Tag Archives: Ulcerative colitis

VTE Protocol for Hospitalized Kids with IBD

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LG Hamant et al JPGN 2023; 76: 610-615. Venous Thromboembolism Prophylaxis in Pediatric Inflammatory Bowel Disease Patients Hospitalized With a Central Line

This article reviews the results of a venous thromboembolism (VTE) protocol that was implemented in 2018 in children with inflammatory bowel disease (IBD). A total of 313 hospitalizations across 187 different patients were identified that met criteria including IBD and central venous access. This retrospective review focused on children with IBD and and central venous catheter (CVC)  Key findings:

  • VTE prophylaxis increased from 5.24% (n = 12) prior to the intervention to 63.10% (n = 53) after the intervention
  • Rate of Doppler US increased from 9.17% (n = 21) prior to the intervention to 17.86% (n = 15) after the intervention
  • Diagnosis of VTE increased from 0.87% (n = 2) prior to the intervention to 7.14% (n = 6) after the intervention (attributed to better detection)

This article provides an algorithm for implementing VTE prophylaxis, recommending prophylaxis if 2 or more risk factors –both IBD and CVCs are risk factors. Mechanical prophylaxis (along with frequent ambulation, if feasible) is generally recommended if there are at least 2 risk factors, whereas anticoagulation prophylaxis is generally recommended if there are at least 4 risk factors. Other risk factors include being post-pubertal, obese, prolonged surgery (>90 minutes) within 2 weeks, altered mobility, and mechanical ventilation (see full protocol in article).

My take: In children at increased risk, the approach to reducing VTE in this article is quite sensible. Nevertheless, more research, especially with regard to institution of anticoagulation, is needed.

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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.

ARCH Study: Higher Doses of Infliximab in Acute Severe Ulcerative Colitis

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KG Whaley et al. Clin Gastroenterol Hepatol 2023; 21: 1338-1347. Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis

This was a multicenter prospective cohort of hospitalized children initiating IFX for ASUC or IBD-unclassified (n=38).

Key findings:

  • Compared to previous publications of pediatric ASUC, there was a low colectomy rate in this cohort of 2.7% at week 26 and 10.8% at 2 years
  • Median initial IFX dose was 9.9 mg/kg
  • Early rapid clearance was strongly associated with colectomy
  • Faster clearance was associated with higher WBC, presence of antibodies to infliximab and lower albumin. Higher platelets were associated with increased volumes of distribution. Concomitant immunomodulator use (26% with methotrexate, 13% thiopurine) “was not a significant covariate for PK parameters”

Discussion points:

  • Higher IFX dosing (10 mg/kg) may sufficiently optimize early outcomes in pediatric ASUC. Prior retrospective studies of adult and pediatric ASUC patients have supported lower colectomy rates with intensified induction regimens compared to standard induction regimens
  • The availability of vedolizumab may also have contributed to a lower colectomy rate
  • WBCs, “specifically neutrophils, may participate in the elimination of IFX”
  • Limitations: observational study, lack of dose standardization, lack of endoscopic outcomes

My take: Especially in pediatric patients, there is ample data to support using 10 mg/kg dosing for infliximab in patients with more severe inflammatory bowel disease, both ulcerative colitis and Crohn’s disease.

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Durability of Biologics in Children with Inflammatory Bowel Disease

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JL Kaplan et al. JPGN 2023; 76: 567-575. Open Access! Use, Durability, and Risks for Discontinuation of Initial and Subsequent Biologics in a Large Pediatric-Onset IBD Cohort

Methods: The authors analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry (n= 17,649) between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation

Key findings:

  • 7585 (43%) were treated with a biologic agent before age 18. 50% of children with Crohn’s disease (CD) received a biologic compared to 25% of children with ulcerative colitis (UC)
  • First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab)
  • Probability of remaining on first biologic in patients with CD: 93% at 6 months, 85% at 12 months, 79% at 24 months, and 74% at 36 months
  • Probability of remaining on first biologic in patients with UC: 84% at 6 months, 75% at 12 months, 66% at 24 months, and 55% at 36 months
  • First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%).

My take: This is an important study that shows that anti-TNF therapy durability was 79% in patients with CD and 66% in patients with UC at 2 years. This pediatric-specific information will help with counseling families when starting biologic therapy. There was improvement in durability after 2013 compared to prior -so perhaps perhaps even better durability is occurring in 2023. It is a little ironic that this study is from ImproveCareNow given that the results are quite dated. There have been a lot of changes in the last seven years. These include the widespread use of dose optimization/therapeutic drug levels and the approval of several new classes of targeted medications.

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Measurement of Exocrine Pancreatic Insufficiency in IBD and the Real-World

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J Fernandez et al. JPGN 2023; 76: 475-479. Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease

Methods: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD

Key findings:

  • 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). 
  • Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). 

In their discussion, the authors assert: “We can confidently recommend ePFT in established or new IBD patients who have stricturing and/or penetrating CD, weight loss, low weight Z-score, or qualify for the diagnosis of malnutrition.”

