Combination Therapy for Eosinophilic Esophagitis

MA Buendia et al. JPGN Reports 3(4):p e273, 2022. DOI: 10.1097/PG9.0000000000000273. Relapse of Eosinophilic Esophagitis on Dupilumab

Yesterday’s post reviewed the landmark study leading to dupilumab’s FDA approval. Today’s case report shows that we have a lot we need to learn about its use.

The authors present a case report of a patient with eosinophilic esophagitis (EoE) who had ongoing active EoE while receiving topical steroids (TS) and PPI (and previously dietary elimination therapy). He achieved remission after the addition of dupilumab. “When his TS were weaned after achieving remission, his disease relapsed with worsening of his dysphagia and a peak eosinophilic count (PEC) of 55 eosinophils per high power field (eos/hpf). Upon restarting TS to his ongoing dupilumab, symptoms fully resolved, and he achieved histologic remission (PEC 10 eos/hpf).”

My take: This study indicates that there are some patients need dupilumab and topical steroids in combination, rather than monotherapy. Reliable biomarkers to more easily determine response and/or to predict optimal therapy are clearly needed.

Sunset at Siesta Key, FL

Landmark Dupilumab Study for Eosinophilic Esophagitis

ES Dellon et al. NEJM 2022; 387; 2317-2330. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis

This study was pivotal for receiving FDA approval of dupilumab (dupixent) for the treatment of EoE (the only FDA approved therapy). Background: “Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis..Standard-of-care treatments for eosinophilic esophagitis include food elimination diets, proton-pump inhibitors (PPIs), swallowed topical glucocorticoids (applied to the esophagus by swallowing), and, in the case of strictures, esophageal dilation.11,12 However, the rates of response are variable (30 to 40% of patients may not have a response to first-line treatments).”

Key findings from three-part study (see images below):

  • Part A: Histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo
  • Part B: Histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo 
  • Dysphagia Symptom Questionnaire (DSQ) scores:  the scores improved with weekly dupilumab as compared with placebo, with differences of –12.32 (95% CI, –19.11 to –5.54) in Part A and –9.92 (95% CI, –14.81 to –5.02) in Part B (both P<0.001) but not with dupilumab every 2 weeks (difference in Part B, –0.51; 95% CI, –5.42 to 4.41)
  • The most common adverse effect was injection site reactions. There were 10 serious adverse events; none of these “were considered by the trial investigators to be related to the trial regimen.”

In the associated commentary, (pg 2379-2380), Dr. Alex Straumann notes that since EoE is localized to the esophagus, whether a patients should be treated with a systemically acting medication, “particularly in light of the fact that topical glucocorticoids have been shown to be as efficacious as systemically acting prednisone.”

My take (borrowed in part from editorial): It remains unclear whether dupilumab “is better than the good old topical glucocorticoids in improving disease outcomes, particularly in light of considerable costs associated with this treatment.” Due to its cost (see below), dupillumab is likely best situated as a 2nd line treatment at this time for most patients.

Related blog posts:

Cost comparison (from Laura Targownwik on twitter):

Dupilumab: FDA Approval for Eosinophilic Esophagitis

U.S. FDA (5/20/22): FDA Approves First Treatment for Eosinophilic Esophagitis, a Chronic Immune Disorder

“Today, the U.S. Food and Drug Administration approved Dupixent (dupilumab) to treat eosinophilic esophagitis (EoE) in adults and pediatric patients 12 years and older weighing at least 40 kilograms (which is about 88 pounds). Today’s action marks the first FDA approval of a treatment for EoE…”

“The efficacy and safety of Dupixent in EoE was studied in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial, that included two 24-week treatment periods (Part A and Part B)…In Part A of the trial, 60% of the 42 patients who received Dupixent achieved the pre-determined level of reduced eosinophils in the esophagus compared to 5% of the 39 patients who received a placebo…. In Part B, 59% of the 80 patients who received Dupixent achieved the pre-determined level of reduced eosinophils in the esophagus compared to 6% of the 79 patients who received a placebo”

My take: We will need to revise our patient handout and decide how best to position this very expensive therapy. Without insurance, Dupixent (2 pens of 300 mg/2 mL) costs $3,649.97 on GoodRx. For those with insurance, Dupixent has a manufacturer’s coupon (Dupixent MyWay).

Related blog posts:

Sandia Mountain Tram