COMMENTARY

Seven Practice-Changing Studies You Need to Know: ACG 2019

David A. Johnson, MD

Disclosures

December 19, 2019

This transcript has been edited for clarity.

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at the Eastern Virginia Medical School in Norfolk, Virginia.

I'm back from the American College of Gastroenterology (AC) annual scientific meeting, which was held in San Antonio, Texas. I always return from these meetings enthused and energized by the latest data being presented, the educational opportunities, and the camaraderie of my colleagues. If you haven't experienced this personally, I encourage you to come to the next meeting.

There's always a wealth of cutting-edge science presented at these meetings, and this year was no different. I came across several studies with potentially game-changing implications, both now and on the immediate horizon. Here are what I consider to be a few of the key studies.

Budesonide Shows Striking Efficacy for Eosinophilic Esophagitis

Dr Ikuo Hirano, an expert in the field of eosinophilic esophagitis, presented results[1] from a multicenter phase 3 study assessing its treatment using budesonide oral suspension at 2 mg twice daily for 12 weeks. Participants, all of whom were nonresponsive to proton pump inhibitors, were randomized 2:1 to receive budesonide or placebo control. The study's primary endpoints were histologic improvement (resolution of eosinophilic infiltration with a target of ≤ 6 eosinophils per high-power field) and dysphagic symptom improvement at 12 weeks.

Budesonide's efficacy seems very good. Histologic improvement was quite striking, occurring in 53% in the active treatment group compared with 1% in the placebo group. Active treatment also led to statistically significant improvements compared with placebo as it relates to the Endoscopic Reference Score (P < .001) and the Dysphagia Symptom Questionnaire (P = .015).

Cortisol levels were checked in these patients, and even if you're using it for a limited period of time, we can't forget that budesonide is a steroid and that the potential for adrenal axis suppression needs to be considered.

We'll await results from an ongoing double-blind placebo-controlled maintenance study to see how this treatment fares with additional follow-up.

Identifying ARFID Is Not so Clear-Cut

The next noteworthy study is a retrospective analysis[2] of avoidant/restrictive food intake disorder (ARFID) that is increasingly being emphasized in adult gastroenterology.

ARFID is a categorization in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the bible, if you will, for mental health. This is a diagnosis that's established by restriction or avoidance of food intake that is associated with weight loss, nutritional deficiencies, dependence on tube feedings or oral supplements, or significant psychosocial impairment. I'm sure you've seen these patients in your practice as well, who say things like, "I just can't eat this," or "It scares me to death to do this."

Among 223 adult gastroenterology patients, a retrospective diagnosis of ARFID was made in 28 (12.6%). However, 0% of these patients actually met the criteria for this diagnosis upon initial review. It was instead picked up on the back end.

Compared with those without ARFID, those with the diagnosis were less likely to have underlying psychologic or psychiatric disorder or use a psychotropic medication (P < .01) and had a statistically similar history of eating disorder (P = .12). This is not what you would expect for a standard patient with ARFID. They were less likely to report body image concerns but were more likely to report frustration with not being able to eat the type of foods they wanted (P < .5).

When encountering patients with ARFID, you may want to start thinking about involving behavioral therapists, a dietary therapist, and particularly someone with an interest in gastrointestinal disease. It's going to take a multidisciplinary team approach to treat them.

This team of investigators have not presented data on treatment interventions yet, but I'm confident that they will soon. In the meantime, I recommend you start thinking about these results regarding ARFID in your adult patients.

Vedolizumab for Ulcerative Colitis: Not Just an IV Treatment Anymore

Douglas Wolf presented results from a phase 3 trial[3] on transitioning patients with ulcerative colitis from IV vedolizumab to a subcutaneous (SC) formulation. Vedolizumab is a monoclonal antibody targeting the alpha-4 beta-7 integrin.

This presentation combined the results from two trials, comprising three different groups transitioning from IV vedolizumab to SC vedolizumab at 108 mg, which is a very low dose that was nonetheless proven to be highly effective in pretrial pharmacokinetic and pharmacodynamic analyses. The first group received two IV infusions and were then randomized to SC maintenance treatment if they achieved clinical response at week 6; the second group received three IV infusions and did not achieve clinical response at week 6 but did so at week 14, at which point they received SC maintenance treatment; and the third group received SC vedolizumab after a year of continued IV treatment.

What was striking was that patients who transitioned to SC vedolizumab after receiving two and three IV infusions had clinical remission rates of 46%-39%, respectively, and clinical response rates of 65% and 48%, respectively, at approximately 1 year. What really caught my eye were the people that were in clinical remission after 52 weeks of IV vedolizumab, approximately 77% of whom maintained clinical remission and clinical response rates for another 26 weeks with SC vedolizumab.

These results indicate that there's a new possibility to roll over patients with ulcerative colitis from IV to SC vedolizumab.

