Adverse Health-Related Quality of Life Outcome Despite Adequate Clinical Response to Treatment in Systemic Lupus Erythematosus

Abstract

Objective: To determine the prevalence of adverse health-related quality of life (HRQoL) outcomes in patients with SLE who achieved an adequate clinical response after a 52-week long standard therapy plus belimumab or placebo, and identify contributing factors. Methods: We included patients who met the primary endpoint of the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials, i.e., SLE Responder Index 4 (total population: N = 760/1,684; placebo: N = 217/562; belimumab 1 mg/kg: N = 258/559; belimumab 10 mg/kg: N = 285/563). Adverse HRQoL outcomes were defined as SF-36 scale scores ≤ the 5th percentile derived from age- and sex-matched population-based norms, and FACIT-Fatigue scores <30. We investigated factors associated with adverse HRQoL outcomes using logistic regression analysis. Results: We found clinically important diminutions of HRQoL in SLE patients compared with matched norms and high frequencies of adverse HRQoL outcomes, the highest in SF-36 general health (29.1%), followed by FACIT-Fatigue (25.8%) and SF-36 physical functioning (25.4%). Overall, frequencies were higher with increasing age. Black/African American and White/Caucasian patients reported higher frequencies than Asians and Indigenous Americans, while Hispanics experienced adverse HRQoL outcome less frequently than non-Hispanics. Established organ damage was associated with adverse physical but not mental HRQoL outcomes; particularly, damage in the cardiovascular (OR: 2.12; 95% CI: 1.07-4.21; P = 0.032) and musculoskeletal (OR: 1.41; 95% CI: 1.01-1.96; P = 0.041) domains was associated with adverse SF-36 physical component summary. Disease activity showed no impact on HRQoL outcomes. In multivariable logistic regression analysis, addition of belimumab to standard therapy was associated with lower frequencies of adverse SF-36 physical functioning (OR: 0.59; 95% CI: 0.39-0.91; P = 0.016) and FACIT-F (OR: 0.53; 95% CI: 0.34-0.81; P = 0.004). Conclusions: Despite adequate clinical response to standard therapy plus belimumab or placebo, a substantial proportion of SLE patients still reported adverse HRQoL outcomes. While no impact was documented for disease activity, established organ damage contributed to adverse outcome within physical HRQoL aspects and add-on belimumab was shown to be protective against adverse physical functioning and severe fatigue.

Keywords: biologic drugs; fatigue; health-related quality of life; patient perscpective; patient-reported outcome; systemic lupus erythematosus.

Figure 1

SF-36 scores among SRI-4 responders and non-responders before and after trial intervention. The bar chart (A) illustrates comparisons of SF-36 component summary scores between SRI-4 responders at week 52 and age- and sex-matched US population-based norms. The height of the bars represents mean scores, while the height of the whiskers above the bars represents standard deviation. The radial charts illustrate comparisons of mean SF-36 subscale scores between (A) SRI-4 responders at week 52 and age- and sex-matched US population-based norms, (B) baseline and week 52 in SRI-4 responders, (C) SRI-4 responders and non-responders at baseline, and (D) SRI-4 responders and non-responders at week 52. Asterisks indicate statistically significant associations. BP, bodily pain; GH, general health; MCID, minimal clinically important difference; MCS, mental component summary; MH, mental health; NP5, normative 5th percentile; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; SLE, systemic lupus erythematosus; VT, vitality; Δ, delta (difference).

Figure 2

Adverse HRQoL outcome despite clinical improvement. This figure illustrates the prevalence of adverse HRQoL outcomes. Panel (A) shows frequencies of adverse HRQoL outcome defined as SF-36 physical and mental scale scores ≤NP5, and panel (B) shows their cumulative frequencies within different age categories. Panel (C) shows frequencies of FACIT-F scores <30, including frequencies within different age categories. BP, bodily pain; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; GH, general health; MCS, mental component summary; MH, mental health; n, number of patients reporting adverse HRQoL outcomes; N, total number of patients with available data; NP5, normative 5th percentile; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; SLE, systemic lupus erythematosus; VT, vitality.

