This transcript has been edited for clarity.
Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.
I've just returned back from San Diego, where Digestive Disease Week 2022 was held.
I wanted to call out 10 abstracts that I thought had potentially practice-changing implications for your practice, as I think they will for my practice as well.
Adenoma Detection Rate in Fecal Immunochemical Testing
Patients with positive results on fecal immunochemical testing should have a high adenoma detection rate (ADR).
We've seen a number of reports and recommendations from the national societies indicating that, rather than the 25% blended rate, this number should be closer to 45%. A recent meta-analysis suggested that this number should be north of that even, in the 48%-49% range.
This first study I'd like to discuss came from a team of investigators in the Netherlands. They looked at high-level adenoma detectors, with 383 endoscopists performing 233,945 colonoscopies. The ADR ranged from 42%-78%, with a median detection of 65%. The investigators found that the rate was particularly driven by high-level adenoma detection, and every 1% increase in the ADR was associated with a 7% risk reduction in interval colon cancers.
The investigators concluded that the standard ADR target now should be raised to 60%, which is well north of 25% for sure. I think this is a practice-changing recommendation. We should be doing this analysis anyway, which would drive us to a higher-level of expectation for ADR.
No Increased Malignancy Risk With Ustekinumab
The second presentation of interest was on malignancies in patients treated with ustekinumab, a human monoclonal antibody that we've used for a number of years now in ulcerative colitis and Crohn's disease. It's also associated with treatment indications for psoriatic arthritis and plaque psoriasis.
This is a cohort analysis of 13 studies, offering long-term safety data out to 5 years in Crohn's disease, 2 years in ulcerative colitis, 5 years in psoriasis, and 1 year in psoriatic arthritis. Investigators identified 6710 patients treated with ustekinumab, which amounted to nearly 14,000 patient-years.
There were no significant signals for malignancy risk. There was a slight increased risk in squamous cell-type cancers in patients with psoriasis, but we should recognize these are patients who are also treated a lot with ultraviolet light and have independent risks in and of themselves. So this is good news as it relates to our patients being treated with ustekinumab, at least in the long-term basis.
Malnutrition in Patients With Inflammatory Bowel Disease
The third potentially practice-changing study comes from a nationwide analysis of malnutrition and nutritional support in hospitalized patients with inflammatory bowel disease (IBD).
Investigators analyzed approximately 1.2 million patients with Crohn's disease, 811,000 with ulcerative colitis, and 240,000 without IBD. The primary focus was for protein-calorie malnutrition.
Patients with IBD were 2.7-2.9 times more likely to have protein-calorie malnutrition. Using multivariate analysis, they were also able to demonstrate that these patients had higher risk for readmission mortality, longer lengths of stay, and higher hospitalization costs.
From my perspective, these results are practice changing. When patients with IBD present, it's recommended to look at nutritional status, assess for it, and potentially offer dietary assistance while they're there. That will allow you to at least get them under the auspices of hospitalization.
Hepatitis B Reactivation During Anti–Tumor Necrosis Factor Therapy
The next study that I thought was quite interesting relates to the role of hepatitis surface antibody for the risk of reactivation for hepatitis B virus during anti–tumor necrosis factor therapy.
Investigators looked at 1375 patients from 19 cohort studies. They defined reactivation by a hepatitis B surface antigen seroconversion when they were hepatitis B core antibody positive.
Lo and behold, there were 25 cases that reactivated, but they were able to find a discriminant threshold of 100 IU/L for the hepatitis B surface antibody titer. Only four cases occurred when this titer was > 100 IU/L.
The authors noted the importance of obtaining a quantitative baseline of the surface antibody level and perhaps giving a booster vaccination if the titer level falls below 100 IU/L and maintaining that going forward. We do not have any of the prospective data to apply this. However, it seems to be easy and relatively low risk to provide this vaccination. I'm going to start doing this in my practice.
A Novel Treatment for Celiac Disease
Next is a very exciting study looking at the safety, tolerability, and pharmacodynamic assessment of a therapy called KAN-101; admittedly, not that catchy of a name.
This is a novel liver-targeted therapy to induce immunologic tolerance to gliadin in celiac disease.
Investigators randomized patients to receive three separate doses of KAN-101 over the course of a week, followed by a gluten challenge for 3 days.
They then looked at gliadin-specific T-cell responses. They found a demonstrable and very significant reduction in intolerance to the gluten challenge.
On the horizon, these results are very promising as it relates to our patients with celiac disease.
Reconsidering Fluid Resuscitation Approaches in Acute Pancreatitis
Something with perhaps more immediate practice-changing implications is the multicenter controlled WATERFALL trial, which compared aggressive vs moderate goal-directed fluid resuscitation for acute pancreatitis.
We've always taught our residents to give such patients lots of fluid when they hit the emergency room. There's a retroperitoneal burn; they're fluid depleted and they need to get more fluid. The national guidelines have suggested this as well.
However, this approach has recently begun to be challenged.
In this prospective study conducted by 18 multinational centers, investigators randomized patients to receive a lactated Ringer's solution 20 mL/kg bolus over a 2-hour period followed by 3 mL/kg/h. This was compared to the moderate fluid resuscitation with a lactated Ringer's bolus of 10 mL/kg in the case of hypovolemia and no bolus in patients with normovolemia.
The patients were then followed up with a maintenance dose of 1.5 mL/kg/h. The patients were assessed at 12, 24, 48, and 72 hours.
