Tezepelumab
Tezepelumab is a monoclonal antibody directed against thymic stromal lymphopoietin (TSLP).[165]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.[166]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 EoO, RPC4046, a monoclonal antibody directed against interleukin (IL)-13, reduced histological and endoscopic features compared with placebo.[167]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 oesophageal 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 biologicals typically used for inflammatory bowel diseases in the management of EoO.[2]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
[106]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 signalling molecule which regulates lymphocyte trafficking and modulates vascular tone and barrier function.[168]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 EoO were randomised 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 oesophageal peak eosinophil count (PEC) and reductions in absolute CFB in EoO-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.[169]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
[170]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 EoO 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.[171]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.[171]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.