Dupilumab in EoE With an Impassable Fibrostenotic Stricture
LIBERTY-TREET, the trial behind dupilumab's EoE approval, excluded patients with an impassable esophageal stricture — leaving a real, currently unanswered question for exactly the fibrostenotic patients most likely to want the drug.
Owen K., 41, has driven long-haul routes for a regional freight company for going on fifteen years, structuring meals around gas-station stops he can eat slowly and alone; he stopped ordering anything but soup or well-blended food at truck stops two years ago without ever telling anyone why. EoE was diagnosed at 34, managed on-and-off with swallowed budesonide he admits he's inconsistent with on the road, and dilated twice for stricture. Three weeks ago a standard adult endoscope could not pass a mid-esophageal stricture that had previously been traversable at 14mm — a real narrowing since his last dilation eighteen months ago, not just a missed follow-up.
His most recent biopsies, taken proximal to the stricture since the scope couldn't reach past it, still show 60 eosinophils/hpf despite the budesonide he reports taking “most days.” Dupilumab is FDA-approved for EoE broadly, but LIBERTY-TREET, the pivotal trial behind that approval, explicitly excluded patients with an esophageal stricture too narrow to pass a standard endoscope — which is precisely Owen's presentation today. That leaves a real evidence gap rather than a settled answer: the trial simply never enrolled anyone whose disease had progressed this far, so nothing in its own data set says whether dupilumab helps, or is even safe to start, in a stricture this severe before dilation restores luminal patency. Neither efficacy nor safety data exist for a presentation like his, then — not because the answer came back negative, but because the question was never asked of anyone with an esophagus this narrow. The eighteen months that carried him from a lumen a scope could cross at 14mm to one it cannot cross at all is the interval any sequencing decision here has to be measured against.
A patient the pivotal trial never enrolled
Dilate first. He can't be re-scoped past the stricture right now, which means we can't even properly assess anything downstream until the lumen is open again. That's a mechanical problem before it's anything else, and no systemic drug fixes a fibrotic ring by itself.
I agree the dilation has to happen regardless — that's not in dispute. What I'd push back on is waiting to start dupilumab until after it. He has 60 eosinophils per high-power field on biopsy despite reported topical therapy; that's active inflammatory disease, and fibrostenotic remodeling in EoE is understood to be driven by exactly that ongoing inflammation over time. If we dilate and do nothing else, we're very likely back here in another eighteen months.
LIBERTY-TREET's own exclusion criterion is worth being honest about here.
I'll say it directly: he is precisely the patient the pivotal trial excluded, so I can't point to trial data showing dupilumab is safe or effective started this early in a stricture this severe. This is a real evidence gap, not a settled extrapolation.
Before we reach for a drug neither of you can point to real trial data for in his exact presentation, I want the adherence question actually answered. He describes his own budesonide use as inconsistent — that means we don't actually know whether adequately-dosed topical therapy has failed him or was simply never given a fair trial. Dilate now because that's urgent and uncontested. Restart budesonide with real administration counseling this time, reassess inflammatory burden once the scope can reach the full esophagus, and treat dupilumab as the next step if that fails — not the first one, in a population the drug's own pivotal trial never actually studied.
Agreed: dilation this admission, restart of budesonide with real dosing/administration counseling (dissolved fully, not swallowed with water, nothing by mouth for 30 minutes after), and a repeat endoscopy with biopsy at 8 weeks to judge both luminal patency and histologic response.
Dupilumab becomes the next step, started with eyes open that his exact presentation sits outside LIBERTY-TREET's own studied population — a real, named gap, not a technicality.
Dilation plus optimized budesonide may be enough on its own, and the dupilumab question doesn't need answering at all.