Systemic Lupus Erythematosus Medications Research Articles

Treatment adherence and quality of life in colombian patients with lupus nephritis.

As with many other chronic diseases, systemic lupus erythematosus (SLE) and lupus nephritis (LN) have significant impacts on the health-related quality of life (HRQoL). Medication non-adherence is a significant challenge in the management of SLE, with consistently up to 75% of patients being non-adherent with their SLE medications. There is a need to assess the patient's perspective using patient-reported outcomes (PROs) to better understand the current impact of LN on HRQoL and treatment adherence in our region. The aim of this study was to explore the relationship between HRQoL and treatment adherence in patients with LN from the Colombian Caribbean. A cross-sectional study was conducted from June to December 2022, including patients with biopsy-proven LN. HRQoL and treatment adherence were assessed using the Lupus Quality of Life (LupusQoL) and the Compliance Questionnaire in Rheumatology 19 (CQR19) instruments, respectively. Patients were categorized as adherent or non-adherent based on medication intake (defined as >80% correct dosage). Principal component analysis (PCA) was employed to identify principal components between adherent and non-adherent patients. A total of 42 patients with LN were included. Of these, 38 (90%) were female, and the mean age was 31 ± 10 years. Proliferative class IV was the predominant histopathological profile (90%). Twenty-five (60%) patients were categorized as non-adherent. Across all LupusQoL domains, a comprehensive range of responses was observed. Pain, planning, and intimate relationships domains remained unaffected, while burden to others domain had the lowest score. Poorer planning score correlated with older age (r = -0.72; p < .05) and longer disease duration (r = -0.74; p < .05). SLEDAI-2K correlated with the pain domain (r = -0.78; p < .05). Non-adherent patients exhibited significantly worse pain domain scores compared to adherent counterparts (p < .05). PCA showed strong interactions between planning and pain, as well as between physical health and body image domains. LupusQoL pain domain scores were significantly worse in non-adherent patients compared to adherent patients. Effective pain management could be a determinant in HRQoL and treatment adherence rates in our population.

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

ObjectivesThis study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients...

Using linked electronic medical record-pharmacy data to examine lupus medication adherence: A retrospective cohort study.

Medication nonadherence is common in systemic lupus erythematosus (SLE) and associated with morbidity and mortality. We explored the reliability of pharmacy data within the electronic medical record (EMR) to examine factors associated with nonadherence to SLE medications. We included patients with SLE who were prescribed ≥1 SLE medication for ≥90 days. We compared two datasets of pharmacy fill data, one within the EMR and another from the vendor who obtained this information from pharmacies and prescription benefit managers. Adherence was defined by medication possession ratio (MPR) ≥80%. In addition to MPR for each SLE medication, we evaluated the weighted-average MPR and the proportion of patients adherent to ≥1 SLE medication and to all SLE medications. We used logistic regression to examine factors associated with adherence. Among 181 patients (median age 36, 96% female, 58% Black), 98% were prescribed hydroxychloroquine, 34% azathioprine, 33% mycophenolate, 18% methotrexate, and 7% belimumab. Among 1276 pharmacy records, 74% overlapped between linked EMR-pharmacy data and data obtained directly from the vendor. Only 9% were available from the vendor but not through linked EMR-pharmacy data. The weighted-average MPR was 57%; 45% were adherent to hydroxychloroquine, 46% to ≥1 SLE medication, and 32% to all SLE medications. Older age was associated with adherence in univariable and multivariable analyses. Our study showed that obtaining linked EMR-pharmacy data is feasible with minimal missing data and can be leveraged in future adherence research. Younger patients were more likely to be nonadherent and may benefit from targeted intervention.

Treatment of systemic lupus erythematosus: Analysis of treatment patterns in adult and paediatric patients across four European countries

ObjectiveMultiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE). MethodsWe conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy. ResultsWe characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80–88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66–83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults. ConclusionTreatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines.

Implementation of a Clinician-led Medication Adherence Intervention Among Patients With Systemic Lupus Erythematosus.

