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BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) trials often stratify patients by prior biologic exposure, including prior biologic failure or intolerance. This study aimed to assess clinical outcomes in IBD patients with prior biologic failure versus intolerance treated with ustekinumab or vedolizumab. METHODS: A post-hoc analysis of ulcerative colitis (UC) and Crohn's disease (CD) clinical trials for ustekinumab (UNITI, UNIFI) and vedolizumab (GEMINI-1, GEMINI-2) was performed. Clinical response, clinical remission, and endoscopic improvement (for UC) were compared among biologic naïve, biologic-failure, and biologic intolerant patients. Statistical analyses, including chi-square tests and logistic regression, were performed. RESULTS: 1178 UC and 1439 CD patients received either ustekinumab or vedolizumab. In UC, biologic intolerant patients exhibited higher clinical response (54.7% vs. 38.8%, aOR 1.87 [95% CI 0.93-3.73]), clinical remission (25.0% vs. 11.0%, aOR 2.84 [95% CI 1.47-5.49]), and endoscopic improvement (40.6% vs. 24.8%, aOR 2.76 [95% CI 1.28-5.94]) compared to biologic failure, with outcomes similar to biologic naïve patients. In biologic-intolerant CD patients, clinical response was similar between prior biologic failure and intolerance (34.2% vs 32.8%), but after adjustment for potential confounders, biologic intolerance was associated with higher odds of clinical response (aOR: 1.67, 95% CI 1.09-2.55), with no significant difference observed for clinical remission (aOR: 1.48, 95% CI 0.88-2.49). CONCLUSION: Improved treatment outcomes were generally observed in patients with biologic intolerance compared to failure, especially in UC, where outcomes were similar to biologic naïve patients. Future clinical trials should meticulously differentiate prior biologic failure versus intolerance to mitigate potential bias.

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INTRODUCTION: It is unclear if steroid tapering protocols can impact clinical trial outcomes in ulcerative colitis (UC), particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals and adaptive steroid tapering utilizes investigator discretion as determined by the patient's response. METHODS: In this post-hoc analysis from six clinical trials of UC (VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE and ULTRA2), responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for treat-through versus re-randomization designs and multivariate regression was performed to account for other potential confounding variables. The primary outcome was corticosteroid-free clinical remission (CR) at one-year and secondary outcomes were CR and endoscopic improvement. RESULTS: There was a total of 861 patients who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid tapering regimens were less likely to achieve corticosteroid-free CR at one year (odds ratio [OR] 0.66 [95% CI 0.48-0.92], p=0.015) but had increased odds for achieving CR at one year (OR 1.9 [95% CI 1.43-2.52], p<0.001). The steroid tapering regimen was not associated with achievement of endoscopic improvement at one year. CONCLUSIONS: Among patients with UC on corticosteroids in clinical trials, patients using adaptive steroid weaning regimens were less likely to achieve corticosteroid-free CR at one year but more likely to achieve CR at one year. Consideration should be given to implementing mandatory fixed steroid weaning protocols in future clinical trials of UC.

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Vedolizumab is a first-line treatment option for ulcerative colitis. There are differences in incidence of ulcerative colitis between males and females, but whether sex affects treatment outcomes is less clear. We examined sex-based differences in patients with ulcerative colitis initiated on vedolizumab from two major randomized controlled trials (RCTs). We conducted a post-hoc analysis on participants with ulcerative colitis from the VARSITY and GEMINI-1 RCTs who received vedolizumab. Outcomes of interest were rates of clinical improvement, clinical remission, and endoscopic improvement at weeks 6, 14, and 52 in male and female participants, as were differences in concentrations of trough vedolizumab and C-reactive protein; 1009 persons in GEMINI-1 and VARSITY trials were included. Male and female patients had similar disease characteristics aside from males being more likely to have Mayo 3 grade endoscopic severity at baseline (62.8 vs. 48.9%, P  < 0.001). At week 6, females were more likely to have endoscopic improvement (47.4 vs. 35.2%, P  = 0.001) and increased vedolizumab trough levels [34.0 (23.0-44.5) vs. 28.9 (19.0-34.6), P  < 0.001]. The probability of achieving clinical remission (28.9 vs. 34.5%, P  = 0.057) or endoscopic improvement (35.5 vs. 39.3%, P  = 0.212) at week 52 was not different between males and females. Females with ulcerative colitis treated with vedolizumab appear more likely to achieve early endoscopic improvement than males, though longer-term outcomes demonstrated no difference. Further studies are required to better understand mechanisms through which sex or sex-associated factors could influence response to therapy in ulcerative colitis.

