Anti-TNF Therapy and Lower Rates of Colon Cancer & Financial Hardship Due to IBD

M Aklkhayyat et al. Inflamm Bowel Dis 2021; 27: 1052-1060. Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy

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.

Related blog posts:

NH Nguyen et al. Inflamm Bowel Dis 1068-1078. National Estimates of Financial Hardship From Medical Bills and Cost-related Medication Nonadherence in Patients With Inflammatory Bowel Diseases in the United States

Using the National Health Interview survey (2015), the authors identified individuals with self-reported IBD and assessed national estimates of financial toxicity. Key findings:

  • 23% reported financial hardships due to medical bills, 16% of patients reported cost-related medication nonadherence, and 31% reported cost-reducing behaviors
  • Approximately 62% of patients reported personal and/or health-related financial distress, and 10% of patients deemed health care unaffordable
  • Inflammatory bowel disease was associated with 1.6 to 2.6 times higher odds of financial toxicity across domains compared with patients without IBD

My take: In addition to the physical and emotional toll of having IBD, there is also significant financial hardships for many.

2021 AGA Guidelines For Crohn’s Disease

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.

JD Feuerstein et al. Gastroenterol 2021; 160: 2496-2508. Full text: AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease

Full text: Spotlight

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.

Other points:

From Spotlight:

Radiomic Imaging in Crohn’s Disease

X Li et al. Gastroenterol 2021; 160: 2303-2316. Development and Validation of a Novel Computed-Tomography Enterography Radiomic Approach for Characterization of Intestinal Fibrosis in Crohn’s Disease

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.

Key findings:

  • 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.

Microscopic Disease Does Not Predict Relapse in Crohn’s Disease

AB Hu et al. Clin Gastroenterol Hepatol 2021; 19: 1226-1233. Full text: Ileal or Colonic Histologic Activity Is Not Associated With Clinical Relapse in Patients With Crohn’s Disease in Endoscopic Remission

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.

Key findings:

  • 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).

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

IBD Updates: Microbiome afer surgery, Anti-TNF agents NOT changing hospitalizations/surgeries, Biobanking Genetics

X Fang et al. Inflamm Bowel Dis 2021; 27: 603-616. Full Text: Gastrointestinal Surgery for Inflammatory Bowel Disease Persistently Lowers Microbiome and Metabolome Diversity

  • 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

C Verdon et al. Inflamm Bowel Dis 2021; 27: 655-661. No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015

Key findings:

  • 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.

K Gettler et al. Gastroenterol 2021; 160: 1546-1557. Full text PDF: Common and Rare Variant Prediction and Penetrance of IBD in a Large, Multi-ethnic, Health System-based Biobank Cohort

  • 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)

For the Next Insurance Appeal: Therapeutic Drug Monitoring in Adalimumab Treatment (Pediatrics) & Satire on Prior Authorizations

There is a lot of data supporting the use of therapeutic drug monitoring (TDM) for anti-TNF agents. A recent study (MJ Kim et al. JPGN 2021; 72: 870-876. Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients With Crohn Disease) adds to this data and supports increased adalimumab (ADL) dosing if below target values.

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.

Related blog posts:

Fort Jefferson, Dry Tortugas. The fort has reportedly 16 million bricks (I didn’t confirm this figure).

More satireOn Prior Authorizations:

Trial by Diet Approach for Crohn’s Disease in Children

RS Boneh et al. Clin Gastroenterol Hepato 2021; 19: 752-759. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn’s Disease

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).

Key findings:

  • 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.

Related blog posts:

Rhododendrum

NY Times: Crohn’s Disease is On the Rise (4/26/21)

NY Times: Crohn’s Disease Is on the Rise

Some excepts:

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…

Related blog posts:

Passive Smoking and Worsening Crohn’s Disease

S Scharrer et al. Inflamm Bowel Dis 2021; 27: 379-385. Passive Smoking Increases the Risk for Intestinal Surgeries in Patients With Crohn’s Disease

This was a retrospective cohort study which included 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking.

Key finding:

  • 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)

The associated editorial (RA John, RB Geary, pgs 386-387, Full Text: Smoking Cessation for Patients With Crohn Disease: Not Just for the Patient?) makes several useful points:

  • 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.”

STRIDE II -Updated Crohn’s Disease Target Goals

From Tauseef Ali’s Twitter Feed — a summary slide of Crohn’s disease targets for both pediatric and adult patients and a slide showing typical response/remission/healing times to medications.

From the following article: D Turner et al. Gastroenterology (12/31/20, Online Ahead of Print): DOI: 10.1053/j.gastro.2020.12.031 STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD

Recommendations were based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in two surveys and two voting rounds.