2022 Digestive Disease Week Annual Meeting

 in San Diego shows the live microbiota therapeutic results in restoring microbe-associated metabolites known to prevent recurrent 

A team, led by Kevin D. Litcofsky, MD, Seres Therapeutics, investigators changes in short, medium, and branched-chain fatty acids based on emerging studies regarding the potential role of microbe-associated metabolites in inhibiting C difficile growth and restoring gut homeostasis.

Recent studies, including a phase 3 trial, have shown that SER-109, an oral investigational microbiome therapeutic made of purified Firmicutes spores, shown promise compared to placebo in reducing the risk of recurrent CDI at week 8.

In the phase 3 trial, the primary endpoint of reducing the risk was superior for patients treated SER-109 compared to placebo (12.4% vs. 39.8%, respectively; RR, 0.32; 95% CI, 0.18-0.58; 

SER-109 also led to a higher engraftment of dose species and rapid conversion of primary to secondary bile acids, known inhibitors of C difficile spore germination and vegetative growth at weeks 1, 2, and 8.

In the study, the investigators examined patients with a history of at least 3 episodes of rCDI. Each patient was randomly assigned to be treated with either placebo or SER-109 following 10-21 days of standard of care antibiotic treatment.

The investigators also looked at a post-hoc analysis in which concentrations of short (acetate, propionate, butyrate), medium (valerate, hexanoate), and branched-chain (2-methylbutyrate, isobutyrate, isovalerate) fatty acids in subjects’ stool samples were measured from baseline to 1, 2, and 8 weeks post-treatment. The measurements were made by targeted liquid chromatography with tandem mass spectrometry.

The team also used two-sided Mann-Whitney U tests to determine statistical significance for metabolite comparisons between the different arms of the trial.

The baseline concentrations of all measured fatty acids were comparable between participants treated with SER-109 and placebo.

The concentrations of butyrate, a short-chain fatty acid, and valerate and hexanoate, medium-chain fatty acids, rapidly and significantly increased in patients treated with SER-109 compared to placebo.

The concentrations of microbe-produced metabolites also remained significantly higher in patients treated with SER-109 at week 2 and week 8 compared to placebo. The changes correlated with a greater magnitude of engraftment of SER-109 dose species through week 8 compared to placebo. However, other short and branched-chain fatty acids did not show consistent treatment related differences across the different time points.

The results show SER-109 could modulate multiple pathways critical to the rapid interruption of the C difficile life cycle.

“Compared to placebo, SER-109 demonstrated a rapid and sustained increase in the concentrations of butyrate, valerate, and hexanoate in parallel with SER-109 engraftment at weeks 1, 2 and 8 in subjects with a history of rCDI,” the authors wrote. “The increase in these microbe-produced metabolites was associated with a reduction in rCDI events suggesting that increasing fatty acid production may improve clinical outcomes.”

The study, “IMPACT OF SER-109, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC, ON STOOL FATTY ACID METABOLITES IN A PHASE 3 RANDOMIZED TRIAL (ECOSPOR III) FOR TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION (CDI),” was published online by 

Articles

The live microbiota therapeutic has shown promise in treating patients with recurrent CDI.

SER-109 Results in Increase in Microbe-Producing Metabolites

This article was originally published in our sister publication 

Investigators evaluating a gene-editing strategy that seeks to reactivate developmentally silenced fetal hemoglobin (HbF, α2γ2) in order to replace defective sickle hemoglobin (HbS, α2βS2) in patients with 

 reported encouraging results in a late-breaking oral presentation at the 

American Society of Gene & Cell Therapy 25th Annual Meeting

 (ASGCT), held in Washington, DC, and virtually May 16-19, 2022.1

Findings from the early stage clinical trial targeting BCL11A erythroid specific enhancer to induce fetal hemoglobin suggest that disruption of the -115 BCL11A repressor binding site in the γ-globin gene promoters can stimulate therapeutically effective levels of HbF and is a promising approach for genomic SCD therapy.

