IBD Briefs -October 2020

EV Loftus et al.  AP&T  2020; 52: 1343-1365. Full text: Long‐term safety of vedolizumab for inflammatory bowel disease

GEMINI long‐term safety (LTS) study results –initiated 2009:

  • Enrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks. Total of 7999 patient years of vedolizumab exposure.
  • Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients.
  • There were no new trends for infections, malignancies, infusion‐related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy
  • Conclusion from authors: “The safety profile of vedolizumab remains favourable with no unexpected or new safety concerns.”

Related blog posts:

AS Faye et al. Inflamm Bowel Dis 2020; 26: 1368-1376. Fertility Impact of Initial Operation Type for Female Ulcerative Colitis Patients (link includes video abstract)

Surgical options include Ileal pouch–anal anastomosis (IPAA), rectal-sparing colectomy with end ileostomy (RCEI), and ileorectal anastomosis (IRA). Conclusions based on “a patient-level state transition microsimulation in TreeAge Pro:”… “Despite an increased risk of infertility, our model results suggest that IPAA may be the optimal surgical strategy for female UC patients aged 20–30 years who desire children. For patients aged 35 years, RCEI should additionally be considered, as QALYs for RCEI and IPAA were similar.”   In older age group, RCEI’s increase rate of childbirth (28%), decrease time to childbirth (14 months) and 77% reduction in IVF are important factors.

Related blog posts:

R Tariq et al. Inflamm Bowel Dis 2020; 26: 1415-1422. Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease

In this retrospective study with 145 patients,  the overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. The authors concluded that “fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.”

Related blog posts:

Isle of Palms (July 2020)

 

What’s Missing In Pediatric IBD Care

A recent single-site cross-sectional survey (HK Michel et al. J Pediatr 2020; 224: 94-101. Gaps Exist in the Comprehensive Care of Children with Inflammatory Bowel Diseases) of parents (n=161) and adolescents(n=84)  identified gaps in the comprehensive care of pediatric patients with inflammatory bowel disease (IBD).

Key points:

  • Discussions about family/peer relationships, school/extracurricular activities, and mood were not addressed in 30%-40% of participants.
  • Adolescents frequently reported that no one had talked to them about substance use (40%), sexual health (50%), or body image (60%)
  • 75% of adolescents and 76% of their parents reported that no one had discussed transitioning to an adult provider.

There is likely a wide variability in addressing psychosocial issues among providers and centers.  Limitations for this type of study includes recall bias and selection bias.

The associated editorial (MJ Ladinsky, MB Cohen, pg 20-22) urge us to ‘Mind the Gap.’  This likely means allowing sufficient time and arranging opportunities for teens to speak directly (& alone) with care provider.  Like other aspects of care, establishing a standardized approach is likely to be helpful.

My take: As noted on this blog previously, emotional health issues are likely more important than other aspects of IBD care that attract more consistent attention (eg. vaccination); the message is clear that these needs need to be addressed.

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

Why We Are Not Making Progress with Probiotics

A recent commentary A Khoruts et al. Gastroenterol 2020; 159: 409-413. Full text: Probiotics: Promise, Evidence, and Hope

Despite the fact that the probiotic industry has ample money which is projected to reach $70 billion yearly, there is very little high quality research.

Key points:

  • Probiotics are regulated by the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC). The FDA, unlike the FTC, regulates products by category (eg, foods, drugs, dietary supplements, medical devices, and cosmetics)…Foods and dietary supplements, unlike drugs, do not require FDA premarket approval. By law, probiotic foods and dietary supplements must be safe. However, food manufacturers are permitted to make a self-determination of whether their product meets the “generally recognized as safe” (GRAS) designation, typically based on history of prior use”
  • Probiotic food and dietary supplement manufacturers do not have to specify on their product labels the strains they use in probiotic products or specify the number of live microbes of each strain that the product delivers through the end of its shelf life; and, although they are required to have validation of label claims, they are not required to submit it to the FDA
  • Dietary supplements can make structure/function claims, even though they cannot claim to treat any specific disease. These claims can sound very promising and consumers may be hard pressed to distinguish between a statement that a product “improves digestion,” a structure/function claim that is so vague that it is literally untestable
  • Rational selection of donor microbiota should be possible based on microbiome-based diagnostics, as well as in vitro technologies that interrogate the functional potential of complex microbial communities. There are parallel, intensive efforts to develop defined microbial communities. A common theme among these different approaches is deployment of complex assemblages of microorganisms rather than single strains. Such complex consortia are likely to have more consistent and predictable effects.
  • The emergence of microbial therapeutics requires development of a new branch of pharmacology. The challenges of formulation, pharmacokinetics, and pharmacodynamics are very distinct from those of small molecule therapeutics or protein biologics.

