Tag Archives: Crohn’s disease

Infliximab Home Infusions

Posted on by

SR Gupta et al. JPGN 2023; 76: 776-781. Outcomes for Standardized Home and Hospital-Based Infusions of Infliximab for Children With Inflammatory Bowel Disease

In this retrospective study with 102 children, key findings:

  • There were similar outcomes among carefully-selected children receiving home infusions (HI), “drug durability, AOs [adverse outcomes], and laboratory values were similar between HI and hospital-based infusions.” 30% of eligible patients received HI.
  • Within 2 years, only 19% remained on 5 mg/kg every 8 week dosing and the remainder required increased dosing or decreased interval.  (Further supporting data showing that 5 mg/kg every 8 week dosing is inadequate in ~80%)

The authors note that HI were arranged with a single home health company with pediatric PALS-trained nurses. In addition, there was “direct communication between the home health nurse and IBD nurse after each infusion.”

Prior studies of HI have shown increased AOs in patients receiving HI including stopping therapy, ER visits, and hospitalizations (Clin Gastroenterol Hepatol 2020; 18: 257-258, Am J Gastroenterol 2020; 115: 1698-1706, JAMA New Open 2021; 4: e2110268).

My take: If set up properly, home infusions could be a reasonable alternative to hospital-based or office-based infusions.

In this article, from May 31, 2023: Sick Workers Tied to 40% of Food Poisoning Outbreaks, C.D.C. Says

“Each year, 48 million people become sick from a food-borne illness, according to C.D.C. estimates. Of those, 128,000 are hospitalized and 3,000 die.”

IBD Updates: Treat-to-Target Uptake, Long-Term Data on Ustekinumab Intensification, and Low Rates of C diff with Tofacitinib (& Clinical Pearl)

Posted on by

JL Yang et al. Inflamm Bowel Dis 2023; 29: 735-743. Utilization of Colonoscopy Following Treatment Initiation in U.S. Commercially Insured Patients With Inflammatory Bowel Disease, 2013-2019

In this study with 39,734 commercially-insured initiators of IBD medications (18-64 year old), 34% had a colonoscopy by 12 months and 42% at 15 months. The authors state that “it is evident that patients without any colonoscopy during this interval are not being followed under an optimal long-term T2T (treat-to-target) paradigm.”

RS Dalal et al. Inflamm Bowel Dis 2023; 29: 830-833. Long-Term Outcomes After Ustekinumab Dose Intensification for Inflammatory Bowel Diseases

This retrospective study examined 123 patients with Crohn’s disease and 40 with ulcerative colitis who had dose intensification with ustekinumab (to either every 4 weeks, n=91, or every 6 weeks, n=72). Dose escalation was effective in both achieving and maintaining corticosteroid-free clinical remission for 61% of patients with Crohn’s disease and 40% with ulcerative colitis at 24 months; endoscopic remission was noted in 43% with Crohn’s disease and 55% with ulcerative colitis.

EV Loftus et al. Inflamm Bowel Dis 2023; 29: 744-751. Open Access! Clostridium difficile Infection in Patients with Ulcerative Colitis Treated with Tofacitinib in the Ulcerative Colitis Program 

Using data from multiple studies with 1157 patients, only 9 tofacitinib patients developed Clostridioides difficile infection (CDI) which was lower than the placebo group. CDI were all mild–moderate in severity and resolved with treatment in 8 patients. Six of 9 patients continued tofacitinib treatment without interruption. The low rate of infection was likely in part due to screening for CDI prior to treatment. In addition, “it is possible than the lower rates of CDI …may be due to better-controlled disease…, thus reducing susceptibility to infection.”

One clinical pearl in the discussion: “When considering treatment [for CDI], initial therapy with oral vancomycin should be considered instead of metronidazole, and treating for at least 21 days should also be considered [in patients with IBD due to]…lower rates of CDI recurrence.”

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.

Lego Art at Tucson Botanical Gardens

How Long to Hold Biologics and Small Molecule Drugs Perioperatively

Posted on by

BL Cohen et al. Clin Gastroenterol Hepatol l2023; 21: 1148-1151. How to Manage Targeted Immune Suppressants (Biologics and Oral Small-molecule Drugs) Perioperatively for Inflammatory Bowel Disease and non-Inflammatory Bowel Disease surgery

This article makes pragmatic recommendations with regard to surgery timing in individuals taking medications that target the immune system.

