Abstract
Introduction
Rapid symptom relief is an important consideration for patients with ulcerative colitis (UC) experiencing a flare. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. We evaluated patient-reported symptomatic improvement from patients in the ELEVATE UC program.
Methods
This study was a post-hoc analysis of pooled daily e-diary data from patients with moderately to severely active UC receiving etrasimod or placebo in the phase III ELEVATE UC 52 and ELEVATE UC 12 trials. During the 12-week induction periods, patients self-reported stool frequency and rectal bleeding on days 1-28. Daily symptomatic response and symptomatic remission were calculated (partial modified Mayo Score).
Results
Overall, 787 patients (527 receiving etrasimod, 260 placebo) were included in the analysis. Etrasimod-treated patients had statistically significantly higher rates of symptomatic response and symptomatic remission during the first 28 days of therapy, with adjusted differences (95% CIs) reaching statistical significance from day 2 (5.6% [0.8-10.3], P = .022) to day 11 (4.7% [0.4-9.0], P = .034), respectively. In patients naïve to biologic/Janus kinase inhibitor therapy, symptomatic response was statistically significantly improved with etrasimod vs placebo from day 3 (8.9% [2.3-15.5], P = .008). Symptomatic improvement rates were similar with and without concomitant corticosteroid use.
Conclusions
In this post-hoc analysis, improvements in UC symptoms occurred in patients receiving etrasimod vs placebo from as early as day 2. These findings indicate a rapid onset of symptomatic effect with etrasimod treatment for moderately to severely active UC.
ClinicalTrials.gov numbers
Keywords: etrasimod, rapid symptom improvement, sphingosine 1-phosphate receptor modulator, ulcerative colitis
Graphical abstract
Graphical Abstract.
Key Messages.
What is already known?
Rapid symptom relief is an important treatment goal for patients with ulcerative colitis (UC), and the potential for early symptom improvement is often a key factor in treatment decisions.
What is new here?
This post-hoc analysis of the ELEVATE UC program demonstrated statistically significant improvements in ulcerative colitis symptoms with etrasimod vs placebo as early as day 2 after starting therapy.
How can this study help patient care?
These findings suggest a rapid onset of symptomatic effect with etrasimod treatment. Such data are valuable to inform treatment decisions and discussion of expected treatment effects with patients initiating etrasimod.
Introduction
Ulcerative colitis (UC) is a chronic, debilitating disease characterized by inflammation of the colon and rectum.1–3 Symptoms include rectal bleeding, bowel urgency, diarrhea, tenesmus, and abdominal cramping, all of which have a negative impact on patient health-related quality of life and daily functioning.1–4 While treatment goals in UC guidelines focus on inducing and maintaining long-term corticosteroid-free remission,3,5,6 it is recognized that rapid symptomatic relief is an important short-term goal for both patients and physicians.7–11 With an increasing number of advanced therapies available for the management of UC, optimizing patient care requires consideration of multiple patient-, disease-, and treatment-related factors.7,12 Among these, time from treatment initiation to symptom relief—particularly improvement of stool frequency and rectal bleeding—is considered a key component of treatment decision-making.11,12
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC.13,14 Etrasimod has demonstrated efficacy and safety in patients with UC across 2 pivotal phase III trials—ELEVATE UC 52 and ELEVATE UC 12.15 In both trials, patients treated with etrasimod demonstrated significantly higher rates of clinical remission than those treated with placebo over 12 weeks of induction therapy.15 Rapid symptom relief was observed, with greater symptomatic improvements with etrasimod vs placebo at week 2.15 However, to inform treatment decisions, patients and physicians need a clearer understanding of early symptomatic improvement during the first weeks of induction therapy.7,12
In this post-hoc analysis, daily symptom scores were evaluated for a pooled population of patients with moderately to severely active UC treated with etrasimod vs placebo in ELEVATE UC 52 and ELEVATE UC 12. Symptomatic response and remission, stool frequency response and normalization, and rectal bleeding response and remission were evaluated over the first 28 days of induction therapy to determine the earliest onset of symptomatic effect with etrasimod.