Medication nonadherence in systemic lupus erythematosus (SLE) leads to poor clinical outcomes. We developed a clinician-led adherence intervention that involves reviewing real-time pharmacy refill data and using effective communication to address nonadherence. Prior pilot testing showed promising effects on medication adherence. Here, we describe further evaluation of how clinicians implemented the intervention and identify areas for improvement. We audio recorded encounters of clinicians with patients who were nonadherent (90-day proportion of days covered [PDC] < 80% for SLE medications). We coded recordings for intervention components performed, communication quality, and time spent discussing adherence. We also conducted semistructured interviews with patients and clinicians on their experiences and suggestions for improving the intervention. We assessed change in 90-day PDC post intervention. We included 25 encounters with patients (median age 39, 100% female, 72% Black) delivered by 6 clinicians. Clinicians performed most intervention components consistently and exhibited excellent communication, as coded by objective coders. Adherence discussions took an average of 3.8 minutes, and 44% of patients had ≥ 20% increase in PDC post intervention. In structured interviews, many patients felt heard and valued and described being more honest about nonadherence and more motivated to take SLE medications. Patients emphasized patient-clinician communication and financial and logistical assistance as areas for improvement. Some clinicians wanted additional resources and training to improve adherence conversations. We provide further evidence to support the feasibility, acceptability, and fidelity of the adherence intervention. Future work will optimize clinician training and evaluate the intervention's effectiveness in a large, randomized trial.

Prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai patients with systemic lupus erythematosus: An age- and sex-matched controlled study.

To determine the prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai systemic lupus erythematosus (SLE) patients, and compare them with age- and sex-matched healthy controls (HCs). Associations between thyroid dysfunctions and SLE disease activity, and associated factors for thyroid dysfunctions in SLE also were determined. One hundred SLE patients, without apparent clinical thyroid disease, attended the Rheumatology Clinic between November 2021 and October 2022, were enrolled into this study. HCs were matched to SLE cases by age and sex (ratio of 1:1). Clinical manifestations, SLE disease activity and medication received were collected in all SLE patients. Thyroid function tests and thyroid autoantibodies (anti-thyroglobulin: anti-TG and anti-thyroid peroxidase: anti-TPO) were collected from all participants. When compared with HCs, SLE patients had higher prevalence of thyroid dysfunctions, hypothyroidism and euthyroid sick syndrome (28% vs. 7%, p < .001, and 12% vs. 2%, p = .010, and 6% vs. 0%, p = .013, respectively). Prevalence of isolated hypothyroxinemia was higher numerically in SLE patients (9% vs. 3%, p = .074). Prevalence of anti-TG or anti-TPO was no different between SLE patients and HCs (16% vs. 18%, p = .707). There was no association between SLE disease activity and abnormal thyroid functions or thyroid autoantibodies. Family history of thyroid disease and prednisolone use (>10 mg/day) were associated factors for thyroid abnormalities with adjusted OR (95% CI) of 6.13 (1.58-23.75), p = .009 and 4.00 (1.37-11.70), p = .011, respectively. Thyroid dysfunctions were more prevalent in SLE patients. Family history of thyroid disease and prednisolone use (>10 mg/day) were independent associated factors of thyroid abnormalities.

Factors associated with non-adherence to medications in systemic lupus erythematosus: Results from a Swedish survey.

