Development and validation of a risk scoring system to identify patients with lupus nephritis in electronic health record data.

OBJECTIVE: Accurate identification of lupus nephritis (LN) cases is essential for patient management, research and public health initiatives. However, LN diagnosis codes in electronic health records (EHRs) are underused, hindering efficient identification. We investigated the current performance of International Classification of Diseases (ICD) codes, 9th and 10th editions (ICD9/10), for identifying prevalent LN, and developed scoring systems to increase identification of LN that are adaptable to settings with and without LN ICD codes. METHODS: Training and test sets derived from EHR data from a large health system. An external set comprised data from the EHR of a second large health system. Adults with ICD9/10 codes for SLE were included. LN cases were ascertained through manual chart reviews conducted by rheumatologists. Two definitions of LN were used: strict (definite LN) and inclusive (definite, potential or diagnostic uncertainty). Gradient boosting models including structured EHR fields were used for predictor selection. Two logistic regression-based scoring systems were developed ('LN-Code' included LN ICD codes and 'LN-No Code' did not), calibrated and validated using standard performance metrics. RESULTS: A total of 4152 patients from University of California San Francisco Medical Center and 370 patients from Zuckerberg San Francisco General Hospital and Trauma Center met the eligibility criteria. Mean age was 50 years, 87% were female. LN diagnosis codes demonstrated low sensitivity (43-73%) but high specificity (92-97%). LN-Code achieved an area under the curve (AUC) of 0.93 and a sensitivity of 0.88 for identifying LN using the inclusive definition. LN-No Code reached an AUC of 0.91 and a sensitivity of 0.95 (0.97 for the strict definition). Both scoring systems had good external validity, calibration and performance across racial and ethnic groups. CONCLUSIONS: This study quantified the underutilisation of LN diagnosis codes in EHRs and introduced two adaptable scoring systems to enhance LN identification. Further validation in diverse healthcare settings is essential to ensure their broader applicability.

Incidence Rate and Factors Associated With Fractures Among Medicare Beneficiaries With Ankylosing Spondylitis in the United States.

OBJECTIVE: We evaluated the incidence rate and factors associated with fractures among adults with ankylosing spondylitis (AS). METHODS: We performed a retrospective cohort study with data from the Rheumatology Informatics System for Effectiveness registry linked to Medicare claims from 2016 to 2018. Patients were required to have two AS International Classification of Diseases codes 30 or more days apart and a subsequent Medicare claim. Then, 1 year of baseline characteristics were included, after which patients were observed for fractures. First, we calculated the incidence rate of fractures. Second, we constructed logistic regression models to identify factors associated with the fracture, including age, sex, race and ethnicity, body mass index, Medicare/Medicaid dual eligibility, area deprivation index, Charlson comorbidity index, smoking status, osteoporosis, historical fracture, and use of osteoporosis treatment, glucocorticoids, and opioids. RESULTS: We identified 1,426 adults with prevalent AS. Mean ± SD age was 69.4 ± 9.8 years, 44.3% were female, and 77.3% were non-Hispanic White. Fractures occurred in 197 adults with AS. The overall incidence rate of fractures was 76.7 (95% confidence interval [CI] 66.4-88.6) per 1,000 person-years. Older age (odds ratio [OR] 2.8, 95% CI 1.39-5.65), historical fracture (OR 5.24, 95% CI 3.44-7.99), and use of more than 30 mg morphine equivalent (OR 1.86, 95% CI 1.08-3.19) conferred increased odds of fracture. CONCLUSIONS: In this large sample of Medicare beneficiaries with AS, increasing age, historical fracture, and use of opioids had higher odds of fracture. Men and women were equally likely to have a fracture. Because opioid use was associated with fracture in AS, this high-risk population should be considered for interventions to mitigate risk.

Association between self-reported race and ethnicity and myositis-specific autoantibodies in a diverse cohort of patients with inflammatory myopathy.

