Tag Archives: incidence

Eosinophilic Esophagitis -Increasing Incidence and Emergence of Biologic Treatments

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1st article: JW Hahn et al. Clin Gastroenterol Hepatol 2023; 21: 3270-3284. Open Access! Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976–2022: A Systematic Review and Meta-analysis

This research utilized 40 studies which met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents.

Key findings:

  • The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years and 40.04 cases per 100,000 inhabitant-years, respectively.
  • The pooled prevalence and incidence of EoE were higher in high-income countries, males, and North America.
  • The pooled prevalence and incidence of EoE have increased from 1976 to 2022.
Time trends of incidence (A) and prevalence (B) of EoE, 1976 to 2022. Pooled estimates, cases per 100,000 inhabitant-years.

2nd Article: DL Snyder, ES Dellon. Clin Gastroenterol Hepatol 2023; 21: 3230-3233. Biologics in the Treatment of Eosinophilic Esophagitis: Ready for Use?

“This review summarizes the data leading to FDA approval for dupilumab and provides a practical approach for clinical use of dupilumab.” Dupilumab, a humanized monoclonal antibody that blocks interleukin (IL)-4 receptor alpha, is currently the only FDA-approved medication for EoE. It is noted that in the trials leading to FDA approval, all patients were PPI refractory and ~70% had received topical steroids (with about half either intolerant or nonresponsive).

Dosing: 300 mg weekly injection with a single-dose prefilled autoinjector pen or a syringe with a needle shield. It is recommended that refrigerated medicine is brought to room temperature for at least 45 minutes prior to injection. It “can remain unrefrigerated up to 14 days.”

In Figure 1, the articles details positioning of use of dupilumab in EoE management algorithm:

  • New diagnosis, patient preference
  • Additional atopic condition with approved dupilumab use (strong indication)
  • Lack of response to current treatment (diet, PPI, swallowed steroids) or adverse effects from current treatment (strong indications)
  • “It is reasonable to repeat endoscopy with biopsy 24 weeks after initiation of dupilumab in many patients…However, endoscopy may be completer earlier” in selected patients.

At least 5 other biologics are in phase 2 or phase 3 studies (listed in Table 1).

My take: EoE is increasing in prevalence and new therapies (often expensive) are emerging.

Related blog posts:

Also, there is a fairly good patient education 7-page pamphlet from the makers of Dupixent encouraging patients with symptoms suggestive of EoE to speak with their physicians.

Link: This is EoE

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Increasing Incidence of Hepatocellular Carcinoma in the U.S.

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A recent study (DL White et al. Gastroenterol 2017; 152: 812-20) provide data showing a striking increase in the incidence of hepatocellular carcinoma (HCC). Using data from the US Cancer Statistics Registry which covers 97% of U.S. population, the authors found the following:

  • HCC incidence rose from 4.4 per 100,000 in 2000 to 6.7 per 100,000 in 2012
  • The annual rate of increase was 4.5% from 2000-2009, but then 0.7% annually from 2010-2012
  • The greatest increase occurred in 55-59 year olds (8.9% annually) and 60-64 year olds (6.4% annually)

The main HCC risk factors are HCV, HBV, and alcoholic liver disease, though obesity-associated HCC is emerging as an important risk factor as well.  The highest rates of HCC are seen in southern and western states, with Texas having the highest rates overall.  The high rate in Texas is in part due to the higher rates of HCC in Hispanics.

Overall, the authors indicate that the rising HCC rates are most closely tied to the peak HCV cohort (1945-65) and speculate that the arrival of direct-acting antivirals may help. At the same time, this HCV cohort is composed “disproportionately [of] minorities and of lower socioeconomic status” and may have less access to these advances in treatment.  Furthermore, in states like Texas which did not adopt Medicaid expansion as part of the Affordable Care Act, there are more uninsured patients who will be less likely to identify preceding risk factors for HCC.

