustekinumab concentrations and reduced efficacy. In psoriasis studies, the majority of patients who were positive for antibodies to ustekinumab had neutralizing antibodies.
In Crohn’s disease and ulcerative colitis clinical studies, 2.9% and 4.6% of patients, respectively, developed antibodies to ustekinumab when treated with STELARA® for approximately one year. No apparent association between the development of antibodies to ustekinumab and the development of injection site reactions was seen.
The following adverse reactions have been reported during post-approval 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: Serious hypersensitivity reactions (including anaphylaxis and angioedema), other hypersensitivity reactions (including rash and urticaria).
Infections and infestations: Lower respiratory tract infection (including opportunistic fungal infections and tuberculosis).
Respiratory, thoracic, and mediastinal disorders: Interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia.
Skin reactions: Pustular psoriasis, erythrodermic psoriasis.