aBio-naive patients include patients who were exposed to a biologic but did not experience treatment failure.
All P-values are RINVOQ treatment arms vs placebo.
US-MULT-240253
Rapid relief of rectal bleeding and stool frequency as early as Week 21*†‡
Clinical remission§ at Week 8 and Week 52, and steroid-free clinical remission|| at Week 521
Endoscopic improvement¶ and histo-endoscopic mucosal improvement# at Week 8 and Week 521
The relationship between histo-endoscopic mucosal improvement to disease progression and long-term outcomes was not evaluated.
*U-ACHIEVE Induction: 60% on RINVOQ 45 mg vs 27% on placebo (P<0.001).2
†U-ACCOMPLISH Induction: 63% on RINVOQ 45 mg vs 26% on placebo (P<0.001).2
‡Clinical response per partial modified Mayo Score is a composite of Mayo stool frequency and rectal bleeding subscores and is defined as a decrease in total score ≥30% and ≥1 point from baseline and a decrease in rectal bleeding subscore ≥1 or rectal bleeding subscore of 0
or 1.
§Clinical remission is defined as stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤1 without friability.
‖Steroid-free clinical remission is defined as clinical remission at Week 52 and corticosteroid-free for ≥90 days immediately preceding Week 52 (among patients achieving remission in induction).
¶Endoscopic improvement was defined as Mayo endoscopic subscore of 0 or 1 without friability. Endoscopic results are based on a full colonoscopy or flexible sigmoidoscopy, depending on the extent of disease at study entry.
#Histo-endoscopic mucosal improvement was defined as an endoscopic subscore ≤1 without friability and Geboes score ≤3.1 (indicating neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue). Endoscopic results are based on a full colonoscopy or flexible sigmoidoscopy, depending on the extent of disease at study entry, and histology results are based on a set of 2 biopsies.
IR=intolerance or inadequate response; TNFi=tumor necrosis factor inhibitor
IR=intolerance or inadequate response; TNFi=tumor necrosis factor inhibitor
Primary endpoints achieved.
All P-values are RINVOQ treatment arms vs placebo.
Recommended
Maintenance Dosing:
A dose of 30 mg may be
considered in patients
with refractory, severe or
extensive disease. Discontinue
if therapeutic response is not
achieved with the 30 mg dose.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
*Clinical remission is defined as stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤1
without friability.
†Among patients who achieved clinical response per modified Mayo Score with RINVOQ at Week 8.
of rectal bleeding and stool frequency at Week 2
(Composite of Rectal Bleeding and Stool Frequency Subscores)
CLINICAL RESPONSE AT WEEK 2:
Data Limitations: The prespecified integrated analysis for Clinical Response at Week 2 and over time is considered supportive of the efficacy results obtained from the individual studies and is intended to be interpreted within this context. No multiplicity adjustment was performed thus no statistical inferences can be made.
Data Limitations: The prespecified integrated analysis for Clinical Response at Week 2 and over time is considered supportive of the efficacy results obtained from the individual studies and is intended to be interpreted within this context. No multiplicity adjustment was performed thus no statistical inferences can be made.
(Daily Patient Diary Data)
In the induction studies, a greater proportion of patients treated with RINVOQ 45 mg once daily compared to placebo had no bowel urgency (U‑ACHIEVE: 48% vs 21%, U‑ACCOMPLISH: 54% vs 26%) at Week 8.1
Data Limitations: Post-hoc analyses were not adjusted for multiplicity thus no statistical inferences can be made. These analyses utilized an as observed approach and did not impute values for missing evaluations.
In the induction studies, a greater proportion of patients treated with RINVOQ 45 mg once daily compared to placebo had no bowel urgency (U‑ACHIEVE: 48% vs 21%, U‑ACCOMPLISH: 54% vs 26%) at Week 8.1
Data Limitations: Post-hoc analyses were not adjusted for multiplicity thus no statistical inferences can be made. These analyses utilized an as observed approach and did not impute values for missing evaluations.
(Daily Patient Diary Data)
Data Limitations: Post-hoc analyses were not adjusted for multiplicity thus no statistical inferences can be made. These analyses utilized an as observed approach and did not impute values for missing evaluations.
Data Limitations: Post-hoc analyses were not adjusted for multiplicity thus no statistical inferences can be made. These analyses utilized an as observed approach and did not impute values for missing evaluations.
