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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

The Impact of Pregnancy Readiness on Lupus Activity, Maternal Mental Health, and Pregnancy Outcomes.

OBJECTIVE: Among individuals with SLE who became pregnant, we explored the impact of medical readiness for pregnancy and personal readiness for pregnancy on the following aspects of maternal health: (1) provider-reported disease activity, (2) patient-perceived disease activity, (3) mood symptoms, (4) pregnancy-related health behaviors, and (5) pregnancy outcomes. METHODS: All study participants were enrolled in a prospective registry, met SLICC criteria for SLE, and had at least one pregnancy. Patient reported outcomes were collected at first rheumatology visit of pregnancy. "Medically ready" for pregnancy was defined as (1) <1g of proteinuria, (2) no rheumatic teratogens at conception, and (3) continuing pregnancy compatible SLE medications after conception. "Personally ready" was defined as planned pregnancy based on a London Measure of Unplanned Pregnancy (LMUP) ≥10. Multivariable logistic regression models estimated the association of pregnancy readiness with each outcome of interest. RESULTS: Among the 111 individuals enrolled, lack of medical readiness for pregnancy was associated with significantly higher rates of active disease and worse pregnancy outcomes; however, these patients did not perceive themselves as having higher disease activity. Lack of personal readiness for pregnancy was associated with significantly higher patient-perceived disease activity. While medical readiness did not impact depressive symptoms substantially, lack of personal readiness for pregnancy was associated with much higher maternal depressive symptoms. CONCLUSION: To improve pregnancy outcomes among individuals with SLE, greater focus is needed on improving medical optimization before conception. For maternal mental health and quality of life, greater focus is needed on decreasing the incidence of unplanned pregnancy.

Reproductive Outcomes for Women With Vasculitis.

OBJECTIVE: There are limited data on the reproductive health of women with vasculitis. This study used a prospective, international vasculitis pregnancy registry to survey women during and after pregnancy. METHODS: The Vasculitis Pregnancy Registry (VPREG) is imbedded within the Vasculitis Patient-Powered Research Network, an international online research infrastructure. Any pregnant woman with a diagnosis of vasculitis can self-enroll. After enrollment, women are invited to complete online surveys at study entry, once per trimester, and postpartum. Descriptive statistics are reported here. RESULTS: Between 2015 and 2022, 147 women with 149 pregnancies enrolled in VPREG from 16 countries. Data on 78 pregnancies with known outcomes were included in this analysis. During pregnancy, women on average experienced low levels of pain related to vasculitis (scale 0-10, median 2 [IQR 1-5]) and preserved feelings of wellness (scale 0-10, median 3 [IQR 1-5]). Thirty-six percent of women reported their vasculitis was active during pregnancy. Of the 14 women requiring hospitalization during pregnancy outside of delivery, 4 cited active vasculitis as the indication. Most women (54/73, 74%) were prescribed medications for vasculitis during pregnancy. Seventy-six (97%) pregnancies resulted in live births, with 64% delivering vaginally and 21% experiencing a preterm delivery. CONCLUSION: These results demonstrate that most women with vasculitis can experience pregnancies that result in live births delivered at term. During pregnancy, a minority of women reported flares of vasculitis or the need for hospitalization due to vasculitis. These data are useful to rheumatologists and patients to inform and facilitate discussions about reproductive health and vasculitis.

Interpreting hydroxychloroquine blood levels for medication non-adherence: a pharmacokinetic study.

OBJECTIVE: Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients. METHODS: We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses. RESULTS: For patients receiving HCQ 400 mg daily, simulated random blood levels <200 ng/mL were exceedingly uncommon in fully adherent patients (<0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were <200 ng/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to <200 ng/mL after 2-4 days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements. CONCLUSIONS: We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy.

Impact of preeclampsia on infant and maternal health among women with rheumatic diseases.

OBJECTIVES: We sought to identify the impact of preeclampsia on infant and maternal health among women with rheumatic diseases. METHODS: A retrospective single-center cohort study was conducted to describe pregnancy and infant outcomes among women with systemic lupus erythematosus (SLE) with and without preeclampsia as compared to women with other rheumatic diseases with and without preeclampsia. RESULTS: We identified 263 singleton deliveries born to 226 individual mothers (mean age 31 years, 35% non-Hispanic Black). Overall, 14% of women had preeclampsia; preeclampsia was more common among women with SLE than other rheumatic diseases (27% vs 8%). Women with preeclampsia had a longer hospital stay post-delivery. Infants born to mothers with preeclampsia were delivered an average of 3.3 weeks earlier than those without preeclampsia, were 4 times more likely to be born preterm, and twice as likely to be admitted to the neonatal intensive care unit. The large majority of women with SLE in this cohort were prescribed hydroxychloroquine and aspirin, with no clear association of these medications with preeclampsia. CONCLUSIONS: We found preeclampsia was an important driver of adverse infant and maternal outcomes. While preeclampsia was particularly common among women with SLE in this cohort, the impact of preeclampsia on the infants of all women with rheumatic diseases was similarly severe. In order to improve infant outcomes for women with rheumatic diseases, attention must be paid to preventing, identifying, and managing preeclampsia.

