Eosinophilic Colitis Is Not a Typical EGID or IBD

T Shoda et al. Gastroenterol 2022; 162: 1635-1642. Open Access: Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study

Methods: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn’s disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing.

Key findings:

  • Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs
  • EoC transcriptome–based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001)

My take: The study indicates that eosinophilic colitis is likely unrelated to other eosinophilic GI disease and is likely unrelated to inflammatory bowel disease.

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Position Paper for Pediatric Breath Testing

IJ Broekaert et al. JPGN 2022; 74: 123-127. Open access: An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology

This is a good article which provides pediatric dosing of breath testing agents and important considerations in methodology and interpretation. In addition, there are 22 graded recommendations (see below) –some may be surprising. For example, the breath testing is NOT recommended for diagnosis of H pylori but is recommended for determination of eradication therapy.

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IBD Shorts: Pediatric Cost Savings with Biosimilars and Multiple Biosimilar Switch Data

GA Morris et al. Inflamm Bowel Dis 2022; 28: 531-538. Increasing Biosimilar Utilization at a Pediatric Inflammatory Bowel Disease Center and Associated Cost Savings: Show Me the Money

Key findings:

  • Biosimilar utilization initiation increased from a baseline of 1% in June 2019 to 96% by February 2021 among eligible patients; 20% of all patients (n-98) had insurance which preferred originator product
  • Estimated cost savings over the project duration were nearly $381,000 (average sales price) over the 20 month study

My take: The introduction of biosimilars have resulted in huge cost savings. In addition, for infliximab, the originator product price has also dropped substantially (more than 60% in some locations)

J Hanzel et al. Inflamm Bowel Dis 2022; 28: 495-501. Open Access: Multiple Switches From the Originator Infliximab to Biosimilars Is Effective and Safe in Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study 

Methods: This was a prospective multicenter cohort study of adult IBD patients (n=176) who underwent 2 switches from the originator IFX to CT-P13 to SB2 (group 1), 1 switch from CT-P13 to SB2 (group 2), and 1 switch from the originator IFX to CT-P13 (group 3).

Key findings:

  • At 12 months after the most recent switch 76.9% (40 of 52, group 1), 65.7% (46 of 70, group 2) and 76.9% (20 of 26, group 3) of patients were in clinical remission. Treatment persistence at 12 months was 85.0%, 87.0%, and 70.1%, respectively.
  • There were no significant differences in the rate of clinical, CRP, FC remission, or treatment persistence at 12 months between the 3 groups.

My take: This study did not identify detrimental effects from multiple successive switching and switching between biosimilars of IFX. Longer followup and more clinical experience will be needed to confirm these findings.

Guselkumab: Expanding the GALAXI of Treatments for Crohn’s Disease

WJ Sandborn et al. Gastroenterol 2022; 162: 1650-1664. Open Access: Guselkumab for the Treatment of Crohn’s Disease: Induction Results From the Phase 2 GALAXI-1 Study

Background: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis.

Methods: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients with moderate to severe Crohn’s disease 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. n=309 with ~50% having disease refractory to prior biologics

Key findings:

  • At week 12, significantly greater reductions in Crohn’s Disease Activity Index from baseline (least squares means: 200 mg: –160.4, 600 mg: –138.9, and 1200 mg: –144.9 vs placebo: –36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo
  • Improvement compared to placebo was evident as early as week 4
  • Safety event rates were generally similar across treatment groups

My take: This is an exciting time for practitioners taking care of patients as there are an increasing number of pharmacologic and dietary treatments for inflammatory bowel disease. With guselkumab, there may be an overlapping mechanism with ustekinumab which targets IL-12/23.

Related blog post: Emerging Data on Risankizumab for Crohn’s Disease

Genetic Diseases and Newborn Unconjugated Hyperbilirubinemia

H Mel et al. J Pediatr 2022; 243: 53-60. Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project

Methods: The researchers used targeted panel sequencing data on 2742 genes including known unconjugated hyperbilirubinemia genes in 1412 neonates (in China). Exclusion criteria included gestational age <35 weeks and congenital malformations. 37% had severe unconjugated hyperbilirubinemia (reaching threshold recommended for exchange transfusion)

Findings:

  • 45 (3%) of the cohort had genetic findings related to their unconjugated hyperbilirubinemia. 26 had variants associated with G6PD deficiency and eight had variants in UGT1A1 (which can cause Gilbert syndrome or Crigler-Najjar syndrome)
  • 11 of 45 of genetic findings were due to more obscure causes including to RBC membrane defects, n=5 (ANK1, SPTB) and due to metabolic/biochemical disorders (GCDH, MMACHC, MUT, DUOX2, DUOXA2, MOCS1)
  • Known clinical causes of hyperbilirubinemia were identified for 68% of patients. The most common clinical cause of unconjugated hyperbilirubinemia group was infection (15%). Other clinical causes included breastfeeding (n=154, 11%), extravascular hemorrhage (147, 10%), hemolytic disease (104, 7%) and inadequate feeding (82, 6%)

My take: About 3% of infants in this cohort had underlying genetic causes contributing to their jaundice; three-fourths of those with a genetic condition had either a variant of G6PD or UGT1A1

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Valley of Fires, New Mexico. The darker areas are lava.

