MEPOLIZUMAB FOR TREATMENT OF ADOLESCENTS AND ADULTS WITH EOSINOPHILIC ESOPHAGITIS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL

Background: Novel treatment options for eosinophilic esophagitis (EoE) are needed. Previous studies have assessed mepolizumab (mepo), a monoclonal antibody against IL-5, with mixed results in EoE, and the efficacy of mepo in an adult and adolescent population has yet to be fully examined.

Aim: To determine whether mepo is more effective than placebo for improving symptoms of dysphagia and decreasing esophageal eosinophil counts in EoE.

Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled, investigator-initiated clinical trial comparing mepo to placebo (PBO) (NCT03656380). Patients aged 16-75 with EoE, PPI non-response, ≥15 eos/hpf on biopsy at screening, and active symptoms of dysphagia (EoE Symptom Activity Index [EEsAI] score ≥27) were eligible. Key exclusion criteria were: inability to pass a standard endoscope due to severe stricturing, and esophageal dilation or systemic steroids within 8 weeks, or topical steroids (tCS) within 4 weeks, of baseline endoscopy. Patients were randomized 1:1 to 3 months of either mepolizumab 300mg SQ monthly or matching PBO SQ, after stratification for prior tCS non-response. Primary outcome was change in dysphagia as measured by EEsAI from baseline to month 3 (M3). Secondary outcomes included change in peak eosinophil counts, histologic response thresholds, change in EoE Endoscopic Reference Score (EREFS), EEsAI thresholds, and safety.

Results: Of 66 patients randomized, 64 completed M3 and were analyzed. Baseline characteristics were generally similar between study groups (Table 1). Of note, >80% of subjects had been treated with tCS, 50% had not responded, and >70% had previously had dilation. At M3, EEsAI decreased 15.4±18.1 points with mepo and 8.3±18.0 with PBO (p=0.14; Fig 1A). While 6% in each group had a M3 EEsAI score ≤20 (clinical remission; p=0.95), 35% on mepo had an EEsAI score decrease ≥20 (clinical response) vs 21% with PBO (p=0.20). At M3, the peak eosinophil count decreased with mepo (113±77 to 36±43) and increased (146±94 to 160±133) with PBO (p<0.001 for post-treatment comparison; Fig 1B). With mepo, 42% and 34% achieved histologic responses of <15 and ≤6 eos/hpf compared to 1% and 3% respectively, with PBO (p<0.001 and 0.02; Fig 1C). The change in EREFS at M3 was also larger with mepo than PBO (1.0±1.1 vs 0.4±1.3; p=0.03; Fig 1D). Mepo was generally well-tolerated, with no medication-related SAEs or new safety signals; the most common AEs were injection site reactions.

Conclusions: In this population of previously difficult to treat EoE patients, mepo as stand-alone therapy for 3 months led to a numerical but not statistically significant improvement in dysphagia symptoms, and significant improvements in eosinophil counts and endoscopic severity, as compared to PBO. Longer-term treatment effects and predictors remain to be assessed.