STELARA® safety and side effects data in adult patients with moderately to severely active UC
The safety of STELARA® was evaluated in 2 randomized, double-blind, placebo-controlled clinical studies in 960 adult patients with moderately to severely active UC.
≥3% of patients treated with STELARA® and higher than placebo | STELARA® 6 mg/kg IV single dose (n=320) | Placebo(n=319) |
---|---|---|
Nasopharyngitis | 7% | 4% |
≥3% of patients treated with STELARA® and higher than placebo | STELARA® 90 mg subQ every 8 weeks(n=176) | Placebo (STELARA® IV Induction Responders randomized to placebo)†(n=175) |
---|---|---|
Nasopharyngitis | 24% | 20% |
Headache | 10% | 4% |
Abdominal pain | 7% | 3% |
Influenza | 6% | 5% |
Fever | 5% | 4% |
Diarrhea | 4% | 1% |
Sinusitis | 4% | 1% |
Fatigue | 4% | 2% |
Nausea | 3% | 2% |
STELARA® 90 mg subQ every 8 weeks | Placebo | |
---|---|---|
N (treated patients)‡ | 176 | 175 |
Average duration of follow-up (weeks) | 42.2 | 42.3 |
Deaths | 0 | 0 |
Percentage of Patients | ||
Adverse events | 77.3% | 78.9% |
Serious adverse events | 8.5% | 9.7% |
Infections | 48.9% | 46.3% |
Serious infections | 1.7% | 2.3% |
<1% Hypersensitivity reactions1
No cases of anaphylactic or delayed hypersensitivity reactions with STELARA® through 1 year in the UC trials. <1% of patients taking STELARA® in the CD trials experienced hypersensitivity reactions.
<1% Malignancy rate1§
STELARA® is an immunosuppressant and may increase the risk of malignancy.
<2% Serious infections2
1.7% of patients in the STELARA® 90 mg subQ every-8-weeks group reported serious infections vs 2.3% in the placebo group during the Phase 3 Maintenance Study.
<5% of patients developed antibodies1,2
4.6% of overall population treated with STELARA® and 3.4% of randomized patients treated with STELARA® 90 mg subQ every 8 weeks developed antibodies to the drug.
The limited number of patients positive for antibodies to STELARA® limits the ability to draw definitive conclusions regarding the relationship between antibodies to STELARA® and clinical efficacy and safety measures. The data above reflect the percentage of patients whose test results were positive for antibodies to STELARA® at any visit in the UC clinical program and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to STELARA® with the incidence of antibodies to other products may be misleading.
STELARA® 90 mg subQ every 8 weeks during the open-label LTE¶ | Placebo# | |
---|---|---|
N (randomized and nonrandomized patients who were treated in the open-label LTE) | 380 | 188 |
Average duration of follow-up (weeks) | 167.6 | 83.4 |
Total patient-years of follow-up | 1224.5 | 301.7 |
Deaths | 0.08 (0.00, 0.46) | 0.00 (0.00, 0.99) |
Adverse events | 217.56 (209.38, 225.98) | 288.04 (269.20, 307.84) |
Serious adverse events | 7.51 (6.06, 9.21) | 10.61 (7.26, 14.97) |
Infections** | 65.01 (60.57, 69.68) | 86.18 (76.02, 97.32) |
Serious infections** | 1.88 (1.19, 2.82) | 3.31 (1.59, 6.10) |
Data are presented by event rates adjusted by 100 patient-years to normalize differences in follow-up between STELARA® and placebo treatment groups.
Additional safety during open-label LTE (week 0 or maintenance study to week 200)
0.65Malignancy per 100 patient-years (95% CI)II¶#
<2 Serious infections per 100 patient-years (95% CI)II¶#**
<7% of patients developed antibodies to STELARA®††‡‡
Antibody formation among randomized patients who were treated in the open-label LTE:
Antibody formation among the overall population who were treated in the open-label LTE:
CD=Crohn's disease; IV=intravenous; LTE=long-term extension; q8w=every 8 weeks; subQ=subcutaneous; UC=ulcerative colitis.
*Week 44 in the maintenance study was equivalent to 1 year after induction dose.
