For the treatment of adult patients with moderately to severely active CD

STELARA®: Safety Profile in CD1

The safety of STELARA® was evaluated in 1,407 patients with moderately to severely active CD (CDAI ≥220 and ≤450) in 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter studies through 1 year.

The overall safety profile of STELARA® in CD through 1 year was consistent with that seen in other approved indications.1

Common Adverse Reactions Through Week 8 in 2 Single IV Induction Studies

≥3% of patients treated with STELARA® and higher than placebo STELARA® 6 mg/kg IV single dose (N=470) Placebo (N=466)
Vomiting 4% 3%

Other less common adverse reactions reported in patients in the 2 single IV induction studies included asthenia (1% vs 0.4%), acne (1% vs 0.4%), and pruritus (2% vs 0.4%).

Common Adverse Reactions Through Week 44 in SubQ Maintenance Study*

≥3% of patients treated with STELARA® and higher than placebo STELARA® 90 mg subQ every 8 weeks (N=131) Placebo (N=133)
Nasopharyngitis 11% 8%
Injection-site erythema 5% 0
Vulvovaginal candidiasis/mycotic infection 5% 1%
Bronchitis 5% 3%
Pruritus 4% 2%
Urinary tract infection 4% 2%
Sinusitis 3% 2%

Adverse Events THROUGH 1 Year1,2

  Patients treated with STELARA®§
90 mg subQ every 8 weeks
Placebo||
N (treated patients) 131 133
Average duration of follow-up (weeks) 35.2 32.0
Deaths 0 0
  Percentage of patients  
Adverse events 81.7% 83.5%
Serious adverse events 9.9% 15.0%
Infections 48.1% 49.6%
Serious infections 2.3% 2.3%

ADDITIONAL SAFETY AT 1 YEAR

<1% Hypersensitivity reactions1

  • One patient (0.08%) experienced signs and symptoms consistent with or related to a hypersensitivity reaction after receiving the initial STELARA® IV dose. One patient (0.1%) experienced signs and symptoms consistent with anaphylaxis# after receiving a single subQ STELARA® dose. In both cases, patients were treated with oral antihistamines or corticosteroids and symptoms were resolved within an hour

<1% Malignancy rate**

  • Nonmelanoma skin cancer developed in 0.2% of both the STELARA® group and the placebo group
  • Other malignancies occurred in 0.2% of patients receiving STELARA® and in none of the patients receiving placebo

STELARA® is an immunosuppressant and may increase the risk of malignancy.

<3% Serious infections2

  • 2.3% of patients treated with STELARA® 90 mg subQ every 8 weeks
  • 2.3% of patients treated with placebo

<3% of patients developed antibodies1,2

  • 2.9% of overall population treated with STELARA® and 2.4% of randomized patients treated with STELARA® 90 mg subQ every 8 weeks developed antibodies to the drug

CD=Crohn’s disease; CDAI=Crohn's Disease Activity Index; IV=intravenous; q8w=every 8 weeks; q12w=every 12 weeks; subQ=subcutaneous; UC=ulcerative colitis.

 

*Week 44 was equivalent to to 1 year after induction dose.1

†Patients who were in clinical response to STELARA® IV induction dosing and were randomized to placebo subQ on entry into this maintenance study.

‡Randomized patients in the maintenance study.1

§Included responders and nonresponders for STELARA® IV induction dosing.2

ǁIncludes: 1) All data for patients who were in clinical response to placebo IV induction dosing and received placebo subQ in the Maintenance Study. 2) The data from Week 8 onward for patients who were in clinical response to STELARA® IV induction dosing and received placebo subQ in this maintenance study.2

Symptoms included chest discomfort, flushing, urticaria, and increased body temperature.1

#Symptoms included tightness of the throat, shortness of breath, and flushing.1

**Malignancy rates included here reflect a combined evaluation of patients treated with STELARA® including those randomized to either the q8w or q12w dosing regimens.1,2

STELARA® Safety Through 1 Year in Combined CD+UC1,2*

ADVERSE EVENTS THROUGH 1 YEAR

Combined Safety (CD+UC)* CD UC
Combined Safety (CD+UC)*
  STELARA®
90 mg subQ every 8 weeks
Placebo
N (treated patients)|| 307 308
Average duration of follow-up (weeks) 39.2 37.8
Deaths 0 0
Percentage of patients
Adverse events 79.2% 80.8%
Serious adverse events 9.1% 12.0%
Infections 48.5% 47.7%
Serious infections 2.0% 2.3%
CD
  STELARA®
90 mg subQ every 8 weeks
Placebo§
N (treated patients)|| 131 133
Average duration of follow-up (weeks) 35.2 32.0
Deaths 0 0
Percentage of patients
Adverse events 81.7% 83.5%
Serious adverse events 9.9% 15.0%
Infections 48.1% 49.6%
Serious infections 2.3% 2.3%
UC
  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%

*Data for combined Crohn’s disease and ulcerative colitis results include Phase 3 maintenance studies (Ulcerative Colitis: CNTO1275UCO3001; Crohn’s Disease: CNTO1275CRD3003); includes data up to the time of meeting loss of response criteria for patients who had Crohn’s disease.

ADDITIONAL SAFETY AT 1 YEAR FOR CD AND UC1

<1% Hypersensitivity reactions

In CD: Following initial STELARA® IV dose: 1 patient (0.08%) experienced signs and symptoms consistent with or related to a hypersensitivity reaction; following single subQ STELARA® dose: 1 patient (0.1%) experienced signs and symptoms consistent with anaphylaxis.# In both cases, patients were treated with oral antihistamines or corticosteroids and symptoms resolved within an hour.

