Long-Term Opioid Therapy Among Patients With Systemic Lupus Erythematosus in the Community: A Lupus Midwest Network (LUMEN) Study.

OBJECTIVE: There is little information about the epidemiology and factors associated with opioid therapy in systemic lupus erythematosus (SLE). We aimed to assess the prevalence of opioid therapy and explore factors associated with long-term opioid therapy (LTOT) in patients with SLE. METHODS: Patients with SLE were matched with controls without SLE in a population-based cohort on January 1, 2015. We captured demographics, manifestations of SLE, comorbidities (ie, fibromyalgia, mood disorders, osteoarthritis, chronic low back pain [CLBP], chronic kidney disease (CKD), avascular necrosis, osteoporosis, fragility fractures, and cancer), and the Area Deprivation Index (ADI). Opioid prescription data were used to assess the prevalence of LTOT, defined as contiguous prescriptions (gaps of < 30 days between prescriptions) and receiving opioid therapy for ≥ 90 days or ≥ 10 prescriptions before the index date. RESULTS: A total of 465 patients with SLE and 465 controls without SLE were included. In total, 13% of patients with SLE and 3% of controls without SLE were receiving opioid therapy (P < 0.001), and 11% of patients with SLE were on LTOT vs 1% of controls without SLE. Among patients with SLE, acute pericarditis (odds ratio [OR] 3.92, 95% CI 1.78-8.66), fibromyalgia (OR 7.78, 95% CI 3.89-15.55), fragility fractures (OR 3.72, 95% CI 1.25-11.07), CLBP (OR 4.00, 95% CI 2.13-7.51), and mood disorders (OR 2.76, 95% CI 1.47-5.16) were associated with LTOT. We did not find an association between opioid therapy and ADI. CONCLUSION: Patients with SLE are more likely to receive LTOT than controls. Among patients with SLE, LTOT was associated with pericarditis and several comorbidities. However, LTOT was not associated with CKD despite the limited pain control options among these patients.

Health Care Utilization in Systemic Lupus Erythematosus in the Community: The Lupus Midwest Network.

OBJECTIVE: The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population. METHODS: This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995-2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups. RESULTS: Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05-3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups. CONCLUSION: Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.

Rising incidence and prevalence of systemic lupus erythematosus: a population-based study over four decades.

OBJECTIVES: To determine the trends in incidence, prevalence and mortality of systemic lupus erythematosus (SLE) in a US population over four decades. METHODS: We identified all the patients with SLE in Olmsted County, Minnesota who fulfilled the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria for SLE during 1976-2018. Age-specific and sex-specific incidence and prevalence rates were adjusted to the standard 2000 projected US population. The EULAR/ACR score was used as a proxy for disease severity. Standardised mortality ratio (SMR) was estimated. RESULTS: There were 188 incident SLE cases in 1976-2018 (mean age 46.3±SD 16.9; 83% women). Overall age-adjusted and sex-adjusted annual SLE incidence per 100 000 population was 4.77 (95% CI 4.09 to 5.46). Incidence was higher in women (7.58) than men (1.89). The incidence rate increased from 3.32 during 1976-1988 to 6.44 during 2009-2018. Incidence rates were higher among the racial and ethnic minority populations than non-Hispanic whites. The EULAR/ACR score did not change significantly over time. Overall prevalence increased from 30.6 in 1985 to 97.4 in 2015. During the study period, there was no improvement in SMR over time (p=0.31). CONCLUSIONS: The incidence and prevalence of SLE are increasing in this US population. The increase in incidence may be at least partially explained by the rising ethnic/racial diversity of the population. There was no evidence that the severity of SLE has changed over time. The survival gap between SLE and the general population remains unchanged. As the US population grows more diverse, we might continue to see an increase in the incidence of SLE.

Population-based incidence and time to classification of systemic lupus erythematosus by three different classification criteria: a Lupus Midwest Network (LUMEN) study.

