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IL-13 Inhibitor Effective, Safe for Long-term Treatment of EoE
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WASHINGTON — RPC4046, an anti-interleukin-13 monoclonal antibody, appeared safe and effective for the long-term treatment of eosinophilic esophagitis, according to results from an open label extension study presented at Digestive Disease Week.
“A recent randomized, placebo-controlled phase 2 trial showed improvements in esophageal eosinophilia, endoscopic severity and symptoms in patients with EoE over 16 weeks of treatment,” Evan S. Dellon, MD, of the University of North Carolina School of Medicine, said during his presentation. “However, the long-term effects of RPC4046 are not known.”
RPC4046 (Receptos) works by blocking the binding of IL-13 to the IL-13R alpha1 and IL-13R alpha2 receptors and is administered weekly through a subcutaneous injection.
The drug was previously tested in a 16-week phase 2 trial known as HEROES in which researchers randomly assigned 99 patients with EoE to receive either 180 mg or 360 mg of RPC4046 or placebo weekly.
Dellon and colleagues then recruited from HEROES patients with a drug compliance greater than 80% and no clinically significant adverse events to join an open-label extension study (n = 86). The patients received a 360-mg dose weekly and had an endoscopy at baseline and at weeks 12, 24 and 52.
Outcome measures included mean and peak eosinophil count, and EoE Endoscopic Reference Score (EREFS), EoE Histologic Scoring System (EoEHSS) score, and EoE Symptom Activity Index (EEsAI).
Dellon and colleagues found that patients recruited from the two treatment arms of the original study maintained similar clinical and histologic improvement throughout the extension trial. Additionally, patients who initially received placebo experienced “rapid” improvement in all study outcome measures.
Basing symptomatic remission on an EEsAI score of less than 20, the investigators found that the percentage of patients in remission increased from 24.4% at baseline to 44.4% at week 12, 52.3% at week 24 and 58.2% at week 52.
Overall incidence of adverse events remained consistent in the open-label extension relative to the HEROES trial, with the most common adverse events being upper respiratory tract infection, nasopharyngitis, oropharyngeal pain, sinusitis and headache.
“Upon [open-label extension] entry, patients who had received placebo during the study period showed improvement by week 12 in esophageal eosinophil count, EREFS score, and EoEHSS grade and stage sores, and this was maintained through week 52,” Dellon said. “Longer-term treatment with RPC4046 was generally safe and well tolerated with no safety concerns through 52 weeks.” – by Alex Young
Reference:
Dellon ES, et al. Abstract 876. Presented at: Digestive Disease Week; June 2-5, 2018; Washington, D.C.
Disclosures : Dellon reports financial ties to Adare, Alivio, Allakos, Banner, Celgene Corporation, Enumeral, GSK, Regeneron, Meritage, Miraca, and Nutricia. Please see the DDW faculty disclosure index for a list of all other authors’ relevant financial disclosures.
Perspective
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Kenneth DeVault, MD, FACG
Eosinophilic esophagitis (EoE) is a common cause of dysphagia. Treatment has relied upon acid suppression, topical steroids and elimination diets. Many patients continue to have symptoms despite these available options, thus several potential agents are undergoing study. This is an inflammatory condition that should respond to agents that suppress that inflammation, like the anti-interleukin antibody reported in this study. The study was a 1-year follow-up to a previously reported acute treatment trial. In both the acute trial and this long-term report, the agent provided control in most patients. It is interesting that the remission rate increased as the study progressed (44.4% at 12 weeks, 58.2% at 52 weeks).
How will agents like this fit into the treatment of EoE? Because a significant subset of EoE patients respond to acid suppression with proton pump inhibitors, that remains a reasonable first step. Those who have ongoing symptoms or inflammation, will usually next either be treated with topical steroids or have an attempt at an elimination diet. If steroid therapy and diet fail, then it may be reasonable to consider an agent like the one reported in this study. Larger studies as well as economic analysis will be needed prior to moving immunomodulators up in the therapeutic hierarchy for this disease.
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