To identify determinants of medication non-adherence in a Swedish population of systemic lupus erythematosus (SLE). Patients with SLE from Karolinska and Örebro University Hospitals participated in a survey-based cross-sectional study. Demographics, disease activity, organ damage, HRQoL (LupusQol, EQ-5D-5L), medication non-adherence (<80% on CQR-19 or MASRI) and beliefs about medicines (BMQ) were registered. MASRI was used to report adherence to different drugs/drug classes, categorised into (i) antimalarial agents (AMA), (ii) glucocorticoids and (iii) other SLE medications. Multivariable logistic regression adjusted for age, sex, disease activity and organ damage. Among 205 respondents, the median age was 52.0years (IQR: 34.0-70.0), 86.3% were women, 66.8% were non-adherent to their medications according to CQR-19, and 6.6% and 6.3% were non-adherent to AMA and glucocorticoids, respectively, according to MASRI. Positive beliefs about glucocorticoids (OR; 95% CI: 0.77; 0.59-0.99; p = .039) and medications overall (0.71; 0.52-0.97; p = .029) were protective against non-adherence to glucocorticoids. Anxiety/depression (3.09; 1.12-8.54; p = .029), medication concerns (1.12; 1.05-1.20; p < .001) and belief that medications are overused (1.30; 1.15-1.46; p < .001) or harmful (1.36; 1.19-1.56; p < .001) were associated with medication non-adherence (CQR-19); beliefs in the necessity of medications (0.73; 0.65-0.82; p < .001) and positive beliefs in medications were protective (0.72; 0.60-0.86; p < .001). No associations were found between other investigated factors and medication non-adherence. Beliefs about medications were a major determinant of medication non-adherence. Patient education may help alleviate the negative impact of misinformation/unawareness on adherence.

Global tuberculosis disease and infection in systemic lupus erythematosus patients: A systematic review and meta-analysis.

Tuberculosis (TB) is one of the most common infections among systemic lupus erythematosus (SLE) patients. We aimed to evaluate the global prevalence of TB infection and disease, its type, and medication risk factors in SLE patients. We searched PubMed, Science Direct, EBSCO, and Web of Science databases from inception to April 30, 2023, and included studies assessing TB among SLE patients. We estimated the prevalence of TB disease (including type of TB disease), TB infection, and SLE medication as TB risk factors. Meta-analysis was performed using Stata 14.2 and Review Manager 5.3. Twenty-seven studies met the eligibility criteria. The global prevalence of TB disease was 4% (95% confidence interval (CI): 3-4%, n = 25) and TB infection was 18% (95% CI: 10-26%, n = 3). The pooled prevalence of pulmonary TB, extrapulmonary TB, and disseminated TB were 2% (95% CI: 2-3%, n = 20), 1% (95% CI: 1-2%, n = 17), and 1% (95% CI: 0-1%, n = 6), respectively. The 1-year cumulative glucocorticoid (GC) dose in SLE patients contracting TB was higher than in those without TB, having a mean difference of 2.56 (95% CI: 0.22-4.91, p < .00001, n = 3). The odd ratio of TB was 2.11 (95% CI: 1.01-4.41, p = .05, n = 3) in SLE patients receiving methylprednisolone (MP) pulse therapy as compared to those without MP pulse therapy. Other immunosuppressive agents were not significantly associated with TB. TB prevalence in SLE was relatively high and associated with GC. Awareness of TB and lowering GC dose are warranted to alleviate the TB burden in SLE.

Predictors of flare-related inpatient or emergency department stay in systemic lupus erythematosus: A real-world analysis of Medicaid claims in the United States.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammation. Medical management of SLE is based on reducing inflammation and tissue damage in the affected organs; however, medications used to treat SLE have been found to contribute to additional organ damage. Therefore, finding new ways to predict and prevent flares that require an inpatient (IP) stay or emergency department (ED) visit is critical for reducing the clinical and economic burden in patients with SLE. To identify risk factors of SLE flares requiring an IP/ED visit among a Medicaid-insured population with SLE. This retrospective study included patients from the Merative MarketScan Medicaid database (2013-2019). To capture patients at all stages of their SLE journey, all SLE claims for a patient were captured, and the index date was randomly selected among those claims that were at least 12 months after the first evidence of SLE. Patients were required to be continuously enrolled 1-year pre-index (year 1) and post-index (year 2). Demographics, clinical characteristics, and health care use and costs were measured in year 1, and flares requiring an IP/ED visit were identified in year 2 using the Garris algorithm. Multivariable logistic regression and classification and regression tree (CART) modeling were used to identify year 1 predictors and combination of factors, respectively, associated with flares-related IP/ED visits. Of the 8,083 patients included in the study, 37.6% of patients (n = 3,039) had a flare. Logistic regression identified ED visits in year 1 as one of the strongest predictors of flares-related IP/ED visits in year 2 (odds ratio = 2.19 [95% CI = 1.93-2.49]). SLE treatment progression to biologics (0.54 [0.42-0.70]) was the strongest predictor of decreased odds. Other strong predictors included other neurological disorders (1.63 [1.43-1.87]), Black race (1.49 [1.32-1.68]), chronic kidney disease/renal failure (1.35 [1.10-1.66]), and opioid use (1.30 [1.17-1.45]). CART modeling identified patients with an ED visit, an IP admission, and a diagnosis of Elixhauser Comorbidity Index-defined other neurological disorders in year 1 as having the highest probability of a flare-related IP/ED visit in year 2 (probability = 0.708), whereas patients without an ED visit had the lowest probability (probability = 0.185). Patients with the highest risk of a flare that required an IP/ED visit were those with a prior ED visit, IP admission, and other neurological disorders. Modeling also identified patients with prior opioid use, Black patients, and patients without SLE medications as subgroups with a high risk of a flare requiring an IP/ED visit.