†Patients who were in clinical response to the STELARA® IV induction dosing and were randomized to placebo subQ on entry into this maintenance study.
‡Randomized patients in the maintenance study.
§Malignancy rates included here reflect a combined evaluation of patients treated with STELARA® including those randomized to either the q8w or q12w dosing regimen.
||Confidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution.
¶Includes 1) patients who were in clinical response to ustekinumab IV induction dosing and were randomized to receive ustekinumab 90 mg subQ q8w on entry into the maintenance study, with data from maintenance Week 0 through Week 156; 2) patients who were in clinical response to ustekinumab IV induction dosing, randomized to receive placebo subQ or ustekinumab 90 mg subQ q12w on entry into the maintenance study, and had a dose adjustment to ustekinumab subQ 90 mg q8w, with data from the time of adjustment onward; and 3) patients who were not in clinical response to ustekinumab at induction Week 8 but were in clinical response at induction Week 16 after a subQ administration of ustekinumab at induction Week 8 and received ustekinumab 90 mg subQ q8w on entry into the maintenance study with data from maintenance Week 0 through Week 156.
#Includes 1) data from maintenance Week 8 onward for patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo subQ on entry into the maintenance study, up to the dose adjustment for patients who had dose adjustment during LTE; and 2) data for Week 0 of maintenance for patients who were in clinical response to placebo IV induction dosing and received placebo subQ on entry into the maintenance study.
**Infection as assessed by the investigator.
††Patients who had at least 1 positive sample at any time after their study agent administration of the induction study through the evaluation visit.
‡‡Denominator is patients with appropriate samples.
References: 1. STELARA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 2. Data on file. Janssen Biotech, Inc. 3. Food and Drug Administration. Guidance for Industry: lmmunogenicity Assessment for Therapeutic Protein Products. Silver Spring, MD: Food and Drug Administration, US Department of Health and Human Services; 2014. fda.gov/regulatory-information/search-fda-guidance-documents/immunogenicity-assessment-therapeutic-protein-products. Accessed October 2, 2019.
INDICATIONS
STELARA® (ustekinumab) is indicated for the treatment of patients 6 years and older with active psoriatic arthritis.
STELARA® (ustekinumab) is indicated for the treatment of patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.
STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.
IMPORTANT SAFETY INFORMATION
STELARA® (ustekinumab) is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or to any of the excipients.
Infections
Treatment with STELARA® should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of STELARA® in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with STELARA® and discontinue STELARA® for serious or clinically significant infections until the infection resolves or is adequately treated.
Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria, Salmonella, and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA® may be susceptible to these types of infections. Consider diagnostic testing, eg, tissue culture, stool culture, as dictated by clinical circumstances.
Pre-Treatment Evaluation of Tuberculosis (TB)
Evaluate patients for TB prior to initiating treatment with STELARA®. Do not administer STELARA® to patients with active tuberculosis infection. Initiate treatment of latent TB before administering STELARA®. Closely monitor patients receiving STELARA® for signs and symptoms of active TB during and after treatment.
Malignancies
STELARA® is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among patients who received STELARA® in clinical trials. The safety of STELARA® has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving STELARA® who had risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving STELARA®, especially those >60 years or those with a history of PUVA or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC.
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA®. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue STELARA®.
Posterior Reversible Encephalopathy Syndrome (PRES)
Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis and Crohn’s disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab.
Monitor all patients treated with STELARA® for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue STELARA®.
Immunizations
Prior to initiating therapy with STELARA®, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with STELARA® should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment with STELARA® or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving STELARA® because of the potential risk for shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of STELARA® may not elicit an immune response sufficient to prevent disease.
Noninfectious Pneumonia
Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of STELARA®. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and, in certain cases, administration of corticosteroids. If diagnosis is confirmed, discontinue STELARA® and institute appropriate treatment.
Allergen 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.
