Prognostic value of 18 FDG-PET at diagnosis and follow-up in giant cell arteritis: An observational restrospective study.

OBJECTIVES: To evaluate the ability of 18FDG PET/CT, at diagnosis of giant cell arteritis (GCA) and during follow-up, to predict occurrence of relapse in large-vessel GCA (LV-GCA). METHODS: We conducted a retrospective study using the French Study Group for Large-Vessel Vasculitis (GEFA) network. Data from patients with LV-GCA diagnosed by PET/CT and who had PET/CT in the following year were collected. For each PET/CT, PET vascular activity score (PETVAS) and total vascular score (TVS) were assessed, and their ability to predict the occurrence of subsequent relapse was assessed. RESULTS: A total of 65 LV-GCA patients were included, of whom 55 had undergone a follow-up PET/CT 3 to 12 months after the diagnosis of GCA. Patients for whom the second PET/CT (PET2) was performed during active GCA were excluded. PETVAS and TVS decreased between PET1 and PET2 in all patients (p < 0.001). There was no correlation between vascular activity scores in PET2 and time to prednisone taper. For relapse prediction, at PET1, the AUC of the TVS and PETVAS were respectively 51.9 and 41.9 at 6 months, 55.3 and 49.7 at 1 year, 55 and 55.7 at 2 years. For PET2, the AUC were respectively 46.1 and 46.7 at 6 months, 52.1 and 48.9 at 1 year, 58.4 and 52.3 at 2 years. CONCLUSION: PET vascular activity scores at diagnosis and at follow-up PET/CT performed outside a period of GCA activity do not display high performance to predict the occurrence of subsequent relapse in LV-GCA patients.

Clinical trial outcomes for SLE: what we have and what we need.

The paradigm of drug approval in SLE currently relies on successful large phase III randomised controlled trials and a set of primary, secondary and additional end points. Taken together, these outcomes offer a nuanced understanding of the efficacy and safety of the investigational agent. In this review, we thoroughly examine the main outcomes used in SLE trials and highlight unmet requirements as well as potential venues for future trial design in SLE. Disease activity indices can be broadly categorised into global-specific and organ-specific indices, in particular for skin, joints and kidneys, but there is no universal consensus about their use in clinical trials. Because each of these instruments has its own intrinsic strengths and weaknesses, the assessment of treatment response has progressed from relying solely on one individual disease activity index to using composite responder definitions. Those are typically measured from the trial baseline to the end point assessment date and may be combined with the need to taper and maintain glucocorticoids (GCs) within prespecified ranges. Remission and low disease activity are two critical states in the perspective of 'Treat-to-Target' trials, but are not fully recognised by regulators. While significant progress has been made in clinical trial outcomes for SLE, there is a clear need for continued innovation. Addressing these challenges will require collaboration between researchers, clinicians, patients as well as with regulatory agencies to refine existing outcome measures, incorporate meaningful and ethnically diverse patient perspectives, foster relevant digital opportunities and explore new therapeutic avenues, including early use of investigational agents. By doing so, we can advance our ability to manage SLE effectively and safely and improve the lives of those living with this complex and impactful autoimmune disease.

Changes in Taste Perception in Patients with Minor and Major Cognitive Impairment Linked to Alzheimer's Disease Recorded by Gustatory Evoked Potentials.

BACKGROUND: The need for early diagnosis biomarkers in Alzheimer's disease (AD) is growing. Only few studies have reported gustatory dysfunctions in AD using subjective taste tests. OBJECTIVE: The main purpose of the study was to explore gustatory functions using subjective taste tests and recordings of gustatory evoked potentials (GEPs) for sucrose solution in patients with minor or major cognitive impairment (CI) linked to AD, and to compare them with healthy controls. The secondary objective was to evaluate the relationships between GEPs and the results of cognitive assessments and fasting blood samples. METHODS: A total of 45 subjects (15 healthy subjects, 15 minor CI patients, 15 major CI patients) were included to compare their gustatory functions and brain activity by recording GEPs in response to a sucrose stimulation. CI groups were combined in second analyses in order to keep a high power in the study. Correlations were made with cognitive scores and hormone levels (ghrelin, leptin, insulin, serotonin). RESULTS: Increased P1 latencies and reduced N1 amplitudes were observed in minor or major patients compared to controls. GEPs were undetectable in 6 major and 4 minor CI patients. Thresholds for sucrose detection were significantly higher in the major CI group than in controls or the minor CI group. No correlation was found with hormone levels. CONCLUSIONS: The cortical processing of sensory taste information seems to be altered in patients with minor or major CI linked to AD. This disturbance was identifiable with subjective taste tests only later, at the major CI stage.