Myositis-specific autoantibodies (MSAs) are highly specific biomarkers for idiopathic inflammatory myopathies (IIMs). We investigated whether self-reported race and ethnicity were associated with the presence of specific MSAs. Charts of patients with IIM seen at 3 large healthcare systems in the same US city were reviewed. Demographic data and MSA test results were abstracted. Associations between race and ethnicity and presence of MSAs were analyzed using bivariate analysis and further characterized using separate unadjusted and adjusted logistic regression models. One hundred twenty-one subjects were included (19% Asian, 10% Black or African American, 27% Latinx or Hispanic, 36% non-Hispanic White, and 7% Other). In a bivariate analysis, anti-Jo-1 and anti-MDA5 autoantibodies were associated with race and ethnicity (p = 0.03 and 0.02, respectively). Black or African American subjects had increased odds of a positive anti-Jo-1 result compared to non-Hispanic White subjects on unadjusted logistic regression analysis (OR 8.61, 95% CI 1.61-46.07), although after adjustment for age and gender this finding was not significant. Subjects categorized as Other had increased odds of a positive anti-MDA5 result compared to non-Hispanic White subjects on both unadjusted (OR 55.0, 95% CI 2.02-1493) and adjusted analyses (OR 44.8, 95% CI 1.55-1298). Anti-Jo-1 and anti-MDA5 autoantibodies were significantly associated with race and ethnicity on bivariate analysis. Black or African American subjects had increased odds of positive anti-Jo-1 autoantibody on unadjusted, but not adjusted, logistic regression analysis. Subjects characterized as Other had increased odds of positive anti-MDA5 autoantibody, although confidence intervals were wide. Key Points • Association found between MSAs and race and ethnicity in diverse US cohort • Anti-Jo-1 and anti-MDA5 associated with race and ethnicity in bivariate analyses.

Causes of Death Among Individuals With Systemic Lupus Erythematosus by Race and Ethnicity: A Population-Based Study.

OBJECTIVE: Non-White populations are at higher risk of developing systemic lupus erythematosus (SLE) and have more severe outcomes, including mortality. The present study was undertaken to examine how specific causes of death vary by race and ethnicity, including Asian and Hispanic individuals. METHODS: The California Lupus Surveillance Project included SLE cases identified among residents of San Francisco County, CA during January 1, 2007 to December 31, 2009. Cases were matched to the National Death Index over a 10-year period. Logistic regression examined age-adjusted differences in causes of death by race, ethnicity, and sex. Age-standardized mortality ratios between individuals with SLE and the corresponding general population were calculated for the leading cause of death, and observed versus expected deaths were estimated. RESULTS: The study included 812 individuals of White (38%), Asian (36%), Black (20%), and mixed/other/unknown (5%) race; 15% identified as Hispanic. One hundred thirty-five deaths were recorded, with a mean ± SD age at death of 62.2 ± 15.6 years. Cardiovascular disease (CVD) was the leading cause of death overall (33%), and across all racial and ethnic groups, followed by rheumatic disease (18%) and hematologic/oncologic conditions (18%). CVD as the underlying cause of death was 3.63 times higher among SLE cases than in the general population. CVD deaths for those with SLE were nearly 4 and 6 times higher for Asian and Hispanic individuals with SLE, respectively, compared to the general population. CONCLUSION: Individuals with SLE experience a disproportionate burden of CVD mortality compared to the general population, which is magnified for Asian and Hispanic groups.

Review of publications evaluating opioid use in patients with inflammatory rheumatic disease.