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BACKGROUND & AIMS: We assessed Modified Multiplier Simple Endoscopic Score for Crohn's Disease (MM-SES-CD) and Simple Endoscopic Score for Crohn's Disease (SES-CD) thresholds that are best associated with low likelihood of long-term disease progression. METHODS: Data from 61 patients with early Crohn's disease (CD) who participated in the CALM long-term extension study were used as the derivation cohort and validated using the McMaster inflammatory bowel disease database (n = 99). The primary outcome was disease progression (new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery) since the end of the CALM trial. Optimal MM-SES-CD and SES-CD thresholds were determined using the maximum Youden index. Receiver operating characteristic curve analyses compared threshold scores of remission definitions on disease progression. RESULTS: In the derivation cohort, based on the maximum Youden index, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD <4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared with patients in the derivation cohort with MM-SES-CD <22.5 (10/17 [58.8%] vs 3/44 [6.8%]; P < .001). Similarly, a significantly greater number of patients with SES-CD ≥ 4 had disease progression compared with those with a SES-CD <4 (11/25 [44.0%] vs 2/36 [5.6%]; P < .001). Compared with other clinical or endoscopic remission definitions, which demonstrated poor to fair accuracy, MM-SES-CD <22.5 performed the best for predicting disease progression (area under the curve = 0.81; 95% confidence interval, 0.68-0.94; P < .001). These thresholds were confirmed in the validation cohort. CONCLUSION: Achievement of MM-SES-CD <22.5 or SES-CD <4 in patients with ileocolonic or colonic CD is associated with low risk of disease progression and may be suitable targets in clinical trials and practice for endoscopic healing.

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BACKGROUND: Brain-derived neurotrophic factor (BDNF) is an important factor in the development and neuroprotection of afferent auditory pathways. In this study, we investigated the expression of BDNF in the afferent auditory pathway after cochlear implantation (CI), hypothesizing that electrical stimulation after CI stimulates BDNF expression in the afferent auditory pathway. METHODS: Archival human temporal bones from eight patients with a history of CI and five patients with normal hearing (ages 65-93 years old) were studied. Temporal bone specimens were immunoreacted with rabbit polyclonal antibodies against BDNF and mouse monoclonal antibodies against pan-neurofilaments. In cases of unilateral CI, the BDNF expression was compared with the contralateral unimplanted ear and normal temporal bones without hearing loss. RESULTS: BDNF immunoreactivity (IR) localized to the spiral ganglion neurons (SGNs) somata and the surrounding satellite cells. BDNF-IR in the spiral ganglia was similar in the apical, middle, and basal hook regions. Neurofilament IR localized to SGN nerve fibers in both implanted and unimplanted cochleae. BDNF-IR in the SGN and satellite cells was significantly increased in the implanted specimens compared with the unimplanted specimens ( p < 0.05) and the normal hearing specimens ( p < 0.05). BDNF-IR expression was similar in the unimplanted cochlea and in the normal cochlea. BDNF protein expression was increased despite complete loss of the organ of Corti hair cells and supporting cells. Even in the cases of CI with a 6-mm first-generation electrode, BDNF expression was upregulated throughout the cochlea. CONCLUSIONS: BDNF expression in the SGN appears to be upregulated by the electrical stimulation from CI. This study provides evidence that the electrical stimulation from CI may stimulate the expression of BDNF, playing a neuroprotective role in the rehabilitation of hearing in the deafened ear.