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

BACKGROUND: Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. METHODS: This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. RESULTS: In this cohort of 244 patients (93% female, mean age 43 years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. CONCLUSIONS: While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

The Type 1 & 2 systemic lupus erythematosus model: Perspectives of people living with systemic lupus erythematosus.

OBJECTIVE: In the new Type 1 & 2 model for systemic lupus erythematosus (SLE), Type 1 SLE represents classic inflammatory manifestations, such as arthritis, while Type 2 SLE encompasses symptoms such as pain and fatigue where the relationship to inflammation is less clear. The objective of this study was to interview individuals living with SLE to determine the content and face validity of the Type 1 & 2 SLE model. METHODS: We conducted a qualitative study using semi-structured interviews with a purposeful sample of participants who met classification criteria for SLE. Participants were asked to describe their experiences with Type 1 & 2 SLE symptoms and treatments, and they indicated if and how their personal experiences aligned with the Type 1 & 2 SLE model. All interviews were audio-recorded and transcribed; applied thematic analysis identified the most frequent and salient themes. RESULTS: We interviewed 42 participants with SLE. Type 2 SLE symptoms, such as pain and fatigue, were very common, with almost all participants experiencing some Type 2 symptoms at some point during their disease course. Participants described Type 1 SLE symptoms as being acute flares and life-threatening and Type 2 SLE symptoms as "everyday lupus" that affected their daily lives and were a dominant part of their SLE disease experience. Most participants stated they want their rheumatologists to discuss Type 2 symptoms during clinical appointments in order to address their full symptom experience. CONCLUSION: We demonstrated content and face validity of the Type 1 & 2 SLE model with people living with SLE. Participants in our study largely understood the model and felt it accurately reflected their experience living with SLE. Type 2 SLE symptoms are very common in individuals with SLE and impact patients' quality of life. Using the model to address Type 2 SLE symptoms allows the rheumatologist to incorporate the patient's perspective and provide patient-centered care.

A qualitative study of facilitators of medication adherence in systemic lupus erythematosus: Perspectives from rheumatology providers/staff and patients.

OBJECTIVE: Systemic lupus erythematosus (SLE) disproportionately affects patients from racial and ethnic minority groups. Medication adherence is lower among these patient populations, and nonadherence is associated with worse health outcomes. We aimed to identify factors that enable adherence to immunosuppressive medications among patients with SLE from racial and ethnic minority groups. METHODS: Using a qualitative descriptive study design, we conducted in-depth interviews with purposefully selected (1) patients with SLE from racial and ethnic minority groups who were taking immunosuppressants and (2) lupus providers and staff. We focused on adherence facilitators, asking patients to describe approaches supporting adherence and for overcoming common adherence challenges and providers and staff to describe actions they can take to foster patient adherence. We used applied thematic analysis and categorized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model. RESULTS: We interviewed 12 patients (4 adherent and 8 nonadherent based on medication possession ratio) and 12 providers and staff. Although each patient described a unique set of facilitators, patients most often described social support, physical well-being, reminders, and ability to acquire medications as facilitators. Providers also commonly mentioned reminders and easy medication access as facilitators as well as patient education/communication and empowerment. CONCLUSION: Using an established behavioral change model, we categorized a breadth of adherence facilitators within each domain of the COM-B model while highlighting patients' individual approaches. Our findings suggest that an optimal adherence intervention may require a multi-modal and individually tailored approach including components from each behavioral domain-ensuring medication access (Capability) and utilizing reminders and social support (Opportunity), while coupled with internal motivation through improved communication and empowerment (Motivation).

Azathioprine metabolite levels and outcomes during pregnancies with rheumatic disease.