PURPOSE OF REVIEW: This article discusses publications assessing the prevalence, efficacy, and safety of opioid analgesics in patients with rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis, and systemic sclerosis. RECENT FINDINGS: Recent studies show long-term opioid use is common in patients with inflammatory rheumatic disease. We did not find any studies demonstrating improved function or pain control with long-term opioid use in people with rheumatic diseases. Some data shows potential adverse effects including increased risk for fractures and opioid poisoning hospitalizations. There is evidence demonstrating an association of opioid use with mental health disorders, fibromyalgia, obesity, and disability, although causative links have not been established. Only minimal reductions in opioid use were observed after initiation of biologic disease modifying antirheumatic drugs (DMARDs). Studies have shown delayed DMARD initiation and reduced DMARD use in patients on opioids, raising concerns that these analgesics may delay care or initially mask symptoms of active disease. SUMMARY: Available literature highlights high levels of opioid use in people with rheumatic disease, without scientific evidence to support efficacy for chronic pain control and increasing evidence of adverse events. These findings strongly suggest that opioids do not have a routine role in the chronic management of inflammatory rheumatic diseases.

Treatment of Sarcoidosis in US Rheumatology Practices: Data From the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) Registry.

OBJECTIVE: Sarcoidosis is often treated with glucocorticoids, although the use of biologics is growing. Prescribing patterns for biologics for patients with sarcoidosis in US rheumatology practices have never been examined. Given that there are no steroid-sparing US Food and Drug Administration-approved therapies for sarcoidosis, we sought to characterize the real-world treatment of sarcoidosis and to assess practice-level variation in prescribing patterns. METHODS: We conducted an observational study of patients with sarcoidosis using data from the Rheumatology Informatics System for Effectiveness (RISE) registry (2014-2018). The RISE registry represents an estimated 32% of the US clinical rheumatology workforce. Adult patients with ≥2 codes for sarcoidosis ≥30 days apart were included. We examined sarcoidosis-specific medication use at any time during the study period. Data were analyzed at the practice level. RESULTS: A total of 3,276 patients with sarcoidosis from 184 practices were included. Of those patients, 75.1% were women, with a mean age of 59.0 ± 12.5 years; 48.3% were White and 27.6% were Black. Overall, 59.3% of patients were prescribed glucocorticoids, and 24.7% received prolonged glucocorticoid therapy (≥10 mg/day for ≥90 days). In all, 12.1% received a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD), most commonly tumor necrosis factor inhibitors. There was wide practice-level variation among 31 practices with ≥30 patients with sarcoidosis; biologic use ranged from 15.6% to 69.2%. Infliximab represented the most common biologic prescribed. CONCLUSION: In a large sample of US rheumatology practices, 12.1% of patients with sarcoidosis received biologics or tsDMARDs. We found high variability in biologic use across practices. The significant use of long-term glucocorticoids suggests unmet therapeutic needs in this patient population.

Quality of Care for Patients With Systemic Lupus Erythematosus: Data From the American College of Rheumatology RISE Registry.

OBJECTIVE: Although multiple national quality measures focus on the management and safety of rheumatoid arthritis, few measures address the care of patients with systemic lupus erythematosus (SLE). Our objective was to apply a group of quality measures relevant to the care of patients with SLE, and we used the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry to assess nationwide variations in care. METHODS: The data derived from RISE and included patients who had ≥2 visits with SLE codes ≥30 days apart in 2017-2018. We calculated performance on 5 quality measures: renal disease screening, blood pressure assessment and management, hydroxychloroquine (HCQ) prescribing, safe dosing for HCQ, and prolonged glucocorticoid use at doses of >7.5 mg/day. We reported performance on these measures at the practice level. We used logistic regression to assess independent predictors of performance after adjusting for sociodemographic and utilization factors. RESULTS: We included 27,567 unique patients from 186 practices; 91.7% were female and 48% White, with a mean age of 53.5 ± 15.2 years. Few patients had adequate screening for the development of renal manifestations (39.5%). Although blood pressure assessment was common (94.4%), a meaningful fraction of patients had untreated hypertension (17.7%). Many received HCQ (71.5%), but only 62% at doses of ≤5.0 mg/kg/day. Some received at least moderate-dose steroids for ≥90 days (18.5%). We observed significant practice variation on every measure. CONCLUSION: We found potential gaps in care for patients with SLE across the US. Although some performance variation may be explained by differences in disease severity, dramatic differences suggest that developing quality measures to address important health care processes in SLE may improve care.

