For the treatment of adults with moderately to severely active Crohn’s disease who have failed or were intolerant to conventional therapy (but never failed treatment with a TNF blocker) or have failed or were intolerant to treatment with one or more TNF blockers
Start Strong With a Single IV Induction Dose for Crohn’s Disease1*
Primary Endpoint
Clinical response at Week 6 (100-point reduction)Patient population: predominantly TNF blocker naïve
Clinical response at Week 6 (100-point reduction)Patient population: predominantly TNF blocker naïve
56%
of patients receiving STELARA® IV induction dose
(n=116/209)
(n=116/209)
29%
of patients receiving placebo
(n=60/209)
(n=60/209)
Clinical response was defined as reduction in Crohn’s Disease Activity Index (CDAI) score of ≥100 points or CDAI score of <150.1
SECONDARY ENDPOINT
Significant response in predominantly TNF blocker–naïve patients at Week 3
(70-point response at Week 3§)
Significant response in predominantly TNF blocker–naïve patients at Week 3 (70-point response§) (n=627; P<0.001)
51%
of patients receiving STELARA®* IV induction dose
(n=106/209)
(n=106/209)
32%
of patients receiving placebo
(n=66/209)
(n=66/209)
Significant response in predominantly TNF blocker–naïve patients at Week 6
(70-point response§) (N=627; P<0.001)
65%
of patients receiving STELARA®* IV induction dose
(n=135/209)
(n=135/209)
39%
of patients receiving placebo
(n=81/209)
(n=81/209)
Clinical response was defined as reduction in Crohn’s Disease Activity Index (CDAI) score of ≥100 points or CDAI score of <150.1
Primary Endpoint
PRIMARY ENDPOINT
Clinical response at Week 6 (100-point reduction)Patient population: TNF blocker failure
Clinical response at Week 6 (100-point reduction)Patient population: TNF blocker failure
34%
of patients receiving STELARA® IV induction dose
(n=84/249)
(n=84/249)
21%
of patients receiving placebo
(n=53/247)
(n=53/247)
Clinical response was defined as reduction in Crohn’s Disease Activity Index (CDAI) score of ≥100 points or CDAI score of <150.1
For the treatment of adults with moderately to severely active Crohn’s disease who have failed or were intolerant to conventional therapy (but never failed treatment with a TNF blocker) or have failed or were intolerant to treatment with one or more TNF blockers
Maintenance Study
Stay the Course With STELARA® A Majority of Patients in the Maintenance Study Were in Clinical Remission at 1 Year After Induction Dose1*†
Primary endpoint
Clinical remission at 1 year after induction dosePatient population: Combined TNF blocker naïve‡ and TNF blocker failure
53%
of patients receiving STELARA® 90 mg subQ every 8 weeks
(n=68/128§;
P<0.01)
(n=68/128§;
P<0.01)
36%
of patients receiving placebo (induction responders)||
(n=47/131)
(n=47/131)
Clinical remission was defined as a CDAI score of <150 points.1
More Than Two-thirds of Patients in Clinical Remission at the Start of the Maintenance Study Were Still in Remission at 1 Year1*†
Secondary Endpoint
Clinical remission at 1 year among patients in remission at the start of maintenance therapyPatient population: Combined TNF blocker naïve and TNF blocker failure
67%
STELARA®
(n=52/78§;
P<0.01)
(n=52/78§;
P<0.01)
46%
placebo (induction responders)||
(n=36/79)
(n=36/79)
Clinical remission was defined as a CDAI score of <150 points.1
A Majority of TNF Blocker–naïve Patients in the Maintenance Study Were in Clinical Remission at 1 Year After Induction Dose1*†
Other endpoint
Clinical remission in TNF blocker–naïve subgroup at 1 year after induction
65%
of patients receiving
STELARA® 90 mg subQ every 8 weeks
(n=34/52§;
P value is not statistically significant)
STELARA® 90 mg subQ every 8 weeks
(n=34/52§;
P value is not statistically significant)
49%
of patients receiving placebo (induction responders)||
(n=25/51)
(n=25/51)
Clinical remission was defined as a CDAI score of <150 points.1
*Data through 1 year of maintenance or 52 weeks after induction dose.2
†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). Patients randomized in the maintenance study were those who had a clinical response to STELARA® IV at Week 8 during either induction study.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
§Patients randomized to the STELARA® 90 mg every-8-weeks group.1
||All patients randomized to placebo in the maintenance study had a single STELARA® IV induction dose.1
For the treatment of adults with moderately to severely active Crohn’s disease who have failed or were intolerant to conventional therapy (but never failed treatment with a TNF blocker) or have failed or were intolerant to treatment with one or more TNF blockers
Maintenance Study and Open-label Long-term Extension (LTE)
Durability of Remission Through 3 Years1,2,4*†
STELARA® CLINICAL TRIAL DESIGN: PHASE 3 STUDIES AND THE OPEN-LABEL LONG-TERM EXTENSION (LTE)1,2,4
BACKGROUND AND ANALYSIS RULES FOR STELARA® OPEN-LABEL LTE STUDY4
Background
Objective: To evaluate the efficacy and safety of STELARA® through 5 years of maintenance treatment. The final efficacy and safety assessments will be performed at Week 252.
