Comparative Efficacy of Infliximab vs Ustekinumab for Maintenance of Clinical Response in Biologic Naïve Crohn’s Disease

Abstract

Background

There is a need to better understand the positioning of biologic therapies for long-term outcomes in biologic-naïve Crohn’s disease (CD). We assessed the comparative effectiveness of infliximab and ustekinumab among induction responders for 1-year outcomes.

Methods

This post hoc analysis included data from 220 biologic-naïve CD participants with response to induction therapy from 2 clinical trial programs. Participants achieving 1-year clinical remission (CR) (Crohn’s disease activity index <150), corticosteroid-free CR, normalization of fecal calprotectin (FC), endoscopic response (Simple Endoscopic Score for CD decrease ≥50% from baseline), and endoscopic remission (ER) (Simple Endoscopic Score for CD <3) were compared. Multivariate logistic regression evaluated the likelihood of achieving the outcomes adjusted for confounders. Propensity score matching created a cohort with similar distribution of baseline covariates.

Results

One-year CR and corticosteroid-free CR rates were similar between infliximab-treated and ustekinumab-treated patients (CR, 66 of 110 [60.0%] vs 63 of 110 [57.3%]; adjusted odds ratio [aOR], 1.15; 95% CI, 0.67-1.98; P = .681; corticosteroid-free CR, 11 of 28 (39.3%) vs 27 of 51 [52.9%]; aOR, 0.58; 95% CI, 0.23-1.47; P = .251). Compared with ustekinumab-treated patients, infliximab-treated participants were more likely to achieve 1-year endoscopic response (43 of 92 [46.7%] vs 6 of 30 [20.0%], aOR, 3.59; 95% CI, 1.34-9.66; P = .011) and ER (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR, 3.35; 95% CI, 1.07-10.49; P = .038). Among patients with FC ≥250 mg/kg at baseline, normalization (<250 mg/kg) at 1-year was similar between groups. Similar results were observed within the propensity matched population for all analyses.

Conclusions

Treatment with infliximab and ustekinumab among induction responders achieved 1-year CR with similar efficacy, but infliximab may confer greater benefit for endoscopic outcomes. Findings should be interpreted with caution as our analyses were unpowered.

Introduction

Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract clinically characterized by periods of remission and relapse or a chronically active course. Biologic therapies have vastly improved the outcomes and quality of life for patients with CD. Early biologics include tumor necrosis alpha (TNF-α) antagonists, such as infliximab, adalimumab, and certolizumab pegol.^1–3 Unfortunately, approximately one-third of biologic-naïve CD patients do not respond to induction therapy, and nearly 45% of initial responders will eventually lose response, with immunogenicity commonly implicated.^4–6 Recently, advances in drug development have expanded the range and modes of action of biologics beyond TNF-α antagonists, offering new strategies to manage patients with moderate to severe CD and inadequate response to TNF-α antagonists. Several novel therapies, including vedolizumab (anti-α4β7 integrin) and ustekinumab (anti-p40) have been approved for moderate to severe CD based on phase 3 placebo-controlled clinical trials.^7–9

Given the availability of different biologic agents, there is increasing interest among clinicians to better understand the positioning of agents. Attempts at indirect comparisons using network meta-analyses have been made. However, these trials are unable to accurately account for patient or trial level confounders including biologic exposure status to inform positioning of therapies. Prior network meta-analyses have suggested that infliximab and adalimumab are ideal first-line therapies, but the recent SEAVUE trial has suggested that adalimumab and ustekinumab have similar efficacy in biologic-naïve patients. Although SEAVUE specifically studied adalimumab, the results bring into question whether infliximab and ustekinumab may also therefore have similar efficacy as first-line agents.