Epidemiology and treatment of Behçet's disease in the USA: insights from the Rheumatology Informatics System for Effectiveness (RISE) Registry with a comparison with other published cohorts from endemic regions.

BACKGROUND: Behçet's disease (BD), a chronic systemic vasculitis, has distinct geographical and ethnic variation. Data regarding the epidemiology of patients with BD in the U.S. are limited; therefore, we sought to describe BD patient characteristics and medication use in the U.S., and compared them with data from patients from endemic regions. METHODS: We conducted a cross-sectional study using data from the RISE registry (2014-2018). Patients aged ≥ 18 years with BD were included. Sociodemographic and treatment information was extracted. We compared patients from the RISE registry to data from other published studies of patients with BD from endemic areas. RESULTS: One thousand three hundred twenty-three subjects with BD from the RISE registry were included. Mean age was 48.7 ± 16.3 years, female to male ratio was 3.8:1, and 66.7% were White. The most frequently used medications included glucocorticoids (67.6%) and colchicine (55.0%). Infliximab and adalimumab were the most used biologics (14.5% and 14.1%, respectively); 3.2% of patients used apremilast. The RISE registry had more women (79.3%), and patients were older compared to previously published BD studies from endemic areas. Methotrexate and TNFi were more commonly reported in RISE (21.8% and 29.4%) compared to studies from Egypt and Turkey. Colchicine, cyclosporine, and cyclophosphamide were more commonly used in cohorts from Egypt, Turkey, and Iran. CONCLUSIONS: Findings from the largest BD dataset in the U.S. suggest that BD patients are predominantly female. Further research is needed to explore the reasons for the higher prevalence of BD among women in the U.S. and its possible impact on disease severity and management.

Neurological manifestations of polyarteritis nodosa: a tour of the neuroaxis by case series.

BACKGROUND: Heterogenous central nervous system (CNS) neurologic manifestations of polyarteritis nodosa (PAN) are underrecognized. We review three cases of patients with PAN that illustrate a range of nervous system pathology, including the classical mononeuritis multiplex as well as uncommon brain and spinal cord vascular manifestations. CASE PRESENTATION: Case 1 presented with mononeuritis multiplex and characteristic skin findings. Case 2 presented with thunderclap headache and myelopathy due to spinal artery aneurysm rupture. Both patients experienced disease remission upon treatment. Case 3 presented with headache and bulbar symptoms due to partially thrombosed intracranial aneurysms, followed by systemic manifestations related to visceral aneurysms. She demonstrated clinical improvement with treatment, was lost to follow-up, then clinically deteriorated and entered hospice care. CONCLUSIONS: Although the peripheral manifestations of PAN are well-known, PAN association with CNS neurovascular disease is relatively underappreciated. Clinician awareness of the spectrum of neurologic disease is required to reduce diagnostic delay and promote prompt diagnosis and treatment with immunosuppressants.

Mortality Among Hospitalized Individuals With Systemic Lupus Erythematosus in the US Between 2006 and 2016.

OBJECTIVE: To evaluate time trends in mortality for hospitalized adults with systemic lupus erythematosus (SLE) compared to the general hospitalized population (GHP), and to identify factors associated with increased risk of death among hospitalized SLE patients. METHODS: We used the National (Nationwide) Inpatient Sample to estimate all-cause mortality for adults discharged from community hospitals in the US between 2006 and 2016. Poisson regression models were used to estimate the risk of in-hospital death among all patients, including demographic characteristics, socioeconomic factors, comorbidity score, hospital region, SLE diagnosis, and race/ethnicity as covariates. RESULTS: Among 340,467,049 hospitalizations analyzed, 1,903,279 had a discharge diagnosis of SLE. In adjusted analysis, the risk of inpatient death decreased among hospitalizations for patients with SLE from 2.2% to 1.5% (P < 0.001) between 2006 and 2016. All of the decrease in SLE mortality occurred between 2006 and 2008; after 2008, mortality stabilized at a rate statistically similar to the GHP. Hospitalizations for Black, Hispanic, and Asian/Pacific Islander patients with SLE were more likely to end in death compared to hospitalizations for either White patients with SLE or individuals of the same non-White race/ethnicity without SLE. CONCLUSION: In the largest study of in-hospital SLE mortality published to date, we found significant improvements in mortality for hospitalized patients with SLE in the US from 2006 until 2008, after which mortality stabilized at a level similar to that of the GHP. Our results also demonstrate a persistently high mortality burden among Black and Hispanic patients with SLE in the US and contribute new data revealing high mortality among Asian/Pacific Islander patients with SLE.

