METHODS: In this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares.
FINDINGS: Between May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent.
INTERPRETATION: Attainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions.
FUNDING: UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.
METHODS: In this prospective cohort study, patients aged 18 years or older with SLE were recruited from 13 centres in eight countries and followed prospectively. Patients with at least two visits over the study period no more than 6 months apart were included in the longitudinal analysis. Patients with no visits in the final year of the study were censored from their last visit. Attainment of the lupus low disease activity state (LLDAS) was assessed at each visit. The primary outcome measure was accrual of irreversible end-organ damage, defined as at least a 1-point increase in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We used time-dependent hazard regression models and generalised linear models to measure the association between LLDAS (attainment at any timepoint, cumulative time in LLDAS, and sustained LLDAS) with accrual of irreversible end-organ damage or flare (key secondary outcome). This study is registered with ClinicalTrials.gov, NCT03138941.
FINDINGS: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Attainment of LLDAS at any timepoint was associated with reduction in damage accrual (hazard ratio 0·59, 0·45-0·76; p<0·0001) and subsequent flare (0·65, 95% CI 0·56-0·75; p<0·0001). Cumulative time in LLDAS was associated with improved outcomes: compared with patients with less than 50% of observed time in LLDAS, those with at least 50% of observed time in LLDAS had reduced risk of damage accrual (0·54, 0·42-0·70; p<0·0001) and flare (0·41, 0·35-0·48; p<0·0001). Similarly, increased durations of sustained LLDAS were associated with incremental reductions in the risk of damage accrual. The association of LLDAS with reduced damage accrual was observed regardless of pre-existing damage or disease activity at study entry.
INTERPRETATION: LLDAS attainment is associated with significant protection against flare and damage accrual in SLE. These findings validate LLDAS as an endpoint for clinical studies in SLE.
FUNDING: The Asia Pacific Lupus Collaboration received project support grants from UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.
OBJECTIVE: This study aims to (1) measure the cost of health resources utilization by MS patients and (2) to examine the difference in utilization and its attributed costs amongst patients who may have a different course of MS and expanded disability status scale (EDSS) scores.
METHODS: A cross-sectional study using Kuwait National MS registry was conducted to estimate the costs of utilization of resources from 2011 to 2015.
RESULTS: Between the period 2011-2015, 1344 MS patients were included in the registry. The average annual cost per MS patient has increased from $10,271 in 2011 to $17,296 in 2015. Utilization of disease-modifying therapies (DMTs) was the main driver of costs reaching 89.9% in 2015. Throughout the five-year period, the occurrence of relapses decreased from 21.8% to 12.2% (p <0.0001). During this same period, ambulatory relapse treatment increased by 5.8% while hospitalizations decreased by 2.6%. Patients with a moderate EDSS score (3.5-6) had the highest average cost (p<0.0001) compared to mild and severe EDSS scores.
CONCLUSIONS: Multiple sclerosis has been a significant economic burden on the Kuwait healthcare system. DMTs are the main driver of cost.
OBJECTIVE: To analyze trends in levels of lipids and apolipoprotein B in US youths during 18 years from 1999 through 2016.
DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional analysis of US population-weighted data for youths aged 6 to 19 years from the National Health and Nutrition Examination Surveys for 1999 through 2016. Linear temporal trends were analyzed using multivariable regression models with regression coefficients (β) reported as change per 1 year.
EXPOSURES: Survey year; examined periods spanned 10 to 18 years based on data availability.
MAIN OUTCOMES AND MEASURES: Age- and race/ethnicity-adjusted mean levels of high-density lipoprotein (HDL), non-HDL, and total cholesterol. Among fasting adolescents (aged 12-19 years), mean levels of low-density lipoprotein cholesterol, geometric mean levels of triglycerides, and mean levels of apolipoprotein B. Prevalence of ideal and adverse (vs borderline) levels of lipids and apolipoprotein B per pediatric lipid guidelines.
RESULTS: In total, 26 047 youths were included (weighted mean age, 12.4 years; female, 51%). Among all youths, the adjusted mean total cholesterol level declined from 164 mg/dL (95% CI, 161 to 167 mg/dL) in 1999-2000 to 155 mg/dL (95% CI, 154 to 157 mg/dL) in 2015-2016 (β for linear trend, -0.6 mg/dL [95% CI, -0.7 to -0.4 mg/dL] per year). Adjusted mean HDL cholesterol level increased from 52.5 mg/dL (95% CI, 51.7 to 53.3 mg/dL) in 2007-2008 to 55.0 mg/dL (95% CI, 53.8 to 56.3 mg/dL) in 2015-2016 (β, 0.2 mg/dL [95% CI, 0.1 to 0.4 mg/dL] per year) and non-HDL cholesterol decreased from 108 mg/dL (95% CI, 106 to 110 mg/dL) to 100 mg/dL (95% CI, 99 to 102 mg/dL) during the same years (β, -0.9 mg/dL [95% CI, -1.2 to -0.6 mg/dL] per year). Among fasting adolescents, geometric mean levels of triglycerides declined from 78 mg/dL (95% CI, 74 to 82 mg/dL) in 1999-2000 to 63 mg/dL (95% CI, 58 to 68 mg/dL) in 2013-2014 (log-transformed β, -0.015 [95% CI, -0.020 to -0.010] per year), mean levels of low-density lipoprotein cholesterol declined from 92 mg/dL (95% CI, 89 to 95 mg/dL) to 86 mg/dL (95% CI, 83 to 90 mg/dL) during the same years (β, -0.4 mg/dL [95% CI, -0.7 to -0.2 mg/dL] per year), and mean levels of apolipoprotein B declined from 70 mg/dL (95% CI, 68 to 72 mg/dL) in 2005-2006 to 67 mg/dL (95% CI, 65 to 70 mg/dL) in 2013-2014 (β, -0.4 mg/dL [95% CI, -0.7 to -0.04 mg/dL] per year). Favorable trends were generally also observed in the prevalence of ideal and adverse levels. By the end of the study period, 51.4% (95% CI, 48.5% to 54.2%) of all youths had ideal levels for HDL, non-HDL, and total cholesterol; among adolescents, 46.8% (95% CI, 40.9% to 52.6%) had ideal levels for all lipids and apolipoprotein B, whereas 15.2% (95% CI, 13.1% to 17.3%) of children aged 6 to 11 years and 25.2% (95% CI, 22.2% to 28.2%) of adolescents aged 12 to 19 years had at least 1 adverse level.
CONCLUSIONS AND RELEVANCE: Between 1999 and 2016, favorable trends were observed in levels of lipids and apolipoprotein B in US youths aged 6 to 19 years.