Dupilumab
Dupilumab, a monoclonal antibody directed against interleukin (IL)-4, has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of EoE for adults and children ages ≥12 years and weighing ≥40 kg. It is also approved by the FDA for use in children ages 1 year to 11 years weighing more than 15 kg.[161]ClinicalTrials.gov. Study to determine the efficacy and safety of dupilumab in adult and adolescent patients with eosinophilic esophagitis (EoE). ClinicalTrials.gov Identifier: NCT03633617. Jun 2023 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03633617
Dupilumab can be used as a second-line or add-on therapy for patients with EoE who do not improve with proton-pump inhibitor (PPI) therapy.[162]Dellon ES, Rothenberg ME, Collins MH, et al. Dupilumab in adults and adolescents with eosinophilic esophagitis. N Engl J Med. 2022 Dec 22;387(25):2317-30.
https://www.nejm.org/doi/10.1056/NEJMoa2205982
http://www.ncbi.nlm.nih.gov/pubmed/36546624?tool=bestpractice.com
In one phase 3 randomized trial conducted in two 24-week treatment periods (parts A and B), patients were randomized to receive either dupilumab or placebo. In part A, 60% (n=42) of patients who received dupilumab achieved the predetermined level of reduced eosinophils in the esophagus, compared with 5% (n=39) of patients who received placebo. Patients who received dupilumab had an average improvement of 22 points in their Dysphagia Symptom Questionnaire (DSQ) score, compared with 10 points in patients who received placebo. In part B, 59% (n=80) of patients who received dupilumab achieved the predetermined level of reduced eosinophils in the esophagus, compared with 6% (n=79) of patients who received placebo. Patients who received dupilumab had an average improvement of 24 points in their DSQ score, compared with 14 points in patients who received placebo.[161]ClinicalTrials.gov. Study to determine the efficacy and safety of dupilumab in adult and adolescent patients with eosinophilic esophagitis (EoE). ClinicalTrials.gov Identifier: NCT03633617. Jun 2023 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03633617
[162]Dellon ES, Rothenberg ME, Collins MH, et al. Dupilumab in adults and adolescents with eosinophilic esophagitis. N Engl J Med. 2022 Dec 22;387(25):2317-30.
https://www.nejm.org/doi/10.1056/NEJMoa2205982
http://www.ncbi.nlm.nih.gov/pubmed/36546624?tool=bestpractice.com
With weekly dupilumab continued until week 52, histologic, symptomatic, endoscopic, and molecular features of EoE were maintained or continued to improve.[161]ClinicalTrials.gov. Study to determine the efficacy and safety of dupilumab in adult and adolescent patients with eosinophilic esophagitis (EoE). ClinicalTrials.gov Identifier: NCT03633617. Jun 2023 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03633617
[163]Rothenberg ME, Dellon ES, Collins MH, et al. Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2023 Nov;8(11):990-1004.
https://www.thelancet.com/journals/langas/article/PIIS2468-1253(23)00204-2/abstract
http://www.ncbi.nlm.nih.gov/pubmed/37660704?tool=bestpractice.com
Budesonide oral suspension
Budesonide oral suspension is the first and only oral therapy approved by the FDA for patients with EoE ages ≥11 years, based on results from clinical trials.[164]Hirano I, Collins MH, Katzka DA, et al. Budesonide oral suspension improves outcomes in patients with eosinophilic esophagitis: results from a phase 3 trial. Clin Gastroenterol Hepatol. 2022 Mar;20(3):525-34.e10.
https://www.cghjournal.org/article/S1542-3565(21)00456-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33887475?tool=bestpractice.com
[165]ClinicalTrials.gov. A study in adolescents and adults with eosinophilic esophagitis (EoE) measuring histologic response and determine if reduction in dysphagia is achieved. ClinicalTrials.gov Identifier: NCT02605837. Jun 2021 [internet publication].
https://clinicaltrials.gov/study/NCT02605837
[166]ClinicalTrials.gov. An extension study to evaluate maintenance of efficacy and long-term treatment effect of oral budesonide suspension (OBS) in adults and adolescents with eosinophilic esophagitis (EoE) (ORBIT2). Feb 2019 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT02736409
[167]ClinicalTrials.gov. Continuation study with budesonide oral suspension (BOS) for adolescent and adult participants with eosinophilic esophagitis (EoE). Sep 2020 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03245840
Treatment up to 12 weeks is recommended. It is not recommended in patients with budesonide hypersensitivity.