Methods
Study designs
The study designs for ELEVATE UC 52 and ELEVATE UC 12 (ClinicalTrials.gov numbers NCT03945188 and NCT03996369, respectively) have been described previously.15 In brief, both were phase III, multicenter, randomized, double-blind, placebo-controlled trials in patients with moderately to severely active UC. The ELEVATE UC 52 study spanned 52 weeks—a 12-week induction phase and a 40-week maintenance period. ELEVATE UC 12 comprised a 12-week induction period only. In both studies, patients were randomized in a 2:1 ratio to receive either etrasimod 2 mg once daily or placebo. The primary endpoint was the proportion of patients with clinical remission, at weeks 12 and 52 in ELEVATE UC 52 and at week 12 in ELEVATE UC 12, defined as a composite of stool frequency subscore (SFS) = 0 or SFS = 1 with a ≥1-point decrease from baseline, rectal bleeding subscore (RBS) = 0, and endoscopic subscore ≤1 (excluding friability).
Patients
Eligibility criteria have been published previously.15 Briefly, enrolled patients had moderately to severely active UC and an inadequate response, loss of response, or intolerance to ≥1 approved UC therapy. Moderately to severely active disease was defined as modified Mayo score (MMS) 4-9 with an endoscopic subscore of ≥2 and RBS of ≥1. Patients with isolated proctitis who met other inclusion criteria were eligible for enrollment up to a cap of 15% of the total study population.
Patients could receive concomitant treatment for UC with stable doses of oral aminosalicylates or corticosteroids during the 12-week induction period (investigators were directed to taper corticosteroids after week 12 in ELEVATE UC 52).15 Patients may have had previous exposure to biologic or Janus kinase inhibitor (JAKi) therapy but were excluded if they had received ≥3 biologics or 2 biologics and a JAKi.15
Assessments
All patients completed an e-diary to evaluate symptoms over the first 28 days of treatment. Patients were required to record stool frequency and rectal bleeding daily, and adherence to e-diary entry was assessed at each visit. Daily SFS was based on patient-reported stool frequency over a 24-hour period on a 4-point scale (0 = normal number of stools; 1 = 1-2 stools more than normal; 2 = 3-4 stools more than normal; 3 = 5+ stools more than normal), and daily RBS was based on patient-reported rectal bleeding over a 24-hour period on a 4-point scale (0 = no blood seen; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood passed alone). Daily partial MMS (pMMS; RBS plus SFS, 0 = none to 6 = severe) was calculated, and changes from baseline in pMMS, SFS, and RBS during the first 28 days of therapy were determined.
Statistical analyses
In this post-hoc analysis we evaluated symptomatic response and remission, stool frequency response and normalization, and rectal bleeding response and remission based on patient e-diary entries over the first 28 days of induction therapy. Symptomatic response was defined as ≥30% decrease from baseline in pMMS, stool frequency response as SFS = 0 or ≥1-point improvement from baseline, and rectal bleeding response as ≥1-point improvement in RBS from baseline. Symptomatic remission was defined as SFS = 0 (or SFS = 1 with ≥1-point improvement from baseline) and RBS = 0, and stool frequency normalization and rectal bleeding remission were defined as SFS = 0 and RBS = 0, respectively. Subgroup analyses for these endpoints were performed according to exposure to prior biologic/JAKi therapy at study entry and concomitant corticosteroid at baseline.
Statistical analyses used pooled data from the full analysis sets (ie, all randomized patients who received ≥1 dose of study treatment) with baseline MMS 4-9 from ELEVATE UC 52 and ELEVATE UC 12. The numbers and proportions of patients achieving each endpoint on each day (up to day 28) were reported by treatment group. The Mantel-Haenszel weighted method was used to assess common risk difference, the 95% CI, and the 2-sided P-value, with stratification by prior biologic/JAKi therapy at study entry (yes/no), baseline corticosteroid use (yes/no), and baseline disease activity (MMS 4-6 or 7-9). Patients with missing data for a specified day were considered non-responders. Reported P-values are not adjusted for multiplicity.