(Daily Patient Diary Data)
Data Limitations: Post-hoc analyses were not adjusted for multiplicity thus no statistical inferences can be made. These analyses utilized an as observed approach and did not impute values for missing evaluations.
Data Limitations: Post-hoc analyses were not adjusted for multiplicity thus no statistical inferences can be made. These analyses utilized an as observed approach and did not impute values for missing evaluations.
FECAL CALPROTECTIN <150 MG/KG
Fecal Calprotectin <150 mg/kg
Data Limitations: Fecal calprotectin <150 mg/kg at Week 2 and Week 8 of the integrated induction data was a prespecified analysis. Change from baseline in median fecal calprotectin at Week 2 and Week 8 was a post-hoc analysis. Neither of these analyses were adjusted for multiplicity thus no statistical inferences can be made.
Fecal calprotectin is not validated as a biomarker to monitor disease progression.
Data Limitations: Fecal calprotectin <150 mg/kg over time of the integrated induction data was a prespecified analysis. Change from baseline in median fecal calprotectin over time was a post-hoc analysis. Neither of these analyses were adjusted for multiplicity thus no statistical inferences can be made.
Clinical Remission
All P-values are RINVOQ treatment arms vs placebo.
*Among patients who achieved clinical response per modified Mayo Score with RINVOQ at Week 8.
In the LTE analysis, the data is segmented as follows:
OLE LIMITATIONS: In an OLE, there is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.
AO DISCLOSURE: In an as observed (AO) analysis, missing visit data was excluded from calculations for that visit, which may increase the percent of responders. All observed data was used regardless of premature discontinuation of study drug, or initiation of concomitant medications. The same patient may not have a response at each timepoint.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
DATA LIMITATIONS FOR POST-HOC ANALYSIS: Symptomatic remission over time is a post-hoc analysis and was not adjusted for multiplicity thus no statistical inferences can be made.
U-ACHIEVE Study
All P-values are RINVOQ treatment arms vs placebo.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients
with refractory, severe or extensive disease.
Discontinue if therapeutic response
is not achieved with the 30 mg dose.
U-ACHIEVE and U-ACTIVATE Studies
*Clinical remission per partial Mayo score (rectal bleeding, stool frequency, physician's global assessment subscores)
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
DATA LIMITATIONS FOR PRESPECIFIED ANALYSIS: These data are based on a prespecified, nonranked endpoint. No multiplicity adjustment was performed thus no statistical inferences can be made.
OLE LIMITATIONS: In an OLE, there is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.
AO DISCLOSURE: In an as observed (AO) analysis missing visit data was excluded from calculations for that visit, which may increase the percent of responders. All observed data was used regardless of premature discontinuation of study drug, or initiation of concomitant medications. The same patient may not have a response at each timepoint.
Endoscopic & Histo-endoscopic Mucosal Improvement Data
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
All P-values are RINVOQ treatment arms vs placebo.
OLE LIMITATIONS: In an OLE, there is a potential for enrichment of the long-term data in the remaining patient populations since patients who are unable to tolerate or do not respond to the drug often drop out.
AO DISCLOSURE: In an as observed (AO) analysis missing visit data was excluded from calculations for that visit, which may increase the percent of responders. All observed data was used regardless of premature discontinuation of study drug, or initiation of concomitant medications. The same patient may not have a response at each timepoint.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
The relationship between this endpoint to disease progression and long-term outcomes was not evaluated.
All P-values are RINVOQ treatment arms vs placebo.
*Among patients who achieved clinical response per modified Mayo Score with RINVOQ at Week 8.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients with refractory, severe or extensive disease. Discontinue if therapeutic response is not achieved with the 30 mg dose.
Recommended Maintenance Dosing:
A dose of 30 mg may be considered in patients
with refractory, severe or extensive disease.
Discontinue if therapeutic response
is not achieved with the 30 mg dose.
See RINVOQ's safety data across clinical trials
RINVOQ is indicated for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers.
Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for ulcerative colitis, or with other potent immunosuppressants such as azathioprine and cyclosporine.
REFERENCES
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113-2128.
3. Data on File. ABVRRTI73441.
4. Loftus Jr. EV, Colombel JF, Takeuchi K, et al. Upadacitinib therapy reduces ulcerative colitis symptoms as early as day 1 of induction treatment. Clin Gastroenterol Hepatol. Preprint published online December 1, 2022. doi:10.1016/j.cgh.2022.11.02
5. Data on File. ABVRRTI75066.
6. Data on File. ABVRRTI76869.