Data from the 28-week extension of the LIBERTY EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Many patients don't respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab's effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.
"The current treatments are [proton pump inhibitors], steroids, or diet — a good proportion of patients don't respond to them. And they're also not targeted," Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dellon presented the research at the annual meeting of the American College of Gastroenterology (ACG).
Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dellon. "You can't compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it's a harder to treat cohort is pretty impressive from that standpoint," said Dellon.
"The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes," said Dellon.
Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.
At ACG 2021, Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% vs 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).
The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.
Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).
Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 vs –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).
Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.
"I thought the data was really impressive and compelling," said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who co-moderated the session. "It'd be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term."
If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said co-moderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.
One concern with dupilumab would be any potential for immune suppression. "It's always something to think about," Hass said.
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dellon has consulted and received research support from numerous pharmaceutical companies. Oxentenko and Hass have disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting: Abstract 52. Presented October 26, 2021.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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Cite this: Dupilumab Shows Long-term Efficacy in EoE - Medscape - Oct 28, 2021.