Health related quality of life, remission and low lupus disease activity state in patients with systemic lupus erythematosus.

OBJECTIVES: To measure the association between systemic lupus erythematosus (SLE) remission and scores of patients reported outcome measures (PRO). METHODS: We performed a prospective cohort study of SLE patients with a 2-year follow-up, recording LupusPRO, LupusQol, SLEQOL, and SF-36 questionnaires. Remission was defined as remission-off-treatment (ROFT) and remission-on-treatment (RONT) according to the DORIS consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT versus no remission, and Lupus Low Disease activity state (LLDAS) versus no LLDAS. RESULTS: A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: "lupus symptoms" (LLDAS: +5 points on the 0-100 scale, RONT: +9 and ROFT: +5), "lupus medication" (LLDAS: +5, RONT: +8 and ROFT: +9), "pain vitality" (LLDAS: +6, RONT: +9 and ROFT: +6) of LupusPRO, "role emotional" (LLDAS: +5, RONT: +8), "role physical" (RONT: +7 and ROFT: +7), "bodily pain" (RONT: +6), "mental health" (RONT: +5) and "social functioning" (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQol and SLEQOL domains. CONCLUSIONS: RONT, ROFT, and LLDAS were associated with significant and clinically relevant higher quality of life in most PRO domains of LupusPRO (disease-specific) and SF-36 (generic) questionnaires, but not with LupusQol and SLEQOL disease-specific questionnaires.

Score to assess the probability of relapse in granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: To develop a score assessing the probability of relapse in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS: Long-term follow-up data from GPA and MPA patients included in five consecutive randomised controlled trials were pooled. Patient characteristics at diagnosis were entered into a competing-risks model, with relapse as the event of interest and death the competing event. Univariate and multivariate analyses were computed to identify variables associated with relapse and build a score, which was then validated in an independent cohort of GPA or MPA patients. RESULTS: Data collected from 427 patients (203 GPA, 224 MPA) at diagnosis were included. Mean±SD follow-up was 80.6±51.3 months; 207 (48.5%) patients experienced ≥1 relapse. Relapse risk was associated with proteinase 3 (PR3) positivity (HR=1.81 (95% CI 1.28 to 2.57); p<0.001), age ≤75 years (HR=1.89 (95% CI 1.15 to 3.13); p=0.012) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² (HR=1.67 (95% CI 1.18 to 2.33); p=0.004) at diagnosis. A score, the French Vasculitis Study Group Relapse Score (FRS), from 0 to 3 points was modelised: 1 point each for PR3-antineutrophil cytoplasmic antibody positivity, eGFR ≥30 mL/min/1.73 m² and age ≤75 years. In the validation cohort of 209 patients, the 5-year relapse risk was 8% for a FRS of 0, 30% for 1, 48% for 2 and 76% for 3. CONCLUSION: The FRS can be used at diagnosis to assess the relapse risk in patients with GPA or MPA. Its value for tailoring the duration of maintenance therapy should be evaluated in future prospective trials.

The mediating effect of fatigue in impaired quality of life in systemic lupus erythematosus: mediation analysis of the French EQUAL cohort.

OBJECTIVES: Mediation analyses were conducted to measure the extent to which musculoskeletal (MSK) flares and depression affected physical health through excessive fatigue. METHODS: Mediation analyses were performed in a large multicentre cohort of SLE patients. Domains of the LupusQoL and SLEQOL questionnaires were selected as outcomes, MSK flares according to the SELENA-SLEDAI flare index (SFI-R) score and depression defined by Center for Epidemiologic Studies-Depression scale (CES-D) scale as exposures and different fatigue domains from MFI-20 and LupusQoL questionnaires as mediators. For each model, total, direct, indirect effects and proportion of effect mediated by fatigue (i.e. proportion of change in health-related quality of life) were determined. RESULTS: Of the 336 patients, 94 (28%) had MSK flares at inclusion and 99 (29.5%) were considered with depression. The proportion of the total effect of MSK flares on physical health impairment explained by fatigue ranged from 59.6% to 78% using the LupusQOL 'Physical health' domain and from 51.1% to 73.7% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. The proportion of the total effect of depression on physical health impairment explained by fatigue ranged from 68.8% to 87.6% using the LupusQOL 'Physical health' domain and from 79.3% to 103.2% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. CONCLUSIONS: The effect of MSK flares and depression on physical health impairment is largely mediated by fatigue. Thus, the patient's perception of disease activity as measured by physical health is largely influenced by fatigue. In addition, fatigue has a significant negative impact on quality of lifeof SLE patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812.

