Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known.
Methods
International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity.
Results
Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: β 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: β 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: β −9.37, 95% CI −12.24, −6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity.
Conclusions
HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician’s communication with decision-making regarding the use of HCQ for SLE management.
StojanGPetriM.Epidemiology of systemic lupus erythematosus: an update. Curr Opin Rheumatol2018; 30: 144–150.
2.
YenEYShaheenMWooJMP, et al. 46-Year trends in systemic lupus erythematosus mortality in the United States, 1968 to 2013: a nationwide population-based study. Ann Intern Med2017; 167: 777–785.
3.
CookRJGladmanDDPericakDUrowitzMB.Prediction of short term mortality in systemic lupus erythematosus with time dependent measures of disease activity. J Rheumatol2000; 27: 1892–1895.
4.
GladmanDDGoldsmithCHUrowitzMB, et al. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index for systemic lupus erythematosus international comparison. J Rheumatol2000; 27: 373–376.
5.
Elera-FitzcarraldCVegaKGamboa-CárdenasRV, et al. Discrepant perception of lupus disease activity: a comparison between patients’ and physicians’ disease activity scores. J Clin Rheumatol2020; 26: S165–S169.
6.
StrandVGladmanDIsenbergDPetriMSmolenJTugwellP.Endpoints: consensus recommendations from OMERACT IV. Outcome measures in rheumatology. Lupus2000; 9: 322–327.
7.
AzizoddinDRJollyMAroraSYelinEKatzP.Patient-Reported outcomes predict mortality in lupus. Arthritis Care Res2019; 71: 1028–1035.
8.
GiannakouIChatzidionysiouKMagderLSGyöriNVan VollenhovenRPetriMA.Predictors of persistent disease activity and long quiescence in systemic lupus erythematosus: results from the Hopkins lupus cohort. Lupus Sci Med2018; 5: e000287.
9.
AouhabZHongHFelicelliCTarplinSOstrowskiRA.Outcomes of systemic lupus erythematosus in patients who discontinue hydroxychloroquine. ACR Open Rheumatol2019; 1: 593–599.
10.
Ruiz-IrastorzaGRamos-CasalsMBrito-ZeronPKhamashtaMA.Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis2010; 69: 20–28.
11.
BabaogluHLiJGoldmanDMagderLSPetriM.Predictors of predominant lupus low disease activity state (LLDAS-50). Lupus2019; 28: 1648–1655.
12.
PetriMPurveySFangHMagderLS.Predictors of organ damage in systemic lupus erythematosus: the Hopkins lupus cohort. Arthritis Rheum2012; 64: 4021–4028.
13.
LeeJSOhJSKimYGLeeCKYooBHongS.Recovery of renal function in patients with lupus nephritis and reduced renal function: the beneficial effect of hydroxychloroquine. Lupus2020; 29: 52–57.
14.
HoKTAhnCWAlarcónGS, et al. Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events. Rheumatology (Oxford)2005; 44: 1303–1307.
15.
ErkanDYaziciYPetersonMGSammaritanoLLockshinMD.A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford)2002; 41: 924–929.
16.
FlorisAPigaMMangoniAABortoluzziAErreGLCauliA.Protective effects of hydroxychloroquine against accelerated atherosclerosis in systemic lupus erythematosus. Mediators Inflamm2018; 2018: 3424136.
17.
Ruiz-IrastorzaGEgurbideMVPijoanJI, et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus2006; 15: 577–583.
18.
AlarcónGSMcGwinGBertoliAM, et al. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis2007; 66: 1168–1172.
19.
VordenbäumenSBrinksRSanderO, et al. Determinants of health-related quality of life in systemic lupus erythematosus: a monocentric, retrospective long-term observational study in Germany. Z Rheumatol2019; 78: 813–819.
20.
JollyMGalicierLAumaîtreO, et al. Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels. Lupus2016; 25: 735–740.
21.
American College of Rheumatology. 1997 update of the 1982 American College of Rheumatology revised criteria for classification of systemic lupus erythematosus, http://tinyurl.com/1997SLEcriteria (accessed 15 March 2012).
22.
PetriMBuyonJKimM.Classification and definition of major flares in SLE clinical trials. Lupus1999; 8: 685–691.
23.
GladmanDGinzlerEGoldsmithC, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum1996; 39: 363–369.
24.
AzizoddinDRWeinbergSGandhiN, et al. Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus. Lupus2018; 27: 728–737.
25.
JollyMKosinskiMGarrisCPOglesbyAK.Prospective validation of the lupus impact tracker: a patient-completed tool for clinical practice to evaluate the impact of systemic lupus erythematosus. Arthritis Rheumatol2016; 68: 1422–1431.
26.
PreacherKJHayesAFContemporary approaches to assessing mediation in communication research. In: HayesAFSlaterAFSnyderLB (eds) The SAGE sourcebook of advanced data analysis methods for communication research. Thousand Oaks: Sage Publications, 2008, pp.13–54.
27.
HayesAFRockwoodNJ.Regression-based statistical mediation and moderation analysis in clinical research: observations, recommendations, and implementation. Behav Res Ther2017; 98: 39–57.
28.
GiangrecoDDevilliersHAnnapureddyNBlockJAJollyM.Lupus impact tracker is responsive to physician and patient assessed changes in systemic lupus erythematosus. Lupus2015; 24: 1486–1491.
29.
JollyMAnnapureddyNArnaudLDevilliersH.Changes in quality of life in relation to disease activity in systemic lupus erythematosus: post-hoc analysis of the BLISS-52 trial. Lupus2019; 28: 1628–1639.
30.
Ugarte-GilMFPons-EstelGJVilaLMMcGwinGAlarcónGS.Time in remission and low disease activity state (LDAS) are associated with a better quality of life in patients with systemic lupus erythematosus: results from LUMINA (LXXIX), a multiethnic,multicentre US cohort. RMD Open2019; 5: e000955.
31.
LiuLHFevrierHBGoldfienRHemmerlingAHerrintonLJ.Understanding nonadherence with hydroxychloroquine therapy in systemic lupus erythematosus. J Rheumatol2019; 46: 1309–1315.
32.
Costedoat-ChalumeauNHoussiauFIzmirlyP, et al. A prospective international study on adherence to treatment in 305 patients with flaring SLE: assessment by drug levels and self-administered questionnaires. Clin Pharmacol Ther2019; 106: 374–382.
33.
AzizoddinDRZamora-RacazaGOrmsethSR, et al. Psychological factors that link socioeconomic status to depression/anxiety in patients with systemic lupus erythematosus. J Clin Psychol Med Settings2017; 24: 302–315.
34.
Zamora-RacazaGAzizoddinDRIshimoriML, et al. Role of psychosocial reserve capacity in anxiety and depression in patients with systemic lupus erythematosus. Int J Rheum Dis2018; 21: 850–858.
35.
MoonSJKangKYKwokSK, et al. Differences in quality of life determinants according to the presence of fibromyalgia in middle-aged female patients with systemic lupus erythematosus: a multicenter, cross-sectional, single-ethnicity cohort. Int J Rheum Dis2018; 21: 1173–1184.