RISE registry reveals potential gaps in medication safety for new users of biologics and targeted synthetic DMARDs.

OBJECTIVE: Immunosuppressant drugs can increase the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) and tuberculosis (TB) reactivation. Using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry, we examined pre-treatment screening among new users of biologic or targeted synthetic disease modifying drugs (DMARDs). METHODS: Data, derived from RISE, included patients ≥ 18 years old who were new users of biologic or targeted synthetic DMARDs. We developed quality measures related to pre-treatment screening for HBV, HCV, and TB in addition to a "composite" measure for all applicable tests. We assessed patient-level screening rates, practice-level variation among practices reporting on ≥ 20 patients, and the frequency of positive results. RESULTS: We included 26,802 patients across 213 rheumatology practices nationwide. Patients were 58 (14) years old, 75.9% female; 59.6% had rheumatoid arthritis, and TNFi were the most common index DMARDs (64.9%). Overall, 44.8% and 40.5% patients had any documented HBV or HCV screening, respectively, prior to the index date; 29.7% had TB screening in the year prior to drug start. Only 15.5% had documentation of screening for all appropriate infections prior to drug start. Practice-level performance on the composite measure was low (range 0 to 48.3%). 2.4% of screening tests were positive. CONCLUSION: We found gaps in documentation of key safety measures among practices participating in RISE. Given the small but significant number of patients with active or latent infections that pose safety risks, developing standardized and reliable strategies to capture safety screening measures is paramount.

Immunosuppressant use and hospitalisations in adult patients with systemic lupus erythematosus admitted to a tertiary academic medical centre.

OBJECTIVES: To describe how immunosuppressant use and hospitalisation patterns for SLE have evolved by comparing admission statistics at one academic centre between 2005 and 2013. METHODS: We identified admissions for SLE and for all hospitalised patients by using the hospital electronic database. For adult patients with SLE, a comprehensive chart review was conducted to identify primary indications for hospitalisation, in-hospital mortality, mean length of stay and immunosuppressant use. RESULTS: The number of yearly SLE patient hospitalisations decreased from 178 to 86 between the two times of observation. Infection was the most common reason for hospitalisation accounting for 39.9% of hospitalisations in 2005 versus 31.4% of hospitalisations in 2013 (p=0.29). Lupus flare accounted for 9.6% of admissions in 2005 versus 8.1% of admissions in 2013 (p=0.72). Seven patients died during their hospitalisation (3.9% of admissions) in 2005 as opposed to no inpatient deaths in 2013. Of the 261 admissions between 2010 and 2013, six admissions resulted in death (2.3% of admissions). SLE patient mean length of hospital stay decreased from 7.6 days to 6.4 days (p=0.36) compared with all patient length of stay, which decreased from 6 days to 5.8 days. Corticosteroid use decreased (79.8% to 61.6%, p=0.11) while hydroxychloroquine (27.0% to 59.3%, p<0.001) use increased over time. CONCLUSIONS: The number of hospitalisations, mortality and length of stay among hospitalised patients with SLE decreased over time. Infection was the primary reason for inpatient hospitalisation. Hydroxychloroquine use more than doubled over this same time period with statistical significance. These pilot data suggest improvements in SLE hospitalisation outcomes over time, but larger studies are needed to examine these trends and to understand the relationship between changing medication prescribing patterns and hospitalisation outcomes in patients with SLE.