PET/CT of cranial arteries for a sensitive diagnosis of giant cell arteritis.

OBJECTIVES: To investigate the performance of cranial PET/CT for the diagnosis of GCA. METHODS: All patients with a suspected diagnosis of GCA were prospectively enrolled in this study and had a digital PET/CT with evaluation of cranial arteries if they had not started glucocorticoids >72 h previously. The diagnosis of GCA was retained after at least 6 months of follow-up if no other diagnosis was considered by the clinician and the patient went into remission after at least 6 consecutive months of treatment. Cranial PET/CT was considered positive if at least one arterial segment showed hypermetabolism similar to or greater than liver uptake. RESULTS: For cranial PET/CT, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were 73.3%, 97.2%, 91.7% and 89.7%, respectively. For extracranial PET/CT, diagnostic performance was lower (Se = 66.7%, Sp = 80.6%, PPV = 58.8%, NPV = 85.3%). The combination of cranial and extracranial PET/CT improved overall sensitivity (Se = 80%) and NPV (NPV = 90.3%) while decreasing overall specificity (Sp = 77.8%) and PPV (PPV = 60%). CONCLUSION: Cranial PET/CT can be easily combined with extracranial PET/CT with a limited increase in examination time. Combined cranial and extracranial PET/CT showed very high diagnostic accuracy for the diagnosis of GCA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05246540.

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients.

BACKGROUND: We evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS). METHODS: IS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity. RESULTS: Among the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages. CONCLUSION: Impaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.

Risk of livedo with antiphospholipid antibodies in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Livedo is a well-known skin condition in patients with systemic lupus erythematosus (SLE) which correspond to small vessels involvement. The influence of antiphospholipid antibodies (aPL) on the occurrence of livedo is controversial. The aim of our study was to estimate the risk of livedo associated with aPL in patients with SLE. METHODS: We conducted a systematic review and meta-analysis of the literature from 1977 to 2021 to estimate the risk of livedo in SLE patients according to different aPL profiles. Data sources were PubMed, Embase, Cochrane Library, hand search, and reference lists of studies. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcome (livedo). Two independent investigators assessed study eligibility, quality, and extracted patient characteristics from each study as well as exposure (aPL) and outcome (livedo). Risk estimates were pooled using random effects models and sensitivity analyses. For all stages of the meta-analysis, we followed the PRISMA guidelines. PROSPERO registration number: CRD42015027377. RESULTS: Of the 2,355 articles identified, 27 were included with a total of 4,810 SLE patients. The frequency of livedo was 25.5% in aPL-positive patients and 13.3% in aPL-negative patients. The overall Odds Ratio (OR) for livedo in aPL-positive patients compared to aPL-negative patients was 2.91 (95% CI; 2.17-3.90). The risk of livedo was significantly increased for most of aPL subtypes, including lupus anticoagulant (LA) (OR = 4.45 [95% CI; 2.21-8.94]), IgG anticardiolipin (OR = 3.95 [95% CI; 2.34-6.65]), and IgG anti-ß2-glycoprotein 1 (OR = 3.49 [95% CI; 1.68-7.27]). CONCLUSIONS: We demonstrated in this meta-analysis an excess risk of livedo in aPL-positive SLE patients compared to aPL-negative patients. For daily practice, in patients with SLE, livedo associated with aPL could correspond to a peculiar group of patients with small vessel disease. Livedo could be a good candidate for inclusion in future classification criteria for antiphospholipid syndrome.

T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients.