First, the research team compared editing of BCL11A (-115) with ZBTB7A (-198) binding motifs to determine which target, when edited with the γ-globin gene promoters, would produce the most robust HbF induction.

“We electroporated Cas9-3xNLS ribonucleoprotein complexes (RNPs) into human primary CD34+ hematopoietic stem and progenitor cells (HSPCs) and attained high editing rates ranging from 76.2% to 85.7%,” investigators reported.

Investigators observed consistent and high indel mutations frequencies of 63.5% to 92.7% in all hematopoietic lineages with no apparent impairment of multilineage differentiation some 17 weeks after transplanting the edited CD34+ cells into immunodeficient 

They noted higher levels of HbF induction in erythroid progeny of CD34+ cells edited at the -115 γ-globin promoter target (31.8%) when compared with those edited at the - 198 ZBTB7A binding site (13%-18%).

The next step to further test the -115 γ-globin promoter editing approach in SCD patient cells was to edit plerixafor-mobilized CD34+ HSPCs from 1 healthy donor and 3 individuals with SCD.

“Seventeen weeks after transplanting edited cells into 

 mice, we observed consistently high rates of editing (75.1%) in all hematopoietic lineages, and substantial levels of HbF (27.6%) in erythroid progeny compared to controls (< 2.9%),” investigators reported. “Single cell western showed expression of gamma globin in a majority of edited erythroblasts (58%) compared to unedited controls (<6%). Moreover, RBCs derived from edited CD34+ cells from SCD patients exhibited significant 3-fold reduction in hypoxia-induced sickling.”

Lead author and presenter Varun Katta, senior research technologist at St. Jude Children's Research Hospital, reported that the team used CHANGE-seq discovery and rhAMP-seq validation and did not detect off-target mutations above background at 194 identified sites. Relying on PacBio-Hifi long-range sequencing, Katta and colleagues did note that a high-frequency large deletion occurred (4.9 kb) and resulted from simultaneous double strand beaks in HBG1 and HBG2 promoters.

“By digital droplet [polymerase chain reaction], we detected an average of 23.9% of this 4.9 kb deletion in engrafted cells at 17 weeks that has no apparent impact on erythropoiesis and HbF induction,” the team reported.

Next steps include plans for a future clinical trial in 2023 at St. Jude called the St. Jude Autologous Genome Edited Stem Cells (SAGES1) clinical trial.

Katta V, O’Keefe K, Wood R, et al. Genome editing of human hematopoietic stem cells to induce fetal hemoglobin for autologous cellular therapy of sickle cell disease. Presented at: American Society of Gene & Cell Therapy 25th Annual Meeting; May 16-19, 2022; Washington, DC. Accessed May 16, 2022. 

https://annualmeeting.asgct.org/global/am22/late-breaking-abstract-publication.aspx

In a late-breaking presentation at ASGCT 2022, investigators shared preclinical results of a gene-editing strategy that seeks to reactivate developmentally silenced fetal hemoglobin (HbF, α2γ2) in order to replace defective sickle hemoglobin (HbS, α2βS2).

Early Momentum for a Genomic Approach to Sickle Cell Disease Therapy

New research indicates that male sexual dysfunction is more common in patients with restorative ileo anal pouch anastomosis (IPAA) after proctocolectomy, a surgery commonly used for patients with ulcerative colitis, than it is in the general population.

2022 Digestive Disease Week (2022) Annual Meeting

 in San Diego, Taha Qazi, MD, Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, explained the results of a new study and what the knowledge of an increased risk of male sexual dysfunction can do for patients.

Qazi said that male sexual dysfunction is likely more common in these patients because of nerve damage caused by the surgery.

Overall, males who have this surgery have twice as likely chance of having male sexual dysfunction.

“This is something that’s common,” Qazi said. “One of the things we don’t talk about as clinicians and physicians is male sexual dysfunction with our patients.”

