Background:Despite improvements in medical care that have contributed to prolonged life expectancy for people living with systemic lupus erythematosus (SLE) over the past decades, they still suffer from substantial diminutions of health-related quality of life (HRQoL) compared with the general population and with other chronic diseases.Some studies have demonstrated that conventional synthetic and biological disease-modifying agents contribute to improvements in SLE patients’ HRQoL, and responders to treatment have been shown to report greater improvements than non-responders. Although these observations are clinically relevant, improvement following a therapeutic intervention does not necessarily signify that the individual has achieved a satisfactory health state perception. In rheumatoid arthritis, significant pain and severe fatigue persist in a substantial proportion of patients who achieve a good clinical response to treatment or remission. This paradoxical observation has not been thoroughly explored in SLE.Objectives:To determine the prevalence of adverse HRQoL outcomes in patients with SLE who achieved an adequate clinical response after a 52-week long period on standard therapy plus belimumab or placebo, within the frame of two phase III clinical trials. We further aimed to compare frequencies of adverse HRQoL outcomes across different age categories and ethnic groups, and sought to identify contributing factors.Methods:We included patients who met the primary endpoint of the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N=760/1684), i.e. attainment of the SLE Responder Index 4 at week 52. Accordingly, evaluation of adverse HRQoL outcomes was based on patient reports at week 52 from treatment initiation, using the Medical Outcomes Study Short Form 36 (SF-36) health survey and the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue) scale. Adverse HRQoL outcomes were defined as (i) SF-36 scale scores ≤ the 5th percentile derived from age- and sex-matched US population-based norms from the SF-36 health survey user manual; and (ii) FACIT-Fatigue scores <30.Pearson’s chi-square or Fisher’s exact tests were used to investigate associations between dichotomous variables. Comparisons of continuous data between SLE patients and age- and sex-matched norms were performed using the Wilcoxon signed-rank test. Multivariable logistic regression models were created in order to assess independence and priority of potential factors associated with adverse HRQoL outcomes.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 less frequently than non-Hispanics. Increasing organ damage was associated with adverse physical but not mental HRQoL outcomes; disease activity showed no impact. 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).Conclusion:Substantial proportions of SLE patients reported adverse HRQoL outcomes despite adequate clinical response to treatment, especially in physical aspects. Particularly high proportions were seen within Black/African American and White/Caucasian patients. Add-on belimumab may be protective against adverse physical functioning and severe fatigue. Our results corroborate that HRQoL diminutions constitute a substantial burden in patients with SLE, and highlight the limitations of current therapeutic strategies.Acknowledgements:The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for sharing the data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials with the Clinical Study Data Request (CSDR) consortium, Dimitris Ladakis, Joaquin Matilla and Martin Pehr for contributing to the management of data, as well as all participating patients.Disclosure of Interests:Alvaro Gomez: None declared, Julius Lindblom: None declared, Victor Qiu: None declared, Arvid Cederlund: None declared, Alexander Borg: None declared, Sharzad Emamikia: None declared, Yvonne Enman: None declared, Jon Lampa: None declared, Ioannis Parodis Grant/research support from: Research funding and/or honoraria from Amgen, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline and Novartis.
Sarcopenia, severe anxiety and increased C-reactive protein are associated with severe fatigue in patients with inflammatory bowel diseases