Table 6Details of Included Induction Studies

UNITI-1UNITI-2
Designs & PopulationsStudy DesignPhase III superiority DB RCT
LocationsNorth America (including Canada), Europe, Asia, the Asia-Pacific region, South Africa, and Brazil (178 sites)North America (including Canada), Europe, Asia, the Asia-Pacific region, South Africa, and Brazil (175 sites)
Randomized (N)N = 769 randomized
N = 741 after study restarta		N = 640
N = 628 after study restarta
Inclusion Criteria
  • Age ≥ 18
  • Moderate-to-severe activeb CD or fistulizing CD of ≥ 3 months’ duration with colitis, ileitis, or ileocolitis (radiographic, histologic, and/or endoscopic confirmation)
  • Inadequate response or intoleranced to ≥ 1 TNF antagonist(s)e
  • Meet criteria for concomitant medication stability, screening laboratory test results, and TB history and testing results
  • Age ≥ 18
  • Moderate-to-severe activec CD or fistulizing CD of ≥ 3 months’ duration with colitis, ileitis, or ileocolitis (radiographic, histologic, and/or endoscopic confirmation)
  • Receiving CS and/or MTX, AZA, or 6-MP
  • Inadequate response or intoleranced to conventional therapy (CS and/or MTX, AZA, or 6-MP) or is CS dependent
  • Not had inadequate response or intolerance to ≥ 1 TNF antagonist(s)d,e
  • Meet criteria for concomitant medication stability, screening laboratory test results, and TB history and testing results
Exclusion Criteria
  • CD complications requiring surgery or precluding use of CDAI to assess response
  • Intra-abdominal abscess within 8 weeks of randomization
  • Bowel resection or diversion within 6 months, or other intra-abdominal surgery within 3 months of randomization
  • Draining stoma or ostomy
  • Positive test for enteric pathogens within 4 months of randomization
  • Previous treatment with: IL-12 or IL-23 inhibitor (e.g., UST or BRI)
  • Received parenteral CS within 3 weeks, immunomodulators other than AZA, 6-MP, or MTX within 6 weeks, biologics within 8 weeks, or TPN within 3 weeks
Active or latent TB, opportunistic infection, HIV, or hepatitis B or C infection
DrugsInterventionA single dose at week 0 of:
UST IV infusion 130 mg
or
UST IV infusion (approximately 6 mg/kg):
  • 260 mg if body weight is ≤ 55 kg
  • 390 mg if body weight is > 55 to ≤ 85 kg
  • 520 mg if body weight is > 85 kg
Comparator(s)Placebo
DurationPhase
 Run-in5 weeks (used for screening)
 Double-blind20 weeks
  • Week 6 primary outcome assessment
  • Week 8 assessment for entry to the maintenance-treatment study (IM-UNITI)
  • Week 9 to 20 follow-up for those not entering the maintenance-treatment study
 Follow-up44-week maintenance study (IM-UNITI)
OutcomesPrimary End PointClinical response at 6 weeks
Other End Points
  • Clinical remission at week 8
  • IBDQ and SF-36 at week 6
  • WLQ, productivity VAS, time lost from work
  • CD-related surgery
  • AE, SAE, WDAE
NotesPublicationsFeagan et al. 201625

6-MP = 6-mercaptopurine; AE = adverse event; AZA = azathioprine; BRI = briakinumab; CD = Crohn’s disease; CDAI = Crohn’s Disease Activity Index; CRP = C-reactive protein; CS = corticosteroid; DB = double-blind; IBDQ = Inflammatory Bowel Disease Questionnaire; IL = interleukin; IV = intravenous; MTX = methotrexate; RCT = randomized controlled trial; SAE = serious adverse event; SF-36 = Short Form (36) Health Survey; TB = tuberculosis; TNF = tumour necrosis factor; TPN = total parenteral nutrition; UST = ustekinumab; VAS = visual analogue scale; WDAE = withdrawal due to adverse event; WLQ = Work Limitations Questionnaire.

a

Twenty-eight patients in UNITI-1 and 12 patients in UNITI-2 were excluded following a study protocol amendment (see Section 3.2.1).

b

Active disease was defined as a CDAI score ≥ 220 but ≤ 450 points.

c

Active disease was defined as a CDAI score ≥ 220 but ≤ 450 points and at least one of the following: 1) an abnormal CRP (> 3.0 mg/L); 2) fecal calprotectin > 250 mg/kg at screening; 3) endoscopy (within 3 months before baseline) with evidence of active Crohn’s disease during the current disease flare.

d

Inadequate response and intolerance to TNF antagonists as defined in the study are presented in Table 9 of this report. Definitions for inadequate response and intolerance to CS and/or immunomodulators were not provided.

e

Protocol-specified TNF antagonists: infliximab, adalimumab, or certolizumab pegol at approved doses.

Source: Clinical Study Reports for UNITI-1 and UNITI-2.7,8

From: 3, RESULTS

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