He said the data should give clinicians comfort to begin conversations with patients because it might be more common than previously believed.

The study, which looked at more than 40,000 patients with ulcerative colitis who had IPAA found 1940 cases of male sexual dysfunction. However, Qazi said the surgery is absolutely necessary for many and the sexual dysfunction can be treated with available medications.

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Patients who have IPAA are more than twice as likely to suffer from male sexual dysfunction.



Taha Qazi, MD: Male Sexual Dysfunction Following Ulcerative Colitis Surgery

New data announced today demonstrate consistent improvements among patients treated with bimekizumab when compared with placebo in patients with axial spondyloarthritis (axSpA), including non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis (AS).

According to UCB, the phase 3 studies, BE MOBILE 1 and BE MOBILE 2 will be presented at the European Congress of Rheumatology (EULAR) 2022, along with the phase 2b BE AGILE study, in which bimekizumab showed maintenance of clinical responses over 3 years in patients with active ankylosing spondylitis.

In the treatment group of both studies patients were given 160 mg of bimekizumab every 4 weeks. The BE MOBILE 1 study included patients with active nr-axSpA and BE MOBILE 2 included patients with active ankylosing spondylitis.

Both studies met their primary endpoint of Assessment of SpondyloArthritis International Society 40 (ASAS40) at week 16 with statistical significance, as well as all ranked secondary endpoints, when compared to placebo.

The first trial demonstrated at week 16 that 47.7% of patients with nr-axSpA who received the treatment achieved ASAS40 compared with 21.4% of those in the placebo group. Similarly, in the second trial, investigators observed 44.8% of patients with ankylosing spondylitis who received treatment achieved ASAS40 compared with 22.5% of placebo. 

According to UCB, response rates increased to week 24 and a rapid achievement of ASAS40 response was seen for patients switching from placebo to bimekizumab at week 16.

“Today’s findings from the BE MOBILE 1 and BE MOBILE 2 studies provide clear evidence supporting the potential of bimekizumab in both nr-axSpA and AS, and highlight the meaningful clinical outcomes that can be achieved by targeting IL-17F in addition to IL-17A," Atul Deodhar, MD, MRCP, Professor of Medicine, Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, 

 "Patients with nr-axSpA and AS have a similar burden of disease and a treatment that could potentially show consistent outcomes across the full spectrum of disease is encouraging.” 

At the start of the trials, most patients (> 97%) had high or very high disease activity. Investigators observered that the outcomes included changes in Ankylosing Spondylitis Disease Activity Score (ASDAS) reports, as well as changes in inflammation in the sacroiliac joints and spine, measured by Magnetic Resonance Imaging (MRI).

Approximately half of the patients treated with bimekizumab from the onset of the study achieved a low disease activity defined as ASDAS<2.1, by week 24. substantial reductions in inflammation in the sacroiliac joints and spine for both AS and nr-axSpA patients at week 16 were also observed among these patients. 

“Patients with axSpA live with a range of debilitating symptoms including chronic back pain and difficulties performing everyday tasks," Désirée van der Heijde, Professor of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands, said in a statement. 

"These interim results from the BE MOBILE 1 and BE MOBILE 2 studies are encouraging, showing that treatment with bimekizumab versus placebo improved signs and symptoms, reduced disease activity and inflammation, and improved physical function," she continued. "We look forward to the 52-week results from these studies expected later this year.”

Bimekizumab Offers Improvements Across Full Spectrum of Axial Spondyloarthritis in Phase 3 Trials

Phase 3 data from 2 studies on bimekizumab for 

 will be presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 . Today, the global pharmaceutical company UCB, announced the results from the research. 

The studies, BE OPTIMAL and BE COMPLETE, evaluated bimekizumab's efficacy in treating adults with active psoriatic arthritis. In BE OPTIMAL, the adults were biologic-naive, and in BE COMPLETE, adults were TNF-inadequate responders.