Risk factors for severe COVID-19 among patients with systemic lupus erythematosus: a real-world analysis of a large representative US administrative claims database, 2020–2021

ObjectivesTo identify risk factors for progression to severe COVID-19 and estimate the odds of severe COVID-19 associated with vaccination among patients with systemic lupus erythematosus (SLE).MethodsThis retrospective cohort study identified...

Medication Cost Concerns and Disparities in Patient-Reported Outcomes Among a Multiethnic Cohort of Patients With Systemic Lupus Erythematosus.

Concerns about the affordability of medications are common in systemic lupus erythematosus (SLE), but the relationship between medication cost concerns and health outcomes is poorly understood. We assessed the association of self-reported medication cost concerns and patient-reported outcomes (PROs) in a multiethnic SLE cohort. The California Lupus Epidemiology Study is a cohort of individuals with physician-confirmed SLE. Medication cost concerns were defined as having difficulties affording SLE medications, skipping doses, delaying refills, requesting lower-cost alternatives, purchasing medications outside the United States, or applying for patient assistance programs. Linear regression and mixed effects models assessed the cross-sectional and longitudinal association of medication cost concerns and PROs, respectively, adjusting for age, sex, race and ethnicity, income, principal insurance, immunomodulatory medications, and organ damage. Of 334 participants, medication cost concerns were reported by 91 (27%). Medication cost concerns were associated with worse Systemic Lupus Activity Questionnaire (SLAQ; beta coefficient [β] 5.9, 95% CI 4.3-7.6; P < 0.001), 8-item Patient Health Questionnaire depression scale (PHQ-8; β 2.7, 95% CI 1.4-4.0; P < 0.001), and Patient-Reported Outcomes Measurement Information System (PROMIS; β for physical function -4.6, 95% CI -6.7 to -2.4; P < 0.001) scores after adjusting for covariates. Medication cost concerns were not associated with significant changes in PROs over 2-year follow-up. More than a quarter of participants reported at least 1 medication cost concern, which was associated with worse PROs. Our results reveal a potentially modifiable risk factor for poor outcomes rooted in the unaffordability of SLE care.

A Flare Risk Index Informed by Select Immune Mediators in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is marked by immune dysregulation linked to varied clinical disease activity. Using a unique longitudinal cohort of SLE patients, this study sought to identify optimal immune mediators informing an empirically refined flare risk index (FRI) reflecting altered immunity prior to clinical disease flare. Thirty-seven SLE-associated plasma mediators were evaluated by microfluidic immunoassay in 46 samples obtained in SLE patients with an imminent clinical disease flare (preflare) and 53 samples obtained in SLE patients without a flare over a corresponding period (pre-nonflare). SLE patients were selected from a unique longitudinal cohort of 106 patients with classified SLE (meeting the American College of Rheumatology 1997 revised criteria for SLE or the Systemic Lupus International Collaborating Clinics 2012 revised criteria for SLE). Autoantibody specificities, hybrid SLE Disease Activity Index (hSLEDAI) scores, clinical features, and medication usage were also compared at preflare (mean ± SD 111 ± 47 days prior to flare) versus pre-nonflare (99 ± 21 days prior to nonflare) time points. Variable importance was determined by random forest analysis with logistic regression subsequently applied to determine the optimal number and type of analytes informing a refined FRI. Preflare versus pre-nonflare differences were not associated with demographics, autoantibody specificities, hSLEDAI scores, clinical features, nor medication usage. Forward selection and backward elimination of mediators ranked by variable importance resulted in 17 plasma mediator candidates differentiating preflare from pre-nonflare visits. A final combination of 11 mediators best informed a newly refined FRI, which achieved a maximum sensitivity of 97% and maximum specificity of 98% after applying decision curve analysis to define low, medium, and high FRI scores. We verified altered immune mediators associated with imminent disease flare, and a subset of these mediators improved the FRI to identify SLE patients at risk of imminent flare. This molecularly informed, proactive management approach could be critical in prospective clinical trials and the clinical management of lupus.