Given the chronic and progressive nature of CD, sustained clinical response is an important treatment target of CD. Clinical trials for CD often assess clinical response at the end of induction as part of rerandomization criteria for entry into the maintenance portion of the study, and CR is typically the primary or coprimary end point at the end of maintenance. However, it is unclear whether early clinical response to induction therapy can inform longer-term outcomes among biologic-naïve CD patients. Hence, we conducted a post hoc analysis of patient-level data from clinical trials of infliximab and ustekinumab, comparing long-term efficacy in biologic-naïve patients with moderate to severe CD with initial response to induction therapy.

Methods

Data Acquisition

We conducted a post hoc analysis of patient-level data from 2 clinical trial programs of patients with moderate to severe CD. Data from patients treated with ustekinumab were obtained from UNITI-2 (NCT01369342) and IM-UNITI (NCT01369355) from the YODA (Yale Open Data Access #2021-4822) Project¹⁰ and with permission from Janssen Inc.^7,11,12 Data from patients treated with infliximab were obtained from a study comparing biosimilar and originator infliximab, herein referred to as the CT-P13 study (NCT02096861) and with permission from Celltrion Inc.¹³ Patients on biosimilar and originator infliximab were pooled in the current analysis. Patients enrolled in UNITI-2 and the CT-P13 study were biologic-naïve. As all patients provided informed written consent as part of the UNITI and CT-P13 studies, local ethics review was unnecessary for the current analysis because data were previously collected and deidentified. We conducted all analyses in accordance with Good Research for Comparative Effectiveness (GRACE) principles (Supplementary Table 1).¹⁴

Patient Population

The design and eligibility criteria of the UNITI studies have been published previously.⁷ Briefly, UNITI-2 was an 8-week induction trial and enrolled biologic-naïve adults with moderate to severe CD with prior failure to conventional therapies. Participants were randomized to receive a single intravenous 130-mg dose of ustekinumab, a 6-mg/kg weight-based dose of ustekinumab, or placebo. Clinical response defined as an improvement in the Crohn’s Disease Activity Index (CDAI) >100 points was assessed at week 8. Patients with a response were rerandomized in the maintenance study, IM-UNITI, which was 44 weeks in duration. The total study duration was 52 weeks. Clinical remission (CR) at week 44 (end of maintenance), defined as CDAI <150, was the primary end point of the maintenance trial. All concomitant medications were stable during the induction study with defined corticosteroid tapering protocols. This analysis included participants from the UNITI studies who responded to ustekinumab at week 6, continued receiving ustekinumab throughout the maintenance portion of the trial, and had endoscopic disease activity at week 6. Patients with no endoscopic disease activity, defined as Simple Endoscopic Score for CD (SES-CD) score of 0, were removed from this analysis.

Details regarding the design of the CT-P13 study have also been published.¹³ Biosimilar infliximab (CT-P13) and originator infliximab were compared in this noninferiority trial of 54 weeks in duration. Patients with moderate to severe CD and previous failure of conventional treatments were randomized in a 1:1:1:1 fashion to receive one of the following regimens: biosimilar continuously to week 30; biosimilar followed by a switch to originator at week 30; originator continuously to week 30; and originator followed by a switch to biosimilar at week 30. All treatments were administered as 5 mg/kg intravenous infusions at a standard induction (week 0, 2, and 6) and maintenance frequency (every 8 weeks thereafter to week 54). In this trial, patients achieved the primary end point if they demonstrated a reduction in CDAI from baseline to week 6 of at least 70 points. Clinical remission was also assessed as week 54. Concomitant medications remained stable during induction therapy, with defined steroid-weaning protocols. This analysis included participants from the CT-P13 study who responded to infliximab at week 6 and continued participating in the trial.

Exposures

The primary exposure of interest was ustekinumab (6 mg/kg intravenously at week 0 and 90 mg every 8 or 12 weeks to week 52) compared with originator and biosimilar infliximab (5 mg/kg intravenously at week 0, 2, 6, and every 8 weeks to week 54).

