S11.3 Low-dose interleukin-2 therapy in active systemic lupus erythematosus (lupil-2): a multi-center, double-blind, randomized and placebo-controlled phase 2 trial. (27th September 2022)

• Record Type: Journal Article
• Authors: Humrich, J; Cacoub, P; Rosenzwajg, M; Pitoiset, F; Pham, H; Guidoux, J; Leroux, D; Vazquez, T; Riemekasten, G; Smolen, J; Tsokos, G; Klatzmann, D
• Is Part Of: Lupus science & medicine. Volume 9(2022)Supplement 2
• Page Start: A16
• Page End: A17
• Publication Date: 2022-09-27
• Subjects: Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2022-elm2022.24
• Languages: English
• ISSNs: 2398-8851

Abstract

Abstract : Purpose: A regulatory T cell (Treg) insufficiency due to shortage of interleukin-2 (IL-2) is central to the pathophysiology of systemic lupus erythematosus (SLE). We performed a multi-center, double-blind, randomized, placebo-controlled phase-2 proof-of-concept trial to evaluate the efficacy of low-dose IL-2 therapy in patients with SLE having moderate-to-severe disease activity while receiving standard treatment. Methods: We randomly assigned 100 patients in a 1:1 ratio to receive either 1.5 million IU/day of subcutaneous IL-2 (ILT-101) or placebo for 5 days followed by weekly injections for 12 weeks. Clinical efficacy was assessed at week-12 in a predefined hierarchical analysis of (1) the SLE responder index-4 (SRI-4) response as a primary endpoint, and of (2) relative and (3) absolute changes in the SELENA-SLEDAI scores as key secondary endpoints. Trial registration: NCT02955615 Results: The primary endpoint was not met in the intention-to-treat population (ILT-101: 68%, placebo: 58%; p=0.3439), due to a 100% SRI-4 response rate in the placebo group at two study sites from the same country. A post-hoc analysis on a pre-specified per-protocol population that excluded patients from these two sites (n=53) showed a statistically significant difference for the SRI-4 response rate (ILT-101: 83.3%; placebo: 51.7%; p=0.0168), and for the two key secondary endpoints, accompanied by differences in several secondary exploratory endpoints. ILT-101 was well tolerated and there was no generation of anti-drug antibodies. Conclusions: The post-hoc hierarchical analysis of the primary and key secondary endpoints in a per-protocol population, complemented by the exploratory analyses of multiple other secondary endpoints, support that low-dose IL-2 is beneficial in active SLE.