Improvement in Cutaneous Lupus Erythematosus After Twenty Weeks of Belimumab Use: A Systematic Review and Meta-Analysis.

Cutaneous lupus erythematosus(CLE), with or without systemic lupus erythematosus(SLE), can be debilitating and cause psychological distress. Belimumab, a monoclonal antibody that inhibits B cell activation, is a Federal Drug Administration-approved SLE medication, but less is known on its use in CLE. Moreover, the time to response after starting belimumab in CLE is unknown, which may lead to premature discontinuation in the absence of early perceivable benefits. Thus, the objectives of this meta-analysis were to examine the efficacy of belimumab, as well as the time to response after starting belimumab in patients with CLE with or without SLE. A comprehensive literature search was performed to include studies that examined clinical response in patients with CLE with or without SLE receiving belimumab. A clinical response at 52 weeks in belimumab users versus nonusers was summarized in a random-effects model. Additionally, we calculated the pooled odds ratio (OR) for each consecutive 4-week observation interval to identify time to a clinical response in CLE with or without SLE after starting belimumab. Among 747 screened studies, 14 were included. The pooled odds of clinical response at 52 weeks in belimumab users were 44% higher compared to nonusers (OR 1.44 [95% confidence interval (95% CI) 1.20-1.74], I2 =0%). A clinical response was first noted after 20 weeks of starting belimumab (OR 1.35 [95% CI 1.01-1.81], I2 =0%), with a sustained clinical response through 1 year. The findings support belimumab as an effective therapy for CLE with SLE. Likewise, the findings inform patient counseling regarding estimates of 20 weeks to achieve a response.

Association of Hurried Communication and Low Patient Self-Efficacy With Persistent Nonadherence to Lupus Medications.

Medication nonadherence is common among patients with systemic lupus erythematosus (SLE), and adherence often fluctuates with time. Underrepresented racial minorities have disproportionately lower rates of medication adherence and more severe SLE manifestations. We aimed to identify modifiable factors associated with persistent medication nonadherence. Patients taking ≥1 SLE medication were enrolled. Adherence data were obtained at baseline and at follow-up roughly 1 year later using both self-reported adherence and pharmacy refill data. Covariates included patient-provider interaction, patient self-efficacy, and clinical factors. We compared characteristics of patients in 3 groups using the Kruskal-Wallis H test: persistent nonadherence (low adherence by self-report and refill rates at both time points); persistent adherence (high adherence by self-report and refill rates at both time points); and inconsistent adherence (the remainder). Among 77 patients (median age 44 years, 53% Black, 96% female), 48% had persistent nonadherence. Compared with other adherence groups, patients with persistent nonadherence were younger and more likely to be Black, have lower income, take ≥2 SLE medications, have higher SLE-related damage at baseline, and have higher physician global assessment of disease activity at follow-up. Persistently nonadherent patients also rated more hurried communication with providers (particularly fast speech and difficult word choice) and had lower self-efficacy in managing medications. Potential avenues to improve medication adherence include optimizing patient-provider communication, specifically avoiding difficult vocabulary and fast speech, and enhancing patient self-efficacy, particularly among younger Black patients with lower income who are at higher risk for nonadherence.

Pilot Intervention to Improve Medication Adherence Among Patients With Systemic Lupus Erythematosus Using Pharmacy Refill Data.