Results
Patients
A total of 787 study participants were included in the pooled analysis (etrasimod, 527 patients; placebo, 260 patients [see Figure S1A and S1B, showing patient flow diagrams for patients in ELEVATE UC 52 and ELEVATE UC 12]). Patient demographics and disease characteristics were similar between groups (see Table S1, showing patient demographics and disease characteristics at baseline) and have been described in full previously.15 Mean (SD) baseline pMMS, SFS, and RBS scores were the same in both the etrasimod and the placebo groups at baseline (4.0 [1.1], 2.4 [0.7], and 1.6 [0.7], respectively).
In the full analysis set, 163 (30.9%) patients in the etrasimod group and 84 (32.3%) in the placebo group had received previous biologic or JAKi therapy. Additionally, 158 (30.0%) etrasimod-treated and 76 (29.2%) placebo-treated patients were on corticosteroids at baseline. The baseline characteristics of these subgroups have been reported previously.16,17
Daily symptomatic response and remission
The proportions of patients achieving symptomatic response and remission were higher with etrasimod than with placebo during the first 28 days of induction therapy (Figure 1A and B). The differences between treatment groups reached significance at day 2 for symptomatic response (16.8% with etrasimod vs 11.2% with placebo; adjusted difference [Δ] 5.6% [95% CI, 0.8-10.3], P = .022 [Figure 1A]) and day 11 for symptomatic remission (13.6% with etrasimod vs 8.7% with placebo; Δ 4.7% [95% CI, 0.4-9.0], P = .034 [Figure 1B]).
Figure 1.
Daily symptomatic response (A) and remission (B) with etrasimod vs placebo.
Symptomatic response was defined as ≥30% decrease from baseline in pMMS (SFS plus RBS). Symptomatic remission was defined as SFS = 0 (or SFS = 1 with ≥1-point improvement from baseline) plus RBS = 0. aDay of first statistically significant adjusted difference between treatment groups. *P < .05, **P ≤ .01, ***P ≤.001 etrasimod vs placebo. pMMS, partial modified Mayo score; RBS, rectal bleeding subscore; SFS, stool frequency subscore; Δ, adjusted difference.
Between-group differences continued to increase to day 28 and were statistically significant at most timepoints after the first day of significant difference. At day 28, 61.6% of patients had achieved a symptomatic response with etrasimod vs 41.6% with placebo (Δ 16.2% [95% CI, 9.0-23.4], P < .0001) and 29.4% of etrasimod-treated vs 18.0% of placebo-treated patients had achieved symptomatic remission (Δ 9.5% [95% CI, 3.7-15.4], P = .002).
Daily stool frequency response and normalization
The proportions of patients achieving stool frequency response and normalization were higher with etrasimod than with placebo during the first 28 days of induction therapy (Figure 2A and B). The difference between treatment groups reached significance at day 8 for stool frequency response (23.4% with etrasimod vs 15.3% with placebo; Δ 7.6% [95% CI, 2.3-13.0], P = .006 [Figure 2A]) and at day 3 for stool frequency normalization (6.2% with etrasimod vs 2.4% with placebo; Δ 3.5% [95% CI, 0.9-6.1], P = .009 [Figure 2B]).
Figure 2.
Daily stool frequency response (A) and normalization (B) with etrasimod vs placebo.
Stool frequency response was defined as SFS = 0 or ≥1 point improvement from baseline. Stool frequency normalization was defined as SFS = 0. aDay of first statistically significant adjusted difference between treatment groups. *P < .05, **P ≤.01, ***P ≤.001 etrasimod vs placebo. SFS, stool frequency subscore; Δ, adjusted difference.
Response rates continued to increase to day 28 and were significantly greater with etrasimod than with placebo at most timepoints after the first statistically significant difference. At day 28, 42.9% of patients had achieved a stool frequency response with etrasimod vs 33.1% with placebo (Δ 7.3% [95% CI, 0.5-14.1], P = .035); 17.9% of etrasimod-treated vs 7.8% of placebo-treated patients had achieved stool frequency normalization (Δ 8.8% [95% CI, 4.4-13.1], P < .0001).
