Tu1726 – The Impact of Early Disease Control with Vedolizumab on Surgery Rates Among Patients with Crohn's Disease: A Post Hoc Analysis of the Gemini Trials

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] <150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score <3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

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Body Mass Index Does Not Impact Clinical Efficacy of Ustekinumab in Crohn’s Disease: A Post Hoc Analysis of the IM-UNITI Trial

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa214 ◽

2020 ◽

Author(s):

Emily C L Wong ◽

John K Marshall ◽

Walter Reinisch ◽

Neeraj Narula

Keyword(s):

Body Mass Index ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Body Mass ◽

Clinical Efficacy ◽

Activity Index ◽

Linear Trend ◽

Post Hoc Analysis ◽

Post Hoc ◽

The Impact

Abstract Background This post hoc analysis aimed to evaluate the impact of BMI on the efficacy of ustekinumab in the IM-UNITI study. Methods The relationship between body mass index (BMI) and efficacy of ustekinumab was evaluated using data from a 44-week maintenance study of ustekinumab in Crohn’s disease (IM-UNITI, NCT01369355, YODA #2019–4105). The primary endpoints of interest were clinical remission (CR), defined as Crohn’s disease activity index <150 and corticosteroid-free CR at week 44. Patients were stratified into the following subgroups according to their BMI at study entry: underweight <18.5 kg/m2, normal 18.5 to 25 kg/m2, overweight 25 to <30 kg/m2, and obese ≥30 kg/m2. The χ 2 test of linear trend was conducted for comparisons of frequencies between the 3 cohorts. Multivariate regression analyses evaluated possible association between BMI and efficacy outcomes of CR and corticosteroid-free CR, with adjustment for variables found significant on univariate analyses. Results are presented as odds ratios with 95% confidence intervals. Data were analyzed using Stata/IC 15. Results A total of 254 patients treated with ustekinumab were included in this analysis. At week 44 of IM-UNITI, rates of CR did not differ among those whose BMI was underweight (67.9%%; 19 of 28 patients), normal (51.3%; 60 of 117), overweight (45.1%; 32 of 71), or obese (55.3%; 21 of 38; P = 0.89). Multivariate logistic analysis did not find BMI to be a significant predictor of CR when adjusted for covariates. Ustekinumab drug level at week 44 was significantly lower in obese patients (median level 2.98 mcg/mL; interquartile range [IQR], 2.86) compared with patients who were overweight (4.84 mcg/mL; IQR, 3.51; P = 0.021) or had underweight or normal BMI (4.43 mcg/m;, IQR, 2.82; P = 0.014). Conclusions Although BMI impacts ustekinumab drug levels, there was no impact of BMI on clinical efficacy. Further studies of the pharmacodynamic effects of ustekinumab in patients with high BMI are needed.

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The impact of ustekinumab on extraintestinal manifestations of Crohn's disease: A post hoc analysis of the UNITI studies

United European Gastroenterology Journal ◽

10.1002/ueg2.12094 ◽

2021 ◽

Author(s):

Neeraj Narula ◽

Achuthan Aruljothy ◽

Emily C. L. Wong ◽

Ravi Homenauth ◽

Abdul‐Aziz Alshahrani ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Extraintestinal Manifestations ◽

Post Hoc Analysis ◽

Post Hoc ◽

The Impact

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P546 Ileal ulcer size significantly impacts the ability to achieve endoscopic remission: a post-hoc analysis from the SONIC trial

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.674 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S465-S465

Author(s):

N Narula ◽

E Wong ◽

A Achuthan ◽

P Dulai ◽

J F Colombel ◽

...

Keyword(s):

Crohn’S Disease ◽

Prognostic Factors ◽

Crohn's Disease ◽

Ulcer Size ◽

Logistic Regression Models ◽

Post Hoc Analysis ◽

Endoscopic Remission ◽

Index Of Severity ◽

Post Hoc ◽

The Impact

Abstract Background Endoscopic remission (ER) is an important target of treatment for Crohn’s disease (CD). However, it is unclear how individual baseline endoscopic characteristics impact the ability to achieve ER. We aimed to determine endoscopic prognostic factors that influence the likelihood of achieving ER in CD. Methods This was a post-hoc analysis of SONIC (NCT00094458; YODA #2019–3980), where data from 172 patients who had endoscopic scores at baseline and at week 26 were evaluated. Individual components of the Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn’s disease (SES-CD) indices were used to evaluate the impact of baseline ulcer depth (CDEIS) and size (SES-CD) on likelihood of achieving ER at week 26. Ileum and colon segments were evaluated separately. Multivariate logistic regression models were used to evaluate the relationship between baseline endoscopic findings and achievement of ER in each segment at week 26, after accounting for known confounders including disease duration and treatment allocation. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results The rate of ulcer improvement in the ileum was significantly lower than rates of healing throughout the colon (p < 0.0001) (see figure). Patients with ulcer size >2 cm in the ileum were less likely to achieve ER of the ileum compared with patients with ulcer size <2 cm (OR 0.31, 95% CI 0.11–0.89, p = 0.03). Ulcer size did not consistently impact likelihood of achieving week 26 ER in colonic segments. Patients with ileal ulcer size > 2 cm that were also deep were less likely to achieve ileal ER, when compared with patients with smaller or superficial ulcers (OR 0.10, 95% CI 0.02–0.68, p = 0.02). High baseline SES-CD score (>16) or CDEIS score (>12) did not impact the likelihood of achieving week 26 ER. Conclusion Ulcer size and depth, but not the overall degree of endoscopic inflammation, seem to impact likelihood of achieving week 26 ER. ER may be more difficult to achieve for patients with larger and deep ulcers in the ileum. These findings may have implications for recruitment into clinical trials and would support the importance of balancing these prognostic factors in trial arms. Further prospective data are needed to validate these findings.

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DOP019 Effect of vedolizumab treatment on extraintestinal manifestations in patients with Crohn’s disease: a GEMINI 2 post hoc analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.056 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S36-S38

Author(s):

B.G. Feagan ◽

W.J. Sandborn ◽

J.-F. Colombel ◽

S. O’Byrne ◽

J.M. Khalid ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Extraintestinal Manifestations ◽

Post Hoc Analysis ◽

Post Hoc

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Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn’s Disease: A Post Hoc Analysis From the CALM Study

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa025 ◽

2020 ◽

Vol 26 (10) ◽

pp. 1562-1571 ◽

Cited By ~ 2

Author(s):

Walter Reinisch ◽

Remo Panaccione ◽

Peter Bossuyt ◽

Filip Baert ◽

Alessandro Armuzzi ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Surrogate Marker ◽

Fecal Calprotectin ◽

Sensitivity Analyses ◽

End Points ◽

Predictive Values ◽

Post Hoc Analysis ◽

Post Hoc ◽

Disease Location

Abstract Background CALM was a randomized phase 3 trial in patients with Crohn’s disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. Results The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization. Conclusion This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD.

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