PHASE 3 CLINICAL TRIAL STUDY DESIGN1,2
Overview of the U-EXCEL and U-EXCEED induction studies and the U-ENDURE maintenance study
†Defined as an average daily very soft or liquid stool frequency (SF) ≥4 and/or average daily abdominal pain score (APS) ≥2, and a centrally-reviewed simple endoscopic score for CD (SES-CD) of ≥6, or ≥4 for isolated ileal disease, excluding the narrowing component.
*Endoscopic response = Decrease in SES-CD >50% from baseline of the induction study (or for patients with an SES-CD of 4 at baseline of the induction study, at least a 2-point reduction from baseline of the induction study).1
‡Clinical remission (SF/APS) = Average daily SF ≤2.8 and APS ≤1.0 and neither greater than baseline.1
§Clinical response (SF/APS) = ≥30% decrease in average daily very soft or liquid SF and/or ≥30% decrease in average daily APS and neither greater than baseline.1
¶RINVOQ patients who did not achieve clinical response at Week 12 in U-EXCEL and U-EXCEED continued in an additional 12-week, open-label, induction extension period with RINVOQ 30 mg QD. Clinical responders following extended induction continued to U-ENDURE Maintenance, however they were not included in the primary analysis.3
STUDY DESIGN: ongoing long-term extension study up to 204 weeks1,2
Patients who completed the 52-week U-ENDURE maintenance study were eligible to continue treatment in the U-ENDURE long-term extension study.
*Clinical responders (SF/APS): Patients who had a ≥ 30% decrease in average daily very soft or liquid SF and/or ≥ 30% decrease in average daily APS and neither greater than baseline.
†All patients who completed the U-ENDURE Maintenance study were eligible to enrol. At Week 0, all patients continued to receive their originally assigned treatment from the U-ENDURE Maintenance study. All patients receiving RINVOQ continued to receive their treatments until the end of the study.
BASELINE CHARACTERISTICS -
1,2
With biologic failure: Inadequate response or intolerance to one or more biologic therapies.
Without biologic failure: Inadequate response or intolerance to conventional therapies but not biologic therapy.
*Stratification factors for randomisation.
†For CDAI, placebo n=171 and RINVOQ 45 mg QD n=322; for FC (median), placebo n=161 and RINVOQ 45 mg n=319; for FC (mean), placebo n=159 and RINVOQ 45 mg QD n=298; for CRP (median), placebo n=176 and RINVOQ 45 mg n=341; for CRP (mean), placebo n=163 and RINVOQ 45 mg QD n= 319; history of conventional therapy failure only.
KEY BASELINE CHARACTERISTICS
4
(Characteristics at entry to induction)
With biologic failure: Inadequate response or intolerance to one or more biologic therapies.1,2
Without biologic failure: Inadequate response or intolerance to conventional therapies but not biologic therapy.1,2
INCLUSION & EXCLUSION CRITERIA2
Patient inclusion criteria
18 to 75 years of age
Moderate-to-severe Crohn’s disease for at least 3 months
U-EXCEL: failure* of one or more conventional or biologic therapies
U-EXCEED failure* of one or more biologic therapies
Patient exclusion criteria
Current diagnosis of ulcerative colitis or indeterminate colitis
Certain known complications of CD‡
Ostomy or ileoanal pouch
Conditions that could interfere with drug absorption e.g. short gut or short bowel syndrome.
Patient with surgical bowel resection within the past 3 months prior to baseline, or a history of >3 bowel resections.
†Defined as an average daily very soft or liquid stool frequency (SF) ≥4 and/or average daily abdominal pain score (APS) ≥2, and a centrally-reviewed simple endoscopic score for CD (SES-CD) of ≥6, or ≥4 for isolated ileal disease, excluding the narrowing component.
*Failure of therapy was defined as an inadequate response to or unacceptable side effects from therapy.
‡Abscess (abdominal or peri-anal); symptomatic bowel strictures; 2 entire missing segments out of the terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; fulminant colitis; toxic megacolon; any other manifestation that might require surgery while enrolled in the study.
These are key inclusion/exclusion criteria. Refer to supplement in paper for the full list.2
1,2
CO-PRIMARY ENDPOINTS: Endoscopic response‡ and clinical remission (SF/APS)* at Week 12 and Week 52.1,2
‡Endoscopic response = Decrease in SES-CD >50% from baseline of the induction study (or for patients with an SES-CD of 4 at baseline of the induction study, at least a 2-point reduction from baseline of the induction study). EMA protocol.1
*SF/APS: Average daily SF ≤ 2.8 and APS ≤ 1.0 and neither greater than baseline.1
APS, abdominal pain score; BMI, body-mass index; CD, Crohn’s disease; CDAI, Crohn’s disease activity index; FC, fecal calprotectin; (hs)CRP, (high-sensitivity) C-reactive protein; ITT, intention to treat; QD, once daily; SD, standard deviation; SES-CD, simple endoscopic score for Crohn's disease; SF, stool frequency.
REFERENCES
- RINVOQ Product Information.
- Loftus EV, et al. N Engl J Med. 2023;388:1966–80 (incl. supplementary appendix).
- D’Haens G, et al. Presented at the Digestive Disease Week Annual Meeting, 6–9 May 2023, Chicago, IL, USA: Tu1705.
- D’Haens G, et al. Presented at the 19th Congress of ECCO, 21–24 Feb 2024, Stockholm, Sweden: OP10.
WARNING: Based on the results from a post-marketing safety study of another JAK inhibitor, RINVOQ should only be used if no suitable treatment alternatives are available in patients: Refer to Product Information. |
PBS Information
RINVOQ: Authority required. Refer to PBS Schedule for full authority information.
Please review the full Product Information (PI) before prescribing, available below.
AU-RNQG-240041. April 2024