“Today’s findings from the BE OPTIMAL and BE COMPLETE studies provide clear evidence supporting the potential of bimekizumab, a dual IL-17A and IL-17F inhibitor, in the treatment of active psoriatic arthritis," Joseph F. Merola, MD, MMSc, Associate Professor, Harvard Medical School and Brigham and Women’s Hospital 

. "This painful, chronic condition can greatly impact patients’ lives. Achieving minimal disease activity is an important goal of treatment, that can ultimately lead to improved quality of life for people with psoriatic arthritis.” 

A consistent clinical response was observed across each population. Both sets of data displayed a higher proportion of patients treated with bimekizumab achieved improvements in joint symptoms at week 16 compared with placebo. 

Using the ACR50 for measurement, 43.9% of those who have never been treated with a biologic before, and 43.4% of adults who had an inadequate response to TNF inhibitors had joint improvement compared with the placebo groups who reported 10% and 6.8% joint improvement, respectively. 

By week 16, high levels of skin clearance were also attained by a majority proportion of patients who received the treatment. Within the biolgic-naive group, 61.3% compared with 2.9% had substantial skin clearance, while 68.8% compared with 6.8% of the TNF-inadequate responders similarly showed the placebo group with much lower success. 

Overall, 40% of adults across both groups treated with bimekizumab achieved minimal disease activity compared with placebo, at week 16. 

The humanized monoclonal l IgG1 antibody was designed to selectively inhibit both interleukin 17A (IL-17A) and interleukin 17F (IL-17F), 2 key cytokines driving inflammatory processes.

In addition, to the 2 phase 3 studies already mentioned, bimekizumab is in development for the treatment of active axial spondyloarthritis with 24-week interim analysis results from BE MOBILE 1 (non-radiographic axial spondyloarthritis) and BE MOBILE 2 (ankylosing spondylitis) studies.

These results will also be presented at EULAR 2022.

While the safety and efficacy of bimekizumab in psoriatic arthritis has not been established and its not approved for use in this patient population by any regulatory authority worldwide, each study met their primary endpoint of ACR50, and all ranked secondary enpoints at week 16. 

The results among both patient groups who received the treatment displayed improved outcomes that were statistically significant when compared with placebo. The patients in the treatment groups were administered 160 mg of bimekizumab every 4 weeks.

Both studies performed were randomized, multicenter, double-blind, placebo-controlled, with a parallel-group.

However, BE OPTIMAL was an active reference (adalimumab), parallel-group, phase 3 study that included patients with active psoritatic arthritis who were biologic disease-modifying anti-rheumatic drug (bDMARD) naive. The presented data represent the 24-week interim analysis for the study, as it's ongoing.

BE COMPLETE enrolled adults with active psoriatic arthritis and an inadequate response to tumor necrosis factor-alpha inhibitors (TNFαi). All enrolled patients had a history of inadequate response, described as a lack of efficacy after at least 3 months of therapy at an approved dose, or intolerance to treatment with 1 or 2 TNFαi for either psoriatic arthritis or psoriasis.

Data from 2 studies evaluating adults with active psoriatic arthritis were announced today in preparation for EULAR 2022. The different population groups who received treatment were biologic-naive patients and TNF-inadequate responders.

New Promising Phase 3 Bimekizumab Data Among Patients with Psoriatic Arthritis

Tumor necrosis factor (TNF)-antagonist treatment does result in better outcomes for post-operative Crohn's disease patients (POCDP).

A team, led by Waseem Ahmed, Weill Cornell Medicine, compared the efficacy of biologics in post-operative patients with Crohn’s disease, controlling for recurrent risk factos and prior TNF-antagonist exposure in data presented at the 

Digestive Disease Week (DDW) 2022 Annual Meeting

There currently is a lack of comparative efficacy data on biologics in post-operative patients with Crohn’s disease and how prior anti-TNF treatment exposure impacts outcomes.

