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. 2022 Dec 5:15:17562848221136331.
doi: 10.1177/17562848221136331. eCollection 2022.

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

William J Sandborn  1 , Bruce E Sands  2 , Séverine Vermeire  3 , Yvette Leung  4 , Xiang Guo  5 , Irene Modesto  6 , Chinyu Su  5 , Wenjin Wang  5 , Julian Panés  7
Affiliations

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

William J Sandborn et al. Therap Adv Gastroenterol. .

Abstract

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.

Keywords: Mayo score; tofacitinib; ulcerative colitis.

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Conflict of interest statement

WJS has received grant support, personal fees, and non-financial support from Pfizer Inc during the conduct of the studies. Outside of the submitted work, WJS has received grant support from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Eli Lilly, Genentech, Gilead Sciences, GSK, Janssen, Pfizer Inc, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Admirx, Alfasigma, Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust), Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), BeiGene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Eli Lilly, Equillium, Escalier Biosciences, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), InDex Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer Inc, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; has stock or stock options in Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Progenity, Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences; and is an employee of Shoreline Biosciences. WJS’s spouse has received consulting fees from Iveric Bio, Oppilan Pharma, and Prometheus Laboratories; has stock or stock options in Oppilan Pharma, Progenity, Prometheus Biosciences, Prometheus Laboratories, Ventyx Biosciences, and Vimalan Biosciences; and is an employee of Prometheus Biosciences. BES has received personal fees and non-financial support from Pfizer Inc during the conduct of the studies. Outside of the submitted work, BES has received personal fees from 4D Pharma, AbbVie, Abivax, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Baxalta Bioscience India, Boehringer Ingelheim, Boston Pharmaceuticals, Capella Bioscience, Celgene, Celltrion, Eli Lilly, F. Hoffmann-La Roche, Ferring, Genentech, Gilead Sciences, GSK, Immunic, InDex Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kallyope, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer Inc, Progenity, Prometheus Biosciences IBD, Prometheus Laboratories, Protagonist Therapeutics, Redhill Biopharma, Rheos Medicines, Salix Pharmaceuticals, Seres Therapeutics, Shire, Sienna Biopharmaceuticals, Surrozen, Takeda, TARGET RWE, Theravance Biopharma R&D, USWM Enterprises, Ventyx Biosciences, Viela Bio, and Vivelix Pharmaceuticals; grant support from Arena Pharmaceuticals, Celgene, and Theravance Biopharma R&D; non-financial support from Eli Lilly, Pfizer Inc, and Takeda; and has stock options in Ventyx Biosciences. SV reports grant support from AbbVie, MSD, Pfizer Inc, Galapagos and Takeda; speaker fees from AbbVie, Dr. Falk Pharma, Ferring, Hospira, MSD, Takeda, and Tillotts; and consulting fees from AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson and Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillots Pharma AG and Zealand Pharma. YL has received consulting fees from AbbVie, Amgen, Janssen, Merck, Pfizer Inc, and Takeda. XG, IM, CS, and WW are employees and shareholders of Pfizer Inc. JP has received personal fees from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Origo, Pandion, Pfizer Inc, Progenity, Takeda, Theravance Biopharma, and Wassermann.