75% (298/397) of randomized subjects who started maintenance phase entered open-label LTE
- All patients completing Week 44 (1 year after induction dose) were eligible to enter the open-label LTE
Database lock was performed after the final patient completed the first and second years of the 4-year open-label LTE of the maintenance study (ie, Week 96 and Week 156 maintenance study visits)
- This represents 3 years of treatment with STELARA®
Study was unblinded after final Week 44 maintenance analysis was completed (August 2015)
- Patients randomized to placebo were discontinued after study unblinding and are not included in the open-label LTE efficacy analyses, but were included in the safety analysis
Analysis Rules
Analyses shown are intent-to-treat
For the open-label LTE efficacy analysis, any patient who met the criteria for treatment failure prior to Week 44 continued to be considered as a treatment failure through the open-label LTE
Patients who discontinued or had missing data were assumed not to be in response or remission. Patients undergoing Crohn’s disease–related surgeries or initiating prohibited medications were considered treatment failures
In the open-label LTE, patients were not allowed to dose adjust upon loss of response but could make changes in steroids or immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate) if medically appropriate. Otherwise, all treatment failure rules were the same as they had been prior to Week 44 (during maintenance trial)
COMBINED TNF BLOCKER–NAÏVE AND TNF BLOCKER–FAILURE POPULATIONS
Blinded Maintenance Phase: Remission at 1 year (primary endpoint)
53%
of patients receiving STELARA® were in remission 1 year after induction dose§§
(n=68/128||||;
P<0.01)
(n=68/128||||;
P<0.01)
36%
of patients receiving placebo††
(n=47/131)
(n=47/131)
Open-label LTE: Remission at nearly 2 years
47%
of patients receiving STELARA® were in remission 100 weeks after induction dose
(n=60/128)
(n=60/128)
Open-label LTE: Remission at 3 years
43%
of patients receiving STELARA® were in remission 160 weeks after induction dose
(n=55/128)
(n=55/128)
- SubQ placebo group (8 weeks to 1 year after induction dose) (n=131)4
- STELARA® 90 mg every 8 weeks (8 weeks to 1 year after induction dose) and open-label LTE (1 year to 160 weeks after induction dose) (n=128)2,4
- Efficacy analysis for the open-label LTE included patients who received STELARA® 90 mg every 8 weeks (n=128)2,4
TNF BLOCKER–NAÏVE SUBGROUP
Blinded Maintenance Phase: Remission at 1 year (other endpoint)
65%
of patients receiving STELARA® were in remission 1 year after induction dose§§
(n=34/52||||;
P value is not statistically significant)
(n=34/52||||;
P value is not statistically significant)
49%
of patients receiving placebo††
(n=25/51)
(n=25/51)
Open-label LTE: Remission at nearly 2 years
56%
of patients receiving STELARA® were in remission 100 weeks after induction dose
(n=29/52)
(n=29/52)
Open-label LTE: Remission at 3 years
54 %
of patients receiving STELARA® were in remission 160 weeks after induction dose
(n=28/52)
(n=28/52)
- SubQ placebo group (8 weeks to 1 year after induction dose) (n=51)4
- STELARA® 90 mg every 8 weeks (8 weeks to 1 year after induction dose) and open-label LTE (1 year to 160 weeks after induction dose) (n=52)2,4
- Efficacy analysis for the open-label LTE included TNF blocker–naïve patients who received STELARA® 90 mg every 8 weeks (n=52)2,4
*Data through 3 years of maintenance or 160 weeks after induction dose.2
†Efficacy assessments done every 12 weeks until study unblinding (then at dosing visits). Clinical remission defined as CDAI score of <150.1,4
‡In both induction studies, patients were randomized to receive STELARA® weight-based dosage regimen (approximately 6 mg/kg), STELARA® 130-mg IV, or placebo. The 130-mg IV dose is not an approved induction dose and therefore is not shown. Clinical response was defined as reduction in Crohn’s Disease Activity Index (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 or less), STELARA® 390 mg (weight more than 55 kg to 85 kg), STELARA® 520 mg (weight more than 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 the 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
‡‡Subjects in the open-label LTE study included those from the nonapproved STELARA® 90 mg subQ every-12-week maintenance arm, which is not represented in the figure above.4
§§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). Patients randomized in the maintenance study were those who had a clinical response to STELARA® IV at Week 8 during either induction study.1
||||Patients randomized to the STELARA® 90 mg every-8-weeks group.1
References: 1. STELARA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 2. Data on file. Janssen Biotech, Inc. 3. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National cooperative Crohn’s disease study. Gastroenterology. 1976;70(3):439-443. 4. Sandborn WJ, Rutgeerts P, Gasink C, et al. Long-term efficacy and safety of ustekinumab for Crohn’s disease through the second year of therapy. Aliment Pharmacol Ther. 2018;48(1):65-77.
CROHN’S DISEASE ACTIVITY INDEX (CDAI) CONSISTS OF THE WEIGHTED SUM TOTAL OF THE FOLLOWING3:
- Number of liquid or soft stools each day for 7 days;
- Abdominal pain;
- General well-being;
- Presence of complications;
- Taking antidiarrheal medications;
- Presence of abdominal mass;
- Hematocrit <0.47 in men and <0.42 in women;
- Percentage deviation from standard weight.
Important Context About the Placebo Arm1
All patients randomized to placebo in the maintenance study had previously received a single STELARA® IV induction dose and achieved clinical response at Week 8 of induction prior to entering the maintenance study. Therefore, the placebo arm in the maintenance study is referred to as “placebo-induction responders.”
STELARA® Clinical Trial Design: Phase 3 Studies and the Open-label Long-term Extension (LTE)1,2,4
*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 Crohn’s Disease Activity Index (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 or less), STELARA® 390 mg (weight more than 55 kg to 85 kg), and STELARA® 520 mg (weight more than 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
**Subjects 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.4