In the study, the investigators collected data on 186 patients with Crohn’s disease following their first post-operative biologic treatment using data from prospectively maintained single-center biobanks.

The investigators sought primary outcomes of comparing deep remission (HBI < 5, CD-PRO2 < 8, or remission stated) and objective (endoscopic (SES-CD < 3, Rutgeert’s 

i2a, or absence of ulcers) or biochemical (FCP < 150 µg/g or CRP < 1mg/dL) remission if endoscopy unavailable) between TNF-antagonists and ustekinumab (UST) at 

They also sought secondary outcomes of comparing clinical and objective remission.

The investigators repeated analyses by prior TNF-antagonist exposure, in patients treated < 6 months post-operatively, and in patients with documentation of objective recurrence at treatment baseline and performed multivariable analysis for the primary outcome analyzing factors associated with deep remission.

Overall, patients treated with TNF-antagonists had a higher deep remission rate compared to patients treated with ustekinumab (45% vs. 22%; 

 <0.01), with conclusions identifcal in patients with prior-TNF antagonist exposure (TNF: 44% vs. UST:19%; 

 = 0.03) and clinical (63% vs. 43%, p = 0.03) remission were also higher with TNF-antagonists compared to ustekinumab.

After conducting the multivariable analysis, the investigators found current TNF-antagonist use was the only factor linked to deep remnission (OR, 4.0; 95% CI, 1.7-9.6; 

Outcomes also additionally favored the patients treated with TNF-antagonist in both patients with treatment initiation < 6 months post-operatively (TNF:48% vs. UST:29%, 

= 0.1) and in patients treated after documentation of post-operative recurrence (TNF:44% vs. UST:16%, 

“In the largest study on ustekinumab in POCD, TNF-antagonists were associated with improved outcomes compared to ustekinumab,” the authors wrote. “This reinforces the use of TNF antagonists as the primary therapy in POCD.”

The study, “Su1502: EFFICACY OF TUMOR NECROSIS FACTOR ANTAGONISTS AND USTEKINUMAB IN POST-OPERATIVE CROHN'S DISEASE,” was published online by 

Patients treated with TNF- antagonists had a higher deep remission rate compared to patients treated with ustekinumab.

TNF-Antagonist Therapy Linked to Better Outcomes for Post-Operative Crohn’s Disease

Despite some promise in early phase trials, vedolizumab has no effect on the disease course for patients with 

non-alcoholic fatty liver disease (NAFLD)

A team, led by Ashraf Almonani, MD, Cleveland Clinic, examined the impact of vedolizumab on the course of NAFLD in patients with inflammatory bowel disease (IBD) in data presented at the 

Patients with IBD often have a higher risk of incidence and prevalence of NAFLD, largely because inflammation plays a key role in the pathogenesis of NAFLD.

There has been recent research that suggests the inhibition of integrin-mediated CD4 T cell recruitment leads to improvement and overall reversal of NAFLD-related metabolic derangements.

One such option could be vedolizumab, an α4β7 integrin-inhibitor currently approved for patients with IBD.

In the retrospective cohort analysis, the investigators identified 79 patients with NAFLD who were treated with vedolizumab at the Cleveland Clinic Foundation. An additional 79 patients were part of the matching control group.

The investigators sought primary outcomes of the response to vedolizumab, defined as Fibrosis-4 (Fib-4) regression to <1.3 points after 1 year of treatment.

They also sought secondary outcomes of the progression of the disease, defined as Fib-4 rise to >1.3 points, and reduction in the number of decompensated cirrhosis episodes among those with NAFLD cirrhosis.

Patients excluded from the study included those with chronic hepatitis B virus (HBV), hemochromatosis, Wilson’s Disease, alcohol abuse, Alpha 1-antitrypsin deficiency, autoimmune hepatitis, cystic fibrosis, biliary cirrhosis, halactosemia, or glycogen storage disease.

The investigators also applied appropriate weights for all analyses.

