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Ustekinumab (Stelara) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Apr.

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Ustekinumab (Stelara) [Internet].

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APPENDIX 4DETAILED OUTCOME DATA

Clinical Remission Subgroup Analyses

Table 27Proportion of Patients Achieving Clinical Remission at Week 8 by Disease Severity (Baseline CDAI Score), Crohn’s Disease–Related Medication History in the Induction Studies

Subgroups, n (%)UNITI-1UNITI-2
PLA (N = 247)UST (N = 249)PLA (N = 210)UST (N = 209)
Baseline CDAI score ≤ 300▬▬▬▬
 Clinical remission at week 8▬▬▬▬
  OR (95% CI)▬▬
  P value▬▬
Baseline CDAI score > 300▬▬▬▬
 Clinical remission at week 8▬▬▬▬
  OR (95% CI)▬▬
  P value▬▬
Inadequate response, intolerant, or contraindication to CS or immunomodulators — Yes▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Inadequate response, intolerant, or contraindication to CS or immunomodulators — No▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Initial response to TNF antagonist —Yes▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Initial response to TNF antagonist — No▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Primary nonresponder to TNF antagonist▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Secondary nonresponder to TNF antagonist▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Intolerance to TNF antagonist▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Failed ≥ 2 TNF antagonists — Yes▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Failed ≥ 2 TNF antagonists — No▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Previously received TNF antagonist — Yes▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬
Previously received TNF antagonist — No▬▬
 Clinical remission at week 8▬▬
  OR (95% CI)▬
  P value▬

CDAI = Crohn’s Disease Activity Index; CI = confidence interval; CS = corticosteroid; OR = odds ratio; PLA = placebo; TNF = tumour necrosis factor; UST = ustekinumab.

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

Table 28Proportion of Patients Achieving Clinical Remission at Week 44 by Disease Severity (Baseline CDAI Score) and Crohn’s Disease Medication History in the Maintenance Study

Subgroups, n (%)IM-UNITI-
PLA (N = 131)UST q.12.w. (N = 129)UST q.8.w. (N = 128)
Baseline CDAI score ≤ 300▬▬▬
Clinical remission at week 44▬▬▬
  OR (95% CI)▬▬
  P value▬▬
Baseline CDAI score > 300▬▬▬
Clinical remission at week 44▬▬▬
  OR (95% CI)▬▬
  P value▬▬
Inadequate response, intolerant, or contraindication to CS or immunomodulators▬▬▬
 Clinical remission at week 44▬▬▬
  OR (95% CI)▬▬
  P value▬▬
TNF antagonist refractory population — Yes (UNITI-1)N = 61N = 57N = 56
 Clinical remission at week 4416 (26.2)22 (38.6)23 (41.1)
  OR (95% CI)▬▬
  P value0.1400.102
TNF antagonist refractory population — No (UNITI-2)N = 70N = 72N = 72
 Clinical remission at week 44NR (44.3)NR (56.9)NR (62.5)
  OR (95% CI)▬▬
  P value0.1460.020
Previously received TNF antagonist — YesN = 19N = 19N = 20
 Clinical remission at week 44NR (31.6)NR (57.9)NR (55.0)
  OR (95% CI)2.9 (0.7 to 11.7)2.5 (0.7 to 9.3)
  P value0.1500.206
Previously received TNF antagonist — NoN = 51N = 53N = 52
 Clinical remission at week 44NR (49.0)NR (56.6)NR (65.4)
  OR (95% CI)1.4 (0.6 to 3.0)2.4 (1.0 to 5.5)
  P value0.5120.041

CDAI = Crohn’s Disease Activity Index; CI = confidence interval; CS = corticosteroid; NR = not reported; OR = odds ratio; PLA = placebo; q.8.w. = every 8 weeks; q.12.w. = every 12 weeks; TNF = tumour necrosis factor; UST = ustekinumab.

Source: Clinical Study Report for IM-UNITI.9

Clinical Response Subgroup Analyses

Table 29Proportion of Patients Achieving Clinical Response at Week 6 by Disease Severity (Baseline CDAI Score), Crohn’s Disease–Related Medication History in the Induction Studies