I think the patients will be very excited about that prospect, as will clinicians about the safety and efficacy of this drug.

Obeticholic Acid's Potential in NASH

We have been hearing more about obeticholic acid, a selective farnesoid X receptor agonist, which regulates bile acid homeostasis. The farnesoid X receptor is a key mediator of liver regeneration.

Results from an interim analysis at 18 months[4] were presented from an ongoing phase 3 trial in patients with nonalcoholic steatohepatitis (NASH) and fibrosis scores of 2 or 3, as well as an exploratory group of fibrosis stage 1 patients with metabolic syndrome. Patients were randomized to receive placebo or obeticholic acid at two doses (10 mg and 25 mg). The intent-to-treat patient population included over 900 patients.

The primary endpoint of fibrosis improvement (≥ 1 stage) was achieved by 12% relative to placebo. This endpoint was achieved by 17.5% of those receiving the 10-mg dose of obeticholic acid, which was superior to placebo (P = .04), and by 23% of those receiving the 25-mg dose. Although fibrosis scores improved with treatment, there wasn't a statistical improvement as it relates to resolution of NASH itself. However, features such as hepatocellular ballooning and lobular inflammation were improved with a 25-mg dose.

Pruritus was the most common side effect, particularly in the 25-mg arm, with about half of these patients experiencing this skin irritation. Most patients in this arm rated the pruritus as mild to moderate, with 5% considering it severe.

The key result to note here is that obeticholic acid led to fibrosis and histologic improvement in a disease state in which we have really not had much luck to date.

Physician, Heal Thyself: Avoiding Endoscopy-Related Injuries

The next study looked at what we as gastroenterologists don't do well: avoiding endoscopic-related musculoskeletal injuries.

Researchers[5] sent out a 38-item survey to AC members through the Women in GI Committee and AC Governing Board sponsorship. Lo and behold, members who completed the survey did report experiencing these musculoskeletal injuries. Specifically, 71% of responders—nearly half of whom were trainees—reported elements of endoscopy-related injury. That's an astounding rate for trainees just beginning their career, who noted particular problems with their thumbs, hands, fingers, neck, and back. Over two thirds of respondents had no training in this in their fellowship, and even those already in practice did not discuss ergonomic strategies to avoid these injuries.

Anybody old enough can relate to having some of these injuries through their involvement in gastroenterology and endoscopy, and it clearly remains a huge unmet need. I'd like to refer readers to an excellent video by Dr Patrick Young posted on the ACG's Educational Universe, which is really a must-see for anybody who performs endoscopy and wants to know more about ergonomic strategies.

No Apparent Increased Risk for Metachronous Lesions in Young Adults With Adenomas

Patients aged younger than 45 years with adenomas are receiving increased interest, thanks in part to a big push for early screening from the American Cancer Society.

Dr Joseph Anderson presented findings from an analysis[6] that he and his colleagues performed using data from the New Hampshire Colonoscopy Registry. They asked whether these younger patients with an index polyp were at an elevated risk for metachronous high-risk adenoma (ie, > 1 cm, with villous histology or high-grade dysplasia, or colorectal cancer). Eligible participants had at least one index adenoma and/or serrated lesion, with a follow-up endoscopy at least 1 year after the index exam. Over 10,000 adults were included in the cohort.

Investigators found that those younger than 40 years were actually at no significant risk for metachronous lesions. Their absolute risk was substantially lower than others, with a P value of < .0001, meaning that it was basically off the charts. This held true for those aged 40-49 years and even those aged 50-59 years. Even when they coadjusted for variants like gender, body mass index, and smoking, it really didn't change that much.

Therefore, rushing to scope these patients early after finding a little adenoma doesn't do much, because they're not at high risk for these metachronous lesions, at least as suggested by this study.

Hyperbaric Oxygen for Refractory Pouchitis

Last, a group from the Cleveland Clinic provided results from a retrospective case series of patients with a history of ileal pouch-anal anastomosis and refractory pouchitis receiving 30 sessions of hyperbaric oxygen over 2 months.[7]

There was a remarkable overall improvement observed. Among 21 patients, 62% experienced subjective improvements in factors like stool frequency and urgency, 81% had endoscopic improvement, and 10% endoscopic remission. I thought it quite striking that among nine patients with fistulas, seven (78%) responded with healing of their fistula tract.

I thought this was an intriguing new intervention. If you have a patient with refractory pouchitis, you may want to consider treatment with hyperbaric oxygen. If you don't have a center for this, as they do at the Cleveland Clinic, you may want to think about referring your patients to one early in the process.

There was certainly lots of new science on display at this year's AC meeting. I think some of these studies will be long-term players, if their results are confirmed in published manuscripts that further explore these concepts. And, certainly, others already seem to be the real deal right now.

I'm Dr David Johnson. Thanks again for listening.

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