My take: Perhaps in 20 years, we will see HCC incidence maps that are improving as HCV treatments become more widely available.  This presumes that other HCC risk factors, including obesity and alcohol, do not worsen significantly.

Related blog posts:

IBD in Ontario: 1 in 200

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A recent study notes an increasing incidence of and high prevalence of inflammatory bowel disease (IBD) in Ontario, Canada (Inflamm Bowel Dis 2014; 20: 1761-69).

This article notes that between 1999-2008, there was an increased incidence of IBD from 21.3 to 26.2 per 100,000.  This affected most age groups less than 65 years, but increased most rapidly in children younger than 10 years (increased 9.7% per year).  The highest incidence remained in adults aged 20 to 29 years. The overall prevalence in Ontario was estimated to be 1 in 200 overall, which is among the highest in the world.  This study relied on a validated health administrative data consisting of all Ontario residents.

The potential for misclassification bias is discussed and the potential difficulties with administrative health data is detailed in three related editorials (pages 1777-79, 1780-81, 182-83).  The editorials are helpful, in part, because a separate study in the same journal (Inflamm Bowel Dis 2014; 20: 1770-76) indicates that the incidence of Crohn’s disease and Ulcerative Colitis declined in Quebec between 2001-08. However, the authors of this study used less-rigorous methods and had a much shorter “washout” period (two years versus eight years).

At the end of the day, with conflicting studies, there remains some uncertainty with regard to IBD epidemiology.  That being said, the first study notes that “75% of CD studies and 60% of UC studies had reported increased incidence in the adult populations.”

This leads back to the question of what environmental exposures are leading to these changes in incidence.

Bottomline: This article and the associated editorials helps highlight the difficulties of using administrative health data and why many data points are needed to assess the epidemiology of IBD.  In all likelihood, the incidence of IBD is increasing.

Related blog post: Global increases in IBD incidence | gutsandgrowth

 

Global increases in IBD incidence

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Two more studies have shown increasing incidence of pediatric inflammatory bowel disease.

First in Victoria, Australia (mostly Melbourne) (Inflamm Bowel Dis 2013; 19: 1-6).

Over a 60-year span (1950-2009), a retrospective review was undertaken of ulcerative colitis (UC) pediatric patients. In total, 342 children were diagnosed with UC. Key finding: The number of reported cases increased by 11-fold during the study period with a marked increase since 1990 (0.15 –>1.61/100,000).  In addition, recently diagnosed children have had more extensive disease.

Next in Spain (Inflamm Bowel Dis 2013; 19: 73-80).

This retrospective study from hospitals’ databases looked at the incidence between 1996-2009 in the pediatric population (<18 years).  A total of 2107 patients were identified: 1165 with Crohn’s disease, 788 ulcerative colitis, and 154 IBD unclassified. Median age at diagnosis was 12.3 years.  Key finding: in the last 14 years, pediatric IBD incidence has almost tripled (0.9 –>2.8/100,000).

Both of these studies have limitations related to large retrospective reviews in terms of potential problems with capturing all of the patients and the potential for misdiagnosis.  However, the trend is clear.  In addition, these studies show incidence rates comparable to several other Western studies.  The increasing incidence of IBD ‘argue for a common environmental factor in their pathogenesis.’  While interest has focused on microbial factors, the basis for this increased incidence currently remains elusive.

Related blog posts:

Why are we seeing so many more cases

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In this month’s Gastroenterology, two articles offer some insight into this question for two separate problems.

With regard to inflammatory bowel disease, (IBD) –both Crohn’s disease and UC –there is an increasing prevalence and incidence worldwide (Gastroenterology 2012; 142: 46-54). This article identified 8444 previous citations and then identified 262 studies with relevant data.  Overall, the highest incidence and prevalence of these disorders occurs in Europe and North America.  In North America, Canada has the highest prevalence with 0.6% of the population having IBD.

