11 Studies to Know From ACG 2021

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 from the annual meeting of the American College of Gastroenterology (ACG), which was recently reported to be the largest gastroenterology association in the world. This year's meeting was held in Las Vegas, live and in person, although there was a hybrid combination of virtual and onsite presence. It was so good to reconnect with colleagues and not have it be on a Zoom call.

ACG 2021 featured around 3500 abstracts, plenaries, and poster presentations. I've reviewed nearly all of them in order to give you my perspectives on the findings I believe to have the greatest practice-changing implications going forward.

Using Adenomas per Colonoscopy for Detecting Colorectal Cancer

Dr Joseph Anderson and colleagues from New Hampshire compared mean adenomas per colonoscopy vs the adenoma detection rate (ADR) as a quality measure for interval cancer protection.^[1] They evaluated 9023 colonoscopies from 138 endoscopists to assess for interval colorectal cancer diagnosed within 3 years.

They found that adenoma per colonoscopy may be as discriminant for interval cancer protection as ADR. An adenoma per colonoscopy cutoff of 0.4 per screening colonoscopy was on par with an ADR of 25%, which is conventionally recognized as the minimum threshold for a mixed-gender population. Increasing the adenoma per colonoscopy cutoff to 0.6 further improved outcomes by about a third.

In light of these results, I'd expect the guideline committees to consider evaluating adenoma per colonoscopy a little bit more. It perhaps makes more sense that rather than a one-and-done adenoma approach, you should be evaluating how many you actually detect over the course of the colonoscopy.

Evaluating Immunotherapy-Mediated Colitis

Immunotherapy-mediated colitis is an adverse event that ranges from mild to moderate in severity, and which we increasingly encounter as immune checkpoint inhibitors are expanded to treat cancers of the skin, breast, lung, and other indications. The question is, do you need a full colonoscopy to make the diagnosis?

In a cross-sectional, single-center study,^[2] researchers analyzed 52 symptomatic patients taking immune checkpoint inhibitors to compare the value of colonoscopy vs a left-sided sigmoidoscopy exam. They found that the sigmoidoscopy diagnosed 100% of patients with immunotherapy-mediated colitis. There was no additional value gained by performing biopsies more proximally.

The teaching points here are that biopsies should be taken from both normal and abnormal mucosa, and that flexible sigmoidoscopy may save patients from having to have a full colonoscopy.

New Data on Ozanimod

There were two presentations on ozanimod, a new treatment for moderate to severe ulcerative colitis approved by the US Food and Drug Administration in May 2021. Ozanimod is an oral sphingosine 1-phosphate receptor modulator administered at a 1 mg daily dose, which is very promising for our patients with ulcerative colitis.

The first presentation,^[3] which was given by Dr Bruce Sands of Mount Sinai in New York City, drew on data from a phase 3 trial assessing the efficacy and safety of ozanimod up to 52 weeks. In a post-hoc analysis, researchers evaluated the impact of prior biologic exposure on the response to ozanimod. The results indicated that prior biologic exposure was not a meaningful predictor for clinical response to ozanimod. It may have taken longer to get a response among those previously exposed to biologics; nonetheless, ozanimod showed a very promising sustained effect at up to 52 weeks in these patients.

The second presentation^[4] was given by Dr Marla Dubinsky, also from Mount Sinai, and offered a follow-up on ozanimod's efficacy and safety over a 52-week window. There are no head-to-head randomized controlled trials with this agent vs other conventional biologics. In the absence of this, researchers used a matching-adjusted indirect comparison with other studies of comparable design. They determined that ozanimod had a superior safety profile to adalimumab at both induction and maintenance. Ozanimod was comparable to vedolizumab at induction, but better over maintenance therapy.

With a new therapy such as this, it's reassuring to see the positive safety profiles extending out for up to a year.

Risankizumab for Crohn's Disease

We have another exciting new agent in the treatment of inflammatory bowel disease. Risankizumab is a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23.

Dr David Rubin from the University of Chicago presented results from dual double-blind, placebo-controlled, randomized, multicenter phase 3 trials of risankizumab in moderate to severe Crohn's disease.^[5]

There was no difference shown between two doses of intravenous risankizumab. However, the Crohn's disease activity index and a composite endpoint, including endoscopic assessment, showed that there was sustained and seemingly increased benefit, both in remission and response, through 12 weeks of treatment.

Biologic therapy seemed to be a bit laggard if you had inadequate or no response to prior biologic therapies going into this trial.

We should keep in mind that these are only 12-week data and we'll need to see more. That being said, I think this treatment is extremely promising for moderate to severe Crohn's disease.

Emerging Microbiome Data

There were two very interesting presentations on the subject of the microbiome.

The first was a randomized, placebo-controlled trial looking at the relapse of Clostridioides difficile.^[6] Dr Jessica Allegretti and colleagues studied a new oral microbiome therapy in patients at high risk for C difficile recurrence. After receiving initial antibiotic treatment, patients underwent a 2-day washout period and were then randomized to receive either the oral therapy or placebo without a bowel preparation. The primary endpoint was sustained clinical cure at week 8.