OBJECTIVE: To estimate the incidence and time-to-classification of SLE by the 1997 ACR (ACR97) criteria, the SLICC criteria, and the European Alliance of Associations for Rheumatology/ACR (EULAR/ACR) criteria. METHODS: We identified all incident SLE cases from 2000-2018 in the well-defined Olmsted County population. Clinical data included in the ACR97, SLICC and EULAR/ACR criteria were manually abstracted from medical records. All incident cases met at least one of the three classification criteria. Time-to-classification was estimated from the first documented lupus-attributable disease manifestation to the time of criteria fulfilment by each of the three definitions. Annual incidence rates were age or age/sex adjusted to the 2000 US population. RESULTS: Of 139 incident cases there were 126 cases by the EULAR/ACR criteria, corresponding to an age/sex-adjusted incidence of 4.5 per 100 000 population (95% CI: 3.7, 5.2). The age/sex-incidence was higher than that of the SLICC criteria (113 cases; 4.0 per 100 000 [95% CI: 3.3, 4.7], P = 0.020) and the ACR97 (92 cases; 3.3 per 100 000 [95% CI: 2.6, 3.9], P < 0.001). The median time from first disease manifestation to criteria fulfilment was shorter for the EULAR/ACR criteria (29.4 months) than the ACR97 criteria (47.0 months, P < 0.001) and similar to the SLICC criteria (30.6 months, P = 0.83). CONCLUSION: The incidence of SLE was higher by the EULAR/ACR criteria compared with the ACR97 and the SLICC criteria, and the EULAR/ACR criteria classified patients earlier that the ACR97 criteria but similar to the SLICC criteria.

Risk of hydroxychloroquine retinopathy in the community.

OBJECTIVES: We aimed to estimate the risk of HCQ retinopathy and its risk factors among incident users in the community. METHODS: Using the Rochester Epidemiology Project, a record-linkage system, a cohort of incident users of HCQ was identified from 27 counties in the American upper Midwest. HCQ retinopathy was defined based on characteristic paracentral automated 10-2 visual field (10-2 AVF) defects and parafoveal retinal photoreceptor layer changes on spectral domain optical coherence tomography. Cumulative incidence rates were estimated adjusting for competing risk of death. Risk factors for HCQ retinopathy were examined using Cox models. RESULTS: The study included 634 incident HCQ users (mean age at initial HCQ use was 53.7 years, 79% females, 91% white). Most common indications for HCQ were RA (57%) and SLE (19%). The average follow-up length was 7.6 years. Eleven patients developed HCQ retinopathy (91% females, 91% white). The majority used HCQ for RA (91%). The cumulative incidence rate at year 5 was 0%, which increased to 3.9% (95% CI 2.0, 7.4) by 10 years. Taking an HCQ dose ≥5 mg/kg was associated with a hazard ratio (HR) of 3.59 (95% CI 1.09, 11.84) compared with lower doses. There was a 48% increase [HR 1.48 (95% CI 1.03, 2.14)] in the risk of HCQ retinopathy for each 100 g of HCQ cumulative dose. CONCLUSION: The risk of HCQ retinopathy at 10 years of use is lower compared with previous prevalence-based estimations. A dose ≥5 mg/kg was associated with higher HCQ retinopathy risk.

Epidemiology of Antiphospholipid Syndrome in the General Population.

PURPOSE OF REVIEW: The epidemiology of antiphospholipid syndrome (APS) is poorly understood. Here, we review the current understanding of the epidemiology of antiphospholipid syndrome in the general population and the frequency of antiphospholipid antibodies in the general population in patients with obstetric morbidity, arterial events, and venous thromboembolism. RECENT FINDINGS: There have been few population-based studies that estimated the prevalence and incidence of APS. The estimated incidence and prevalence among most these studies ranged between 1 and 2 cases per 100,000 and 40 and 50 cases per 100,000 respectively. The prevalence of antiphospholipid antibodies in patients with obstetric morbidity was 6-9%, while in arterial events and venous thromboembolism is 9-10%. However, this data remains limited. Mortality of patients with APS is 50-80% higher than the general population. The epidemiology of APS has been difficult to elucidate. Population-based studies patients with diverse age, racial, and ethnic backgrounds are needed.

Incidence, Prevalence, and Mortality of Lupus Nephritis: A Population-Based Study Over Four Decades Using the Lupus Midwest Network.