Key points:

  • Several recent large studies have “observed no association between biologic exposure and postoperative infectious outcomes.”
  • The primary risk factor for infectious complications has been corticosteroid/glucocorticoid use.
  • For IBD Surgery: “If patients are deriving therapeutic benefit, including reducing the need for steroids, we propose continuing treatment until surgery…It may be practical to perform the surgery mid to late dosing interaval in the case of biologics with longer half-lives…Our expert opinion is that therapy may be resumed 14 days postoperatively or when recovered from infectious complications.”
  • For Non-IBD surgery: “Expert opinion suggests medications may be re-dosed by 14 days postoperatively if there have been no complications. Consideration should be given to resuming oral small molecules earlier given their short half-lives.”
  • Emergency or urgent surgeries “should be performed promptly regardless of targeted immune suppressant use.”
David Yetman Trail (Tucson)

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.

VTE Protocol for Hospitalized Kids with IBD

Posted on by
Tucson Botanical Gardens

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.

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.

When Will Intestinal Ultrasound for IBD Become Practical?

Posted on by

M Allocca et al. Gastroenterol 2023; 164: 851-855. Open Access! Intestinal Ultrasound in the Assessment and Management of Inflammatory Bowel Disease: Is It Ready for Standard Practice?

This short article outlines the indications, availability, technical skills, cost-effectiveness and potential value of intestinal ultrasound (IUS). Some key points:

  • Goal: “IUS is used as a first-line investigation and can avoid or delay the need for more invasive and expensive testing (CT, MRI, or colonoscopy). Thus, costs are minimized and patient convenience is optimized”
  • Availability: “IUS is quite widespread in many European countries, but its uptake has been significantly less in other parts of the world, including the United States. Limitations to its use include the absence of standardized and reproducible protocols, lack of local expertise, and the perception that IUS is an operator-dependent tool, feasible only by highly experienced operators. In reality, however,…. studies specifically addressing sonographer variability demonstrate substantial agreement for color Doppler signals and almost perfect agreement for bowel-wall thickness, as the most relevant IUS parameter.”
  • Expertise: Trainees “have to perform at least 300 supervised ultrasound examinations in Italy and 400 in Germany to achieve full competency…It is believed that learners can achieve competency in IUS after approximately 200 supervised examinations, but it is important to acknowledge that a formal learning curve and the criteria for competency assessment have not yet been fully defined”

My take: Despite all the interest in this useful point-of-care tool, for IUS to become more widespread in the U.S. it will need to be incorporated in training programs. The threshold for competency is not achievable with a weekend seminar. It will be interesting to see how this test affects cost, management, and outcomes. Will it reduce or increase other cross sectional imaging testing? Is the information from IUS more useful than a calprotectin (stool biomarker) which could also be a point-of-care test?

Related blog posts:

The Oro Valley/Tucson Loop shared use bike path extends over 130 car free miles throughout unincorporated Pima County, Marana, Oro Valley, and Tucson.

Durability of Biologics in Children with Inflammatory Bowel Disease

Posted on by

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.

Related blog posts:

Tucson Botanical Gardens

Landmark Study: Oral Biologic for Crohn’s –Upadacitinib

Posted on by

EV Loftus et al. N Engl J Med 2023; 388:1966-1980. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease

This study is the basis for the FDA’s approval of updacitnib (Rinvoq) for Crohn’s disease in adults: New FDA Rinvoq (upadacitinib) Indication: Oral Treatment For Crohn’s

This publication describes the results of two multicenter, double-blind, randomized, placebo-controlled induction trials (n=1021 adults,U-EXCEL, U-ECEED) and one maintenance trial (n=502, U-ENDURE) with Upadacitinib (Rinvoq). The induction trials involved an early mandatory glucocorticoid taper.

Key findings:

  • A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons).
  • There was a rapid onset of action with a difference in clinical response compared to placebo at 2 weeks
  • Maintenance Trial of clinical responders: At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons).
  • Adverse effects included gastrointestinal perforations (6 in study medication, 1 in placebo), neutropenia in up to 2.6%, and increased Herpes Zoster infections in patients receiving study medication (1.5% to 3%).