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INTRODUCTION: Differences in 1-year outcomes among early and delayed responders have been demonstrated with some therapies in ulcerative colitis. However, it is unclear whether similar differences exist in patients with Crohn's disease (CD) treated with biologic therapies. METHODS: This was a post hoc analysis of patient-level data from the SEAVUE clinical trial program. Ustekinumab-treated and adalimumab-treated patients with clinical response at week 8, defined as a reduction in Crohn's Disease Activity Index (CDAI) score of at least 100 points from baseline or CDAI score <150, were deemed early responders and their outcomes were compared with delayed responders (week 8 nonresponders who subsequently responded at week 16) and nonresponders (no response at week 8 or 16). The primary outcome assessed was clinical remission at week 56, defined as CDAI <150. RESULTS: A total of 373 participants (187 treated with ustekinumab and 186 treated with adalimumab) were included in this analysis. The overall rate of delayed clinical response was low in the SEAVUE clinical trial program (13.1%). No differences were observed for week 56 clinical remission among early vs delayed responders to ustekinumab or adalimumab nor were there significant differences for secondary outcomes assessed. Delayed responders to ustekinumab and adalimumab had a significant decline in C-reactive protein by week 8 when compared with nonresponders. DISCUSSION: Among patients with moderate-to-severe CD, early and delayed responders to adalimumab and ustekinumab have similar 1-year clinical outcomes. Biomarker decline can be observed through the initial 8 weeks of therapy in patients who will eventually be delayed responders, which may help differentiate from nonresponders.

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INTRODUCTION: We developed and internally validated a prognostic scoring index for ulcerative colitis (UC) patients that includes baseline patient-reported outcomes (PROs), biomarkers, endoscopy, and histology for achieving 1-year endoscopic improvement (EI). METHODS: This post hoc analysis included 644 patients treated with ustekinumab induction therapy. Data were randomly split to obtain a 70% training and 30% testing cohort. Multivariate analyses assessed baseline variables and those with P < .05 were assigned weights based on their relative prognostic value from logistic regression modeling for predicting 1-year EI (Mayo endoscopic score ≤1). A cutoff was obtained by calculating the maximum Youden index and validated in the testing cohort. RESULTS: Prior biologic failure, albumin <40 g/L, C-reactive protein >5 mg/L, Mayo stool frequency subscore, endoscopic erosions/ulcerations, and chronic histologic structural/architectural changes demonstrated significant associations with 1-year EI and were included in the final model. The Ulcerative Colitis Severity Index (UCSI) had acceptable discriminative ability for 1-year EI in the training (area under the curve [AUC], 0.78; 95% confidence interval, 0.70-0.86) and testing cohort (AUC, 0.76; 95% CI, 0.68-0.85). Compared with the UCSI, the Mayo Clinic score demonstrated poor accuracy (AUC, 0.49; 95% CI, 0.40-0.58) for predicting 1-year EI (P = .0006). The UCSI predicted 1-year endoscopic healing (Mayo endoscopic score = 0), clinical remission (total Mayo Clinic score ≤2 and no subscore >1), partial Mayo score remission <2, and 2-item Patient-Reported Outcome score (Mayo stool frequency and rectal bleeding subscore = 0) with significantly greater accuracy compared with the Mayo Clinic score. DISCUSSION: The UCSI is an internally validated prognostic scoring tool that accurately predicts 1-year EI at baseline among moderate-to-severe UC patients initiating therapy. Further validation with additional datasets is needed.

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OBJECTIVE: To characterize the demographics of children receiving cochlear implantations, identify factors associated with delayed implantations, and trend these factors over time. DESIGN: Retrospective cross-sectional study. SETTING: Healthcare Cost and Utilization Project California State Ambulatory Surgery Database for calendar years 2018-2020. PATIENTS: Children 5 years or younger undergoing cochlear implantation. INTERVENTIONS: Cochlear implantation. MAIN OUTCOMES MEASURES: The population-controlled number of cochlear implantations was calculated and stratified by race and insurance. Early implantation was defined as implantation at age 2 years or younger. A mixed-effects logistic regression model was generated to identify factors associated with early implantation and how that association changed from 2018 to 2020. RESULTS: The final cohort included 467 children. The number of implantations increased from 141 to 175 implants from 2018 to 2020 (24.1% increase); 229 (49.0%) children were implanted at 2 years or younger. Medicaid insurance was associated with decreased odds of early implantation (odds ratio, 0.18 [95% confidence interval, 0.15-0.23], p < 0.001); this association with Medicaid insurance was significant when stratified across all racial groups. The percentage of children with Medicaid who were implanted at 2 years or younger increased from 20.9 to 62.0% from 2018 to 2020. CONCLUSIONS AND RELEVANCE: Among children in California, socioeconomic factors, in particular public insurance, are correlated with age of cochlear implantation. These disparities improved significantly from 2018 to 2020. Further investigation into changes and initiatives in California during this time frame may aid in directing national efforts to improve pediatric cochlear implantation access.