Overall, there was no statistically significant difference in response (

 = 1.000), or change in the number of cirrhosis decompensation episodes among those treated with vedolizumab.

“In this retrospective cohort analysis, and unlike in the animal model, Vedolizumab was not associated with statistically significant improvement or progression in the Fib-4 score after one year of treatment, and among those with NAFLD-cirrhosis, there was no statistical difference in the complication rates,” the authors wrote.

Su1364: VEDOLIZUMAB HAS NO EFFECT ON THE COURSE OF NON-ALCOHOLIC FATTY LIVER DISEASE: A RETROSPECTIVE COHORT ANALYSIS

Patients with IBD are often at an increased risk of developing NAFLD.

DDW Research Shows No Efficacy for Vedolizumab in Treating NAFLD

New findings suggest patients with obesity who underwent bariatric surgery had improved outcomes when hospitalized with myocardial infarction, as data show lower inpatient mortality and lower rates of multi-organ failure.

“Bariatric Surgery improves outcomes of [myocardial infarction] and should be considered life-saving for patients with obesity who have a risk for cardiovascular disease,” wrote study author Roberto Simons-Linares, MD, Cleveland Clinic.

Simons-Linares and colleagues investigated the inpatient mortality of those with obesity hospitalized with MI and compared those with a history of bariatric surgery, versus no history. They conducted a case-control study with a patient population obtained from the 2016 and 2017 National Inpatient Sample (NIS). Investigators used ICD10-CM and PCS code to identify patients with obesity hospitalized with MI and individuals with a history of bariatric surgery.

They explained primary outcomes as the differences in mortality rate and rates of inpatient outcomes and complications between patients with bariatric surgery and then those without, considered the control cohort. These were followed by secondary outcomes of organ failure, including acute kidney injury (AKI), respiratory failure requiring mechanical ventilation, shock, sepsis, and length of stay. Investigators constructed multivariate regression models to adjust for confounders and hospital characteristics.

A total of 290,450 (weighted) hospitalizations were included in the study. From this population, 3,805 had a history of bariatric surgery. Data show inpatient mortality rates were lower in patients with history of bariatric surgery (0.8% vs 2.3%; 

They additionally observed bariatric surgery was a protective factor, having lower odds of inpatient mortality after MI (odds ratio [OR], 0.34; 95% CI, 0.15 - 0.76; 

 = .01). When adjusting for multiple comorbidities and baseline characteristics between each group, bariatric surgery still had a protective effect (adjusted OR, 0.44; 95% CI, 0.19 - 0.98; 

Then, investigators noted bariatric surgery patients had lower rates of respiratory failure requiring mechanical ventilation (OR, 0.52; 

 <.01), and shorter length of stay (OR, 0.51; 

The study, “Bariatric Surgery Decreases Mortality When Hospitalized With Myocardial Infarction,” was presented at 

New data from DDW 2022 show inpatient mortality rates were lower in patients with history of bariatric surgery. 

Bariatric Surgery Linked to Improved Outcomes After Myocardial Infarction

New findings suggest the microbiota-based investigational live biotherapeutic, RBX2660, restored microbiome and bile acid compositions concurrent with clinical response in patients with recurrent C.difficile infection. 

The findings additionally suggest the restorative changes may be characteristic of shifts from a post-antibiotic dysbiosis state to a healthier state.  

Digestive Disease Week 2022 Annual Meeting, 

Ken Blount, PhD, Chief Scientific Officer, Rebiotix and VP Microbiome Research, Ferring Pharmaceuticals, provided his perspective on the poster of distinction. 

Blount noted that the investigational treatment at one week of treatment led to a restoration of both bacteroidia and clostridia in the 3 clinical trials, which continued until the end of the follow-up period, including up to 24 months.  

"All of that told us that we were doing what we set out to do, which was to shift the microbiota in those trials from before to after treatment in a way that we felt could help resist or reduce recurrent C Diff infections," Blount said. 