My take: In my real-world experience (~30 years), I have yet to have one patient presenting with IBD who needed pancreatic enzyme supplementation to reverse growth failure/malnutrition. As a consequence, I have a difficult time accepting the premise that more than 50% have EPI. To me, this suggests that testing children when they are acutely-ill or malnourished is yielding unreliable results.

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Targeting Calprotectin Levels Below 80 for Ulcerative Colitis Plus Obesity Medication Pushback

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K Kawashima et al. Inflamm Bowel Dis 2023; 29: 359-366. Low Fecal Calprotectin Predicts Histological Healing in Patients with Ulcerative Colitis with Endoscopic Remission and Leads to Prolonged Clinical Remission

In this prospective study (n=76), patients with UC in clinical and endoscopic remission, defined as a partial Mayo score (PMS) ≤ 2 points and a Mayo endoscopic subscore 0–1, were enrolled and followed for 2 years or until relapse, defined as a PMS > 2 or medication escalation.

Key findings:

  • The median fecal calprotectin (FC) value in patients with histologic healing (HH) (n = 40) was 56.2 µg/g, significantly lower than that in those with histological activity (118.1 µg/g; P < .01)
  • The optimal FC cutoff value to predict prolonged CR was 84.6 µg/g (72% sensitivity; 85% specificity; P < .01)

My take: Even among ulcerative colitis in clinical & endoscopic remission, fecal calprotectin levels are an objective way to identify histologic healing and to stratifying likelihood of prolonged remission.

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It is good to see some skepticism regarding the new obesity medications. 4/2/23 USA Today: Why experts worry the ‘magic’ in new weight loss medications carries a dark side

IBD Updates: Low Lymphoma Risk, Fewer Biopsies for Ulcerative Colitis, MRE Distinguishes Backwash Ileitis, Beta-Fructans and IBD Activity

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M Egberg et al. AJC 2023: 118: 354-359. Low Risk of Lymphoma in Pediatric Patients Treated for Inflammatory Bowel Disease

Key finding:

  • Using a database with 10,777 pediatric patients (2007-2018) with more than 28,000 patient years, there were 5 lymphomas reported. 4 had received thiopurines and none received anti-TNF monotherapy.

My take: This is a very reassuring study for the safety of anti-TNF agents.

AE Mikolajczyk et al. Inflamm Bowel Dis 2023; 29: 222-227. Assessment of the Degree of Variation of Histologic Inflammation in Ulcerative Colitis

  • In this retrospective study with 92 patients (182 colonoscopies), the authors found “minimal variability between degree of inflammation among biopsy fragments within and among different colorectal segments in UC, suggesting that even a single biopsy would adequately reflect the inflammation of the entire colorectum.”

My take: This study suggests that taking biopsies from every segment of the colon (when it looks uniform) is usually not needed, unless the purpose is to look for dysplasia. Also, it is worth recognizing that individuals with primary sclerosing cholangitis often have greater histologic activity in the right colon.

References only:

“Is Salt at Fault?” in Inflammatory Bowel Disease

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R Kuang et al. Inflamm Bowel Dis 2023; 29: 140-150. Is Salt at Fault? Dietary Salt Consumption and Inflammatory Bowel Disease

This review looks at the potential role of salt in relation to the epidemiology of inflammatory bowel disease. The general focus is that the prevalence/incidence of IBD has been increasing and there must be environmental/dietary factors involved. Could salt be one of those causal factors or is it merely a temporal association?

Key points:

  • Ultra-processed foods make up more than half of the daily caloric intake in developed countries such as the United States! and Canada and between one-third to one-fifth of diets in middle-income countries such as Brazil and Mexico.. Ultra-processed foods involve “fractioning of whole foods into substances, chemical modifications of these substances, frequent use of cosmetic additives and sophisticated packaging that allow producers to create highly profitable, convenient, and hyperpalatable products.” Ultra-processed foods are typically high in sugar, unhealthy fats, and salt and low in dietary fiber, protein, vitamins, and minerals. They are also calorie dense. For Americans, the primary source of sodium in the diet is from commercially processed foods.
  • At present, the typical American consumes over 40% more salt on a daily basis than is re-commended. Added salt is a key component of UPFs, whose increased consumption has been closely linked to this rise in the IBD incidence. Even though salt is a key component of UPFs, it has received limited attention in the investigation of IBD...Excess salt contributes to greater monocyte and T-cell-driven inflammation and a parallel loss of immunoregulatory mechanisms involving M2 macrophages and Tregs in the Th17 axis.
  • The authors argue that improvement in IBD with exclusive enteral nutrition is another factor indicating a potential role for salt reduction as beneficial. “Although these ultra-processed liquid nutrition formulas were high in sugars, emulsifiers, and carrageenan, they were very low in sodium content.”

My take: It is not clear what impact salt has on IBD. However, too much salt causes problems well beyond hypertension and may contribute to several inflammatory conditions, including IBD, asthma, and rheumatoid arthritis.