After going through the statistics, the authors offer some discussion on why IBD is increasing.  In the developing parts of the world, some of the increase is due to the ability to detect and differentiate these disorders due to improving access to medical care/colonoscopy.  In the areas of the world with the highest incidence/prevalence, environmental risk factors are playing an important role.  Potential factors include microbial exposures, sanitation, lifestyle behaviors, medications, and pollution.  These factors are supported by other epidemiological studies which show that individuals who move from low prevalence areas to higher ones are at increased risk for IBD, especially among first generation children (Gut 2008; 57: 1185-91).  Furthermore, in low prevalence regions, IBD is increasing with more industrialization (Chin J Dig Dis 2005; 6: 175-81, Indian J Gastroenterol 2005; 24: 23-24.)  Exact mechanisms are poorly understood; however, even in the U.S. it is recognized that rural/farm exposure at a young age reduces the likelihood of developing IBD at a later age (Pediatrics 2007; 120: 354).

Celiac disease, likewise, has seen an increase in prevalence.  With celiac disease, the proliferation of widely available and more accurate serology has been crucial in the identification of more patients.  However, like IBD, there is likely a role for changing microbial environment contributing to an increasing case burden.  Recently, reports have shown that the risk of celiac disease can be influenced at birth (Gastroenterology 2012; 142: 39-45).  Although the absolute risk was modest, there was an increased risk demonstrated with elective but not emergent cesarean delivery among a large nationwide case-control study from Sweden.  Among the cohort of 11,749 offspring with biopsy-proven celiac (with matched control group of 53,887), elective cesarean delivery resulted in an odds ratio of 1.15 (confidence intervals 1.04-1.26).  This study confirmed other studies which have shown an increased risk with cesarean delivery (Pediatrics 2010; 125: e1433-e1440).  Some of the strengths of this Swedish study, included the fact that the deliveries were separated based on elective or emergency cesarean delivery and were controlled for whether the mother had celiac disease.  (Pregnant women with celiac disease have an increased risk of cesarean delivery.)  The authors speculate that the reason why elective cesarean deliveries increase the risk of celiac disease is that microbial exposures at birth likely influences perinatal colonization –>affects intestinal immune response and mucosal barrier function. Offspring of women with emergency cesarean delivery would be more likely to be exposed to bacteria from the birth canal and no significant increase risk of celiac disease could be identified in this group.

Thus how we are born and where we live make a big impact on the likelihood of developing these GI disorders.

Additional References:

  • -Gut 2011; 60: 49-54. n=577,627 Danish children. Use of antibiotics associated with increase risk of Crohn’s disease (but not UC), especially at younger ages (3-11month of age, & 2-3yrs of age). Each course increased risk by 18%. In children with >7 courses, relative risk was 7.3. especially penicillins.
  • -NEJM 2011; 364: 701, 769. Living on a farm decreases risk of childhood asthma.
  • -Nature 2011; 476: 393. ‘Stop killing beneficial bacteria.’  For example, killing H pylori likely increases risk of esophageal adenocarcinoma
  • -Gastroenterology 2011; 141: 28, 208. GM-CSF receptor (CD116) defective expression & function in 85% of IBD pts. n=52.
  • -Gastroenterology 2010; 139: 1816, 1844. Microbiome & affect on IBD vs mucosal homeostasis
  • -J Pediatr 2010; 157: 240. Microbiota in pediatric IBD -increased E coli and decreased F praunsitzil in IBD pts.
  • -J Pediatr 2009; 155: 781. early child care exposures lessens risk for asthma.
  • -IBD 2008; 14: 575.  Role of E coli in Crohn’s
  • -Lab Invest 2007; 87: 1042-1054. Role of E coli in Crohn’s
  • -Pediatrics 2007; 120: 354. Crohn’s less common after repeated exposure to farm animals in 1st year of life.

More practical information and links to other websites can be found at http://www.gicareforkids.com.