For US Healthcare Professionals
For US Healthcare Professionals
For US Healthcare Professionals
TREMFYA® ADDITIONAL ACTIVE COMPARATOR STUDIES
ECLIPSE Study Design:
TREMFYA® vs Cosentyx® (secukinumab)
ECLIPSE: PHASE 3, DOUBLE-BLIND TRIAL (n=1048)1,2
Cosentyx® is a registered trademark of Novartis AG.
PATIENT ELIGIBILITY
- ≥18 years of age
- Moderate to severe plaque psoriasis (IGA score ≥3; PASI score ≥12, BSA involvement ≥10%) for at least 6 months
- Candidates for phototherapy and/or systemic treatment
OVERALL STUDY POPULATION1
ECLIPSE Statistical Methods
This study utilized a step-down approach to control for multiple testing. The first major secondary endpoint did not achieve statistical significance for superiority; therefore, the remaining P values are nominal and not included in the presentation.
| ENDPOINT TESTED | TESTING PLAN |
| PRIMARY ENDPOINT | |
| PASI 90 at Week 48 | |
| MAJOR SECONDARY ENDPOINTS | |
| PASI 75 at both Week 12 and 48* | |
| PASI 90 at Week 12 | |
| PASI 75 at Week 12 | |
| PASI 100 at Week 48 | |
| IGA 0 at Week 48 | |
| IGA 0/1 at Week 48 | |
NRI methods were used for analysis.
*Superiority for the first major secondary endpoint, PASI 75 at both Week 12 and 48, was not achieved (TREMFYA® 84.6% vs Cosentyx® 80.2%; P=0.062); therefore, the remaining P values are nominal and not included in the presentation.
TREMFYA® DEMONSTRATED SUPERIORITY vs COSENTYX® FOR PASI 90* RESPONSE AT WEEK 481,2
ECLIPSE: PRIMARY ENDPOINT AT WEEK 48
PASI 90
PASI 75 AND IGA 0/1 AT WEEK 12
Secondary Endpoints at Week 12
- PASI 75‡: TREMFYA® 89% (477/534), Cosentyx® 92% (471/514)
- IGA 0/1§: TREMFYA® 86% (457/534), Cosentyx® 86% (444/514)
Due to the results of the step-down approach to control for multiple testing, nominal P values for PASI 75 at Week 12 are not presented and efficacy comparisons cannot be made.
IGA 0/1 at Week 12 was a prespecified exploratory endpoint that was not adjusted for multiplicity; P value was considered nominal.
Results based on ECLIPSE, a single study of TREMFYA® vs Cosentyx®.
NRI methods were used for analysis.
There were no new safety findings observed for either TREMFYA® or Cosentyx® in this study.
Results based on ECLIPSE: a single study of TREMFYA® vs Cosentyx®.
*PASI 90=Proportion of patients who achieved 90% or more reduction (or improvement) in PASI score from baseline.
‡PASI 75=Proportion of patients who achieved 75% or more reduction (or improvement) in PASI score from baseline.
§IGA 0/1=Proportion of patients who achieved an IGA score of cleared (0) or minimal (1) using a 5-point scale where psoriatic lesions are graded by the investigator for induration, erythema, and scaling on a scale of 0 to 4: cleared, except for discoloration (0), minimal (1), mild (2), moderate (3), or severe (4).
TREMFYA®: IGA 0* AND PASI 100† AT WEEK 481,2
Due to the results of the step-down approach to control for multiple testing, nominal P values for IGA 0, PASI 100, and IGA 0/1 at Week 48 are not presented and efficacy comparisons cannot be made.
ECLIPSE: MAJOR SECONDARY ENDPOINTS AT WEEK 48
Results at Week 48
NRI methods were used for analysis.
Results based on ECLIPSE: a single study of TREMFYA® vs Cosentyx®.
*IGA 0=Proportion of patients who achieved an IGA score of cleared (0) using a 5-point scale where psoriatic lesions are graded by the investigator for induration, erythema, and scaling on a scale of 0 to 4: cleared, except for discoloration (0), minimal (1), mild (2), moderate (3), or severe (4).
†PASI 100=Proportion of patients who achieved 100% or more reduction (or improvement) in PASI score from baseline.
PASI 90 RESPONSE WITH TREMFYA® AT WEEK 48 BY BASELINE BODY WEIGHT QUARTILE1
ECLIPSE: POST HOC ANALYSIS OF BODY WEIGHT—PASI 90 AT WEEK 48
BODY WEIGHT
NRI methods were used.
This is a post hoc analysis; statistical significance has not been established.
The quartile cutoffs are based on the overall population (not by treatment group).