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BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus. Current treatment options are limited. One experimental therapy is antibodies against interleukin-5 (IL-5). However, it is unknown why some patients respond to anti-IL-5 treatment whereas others do not. We sought to delineate predictors of histologic response to anti-IL-5 therapy in pediatric EoE. METHODS: This post hoc analysis of a multicenter, double-blind clinical trial (ClinicalTrial.gov identifier: NCT00358449) evaluated mepolizumab for the treatment of EoE in pediatric patients. Predictors were assessed for their association with a histologic response at week 12 of treatment. A histologic response was defined as either <15 eosinophils per hpf or a reduction in peak eosinophil counts by ≥50%. Predictors on univariate analysis with P < 0.10 were included in multivariate logistic regression models. Statistical significance for multivariate comparisons was set at P < 0.05. RESULTS: Patients with a higher BMI were more likely to attain histologic response at week 12, defined as <15 eosinophils per hpf [aOR, 1.31; 95% confidence interval (CI), 1.07-1.60; P = 0.008]. Higher BMI (aOR, 1.70; 95% CI, 1.06-2.74; P = 0.029) and signs of exudate plaques on endoscopy (aOR, 18.30; 95% CI, 2.11-158.53; P = 0.008) were significant predictors of histologic response at week 12 where a histologic response was defined as a reduction in peak eosinophil counts by ≥50. CONCLUSION: Higher BMI and signs of exudative plaques on endoscopy may be predictors of histologic response in pediatric EoE patients treated with antibodies against IL-5. Further studies are needed to validate our findings.

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BACKGROUND & AIMS: Differences in 1-year outcomes among early compared with delayed responders to vedolizumab have been shown in ulcerative colitis. However, it is unclear whether similar differences exist with ustekinumab, and what factors differentiate delayed responders from nonresponders. METHODS: This study was a post hoc analysis of patient-level data from the UNIFI clinical trial. Ustekinumab-treated patients with clinical response, defined as a reduction in total Mayo score of 30% or more and 3 or more points from baseline with a reduction in their rectal bleeding subscore of 1 or more or a rectal bleeding subscore of 1 or less, at week 8 were deemed early responders and their outcomes were compared with delayed responders (week 8 nonresponders who subsequently responded at week 16). The primary outcome assessed was 1-year clinical remission, defined as a total Mayo score of 2 or less and no subscore greater than 1. RESULTS: We included 642 ustekinumab-treated patients, including 321 (50%) early responders, 115 (17.9%) delayed responders, and 205 (32.1%) nonresponders. No differences were observed for 1-year clinical remission among early vs delayed responders (132 of 321 [41.1%] vs 40 of 115 [34.8%]; P = .233), or for other outcomes assessed regardless of induction dose. Compared with early responders, delayed responders had more severe baseline Mayo endoscopic disease (88 of 115 [76.5%] vs 206 of 321 [64.2%]; P = .015) and abnormal baseline C-reactive protein level greater than 3 mg/L (83 of 115 [72.2%] vs 183 of 321 [57%]; P = .004). Compared with nonresponders, delayed responders had a significant decrease in C-reactive protein level (F-value [degrees of freedom, mean squares] [4, 844]; P < .0001) and fecal calprotectin level (F[4, 818]; P < .0001) through week 16. CONCLUSIONS: Compared with early ustekinumab responders, delayed responders had a greater inflammatory burden at baseline. Early and delayed responders had similar 1-year outcomes. Biomarker decline observed in delayed responders can help differentiate them from nonresponders.