Daily rectal bleeding response and remission
The proportions of patients achieving rectal bleeding response and remission were higher with etrasimod than with placebo during the first 28 days of induction therapy (Figure 3A and B). The difference between treatment groups reached significance at day 12 for rectal bleeding response (46.1% with etrasimod vs 37.6% with placebo; Δ 7.9% [95% CI, 0.8-15.1], P = .030 [Figure 3A]) and day 15 for rectal bleeding remission (31.4% with etrasimod vs 25.2% with placebo; Δ 6.3% [95% CI, 0.1-12.5], P = .045 [Figure 3B]).
Figure 3.
Daily rectal bleeding response (A) and remission (B) with etrasimod vs placebo.
Rectal bleeding response was defined as ≥1-point improvement in RBS from baseline. Rectal bleeding remission was defined as RBS = 0. aDay of first statistically significant adjusted difference between treatment groups. *P < .05, **P ≤.01, ***P ≤.001 etrasimod vs placebo. RBS, rectal bleeding subscore; Δ, adjusted difference.
Response rates with etrasimod continued to increase to day 28 and were statistically significantly greater than with placebo at all timepoints after the first significant difference. At day 28, 64.9% of patients had achieved a rectal bleeding response with etrasimod vs 46.1% with placebo (Δ 15.0% [95% CI, 7.7-22.4], P < .0001), and 48.7% of etrasimod-treated vs 29.8% of placebo-treated patients had achieved rectal bleeding remission (Δ 15.8% [95% CI, 9.0-22.7], P < .0001).
Impact of biologic/JAKi therapy
During the first 28 days of therapy, the proportions of patients achieving symptomatic response and remission were higher with etrasimod than with placebo both for patients who were biologic/JAKi-naïve and for those who had previously received biologic/JAKi therapy (Figure 4A and B).
Figure 4.
Symptomatic response (A) and remission (B) by prior exposure to biologic/JAKi therapy.
Symptomatic response was defined as ≥30% decrease from baseline in pMMS (SFS plus RBS). Symptomatic remission was defined as SFS = 0 (or SFS = 1 with ≥1-point improvement from baseline) plus RBS = 0. aDay of first statistically significant adjusted difference between treatment groups among patients naïve to biologic/JAKi therapy. bDay of first statistically significant adjusted difference between treatment groups among patients previously exposed to biologic/JAKi therapy. *P < .05, **P ≤.01, ***P ≤.001 etrasimod vs placebo. JAKi, Janus kinase inhibitor; pMMS, partial modified Mayo score; RBS, rectal bleeding subscore; SFS, stool frequency subscore; Δ, adjusted difference.
Patients who were biologic/JAKi-naïve had a statistically significantly higher symptomatic response rate with etrasimod vs placebo as early as day 3 (24.1% vs 14.9%; Δ 8.9% [95% CI, 2.3-15.5], P = .008 [Figure 4A]), and a statistically significantly higher symptomatic remission rate at day 15 (18.7% vs 12.5%; Δ 6.1% [95% CI, 0.1-12.1], P = .046 [Figure 4B]). For patients who had previously received biologic/JAKi therapy, the difference between groups reached significance at day 18 for both symptomatic response (47.0% with etrasimod vs 32.4% with placebo; Δ 14.3% [95% CI, 2.0-26.6], P = .022 [Figure 4A]) and symptomatic remission (24.5% with etrasimod vs 10.8% with placebo; Δ 12.7% [95% CI, 3.7-21.7], P = .006 [Figure 4B]), although statistical significance was not consistently maintained over subsequent timepoints.
At day 28, of those patients who were biologic/JAKi-naïve, 67.1% and 31.1% in the etrasimod-treated group achieved symptomatic response and symptomatic remission, respectively, compared with 44.1% and 18.5%, respectively, in the placebo-treated group.
Daily stool frequency response, stool frequency normalization, rectal bleeding response, and rectal bleeding remission rates were generally increased with etrasimod vs placebo both for patients naïve to and those previously treated with biologic/JAKi therapy, with statistically significant differences between treatment groups reached earliest among patients who were biologic/JAKi-naïve [see Figure S2A-D, showing stool frequency response, stool frequency normalization, rectal bleeding response, and rectal bleeding remission by prior exposure to biologic/JAKi therapy].
