RINVOQ® (upadacitinib) is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.1
RINVOQ achieved the primary endpoints of clinical remission per adapted Mayo score at Induction Week 8 and Maintenance Week 521,2
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
A Phase 3 trial program involving 3 studies: 2 replicate induction studies (U-ACHIEVE Induction and U-ACCOMPLISH) and 1 maintenance study (U-ACHIEVE Maintenance). A total of 988 patients with moderately to severely active UC evaluating RINVOQ 45 mg QD vs placebo for induction and RINVOQ 15 mg QD and 30 mg QD vs placebo for maintenance treatment (N=451).1*
*Patients who achieved clinical response per adapted Mayo score with 8-week RINVOQ 45 mg QD induction treatment entered maintenance.
This post hoc analysis evaluated the comparative benefit-risk profile of RINVOQ vs placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.3*
The RINVOQ UC program enrolled patients with active disease, inadequate response, loss of response, or intolerance to ≥1 oral aminosalicylate, corticosteroid, immunosuppressant, and/or biologic therapy to 3 induction trials (U-ACHIEVE [one Phase 2b and one Phase 3]), U-ACCOMPLISH (Phase 3), and the Phase 3 U-ACHIEVE maintenance study.3
Limitations of this post hoc analysis:
- Restriction to an 8-week induction and 52-week maintenance therapeutic regimen with limited patient exposure might limit detection and interpretation of adverse events with low incidences (e.g., malignancy).2
- Lack of dose adjustment during maintenance treatment (e.g., patients could not increase to 30 mg if the 15 mg dose was ineffective).2
Post-hoc analyses should not be used for individual prescribing decisions or dose comparison. The RINVOQ Summary of Product Characteristics should be consulted and a benefit-risk assessment should be conducted for individual patients before starting RINVOQ therapy.
AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication.
*Results are based on nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19. The point estimate and 95% CI for treatment difference are based on Cochran-Mantel-Haenszel tests adjusted for strata (induction: stratified by corticosteroid use at baseline [yes vs no], adapted Mayo score at baseline [≤7 vs >7], and bio-IR status [bio-IR vs non-bio-IR]; maintenance: stratified by bio-IR status [bio-IR vs non-bio-IR], corticosteroid use at Week 0 of maintenance [yes vs no], and clinical remission status at Week 0 of maintenance [yes vs no]).
A positive value indicates more favorable efficacy with RINVOQ vs placebo; a negative value indicates more favorable safety with RINVOQ vs placebo.
*Patients were inducted onto therapy either in the placebo group (n=328) or RINVOQ 45 mg QD group (n=660). The safety population included all patients who received ≥1 dose of study therapy (intent-to-treat population). †Adapted Mayo score ≤2, stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore=0, and ESS ≤1 without friability. ‡ESS ≤1. §ESS=0. IIESS ≤1 without friability and Geboes score ≤3.1. ¶ESS=0 and Geboes score <2. #The placebo event occurred in the Phase 3 study and the RINVOQ 45 mg QD event in a Phase 2b induction study.
In the induction period, 27 (7.1%) patients discontinued treatment because of an adverse event (AE) with placebo, compared with 17 (2.4%) with RINVOQ 45 mg QD. In the maintenance period, 25 (10.2%), 10 (4.0%), and 18 (7.2%) patients discontinued treatment due to an AE with placebo, RINVOQ 15 mg QD, and RINVOQ 30 mg QD, respectively.
A positive value indicates more favorable efficacy with RINVOQ vs placebo; a negative value indicates more favorable safety with RINVOQ vs placebo.
*Patients who achieved a clinical response after 8 weeks of induction treatment (RINVOQ 45 mg QD) were rerandomized to RINVOQ 15 mg or 30 mg QD or placebo for 52 weeks. 681 patients progressed onto maintenance therapy and were analyzed for efficacy (placebo, n=223; RINVOQ 15 mg, n=225; and RINVOQ 30 mg, n=233), and 746 for safety (n=245, n=250, and n=251, respectively). The safety population included all patients who received ≥1 dose of study therapy (intent-to-treat population plus patients who received up to 44 weeks of maintenance therapy under earlier versions of protocol amendments). †Adapted Mayo score ≤2, stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore=0, and ESS ≤1 without friability. ‡Among patients with clinical remission at the end of the induction therapy. §ESS ≤1. IIAmong patients with endoscopic improvement at the end of the induction therapy. ¶ESS=0. #ESS ≤1 without friability and Geboes score ≤3.1. **ESS=0 and Geboes score <2. ‡‡The placebo event occurred in the Phase 3 study and the RINVOQ 45 mg QD event in a Phase 2b induction study.