Investigators observed no change in pancreatitis. However, there was a significant change related to pancreatic fluid overload. Patients treated with the aggressive approach developed signs of fluid overload at a nearly three-times-greater rate than those with the moderate approach. There was a trend as it relates to organ failure or any type of peripancreatic necrosis.
We're starting to recognize that we can give too much of a good thing with fluids. In fact, they stopped this trial at the interim analysis, recognizing the risk. So take a step back on your fluids, consider goal-directed fluid resuscitation, and assess their fluid volume status when they come in.
Extended Budesonide Appears Safe in Microscopic Colitis
The next study, which came from investigators at the Mayo Clinic, dealt with budesonide in microscopic colitis.
They identified 450 patients with microscopic colitis that was lymphocytic or collagenous but were grouped together for this presentation. Of these patients, 162 were treated with budesonide. The median age of these patients was 67 years, although it ranged from 23 to 91 years, and 78% were women.
The good news was that 80.2% of patients treated with budesonide had a complete response, 13.6% had a partial response, and 4.9% had no response.
But after induction, 63.2% had recurrence after discontinuation, which is something we also see in clinical practice. Of these, 28.1% required further budesonide induction without maintenance, 58.3% required long-term budesonide maintenance, and 13.5% received other treatments like a bile acid binder of bismuth subsalicylate.
The median time to recurrence after induction was 98 days, with a range of 7-221 days.
All patients responded who received budesonide maintenance. So once they relapsed, if they came back and they needed to be retreated, 98% of patients had complete response. But after discontinuation of maintenance, they tended to have a relapse, with 46.4% having recurrence. Budesonide was then restarted in 88.5% of these patients, again with a very high sustained response. The cumulative duration of the maintenance treatments was 62 weeks, which ranged anywhere from 16 weeks to 469 weeks, so there was an extended follow-up in this study.
They did not provide any data regarding adrenal axis assessment, but there were no significant or major problems that they identified.
Using steroids does have implicit risks, but it's seemingly safe as it relates to extended budesonide. Certainly, patients who relapse have a high rate of response.
The First Approved Drug for Eosinophilic Esophagitis
Next was a very exciting study with dupilumab, which was approved the same week of the meeting by the US Food and Drug Administration.
Dupilumab is a human monoclonal antibody that blocks a shared receptor for interleukin (IL)-4 and IL-13. These are the key drivers for the type 2 inflammation we see in eosinophilic esophagitis.
In the phase 3 study, 240 patients were randomized to two doses of dupilumab and placebo. In fact, the higher dose, the 300-mg weekly, was the dose that was most effective as it relates to the targeted endpoint of the resolution of their symptoms.
The secondary outcomes included the change in Dysphagia Symptom Questionnaire and Endoscopic Reference Score, as well as driving the eosinophil count to ≤ 6.
This was accomplished in approximately 58% of the patients who received the 300 mg dose weekly. The every-two-week dose seemed to be effective but didn't meet the same objectives.
These results are what led the FDA to recently approve the first drug for eosinophilic esophagitis. It's a subcutaneous injection and seems to be very well tolerated. Its safety profile seems to be quite good as well. We can say this study has practice-changing implications in the short term.
Promising Phase 3 Results for Mirikizumab in Ulcerative Colitis
The next was a trial of another exciting drug for ulcerative colitis, mirikizumab, a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23.
Because this is a phase 3 study, patients who had responded in the induction series were then re-randomized in a 2:1 ratio, giving a 200-mg subcutaneous dose every 4 weeks for 40 weeks and compared with placebo.
At week 40, there was a combined clinical remission — this included endoscopic, histologic, and symptom-directed analyses — of approximately 50% compared with placebo. That's a 25% absolute risk reduction. It was also well tolerated with no safety signals.
So again, on the short-term horizon, this is a new drug for ulcerative colitis with a very good response rate, particularly once patients have achieved initial remission.
A New Class of Treatments for Erosive Esophagitis
The last study looked at vonoprazan, which is among the class of drugs called a potassium-competitive acid blocker, or a P-CAB. There have been a number of these under investigation. This one is currently available in the United States as a treatment of Helicobacter pylori.
This was a double-blind trial conducted in adult patients in the United States and Europe with H pylori–negative erosive esophagitis. Investigators compared patients at an 8-week healing phase as well as at week 24 for maintenance. This is a dose-ranging study of vonoprazan and lansoprazole.
The investigators found that vonoprazan was noninferior to lansoprazole in mean free-heartburn days but superior as it relates to absolute healing of esophagitis, across all grades of esophagitis.
The relative risk reduction in the 8-week data was approximately 8%. As it relates to severe esophagitis, the absolute risk reduction was closer to 20%, particularly when you got to the higher 20-mg dose of vonoprazan.
This was particularly true for the maintenance dose, where the discriminant difference was 8% for the 20-mg dose (P < .007) and a little north of 7% (P < .022) for the 10-mg dose.
Healing continued with the maintenance dose. The absolute maintenance risk reduction was approximately 7%, and compared with the two doses of vonoprazan, it was a little higher with the 20-mg dose.
Interestingly, there was no difference in heartburn-relief–free days, despite these two doses and the lansoprazole.
There are short-term implications for this on the horizon. We have it as a target for H pylori, but it will also likely soon be available for patients with more severe esophagitis, which is where I really think this treatment would find a unique place.
In summary, there was lots of new data with potentially practice-changing implications on both the short- and long-term horizon. Hopefully, these brief summaries have given you some good perspective on what went on at Digestive Disease Week 2022.
Thanks for listening.
David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.
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Cite this: David A. Johnson. 10 Highlights From Digestive Disease Week 2022 - Medscape - Jun 08, 2022.