OBJECTIVE: Despite widespread use of azathioprine (AZA) during pregnancy, no studies evaluated the impact of pregnancy on AZA metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN) disposition in rheumatic diseases. This study characterises changes in AZA metabolite concentrations throughout pregnancy in women with rheumatic disease and explores relationships between metabolite concentrations, maternal disease activity, and neonatal outcomes. METHODS: Patients with rheumatic disease from a single centre prescribed AZA prior to pregnancy and ≥1 blood sample during pregnancy (5/2016 to 4/2022) were included. Commercial laboratories quantified AZA metabolite concentrations. The upper safety limit for 6-MMPN was >5700 pmol/8×108 RBC. The therapeutic target for 6-TGN was ≥159 pmol/8×108 RBC. Repeated correlation measures were used to evaluate the relationship between metabolite concentrations and pregnancy duration, and the relationship between 6-TGN concentration and SLE Physician Global Assessment (PGA). The relationship between pregnancy average 6-TGN and neonatal gestational age at birth was analysed using linear regression. RESULTS: Thirty-seven pregnancies in 35 women with 108 serum samples were included. There was no significant difference in dose-adjusted 6-TGN concentrations across pregnancy and peripartum, whereas 6-MMPN concentrations appeared higher during pregnancy. No elevated transaminases or cholestasis were observed concurrently with 6-MMPN above 5700 pmol/8×108 RBC. Metabolite concentrations were related to total AZA dosage, weight-based dosage and TPMT phenotype. In pregnant women with SLE achieving average 6-TGN in the therapeutic range, we observed a non-significant reduction in PGA and increase in neonatal gestational age at birth. CONCLUSIONS: In this exploratory study, we did not observe systematic changes in 6-TGN concentrations throughout pregnancy and peripartum, whereas 6-MMPN concentrations were higher during pregnancy. Monitoring AZA metabolite concentrations in pregnancy is a potential tool to identify medication non-adherence as well as patients with high 6-MMPN in whom dosage adjustment or close laboratory monitoring may optimise safety.

Implications of the accuracy of diagnostic algorithms for systemic lupus on our understanding of racial disparities in pregnancy outcomes.

OBJECTIVE: Disparities in pregnancy outcomes among women with SLE remain understudied, with few available racially diverse datasets. We sought to identify disparities between Black and White women in pregnancy outcomes within academic institutions in the United States. METHODS: Using the Common Data Model electronic medical record (EMR)-based datasets within the Carolinas Collaborative, we identified women with pregnancy delivery data (2014-2019) and ≥1 SLE International Classification of Diseases 9 or 10 code (ICD9/10) code. From this dataset, we identified four cohorts of SLE pregnancies, three based on EMR-based algorithms and one confirmed with chart review. We compared the pregnancy outcomes identified in each of these cohorts for Black and White women. RESULTS: Of 172 pregnancies in women with ≥1 SLE ICD9/10 code, 49% had confirmed SLE. Adverse pregnancy outcomes occurred in 40% of pregnancies in women with ≥1 ICD9/10 SLE code and 52% of pregnancies with confirmed SLE. SLE was frequently over-diagnosed in women who were White, resulting in 40-75% lower rates of adverse pregnancy outcomes in EMR-derived vs confirmed SLE cohorts. Over-diagnosis was less common for Black women with pregnancy outcomes 12-20% lower in EMR-derived vs confirmed SLE cohorts. Black women had higher rates of adverse pregnancy outcomes than White women in the EMR-derived, but not the confirmed cohorts. CONCLUSION: EMR-derived cohorts of pregnancies in women who are Black, but not White, provided accurate estimations of pregnancy outcomes. The data from the confirmed SLE pregnancies suggest that all women with SLE, regardless of race, referred to academic centres remain at very high risk for adverse pregnancy outcome.

Patient and Physician Perspectives of Systemic Lupus Erythematosus Flare: A Qualitative Study.

OBJECTIVE: Systemic lupus erythematosus (SLE) flares are associated with increased damage and decreased health-related quality of life. We hypothesized that there is discordance between physicians' and patients' views of SLE flare. In this study, we aimed to explore patient and physician descriptions of SLE flares. METHODS: We conducted a qualitative descriptive study using in-depth interviews with a purposeful sample of patients with SLE (who met 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) and practicing rheumatologists. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. RESULTS: Forty-two patient participants with SLE, representing a range of SLE activity, completed interviews. The majority described flare symptoms as joint pain, fatigue, and skin issues lasting several days. Few included objective signs or laboratory measures, when available, as features of flare. We interviewed 13 rheumatologists from 10 academic and 3 community settings. The majority defined flare as increased or worsening SLE disease activity, with slightly more than half requiring objective findings. Around half of the rheumatologists included fatigue, pain, or other patient-reported symptoms. CONCLUSION: Patients and physicians described flare differently. Participants with SLE perceived flares as several days of fatigue, pain, and skin issues. Providers defined flares as periods of increased clinical SLE activity. Our findings suggest the current definition of flare may be insufficient to integrate both perceptions. Further study is needed to understand the pathophysiology of patient flares and the best way to incorporate patients' perspectives into clinical assessments.