A good commentary of this study is in the same issue: M Abreu. N Engl J Med 2023; 388:2005-2009. It is noted that upadacitinib showed a good response even though a different JAK inhibitor, tofacitinib, had disappointing results for patients with Crohn’s disease. Other points:

  • “It is hard to compare findings across studies because of differences in the characteristics of patients and end points. That being said, the incidences of clinical remission observed by Loftus et al. were greater than those observed in most studies of biologic drugs to treat Crohn’s disease. Moreover, upadacitinib was more likely than placebo to resolve extraintestinal manifestations.”
  • “They did not find evidence of cardiovascular or thromboembolic complications, which were previously observed in patients with rheumatoid arthritis treated with tofacitinib and which led to a black-box warning.10 However, the treatment of greater numbers of patients for a longer duration will be required to determine whether upadacitinib is asssociated with a risk of such complications.”
  • “Among the most common upadacitinib-specific adverse events were anemia [6.9%] and acne [6.3%]. The increase in anemia may be due to off-target effects of upadacitinib on erythropoietin signaling through JAK2.”

My take: This is great news for patients with Crohn’s disease. In addition to having a new option for refractory disease, this option does not require IV administration. When will pediatric data be available?

How Does Bowel Ultrasound Stack Up to MRE for Crohn’s Disease?

Posted on by

A Rispo et al. Inflamm Bowel Dis 2023; 29: 563-569. David Against Goliath: Direct Comparison of Handheld Bowel Sonography and Magnetic Resonance Enterography for Diagnosis of Crohn’s Disease

Lately, there has been a lot of ‘buzz’ about the potential use of point-of-care bowel sonography (aka intestinal ultrasound). This study (2019-2021) prospectively enrolled patients with a high likelihood of Crohn’s disease (CD) and compared handheld bowel sonography (HHBS), MRE (all patients, n=85, had ileocolonoscopy)

Key findings:

  • Sensitivity, specificity, positive predictive values, and negative predictive values for CD diagnosis were 87.50%, 91.89%, 93.33%, and 85% for HHBS; and 91.67%, 94.59%, 95.65%, and 89.74% for MRE, without significant differences in terms of diagnostic accuracy (89.41% for HHBS vs 92.94% for MRE, P = NS)
  • Magnetic resonance enterography was superior to HHBS in defining CD extension (r = 0.67; P < .01) with a better diagnostic performance than HHBS for detecting location (k = 0.81; P < .01), strictures (k = 0.75; P < .01), abscesses (k = 0.68; P < .01), and fistulas (k = 0.65; P < .01).

My take: In this study, MRE was clearly superior at defining CD complications. This study suggests that HHBS could be an effective screening tool but is not likely a definitive imaging study. In terms of bedside monitoring, it would be helpful to see how clinical monitoring with HBSS compares with a highly sensitive marker like a calprotectin. I also worry that HBSS could perform more poorly with more widespread application due to potential increase in operator error.

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

Posted on by

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.

Related blog posts:

Tumamoc Hill, Tucson AZ

Isolated Ileitis in Children

Posted on by

A Alper et al. JPGN 2023; 76: 338-342. Isolated Terminal Ileitis in Children

This single center retrospective study reviewed 640 colonoscopies in symptomatic children.

Key findings:

  • Thirty-three children had isolated histologically-defined terminal ileitis. Seventeen children were diagnosed with CD and 18 children had idiopathic terminal ileitis (3 lost to followup)
  • Children with CD had higher prevalence of abnormal C-reactive protein levels, severe inflammation, and radiological evidence of bowel wall thickening compared with children with idiopathic ileitis.
  • Two children with idiopathic ileitis were later diagnosed with CD; the remaining 13 did not develop CD over a follow-up period of 83 months.
  • From the data presented, it appeared that the center had a low rate of ileal intubation (316 colonoscopies were excluded for this reason)
  • 75% of those with histologic ileitis had normal endoscopic appearance

When our group looked at colonoscopies (n=374) in our outpatient endoscopy center, we identified isolated ileitis in 10% (6% grossly abnormal, 4% with only histologically abnormal) (related blog post: Our Study: Provider Level Variability in Colonoscopy Yield). Higher rates of ileal intubation (90% in our study) should be considered a quality metric given that 5-10% of children may have disease isolated in ileum.

My take: This study provides reassurance that most children with histologic ileitis will not progress to CD if the ileum is visually-normal (in the absence of abnormal blood tests and/or imaging).

Related blog posts:

Chattahoochee River, Sandy Springs, GA