For the treatment of adult patients with moderately to severely active CD
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
| ≥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%).
| ≥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% |
|
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% |
<1% Hypersensitivity reactions1
<1% Malignancy rate**
STELARA® is an immunosuppressant and may increase the risk of malignancy.
<3% Serious infections2
<3% of patients developed antibodies1,2
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 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® 90 mg subQ every 8 weeks |
Placebo† |
STELARA®‡ 90 mg subQ every 8 weeks |
Placebo§ |
STELARA® 90 mg subQ every 8 weeks |
Placebo | |
|---|---|---|---|---|---|---|
| N (treated patients)|| | 307 | 308 | 131 | 133 | 176 | 175 |
| Average duration of follow-up (weeks) | 39.2 | 37.8 | 35.2 | 32.0 | 42.2 | 42.3 |
| Deaths | 0 | 0 | 0 | 0 | 0 | 0 |
| Percentage of patients | ||||||
| Adverse events | 79.2% | 80.8% | 81.7% | 83.5% | 77.3% | 78.9% |
| Serious adverse events | 9.1% | 12.0% | 9.9% | 15.0% | 8.5% | 9.7% |
| Infections | 48.5% | 47.7% | 48.1% | 49.6% | 48.9% | 46.3% |
| Serious infections | 2.0% | 2.3% | 2.3% | 2.3% | 1.7% | 2.3% |
|
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% |
|
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% |
|
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.
<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.
|
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.
0.99 Malignancy per 100 patient-years2II¶
<4 Serious infections per 100 patient-years2§II
<5%of patients developed antibodies to STELARA®2
Antibody formation among randomized patients who entered open-label LTE:
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.
CDAI=Crohn's Disease Activity Index; IV=intravenous; LTE=long-term extension; subQ=subcutaneous; TNF=tumor necrosis factor.
*In both induction studies, patients were randomized to receive STELARA® weight-based dosage regimen (approximately 6 mg/kg), STELARA® 130-mg IV, or IV placebo. The 130-mg IV dose is not an approved induction dose and therefore is not shown. Clinical response was defined as reduction in CDAI score of ≥100 points or CDAI score of <150.1
†69% of patients were TNF blocker naïve. Remaining population were patients previously exposed to, but who did not fail, treatment with TNF blockers. All patients in the study failed or were intolerant to conventional treatment (eg, azathioprine, 6-mercaptopurine, methotrexate, or corticosteroids).1
‡Weight-based induction dosage regimen: STELARA® 260 mg (weight ≤55 kg), STELARA® 390 mg (weight >55 kg to 85 kg), and STELARA® 520 mg (weight >85 kg).1
§Patients were intolerant to or failed TNF blocker therapy.1
||The maintenance study included a third randomized arm where patients received STELARA® 90 mg subQ every 12 weeks. STELARA® 90 mg subQ every 12 weeks is not an approved maintenance dose and therefore is not shown. Patients randomized in the maintenance study were those who had a clinical response to STELARA® IV at Week 8 during either induction study.1,2
¶Clinical remission was defined as a CDAI score of <150. Week 44 of the maintenance study was defined as 1 year from initiation of the induction dose (8-week induction + 44-week maintenance study=1 year).1
#All patients randomized to placebo in the maintenance study had a single STELARA® IV induction dose.1
**Patients in the LTE study included those from the nonapproved STELARA® 90 mg subQ every-12-week maintenance arm, which is not represented in the figure above.2
CDAI=Crohn's Disease Activity Index; IV=intravenous; LTE=long-term extension; subQ=subcutaneous; TNF=tumor necrosis factor.