Using PROMIS-29 to determine symptom burdens in the context of the Type 1 and 2 systemic lupus erythematosus (SLE) model: a cross sectional study.

OBJECTIVE: To account for heterogeneity in systemic lupus erythematosus (SLE) and bridge discrepancies between patient- and physician-perceived SLE activity, we developed the Type 1 and 2 SLE model. We examined PROMIS-29 scores, a composite patient-reported outcome (PRO) measure, through the lens of the model. METHODS: Patients completed PROMIS-29 and the polysymptomatic distress scale (PSD). Rheumatologists completed the SLE disease activity index (SLEDAI), and physician's global assessments (PGAs) for Type 1 and 2 SLE. We defined Type 1 SLE using SLEDAI, Type 1 PGA, and active nephritis, and Type 2 SLE using PSD and Type 2 PGA. We compared PROMIS-29 T-scores among Type 1 and 2 SLE groups and explored whether PROMIS-29 can predict Type 1 and 2 SLE activity. RESULTS: Compared to the general population, patients with isolated Type 1 SLE reported greater pain and physical dysfunction but less depression and improved social functions; patients with high Type 2 SLE (irrespective of Type 1 activity) reported high levels of pain, fatigue, and social and physical limitations. Patients with minimal Type 1 and 2 SLE had less depression and greater physical functioning with other domains similar to national norms. PROMIS-29 predicted Type 2 but not Type 1 SLE activity. CONCLUSION: PROMIS-29 similarities in patients with high Type 2 SLE, with and without active Type 1 SLE, demonstrate the challenges of using PROs to assess SLE inflammation. In conjunction with the Type 1 and 2 SLE model, however, PROMIS-29 identified distinct symptom patterns, suggesting that the model may help clinicians interpret PROs.

Development and psychometric evaluation of a physician global assessment for type 2 systemic lupus erythematosus symptoms.

OBJECTIVE: Manifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation). While measures of type 1 SLE activity exist, most current physician-reported measures do not encompass type 2 SLE manifestations. To better evaluate type 2 SLE symptoms, we developed and psychometrically evaluated a physician-reported measure of type 2 symptoms, the Type 2 Physician Global Assessment ('Type 2 PGA'). METHODS AND ANALYSIS: The Type 2 PGA was developed and evaluated by six rheumatologists practising in the same academic lupus clinic. The study began with a roundtable discussion to establish consensus guidelines for scoring the Type 2 PGA. Following the roundtable, the Type 2 PGA was psychometrically evaluated using data prospectively collected from 263 patients with SLE enrolled in the Duke Lupus Registry. RESULTS: There was strong intra-rater and inter-rater reliability (intraclass correlation coefficient=0.83), indicating the Type 2 PGA scores were consistent within a rheumatologist and across rheumatologists. The Type 2 PGA was correlated with patient-reported symptoms of polysymptomatic distress (r=0.76), fatigue (r=0.68), cognitive dysfunction (r=0.63), waking unrefreshed (r=0.62) and forgetfulness (r=0.60), and weakly correlated with the Type 1 PGA and the Systemic Lupus Erythematosus Disease Activity Index. CONCLUSION: The Type 2 PGA performed well as a physician-reported measure of type 2 SLE symptoms. The incorporation of the Type 2 PGA into a routine rheumatology visit may improve patient care by bringing the provider's attention to certain symptoms not well represented in conventional measures of disease activity.

