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

Abstract

Objectives To investigate the discriminative ability of EQ-5D-3L full health state (FHS) in clinical trials of SLE, and identify factors associated with FHS after treatment. Methods Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials of belimumab (N = 1684) were utilised. 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 chi-square 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 versus ST alone (26.1% versus 19.4%; P = 0.001; week 52), and within SRI-4 responders versus non-responders (27.0% versus 19.8%; P < 0.001; week 52) from week 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 versus non-users (29.9% versus 20.1%; P = 0.011), and in anti-dsDNA and anti-Sm positive versus negative patients (31.4% versus 13.4%; P < 0.001 and 33.0% versus 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.

EQ-5D full health state after therapy heralds reduced hazard to accrue subsequent organ damage in systemic lupus erythematosus

“…Inevitably, the more precise the instrument is, the more time and effort it requires from the respondent to fill in the instrument, which may also result in decreased response frequencies or recruitment of participants in studies, incomplete responses, and incorrect completion ( 30 ). For this reason, the briefness of the EQ-5D format paired with its known-group validity ( 17 ) and its satisfactory psychometric properties ( 14 ) in SLE patients along with its ability to predict long-term disease outcome as shown in the present study suggest that EQ-5D is a feasible and clinically relevant HRQoL instrument to use in SLE practices and studies.…”

“…Another important limitation was the different follow-up times of 52 and 76 weeks in the BLISS-52 and BLISS-76 clinical trials, respectively, which may have favoured attainability of "no problems" in the different EQ-5D dimensions or FHS in BLISS-76 where the patients were followed for approximately 50% longer time than in BLISS-52 before entering the open-label phase. However, a previous analysis from our group showed that proportions of EQ-5D-3L FHS responses plateaued from week 52 through week 76 in BLISS-76 (17). Furthermore, the selected population of the trials consisting mainly of articular and/or mucocutaneous SLE and excluding severe active renal and CNS lupus may not be considered fully representative of real-life clinical settings.…”

“…Three-level version of EQ-5D FHS was reported at a higher frequency among patients who received non-biological standard therapy plus belimumab than among patients who received standard therapy alone as well as in responders than in non-responders in a large clinical trial SLE population ( 17 ). However, the association between EQ-5D-3L FHS and long-term outcomes e.g., organ damage accrual in SLE remains unknown.…”

Impact of Belimumab on Patient-Reported Outcomes in Systemic Lupus Erythematosus: Insights from Clinical Trials and Real-World Evidence

“… No significant differences for SF-36 PCS/MCS and other SF-36 subscales NA SRI-4 responders reported lower SF-36 subscale scores than population-based norms Borg et al, 2021 39 FACIT-Fatigue OR FACIT-Fatigue <30 for BLM use vs PBO: 0.76 (0.61–0.96; p=0.034) NA NA SF-36 OR SF-36 PF <NP5 for BLM use vs PBO: 0.78 (0.63–0.97; p=0.025). No significant differences for SF-36 PCS/MCS and other SF-36 subscales NA NA Lindblom et al, 2021 36 EQ-5D NA NA Proportion of patients with EQ-5D FHS a at week 52: PBO: 19.4% BLM 1 mg/kg: 23.6% (p=0.029) BLM 10 mg/kg: 26.1% (p=0.001) US population-based norms: 48.7% Maslen et al, 2021 58 SF-36 SF-36 PCS LS-means at w52: PBO 4.2 ± 0.7 BLM: 5.4 ± 0.7 (p=0.065) NA NA BEL 112233 (Strand et al, 2019) 41 FACIT-Fatigue Mean change from baseline: sustained increase >MCID throughout 5 years. Increase at year 6: 3.7 % of patients with increase ≥ 4 at year 6: 46.4% NA SF-36 Mean change from baseline SF-36 PCS: sustained increase >MCID throughout 6 years.…”

“…In subsequent post-hoc analyses, the proportion of patients who reported EQ-5D full health state at week 52 was greater in belimumab-treated patients compared with placebo-receivers, as well as in SRI-4 responders compared with non-responders. 36 Moreover, greater proportions of patients in the belimumab 10 mg/kg arm versus placebo reported “no problems” at week 52 regarding mobility (odds ratio, OR: 1.32; 95% confidence interval, CI: 1.00–1.74; P = 0.049), self-care (OR: 1.46; 95% CI: 1.02–2.10; P = 0.038), and pain/discomfort (OR: 1.51; 95% CI: 1.14–1.99; P = 0.004).…”