Outcome Assessments

CDAI

The CDAI is used to assess disease activity in CD and includes patient symptoms (eg, abdominal pain, stool frequency, and general well-being), findings from physical examination (eg, abdominal mass, body weight), laboratory findings (eg, hematocrit level), presence of extraintestinal manifestations, and use of antidiarrheal medication. A CDAI score <150 is often used as the primary maintenance end point in clinical trials of CD.

SES-CD

The Simple Endoscopic Score for CD (SES-CD) is routinely used in clinical trials of CD to assess the degree of endoscopic disease. The SES-CD is composed of 4 endoscopic parameters scored from a scale of 0 to 3 across each of the ileocolonic segments, with greater scores indicating more severe disease. Guidelines from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) have suggested that endoscopic remission (ER) can be defined as SES-CD <3.¹⁵ In UNITI and CT-P13, endoscopic scoring was conducted by blinded central readers.

MM-SES-CD

The Modified Multiplier of the SES-CD (MM-SES-CD) is an internally validated scoring tool that takes into consideration the relative prognostic value of each parameter of the SES-CD for achieving ER while on therapy.¹⁶ Descriptive statistics on the MM-SES-CD scores of the study population were reported as part of exploratory analyses.

Outcomes

The primary outcome of this study was CR at 1 year, defined as CDAI <150. Secondary outcomes at 1 year included corticosteroid-free CR among those with steroid use at the start of maintenance, endoscopic response (reduction in SES-CD ≥50%), endoscopic remission (ER, defined as SES-CD <3), and achievement of fecal calprotectin (FC) <250 mg/kg and <50 mg/kg at 1 year among those with elevated FC (>250 mg/kg) at baseline. C-reactive protein was not assessed in this analysis, as different assays were used in the UNITI and CT-P13 studies.

Statistical Analysis

Although this was not a direct head-to-head randomized controlled trial, we used several strategies to mitigate the effect of confounding factors. In univariate analyses, we identified covariates significantly associated with the outcome of interest and adjusted for these covariates in multivariate logistic regression models. Additionally, we created a cohort of participants with a similar distribution of baseline covariates by calculating and matching participants based on their propensity score for clinical and endoscopic outcomes.

We conducted multivariate logistic regression analyses to evaluate the effect of treatment on CR at 1 year, with adjustment for confounders found to have a significant association with the outcome on univariate analyses. Univariate analyses assessed baseline variables including age, baseline CDAI score, baseline SES-CD score, concomitant immunomodulator use, concomitant steroid use, disease duration, disease location, baseline FC (mcg/L), sex, and presence of nonpassable strictures at baseline. Variables with a P value <0.15 on univariate analysis were included in the multivariate model.

Propensity score matching was conducted on a one-to-one basis using k-nearest neighbor without replacement for 1-year clinical outcomes. A cohort of patients treated with ustekinumab and infliximab from the UNITI and CT-P13 studies was created with a similar distribution of baseline characteristics. For the evaluation of endoscopic outcomes, because there were fewer participants in UNITI with endoscopic data and lower rate of 1-year endoscopic outcomes compared with CT-P13, propensity score matching was also conducted to obtain a separate cohort of participants matched in a 1:2 ratio of ustekinumab to infliximab. Propensity scores were obtained from a nonparsimonious logistic regression model that included current smoking status, disease duration, disease location, presence of nonpassable strictures, concomitant steroid use, concomitant immunosuppressant use, CDAI score at baseline, and FC >250 mcg/L at baseline. Compared with models obtained from multivariate logistic regression, a greater number of variables were used as the occurrence of treatment is more common than the outcome.¹⁷ The propensity score is the probability of treatment assignment, conditional on the observed covariates. Propensity scores were graphed, and the degree of overlap between groups was assessed using the region of common support. Matched pairs were included in this analysis to assess the comparative effectiveness of treatments.