PASI 90 RESPONSE WITH TREMFYA® AT WEEK 48 BY BASELINE BMI CATEGORY1
ECLIPSE: PRESPECIFIED SUBGROUP ANALYSIS OF BMI CATEGORY—PASI 90 AT WEEK 48
NRI methods were used.
This is a prespecified subgroup analysis; statistical significance has not been established.
References: 1. Data on file. Janssen Biotech, Inc. 2. Reich K, Armstrong AW, Langley RG, et al. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. Lancet. 2019;394(10201):831-839.
NAVIGATE Study Design:
TREMFYA® vs STELARA® (ustekinumab)
NAVIGATE: PHASE 3, DOUBLE-BLIND TRIAL (n=81)1*
PATIENT ELIGIBILITY
- ≥18 years of age
- Moderate to severe plaque psoriasis (IGA score ≥3; PASI score ≥12; BSA involvement ≥10%) for at least 6 months
- Candidates for phototherapy and/or systemic treatment
Analyses were nonresponder imputation (NRI).
*NAVIGATE was a phase 3 trial with a 16-week, open-label treatment period; a 28-week randomized, double-blinded, active-treatment period; and a 16-week follow-up period. This study evaluated the efficacy of 24 weeks of treatment with TREMFYA® in subjects (n=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with US-licensed STELARA® (dosed 45 mg or 90 mg according to the subject’s baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with US-licensed STELARA® treatment every 12 weeks or switch to TREMFYA® 100 mg at Weeks 16, 20, and q8w thereafter.
†All patients received open-label STELARA® (45 mg for patients weighing ≤100 kg; 90 mg for patients weighing >100 kg) at Weeks 0 and 4.
‡US-licensed STELARA® (dosed 45 mg or 90 mg according to the patient’s baseline weight at Week 0 and Week 4).
IN PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS WITH AN INADEQUATE RESPONSE TO STELARA®*
SIGNIFICANT SKIN CLEARANCE vs STELARA®1
NAVIGATE: MAJOR SECONDARY ENDPOINT AT WEEK 28 (12 WEEKS AFTER RANDOMIZATION)†
†More than twice as many patients treated with TREMFYA® achieved IGA 0/1§ (with a ≥2-grade improvement) at Week 28.
*IGA ≥2 at Week 16 after initial treatment with US-licensed STELARA® (dosed 45 mg or 90 mg according to the patient’s baseline weight at Week 0 or Week 4).
§IGA 0/1=Proportion of patients who achieved an IGA score of cleared (0) or minimal (1) using a 5-point scale where psoriatic lesions are graded by the investigator for induration, erythema, and scaling on a scale of 0 to 4: cleared, except for residual discoloration (0), minimal (1), mild (2), moderate (3), or severe (4).
IN PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS WITH AN INADEQUATE RESPONSE TO STELARA®*
PASI 90* RESPONSE RATES FROM WEEK 16 THROUGH WEEK 521,2
NAVIGATE: PRESPECIFIED EXPLORATORY ENDPOINT FROM WEEK 16 TO WEEK 52†
PASI 90
The same patients may not have responded at each time point.
*PASI 90=Proportion who achieved 90% or more reduction (or improvement) in PASI score from baseline.
†Proportion of patients who achieved PASI 90 from Week 16 through Week 52 was a prespecified exploratory endpoint that was not adjusted for multiplicity; P values were considered nominal.
References: 1. Langley RG, Tsai, TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018;178(1):114-123. 2. Data on file. Janssen Biotech, Inc.
STELARA® (ustekinumab) Important Safety Information
STELARA® (ustekinumab) is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or to any of the excipients.
Infections
STELARA® may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections requiring hospitalization or otherwise clinically significant infections were reported. In patients with psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.
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 consider discontinuing 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. Appropriate diagnostic testing should be considered (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 studies. 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 recommended by current guidelines. Patients being treated with STELARA® should not receive live vaccines. BCG vaccines should not be given during treatment or within one year of initiating or discontinuing STELARA®. Exercise caution when administering live vaccines to household contacts of STELARA® patients, as shedding and subsequent transmission to STELARA® patients may occur. Non-live vaccinations received during a course of STELARA® may not elicit an immune response sufficient to prevent disease.
Concomitant Therapies
The safety of STELARA® in combination with other biologic immunosuppressive agents or phototherapy was not evaluated in clinical studies of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of STELARA®. In Crohn’s disease and ulcerative colitis induction studies, concomitant use of 6-mercaptopurine, azathioprine, methotrexate, and corticosteroids did not appear to influence the overall safety or efficacy of STELARA®.
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 psoriasis clinical studies 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) studies, 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 studies, 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 study, 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 study, 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 study, 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-124933v3
Indications
STELARA® (ustekinumab) is indicated for the treatment of adult patients with active psoriatic arthritis. STELARA® can be used alone or in combination with methotrexate (MTX).