For analysis of efficacy, point estimates and 95% confidence intervals of the placebo-adjusted treatment effect were calculated across the primary and key secondary endpoints in the intent-to-treat population.
For the safety risk analysis, the exposure-adjusted event rate (events/100 patient years) was calculated for selected adverse events of special interest (AESIs) in the initial induction phase with RINVOQ 45 mg QD and the maintenance phase with RINVOQ 15 mg QD and 30 mg QD.
- The placebo-adjusted risk was then calculated for each AESI.
For analysis of efficacy, point estimates and 95% confidence intervals of the placebo-adjusted treatment effect were calculated across the primary and key secondary endpoints in the intent-to-treat population.
For the safety risk analysis, the exposure-adjusted event rate (events/100 patient years) was calculated for selected adverse events of special interest (AESIs) in the initial induction phase with RINVOQ 45 mg QD and the maintenance phase with RINVOQ 15 mg QD and 30 mg QD.
- The placebo-adjusted risk was then calculated for each AESI.
For analysis of efficacy, point estimates and 95% confidence intervals of the placebo-adjusted treatment effect were calculated across the primary and key secondary endpoints in the intent-to-treat population.
For the safety risk analysis, the exposure-adjusted event rate (events/100 patient years) was calculated for selected adverse events of special interest (AESIs) in the initial induction phase with RINVOQ 45 mg QD and the maintenance phase with RINVOQ 15 mg QD and 30 mg QD.
- The placebo-adjusted risk was then calculated for each AESI.
AE: adverse event; AESI: adverse event of special interest; rase; aMs: adapted Mayo score; bio-IR: biologic inadequate response; CI: confidence interval; CPK: creatine phosphokinase; CYP3A4: cytochrome P450 3A4; ESS: endoscopic subscore; IR: inadequate response; JAK: Janus kinase; MACE: major adverse cardiac event; NMSC: non-melanoma skin cancer; PY: patient-years; QD: once daily; RBS: rectal bleeding score; UC: ulcerative colitis; URTI: upper respiratory tract infection; VTE: venous thromboembolism.
Study designs: U-ACHIEVE Induction (UC-1) and U-ACCOMPLISH (UC-2) were replicate induction studies, both of which were multicenter, double-blind, placebo-controlled clinical studies. In UC-1 and UC-2, 988 patients (473 and 515 patients, respectively) were randomized to RINVOQ 45 mg QD or placebo for 8 weeks with a 2:1 treatment allocation ratio and included in the efficacy analysis. All enrolled patients had moderately to severely active UC defined as aMs of 5 to 9 with an ESS of 2 or 3 and demonstrated prior treatment failure including inadequate response, loss of response, or intolerance to prior conventional and/or biologic treatment. U-ACHIEVE Maintenance (UC-3) was a multicenter, double-blind, placebo-controlled clinical study with 451 patients who achieved clinical response per aMs (decrease ≥2 points and ≥30% from baseline and a decrease in RBS ≥1 from baseline or an absolute RBS ≤1) with 8-week RINVOQ 45 mg QD induction treatment. Patients were rerandomized 1:1:1 to receive either RINVOQ 15 mg QD, 30 mg QD, or placebo.1,2
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Learn more about RINVOQ’s safety profile during a Phase 3 induction and maintenance clinical study program through Weeks 8 and 52.1,2
< Affiliate to link to locally approved project ALL-RNQG-220028 >
< Affiliate to link to locally approved project ALL-RNQG-220006 >
RINVOQ is an oral, once daily, selective and reversible JAK inhibitor now approved for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.1
RINVOQ can be taken at any time of the day, with or without food.1
A Phase 3 clinical trial program involving 3 studies: 2 replicate induction studies and 1 maintenance study evaluated RINVOQ 45 mg QD vs placebo for induction and RINVOQ 15 mg QD and 30 mg QD vs placebo for maintenance treatment.1,2
[Please insert local summary of safety]
REFERENCES
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; December 2023.
- 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. doi:10.1016/S0140-6736(22)00581-5
- Panaccione R, Blumenstein I, Irving P, et al. Benefit-risk assessment of upadacitinib treatment in patients with moderately to severely active ulcerative colitis. Poster presented at: United European Gastroenterology Week; October 8-11, 2022; Vienna, Austria. P243.
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ALL-RNQG-220224 Date of preparation: February 2024
Adverse events should also be reported to AbbVie on GBPV@abbvie.com