Proportions or percentages were used to present dichotomous variables, and means (and standard deviations [SDs]) or medians (interquartile ranges [IQRs]) were used to present continuous variables. The χ² or Mann-Whitney U test was used to evaluate differences in baseline characteristics. Proportions of patients achieving 1 year outcomes were compared between treatment groups using the χ ² test. Unadjusted odds ratios (ORs) and adjusted ORs (aORs) for each outcome are provided, with accompanying 95% confidence intervals (CIs). The threshold for statistical significance was set at a P value <0.05. Data were analyzed using Stata IC version 15.0.

Results

Supplementary Figure 1 outlines the selection of participants for this analysis. A total of 220 participants (110 in each treatment group) were included. Of the 220 participants in the CT-P13 study who received biosimilar or originator infliximab, 110 were excluded for nonresponse to induction therapy, leaving 110 participants in the infliximab cohort. All participants in the infliximab cohort had evidence of endoscopic disease (ie, SES-CD >0) at the end of induction. From UNITI-2, of the 628 participants randomized, 209 participants received 6 mg/kg of ustekinumab; however, 96 of these patients were excluded for nonresponse to induction therapy, and 3 were excluded for lack of endoscopic disease activity (ie, SES-CD of 0) at the end of induction, leaving 110 participants in the ustekinumab cohort.

Table 1 demonstrates the baseline characteristics of participants included in this analysis. Ustekinumab-treated participants were more likely to be receiving corticosteroids concomitantly (51 of 110 [46.4%] vs 28 of 110 [25.5%]; P = .001) and had greater baseline CDAI scores (308.4 [SD 5.9] vs 286.6 [SD 58.1]; P = .001), which deceased by week 6 (129.3 [SD 69.3] vs 165.0 [SD 94.0]; P = .002). Patients treated with ustekinumab had lower inflammatory burden as demonstrated by the number of involved segments at baseline and lower prevalence of nonpassable structures (26 of 110 [23.6%] vs 7 of 110 [6.4%]; P < 0.001). Otherwise, both groups were similar.

From this study population, a cohort of 190 participants treated with ustekinumab and infliximab were matched based on their propensity scores for the evaluation of clinical outcomes and 115 participants for the evaluation of endoscopic outcomes. Baseline characteristics of the propensity score–matched population are provided in Table 2. and distributions of propensity scores before and after matching are provided in Supplementary Figures 2 and 3. Several differences were observed between groups, including age, sex, number of involved segments, and concomitant steroid use. However, none of these variables demonstrated an association with 1-year CR on univariate analysis. Results from univariate analyses for the primary outcome of CR at 1 year are provided in Supplementary Table 2. Of the variables assessed, only disease duration had a P value <0.15 and was included in multivariate logistic regression models.

Achievement of Clinical Outcomes Using Infliximab vs Ustekinumab

Clinical outcomes among patients treated with ustekinumab and infliximab are presented in Tables 3 and 4. A similar proportion of infliximab-treated patients achieved CR at 1 year compared with those treated with ustekinumab (66 of 110 [60.0%] vs 63 of 110 [57.3%]; aOR 1.15; 95% CI, 0.67-1.98; P = .611). A total of 28 participants treated with infliximab and 51 participants treated with ustekinumab had concomitant corticosteroid use at the start of maintenance. Among these participants, no significant difference was observed for the outcome of 1-year corticosteroid-free CR (11 of 28 [39.3%] vs 27 of 51 [52.9%]; aOR 0.58; 95% CI, 0.23-1.47; P = .251).

In the propensity score–matched population, no differences were observed when infliximab-treated participants were compared with ustekinumab-treated participants for the outcome of 1-year CR (55 of 95 [57.9%] vs 56 of 95 [58.9%]; aOR 0.98; 95% CI, 0.55-1.74; P = .935) or corticosteroid-free CR (10 of 26 [38.5%] vs 23 of 43 [53.5%]; aOR 0.54; 95% CI, 0.20-1.47; P = .228; Tables 5 and 6).