Despite high rates of medication nonadherence among patients with systemic lupus erythematosus (SLE), effective interventions to improve adherence in SLE are limited. We aimed to assess the feasibility of a pilot intervention and explore its effect on adherence. The intervention used pharmacy refill data to monitor nonadherence and prompt discussions surrounding SLE medications during clinic encounters. Over 12 weeks, the intervention was delivered through routine clinic visits by providers to patients with SLE who take SLE-specific medications. We measured acceptability, appropriateness, and feasibility using provider surveys. We also measured acceptability by patient surveys and feasibility by medical record documentation. We explored change in adherence by comparing percent of patients with medication possession ratio (MPR) ≥80% 3 months before and after the intervention visit using the McNemar's test. Six rheumatologists participated; 130 patients were included in the analysis (median age 43, 95% female, and 59% racial and ethnic minorities). Implementation of the intervention was documented in 89% of clinic notes. Provider surveys showed high scores for feasibility (4.7/5), acceptability (4.4/5), and appropriateness (4.6/5). Among patient surveys, the most common reactions to the intervention visit were feeling determined (32%), empowered (32%), and proud (19%). Proportion of patients with MPR ≥80% increased from 48% to 58% (P=0.03) after the intervention visit. Our intervention showed feasibility, acceptability, and appropriateness and led to a statistically significant improvement in adherence. Future work should refine the intervention, assess its efficacy in a controlled setting, and adapt its use among other clinic settings.

Malignancies among newly diagnosed systemic lupus erythematosus patients and their survival.

The objective of this study was to evaluate the incidence of malignancies among newly diagnosed systemic lupus erythematosus (SLE) patients compared to reference individuals. Another aim was to assess the survival of SLE patients with malignancy compared to references with malignancy. Finnish adult (>17years) newly diagnosed SLE patients were identified by their drug reimbursement decisions made during 1.1.2000-31.12.2014 from the register of the Social Insurance Institution. For each case, three population controls were individually selected by age, sex and place of residence. Overall, 1006 SLE patients (women 84%), with a mean age of 45.5years (SD 16years) and 3005 population controls were linked to Finnish Cancer Registry, and the information about incident malignancies was retrieved from the day the special reimbursement decision for SLE medication was accepted (index day, ID) until 31.12.2018 or until death. The patients diagnosed with malignancy were followed up until 31.12.2019 considering survival. During the follow-up, 85 SLE patients (women 78%) and 192 controls (women 78%) had developed one or more malignancy after the ID. The incidence rate ratio for any malignancy was 1.41 (95% CI 1.08-1.85). The most common malignancy in SLE patients was non-Hodgkin lymphoma, with twelve cases. SLE patients with malignancy had a lower adjusted 15-year survival than controls with malignancy, 27.1% versus 52.4%, and the adjusted hazard ratio for death was 1.68 (95% CI 1.17-2.43). Our results confirm that SLE patients have a higher risk for overall malignancy. The results also suggest that SLE patients with malignancy have lower survival than their references with malignancy.