From the bile acid analysis in the study, investigators observed that prior to treatment, secondary bile acids were very low and primary bile acids were very high. After seven days of treatment in these trials, they found restoration towards predominance of the secondary bile acides produced by healthy microbiota. 

"That sets up a very clear model in which prior to treatment patients are very vulnerable to see deferred growth and potentially recurrence whereas after treatment in these trials, they shifted to a state that you would call colonization resistance," Blount explained. 

Blount continued to discuss safety signals of RBX2660, using the investigational agent for treatment of other diseases outside of C.diff, and the potential for other studies looking into the biotherapeutic. 

The study, "Microbiome and Bile Acid Restoration Was Consistent Across Three Clinical Trials of RBX2660 for Recurrent Clostridiodes Difficile Infection: A Combined Analysis," was presented at 

Dr. Blount discusses the DDW 2022 poster of distinction on the investigational live biotherapeutic. 

Ken Blount, PhD: Effect of RBX2660 on Microbiome and Bile Acid Composition 

According to new findings, patients with with eosinophilic esophagitis (EoE) exhibit persistence of significant accelerated molecular aging of the esophagus relative to patient chronologic age after an initial 8-week course of topical steroids, irrespective of histologic treatment response.

“Long term assessments are needed to evaluate the implications of accelerated aging on disease progression, complications, and comorbidities,” wrote study author Elizabeth T Jensen, MPH, PhD, Wake Forest University School of Medicine. 

Previous findings showed that individuals with EoE exhibit accelerated epigenetic molecular aging of the esophagus relative to patient chronologic age. The implications of advanced molecular aging in patients with EoE are unknown and post-treatment molecular aging has not previously been examined, investigators said.

Thus, the current study aimed to determine whether post-treatment esophageal cells from EoE patients exhibit molecular aging, as well as compare post-treatment molecular age to pre-treatment molecular age. Further, it aimed to determine whether post-treatment molecular age relative to chronologic age differs as a result of treatment response.

Investigators extracted from esophageal biopsies obtained at the diagnostic endoscopy and initial post-treatment endoscopy following 8 weeks of topical corticosteroid treatment. The histologic treatment response was defined as an absence of any esophageal eosinophilia (0 eos/hpf)

Additionally, the study authors noted that pre- and post-treatment DNA methylation was assayed on the Illumina Human Methylation450 and MethylationEPIC BeadChips, respectively. Arrays were processed using standard protocol and best practices for normalization and quality control, investigators said.

Furthermore, normalized β values for 353 CpG probes were submitted to an online DNA methylation age calculator in order to calculate a patient’s methylation age. A Mann Whitney U test evaluated the difference between molecular age and chronologic age post-treatment, molecular age post- and pre-treatment and responded versus non-responder.

From a total of 14 individuals with both pre- and post-treatment samples, there were 7 responders (57% female: 100% white, 100% atopic) and 7 non-responders (57% female; 100% white; 71% atopic).

In the responder cohort, peak eosinophils decreased from 155 ± 108 eos/hpf to 0 ± 0 eos/hpf post-treatment, but were unchanged in the non-responders (baseline: 137±152 eos/hpf; post-treatment 147 ± 82 eos/hpf).

The median patient chronological age at diagnosis was 36.5 years. The median molecular age was 48.9 years pre-treatment and 46.4 years post-treatment. Then, investigators noted that post-treatment, molecular age remained significantly greater than chronological age (

 <.001), with a median difference of 18.6 years.

No difference in median molecular age was found when comparing pre- and post-treatment (

 <.44), according to investigators. Moreover, no significant difference in accelerated aging was seen by treatment responder status.

The study, “Accelerated Molecular Aging Persists Despite Successful Treatment and Histologic Resolution in Eosinophilic Esophagitis,” was presented at 

Post-treatment, data show molecular age remained significantly greater than chronological age at a median difference of 18.6 years. 


Long-Term Assessments Needed to Evaluate Impact of Accelerated Aging on EoE Progression

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