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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
  1. J Humrich2,
  2. P Cacoub1,
  3. M Rosenzwajg3,
  4. F Pitoiset3,
  5. H Pham4,
  6. J Guidoux4,
  7. D Leroux4,
  8. T Vazquez4,
  9. G Riemekasten2,
  10. J Smolen5,
  11. G Tsokos6 and
  12. D Klatzmann3
  1. [1]Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology ~ Paris ~ France
  2. 2University Hospital Schleswig-Holstein, Department of Rheumatology and Clinical Immunology ~ Lübeck ~ Germany
  3. 3Sorbonne Université, INSERM, Immunology-Immunopathology-Immunotherapy (i3) ~ Paris ~ France
  4. 4ILTOO Pharma ~ Paris ~ France
  5. 5Medical University of Vienna, Division of Rheumatology, Department of Medicine 3 ~ Vienna ~ Austria
  6. 6Beth Israel Deaconess Medical Center and Harvard Medical School, Division of Rheumatology and Clinical Immunology, Department of Medicine ~ Boston ~ USA


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.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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