Long-term effect of anifrolumab on patient-reported outcomes in systemic lupus erythematosus (TULIP-LTE): a randomised, placebo-controlled, phase 3 long-term extension trial.

Abstract

Background: In the TULIP-1 and TULIP-2 phase 3 trials, anifrolumab treatment was associated with clinical efficacy and clinically meaningful improvements in multiple patient-reported outcomes over 52 weeks in patients with moderate-to-severe systemic lupus erythematosus (SLE). At the end of TULIP-1 and TULIP-2 (week 52), eligible patients could reconsent to enter a 3-year long-term extension trial (TULIP-LTE). Here, we investigated changes in patient-reported outcomes during treatment with anifrolumab or placebo for up to 4 years in patients with SLE who were receiving standard therapy.

Methods: TULIP-LTE was a 3-year randomised, double-blind, placebo-controlled, phase 3 long-term extension of the 1-year TULIP-1 and TULIP-2 trials. Patients who were randomly assigned to receive anifrolumab 300 mg (n=257) or placebo (n=112) every 4 weeks in the TULIP-1 and TULIP-2 trials and who continued the same treatment in TULIP-LTE were assessed. Exploratory endpoints were changes from baseline in patient-reported outcomes (Short Form-36 version 2 acute recall [SF-36v2 (acute)], Patient Global Assessment of disease activity, EuroQoL 5 Dimensions-5 Levels [EQ-5D-5L], and Work Productivity and Activity Impairment-Lupus) and health utility indices, Short-Form 6-Dimension (SF-6D), derived from SF-36v2 (acute), and EQ-5D-5L. All analyses were done in the modified intention-to-treat population, which included all randomly assigned patients from TULIP-1 and TULIP-2 who received at least one dose of the same treatment during the long-term extension phase. Least-squares mean patient-reported outcome scores were adjusted using a repeated measures model. No people with lived experience were directly involved in the study design or implementation. This trial was registered with ClinicalTrials.gov, NCT02794285.

Findings: Between June 30, 2016, and Oct 12, 2018, 369 patients entered the long-term extension study and were included in this exploratory analysis (257 in the anifrolumab group and 112 in the placebo group). Mean age of patients was 42·8 years (SD 11·5), 340 (92%) of 369 patients were women and 29 (8%) were men, 250 (68%) patients were White and 82 (22%) self-identified as Hispanic or Latino. Patient-reported outcome scores improved from baseline in both groups during the 4-year treatment period. At week 208, improvement from baseline in SF-36v2 (acute) was numerically higher in the anifrolumab group than the placebo group for the bodily pain domain (least-squares mean difference 5·9 [95% CI -0·7 to 12·5]) and the mental health domain (3·7 [-1·2 to 8·6]). Improvements from baseline in SF-6D were generally greater in the anifrolumab group than the placebo group, with numerical differences between groups evident from as early as week 24 (least-squares mean difference 0·013 [-0·007 to 0·032]) and maintained at week 208 (0·016 [-0·010 to 0·042]).

Interpretation: Over 4 years of treatment, patients reported improvements in health status and health-related quality of life, including differences favouring anifrolumab compared with placebo. These numerical improvements in patient-reported outcomes occurred alongside improvements in disease activity, reduced glucocorticoid doses, and a tolerable safety profile. These data suggest that anifrolumab is an effective treatment option that might improve health-related quality of life.

Funding: AstraZeneca.