Impact of concomitant corticosteroids
Overall, patients treated with etrasimod who received concomitant corticosteroids had symptomatic response and remission rates similar to those in patients who did not receive concomitant corticosteroids during the first 28 days of induction therapy (Figure 5A and 5B). Among patients who were not receiving concomitant corticosteroids, those treated with etrasimod vs placebo achieved a statistically significantly higher rate of symptomatic response at day 3 (24.4% vs 13.9%; Δ 10.4% [95% CI, 3.9-16.8], P = .002 [Figure 5A]), and a statistically significantly higher rate of symptomatic remission at day 11 (14.5% vs 7.5%; Δ 6.6% [95% CI, 1.5-11.6], P = .011 [Figure 5B]). A slower time to response was observed in patients receiving concomitant corticosteroids who achieved a statistically significantly higher symptomatic response with etrasimod vs placebo at day 18 (56.9% vs 32.9%; Δ 20.8% [95% CI, 8.0-33.5], P = .001 [Figure 5A]). A statistically significant difference in symptomatic remission rate with etrasimod vs placebo was observed at day 20 (26.6% vs 11.6%; Δ 12.9% [95% CI, 3.3-22.6], P = .009 [Figure 5B]).
Figure 5.
Symptomatic response (A) and remission (B) by concomitant corticosteroid use.
Symptomatic response was defined as ≥30% decrease from baseline in pMMS (SFS plus RBS). Symptomatic remission was defined as SFS = 0 (or SFS = 1 with ≥1-point improvement from baseline) plus RBS = 0. Patients in the “with corticosteroid” group received stable doses of concomitant oral corticosteroids for UC during the 12-week induction period. aDay of first statistically significant adjusted difference between treatment groups among patients not receiving concomitant corticosteroids. bDay of first statistically significant adjusted difference between treatment groups among patients receiving concomitant corticosteroids. *P < .05, **P ≤.01, ***P ≤.001 etrasimod vs placebo. pMMS, partial modified Mayo score; RBS, rectal bleeding subscore; SFS, stool frequency subscore; UC, ulcerative colitis; Δ, adjusted difference.
Daily stool frequency response, stool frequency normalization, rectal bleeding response, and rectal bleeding remission rates were also generally similar among patients with and those without concomitant corticosteroid treatment; however, patients not receiving concomitant corticosteroids reached a statistically significant difference between groups earlier than those receiving concomitant corticosteroids [see Figure S3A-D, showing stool frequency response, stool frequency normalization, rectal bleeding response, and rectal bleeding remission by concomitant corticosteroid use].
Discussion
In this post-hoc analysis of e-diary pooled data from ELEVATE UC 52 and ELEVATE UC 12, etrasimod was associated with a statistically significantly greater rate of symptomatic response compared with placebo from as early as day 2. A statistically significant difference in stool frequency response was observed from day 8 and in rectal bleeding response from day 12. Statistically significant differences in symptomatic remission were observed from day 11, stool frequency normalization from day 3, and rectal bleeding remission from day 15. Unlike other S1P receptor modulators, etrasimod uniquely provides a therapeutic dose from day 1 of treatment without the need for dose titration, which may contribute to the rapid onset of symptom relief among patients with moderately to severely active UC.15
For patients with UC, rapid symptom relief is one of the most important features of treatment.7–11 In this analysis, patients reported improvements that may differ from expected treatment effect patterns in UC; for example, it was observed that stool frequency demonstrated an earlier (day 8) separation from placebo than rectal bleeding (day 12). However, daily e-diary data in these studies used a shorter 24-hour recall period rather than a rolling 3-5 day average as commonly reported in other trials.18 Shorter recall periods reduce recall bias and improve data quality compared with longer ones. Importantly, in daily e-diary reporting, etrasimod-treated patients had rapid symptomatic improvements for both stool frequency and rectal bleeding within a period of a few days. Wide variations have been observed in time to clinical response among available treatment options, and understanding the expected time to achieve symptomatic relief is critical to optimizing treatment strategies.7,12 Patients have also expressed the negative impact of uncertainty surrounding the onset of action of new treatments.7 This post-hoc analysis of time to the earliest onset of symptom relief with etrasimod provides clinicians and patients with valuable data to inform treatment decisions and support discussion of the expected effects of etrasimod in UC. These data show that symptomatic improvements may occur as early as 2 days following treatment initiation, with rates of symptomatic response and remission continuing to increase through day 28. This rapidity of response with etrasimod is similar to that previously reported with JAKi therapy.19–22 Further research including head-to-head studies are needed to provide robust comparisons of the time to onset of response across advanced therapies.
