Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials

Danese, Silvio; Vermeire, Séverine; Zhou, Wen; Pangan, Aileen L.; Siffledeen, Jesse; Greenbloom, Susan; Hébuterne, Xavier; D’Haens, Geert; Nakase, Hiroshi; Panés, Julián; Higgins, Peter; Juillerat, Pascal; Lindsay, James O.; Loftus, Edward V.; Sandborn, William J.; Reinisch, Walter; Chen, Minhu; González, Yuri Sánchez; Huang, Bidan; Xie, Wenhui; Liu, John; Weinreich, Michael; Panaccione, Remo

doi:10.1016/s0140-6736(22)00581-5

Cited by 315 publications

(292 citation statements)

References 29 publications

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“… 7 The phase III clinical trial program went on to measure the primary endpoint of clinical remission as defined by the mMayo score. 14 Furthermore, a recent phase III randomized controlled trial, evaluating the interleukin-12/-23 antagonist ustekinumab for the treatment of moderately to severely active UC, utilized the mMayo score in an alternative definition for the primary endpoint of clinical remission, in addition to clinical remission based on the Mayo score. 6 The study reported that the proportion of patients with clinical remission following induction or maintenance therapy was similar regardless of inclusion of PGA subscore in the assessment, supporting the findings reported in this post hoc analysis of tofacitinib efficacy.…”

Section: Discussionmentioning

confidence: 99%

Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program

Sandborn

Sands

Vermeire

et al. 2022

Therap Adv Gastroenterol

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Objectives: The subjectivity of the Physician Global Assessment (PGA) is a limitation of the Mayo score in assessing severity of ulcerative colitis (UC). We compared treatment efficacy using endpoint definitions based on modified Mayo (mMayo) score, versus those based on Mayo score, using data from the tofacitinib OCTAVE program. Design: This post hoc analysis included data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain). Methods: Remission and clinical response [with nonresponder imputation (NRI)] were assessed using mMayo (without PGA) and Mayo scores, and further stratified by prior tumor necrosis factor inhibitor (TNFi) failure status. Results: At week 8 of OCTAVE Induction 1 and 2, remission rates with placebo and tofacitinib 10 mg twice daily (BID), respectively, were 7.7% and 24.8% (mMayo) and 6.0% and 17.6% (Mayo). At week 52 of OCTAVE Sustain, remission rates with placebo, tofacitinib 5 and 10 mg BID, respectively, were 12.1%, 35.9%, and 42.1% (mMayo) and 11.1%, 34.3%, and 40.6% (Mayo). A statistically significant ( p < 0.05) treatment effect of tofacitinib versus placebo was observed for remission and clinical response at all time points, regardless of scoring definition or prior TNFi failure status. Conclusions: A significant effect of tofacitinib versus placebo was demonstrated across efficacy endpoints using mMayo score, consistent with previously reported data using Mayo score. Treatment effect sizes were generally similar regardless of scoring definition. This observation may help contextualize tofacitinib therapy outcomes with those of new UC therapies and support the use of Mayo score-based endpoints in UC clinical trials. Trail registration: ClinicalTrials.gov identifiers: NCT01465763; NCT01458951; NCT01458574.

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Section: Discussionmentioning

confidence: 99%

Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program

Sandborn

Sands

Vermeire

et al. 2022

Therap Adv Gastroenterol

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“… Key advances Clinical trials of the IL-23p19 antibodies guselkumab and risankizumab have demonstrated that they are safe and effective for induction and maintenance of remission in moderately to severely active Crohn’s disease 1 – 3 . A phase III trial of the novel Janus kinase inhibitor upadacitinib demonstrated its efficacy in patients with moderately to severely active ulcerative colitis who either had or had not previously received biologic therapy 5 . A phase III trial of the oral integrin α4 inhibitor carotegrast methyl (AJM300) demonstrated its efficacy as an induction therapy in mildly to moderately active ulcerative colitis; the drug is now approved for clinical use in Japan 6 .…”

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confidence: 99%

Improving IBD outcomes in the era of many treatment options

Hibi

2023

Nat Rev Gastroenterol Hepatol

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“…Another selective JAK1 inhibitor, upadacitinib (ABT‐494 or Rinvoq®), currently approved for the treatment of psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis and atopic dermatitis, is also currently under evaluation in IBD 53 . The efficacy of upadacitinib in UC was demonstrated in a phase 2b study and confirmed in three phase 3 studies 58,59 . In the two phase 3 induction studies (U‐ACHIEVE induction/UC1 and U‐ACCOMPLISH/UC2), statistically significantly more patients achieved clinical remission with upadacitinib 45 mg PO once daily (26% in UC1 and 33% in UC2) than in the PBO group (5% in UC1 and 4% in UC2; p < 0.0001 for both UC1 and UC2), regardless baseline disease characteristics 60 .…”

Section: Drug Being Evaluated In a Phase 3 Clinical Trialmentioning

confidence: 99%

“… 53 The efficacy of upadacitinib in UC was demonstrated in a phase 2b study and confirmed in three phase 3 studies. 58 , 59 In the two phase 3 induction studies (U‐ACHIEVE induction/UC1 and U‐ACCOMPLISH/UC2), statistically significantly more patients achieved clinical remission with upadacitinib 45 mg PO once daily (26% in UC1 and 33% in UC2) than in the PBO group (5% in UC1 and 4% in UC2; p < 0.0001 for both UC1 and UC2), regardless baseline disease characteristics. 60 The rate of patients reaching primary endpoints at week 8 with upadacitinib 45 mg was greater in biologic‐naive patients (35.2% in UC1 and 37.5% in UC2) than in biologic‐experienced patients (17.9% in UC1 and 29.6% in UC2), but superior to PBO in all cases.…”

Section: Drug Being Evaluated In a Phase 3 Clinical Trialmentioning

confidence: 99%

Landscape of new drugs and targets in inflammatory bowel disease

et al. 2022

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Although the therapeutic armamentarium of Inflammatory bowel diseases (IBD) physicians has expanded rapidly in recent years, a proportion of patients remain with a suboptimal response to medical treatment due to primary no response, loss of response or intolerance to currently available drugs. Our growing knowledges of IBD pathophysiology has led to the development of a multitude of new therapies over time, which may, 1 day, be able to address this unmet medical need. This review aims to provide physicians an update of emerging therapies in IBD by focusing on drugs currently in phase 3 clinical trials. Among the most promising molecules are anti-IL-23, JAK-inhibitors, anti-integrins and S1P modulators. While the results in terms of efficacy and safety are fairly clear for some classes, the question of safety remains more uncertain for other classes. Molecules at a more preliminary stage of development (phase 1 and 2), one of which may 1 day offer an optimal benefit-risk ratio, will also be presented as well as their respective mechanisms of action.

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Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials

Cited by 315 publications

References 29 publications

Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program

Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program

Improving IBD outcomes in the era of many treatment options

Landscape of new drugs and targets in inflammatory bowel disease

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