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

INDUCTION STUDY

STELARA®*DELIVERED RAPID RESPONSE AS EARLY AS WEEK 6 (CLINICAL RESPONSE) AND WEEK 3 (70-POINT RESPONSE)

Clinical response was defined as reduction in CDAI score of ≥100 points or CDAI score of <1501

CD=Crohn’s disease; CDAI=Crohn’s Disease Activity Index; IV=intravenous; TNF=tumor necrosis factor.

 

*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

The induction studies each included a third randomized arm where patients received a single 130-mg IV administration dose of STELARA®. The 130-mg IV dose is not an approved induction dose.1,2

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).1,2

§70-point response was defined as reduction in CDAI score of ≥70 points.1

 

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

SYMPTOM IMPROVEMENT: ABDOMINAL PAIN/STOOL FREQUENCY SCORE

MEAN CHANGE IN ABDOMINAL PAIN AND STOOL FREQUENCY FROM BASELINE WITHIN THE FIRST 2 WEEKS4

(POST HOC ANALYSIS OF ABDOMINAL PAIN AND STOOL FREQUENCY SUBSCORE: UNITI-1 TNF BLOCKER–FAILURE PATIENTS)

Methodology: In the UNITI-1 IV induction study, patients with moderately to severely active CD (CDAI 220-450) who were intolerant or refractory (as either primary or secondary nonresponders) to TNF blocker biologics. Patient CDAI daily data (Day –7 to +14) were compiled and analyzed post hoc for the patient-reported CDAI components, where patient diary cards were available. The mean change in daily CDAI component scores with STELARA® IV was compared with placebo. The CDAI subscore was calculated as the sum of the SF and AP scores over the 7 days (SFx2, APx5) and assessed as the proportion of patients with ≥50-point improvement in this CDAI subscore.4

AP=abdominal pain; CD=Crohn’s disease; CDAI=Crohn’s Disease Activity Index; IV=intravenous; SF=stool frequency; TNF=tumor necrosis factor.

 

*Abdominal pain was graded from 0 (none) to 3 (severe) on severity per day; Stool frequency was determined by the number of liquid or soft stools per day.

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

MAINTENANCE STUDY

STELARA®: LASTING REMISSION AT 1 YEAR

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

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

Clinical remission was defined as a CDAI score of <150 points.1 Patients in clinical remission at the end of maintenance therapy who were in remission at the start of maintenance therapy. This does not account for any other time point during maintenance therapy.

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

Clinical remission was defined as a CDAI score of <150 points.1

CD=Crohn's disease; CDAI=Crohn's Disease Activity Index; IV=intravenous; subQ=subcutaneous; TNF=tumor necrosis factor.

 

*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 adult patients with moderately to severely active CD

Maintenance Study and Open-label LTE
STELARA®: LASTING Remission Through ≈5 Years1,2*

Studies That Assessed Efficacy and Safety From Week 3 to ≈5 Years1,2*

STELARA® Clinical Trial Design: Phase 3 Studies (COMPLETED) and Open-label LTE (COMPLETED)

 

BACKGROUND AND ANALYSIS RULES FOR STELARA® OPEN-LABEL LTE STUDY2

Background

Objective: To evaluate the efficacy and safety of STELARA® through 5 years of maintenance treatment. The final efficacy assessment was performed at Week 252 and the final safety assessment was performed at Week 272.

 

75% (298/397) of randomized patients 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, second, and fourth years of the 4-year, open-label LTE of the Maintenance Study (ie, Week 96, Week 156, and Week 272 Maintenance Study visits)

  • This represents 5 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 CD‑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)

CLINICAL REMISSION: OVERALL POPULATION (TNF BLOCKER NAÏVE AND TNF BLOCKER FAILURE)


At the ≈Year 5 visit, 95% (n=42/44) of STELARA® patients in clinical remission were also steroid free2¶¶##***†††(Post hoc analysis)

53% of patients who responded to the induction dose were in clinical remission at 1 year and 34% at ≈5 years1,2
  • SubQ placebo group (8 weeks to 1 year after induction dose) (n=131)2
  • 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
  • Efficacy analysis for the open-label LTE included patients who received STELARA® 90 mg every 8 weeks (n=128)2
  • In the LTE, steroids or immunomodulators could be added if medically appropriate and not considered a treatment failure

TNF BLOCKER–NAÏVE SUBGROUP


At the ≈Year 5 visit, 100% (n=23/23) of TNF blocker–naïve patients in clinical remission with STELARA® were also steroid free2¶¶##***†††(Post hoc analysis)

65% of TNF blocker–naïve patients who responded to the induction dose were in clinical remission at 1 year and 44% at ≈5 years1,2
  • SubQ placebo group (8 weeks to 1 year after induction dose) (n=51)2
  • 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
  • Efficacy analysis for the open-label LTE included TNF blocker–naive patients who received STELARA® 90 mg every 8 weeks (n=52)2
  • In the LTE, steroids or immunomodulators could be added if medically appropriate and not considered a treatment failure

CD=Crohn's disease; CDAI=Crohn's Disease Activity Index; IV=intravenous; LTE=long-term extension; subQ=subcutaneous; TNF=tumor necrosis factor.

 

*Data through 5 years of maintenance or 260 weeks after induction dose.2 Open-label LTE is completed.

Efficacy assessments done every 12 weeks until study unblinding (then at dosing visits). Clinical remission defined as CDAI score of <150.1,2

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 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), 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 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

‡‡Patients 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.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

||||Patients randomized to the STELARA® 90 mg every-8-weeks group.1

¶¶Patients who had a prohibited CD-related surgery and had a loss of response (from Week 8 to Week 32) or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be of worsening CD after Week 44 and prior to the designated analysis timepoint were not considered to be in clinical remission, regardless of their CDAI score.

##Patients who had insufficient data to calculate the CDAI score at the designated analysis timepoint were not considered to be in clinical remission.

***Patients who had a missing value in corticosteroid use at designated analysis timepoint had their last value carried forward.

†††Steroid free is defined as not taking steroids during the 7-day period that the CDAI was being collected.

 

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, Yeager B, Gasink C, et al. Ustekinumab IV induction results in Crohn's disease symptoms improvement within the first week in anti-TNF refractory patients. Presented at: World Congress of Gastroenterology at ACG 2017; October 13-18, 2017; Orlando, Florida. Poster 2145.

close tooltip
CROHN’S DISEASE ACTIVITY INDEX (CDAI) CONSISTS OF THE WEIGHTED SUM TOTAL OF THE FOLLOWING3:
  1. Number of liquid or soft stools each day for 7 days;
  2. Abdominal pain;
  3. General well-being;
  4. Presence of complications;
  5. Taking antidiarrheal medications;
  6. Presence of abdominal mass;
  7. Hematocrit <0.47 in men and <0.42 in women;
  8. Percentage deviation from standard weight.
close tooltip
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.”