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OBJECTIVE: In the absence of head-to-head clinical trials, indirect comparative studies are needed to help position therapies in ulcerative colitis (UC). We aimed to compare the efficacy of infliximab vs. tofacitinib for moderate-severe UC among biologic-naïve participants at post-induction. METHODS: This was a post-hoc analysis of patient-level data from four clinical trials including 659 biologic-naïve UC participants. We compared proportions of patients achieving week 8 clinical remission (CR), endoscopic improvement, and endoscopic remission. Clinical response at week 2 was also assessed. Multiple logistic regression models were adjusted for potential confounders identified as having an association with the outcome of interest on univariate analysis. Propensity scores were calculated to create a cohort of participants with similar distribution of baseline co-variates. RESULTS: Patients treated with infliximab had significantly greater odds of CR at week 8 compared to tofacitinib [88/242 (36.4%) vs. 100/417 (24.0%), aOR: 1.65 (95% CI 1.11-2.44), p = 0.013]. Endoscopic improvement at week 8 was also significantly greater among infliximab-treated patients [149/242 (61.6%) vs. 159/417 (38.1%), aOR: 2.12 (95% CI 1.45-3.10), p < 0.001]. Similar findings were observed with week 8 endoscopic remission [61/242 (25.2%) vs. 43/417 (10.3%); aOR: 2.72 (95% CI 1.66-4.46), p < 0.001]. A similar proportion of participants attained clinical response at week 2 [205/242 (84.7%) vs. 334/417 (80.1%), aOR: 1.48 (95% CI 0.93-2.37), p = 0.101]. Similar results were observed among the propensity score matched cohort. CONCLUSION: Based on the efficacy observed in this post-hoc analysis, consideration should be given to use of infliximab over tofacitinib for treatment of moderate to severe biologic-naïve UC. However, baseline characteristic mismatches persisted despite propensity score matching, and further studies are needed to confirm our findings.

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BACKGROUND AND AIMS: Evaluating histological outcomes in ulcerative colitis [UC] has become common in recent clinical trials. In this study, we explored the additional value of the combined endpoint of histo-endoscopic mucosal improvement [HEMI] compared with endoscopic improvement [EI] at post-induction [Week 14] and post-maintenance [1 year]. METHODS: This post hoc analysis included 620 UC participants with available data from the VARSITY trial. Participants achieving post-induction and post-maintenance HEMI [Mayo endoscopic subscore ≤1 and Geboes score <3.2] were compared across clinical outcomes, patient-reported outcomes [PROs], and inflammatory markers. Univariate analyses were performed to identify variables associated with the outcome of interest. Multivariate analyses included covariates with a p <0.05 on univariate analyses. RESULTS: Among the 468 patients with 1-year data available, a total of 166 [35.5%] attained HEMI and 209 [44.7%] attained EI at post-induction. No difference in achievement of clinical remission [CR] at 1 year was observed among those who attained post-induction HEMI vs EI (121/166 [72.9%] vs 147/209 [70.3%], p = 0.903). Similar findings were observed for the outcome of 1-year treatment failure (45/166 [27.1%] vs 55/209 [26.3%], p = 0.781). Patients who achieved HEMI at post-induction had lower total and partial Mayo scores and had the largest improvement from baseline. Faecal calprotectin and C-reactive protein [CRP] were also significantly lower among HEMI achievers at post-induction [p <0.001]. Similar findings were observed at post-maintenance. CONCLUSIONS: In this post hoc analysis, at post-induction, HEMI did not demonstrate additional prognostic value in predicting 1-year outcomes over EI. However, HEMI was associated with lower clinical disease activity at post-induction and at 1 year compared with endoscopic or histological outcomes in isolation.

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BACKGROUND & AIMS: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. METHODS: From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. RESULTS: A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I2 = 0%). CONCLUSIONS: Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.

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BACKGROUND: Indirect treatment comparisons using patient-level data are increasing in popularity within inflammatory bowel disease research. We compared the efficacy of adalimumab and vedolizumab for biologic-naïve moderate-severe ulcerative colitis (UC) using indirect comparisons of phase 3 clinical trials and compared the results to the RCT VARSITY. DESIGN: Pooled analysis of patient-level data from 518 biologic-naïve patients with UC was performed using GEMINI-1 and ULTRA-1. Proportions of patients achieving week 6 clinical remission and clinical response were compared, and propensity score matching and multivariate logistic regression were used to account for potential confounders. These results were compared to those derived from VARSITY. RESULTS: A numerically greater proportion of vedolizumab-treated patients from GEMINI-1 achieved week 6 clinical remission compared to those treated with adalimumab [136/388 (35.1%) vs. 38/130 (29.2%)]. Similar findings were observed among the propensity score matched cohort [33/110 (30.0%) vs. 25/110 (22.7%), adjusted OR (aOR) 1.56 (95% confidence interval (CI) 0.81-3.02), p = 0.187]. A similar magnitude for absolute difference in the proportions of patients achieving week 6 clinical remission was observed from VARSITY in vedolizumab compared to adalimumab [131/305 (43.0%) vs. 114/307 (37.1%), OR 1.27 (95% CI 0.92-1.76), p = 0.142]. CONCLUSIONS: In this post hoc analysis, a similar magnitude in the absolute difference of efficacy at week 6 among biologic-naïve patients was observed using indirect comparisons of phase 3 clinical trial data as was observed in VARSITY. Indirect comparisons using patient-level clinical trial data could be used to inform drug choices for future head-to-head trials and guide positioning of drugs in the absence of head-to-head trials.