*In both induction studies, patients were randomized to receive STELARA® weight-based dosage regimen (approximately 6 mg/kg), STELARA® 130-mg IV dose, or IV placebo. The 130-mg IV dose is not an approved induction dose and therefore is not shown. Clinical response was defined as reduction in CDAI score of ≥100 points or CDAI score of <150.1
†69% of patients were TNF blocker naïve. Remaining population was patients previously exposed to, but who did not fail, treatment with TNF blockers. All patients in the study failed or were intolerant to conventional treatment (eg, azathioprine, 6-mercaptopurine, methotrexate, or corticosteroids).1,2
‡Weight-based induction dosage regimen: STELARA® 260 mg (weight ≤55 kg), STELARA® 390 mg (weight >55 kg to 85 kg), STELARA® 520 mg (weight >85 kg).1
§Patients were intolerant to or failed TNF blocker therapy.1
||The maintenance study included a third randomized arm where patients received STELARA® subQ 90 mg every 12 weeks. STELARA® 90 mg subQ every 12 weeks is not an approved maintenance dose.1,2
¶Clinical remission was defined as a CDAI score of <150.1
#All patients randomized to placebo in the maintenance study had a single STELARA® IV induction dose.1
INDUCTION STUDY
MAJOR SECONDARY ENDPOINTS INCLUDED:
MAINTENANCE STUDY
MAJOR SECONDARY ENDPOINTS INCLUDED:
OPEN-LABEL LTE
All patients completing the Maintenance Study were eligible to enter the LTE. Placebo subQ patients were discontinued after unblinding at 1 year after induction dose. Efficacy measures were collected every 12 weeks thereafter. Safety was evaluated throughout.
Adult patients with moderately to severely active UC who had an inadequate response to or failed to tolerate biologic (ie, TNF blocker and/or vedolizumab) or conventional (ie, corticosteroids and/or the immunomodulators 6-mercaptopurine or azathioprine) therapy.
IV=intravenous; LTE=long-term extension; subQ=subcutaneous; TNF=tumor necrosis factor; UC=ulcerative colitis
*In the induction study, patients were randomized to receive STELARA® weight-based dosage regimen (approximately 6 mg/kg), STELARA® 130-mg IV dose, or IV placebo. The 130-mg IV dose is not an approved induction dose and therefore is not shown.
†Clinical remisssion was defined as Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0, and Mayo endoscopy subscore of 0 or 1 (modified so that 1 does not include friability).
‡Weight-based induction dosage regimen: STELARA® 260 mg (weight 55 kg or less), STELARA® 390 mg (weight >55 kg to 85 kg), and STELARA® 520 mg (weight >85kg).
§The maintenance study included a third randomized arm where patients received STELARA® 90 mg subQ every 12 weeks. STELARA® 90 mg subQ every 12 weeks is not an approved maintenance dose and therefore is not shown. Patients randomized in the maintenance study were those who had a clinical response to STELARA® IV at Week 8 during the induction study.
||Week 44 of the Maintenance Study was defined as 1 year from initiation of the induction (8-week induction study + 44-week maintenance study=1 year).
¶Symptomatic remission was defined as no rectal bleeding (Mayo rectal bleeding subscore of 0) and normal to near-normal stool frequency (Mayo stool frequency subscore of 0 or 1), no endoscopic assessment was performed.
#Clinical response was defined as a decrease from baseline in the Mayo score by ≥30% and ≥2 points, with either a decrease from baseline in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1.
**Endoscopic improvement was defined as Mayo endoscopy subscore of 0 or 1 (modified so that 1 does not include friability).
††Patients who achieved clinical response to STELARA® at the end of the induction study.
‡‡Steroid free clinical remission was defined as patients in clinical remission and not receiving corticosteroids at 1 year.
§§Maintenance of clinical remission at 1 year was defined as remission at Week 44 in patients who achieved clinical remission 8 weeks after induction.
IIIIHEMI was defined as combined endoscopic improvement (Mayo endoscopy subscore of 0 or 1) and histologic improvement of the colon tissue (neutrophil infiltration <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue).
References: 1. STELARA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 2. Data on file. Janssen Biotech, Inc.