Subgroups, n (%)UNITI-1UNITI-2
PLA (N = 247)UST (N = 249)PLA (N = 210)UST (N = 209)
Baseline CDAI score ≤ 300N = 104N = 94N = 123N = 119
 Clinical response at week 6NR (17.3)NR (28.7)NR (24.4)NR (51.3)
  OR (95% CI)2.0 (1.0 to 3.9)3.3 (1.9 to 5.7)
  P value0.048< 0.001
Baseline CDAI score > 300N = 143N = 155N = 86N = 90
 Clinical response at week 6NR (24.5)NR (36.8)NR (34.9)NR (61.1)
  OR (95% CI)1.8 (1.1 to 3.0)3.2 (1.7 to 6.0)
  P value0.023< 0.001
Inadequate response, intolerant, or contraindication to CS or immunomodulators — YesN = 215N = 217
 Clinical Response at week 6NR (20.9)NR (33.6)
  OR (95% CI)1.9 (1.2 to 3.0)
  P value0.005
Inadequate response, intolerant, or contraindication to CS or immunomodulators — NoN = 32N = 32
 Clinical Response at week 6NR (25.0)NR (34.4)
  OR (95% CI)1.5 (0.5 to 4.8)
  P value0.485
Initial response to TNF antagonist —YesN = 187N = 190
 Clinical response at week 6NR (20.3)NR (38.4)
  OR (95% CI)2.5 (1.6 to 3.9)
  P value< 0.001
Initial response to TNF antagonist — NoN = 60N = 59
 Clinical response at week 6NR (25.0)NR (18.6)
  OR (95% CI)0.7 (0.3 to 1.7)
  P value0.376
Primary nonresponder to TNF antagonistN = 74N = 72
 Clinical Response at week 6NR (23.0)NR (23.6)
  OR (95% CI)1.1 (0.5 to 2.4)
  P value0.816
Secondary nonresponder to TNF antagonistN = 170N = 171
 Clinical response at week 6NR (20.0)NR (36.8)
  OR (95% CI)2.3 (1.4 to 3.8)
  P value< 0.001
Intolerance to TNF antagonistN = 87N = 105
 Clinical response at week 6NR (24.1)NR (34.3)
  OR (95% CI)1.6 (0.8 to 3.0)
  P value0.188
Failed ≥ 2 TNF antagonists — YesN = 134N = 126
 Clinical response at week 6NR (19.4)NR (34.9)
  OR (95% CI)2.1 (1.2 to 3.8)
  P value0.008
Failed ≥ 2 TNF antagonists — NoN = 113N = 123
 Clinical response at week 6NR (23.9)NR (32.5)
  OR (95% CI)1.5 (0.8 to 2.7)
  P value0.176
Previously received TNF antagonist — YesN = 74N = 65
 Clinical remission at week 8NR (21.6)NR (53.8)
  OR (95% CI)4.3 (2.0 to 9.2)
  P value< 0.001
Previously received TNF antagonist — NoN = 135N = 144
 Clinical remission at week 8NR (32.6)NR (56.3)
  OR (95% CI)2.8 (1.7 to 4.6)
  P value< 0.001

CDAI = Crohn’s Disease Activity Index; CI = confidence interval; CS = corticosteroid; NR = not reported; OR = odds ratio; PLA = placebo; TNF = tumour necrosis factor; UST = ustekinumab.

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

Inflammatory Bowel Disease Questionnaire and Short Form (36) Health Survey Additional Data

Table 30Summary of Change From Baseline in the IBDQ Dimension Scores in the Induction Studies

ParameterUNITI-1UNITI-2
PLA (N = 247)UST (N = 249)PLA (N = 210)UST (N = 209)
Change in bowel score at week 8
 Baseline score, mean (SD)▬▬▬▬
 Change from baseline, mean (SD)▬▬▬▬
 P value▬▬
Change in emotional score at week 8
 Baseline score, mean (SD)▬▬▬▬
 Change from baseline, mean (SD)▬▬▬▬
 P value▬▬
Change in systemic score at week 8
 Baseline score, mean (SD)▬▬▬▬
 Change from baseline, mean (SD)▬▬▬▬
 P value▬▬
Change in social score at week 8
 Baseline score, mean (SD)▬▬▬▬
 Change from baseline, mean (SD)▬▬▬▬
 P value▬▬

PLA = placebo; SD = standard deviation; UST = ustekinumab.

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

Table 31Responder Analyses for Change From Baseline in Inflammatory Bowel Disease Questionnaire and Short Form (36) Health Survey in the Induction Studies

ParameterUNITI-1UNITI-2
PLA (N = 247)UST (N = 249)PLA (N = 210)UST (N = 209)
≥ 16 point improvement from baseline in IBDQ total score at week 8
 n (%)89 (36.5)136 (54.8)85 (41.1)141 (68.1)
 P value< 0.001< 0.001
≥ 5 point improvement from baseline in SF-36 PCS score at week 8▬▬▬▬
 n (%)▬▬▬▬
 P value▬▬
≥ 5 point improvement from baseline in SF-36 MCS score at week 8▬▬▬▬
 n (%)▬▬▬▬
 P value▬▬

IBDQ = Inflammatory Bowel Disease Questionnaire; MCS = mental component score; PCS = physical component score; PLA = placebo; SF-36 = Short Form (36) Health Survey; UST = ustekinumab.