INTRODUCTION: This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection. PATIENTS AND METHODS: Patients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not. RESULTS: Thirty-seven patients (18 men, 19 women) were included; 11 (30%) progressed to critical infection. At admission, the critical infection patients were older (P = 0.021), had higher creatinine levels (P = 0.003), and decreased percentages of circulating B cells (P = 0.04), T cells (P = 0.009), and CD4+ T cells (P = 0.004) than those with a favorable course. Among T cell subsets, there was no significant difference between the two groups except for the percentage of Th17 cells, which was two-fold higher in patients who progressed to critical infection (P = 0.028). Plasma IL-6 at admission was also higher in this group (P = 0.018). In multivariate analysis, the percentage of circulating Th17 cells at admission was the only variable associated with higher risk of progression to critical SARS-Cov2 infection (P = 0.021). CONCLUSION: This study suggests that an elevated percentage of Th17 cells in patients hospitalized for SARS-Cov2 infection is associated with an increased risk of progression to critical disease. If these data are confirmed in a larger study, this marker could be used to better target the population of patients in whom tocilizumab could decrease the risk of progression to critical COVID-19.

Quality of Life in the First Year after Ischemic Stroke Treated with Acute Revascularization Therapy.

(1) Background: we aimed to describe the disease-specific quality of life (QoL) of ischemic stroke patients treated with acute revascularization therapy, its evolution from 6 months to 12 months, and associated factors. (2) Methods: QoL was assessed with the SS-QoL in consecutive patients treated with either intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT). Variables associated with QoL scores and its evolution were studied using multivariate mixed models, and interaction with time. Analyses were performed in four domains of SS-QoL: self-care, mobility, mood, and social roles. (3) Results: Among the 501 included patients (mean (sd) age 68.9 (14.5), 49% women), lower post-stroke QoL was independently related to lower level of school education, prestroke mRS > 2, and 24 h NIHSS score > 4. Independent predictors of unfavorable evolution of QoL over time were age <75 years (Mobility p = 0.0194 and Mood p = 0.0015), NIHSS score ≤ 4, (Self-care p = 0.0053 and Mood p = 0.0048), and modified Rankin Scale score ≤ 2 (Social roles, p = 0.0006). Revascularization therapy had no significant effect on the QoL scores, but patients treated with MT (alone or as bridging therapy) had significantly greater improvement in mobility score between 6 and 12 months than patients treated with IVT alone (p = 0.0072). (4) Conclusion: QoL evolution over one year had only slight variation and was associated with the modalities of acute treatment, age, and stroke severity.

Cognitive assessment scale for stroke patients (CASP): A multicentric validation study.

BACKGROUND: The Mini Mental State Examination and Montreal Cognitive Assessment are commonly used as short screening batteries for assessing cognitive impairment after stroke. However, aphasia or hemispatial neglect may interfere with the results. For this reason, we developed the Cognitive Assessment scale for Stroke Patients (CASP), which takes these conditions into consideration and previously demonstrated its superiority over these scales in terms of feasibility. OBJECTIVES: Our goal was to verify the psychometric properties of the (original) French version of the CASP. METHODS: We included 201 patients with a recent first hemispheric stroke and 50 controls. Stroke patients were examined 4 times (visit 1 [V1] to visit 4 [V4]) in the subacute post-stroke phase. The structural validity of the CASP was studied by principal factorial analysis, convergent validity by comparison with several variables including a comprehensive neuropsychological assessment, divergent validity by comparison with the total score between stroke patients and controls, and sub-scores between right and left stroke. Internal consistency, reproducibility and sensitivity to change were assessed. We propose the Minimal Clinically Important Difference (MCID) value and a pathological threshold as well as a threshold to predict cognitive change between V1 and V4. RESULTS: Of the 201 participants included (63% male; mean [SD] age 63 [13] years), CASP data were available for 199/150/133/93 at V1/V2/V3/V4, respectively. CASP has a one-dimensional structure. The hypotheses of convergent/divergent validities were confirmed. Internal consistency was good and reliability excellent. Responsiveness was small to moderate, but the MCID could still be estimated. We discuss the choice of a pathological threshold and a predictive threshold of V1 over V4. CONCLUSIONS: CASP has good psychometric properties for screening cognitive impairment in the subacute post-stroke phase, which is consistent with its Italian and Korean versions. It can be used for patients with severe motor aphasia or left hemispatial neglect but not in case of severe oral comprehension or visual impairment.