Most Common Adverse Reactions
The most common adverse reactions (≥3% and higher than that with placebo) in adults from plaque psoriasis clinical trials for STELARA® 45 mg, STELARA® 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively. The safety profile in pediatric patients with plaque psoriasis was similar to that of adults with plaque psoriasis. In psoriatic arthritis (PsA) trials, a higher incidence of arthralgia and nausea was observed in patients treated with STELARA® when compared with placebo (3% vs 1% for both). In Crohn’s disease induction trials, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 8 for STELARA® 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In the Crohn’s disease maintenance trial, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 44 for STELARA® 90 mg subcutaneous injection or placebo were: nasopharyngitis (11% vs 8%), injection site erythema (5% vs 0%), vulvovaginal candidiasis/mycotic infection (5% vs 1%), bronchitis (5% vs 3%), pruritus (4% vs 2%), urinary tract infection (4% vs 2%) and sinusitis (3% vs 2%). In the ulcerative colitis induction trial, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 8 for STELARA® 6 mg/kg intravenous single infusion or placebo included: nasopharyngitis (7% vs 4%). In the ulcerative colitis maintenance trial, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 44 for STELARA® 90 mg subcutaneous injection or placebo included: 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%).
Please see full Prescribing Information and Medication Guide for STELARA® . Provide the Medication Guide to your patients and encourage discussion.
cp-124933v7
INDICATIONS
STELARA® (ustekinumab) is indicated for the treatment of patients 6 years and older with active psoriatic arthritis.
STELARA® (ustekinumab) is indicated for the treatment of patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.
STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.
IMPORTANT SAFETY INFORMATION
STELARA® (ustekinumab) is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or to any of the excipients.
Infections
Treatment with STELARA® should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of STELARA® in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with STELARA® and discontinue STELARA® for serious or clinically significant infections until the infection resolves or is adequately treated.
Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria, Salmonella, and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA® may be susceptible to these types of infections. Consider diagnostic testing, eg, tissue culture, stool culture, as dictated by clinical circumstances.
Pre-Treatment Evaluation of Tuberculosis (TB)
Evaluate patients for TB prior to initiating treatment with STELARA®. Do not administer STELARA® to patients with active tuberculosis infection. Initiate treatment of latent TB before administering STELARA®. Closely monitor patients receiving STELARA® for signs and symptoms of active TB during and after treatment.
Malignancies
STELARA® is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among patients who received STELARA® in clinical trials. The safety of STELARA® has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving STELARA® who had risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving STELARA®, especially those >60 years or those with a history of PUVA or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC.
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA®. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue STELARA®.
Posterior Reversible Encephalopathy Syndrome (PRES)
Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis and Crohn’s disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab.
Monitor all patients treated with STELARA® for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue STELARA®.
Immunizations
Prior to initiating therapy with STELARA®, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with STELARA® should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment with STELARA® or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving STELARA® because of the potential risk for shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of STELARA® may not elicit an immune response sufficient to prevent disease.
Noninfectious Pneumonia
Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of STELARA®. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and, in certain cases, administration of corticosteroids. If diagnosis is confirmed, discontinue STELARA® and institute appropriate treatment.
Allergen 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.
Most Common Adverse Reactions
The most common adverse reactions (≥3% and higher than that with placebo) in adults from plaque psoriasis clinical trials for STELARA® 45 mg, STELARA® 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively. The safety profile in pediatric patients with plaque psoriasis was similar to that of adults with plaque psoriasis. In psoriatic arthritis (PsA) trials, a higher incidence of arthralgia and nausea was observed in patients treated with STELARA® when compared with placebo (3% vs 1% for both). In Crohn’s disease induction trials, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 8 for STELARA® 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In the Crohn’s disease maintenance trial, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 44 for STELARA® 90 mg subcutaneous injection or placebo were: nasopharyngitis (11% vs 8%), injection site erythema (5% vs 0%), vulvovaginal candidiasis/mycotic infection (5% vs 1%), bronchitis (5% vs 3%), pruritus (4% vs 2%), urinary tract infection (4% vs 2%) and sinusitis (3% vs 2%). In the ulcerative colitis induction trial, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 8 for STELARA® 6 mg/kg intravenous single infusion or placebo included: nasopharyngitis (7% vs 4%). In the ulcerative colitis maintenance trial, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 44 for STELARA® 90 mg subcutaneous injection or placebo included: 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%).
Please see full Prescribing Information and Medication Guide for STELARA® . Provide the Medication Guide to your patients and encourage discussion.
cp-124933v7