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Article Dans Une Revue Annals of the Rheumatic Diseases Année : 2018

Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial

Hang Phuong Pham
  • Fonction : Auteur
Francis Berenbaum
Christophe Corpechot
Bruno Fautrel
Arsene Mekinian
Elodie Régnier
  • Fonction : Auteur
  • PersonId : 1205775
Jérémie Sellam
  • Fonction : Auteur
  • PersonId : 918443
Philippe Seksik
  • Fonction : Auteur
  • PersonId : 990297
Valérie Doppler
  • Fonction : Auteur
  • PersonId : 938913
Jéremie Mariau
  • Fonction : Auteur

Résumé

Objective : Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential. Aim : We aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases. Methods : We performed a prospective, open-label, phase I–IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet’s disease, granulomatosis with polyangiitis, Takayasu’s disease, Crohn’s disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation. Results : ld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed. Conclusion : The dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.
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Dates et versions

hal-01960735 , version 1 (08-01-2019)

Identifiants

  • HAL Id : hal-01960735 , version 1

Citer

Michelle Rosenzwajg, Roberta Lorenzon, Patrice Cacoub, Hang Phuong Pham, Fabien Pitoiset, et al.. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Annals of the Rheumatic Diseases, 2018, pp.annrheumdis-2018-214229. ⟨hal-01960735⟩
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