OBJECTIVE: There is a paucity of population-based studies investigating the epidemiology of lupus nephritis (LN) in the US and long-term secular trends of the disease and its outcomes. We aimed to examine the epidemiology of LN in a well-defined 8-county region in the US. METHODS: Patients with incident LN between 1976 and 2018 in Olmsted County, Minnesota (1976-2009) and an 8-county region in southeast Minnesota (2010-2018) were identified. Age- and sex-specific incidence rates and point prevalence over 4 decades, adjusted to the projected 2000 US population, were determined. Standardized mortality ratios (SMRs), survival rates, and time to end-stage renal disease (ESRD) were estimated. RESULTS: There were 72 patients with incident LN between 1976 and 2018, of whom 76% were female and 69% were non-Hispanic White. Mean ± SD age at diagnosis was 38.4 ± 16.24 years. Average annual LN incidence per 100,000 population between 1976 and 2018 was 1.0 (95% CI 0.8-1.3) and was highest in patients ages 30-39 years. Between the 1976-1989 and 2000-2018 time periods, overall incidence of LN increased from 0.7 to 1.3 per 100,000, but this was not statistically significant. Estimated LN prevalence increased from 16.8 per 100,000 in 1985 to 21.2 per 100,000 in 2015. Patients with LN had an SMR of 6.33 (95% CI 3.81-9.89), with no improvement in the mortality gap in the last 4 decades. At 10 years, survival was 70%, and 13% of LN patients had ESRD. CONCLUSION: The incidence and prevalence of LN in this area increased in the last 4 decades. LN patients have poor outcomes, with high rates of ESRD and mortality rates 6 times that of the general population.

Epidemiology of Childhood-Onset Systemic Lupus Erythematosus: A Population-Based Study.

OBJECTIVE: To characterize the incidence and prevalence of childhood-onset systemic lupus erythematosus (SLE), and to estimate the proportion of patients who are diagnosed with SLE during childhood. METHODS: A cohort of patients with incident childhood-onset SLE from 1976 to 2018 from an 8-county region in the US were identified based on comprehensive medical record review. All patients met the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE or the ACR SLE classification criteria from 1997 at or before age 18 years. Incidence rates were estimated using Poisson methods. We estimated the childhood-onset SLE point prevalence for January 1, 2015. Results were sex and age adjusted to the US 2000 population. Among all the SLE patients living in the 8-county region on January 1, 2015, the proportion of patients diagnosed at ≤18 years was estimated. RESULTS: A total of 13 children were diagnosed with childhood-onset SLE during the study period (using the EULAR/ACR definition; mean age at diagnosis 15.1 years, 85% female, 69% White). Childhood-onset SLE overall adjusted incidence rate was 0.7 (95% confidence interval [95% CI] 0.2-1.1) per 100,000 children. The incidence rate in girls was 1.2 (95% CI 0.5-1.9) per 100,000 children, while in boys it was 0.2 (95% CI 0.0-0.5) per 100,000. The adjusted prevalence of childhood-onset SLE was 1.1 (95% CI 0.0-3.1) per 100,000 children. The proportion of patients with SLE diagnosed as children was 9% (95% CI 6-13%). CONCLUSION: In this population-based study, both the incidence and prevalence rates of childhood-onset SLE were ~1 per 100,000 children. One in 10 adults with SLE was diagnosed in childhood. More studies are needed to further characterize the epidemiology of childhood-onset SLE in minorities.

Epidemiology of Cutaneous Lupus Erythematosus Among Adults Over Four Decades (1976-2018): A Lupus Midwest Network (LUMEN) Study.

OBJECTIVE: To characterize the epidemiological trends and mortality of cutaneous lupus erythematosus (CLE) between 1976 and 2018 in Olmsted County, Minnesota. PATIENTS AND METHODS: In this retrospective population-based cohort study, all incident and prevalent CLE cases among adult residents in Olmsted County, Minnesota, between January 1, 1976, and December 31, 2018, were identified and categorized by subtype through medical record review using the resources of the Rochester Epidemiology Project. RESULTS: The overall incidence rate of CLE between 1976 and 2018 was 3.9 (95% CI, 3.4 to 4.5) per 100,000. The incidence of CLE was relatively stable, with no major trend across sexes or age groups. The age- and sex-adjusted prevalence of CLE was 108.9 per 100,000 on January 1, 2015. Mortality in CLE patients was similar to that of the general population, with a standardized mortality ratio of 1.23 (95% CI, 0.88 to 1.66) with no observed trends in mortality over time. CONCLUSION: In the past 4 decades, the incidence of CLE remained stable. Patients with CLE have mortality comparable to that of the general population.