They found that use of the oral therapy was associated with a statistically significant benefit of approximately 13%. This would translate into a number-needed-to-treat of around 7 to 8.

These results indicate that this intervention does seem to change microbial diversity. It therefore represents a new potential therapy that, once approved, may prove helpful for preventing C difficile relapse in such patients.

The second study^[7] set forth an interesting therapeutic concept by using fecal microbiota transplants (FMT) for hepatic encephalopathy. Researchers from the University of Michigan looked at 10 patients who received FMT capsules derived from five healthy donors, administered five times over 3 weeks.

The investigators looked at the 6-month composite scores for hepatic encephalopathy and showed that there was a significant benefit for the patients receiving FMT. This positive effect didn't seem to correlate with changes in Model for End-Stage Liver Disease scores or venous ammonia scores among those receiving FMT. These patients were also receiving rifaximin and lactulose, so the effect seems to be additive to those current standards as well.

Predicting Relapse Following TIPS Placement

Renal function is something that we don't traditionally use to predict relapse following transjugular intrahepatic portosystemic shunt (TIPS)-related hepatic encephalopathy.

Researchers assessed the value of stratifying relapse risk by glomerular filtration rate (GFR) in 201 patients receiving TIPS for refractory ascites, approximately 40% of whom met the criteria for chronic kidney disease; of these, 21% were hemodialysis dependent. They found that among those with a GFR < 30 at the time of TIPS, the odds ratio for hepatic encephalopathy was 3.5 times greater at 6 months.^[8]

This indicates that perhaps we really need to get better at stratifying for prediction of hepatic encephalopathy in these patients. This stratification system may be a way of doing that, although further work is certainly needed.

Impact of Changing Age Recommendations for Colonoscopy

New guidelines have recommended lowering the age to initiate colorectal cancer screening to 45 years.

Dr Aasma Shaukat and colleagues used the GIQuIC registry to determine whether lowering that threshold to 45 years would change our ADR benchmarking.^[9] They looked at over 3 million colonoscopies, of which approximately 180,000 were in this new age range of 45-49 years.

They found that the ADR was 39% for men and 27% for women aged 50-54 years. Therefore, the composite ADR was 36.8%, which is way above the conventionally recognized 25% threshold for ADR. But by now incorporating those aged 45-49 years, the ADR changed only modestly to 34.4% for men and 31.8% for women.

In fact, if a quarter of the patients you screened in your practice were in the age range of 45-49 years, the authors extrapolated that your ADR would fall by 2%. And if this age group accounted for half of your screening colonoscopies, which is likely inconceivable, your ADR would fall by just 5%.

These results indicate that ADRs are unlikely to change substantially as a result of these updated guidelines. However, we must recognize that these ADR benchmarks are much higher than the 25% threshold we previous defined as quality, so we need to move the goalposts.

Concerning Findings About Pancreatic Cancer

There has been an increasing rise of pancreatic cancer over the past two decades, according to an analysis from the Surveillance, Epidemiology, and End Results (SEER) database.^[10]

Researchers reviewed data from 2000 to 2018 and found an incremental rise in the risk for pancreatic cancer for men and women, but with a notable discriminant. At 50 years and older, incidence rates in men seemingly continue to rise, with no evident parallel trend for women. But in the lower threshold ages — in particular, those aged 15-34 years — there was a phenomenal difference as it relates to women: The incidence rate of pancreatic cancer is projected to be 400% that of men by 2040.

These are eye-opening, earth-shattering numbers. We need to be looking more closely at younger women. We may need to offer improved screening, but we need to improve upon our diagnosis of onset of early symptoms. That may lead us to better therapies, which remain pretty abysmal for pancreatic cancer.

Eosinophilic-Related Gastrointestinal Disorders

We're certainly aware of the risks posed by eosinophilic gastrointestinal (GI) diseases north of the stomach when it comes to eosinophilic esophagitis, but we need to be conscious of those south of the esophagus as well.

An international multicenter study coordinated by Dr Nicholas Talley recruited over 550 patients with moderate to severe chronic GI symptoms ranging from irritable bowel syndrome to functional dyspepsia.^[11] Researchers performed programmatic biopsies (eight gastric, four duodenal) in these patients, looking at both normal and abnormal tissue, which were then read by blinded GI pathologists.

Lo and behold, they found that using the threshold of ≥ 30 eosinophils per high-power field in five gastric fields and in three duodenal fields led to the diagnosis of these eosinophilic-associated gastrointestinal diseases in 45% of these patients compared with 6% of healthy controls. These results tell us that we need to biopsy more in both normal and abnormal tissues. More diagnoses seemed to come from the antrum.

So, we need to look at expanding the diagnosis and consider changing therapies. Treatment strategies are evolving in this class of diseases. We should recognize the eosinophilic diseases that lay south of the esophagus, and we need to do better at defining them.

In summary, ACG 2021 offered lots of exciting new concepts. Hopefully you will find this overview meaningful to your practice.

I'm Dr David Johnson. 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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