Achievement of Endoscopic Outcomes Using Infliximab vs Ustekinumab

We also compared the effectiveness of infliximab and ustekinumab for achieving endoscopic outcomes in planned secondary analyses (Tables 3 and 4). This analysis was limited to 92 participants in CT-P13 and 30 participants in UNITI-2 with a baseline colonoscopy and evidence of endoscopic disease. A significantly greater proportion of participants treated with infliximab achieved ER at 1 year compared with participants treated with ustekinumab (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR 3.35; 95% CI, 1.07-10.49; P = .038). Similar findings were observed for the outcome of endoscopic response at 1 year (43 of 92 [46.7%] vs 6 of 30 [20.0%]; aOR 3.59; 95% CI, 1.34-9.66; P = .011). Among participants with nonpassable strictures at baseline, a similar proportion of participants treated with infliximab compared with ustekinumab had nonpassable strictures that persisted at 1 year (5 of 26 [19.2%] vs 1 of 7 [14.3%]; P = .763).

Similarly, in the propensity score–matched population, a greater proportion of infliximab-treated participants achieved 1-year ER (29 of 86 [33.7%] vs 3 of 29 [10.3%]; aOR 4.42 [95% CI, 1.23-15.86]; P = .015) and endoscopic response (37 of 82 [45.1%] vs 5 of 30 [16.7%]; aOR 4.41; 95% CI, 1.54-12.67]; P = .006). The proportion of participants with nonpassable strictures at baseline that persisted at 1 year were similar between groups (19 of 36 [52.8%] vs 4 of 5 [80.0%]; P = .250; Tables 5 and 6).

Normalization of Fecal Calprotectin Using Infliximab vs Ustekinumab

Among participants with a baseline FC >250 mcg/L, infliximab and ustekinumab demonstrated a similar ability to normalize FC to a level of <250 mcg/L by 1 year (16 of 71 [22.5%] vs 22 of 76 [29.0%]; aOR 0.68; 95% CI, 0.32-1.45; P = .317). As demonstrated in Tables 3 and 4, no significant differences were observed in the odds of achieving FC <50 mcg/L by 1 year among participants with FC >250 mcg/L at baseline (5 of 71 [7.0%] vs 11 of 76 [14.5%]; aOR 0.68; 95% CI, 0.32-1.45; P = .317).

Normalization of FC at 1 year was also compared in the propensity score–matched population (Tables 5 and 6). Again, no significant differences were seen between infliximab-treated and ustekinumab-treated participants for normalization of FC <250mcg/L (15 of 63 [23.8%] vs 21 of 70 [30.0%]; aOR 0.68; 95% CI, 0.31-1.51; P = .347) or <50mcg/L (5 of 63 [7.9%] vs 10 of 70 [14.3%]; aOR 0.43; 95% CI, 0.13-1.40; P = .163).

Discussion

In this post hoc analysis of data from 2 clinical trial programs of CD, several key findings emerged. First, infliximab and ustekinumab demonstrated similar efficacy for achieving 1-year CR among biologic-naïve CD participants with postinduction response. When we assessed corticosteroid-free CR at 1 year among those with corticosteroid use at the start of maintenance, no differences were observed between infliximab-treated and ustekinumab-treated participants. Second, favorable 1-year endoscopic outcomes were achieved among infliximab-treated patients, with a greater than 3-fold likelihood of achieving 1-year ER. Third, we observed no difference between infliximab and ustekinumab in the ability to normalize FC <250 mcg/L or <50mcg/L at 1 year among those with elevated FC >250 mcg/L at baseline.