With an increasing number of therapeutic options, the sequencing of advanced therapy is an important consideration in optimizing patient care. Previously reported subgroup analyses have demonstrated that both biologic/JAKi-naïve and biologic/JAKi-experienced patients achieve induction and maintenance of clinical remission with etrasimod; however, response and remission rates were highest among those who were biologic/JAKi-naïve.16 The present post-hoc analyses are consistent with the earlier findings, with etrasimod-treated patients who were biologic/JAKi-naïve demonstrating sustained symptomatic response from as early as day 3, while patients with prior exposure to biologic/JAKi therapy took a slightly longer time (starting day 18) to demonstrate a response. These findings further support the use of etrasimod as a first advanced therapy for treatment of moderately to severely active UC, which is reflected in recent updates to the American Gastroenterological Association guidelines that recommend etrasimod as a higher-efficacy treatment option for patients naïve to advanced therapies.5
Previous subgroup analyses showed that patients with and those without concomitant corticosteroid use during the 12-week induction periods of ELEVATE UC 52 and ELEVATE UC 12 had higher rates of clinical remission with etrasimod vs placebo.17 Further post-hoc analyses of the ELEVATE UC trials found no additional benefit of concomitant corticosteroids in etrasimod-treated patients at week 12 or week 52 of treatment, and safety was comparable across the subgroups.23 Similar findings have also been observed in participants in upadacitinib and tofacitinib UC studies, in which baseline corticosteroid use did not affect treatment differences compared with placebo or the speed of treatment response of either compound.20,21 The current post-hoc analysis demonstrated similar trends during the first 28 days of therapy, with comparable rates of symptomatic improvement among patients with and those without concomitant corticosteroid treatment. Differences between treatment groups reached significance earlier in the subgroup of patients not receiving concomitant corticosteroids; however, this finding was likely affected by sample size, and the magnitude of response was similar between the subgroups over time. This similarity in the magnitude of response suggests the potential for etrasimod to provide rapid symptomatic relief for patients with moderately to severely active UC without the use of corticosteroids, and it will be important to investigate etrasimod as a possible corticosteroid-sparing induction therapy in future studies.
Other areas for future research include real-world comparisons of symptomatic relief achieved with etrasimod vs other advanced therapies in UC in routine clinical practice, and correlation of early symptomatic improvements with longer-term outcomes. Biomarker analyses will also be of interest to identify reliable predictors of symptomatic response and remission, and the time to onset of treatment effects.
Limitations
As with all post-hoc analyses, this study is associated with inherent limitations, and the findings require validation through further studies. The small sample size of some subgroups may limit broader interpretation and generalizability of the data, particularly when considering the statistical significance of treatment differences at specific timepoints; however, the trends observed may inform future research. The analysis also uses data reported each day rather than a rolling average of responses over 3-5 days, which may increase observed variability in response rates over time.
Conclusions
This post-hoc analysis of ELEVATE UC 52 and ELEVATE UC 12 e-diary data demonstrates that etrasimod has a rapid treatment effect, with symptomatic improvement in patients with moderately to severely active UC as early as day 2 for the overall population and day 3 for patients with no prior biologic or JAKi exposure.
Supplementary Material
Acknowledgments
The authors thank Séverine Vermeire of Universitair Ziekenhuis Leuven, Leuven, Belgium, for her involvement with the initial data analysis. Editorial/medical writing support under the guidance of the authors was provided by Abegale Templar, PhD, Elizabeth Harvey, PhD, and Andrea Bothwell, BSc, of the Galanthus Scientific Group and was funded by Pfizer Inc, in accordance with Good Publication Practice (GPP 2022) guidelines. All authors had access to study data and reviewed and approved the final manuscript. All patients in the study provided written informed consent.