Complement activation products vs standard ANA testing: Treatment outcomes, diagnosis, and economic impact (CAPSTONE) in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex clinical diagnosis historically aided by imperfect biomarkers. The advent of a multianalyte assay panel incorporating innovative cell-bound complement activation markers necessitates a comparison of its clinical utility to conventional autoantibodies for the diagnosis and treatment of SLE. OBJECTIVES: To compare the likelihood of SLE diagnosis, SLE treatment initiation, and the downstream impact on health care utilization among patients tested with AVISE Lupus (AVISE) vs standard-of-care laboratory testing with the traditional antinuclear antibody (ANA) testing strategy cohort (tANA). METHODS: An observational retrospective cohort study was conducted using electronic health record (EHR) data from the Illumination Health registry, which integrates EHR records from more than 300 rheumatologists across the US. Health records from January 2016 to December 2020 and administrative claims with cost data for a subset of patients linkable to the HealthCore Integrated Research Database and Medicare data were analyzed. The AVISE and tANA test results were classified as positive, negative, or indeterminate, and outcomes were stratified based on test results. Two cohorts were established: AVISE testing strategy and the tANA approach. Analyses included test impact on SLE diagnosis, treatment initiation, patterns of repeat testing, and downstream health care utilization. Multivariable logistic regression was used to estimate odds ratios (ORs) comparing the likelihood of SLE medication initiation and SLE diagnosis between the AVISE and tANA cohorts. RESULTS: The main cohort included 21,827 AVISE testing episodes and 22,778 tANA testing episodes. A total of 2,437 (11.2%) patients tested positive by AVISE compared with 5,364 (23.6%) of tANA positive patients. Among patients with no baseline prescription for SLE medication(s), patients with a positive AVISE test result were more likely to initiate SLE medications compared with tANA positive patients (43% vs 32%; OR = 1.57; 95% CI = 1.41-1.76). The treatment effect was larger in patients new to the practice within the preceding year (55% vs 33%; adjusted OR = 2.77; 95% CI = 2.31-3.32). AVISE positive patients were more than 5-fold more likely to be diagnosed with SLE, as compared with the tANA patients (31% vs 8%; OR = 5.11; 95% CI = 4.43-5.89), and similar in the new patient cohort (30% vs 6%; OR = 6.34; 95% CI = 5.12-7.86). Linked EHR-Medicare data revealed a greater decrease in posttest vs pretest mean annualized outpatient laboratory testing in AVISE negative (-$985; P < 0.0001) vs tANA negative (-$356; P < 0.0001) patients. A similar analysis in the EHR-HealthCore linked data revealed similar numerical trends as the Medicare data for outpatient laboratory testing but did not reach significance (P > 0.05). Cost comparisons in the categories of hospitalization, emergency department, outpatient imaging, and pharmacy costs did not yield significant differences. CONCLUSIONS: The significantly greater likelihood of SLE diagnosis and SLE medication initiation in AVISE positive vs tANA positive patients is consistent with improved clinical actionability, potentially shortening time to diagnosis. AVISE negative patients experienced a greater decrease in outpatient laboratory testing posttest relative to tANA negative patients, supporting the improved negative predictive value of AVISE vs tANA. DISCLOSURES: Mr O'Malley and Dr Zack are employed by Exagen Inc. Drs Curtis and Xie, Ms Su, and Ms Clinton are affiliated with the University of Alabama at Birmingham. Mr Haechung and Dr Grabner are employees of HealthCore, Inc., which received funding from Bendcare (owner of the Illumination Health Registry) for the conduct of parts of the study on which this manuscript is based. Exagen Inc. provided funding to Bendcare for the conduct of the study. Dr Grabner is also a shareholder of Anthem, Inc.

Development and Initial Validation of a Systemic Lupus Erythematosus-Specific Measure of the Extent of and Reasons for Medication Nonadherence.

Medication nonadherence is common in patients with systemic lupus erythematosus (SLE) and negatively affects outcomes. To better recognize and address nonadherence in this population, there is a need for an easily implementable tool with interpretable scores. Domains of Subjective Extent of Nonadherence (DOSE-Nonadherence) is a measure that captures both extent of and reasons for nonadherence. We refined and evaluated DOSE-Nonadherence for patients with SLE. We refined the reasons for the nonadherence domain of DOSE-Nonadherence through rheumatologist feedback and patient cognitive interviewing. We then administered the refined instrument to patients prescribed oral SLE medications and compared the results to the Beliefs About Medicines Questionnaire (BMQ), the Medication Adherence Self-Report Inventory (MASRI), medication possession ratios (MPRs), and hydroxychloroquine (HCQ) blood levels using Pearson correlations. Five rheumatologists provided feedback; 16 patients (median age 43 yrs, 100% female, 50% Black) participated in cognitive interviews and 128 (median age 49 yrs, 95% female, 49% Black, 88% on antimalarials, and 59% on immunosuppressants) completed the refined instrument. Items assessing extent of nonadherence produced reliable scores (α 0.89) and identified 47% as nonadherent. They showed convergent validity with MASRI (r = -0.57), HCQ blood levels (r = -0.55), to a lesser extent MPRs (r = -0.34 to -0.40), and discriminant validity with BMQ domains (r = -0.27 to 0.32). Nonadherent patients reported on average 3.5 adherence barriers, the most common being busyness/forgetting (62%), physical fatigue (38%), and pill fatigue (33%). Our results support the reliability and validity of DOSE-Nonadherence for SLE medications. This refined instrument, DOSE-Nonadherence-SLE, can be used to identify, rigorously study, and guide adherence intervention development in SLE.