Benralizumab
A humanized monoclonal antibody that targets interleukin (IL)-5, benralizumab has been granted orphan drug designation by the FDA for the treatment of EoE. A phase 3 trial investigating its use in EoE is ongoing.[168]EU Clinical Trials Register. A multicenter, randomized, double-blind, parallel-group, placebo-controlled study to investigate the use of benralizumab for eosinophilic esophagitis (MESSINA). Jan 2020 [internet publication].
https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-002871-32/DE
Benralizumab is currently approved for the treatment of eosinophilic asthma. The lack of randomized controlled trials means that, despite showing promise, novel biologics used to treat other allergic conditions cannot currently be recommended by UK guidelines.[4]Dhar A, Haboubi HN, Attwood SE, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. 2022 Aug;71(8):1459-87.
https://gut.bmj.com/content/71/8/1459
http://www.ncbi.nlm.nih.gov/pubmed/35606089?tool=bestpractice.com
Tezepelumab
Tezepelumab is a monoclonal antibody directed against thymic stromal lymphopoietin (TSLP).[169]Hoy SM. Tezepelumab: first approval. Drugs. 2022 Mar;82(4):461-8.
http://www.ncbi.nlm.nih.gov/pubmed/35184265?tool=bestpractice.com
TSLP activates a broad range of immune cells to support a Th2 cell inflammatory response.[170]Varricchi G, Pecoraro A, Marone G, et al. Thymic stromal lymphopoietin isoforms, inflammatory disorders, and cancer. Front Immunol. 2018;9:1595.
https://www.doi.org/10.3389/fimmu.2018.01595
http://www.ncbi.nlm.nih.gov/pubmed/30057581?tool=bestpractice.com
Tezepelumab has been granted orphan drug designation by the FDA.
RPC4046
In one phase 2 trial of patients with EoE, RPC4046, a monoclonal antibody directed against interleukin (IL)-13, reduced histologic and endoscopic features compared with placebo.[171]Hirano I, Collins MH, Assouline-Dayan Y, et al. RPC4046, a monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis. Gastroenterology. 2019 Feb;156(3):592-603.
https://www.gastrojournal.org/article/S0016-5085(18)35208-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30395812?tool=bestpractice.com
Immunomodulators
Mercaptopurine and azathioprine can suppress esophageal eosinophilia. They may play a role in maintaining long-term remission in limited cases: for example, those with refractory disease or those in whom corticosteroid therapy is contraindicated. At present, however, there is insufficient evidence to recommend immunomodulators and biologics typically used for inflammatory bowel diseases in the management of EoE.[4]Dhar A, Haboubi HN, Attwood SE, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. 2022 Aug;71(8):1459-87.
https://gut.bmj.com/content/71/8/1459
http://www.ncbi.nlm.nih.gov/pubmed/35606089?tool=bestpractice.com
[135]Franciosi JP, Gordon M, Sinopoulou V, et al. Medical treatment of eosinophilic esophagitis. Cochrane Database Syst Rev. 2023 Jul 20;7(7):CD004065.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004065.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/37470293?tool=bestpractice.com
Etrasimod
Etrasimod is a selective sphingosine-1 phosphate (S1P) receptor modulator. S1P is an extracellular signaling molecule which regulates lymphocyte trafficking and modulates vascular tone and barrier function.[172]Blaho VA, Hla T. An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res. 2014 Aug;55(8):1596-608.
https://www.doi.org/10.1194/jlr.R046300
http://www.ncbi.nlm.nih.gov/pubmed/24459205?tool=bestpractice.com
In the phase 2 VOYAGE study, 108 patients with EoE were randomized to receive oral etrasimod at different doses (n=41 and n=39) or placebo (n=28). Statistically significant reductions in percentage change from baseline (CFB) in esophageal peak eosinophil count (PEC) and reductions in absolute CFB in EoE-Histology Scoring System grade and stage scores were observed at week 24 with both doses, with no serious treatment-emergent adverse effects. A 46.1% decrease in PEC (P=0.0103) at week 16 was observed with the higher dose of etrasimod, thus meeting the primary endpoint. Further evaluation is warranted.[173]Dellon ES, Collins MH, Bredenoord AJ, et al. Efficacy and safety of the selective sphingosine 1-phosphate receptor modulator, etrasimod, in adult patients with eosinophilic esophagitis: primary results from the phase 2 VOYAGE study. American Journal of Gastroenterology. 2023 Oct;118(10S):S330-1.
https://journals.lww.com/ajg/fulltext/2023/10001/s455_efficacy_and_safety_of_the_selective.811.aspx
[174]US National Library of Medicine. ClinicalTrials.gov. A study to assess the safety and efficacy of oral etrasimod in adult participants with eosinophilic esophagitis (VOYAGE). April 2022 [internet publication].
https://www.clinicaltrials.gov/ct2/show/NCT04682639
Immune-resetting peptides
An immune-resetting peptide known as ‘1104 has been granted orphan drug designation by the FDA. The designation is based on findings of one phase 2A trial comprising patients with EoE in whom a statistically significant improvement in DSQ was observed with ′1104, compared with the placebo, which sustained for four weeks post the last dose.[175]ClinicalTrials.gov. A study to assess the efficacy, safety and tolerability of IRL201104 in adults with active eosinophilic esophagitis. ClinicalTrials.gov Identifier: NCT05084963. Oct 2023 [internet publication].
https://clinicaltrials.gov/study/NCT05084963
Additionally, a statistically significant reduction in eosinophils, CD4+, and CD8+ cells from baseline is reported.[175]ClinicalTrials.gov. A study to assess the efficacy, safety and tolerability of IRL201104 in adults with active eosinophilic esophagitis. ClinicalTrials.gov Identifier: NCT05084963. Oct 2023 [internet publication].
https://clinicaltrials.gov/study/NCT05084963
A phase 2B trial is planned.