Using a selected sample from a database with >62 million patients, this retrospective cohort study determined the rates of colorectal cancer among patients with IBD. Key finding:
Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn’s disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P < 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.0001.
My take: This study found an association between anti-TNF therapy and a reduced risk of CRC in patients with IBD.
A series of articles details the 2021 AGA Guidelines for Crohn’s disease (CD) including a clinical practice guideline (pg 2496-2508), a clinical decision support tool (2509-2510), a spotlight summary (pg 2511), a technical review (2512-2557), and a review of the recommendations (pg 2557-2262). I will highlight the first article.
For me the most important of their recommendations was #7:
In adult outpatients with moderate to severe CD, the AGA suggests early introduction with a biologic with or without an immunomodulator rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.
For moderate to severe CD, the authors support the use of anti-TNF therapy in combination with immunomodulators, support the use of ustekinumab and vedolizumab, and support the use of SC/IM (but not oral) methotrexate.
The authors are AGAINST the use of mesalamine/sulfasalazine products as well as corticosteroids for maintenance of remission for CD
Methods: This article describes the development a computed-tomography enterography (CTE)–based radiomic model (RM). This retrospective multicenter study included 167 CD patients who underwent preoperative CTE and bowel resection. 1454 radiomic features were extracted from venous-phase CTE and a machine learning–based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers.
In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate–severe from none–mild intestinal fibrosis was 0.888.
In the test cohort, the RM had an AUC of 0.816.
RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort
My take: This CT approach with RM allowed for accurate characterization of intestinal fibrosis in CD. The images look pretty cool too.
In this retrospective study with 129 patients (mean age 25 yrs, mean disease duration 14.5 yrs) whose CD was in clinical/endoscopic remission, the authors examined factors associated with clinical relapse within 2 years; this included dose escalation, change in therapy, need for systemic steroids, or CD-related hospitalization or surgery.
Within 2 y of endoscopic evaluation, 42 patients (32.6%) had a clinical relapse.
There were no significant differences in proportions of patients with active ileal CD (23.8%), quiescent CD (28.6%), or normal histology (37%) between those who relapsed and those remaining in remission (P = .43). In addition, there was no no association between histologic features of active disease in ileal histology biopsies and symptom scores (Harvey Bradshaw index and simple inflammatory bowel disease questionnaire scores)
There were no significant differences in proportions of relapses among patients with active colonic disease (38.1%), quiescent disease (35.0%), or normal histology (27.9%, P = .73).
My take: In terms of outcomes, clinical and endoscopic remission are important but whether histologic remission is needed is unclear (at this time).
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Methods: The UC San Diego IBD Biobank was used to prospectively collect 332 stool samples (every 6 months) from 129 subjects (50 ulcerative colitis; 79 Crohn’s disease). Of these, 21 with Crohn’s disease had ileocolonic resections, and 17 had colectomies.
Key finding: Intestinal surgeries in IBD patients seem to reduce the diversity of the gut microbiome and metabolome in IBD patients. Colectomy has a larger effect than ileocolonic resection.
Limitations: Confounding variables (eg. antibiotics) and selection bias (patients with more severe disease
34,644 newly diagnosed patients with IBD (CD = 59.5%)
The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs. However, the authors note that “in the present study, biologics use under the public reimbursement plan was 13% in patients with UC and 16% in patients with CD.”
My take: This study is provocative but probably misleading; it is quite likely that use of anti-TNF agents do lower the risk of hospitalization and surgery.
Methods: The authors used the Mount Sinai BioMe Biobank, which contains genetic data on 32,595 patients. After rigorous phenotype validation, 19,541 individuals were retained, of whom 339 were IBD patients (273 CD, 28 UC, and 37 individuals who were classified as both) and 19,202 were controls
Key findings: In this study, the authors identified several rare VEO-IBD variants with high genetic penetrance using the biobank samples and then replicated results in large case control African American and European data sets.
One of the variants with the highest genetic penetrance located in the gene LRBA was predicted to result in a deleterious change to the amino acid structure. Reduced expression of CTLA-4 secondary to the variants we identified in LRBA may result in autoinflammation that contributes to IBD. “Targeting reduced CTLA-4 expression is an exciting treatment venue, because expression of CTLA-4 has been shown to be increased by chloroquine treatment in vitro.”