Barriers to Taking Medications for Systemic Lupus Erythematosus: A Qualitative Study of Racial Minority Patients, Lupus Providers, and Clinic Staff.

Underrepresented racial and ethnic minorities are disproportionately affected by systemic lupus erythematosus (SLE). Racial and ethnic minorities also have more severe SLE manifestations that require use of immunosuppressive medications, and often have lower rates of medication adherence. We aimed to explore barriers of adherence to SLE immunosuppressive medications among minority SLE patients. We conducted a qualitative descriptive study using in-depth interviews with a purposive sample of racial minority SLE patients taking oral immunosuppressants (methotrexate, azathioprine, or mycophenolate), and lupus clinic providers and staff. Interviews were audiorecorded, transcribed, and analyzed using applied thematic analysis. We grouped themes using the Capability, Opportunity, Motivation, Behavior conceptual model. We interviewed 12 SLE patients (4 adherent, 8 nonadherent) and 12 providers and staff. We identified capability barriers to include external factors related to acquiring medications, specifically cost-, pharmacy-, and clinic-related issues; opportunity barriers to include external barriers to taking medications, specifically logistic- and medication-related issues; and motivation factors to include intrinsic barriers, encompassing patients' knowledge, beliefs, attitudes, and physical and mental health. The most frequently described barriers were cost, side effects, busyness/forgetting, and lack of understanding, although barriers differed by patient and adherence level, with logistic and intrinsic barriers described predominantly by nonadherent patients and side effects described predominantly by adherent patients. Our findings suggest that interventions may be most impactful if they are designed to facilitate logistics of taking medications and increase patients' motivation while allowing for personalization to address the individual differences in adherence barriers.

Nonlinear Population Pharmacokinetics of Anifrolumab in Healthy Volunteers and Patients With Systemic Lupus Erythematosus.

We characterized the population pharmacokinetics of anifrolumab, a type I interferon receptor–blocking antibody. Pharmacokinetic data were analyzed from the anifrolumab (intravenous [IV], every 4 weeks) arms from 5 clinical trials in patients with systemic lupus erythematosus (SLE) (n = 664) and healthy volunteers (n = 6). Population pharmacokinetic modeling was performed using a 2‐compartment model with parallel linear and nonlinear elimination pathways. The impact of covariates (demographics, interferon gene signature [IFNGS, high/low], disease characteristics, renal/hepatic function, SLE medications, and antidrug antibodies) on pharmacokinetics was evaluated. Time‐varying clearance (CL) was characterized using an empirical sigmoidal time‐dependent function. Anifrolumab exposure increased more than dose‐proportionally from 100 to 1000 mg IV every 4 weeks. Based on population pharmacokinetics modeling, the baseline median linear CL was 0.193 L/day in IFNGS‐high patients and 0.153 L/day in IFNGS‐low/healthy volunteers. After a year, median anifrolumab linear CL decreased by 8.4% from baseline. Body weight and IFNGS were significant pharmacokinetic covariates, whereas age, sex, race, disease activity, SLE medications, and presence of antidrug antibodies had no significant effect on anifrolumab pharmacokinetics. Anifrolumab at a concentration of 300 mg IV every 4 weeks was predicted to be below the lower limit of quantitation in 95% of patients ≈10 weeks after a single dose and ≈16 weeks after stopping dosing at steady state. To conclude, anifrolumab exhibited nonlinear pharmacokinetics and time‐varying linear CL; doses ≥300 mg IV every 4 weeks provided sustained anifrolumab concentrations. This study provides further evidence to support the use of anifrolumab 300 mg IV every 4 weeks in patients with moderate to severe SLE.