A Phase 3 trial program involving 3 studies:1 2 replicate induction studies (U-ACHIEVE Induction and U-ACCOMPLISH) and 1 maintenance study (U-ACHIEVE Maintenance). 988 moderately to severely active UC patients evaluating RINVOQ 45 mg vs placebo for induction, and RINVOQ 15 mg and 30 mg 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.
Ulcerative colitis is an unpredictable, chronic condition which can pose a significant risk to patients through its varying disease course.3
Uncontrolled UC can lead to increased risk of flares and relapse.4,5 Current ECCO guidelines state that courses of corticosteroids should be restricted to a maximum of 3 months.6
In order to induce and maintain clinical response and remission rates in the treatment of moderately to severely active UC, it is beneficial to look beyond disease symptoms when making clinical decisions, as per current STRIDE-II guidelines.7
The primary endpoints of both studies was achievement of remission per adapted Mayo score at Week 8.1,2
Study design: 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.1,2
Maintenance of clinical remission per adapted Mayo score at Week 52 was a ranked secondary endpoint and was assessed as Clinical Remission per adapted Mayo score at Week 52 among patients who achieved clinical remission per adapted Mayo score at Week 8 of RINVOQ 45 mg induction treatment (n=159).2
Study design: U-ACHIEVE SS3 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 and efficacy vs for both doses vs placebo was assessed at 52 weeks.1,2
Corticosteroid-free remission at Week 52 was a ranked secondary endpoint and was assessed in patients who achieved clinical remission per adapted Mayo score with 8-week RINVOQ 45 mg QD induction treatment.1,2 Clinical remission per adapted Mayo score: stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0 and endoscopic subscore of 0 or 1 without friability.1,2
Study design: 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
AE: adverse event; AESI: adverse event of special interest; aMs: adapted Mayo score; CI: confidence interval; CPK: creatine phosphokinase; ESS: endoscopic subscore; GI: gastrointestinal; ITT: intention to treat; MACE: major adverse cardiac event; NMSC: non-melanoma skin cancer; NRI-C: non-responder imputation incorporating multiple imputations to handle missing data due to coronavirus disease 2019 (COVID-19); paMs: partial adapted Mayo score; QD: once-daily; RBS: rectal bleeding score; TEAE: treatment-emergent adverse event; UC: ulcerative colitis; URTI: upper respiratory tract infection; VTE: venous thromboembolism.
REFERENCES
- RINVOQ Summary of Product Characteristics [DRAFT].
- Danese S, Vermeire S, Zhou W, et al. Lancet. Published online May 26, 2022. doi: https://doi.org/10.1016/S0140-6736(22)00581-5.
- Lichtenstein GR, Rutgeerts P. Inflamm Bowel Dis. 2010; 16(10):338–346.
- Atreya R, Neurath MF. Visc Med. 2017; 33(1):82–88.
- Matsuoka K, Igarashi A, Sato N, et al. J Crohns Colitis. 2021;15(3):358-366.
- Raine T, Bonovas S, Burisch J, et al. J Crohns Colitis. 2022;16(1):2-17.
- Turner D, Ricciuto A, Lewis A, et al. Gastroenterology. 2021;160:1570-1583.