My take: “These next-generation probiotics will need to be tested for safety and efficacy in well-designed and properly powered clinical trials.”  Probably the only way that will happen is to empower regulatory agencies to insist that these products are treated like medications.  Given the fact that probiotics are so profitable now with little evidence of efficacy for most strains, I am not optimistic about any changes in the near future.

Related blog posts:

Best Screening For Celiac At All Ages

Another study (MR Khan et al. J Pediatr 2020; 224: 158-61. The Utility of IgA-Based Serologic Markers in Diagnosing Celiac Disease in Children 24 Months of Age or Younger) shows that tissue transglutaminase (TTG) IgA is the best first test, even in children less than 2 years of age.

This was a multicenter retrospective study with 150 children, mean age was 18 months.

Key findings:

  • ~98% of children <2 years of age with celiac disease had an elevated TTG IgA
  • “These findings are consistent with recently published European guidelines, which endorse TTG IgA…as the initial screening test regardless of age.”
  • IgG-based test should be reserved for IgA-deficient children, which was noted in 5.5% of this cohort.
  • Endomysial antibody (EMA) had excellent specificity in this study but was less sensitive; it was negative in 13 of 66 (19.7%) of children with celiac disease (positive in 80%).

My take: TTG IgA is a good first step; based on clinical presentation, further testing (eg. endoscopy) could be warranted in highly-selected cases with negative results.

Related blog posts:

Leading Medical Journals Condemn U.S. Pandemic Response

Multiple prestigious journals have weighed in on the U.S. pandemic response.

 

From Science Editor-in-Chief
From Nature
Also, from Nature

From The Lancet:

“If logic and justice prevail in the next presidential
administration, universal health coverage, a fairer society,
stronger health institutions, more energetic global
engagement, and a robust research agenda will be the
foundations for America’s renewal. We all have a stake in
America’s success.”

Transanal Irrigation Device -Pediatric Experience

A recent retrospective study (S Patel et al. JPGN 2020; 71: 292-297Impact of Transanal Irrigation Device in the Management of Children With Fecal Incontinence and Constipation) provides some useful experience in the management of constipation related to bowel dysfunction (n=147), including patients with neurogenic bowel dysfunction (NBD) related to spinal cord defects (NBD, n=85), refractory constipation (RC, n=43), or anorectal malformations (ARMs, n=19).

The authors elaborate on their protocol which includes flushing with warm tap water (on average) 15 mL/kg, generally once a day.  They note that the device is contraindicated in patients <2 years of age and/or within 3 months of anal/colorectal surgery.  The Peristeen device has been FDA approved since 2012.

Key findings:

  • For all patient groups, there was significant improvement in symptoms of fecal incontinence and constipation (P ≤ 0.001).
  • Abdominal pain was improved in the NBD and RC group, but not significantly in the ARM group.

My take: As with other treatment options for these problems, the key to success is adequate upfront training.  The authors note that their training sessions typically last 1-2 hours. A limiting factor with this treatment can be cost.

Useful link: Peristeen Bowel Management

Related blog entries:

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

 

ANMS Virtual Symposia on Constipation

For those wanting a state-of-the-art review on constipation:

YouTube (1:01) ANMS Virtual Symposia on Constipation

Dr. Jose Garza (one of my partners) gives the first lecture focused on pediatrics -first 18 minutes.

A few points:

  • Miralax is safe (time: 13:45)
  • Senna and bisacodyl are safe and have not been shown to cause dependence (time 14:55)

Study: No Increased Cancer Risk with Ranitidine

Despite theoretical concerns that impurities with N-nitrosodimethylamine (NMDA) identified in samples of ranitidine (trade name: Zantac) could increase the risk of cancer, a recent study (N Mohyuddin et al. DDW 2020; Abstract#152. RISK OF CANCER WITH USE OF RANITIDINE: RESULTS OF A COHORT STUDY OF 65 MILLION US ADULTS) did not find any evidence of this.