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.
ECLIPSE Study Design: TREMFYA® vs Cosentyx® (secukinumab)
ECLIPSE: PHASE 3, DOUBLE-BLIND TRIAL (N=1048)1,2
Cosentyx® is a registered trademark of Novartis AG.
PATIENT ELIGIBILITY
- ≥18 years of age
- Moderate to severe plaque psoriasis (IGA score ≥3; PASI score ≥12, BSA involvement ≥10%) for at least 6 months
- Candidates for phototherapy and/or systemic treatment
OVERALL STUDY POPULATION1
ECLIPSE STATISTICAL METHODS
This study utilized a step-down approach to control for multiple testing. The first major secondary endpoint did not achieve statistical significance for superiority, therefore the remaining P values are nominal and not included in the presentation.
| ENDPOINT TESTED | TESTING PLAN |
| PRIMARY ENDPOINT | |
| PASI 90 at Week 48 | |
| MAJOR SECONDARY ENDPOINTS | |
| PASI 75 at both Week 12 and 48* | |
| PASI 90 at Week 12 | |
| PASI 75 at Week 12 | |
| PASI 100 at Week 48 | |
| IGA 0 at Week 48 | |
| IGA 0/1 at Week 48 | |
NRI methods were used for analysis.
*Superiority for the first major secondary endpoint, PASI 75 at both Week 12 and 48, was not achieved (TREMFYA® 84.6% vs Cosentyx® 80.2%; P=0.062); therefore, the remaining P values are nominal and not included in the presentation.
TREMFYA® DEMONSTRATED SUPERIORITY vs COSENTYX® FOR PASI 90* RESPONSE AT WEEK 481,2
ECLIPSE: PRIMARY ENDPOINT AT WEEK 48
PASI 90
PASI 75 AND IGA 0/1 AT WEEK 12
Secondary Endpoints at Week 12
- PASI 75‡: TREMFYA® 89% (477/534), Cosentyx® 92% (471/514)
- IGA 0/1§: TREMFYA® 86% (457/534), Cosentyx® 86% (444/514)
Due to the results of the step-down approach to control for multiple testing, nominal P values for PASI 75 at Week 12 are not presented and efficacy comparisons cannot be made.
IGA 0/1 at Week 12 was a prespecified exploratory endpoint that was not adjusted for multiplicity; P value was considered nominal.
Results based on ECLIPSE, a single study of TREMFYA® vs Cosentyx®.
NRI methods were used for analysis.
There were no new safety findings observed for either TREMFYA® or Cosentyx® in this study.
*PASI 90=Proportion of patients who achieved 90% or more reduction (or improvement) in PASI score from baseline.
‡PASI 75=Proportion of patients who achieved 75% or more reduction (or improvement) in PASI score from baseline.
§IGA 0/1=Proportion of patients who achieved an IGA score of cleared (0) or minimal (1) using a 5-point scale where psoriatic lesions are graded by the investigator for induration, erythema, and scaling on a scale of 0 to 4: cleared, except for discoloration (0), minimal (1), mild (2), moderate (3), or severe (4).
TREMFYA®: IGA 0* AND PASI 100† AT WEEK 481,2
Due to the results of the step-down approach to control for multiple testing, nominal P values for IGA 0, PASI 100, and IGA 0/1 at Week 48 are not presented and efficacy comparisons cannot be made.
ECLIPSE: MAJOR SECONDARY ENDPOINTS AT WEEK 48
Results at Week 48
NRI methods were used for analysis.
Results based on ECLIPSE: a single study of TREMFYA® vs Cosentyx®.
*IGA 0=Proportion of patients who achieved an IGA score of cleared (0) using a 5-point scale where psoriatic lesions are graded by the investigator for induration, erythema, and scaling on a scale of 0 to 4: cleared, except for discoloration (0), minimal (1), mild (2), moderate (3), or severe (4).
†PASI 100=Proportion of patients who achieved 100% or more reduction (or improvement) in PASI score from baseline.
PASI 90 RESPONSE WITH TREMFYA® AT WEEK 48 BY BASELINE BODY WEIGHT QUARTILE1
ECLIPSE: POST HOC ANALYSIS OF BODY WEIGHT—PASI 90 AT WEEK 48
BODY WEIGHT
NRI methods were used.
This is a post hoc analysis; statistical significance has not been established.
The quartile cutoffs are based on the overall population (not by treatment group).
PASI 90 RESPONSE WITH TREMFYA® AT WEEK 48 BY BASELINE BMI CATEGORY1
ECLIPSE: PRESPECIFIED SUBGROUP ANALYSIS OF BMI CATEGORY—PASI 90 AT WEEK 48
BMI
NRI methods were used.