Figure 3

Adverse HRQoL outcome despite clinical improvement across different ancestries. This figure illustrates comparisons of the prevalence of adverse HRQoL outcomes at week 52 from treatment initiation across patients with SLE of Asian, Black/African American, Indigenous American, and White/Caucasian ancestries. (A,B) Delineate proportions of patients reporting SF-36 scores below or equal to the 5th percentile of the corresponding scores as derived from a general population of the same age and sex, within physical and mental aspects, respectively. (C) Delineates proportions of patients reporting FACIT-F scores <30, signifying severe fatigue. The number of patients reporting adverse HRQoL outcomes (n) is indicated below the respective bar. P-values derived from chi-square tests. BP, bodily pain; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; GH, general health; MCS, mental component summary; MH, mental health; NP5, normative 5th percentile; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; VT, vitality.

Figure 4

Adverse HRQoL outcome despite clinical improvement across different country groups. This figure illustrates comparisons of the prevalence of adverse HRQoL outcomes at week 52 from treatment initiation across patients with SLE from Asia Pacific, Canada/USA, Europe, and Latin America. (A,B) Delineate proportions of patients reporting SF-36 scores below or equal to the 5th percentile of the corresponding scores as derived from a general population of the same age and sex, within physical and mental aspects, respectively. (C) Delineates proportions of patients reporting FACIT-F scores <30, signifying severe fatigue. The number of patients reporting adverse HRQoL outcomes (n) is indicated below the respective bar. P-values derived from chi-square tests. BP, bodily pain; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; GH, general health; MCS, mental component summary; MH, mental health, NP5, normative 5th percentile; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; VT, vitality.

Figure 5

Adverse HRQoL outcome despite clinical improvement in Hispanics versus non-Hispanics. This figure illustrates comparisons of the prevalence of adverse HRQoL outcomes at week 52 from treatment initiation between patients with SLE of Hispanic/Latin American and non-Hispanic ethnicity. (A,B) Delineate proportions of patients reporting SF-36 scores below or equal to the 5th percentile of the corresponding scores as derived from a general population of the same age and sex, within physical and mental aspects, respectively. (C) Delineates proportions of patients reporting FACIT-F scores <30, signifying severe fatigue. In the forest plots, circles designate the corresponding unadjusted odds ratios and whiskers designate 95% confidence intervals. The number of patients reporting adverse HRQoL outcomes (n) is indicated below the respective bar. P-values derived from chi-square tests. Significant P-values are indicated with asterisks. BP, bodily pain; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; GH, general health; MCS, mental component summary; MH, mental health; NP5, normative 5th percentile; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; VT, vitality.

Figure 6

Factors associated with adverse HRQoL outcomes. The forest plots illustrate results from multivariable logistic regression models, with the SF-36 component summary scores ≤NP5 (A), physical subscale scores ≤NP5 (B), mental subscale scores ≤NP5 (C) and FACIT-F scores <30 (A) at week 52 from treatment initiation as the dependant variables. Diamonds represent odds ratios and whiskers represent 95% confidence intervals. Asterisks indicate statistically significant associations. BP, bodily pain; CI, confidence interval; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; GH, general health; MCS, mental component summary; MH, mental health; NP5, normative 5th percentile; OR, odds ratio; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; VT, vitality.

Figure 7

Associations between SDI organ domains and adverse HRQoL outcomes. The heatmaps illustrate ORs deriving from univariable (A) and multivariable (B) logistic regression models, with the SF-36 scale scores ≤NP5 and FACIT-F scores <30 at week 52 as the dependant variables. Dots indicate statistically significant associations. BP, bodily pain; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; GH, general health; MCS, mental component summary; MH, mental health; OR, odds ratio; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, short form 36 health survey; VT, vitality.