EQ-5D-3L full health state discriminates between drug and placebo in clinical trials of systemic lupus erythematosus

Abstract

Objectives: The objectives of this study were to investigate the discriminative ability of EQ-5D-3L full health state (FHS) in clinical trials of SLE, and to identify factors associated with FHS after treatment.

Methods: Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials of belimumab (N = 1684) were utilized. FHS was defined as a response of no problems in all five EQ-5D-3L dimensions, yielding an index score of 1. The Pearson's χ2 or Fisher's exact test was employed for comparisons, and logistic regression for adjustments and assessment of independence.

Results: We demonstrated higher EQ-5D-3L FHS frequencies among patients given standard therapy (ST) plus the licensed belimumab dose vs ST alone (26.1% vs 19.4%; P = 0.001; week 52), and within SRI-4 responders vs non-responders (27.0% vs 19.8%; P < 0.001; week 52) from weeks 36 to 52. In multivariable regression analysis, SLEDAI-2K (OR: 0.90; 95% CI: 0.87, 0.94; P < 0.001) and SLICC/ACR Damage Index (OR: 0.79; 95% CI: 0.69, 0.91; P = 0.001) scores were independently associated with lower FHS frequencies at week 52, while adding monthly infusions of belimumab 10 mg/kg to ST favoured FHS perception (OR: 1.60; 95% CI: 1.15, 2.24; P = 0.006). Add-on belimumab 10 mg/kg yielded higher FHS frequencies in antimalarial users vs non-users (29.9% vs 20.1%; P = 0.011), and in anti-dsDNA- and anti-Sm- positive vs negative patients (31.4% vs 13.4%; P < 0.001 and 33.0% vs 22.6%; P = 0.010, respectively), whereas no significant differences were observed in patients given ST alone.

Conclusion: EQ-5D-3L FHS distinguished belimumab from placebo and responders from non-responders, and exhibited known-group validity in subgroup analysis. FHS may prove a useful patient-reported outcome in SLE studies.

Keywords: health-related quality of life; outcomes research; patient perspective; patient-reported outcomes; systemic lupus erythematosus.

Fig. 1

Ability of EQ-5D-3L full health state to discriminate between belimumab and placebo Proportions of patients in EQ-5D-3L FHS at baseline and every fourth week in the pooled BLISS study population (A; see Supplementary Table S4, available at Rheumatology online for actual data), the BLISS-52 trial (B; see Supplementary Table S5, available at Rheumatology online for actual data) and the BLISS-76 trial (C; see Supplementary Table S6, available at Rheumatology online for actual data), including stratification by treatment arm. Longitudinal perception of FHS was adjusted for baseline status using logistic regression analysis. Statistically significant differences are denoted by asterisks. FHS: full health state.

Fig. 2

Ability of EQ-5D-3L full health state to discriminate between SRI-4 responders and non-responders Proportions of patients in EQ-5D-3L FHS at baseline and every fourth week among SRI-4 responders vs non-responders in the pooled BLISS study population (A; see Supplementary Table S7, available at Rheumatology online for actual data), the BLISS-52 trial (B; Supplementary Table S8, available at Rheumatology online) and the BLISS-76 trial (C; Supplementary Table S9, available at Rheumatology online). Bars illustrate EQ-5D-3L FHS proportions at week 52, and the forest plots illustrate the corresponding ORs (diamonds) and 95% CIs (whiskers). Longitudinal perception of FHS was adjusted for baseline status using logistic regression analysis. Statistically significant differences are denoted by asterisks. FHS: full health state; OR: odds ratio; SRI-4: SLE Responder Index 4.

Fig. 3

Discriminative ability of level 1 response by EQ-5D dimension Proportions of patients with a level 1 (i.e. “no problems”) response at week 52 across treatment arms (A; see Supplementary Table S10, available at Rheumatology online for actual data) and among SRI-4 responders vs non-responders in the pooled BLISS study population (B; see Supplementary Table S11, available at Rheumatology online for actual data). Comparisons were adjusted for baseline status using logistic regression analysis. Statistically significant differences are denoted by asterisks. SRI-4: SLE Responder Index 4.

Fig. 4

Factors associated with EQ-5D-3L full health state at week 52 Forest plot illustrating ORs (diamonds) and 95% CIs (whiskers) deriving from multivariable logistic regression analysis, with EQ-5D-3L FHS at week 52 as the dependent variable. FHS at baseline was included among covariates in the model (not shown). Statistically significant P values are denoted by asterisks. Actual data are presented in Supplementary Table S13, available at Rheumatology online. C3: complement component 3; C4 complement component 4; FHS: full health state; OR: odds ratio; SDI: SLICC/ACR Damage Index.

Fig. 5

EQ-5D-3L full health state frequencies at week 52 in relation to selected variables Green bars represent EQ-5D-3L FHS frequencies at week 52 within the entire BLISS study population, stratified by selected binomial variables, i.e. sex (A), Black/African American ancestry vs all other ancestries (B), SDI score >0 vs 0 (C), anti-dsDNA (D), anti-Sm (E) and aCL IgM positivity vs negativity (F), antimalarial agents use (G). Grey and blue bars represent FHS frequencies within the placebo and the belimumab 10 mg/kg patient subgroup, respectively. P values are derived from Pearson’s χ² test, or logistic regression analysis where adjustment for baseline status was applied (comparisons between belimumab and placebo). Statistically significant differences are denoted by asterisks. FHS: full health state; SDI: SLICC/ACR Damage Index.