Methods: The authors utilized the Explorys database (IBM, New York) which is a source of longitudinal real world deidentified data collected from electronic medical records from over 40 health systems nationwide (65 million) from 1999-2019.

Key findings:

  • 1.62 million users of ranitidine were identified, 3.37 million users of famotidine, and 59.63 million individuals who did not use either H2 blocker.
  • Users of ranitidine and famotidine when compared to the general population, and users of famotidine when compared to ranitidine, were older (p<0.001), smokers (p<0.001), obese (p<0.001), had liver cirrhosis (p<0.001), a history of alcohol use (p<0.001), and a family history of cancer (p<0.001).
  • Ranitidine users had a numerically lower risk for GI cancers (liver, stomach, esophageal, colorectal, and pancreatic cancers) compared to famotidine. Among subjects without risk factors including smoking, obesity, alcohol use, family history, cirrhosis and GERD, the risk of all cancers (excluding non-melanoma skin cancers) was identical for ranitidine and famotidine (OR=1, CI=1.01-1.02, p=0.001).

My take: This large database did NOT identify an increased risk of malignancy with ranitidine over a 20 year span.  Despite this, I don’t expect that the FDA will reverse its recall.

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

Missing Care Due to COVID-19

When analyzing health care expenditures, it has been well-recognized that many patients/families cut back on both necessary and unnecessary care when faced with increased costs; that is, individuals are not very good at selecting care that is truly essential.  This is one reason why many health care policy advisors are opposed to  high copays and deductibles as a way of reducing health care costs.

I have seen the same type of problem amidst the pandemic.  Due to fears of contracting SARS-CoV-2 (rather than mainly cost), individuals/families are deferring routine medical care.  This is leading to delays in diagnosis of many serious illnesses and missing opportunities to prevent illnesses (eg. vaccines).  A recent study has shown some of the impact with regard to cancer that happened early in the pandemic (and may be ongoing).

HW Kaufman et al. JAMA Netw Open. 2020;3(8):e2017267. doi:10.1001/jamanetworkopen.2020.17267. Full text: Changes in the Number of US Patients With Newly Identified Cancer Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic

Introduction/Background:  In this study, we analyzed weekly changes in the number of patients with newly identified cancer before and during the COVID-19 pandemic.

Methods: This cross-sectional study included patients across the United States who received testing for any cause by Quest Diagnostic; data was compared between baseline period (January 6, 2019, to February 29, 2020) and the COVID-19 period (March 1 to April 18, 2020). n=278 778 patients. Study evaluated  breast cancer,  colorectal cancer, lung cancer,  pancreatic cancer, gastric cancer, and esophageal cancer.

Key findings:

  • During the pandemic period, the weekly number fell 46.4% (from 4310 to 2310) for the 6 cancers combined, with significant declines in all cancer types, ranging from 24.7% for pancreatic cancer (from 271 to 204; P = .01) to 51.8% for breast cancer (from 2208 to 1064; P < .001)

The authors noted a similar problem has been reported with cardiovascular disease.  A study from 9 high-volume US cardiac catheterization laboratories found a 38% decrease in patients treated for ST-elevation myocardial infarction, considered a life-threatening condition.

My take: It is difficult to calculate the actual toll of this pandemic which includes a great deal of secondary problems: delays in diagnosis of life-threatening conditions, mental health/suicides, death from poverty, setbacks in the opioid crisis & overdose deaths, and enormous setbacks in global health projects.

Related blog posts:

Elevated Ferritin Evaluation (in adults)

This is a useful article in evaluation of elevated ferritin levels in adults.  This approach is NOT applicable in young children but may have some use in adolescents.  In young children, other considerations include HLH and macrophage activation. In newborns, elevation of ferritin (along with liver dysfunction) may be indicative of GALD (gestational alloimmune liver disease).

W. Palmer et al. AJG 2020; 115: 1353-55. How I Approach Patients With Elevated Serum Ferritin

Image from ACG Twitter Link