Contributor Information
Marla C Dubinsky, Department of Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
María Chaparro, Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
Peter M Irving, IBD Unit, Guy’s and St Thomas’ National Health Service Foundation Trust, London, United Kingdom.
Peter Hur, HTA, Value & Evidence, Pfizer Inc, New York, NY, United States.
Sarah Sidhu, Global Medical Affairs, Pfizer Inc, New York, NY, United States.
John C Woolcott, Global Medical Affairs, Pfizer Inc, Collegeville, PA, United States.
Wenjin Wang, Pfizer Inc, Collegeville, PA, United States.
Martina Goetsch, I&I Research and Development, Pfizer AG, Zurich, Switzerland.
Joana Torres, Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Lisbon, Portugal; Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal; Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Remo Panaccione, Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.
Author contributions
Conceptualization: M.G.; data curation: M.G.; methodology: M.G.; formal analysis: S.S., J.C.W., W.W., M.G.; writing—review and editing: M.C.D, M.C., P.M.I., P.H., S.S., J.C.W., W.W., M.G., J.T., R.P.; data interpretation: M.C.D., M.C., P.M.I, P.H., S.S., J.C.W., W.W., M.G., J.T., R.P.; final approval: M.C.D, M.C., P.M.I, P.H., S.S., J.C.W., W.W., M.G., J.T., R.P; S.S. is a former Pfizer employee and was involved in the design of the study, developing the study protocol, and analyzing the data.
Supplementary data
Supplementary data are available at Inflammatory Bowel Diseases online.
Funding
This study was sponsored by Pfizer Inc. The sponsor participated in study design, data collection, data analysis, data interpretation, and review and approval of the manuscript.
Conflicts of interest
M.C.D. has been a consultant and advisor for AbbVie, Abivax, AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, F. Hoffmann-La Roche Ltd, Janssen Pharmaceuticals, Johnson & Johnson, Merck, Pfizer Inc, Prometheus Labs, Sanofi, Spyre, and Takeda Pharmaceuticals. M.C. has served as speaker or consultant or received research or education funding from AbbVie, Biogen, Dr Falk Pharma, Ferring, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Shire Pharmaceuticals, Takeda, and Tillotts Pharma. P.M.I. has received lecture fees from AbbVie, BMS, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, Janssen, Lilly, MSD, Pfizer, Sandoz, Sapphire Medical, Shire, Takeda, Tillotts, and Warner Chilcott; received financial support for research from Celltrion, Galapagos, MSD, Pfizer, and Takeda; and has been an advisor for AbbVie, Arena, Boehringer-Ingelheim, BMS, Boomerang Medical, Celgene, Celltrion, Elasmogen, Endpoint Health, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Samsung Bioepis, Sandoz, Takeda, Topivert, VH2, Vifor Pharma, and Warner Chilcott. P.H. is an employee and shareholder of Pfizer Inc. S.S. was an employee and shareholder of Pfizer Inc at the time of the study. J.C.W. is an employee and shareholder of Pfizer Inc. W.W. is an employee and shareholder of Pfizer Inc. M.G. is an employee and shareholder of Pfizer Inc. J.T. has received advisory board/speaker fees from AbbVie, Janssen, Lilly, Pfizer, Sandoz, and Takeda, and has received grant support from AbbVie and Janssen. R.P. has been a consultant for Abbott, AbbVie, Abbivax, Alimentiv, Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Inviva, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mirador, Novartis, Oppilan Pharma, Odyssey, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Teva, Tillots, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; has received speaker fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals, and has been an advisory board member for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.
Ethical approval
Both studies were performed in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Study protocols and procedures were approved by the institutional review boards and/or independent ethics committees at each site.
Data transparency statement
These studies were preregistered with an analysis plan at ClinicalTrials.gov (NCT03945188 and NCT03996369). Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual deidentified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.
Declaration of generative AI and AI-assisted technologies in the writing process
A generative artificial intelligence tool (01/31/2025; Pfizer; GPT-4o) was used in the production of this manuscript to assist with drafting the Methods and Results sections. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the integrity of the content of the publication.
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