Enteropathy is present in 63% of all known individuals with LRBA deficiency, with 27% having chronic diarrhea as the presenting symptom
Mangroves in John Pennekamp State Park (Key Largo)
In this prospective study of 31 pediatric patients with Crohn’s disease, the authors found correlations between ADL values and the endpoints of clinical remission (CR) and mucosal healing (MH). The authors checked TLs at 4 months, 1, 2, and 3 years. Key findings:
The median trough levels (TLs) of ADL were higher in patients in CR (7.6 ± 3.5 μg/mL) than in patients with active disease (5.1 ± 2.2 μg/mL).
ADL TLs were significantly higher in patients who achieved MH than in those who did not (14.2 ± 7.6 vs 7.8 ± 5.2 μg/mL).
The optimal cut-point for predicting MH at 1 year of ADL treatment was 8.18 μg/mL
MH was noted in 42% at 4 months and 55% at 1 yr; CR was noted in 90% at 4 months and 84% at 1 yr. ADL treatment was associated with positive effects on growth indicators as well.
The authors discuss TDM for anti-TNF therapy, noting that for infliximab, the AGA recommends values >5 mcg/mL and the ACG >7.5 mcg/mL. There are fewer studies of ADL TDM -prior studies have indicated goals of >5.8, >7.1, >8, and >8.1; thus, this study is in agreement with these prior studies.
My take: This study further supports the value of TDM; better drug levels correlate with better outcomes.
AGA 2017 Guidelines on Therapeutic Monitoriing Proactive drug monitoring: “careful and selective use of proactive TDM could be beneficial, but current evidence for its routine use is limited and its overall benefits remain uncertain”
Fort Jefferson, Dry Tortugas. The fort has reportedly 16 million bricks (I didn’t confirm this figure).
The authors collected data from a multicenter randomized trial of the CD exclusion diet (CDED) in children (mean age, 14.2 ± 2.7 y) with Crohn’s disease who were randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (PEN) (n = 39).
The CDED has been discussed previously on this blog; it aims to avoid animal and saturated fat, milk fat, gluten, specific emulsifiers, taurine, red (reduced heme) and processed meat, and certain fibers from some fruits and vegetables. In addition to excluding patients who received competing therapies (eg. steroids, immunomodulators, and biologics), the authors excluded patients with isolated large bowel disease (L2).
At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a dietary response or remission. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001)
Among the 49 patients in remission at week 6, 46 patients (94%) had had a diet response or remission by week 3 and 81% were in clinical remission by week 3
The authors note that the rapid response to dietary therapy suggests a role for a ‘trial by diet’. As such, dietary therapy could be used as monotherapy, for patients failing other therapies, or as a bridge to biological therapy. The authors note that the exact reasons for response to dietary therapy are unsettled and could be “due to both foods excluded and foods enriched in the diet.” In addition, they note that diet appears to be a trigger for inflammation and that reintroduction of foods leads to rebound in inflammation (eg. higher calprotectin) and dysbiosis.
My take: This study shows that dietary therapy works quickly. In this small study, the effectiveness of combined CDED with 50% PEN was similar to EEN.
Dr. Joseph D. Feuerstein, gastroenterologist at Beth Israel Deaconess Medical Center in Boston… “It’s rising in incidence and prevalence throughout the world,” he said, and gastroenterologists are still trying to figure out why it shows up when it does in different people.
Crohn’s disease was first described in 1932 by Dr. Burrill B. Crohn…
Prompt diagnosis and appropriate therapy to suppress inflammation in the digestive tract are extremely important because a delay can result in scar tissue and strictures that are not reversed by medication…
Crohn’s is not curable and most patients have to stay on medication indefinitely. That can create yet another stumbling block. The biologics are very costly…
This was a retrospective cohort study which included 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking.
Exposed patients were more likely to undergo intestinal surgery than nonexposed patients (67% vs 30%; P < 0.001). Multivariate Cox regression analysis revealed that passive smoking was an independent risk factor for intestinal surgeries (hazard ratio, 1.7; 95% CI, 1.04–2.9; P = 0.034)
Smoking has long been identified as one of the strongest environmental risk factors for both the development of Crohn disease (CD) and the worsening of the disease course.
Studies in smokers with CD have reported that the risk of flares and complications matches that of nonsmokers with CD after 1 year of abstinence.
It would be reasonable to expect that a similar risk reduction exists for patients who can become passive-smoke-free. In addition, their likelihood of remaining smoke-free themselves is increased if they live in a smoke-free household.
My take (from editorial): “Clinicians should consider widening the scope of smoking cessation counseling to include not just patients but also their cohabitants.”