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Unrelated website information: IBD-EII is a website which has tried to organize/summarize some of the more important IBD articles including a timeline of these publications and evidence for specific medications.

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Tofacitinib Outperformed Vedolizumab in Anti-TNF-experienced Ulcerative Colitis

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T Straamijer et al. Clin Gastroenterol Hepatol 2023; 21: 182-191. Open Access! Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study

Methods: Adults with ulcerative colitis (UC) previously who failed anti-TNF treatment and initiated vedolizumab (n=83) or tofacitinib (n=65) treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands.

Key findings (Vedolizumab is in gray):

  • There was no difference in infection rate or severe adverse events.

My take: Coupled with more recent reassuring safety data on JAK inhibitors, this study makes a strong case for positioning Tofacitinib (or other JAK inhibitor) earlier in patients with moderate-to-severe ulcerative colitis. Given that vedolizumab outperformed adalimumab in a head-to-head study, this indicates that tofacitinib is a very effective therapy.

Related article: B Chen et al. Gastroenterology 2022; 163: 1555-1568. Efficacy and Safety of Ivarmacitinib in Patients With Moderate-to-Severe, Active, Ulcerative Colitis: A Phase II Study This phase 2 study with 146 patients examined the effectiveness of the selective JAK inhibitor Ivarmacitinib found a week 8 clinical response in 46% of those receiving 8 mg per day. The week 8 clinical remission rate was 22%-24% in the treatment groups compared to 5% in the placebo group.

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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: Rising Burden of IBD, Calprotectin in Severe Colitis, Postoperative Therapeutic Drug Monitoring, Formula Choice for EEN

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M Agrawal et al. Gastroenterol 2022; 163: 1547-1554. Open Access! The Rising Burden of Inflammatory Bowel Disease in Denmark Over Two Decades: A Nationwide Cohort Study

Key findings:

  • Between 1995 and 2016, the incidence rate (95% confidence interval) per 100,000 person-years rose from 9.1 (8.3–10.0) to 17.8 (16.8–19.0) for CD, and from 21.0 (19.8–22.3) to 28.4 (27.0–29.8) for UC.
  • The highest increase in CD and UC incidence rates occurred in children and young adults, respectively.
  • The prevalence of IBD doubled from 1995 to 2016; the greatest increase (2.5-fold) was in UC prevalence among individuals aged >40 years. During this period, the median age of the IBD population increased by 6 to 7 years.

Y Pan et al. Inflamm Bowel Dis 2022; 28: 1865-1871. Utility of Therapeutic Drug Monitoring for Tumor Necrosis Factor Antagonists and Ustekinumab in Postoperative Crohn’s Disease

In this retrospective study (n=130), therapeutic drug levels in the postoperative period were associated with improved outcomes for anti-TNF agents (infliximab (IFX) or adalimumab (ADA) but NOT for ustekinumab (UST):

  • In patients with IFX ≥3 µg/mL, higher rates of deep remission (39% vs 0%; P = .02) existed compared with those with IFX less than 3 µg/mL. This was true for clinical remission (44% vs 9%; P = .04) and objective (83% vs 62%; P = .1) remission. 
  •  In patients with ADA ≥7.5 µg/mL, rates of deep (42% vs 0%; P = .02), clinical (42% vs 0%; P = .02), and objective (88% vs 40%; P = .007) remission were higher than patients with lower concentrations.
  • For UST, rates of deep (28% vs 17%; P = 1.0), clinical (33% vs 33%; P = 1.0), and objective (70% vs 67%; P = 1.0) remission were similar between patients regardless of drug concentration.

S Sasidharan et al. Inflamm Bowel Dis 2022; 28: 1833-1837. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis

In this retrospective study (n=147), a fecal calprotectin >800 mcg/g independently predicted the need for inpatient medical rescue therapy (odds ratio, 2.61; 95% CI, 1.12-6.12). An admission calprotectin >800 mcg/g independently predicted surgery within 3 months (odds ratio, 2.88; 95% CI, 1.01-8.17). My take: This is the least surprising study I’ve read this past month —those with more severe colitis, based on calprotectin values, were more likely to need more intensive treatments.

R Dawson et al. Inflamm Bowel Dis 2022; 28: 1859-1864. Comparing Effectiveness of a Generic Oral Nutritional Supplement With Specialized Formula in the Treatment of Active Pediatric Crohn’s Disease

In this retrospective pediatric study (n=171), the authors found that a generic oral supplement (Fortsip) was as effective as a specialized formula (Modulen IBD) for enteral nutrition. “No difference was demonstrated in remission rate (Fortisip n = 67 of 106 [63%] vs Modulen IBD n = 41 of 64 [64%], P = .89), nonadherence rate (Fortisip n = 7 of 106 [7%] vs Modulen IBD 3 of 64 [5%], P = .57) or method of administration.” The main difference in outcome was a lower expense in the group receiving the generic formula. My take: This study is in agreement with previous studies.

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