Our findings provide novel insights when considered alongside previous analyses evaluating the comparative effectiveness of biologic agents in CD. Several comparative effectiveness studies have been conducted on biologic-naïve CD populations.^18–21 We previously reported similar rates of CR and clinical response at the end of induction therapy among biologic-naïve CD patients treated with infliximab and ustekinumab.²¹ Building on this evidence, network meta-analyses have attempted to position these biologic therapies. However, trials included in the evaluation of maintenance outcomes were designed to rerandomize responders to induction therapy regardless of previous biologic exposure.²² Therefore, the optimal positioning of biologic therapies for biologic-naïve CD remains unclear.

While head-to-head trials are ideal, only 1 trial in CD has been reported to date. The SEAVUE trial (NCT03464136) compared adalimumab and ustekinumab among biologic-naïve CD patients. Ustekinumab demonstrated similar efficacy for the achievement of clinical and endoscopic outcomes compared with adalimumab.²³ Similar rates of CR at 1 year were reported in SEAVUE (64.9% ustekinumab vs 61% adalimumab) as in our analysis (57.3% ustekinumab vs 60% infliximab). However, patients enrolled in SEAVUE were treated continuously with either ustekinumab or adalimumab, and it is unclear how outcomes differed among responders to induction therapy. Additionally, patients in SEAVUE had milder endoscopic disease with lower SES-CD scores compared with those observed in our analysis and were only required to have a single ileocolonic ulcer as assessed by the local endoscopist to be eligible for inclusion. As the body of evidence informing the optimal positioning of therapies in biologic-naïve CD continues to grow, several important considerations in treatment decision-making are worth noting. In SEAVUE, although there was no difference in efficacy and safety between ustekinumab and adalimumab, ustekinumab demonstrated longer retention and lower immunogenicity and has practical advantages over adalimumab, including less frequent dosing intervals (every 8 weeks for ustekinumab vs every 2 weeks for adalimumab) while providing similar efficacy. In real-world settings, additional factors such as patient preference, mode of administration, insurance reimbursement policies, and clinician judgment are often considered alongside treatment algorithms, allowing for a more nuanced decision-making process.

Our study has several strengths, including use of data from phase 3 clinical trial programs of CD with blinded central reading of endoscopies. However, our analyses are not without limitations. First, this was not a head-to-head trial of ustekinumab and infliximab, and we were unable to account for all confounding factors. Second, a cohort of participants in the UNITI studies participated in the endoscopic substudy, and we cannot rule out the possibility of selection bias for analyses evaluating endoscopic outcomes. However, in an attempt to mitigate the potential effect of selection bias on our findings, we excluded 3 patients with lack of endoscopic disease activity by week 6 and created a separate propensity score–matched cohort in a 1:2 ratio of ustekinumab-treated to infliximab-treated patients. Third, although the trials included in this analysis differed in design, we restricted the study population in both trials to those who responded to induction therapy at week 6 to mitigate this bias. It is worth noting that clinical response after induction was defined differently in CT-P13 (decrease in CDAI ≥70 points) and UNITI (decrease in CDAI ≥100 points or CDAI <150). Although we restricted analyses evaluating 1-year corticosteroid-free CR to those receiving corticosteroids at the beginning of maintenance, both IM-UNITI and CT-P13 trials had different steroid-weaning protocols. Patients entering IM-UNITI were required to demonstrate clinical response, and tapering was required at any point clinical response occurred. In contrast, patients entering CT-P13 had active CD, and tapering did not occur in CT-P13 until week 6. However, this is not felt to be a major source of bias considering differences in trial design and enrollment criteria.

