Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

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.

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

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.

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

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.

scholarly journals Vedolizumab in Combination With Corticosteroids for Induction Therapy in Crohn’s Disease: A Post Hoc Analysis of GEMINI 2 and 3

2019 ◽  
Vol 25 (8) ◽  
pp. 1375-1382 ◽  
Author(s):  
Bruce E Sands ◽  
Gert Van Assche ◽  
David Tudor ◽  
Gamar Akhundova-Unadkat ◽  
Rebecca I Curtis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Activity Index ◽  
Combined Therapy ◽  
Disease Activity Index ◽  
Efficacy And Safety ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background Combined therapy with vedolizumab and corticosteroids may improve clinical response or remission in Crohn’s disease. The aim of this study is to assess efficacy and safety/tolerability of vedolizumab plus stable doses of corticosteroids at baseline during induction therapy in moderately to severely active Crohn’s disease. Methods A post hoc exploratory analysis was performed on data from GEMINI 2 (NCT00783692) and GEMINI 3 (NCT01224171), which assessed outcomes following induction therapy over 6- and 10-week periods, respectively. Patients receiving vedolizumab or placebo were stratified by corticosteroid use at baseline. Efficacy endpoints were clinical remission (CR; Crohn’s Disease Activity Index [CDAI] score ≤150 points) and enhanced clinical response (ECR; decrease of ≥100 points in CDAI score from baseline), assessed at week 6 (GEMINI 2 and GEMINI 3) and week 10 (GEMINI 3). Safety endpoints included the incidence of adverse events. Results Vedolizumab plus corticosteroids resulted in higher CR rates than placebo plus corticosteroids at week 6 in GEMINI 2 and at week 6 and week 10 in GEMINI 3. More patients receiving vedolizumab plus corticosteroids achieved CR at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Vedolizumab plus corticosteroids also resulted in significantly higher ECR rates than placebo plus corticosteroids at all timepoints in both studies. More patients receiving vedolizumab plus corticosteroids achieved higher ECR rates at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Adverse event incidence was similar across groups. Conclusions Vedolizumab in combination with stable doses of corticosteroids at baseline may improve induction of clinical response or remission in moderately to severely active Crohn’s disease. Trial registration numbers NCT00783692, NCT01224171.

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

2019 ◽  
Vol 156 (6) ◽  
pp. S-1100
Author(s):  
Parambir S. Dulai ◽  
Laurent Peyrin-Biroulet ◽  
Kristen Hahn ◽  
Natasha Khalife ◽  
Dirk Lindner ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Control ◽  
Early Disease ◽  
Post Hoc Analysis ◽  
Surgery Rates ◽  
Post Hoc ◽  
The Impact

Week 6 Calprotectin Best Predicts Likelihood of Long-term Endoscopic Healing in Crohn’s Disease: A Post-hoc Analysis of the UNITI/IM-UNITI Trials

2020 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Predictive Performance ◽  
Drug Level ◽  
Symptom Improvement ◽  
Faecal Calprotectin ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
The Relationship

Abstract Objectives There is need for biomarkers as predictors of outcome of medical treatment in Crohn’s disease. The purpose of this study was to evaluate the predictive performance of faecal calprotectin for short- and long-term clinical and endoscopic outcomes. Methods This post-hoc analysis of the UNITI/IM-UNITI studies [NCT01369329, NCT01369342, and NCT01369355; YODA #2019–4026] included 677 patients to evaluate the relationship of Week 6 calprotectin cut-offs and changes from baseline assessments in calprotectin for prediction of outcomes at Weeks 8, 32, and 52, using receiver operating characteristic curves with comparisons of areas under the curve [AUC]. The relationship between clinical and biomarker assessments at Week 6 and endoscopic remission [ER] at Week 52 was evaluated using multivariate logistic regression models adjusted for confounders. Results A Week 6 calprotectin <250 mg/kg demonstrated a significant ability to predict Week 52 ER (AUC 0.709, 95% confidence interval [CI] 0.566–0.852, p = 0.014) with fair accuracy, and performed better than other calprotectin cut-offs and deltas from baseline for prediction of Week 52 ER. When adjusted for covariates, patients with a Week 6 faecal calprotectin <250 mg/kg had 3.48 times [95% CI 1.31–9.28, p = 0.013] increased odds of Week 52 ER. No other Week 6 clinical assessment [clinical remission or clinical response] or biomarker [CRP <5 or drug level] had an association with Week 52 ER. Conclusions In summary, the results of this post-hoc analysis suggest that Week 6 calprotectin levels < 250 mg/kg can be predictive of future endoscopic healing and may be more informative than clinical symptom improvement. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