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BACKGROUND: We compared the Simple Endoscopic Score for Crohn's Disease (SES-CD) and Modified Multiplied SES-CD (MM-SES-CD) scores with the Rutgeerts score for predicting clinical recurrence (CR) of postoperative Crohn's disease (CD). METHODS: This post hoc analysis of the prospective, multicenter, randomized, double-blind, placebo-controlled trial comparing remicade and placebo in the prevention of recurrence in Crohn's disease patients undergoing surgical resection who are at an increased risk of recurrence (PREVENT) study used receiver operating characteristic curve analyses to compare the Rutgeerts, SES-CD, and MM-SES-CD scores at week 76 for subsequent CR by week 104 in 208 participants. Multivariate logistic regression models evaluated cutoffs for the odds of experiencing CR by week 104, after adjustment for confounders. CR was defined as Crohn's Disease Activity Index score ≥200 and ≥70-point increase from baseline (or development of fistulas, abscesses, or treatment failure) and endoscopic recurrence by week 104, defined as Rutgeerts score ≥i2. RESULTS: The week 76 Rutgeerts score predicted CR by week 104 with fair accuracy (area under the receiver-operating characteristic curve [AUC], 0.74; 95% confidence interval [CI], 0.65-0.83), which was similar to the SES-CD ileum score (AUC, 0.72; 95% CI, 0.64-0.80) and the MM-SES-CD ileum score (AUC, 0.72; 95% CI, 0.63-0.80). Compared with cutoffs by the other scores, the MM-SES-CD total score ≥26 at week 76 had the highest odds ratio to predict CR by week 104. Patients with a week 76 MM-SES-CD total score ≥26 were 4.41 times (95% CI, 2.06-9.43, P < .001) more likely to have CR by week 104 compared with those with an MM-SES-CD total score <26. CONCLUSIONS: The SES-CD and MM-SES-CD perform similarly to the Rutgeerts score for predicting subsequent CR of postoperative CD. The MM-SES-CD threshold of ≥26 was predictive of postoperative CR. Clinicians and trialists could consider using the SES-CD or MM-SES-CD to assess postoperative CD given their ability to capture colonic disease recurrence and predict CR.

This post hoc analysis of clinical trial data demonstrated that the Simple Endoscopic Score for Crohn's Disease (SES-CD) and Modified Multiplied SES-CD (MM-SES-CD) perform similarly to the Rutgeerts score for predicting subsequent recurrence of postoperative Crohn's disease (CD). Clinicians and trialists could consider using the SES-CD or MM-SES-CD to assess postoperative CD.

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BACKGROUND: This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn's disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (ER). METHODS: This post hoc analysis of 2 clinical trials of infliximab in CD included 601 patients and evaluated baseline PRS variables (abdominal pain, stool frequency, and general well-being) as measured by the Crohn's disease activity index and their association with 6-month clinical remission (CR) (Crohn's Disease Activity Index<150), corticosteroid-free CR, and week 26/54 ER (absence of mucosal ulceration). Logistic regression models assessed the relationships between PRS and outcomes of interest. Receiver operating characteristic curve analyses compared the sensitivity and specificity of the different baseline PRS compared with baseline endoscopic scores for achievement of ER at weeks 26 and 54. RESULTS: No difference was found comparing patients with higher baseline PRS to those with lower PRS in achieving 6-month CR, 6-month corticosteroid-free CR, or week 26/54 ER. Modified multiplier of the SES-CD (MM-SES-CD) at baseline demonstrated a significant ability to predict week 54 ER (area under the curve, 0.71; 95% CI 0.65-0.78; P =0.017). CONCLUSIONS: Baseline PRS in CD is not prognostic of clinical or endoscopic response. In contrast, active endoscopic disease as measured by the MM-SES-CD, more accurately predicts endoscopic outcomes. Endoscopic scores such as the MM-SES-CD may be considered for selection criteria and as a primary outcome of interest in CD trials, with PRS as a co-primary or secondary endpoint.