This is a prespecified subgroup analysis; statistical significance has not been established.
References: 1. Data on file. Janssen Biotech, Inc. 2. Reich K, Armstrong AW, Langley RG, et al. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. Lancet. 2019;394(10201):831-839.
NAVIGATE Study Design: TREMFYA® vs STELARA® (ustekinumab)
NAVIGATE: PHASE 3, DOUBLE-BLIND TRIAL (n=81)1*
PATIENT ELIGIBILITY
- ≥18 years of age
- Moderate to severe plaque psoriasis (IGA score ≥3; PASI score ≥12; BSA involvement ≥10%) for at least 6 months
- Candidates for phototherapy and/or systemic treatment
Analyses were nonresponder imputation (NRI).
*NAVIGATE was a phase 3 trial with a 16-week, open-label treatment period; a 28-week randomized, double-blinded, active-treatment period; and a 16-week follow-up period. This study evaluated the efficacy of 24 weeks of treatment with TREMFYA® in subjects (n=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with US-licensed STELARA® (dosed 45 mg or 90 mg according to the subject’s baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with US-licensed STELARA® treatment every 12 weeks or switch to TREMFYA® 100 mg at Weeks 16, 20, and q8w thereafter.
†All patients received open-label STELARA® (45 mg for patients weighing ≤100 kg; 90 mg for patients weighing >100 kg) at Weeks 0 and 4.
‡US-licensed STELARA® (dosed 45 mg or 90 mg according to the patient’s baseline weight at Week 0 and Week 4).
IN PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS WITH AN INADEQUATE RESPONSE TO STELARA®*
SIGNIFICANT SKIN CLEARANCE vs STELARA®1
NAVIGATE: MAJOR SECONDARY ENDPOINT AT WEEK 28 (12 WEEKS AFTER RANDOMIZATION)†
IGA 0/1 WITH A ≥ 2 GRADE IMPROVEMENT
†More than twice as many patients treated with TREMFYA® achieved IGA 0/1§ (with a ≥2-grade improvement) at Week 28.
*IGA ≥2 at Week 16 after initial treatment with US-licensed STELARA®. (dosed 45 mg or 90 mg according to the patient’s baseline weight at Week 0 or Week 4).
§IGA 0/1=Proportion of patients who achieved an IGA score of cleared (0) or minimal (1) using a 5-point scale where psoriatic lesions are graded by the investigator for induration, erythema, and scaling on a scale of 0 to 4: cleared, except for residual discoloration (0), minimal (1), mild (2), moderate (3), or severe (4).
IN PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS WITH AN INADEQUATE RESPONSE TO STELARA®*
PASI 90* RESPONSE RATES FROM WEEK 16 THROUGH WEEK 521,2
NAVIGATE: PRESPECIFIED EXPLORATORY ENDPOINT FROM WEEK 16 TO WEEK 52†
PASI 90
The same patients may not have responded at each time point.
*PASI 90=Proportion who achieved 90% or more reduction (or improvement) in PASI score from baseline.
†Proportion of patients who achieved PASI 90 from Week 16 through Week 52 was a prespecified exploratory endpoint that was not adjusted for multiplicity; P values were considered nominal.
References: 1. Langley RG, Tsai, TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018;178(1):114-123. 2. Data on file. Janssen Biotech, Inc.
STELARA® (ustekinumab) Important Safety Information
STELARA® (ustekinumab) is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or to any of the excipients.
Infections
STELARA® may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections requiring hospitalization or otherwise clinically significant infections were reported. In patients with psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.
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 consider discontinuing 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. Appropriate diagnostic testing should be considered (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 studies. 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 recommended by current guidelines. Patients being treated with STELARA® should not receive live vaccines. BCG vaccines should not be given during treatment or within one year of initiating or discontinuing STELARA®. Exercise caution when administering live vaccines to household contacts of STELARA® patients, as shedding and subsequent transmission to STELARA® patients may occur. Non-live vaccinations received during a course of STELARA® may not elicit an immune response sufficient to prevent disease.
Concomitant Therapies
The safety of STELARA® in combination with other biologic immunosuppressive agents or phototherapy was not evaluated in clinical studies of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of STELARA®. In Crohn’s disease and ulcerative colitis induction studies, concomitant use of 6-mercaptopurine, azathioprine, methotrexate, and corticosteroids did not appear to influence the overall safety or efficacy of STELARA®.
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 psoriasis clinical studies 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) studies, 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 studies, 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 study, 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 study, 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 study, 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-124933v3
Indications
STELARA® (ustekinumab) is indicated for the treatment of adult patients with active psoriatic arthritis. STELARA® can be used alone or in combination with methotrexate (MTX).
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.