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

Table 32Summary of Change From Baseline in the Inflammatory Bowel Disease Questionnaire Dimension Scores in the Maintenance Study

ParameterIM-UNITI
PLA (N = 131)UST q.12.w. (N = 129)UST q.8.w. (N = 128)
Change in bowel score at week 44
 Baseline score, mean (SD)▬▬▬
 Change from baseline, mean (SD)▬▬▬
 P value▬▬
Change in emotional score at week 44
 Baseline score, mean (SD)▬▬▬
 Change from baseline, mean (SD)▬▬▬
 P value▬▬
Change in systemic score at week 44
 Baseline score, mean (SD)▬▬▬
 Change from baseline, mean (SD)▬▬▬
 P value▬▬
Change in social score at week 44
 Baseline score, mean (SD)▬▬▬
 Change from baseline, mean (SD)▬▬▬
 P value▬▬

PLA = placebo; q.8.w. = every 8 weeks; q.12.w. = every 12 weeks; SD = standard deviation; UST = ustekinumab.

Source: Clinical Study Report for IM-UNITI.9

Table 33Responder Analyses for Change From Baseline in Inflammatory Bowel Disease Questionnaire and Short Form (36) Health Survey in the Maintenance Study

ParameterIM-UNITI
PLA (N = 131)UST q.12.w. (N = 129)UST q.8.w. (N = 128)
≥ 16 point improvement from baseline in IBDQ total score at week 44
 n (%)▬▬▬
 P value▬▬
≥ 5 point improvement from baseline in SF-36 PCS score at week 44▬▬▬
 n (%)▬▬▬
 P value▬▬
≥ 5 point improvement from baseline in SF-36 MCS score at week 44▬▬▬
 n (%)▬▬▬
 P value▬▬

IBDQ = Inflammatory Bowel Disease Questionnaire; MCS = mental component score; PCS = physical component score; PLA = placebo; q.8.w. = every 8 weeks; q.12.w. = every 12 weeks; SF-36 = Short Form (36) Health Survey; UST = ustekinumab.

Source: Clinical Study Report for IM-UNITI.9

Table 34Clinical Remission at Week 44 of Maintenance Study by Ustekinumab Induction Regimen

Subgroups, n (%)IM-UNITI
PLA (N = 131)UST q.12.w. (N = 129)UST q.8.w. (N = 128)
UST 130 mg IV induction regimen▬▬▬
Clinical remission at week 44▬▬▬
 OR (95% CI)▬▬
 P value▬▬
UST 6 mg/kg IV induction regimen▬▬▬
Clinical remission at week 44▬▬▬
 OR (95% CI)▬▬
 P value▬▬

CI = confidence interval; IV = intravenous; OR = odds ratio; PLA = placebo; q.8.w. = every 8 weeks; q.12.w. = every 12 weeks; UST = ustekinumab.

Source: Clinical Study Report for IM-UNITI.9

Table 35Summary of Results for Endoscopic Outcomes at Week 8 of Induction and Week 44 of Maintenance Study

ParameteraPLA (N = 97)USTb (N = 155)
Change from baseline in SES-CD at week 8 of induction, mean (SD)−0.7 (4.97)−2.8 (5.68)
P value0.012
Change from induction baseline in the SES-CD score at week 44 of maintenance, mean (SD)Not reportedNot reported
P value
Patients with mucosal healing at week 44 of maintenance, n (%)
P value
Patients with mucosal healing at week 8 of induction, n (%)4 (4.1)14 (9.0)
P value0.141c

PLA = placebo; SD = standard deviation; SES-CD = Simplified Endoscopic Activity Score for Crohn’s Disease; UST = ustekinumab.

a

Only the primary outcome (i.e., change from baseline in the SES-CD score at week 8 of induction) and key secondary outcomes pre-specified and part of the hierarchical analysis plan in the endoscopy substudy are reported.

b

Ustekinumab 130 mg and tiered ustekinumab doses ~6 mg/kg combined.

c

Note that the statistical analysis hierarchy also failed at a higher-order comparison.

Source: Manufacturer’s submission to CDR.26

Copyright © CADTH 2017.

Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/

Bookshelf ID: NBK476205
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