Advances in science have led to the development of multiple biologics and small molecules for the treatment of inflammatory bowel diseases (IBDs). This growth in advanced medical therapies has been ...accompanied by an increase in methodological innovation to study and compare therapies. Guidelines provide an evidence-based approach to integrating therapies into routine practice, but they are often unable to provide timely recommendations as new therapies come to market, and they have limited incorporation of real-world evidence when making recommendations. This limits the scope and usability of guidelines, and a gap remains in defining how best to position and integrate advanced medical therapies for IBD. In this review, we provide a framework for clinicians and researchers to understand key differences in sources of evidence, how different methodologies are applied to study the comparative effectiveness of advanced medical therapies in IBD, and considerations for how these sources of evidence can be used to better integrate current guideline recommendations. Over time, we anticipate this framework will allow for a transition to living guidelines and/or practice recommendations.
This study assesses two different disease activity measures, the MTWSI and the partial Mayo score, in hospitalized acute severe UC patients for prediction of post-discharge corticosteroid-free ...clinical remission and endoscopic improvement to help guide future considerations for disease activity assessment. In this post-hoc analysis from the TRIUMPH trial, these results suggest resolution of Mayo rectal bleeding sub-score may have high prognostic utility and could be considered as a primary endpoint for hospitalized UC trials. The study underscores the need for further research on patient-reported outcomes and endoscopic indices in larger populations for inpatient UC trials.
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.
The endoscopic scoring of ulcerative colitis is routinely used for both individual patient management and as an endpoint in clinical trials. The most commonly used scoring system is the Mayo ...endoscopic subscore, which scores endoscopic disease activity on a scale between 0 and 3. With only four possible scores and consideration of only the most involved area of the colon, the Mayo endoscopic subscore lacks sensitivity to change in measuring the totality of the endoscopic inflammatory involvement in patients with ulcerative colitis. Here, we present one case study from clinical practice and one from clinical trials in which using the Mayo endoscopic score leads to potentially incorrect conclusions. Further, in a post-hoc analysis, we re-examined endoscopic videos from a clinical trial and demonstrate that assessing involved ulcerated and affected areas on a segmental level of the colon or summing Mayo scores of colonic segments can identify improvements in endoscopic disease activity in almost twice as many subjects as identified by the Mayo endoscopic subscore alone. Although the alternative scoring systems we have used in this report will need further validation, our findings demonstrate the need for a more sensitive endoscopic scoring system in ulcerative colitis.
AbstractObjectiveTo evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD).DesignProspective cohort study.Setting21 low, middle, and high income ...countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China).Participants116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years.Main outcome measuresThe main outcome was development of IBD, including Crohn’s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals.ResultsParticipants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn’s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn’s disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD.ConclusionsHigher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods.Study registrationClinicalTrials.gov NCT03225586.
Background and Aim
Vedolizumab is a novel monoclonal antibody used in patients with inflammatory bowel disease, often affecting women of child‐bearing age. We aimed to compare maternal and fetal ...adverse outcomes in pregnancies of women with inflammatory bowel disease exposed to vedolizumab versus those on other treatment.
Methods
We performed a systematic literature search through December 2020 looking for studies including outcomes from pregnancies of female inflammatory bowel disease patients treated with vedolizumab. Our primary outcome was a composite of adverse pregnancy‐related events in pregnancies of female patients on vedolizumab compared with those of disease‐matched controls on other medication regimens. Events of interest included preterm births, early loss of pregnancy, late fetal death, elective termination of pregnancy, and congenital anomalies.
Results
Four studies were included in our review meeting criteria for our primary analysis. Compared with those with no vedolizumab exposure, pregnancies with vedolizumab exposure had an increase in overall adverse pregnancy‐related outcomes (odds ratio OR 2.18, 95% confidence interval CI, 1.52–3.13). The vedolizumab group also had increased preterm births (OR 2.16, 95% CI, 1.28–3.66), and early loss of pregnancies (OR 1.79, 95% CI, 1.06–3.01) but no difference in number of live births (OR 0.60, 95%CI, 0.36–1.00), or congenital malformations (OR 1.56, 95% CI, 0.56–4.37).
Conclusions
Our systematic review highlights possible concern with the general safety of vedolizumab in pregnancy, as an increase in overall total unfavorable outcomes was observed. Premature births and early loss of pregnancy were also more prevalent in pregnant female patients on vedolizumab. It is possible these findings are confounded by disease activity, and further prospective cohort studies of vedolizumab and pregnancy outcomes are warranted.
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