Although we conducted propensity score matching as an additional sensitivity analysis, several differences between groups remained. Univariate analyses of these variables did not demonstrate any significant association with the outcomes of interest. In addition, analyses evaluating FC were limited to those with available data, and C-reactive protein was not evaluated, as different assays were used in the UNITI and CT-P13 trials. Treatments for CD should demonstrate an ability to reduce inflammatory markers of disease such as C-reactive protein and FC; future comparative effectiveness studies should evaluate this outcome. In our analysis, we observed a disconnect between FC levels and endoscopic outcomes at 1 year. Even though FC levels correlate well with endoscopy compared with endoscopy, FC tends to be less accurate, particularly in CD.²⁴ Several factors could lead to falsely elevated levels, including anastomotic ulcers, pseudopolyps, and use of nonsteroidal anti-inflammatories.²⁵ Although FC is a reliable biomarker for assessing endoscopic healing, it remains unclear if routine monitoring with FC alone can reliably replace endoscopic assessments of mucosal healing. To this end, a more nuanced approach may be appropriate, as the disconnect observed in our study provides evidence to suggest variation between patients with several factors aforementioned that can impact the accuracy of FC. Lastly, our analyses were not powered for endoscopic outcomes, which had small sample sizes, and it is possible statistical significance was not reached for some of the outcomes (eg, stricturing disease) evaluated due to low power. The estimates presented throughout this study had wide CIs and as a result should be interpreted with caution. Many of these limitations can be overcome in dedicated head-to-head trials, and the results of our study are meant to be hypothesis-generating and should not be considered confirmatory. Further studies are required to understand the comparative effectiveness of biologics.

In this post hoc analysis, ustekinumab and infliximab performed similarly in improving clinical outcomes among biologic-naïve CD patients. However, endoscopic disease at 1 year was significantly improved among patients treated with infliximab, which may be associated with better longer-term outcomes such as reduction in surgery rates. As more therapies become available for the treatment of CD, the need for head-to-head trials to inform the positioning of therapies continues to grow. However, to our knowledge, trials comparing ustekinumab and infliximab among biologic-naïve CD patients do not exist. In the absence of head-to-head clinical trials, our findings provide additional evidence in the evolving treatment paradigm of biologic-naïve CD.

Abbreviations

Abbreviations
 
• GRACE

  Good ReseArch for Comparative Effectiveness

 
• CD

  Crohn’s disease

 
• CR

  Clinical remission

 
• TNF-α

  Tumor necrosis alpha

 
• YODA

  Yale Open Data Access

 
• CDAI

  Crohn’s disease activity index

 
• SES-CD

  Simple Endoscopic Score for CD

 
• ER

  Endoscopic remission

 
• FC

  Fecal calprotectin

 
• OR

  Odds ratio

 
• aOR

  Adjusted odds ratio

 
• 95% CI

  95% confidence interval

 
• SD

  Standard deviation

 
• IQR

  Interquartile range

 
• MM-SES-CD

  Modified Multiplier of the SES-CD

Acknowledgments

This study, carried out under YODA Project # 2021-4822, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C.. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.

Author Contributions

E.W.—study concept and design; acquisition and compilation of data; statistical analysis; drafting of the manuscript

P.D.—study concept and design; data interpretation; drafting of the manuscript

J.M.—study design; drafting of the manuscript

V.J.—study design, drafting of the manuscript

W.R.—study concept and design; acquisition and compilation of data; data interpretation; drafting of the manuscript

N.N.—study concept and design; acquisition and compilation of data; statistical analysis; data interpretation; drafting of the manuscript

All authors approved the final version of the manuscript.

Funding

None.

Conflicts of Interest

P.D. is supported by a Research Scholar Award from the American Gastroenterology Association. Research support and/or consulting from Takeda, Janssen, Pfizer, Abbvie, Gilead, Lily, BMS, Novartis; stock options and board member for DigbiHealth; licensing royalties from Precidiag.

J.M. has received honoraria from Janssen, AbbVie, Allergan, Bristol-Meyer-Squibb, Ferring, Janssen, Lilly, Lupin, Merck, Pfizer, Pharmascience, Roche, Shire, Takeda and Teva.

V.J. has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, Teva, Topivert; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda.

W.R. has received support for the following:

Speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult,

Consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC,

Advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC.

N.N. has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Novartis, and Ferring.

No other authors have any relevant conflicts of interest.

Data Availability Statement

Data can be made available upon request to third parties.

References