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

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

Mo1864 ILEAL AND RECTAL ULCER SIZE IMPACTS ABILITY TO ACHIEVE ENDOSCOPIC REMISSION IN CROHN'S DISEASE: A POST-HOC ANALYSIS OF THE SONIC TRIAL

2020 ◽  
Vol 158 (6) ◽  
pp. S-954
Author(s):  
Neeraj Narula ◽  
Emily C. Wong ◽  
Achuthan Aruljothy ◽  
Parambir Dulai ◽  
Jean Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Rectal Ulcer ◽  
Ulcer Size ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc

scholarly journals The Ultimate Therapeutic Goal: Establishing and Maintaining Quality of Life

2004 ◽  
Vol 18 (7) ◽  
pp. 465-466
Author(s):  
Remo Panaccione
Keyword(s):  
Quality Of Life ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Related Quality ◽  
Disease Study ◽  
National Cooperative ◽  
The Impact

Outcomes in Crohn's disease clinical trials are traditionally reported in terms of remission and response rates according to the Crohn's Disease Activity Index (CDAI), which was developed as part of the National Cooperative Crohn's Disease Study (1). However, it has been argued that the CDAI does not measure the overall burden of the illness experienced by patients. An alternative is to assess the impact of a particular therapy on health-related quality of life (HRQL). HRQL not only measures the benefits of the therapy on disease symptoms but also is probably better at evaluating the trade-off between therapeutic efficacy and potential adverse effects.

Location but Not Severity of Endoscopic Lesions Influences Endoscopic Remission Rates in Crohn's Disease: A Post Hoc Analysis of TAILORIX

2020 ◽  
Vol 116 (1) ◽  
pp. 134-141 ◽  
Author(s):  
Pauline Rivière ◽  
Geert D'Haens ◽  
Laurent Peyrin-Biroulet ◽  
Filip Baert ◽  
Guy Lambrecht ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Remission Rates ◽  
Post Hoc

scholarly journals Anti-Mycobacterial Antibiotic Therapy Induces Remission in Active Paediatric Crohn’s Disease

2020 ◽  
Vol 8 (8) ◽  
pp. 1112 ◽  
Author(s):  
Gaurav Agrawal ◽  
Harrison Hamblin ◽  
Annabel Clancy ◽  
Thomas Borody
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Antibiotic Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Disease Activity Index ◽  
Mucosal Healing ◽  
Paediatric Patients ◽  
Endoscopic Remission ◽  
Paediatric Crohn’S Disease

Crohn’s disease is increasing in incidence and prevalence in younger people and is of a particularly aggressive nature. One emerging treatment targets Mycobacterium avium paratuberculosis (MAP), an organism implicated in the causation of Crohn’s disease. This study reviewed a cohort of paediatric patients with active Crohn’s disease treated with Anti-Mycobacterial Antibiotic Therapy (AMAT). Sixteen paediatric patients, the majority of whom had failed conventional immunosuppressive therapy, were treated with AMAT. Endoscopic remission was scored using the Simple Endoscopic Score for Crohn’s Disease and clinical remission was assessed using the Weighted Paediatric Crohn’s Disease Activity Index (wPCDAI). Inflammatory blood markers were also routinely recorded. Patients were followed up clinically and endoscopically during treatment after an average of two months (range 1–6) and 17 months (range 2–49), respectively. A significant reduction in both scores assessing clinical improvement (p < 0.001) and mucosal healing (p < 0.0078) was observed at these timepoints; 47% of patients had achieved clinical remission and 63% endoscopic remission. Haemoglobin and serum inflammatory markers normalised for more than 50% of the cohort by six months of treatment. No adverse effects were reported throughout treatment. This is the first report of Anti-Mycobacterial Antibiotic Therapy offering a safe and efficacious therapy for paediatric patients with Crohn’s disease. Further larger randomised studies are required in order to validate these findings.

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