No cases of anaphylactic or delayed hypersensitivity reactions with STELARA® through 1 year in the UC trials.

<1% Malignancy rates**

In CD: Nonmelanoma skin cancer developed in 0.2% of both the STELARA® group and the placebo group; other malignancies occurred in 0.2% of patients receiving STELARA® and in no patients receiving placebo.

In UC: Nonmelanoma skin cancer: STELARA®: 0.4%; placebo: 0.0%; other malignancies: STELARA®: 0.5%; placebo: 0.2%.
STELARA® is an immunosuppressant and may increase the risk of malignancy.

≈2% Serious infections

In CD: 2.3% of patients in both the STELARA® 90 mg subQ every-8-weeks group and placebo group.

In UC: 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 antibodies

In CD: 2.9% of overall population treated with STELARA®; 2.4% of randomized patients treated with STELARA® 90 mg subQ every 8 weeks.

In UC: 4.6% of overall population treated with STELARA®; 3.4% of randomized patients treated with STELARA® 90 mg subQ every 8 weeks.

CD=Crohn’s disease; IV=intravenous; q8w=every 8 weeks; q12w=every 12 weeks; subQ=subcutaneous; UC=ulcerative colitis.

 

†Patients who were in clinical response to STELARA® IV induction dosing and were randomized to placebo subQ on entry into this maintenance study.

‡Included responders and nonresponders for STELARA® IV induction dosing.

§Includes: 1) All data for patients who were in clinical response to placebo IV induction dosing and received placebo subQ in the maintenance study 2) The data from Week 8 onward for patients who were in clinical response to STELARA® IV induction dosing and received placebo subQ in this maintenance study.

||Randomized patients in the maintenance study.

Symptoms included chest discomfort, flushing, urticaria, and increased body temperature.

#Symptoms included tightness of the throat, shortness of breath, and flushing.

**Malignancy rates included here reflect a combined evaluation of patients treated with STELARA® including those randomized to either the q8w or q12w dosing regimens.

ADVERSE EVENTS THROUGH UP TO 5 YEARS IN CD2

NUMBER OF EVENTS PER 100 PATIENT-YEARS OF FOLLOW-UP (95% CI)*

  STELARA®
90 mg subQ every 8 weeks
Placebo
N (patients treated) 607 593
Average duration of follow-up (weeks) 122.55 37
Total patient years of follow-up 1431 422
Deaths 0.14
(0.02, 0.51)
0
(0.00, 0.71)
Adverse events 394.18
(383.96, 404.60)
545.86
(523.79, 568.62)
Serious adverse events 21.18
(19.46, 24.37)
29.15
(24.23, 34.78)
Infections§ 99.19
(94.10, 104.49)
118.51
(108.35, 129.37)
Serious infections§ 3.50
(2.59, 4.61)
6.16
(4.03, 9.03)

Data are presented by event rates adjusted by 100 patient-years to normalize difference in follow-up time between STELARA® and placebo treatment groups.

ADDITIONAL SAFETY THROUGH UP TO 5 YEARS2

0.99 Malignancy per 100 patient-years2II¶

  • STELARA® 90 mg every 8 weeks: 0.99 (n=354)#
  • Placebo: 1.70 (n=151)**
  • Patient-years of follow-up from Week 44 through the final safety visit for STELARA® (1110) and placebo (177)

<4 Serious infections per 100 patient-years2§II

  • STELARA® 90 mg every 8 weeks: 3.50
  • Placebo: 6.16

<5%of patients developed antibodies to STELARA®2

Antibody formation among randomized patients who entered open-label LTE:

  • 4.7% (50/1073) of all patients treated with at least 1 dose of STELARA® and 2.9% (3/102) of patients randomized to STELARA® 90 mg subQ every 8 weeks developed antibodies to the drug

IIData are presented by event rates adjusted by 100 patient-years to normalize difference in follow-up time between STELARA® and placebo treatment groups.

CD=Crohn's disease; CI=confidence interval; IV=intravenous; LTE=long-term extension; q8w=every 8 weeks; subQ=subcutaneous.

 

*Confidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution.

Includes data from Week 0 of induction onward for patients who were rerandomized to ustekinumab 90 mg subQ q8w maintenance or patients who were not in clinical response to ustekinumab IV at Week 8 of the induction studies and received ustekinumab 90 mg subQ on entry into the maintenance study.

Includes data from Week 0 of induction onward up to the first ustekinumab dose for patients who were initially treated with placebo IV; includes data at or after 16 weeks from the first ustekinumab IV onward, up to the dose adjustment if patients had a dose adjustment, for patients who were rerandomized to placebo maintenance.

§Infections as assessed by the investigator.

Malignancy data are between Week 44 and Year 5 for patients who entered LTE.

#Includes: Patients who were in clinical response to ustekinumb IV induction dosing, randomized on entry into the maintenance study, received ustekinumab 90 mg subQ q8w, or met loss of response criteria from Week 8 through Week 32 and received ustekinumab 90 mg subQ q8w thereafter; Patients who were not in clinical response to ustekinumab IV induction dosing, received ustekinumab 90 mg subQ at Week 0, achieved clinical response at Week 8, and initiated ustekinumab 90 mg subQ q8w.

**Includes: Patients who were in clinical response to ustekinumab IV induction dosing and received placebo subQ on entry into the maintenance study did not meet loss of response criteria from Week 8 through Week 32; patients who were in clinical response to placebo IV induction dosing and received placebo subQ on entry into the maintenance study.

References: 1. STELARA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 2. Data on file. Janssen Biotech, Inc.