Cardiovascular outcomes after cardiac resynchronization therapy in cardiac amyloidosis.

AIMS: Cardiac resynchronization therapy (CRT) is highly effective in dilated cardiomyopathy (DCM) patients with impaired left ventricular ejection fraction (LVEF) and left bundle block branch. In cardiac amyloidosis (CA) patients, left ventricular dysfunction and conduction defects are common, but the potential of CRT to improve cardiac remodelling and survival in this particular setting remains undefined. We investigated cardiovascular outcomes in CA patients after CRT implantation in terms of CRT echocardiographic response and major cardiovascular events (MACEs). METHODS AND RESULTS: Our retrospective study included 47 CA patients implanted with CRT devices from January 2012 to February 2020, in nine French university hospitals (77 ± 6 years old, baseline LVEF 30 ± 8%) compared with propensity-matched (1:1 for age, LVEF at implantation, and CRT indication) DCM patients with a CRT device. CA patients had lower rates of CRT response (absolute delta LVEF ≥ 10%) compared with DCM patients (36% vs. 70%, P = 0.002). After multivariate Cox analysis, CA was independently associated with MACE (hospitalization for heart failure/cardiovascular death) [hazard ratio (HR) 3.73, 95% confidence interval (CI) 1.85-7.54, P < 0.001], along with the absence of CRT response (HR 3.01, 95% CI 1.56-5.79, P = 0.001). The presence of echocardiographic CRT response (absolute delta LVEF ≥ 10%) was the only predictive factor of MACE-free survival in CA patients (HR 0.36, 95% CI 0.15-0.86, P = 0.002). CONCLUSION: Compared with a matched cohort of DCM patients, CA patients had a lower rate of CRT response and consequently a worse cardiovascular prognosis after CRT implantation. However, CRT could be beneficial even in CA patients given that CRT response was associated with better cardiac outcomes in this population.

Assessment of Prescriptions in Elderly Patients Hospitalized in Medicine Departments.

Drug-related iatrogenesis is an important issue in the elderly population, and preventing iatrogenic accidents helps to reduce hospitalizations. Our study's objective was to evaluate prescriptions in the geriatric population of our establishment. The study conducted is a targeted clinical audit. Ten criteria were tested on the hospital prescriptions of people over 75 years old in 11 medical departments, before and after improvement actions. The non-compliance threshold was set at 10% of prescriptions for each criterion. In each phase, 165 patients were included. Four criteria were non-compliant (NC) in the first phase: the presence of Potentially Inappropriate Medications for the Elderly (PIMs) (NC = 57.6%), the adaptation of the medication to renal clearance (NC = 24.9%), the presence of illogical combination (NC = 9.7%), and the total anti-cholinergic score of the prescription (NC = 12.1%). After the implementation of improvement actions, the number of non-compliant criteria decreased between the two phases, from four to two. We obtained a significant improvement for three of the four criteria found to be non-compliant in the first phase. The criterion adaptation to renal function is close to compliance (NC = 10.1%) and the PIMs criterion remained non-compliant after reassessment (NC = 32.1%). Vigilance must be ongoing in order to limit drug iatrogeny, particularly in frail elderly patients.

Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis.

OBJECTIVES: To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab. METHODS: Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab (n = 20) or glucocorticoids (n = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T-cell (Teff) proliferation and polarisation into Th1 and Th17 cells. RESULTS: Treg (CD4+CD25highFoxP3+) frequency in total CD4+ T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P < 0.001) and increased after treatment with tocilizumab but worsened after treatment with glucocorticoids alone. Treg lacking exon 2 of FoxP3 were increased in GCA patients when compared to controls (23% vs. 10% of total Treg, P = 0.0096) and normalised after treatment with tocilizumab + glucocorticoids but not glucocorticoids alone. In GCA patients, Treg were unable to control Teff proliferation and induced ˜50% increase in the amount of IL-17+ Teff, which was improved after in vitro blockade of the IL-6 pathway by tocilizumab. CONCLUSION: This study reports quantitative and functional disruptions in the regulatory immune response of GCA patients and demonstrates that, unlike glucocorticoids, tocilizumab improves Treg immune response.

Does hydroxychloroquine improve patient reported outcomes in patients with lupus?

BACKGROUND: 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: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -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.