What is Stelara (ustekinumab)?

Stelara is a monoclonal antibody used to treat adults 18 years and older with moderate or severe psoriasis that involves large areas or many areas of their body, who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills). Stelara may improve psoriasis but may also lower the ability of the immune system to fight infections. 

Common side effects of Stelara include:

Serious side effects of Stelara include lowered ability of the immune system to fight infections and increased risk of infections. This may also increase the risk for certain types of cancer.

Some people have serious infections while taking Stelara, including:

  • tuberculosis (TB), and
  • infections caused by bacteria, fungi, or viruses. Some people have to be hospitalized for treatment of their infection.

Stelara may also rarely cause reversible posterior leukoencephalopathy syndrome (RPLS), a rare condition that affects the brain and can cause death. Symptoms of RPLS include headache, seizures, confusion, and vision problems.

Drug interactions of Stelara include other medicines that affect your immune system, certain medicines that can affect how your liver breaks down other medicines, and live vaccines. Tell your doctor if you are pregnant or planning to become pregnant. It is not known if Stelara will harm a fetus.

It is thought that Stelara passes into breast milk. Consult your doctor before breastfeeding.

What are the important side effects of Stelara (ustekinumab)?

The most common side effects of ustekinumab are:

Ustekinumab may reduce the ability the immune system to fight infections, increasing the risk of infections such as tuberculosis (TB), and infections caused by bacteria, fungi, or viruses.

Ustekinumab also may increase the risk of certain types of cancer and cause posterior leukoencephalopathy syndrome (RPLS). RPLS is a rare condition that affects the brain and can cause death. The cause is unknown but if detected early and treated, most people recover.

Symptoms may include:

Stelara (ustekinumab) side effects list for healthcare professionals

The following serious adverse reactions are discussed elsewhere in the label:

  • Infections
  • Malignancies
  • Hypersensitivity Reactions
  • Reversible Posterior Leukoencephalopathy Syndrome

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.

Table 4: Adverse Reactions Reported by ≥1% of Subjects through Week 12 in Ps STUDY 1 and Ps STUDY 2

Stelara®PlaceboSTUDY 2
45 mg90 mg
Subjects treated665664666
Nasopharyngitis51 (8%)56 (8%)49 (7%)
Upper respiratory tract infection30 (5%)36 (5%)28 (4%)
Headache23 (3%)33 (5%)32 (5%)
Fatigue14 (2%)18 (3%)17 (3%)
Diarrhea12 (2%)13 (2%)13 (2%)
Back pain8 (1%)9 (1%)14 (2%)
Dizziness8 (1%)8 (1%)14 (2%)
Pharyngolaryngeal pain7 (1%)9 (1%)12 (2%)
Pruritus9 (1%)10 (2%)9 (1%)
Injection site erythema3 (<1%)6 (1%)13 (2%)
Myalgia4 (1%)7 (1%)8 (1%)
Depression3 (<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:

One case of RPLS occurred during clinical studies.

Infections
  • 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).
Malignancies
  • 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.

Psoriatic Arthritis

  • 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.

Crohn's Disease

  • 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 CD2 there were 470 patients who received Stelara 6 mg/kg as a weight-based single intravenous induction dose and 466 who received 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.

Table 5: Common adverse reactions through Week 8 in Studies CD-1 and CD-2 occurring in ≥3% of Stelara®-treated patients and higher than placebo

Placebo
N=466
Stelara 6 mg/kg single intravenous induction dose
N=470
Vomiting3%4%

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%).

Table 6: Common adverse reactions through Week 44 in Study CD-3 occurring in ≥3% of Stelara-treated patients and higher than placebo

Placebo
N=133
Stelara® 90 mg subcutaneous maintenance dose every 8 weeks
N=131
Nasopharyngitis8%11%
Injection site erythema05%
Vulvovaginal candidiasis/mycotic infection1%5%
Bronchitis3%5%
Pruritus2%4%
Urinary tract infection2%4%
Sinusitis2%3%

Infections

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.

Malignancies
  • 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.

Ulcerative Colitis

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:

Infections

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.

Malignancies
  • 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).

Immunogenicity

  • 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.

Postmarketing Experience

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).

Respiratory, thoracic and mediastinal disorders: Interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia.

Skin reactions: Pustular psoriasis, erythrodermic psoriasis.

What drugs interact with Stelara (ustekinumab)?

Live Vaccines

  • Avoid use of live vaccines with Stelara.

Concomitant Therapies

  • In psoriasis studies the safety of Stelara in combination with immunosuppressive agents or phototherapy has not been evaluated. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of Stelara.
  • In Crohn's disease and ulcerative colitis induction studies, immunomodulators (6-MP, AZA, MTX) were used concomitantly in approximately 30% of patients and corticosteroids were used concomitantly in approximately 40% and 50% of Crohn's disease and ulcerative colitis patients, respectively.
  • Use of these concomitant therapies did not appear to influence the overall safety or efficacy of Stelara.

CYP450 Substrates

  • The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFa, IFN) during chronic inflammation.
  • Thus, Stelara, an antagonist of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Upon initiation of Stelara in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, monitoring for therapeutic effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) should be considered and the individual dose of the drug adjusted as needed.

Allergen Immunotherapy

  • Stelara has not been evaluated in patients who have undergone allergy immunotherapy.
  • Stelara may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy.
  • Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis.

Summary

Stelara (ustekinumab) is a monoclonal antibody used to treat adults 18 years and older with moderate or severe psoriasis that involves large areas or many areas of their body, who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills). Common side effects of Stelara include upper respiratory infections, headache, and tiredness. Tell your doctor if you are pregnant or planning to become pregnant. It is not known if Stelara will harm a fetus. It is thought that Stelara passes into breast milk. Consult your doctor before breastfeeding.

Treatment & Diagnosis

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Medically Reviewed on 5/21/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.

1 Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence -SEER 6.6.2 Regs Research Data, Nov 2009 Sub (19732007) -Linked To County Attributes -Total U.S., 1969-2007 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2010, based on the November 2009 submission.
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