Figures

Figure 1.
Figure 1.
Proportions of patients (a) in remission and (b) with clinical response, defined by mMayo score and Mayo score at week 8 of OCTAVE Induction 1 and 2, overall and stratified by prior TNFi failure status (FAS, NRI). Remission was defined as a total Mayo score (including PGA subscore) of ⩽2 with no individual subscore >1, and a rectal bleeding subscore of 0. Modified remission was defined as an endoscopic subscore of ⩽1, a stool frequency subscore of ⩽1, and a rectal bleeding subscore of 0. Clinical response was defined as a decrease from induction study baseline total Mayo score (including PGA subscore) of ⩾3 points and ⩾30%, plus a decrease in rectal bleeding subscore of ⩾1 point or an absolute rectal bleeding subscore of 0 or 1. Modified clinical response was defined as a decrease from induction study baseline mMayo score (excluding PGA subscore) of ⩾2 points and ⩾30%, plus a decrease in rectal bleeding subscore of ⩾1 point or an absolute rectal bleeding subscore of 0 or 1. Endoscopic subscore was based on central read. p values versus placebo were based on the Cochran-Mantel-Haenszel chi-squared test, stratified by study, prior treatment with TNFi, corticosteroid use at baseline, and geographical region. **p < 0.01 versus placebo. ***p < 0.001 versus placebo. BID, twice daily; CI, confidence interval; FAS, full analysis set; mMayo, modified Mayo; N, number of patients in the analysis set; n, number of patients achieving endpoint; NRI, nonresponder imputation; PGA, Physician Global Assessment; TNFi, tumor necrosis factor inhibitor.
Figure 2.
Figure 2.
Proportions of patients in remission, defined by mMayo score and Mayo score at week 24, week 52, and at both time points (sustained) in OCTAVE Sustain, (a) overall and (b) stratified by prior TNFi failure status (FAS, NRI). Remission was defined as a total Mayo score (including PGA subscore) of ⩽2 with no individual subscore >1, and a rectal bleeding subscore of 0. Modified remission was defined as an endoscopic subscore of ⩽1, a stool frequency subscore of ⩽1, and a rectal bleeding subscore of 0. Endoscopic subscore was based on central read. p values versus placebo were based on the Cochran-Mantel-Haenszel chi-squared test, stratified by induction study treatment and baseline remission status. *p < 0.05 versus placebo. **p < 0.01 versus placebo. ***p < 0.001 versus placebo. BID, twice daily; CI, confidence interval; FAS, full analysis set; mMayo, modified Mayo; N, number of patients in the analysis set; n, number of patients achieving endpoint; NRI, nonresponder imputation; PGA, Physician Global Assessment; TNFi, tumor necrosis factor inhibitor.
Figure 3.
Figure 3.
Proportions of patients with clinical response, defined by mMayo score and Mayo score at week 24 or week 52 in OCTAVE Sustain, (a) overall and (b) stratified by prior TNFi failure status (FAS, NRI). Clinical response was defined as a decrease from induction study baseline total Mayo score (including PGA subscore) of ⩾3 points and ⩾30%, plus a decrease in rectal bleeding subscore of ⩾1 point or an absolute rectal bleeding subscore of 0 or 1. Modified clinical response was defined as a decrease from induction study baseline mMayo score (excluding PGA subscore) of ⩾2 points and ⩾30%, plus a decrease in rectal bleeding subscore of ⩾1 point or an absolute rectal bleeding subscore of 0 or 1. Endoscopic subscore was based on central read. p values versus placebo were based on the Cochran-Mantel-Haenszel chi-squared test, stratified by induction study treatment and baseline remission status. ***p < 0.001 versus placebo. BID, twice daily; CI, confidence interval; FAS, full analysis set; mMayo, modified Mayo; N, number of patients in the analysis set; n, number of patients achieving endpoint; NRI, nonresponder imputation; PGA, Physician Global Assessment; TNFi, tumor necrosis factor inhibitor.
Figure 4.
Figure 4.
Proportions of patients in remissiona at baseline of OCTAVE Sustain who achieved sustained steroid-free remission at weeks 24 and 52 of OCTAVE Sustain, defined by mMayo score and Mayo score, overall and stratified by prior TNFi failure status (FAS, NRI). Remission was defined as a total Mayo score (including PGA subscore) of ⩽2 with no individual subscore >1, and a rectal bleeding subscore of 0. Modified remission was defined as an endoscopic subscore of ⩽1, a stool frequency subscore of ⩽1, and a rectal bleeding subscore of 0. Sustained steroid-free remission was defined as being in remission and steroid-free (not requiring corticosteroid treatment for at least 4 weeks prior to study visit) at both weeks 24 and 52. Endoscopic subscore was based on central read. p values versus placebo were based on the Cochran-Mantel-Haenszel chi-squared test, stratified by induction study treatment. aSustained steroid-free modified remission at weeks 24 and 52 was evaluated among patients in modified remission at baseline; sustained steroid-free remission at weeks 24 and 52 was evaluated among patients in remission at baseline. *p < 0.05 versus placebo. **p < 0.01 versus placebo. ***p < 0.001 versus placebo. BID, twice daily; CI, confidence interval; FAS, full analysis set; mMayo, modified Mayo; N, number of patients in the analysis set; n, number of patients achieving endpoint; NRI, nonresponder imputation; ns, not significant; PGA, Physician Global Assessment; TNFi, tumor necrosis factor inhibitor.
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