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Although inflammatory bowel disease [IBD] affects an increasingly diverse patient population, most patients in IBD clinical trials are White. Acknowledging current barriers and taking meaningful action is required at multiple levels to improve racial diversity across clinical trials in IBD. Ultimately, improving racial diversity in trials can in turn improve the care received by the diverse patients seen in clinical practice.

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BACKGROUND & AIMS: High placebo response rates in clinical trials of ulcerative colitis (UC) have been reported previously. However, data from patient-level analyses are lacking. We assessed factors associated with clinical and endoscopic placebo response among placebo-treated patients in clinical trials of UC. METHODS: We performed a post hoc analysis of pooled clinical trial data from GEMINI-1, ACT-1, ACT-2, PURSUIT, ULTRA-2, OCTAVE-1, and OCTAVE-2. Predictors were assessed in placebo-treated patients for their association with end of induction (week 6 of 8) clinical response (reduction in total Mayo score of ≥3 and ≥30% from baseline with ≥1 point decrease in rectal bleeding subscore [RBS] or absolute RBS ≤1); clinical remission (total Mayo score ≤2 and no subscore >1); endoscopic healing (Mayo endoscopic subscore ≤1); partial Mayo score of 0; patient-reported outcome 2-item remission (RBS of 0 and stool frequency ≤1), resolution of rectal bleeding, and stool frequency normalization. Predictors on univariate analyses with P < .05 were included in multivariate logistic regression models. RESULTS: Placebo-treated patients with normal serum C-reactive protein and albumin levels were more likely to attain clinical response (71 of 437 [16.3%] vs 49 of 660 [7.4%]; adjusted odds ratio, 2.76; 95% confidence interval, 1.19-5.41; P = .018). Compared with patients with a Mayo endoscopic score of 2, patients with a Mayo endoscopic score of 3 were less likely to attain clinical response (105 of 556 [18.8%] vs 179 of 675 [25.9%]; adjusted odds ratio, 0.33; 95% confidence interval, 0.16-0.68; P = .003). Similar findings were observed for clinical remission and resolution of rectal bleeding. CONCLUSIONS: Biomarkers such as normal serum C-reactive protein and albumin and baseline endoscopic severity were found to affect placebo response rates in clinical trials of UC. These findings have implications for clinical trial design in UC.

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BACKGROUND: In placebo-controlled clinical trials for Crohn's disease (CD), some placebo-treated patients demonstrate improvement. However, it is unclear what factors contribute to placebo response and remission. METHODS: This was a post hoc analysis of 3 placebo-controlled clinical trial programs (GEMINI-2, UNITI-1/2, and CLASSIC-1) of moderate-severe CD evaluating the efficacy of vedolizumab, ustekinumab, and adalimumab. Baseline predictors of clinical remission at the end of induction (week 4/6), defined as Crohn's Disease Activity Index <150 were evaluated among placebo-treated patients. Clinical response (decrease in Crohn's Disease Activity Index ≥100 points from baseline) at the end of induction was also evaluated. Univariate analyses were performed and predictors with P < .10 were included in multivariable analyses. RESULTS: A total of 683 patients (148 from GEMINI-2, 470 from UNITI-1/2, and 65 from CLASSIC-1) treated with placebo were included. Of the predictors evaluated, C-reactive protein <5 mg/L (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.04-2.67; P = .035), albumin >40 g/L (OR, 1.57; 95% CI, 1.05-2.93; P = .023), and disease duration <5 years (OR, 1.70; 95% CI, 1.05-2.75; P = .032) were included in the multivariable model for clinical remission. Disease duration <5 years was the only variable that retained significance on multivariable analysis (adjusted OR, 1.67; 95% CI, 1.02-2.73; P = .040). For clinical response, isolated ileal disease and disease duration <1 year were included in the multivariable model, of which only the latter retained significance (adjusted OR, 1.84; 95% CI, 1.04-3.24; P = .035). CONCLUSIONS: Strategies that reduce placebo response rates in clinical trials of CD should be considered, including stratification or exclusion of subjects by disease duration and mild disease severity as measured by objective biomarkers.

Disease duration <5 years was independently associated with clinical remission at the end of induction. To reduce the placebo response rates in clinical trials, consideration should be given to stratification or exclusion of subjects by disease duration and mild disease severity as measured by objective biomarkers.

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