Dupilumab: FDA Approval for Eosinophilic Esophagitis

U.S. FDA (5/20/22): FDA Approves First Treatment for Eosinophilic Esophagitis, a Chronic Immune Disorder

“Today, the U.S. Food and Drug Administration approved Dupixent (dupilumab) to treat eosinophilic esophagitis (EoE) in adults and pediatric patients 12 years and older weighing at least 40 kilograms (which is about 88 pounds). Today’s action marks the first FDA approval of a treatment for EoE…”

“The efficacy and safety of Dupixent in EoE was studied in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial, that included two 24-week treatment periods (Part A and Part B)…In Part A of the trial, 60% of the 42 patients who received Dupixent achieved the pre-determined level of reduced eosinophils in the esophagus compared to 5% of the 39 patients who received a placebo…. In Part B, 59% of the 80 patients who received Dupixent achieved the pre-determined level of reduced eosinophils in the esophagus compared to 6% of the 79 patients who received a placebo”

My take: We will need to revise our patient handout and decide how best to position this very expensive therapy. Without insurance, Dupixent (2 pens of 300 mg/2 mL) costs $3,649.97 on GoodRx. For those with insurance, Dupixent has a manufacturer’s coupon (Dupixent MyWay).

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Sandia Mountain Tram

Partisan Divide, Misinformation and Risk of COVID-19 Death

NPR: Pro-Trump counties continue to suffer far higher COVID death tolls

Since May 2021, “those living in counties that voted 60% or higher for Trump in November 2020 had 2.26 times the death rate of those that went by the same margin for Biden. Counties with a higher share of Trump votes had even higher mortality rates…. previous polling has shown that belief in misinformation is highly correlated with being unvaccinated. Kaiser examined several common pieces of misinformation such as the idea that the government is exaggerating the severity of the pandemic, or that the vaccines contain a microchip. Kaiser’s poll found that 94% of Republicans believed one or more false statements about the vaccines.”

Related blog post: Perception of COVID-19 Risk, Vaccine Uptake and Media Source

Do Health Care Workers Need Peace Agreements?

I have not paid close attention to the movement to unionize health care workers in the U.S. As such, I learned a few things in this past weekend NY Times article: Doctors and Nurses Shouldn’t Have to Strike (online version titled “When Health Care Workers Are Protected, Patients Are, Too”)

Excerpts:

Since the pandemic began, the health care work force — the country’s largest industry by employment — has shrunk by nearly 2 percent… Now, with astronomical turnover and rising demand as patients seek care that they may have put off during the height of the pandemic, hospitals, clinics, nursing homes and home care agencies across the country lack sufficient staff members to adequately care for patients…

Most hospitals might be private companies in their formal legal identity, but the reality is that government has shaped the health care system every step of the way of its modern existence…

Unionized health care workers all over the country are fighting back against untenable conditions in the health care industry, and they are often met with harsh treatment by employers for doing so…

Peace agreements are popular with unions because they help prevent the type of devastating reprisals that drive many workers out of their jobs, but employers often refuse to accept them…

By giving weight to workers’ on-the-job needs, while eliminating strikes, labor peace policies in health care facilities benefit patients because they give workers more power to manage their work environments. They also make establishing unions easier for workers, and data suggests that unionization in health care improves patient care.

My take: In our hospital system, recent staffing shortages have forced the hospital to close a significant number of intensive care unit beds. This will inevitably lead to postponement or cancellation (often at last minute) of needed surgical procedures (that often require availability of an ICU bed). The fix for some of the ills in our hospital system is going to be difficult. Adequate staffing with highly-trained health care workers needs to be the top priority.

Another sign that helps keep folks on the designated walking areas
–this one was at the Valley of Fires State Park, NM

ENTERPRISE Study: Vedolizumab for Perianal Fistulizing Crohn’s Disease

DA Schwartz et al. Clin Gastroenterol Hepatol 2022; 20: 1059-1067. Open Access: Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn’s Disease: ENTERPRISE Study

Methods: “Patients with moderately to severely active CD and 1–3 active perianal fistulae (identified on magnetic resonance imaging [MRI]) received vedolizumab 300 mg intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an additional vedolizumab dose at week 10 (VDZ + wk10)… Enrollment was stopped prematurely because of recruitment challenges”

Key findings:

  • “Rapid and sustained fistula closure was observed; 53.6% (VDZ, 64.3%; VDZ + wk10, 42.9%) and 42.9% (VDZ, 50.0%; VDZ + wk10, 35.7%) of patients achieved ≥50% decrease in draining fistulae and 100% fistulae closure, respectively, at week 30”
  • “MRI healing, defined as the disappearance of T2 hyperintensity signal and absence of gadolinium contrast enhancement,3 was not reached in this study…gadolinium contrast enhancement showed improvement at week 30…MRI studies have shown that internal fistulae healing lags behind clinical remission by a median of 12 months”
Figure 1
Figure 2 B

The study findings are limited by relatively small size and lack of control group (eg. placebo or seton/antibiotic group). However, the rate of response in this study is significantly higher than placebo studies which have shown “~1 in 6” who experienced fistula closure.

My take: Vedolizumab is another option for treating Crohn’s disease with perianal fistula. Both regimens in this study were associated with response, though the additional 10-week dose (in one group) did not improve outcomes.

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