The impact of pregnancy planning and medical readiness on reproductive outcomes in women with systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) who get pregnant while SLE is active or while on teratogens have higher risk of poor pregnancy outcomes. The American College of Rheumatology (ACR) Reproductive Health Guidelines recommend women conceive when SLE is well controlled and treated with pregnancy-compatible medications. The Healthy Outcomes in Pregnancy with SLE Through Education of Providers (HOP-STEP) Intervention was created to ascertain pregnancy interest and contraceptive use followed by a personalized pregnancy prevention and/or planning discussion (https://www.LupusPregnancy.org). All study participants were adult females enrolled in a prospective registry who met ACR or SLICC criteria. Women were defined as "not medically ready for pregnancy" if they were currently prescribed a teratogen, had proteinuria ≥500 mg, or had elevated SLE activity according to the physician's global assessment. Two time periods were assessed: 2/2018-12/2019 and 10/2020-4/2021 to evaluate pre- and post-pandemic periods, with some post-pandemic visits taking place via telehealth. The interest in pregnancy was similar between the first time period (17%) and the second time period, whether in-person (18%) or virtual (18%). Pregnancy interest was assessed significantly more frequently during in-person visits (90%) compared to virtual encounters (67%) (p = .02). Contraceptive use was not significantly different during either time period with use of a teratogen or increased SLE activity. Of the 52 women in both time periods who were not medically ready for pregnancy and were not on effective contraception, three women (5.8%) conceived. None of the women who were using moderate or highly effective contraception became pregnant. Pregnancy outcomes were similar between unintended or high-risk and well-timed pregnancies. The HOP-STEP Intervention effectively identified pregnancy interest, giving rheumatologists the opportunity to address patient reproductive goals, optimize disease activity, and adjust medication regimens prior to conception.

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget's Disease of Bone.

Paget's Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (GRK3) is an important negative regulator of G protein-coupled receptor (GPCR) signaling. GRK3 is known to regulate GPCR function in osteoblasts and preosteoblasts, but its regulatory function in osteoclasts is not well defined. Here, we report that Grk3 expression increases during osteoclast differentiation in both human and mouse primary cells and established cell lines. We also show that aged mice deficient in Grk3 develop bone lesions similar to those seen in human PDB and other Paget's Disease mouse models. We show that a deficiency in Grk3 expression enhances osteoclastogenesis in vitro and proliferation of hematopoietic osteoclast precursors in vivo but does not affect the osteoclast-mediated bone resorption function or cellular senescence pathway. Notably, we also observe decreased Grk3 expression in peripheral blood mononuclear cells of patients with PDB compared with age- and gender-matched healthy controls. Our data suggest that GRK3 has relevance to the regulation of osteoclast differentiation and that it may have relevance to the pathogenesis of PDB and other metabolic bone diseases associated with osteoclast activation.

Hospital Admissions and Mortality in Patients With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND/OBJECTIVES: Anti-neutrophil cytoplasmic antibody-associated vasculitis has reported hospital mortality rates ranging between 10% and 20% with inadequate information regarding causes and outcomes of these hospitalizations. Characterization of outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis can improve patient care and prognostication following hospitalization. METHODS: A medical records review of all hospitalizations between October 1, 2015, and December 31, 2018, of adults with granulomatosis with polyangiitis or microscopic polyangiitis at a single academic medical center was performed. Chart review confirmed diagnoses in patients identified by International Classification of Diseases, Tenth Revision code. Vasculitis activity was determined based on clinical data and treatment during the hospitalization. Differences in outcome measures were analyzed using Fisher exact test, t test, and Wilcoxon signed-rank test. RESULTS: Of the 127 hospitalizations among 54 patients, active vasculitis was identified in 43 hospitalizations (33.9%). A total of 15 patients with active disease, including 10 patients with a new diagnosis, required intensive care unit (ICU)-level care. Of 84 hospitalizations when vasculitis was inactive, infection was diagnosed in 31 admissions (36.9%), with inactive disease representing 44% of all ICU admissions. Overall mortality was 7% for hospitalized patients and 15% for those admitted to the ICU. An additional 5 patients died within 28 days of discharge, for an overall mortality rate of 17%. All 4 hospital deaths and 3 of 5 postdischarge deaths were in the setting of known infection. CONCLUSION: Most hospitalizations and patient deaths were in the context of inactive vasculitis, with infection being the most common cause. Infection and ICU admission were associated with patient death.

Molecular endotypes of type 1 and type 2 SLE.

OBJECTIVE: To character the molecular landscape of patients with type 1 and type 2 SLE by analysing gene expression profiles from peripheral blood. METHODS: Full transcriptomic RNA sequencing was carried out on whole blood samples from 18 subjects with SLE selected by the presence of manifestations typical of type 1 and type 2 SLE. The top 5000 row variance genes were analysed by Multiscale Embedded Gene Co-expression Network Analysis to generate gene co-expression modules that were functionally annotated and correlated with various demographic traits, clinical features and laboratory measures. RESULTS: Expression of specific gene co-expression modules correlated with individual features of type 1 and type 2 SLE and also effectively segregated samples from patients with type 1 SLE from those with type 2 SLE. Unique type 1 SLE enrichment included interferon, monocytes, T cells, cell cycle and neurotransmitter pathways, whereas unique type 2 SLE enrichment included B cells and metabolic and neuromuscular pathways. Gene co-expression modules of patients with type 2 SLE were identified in subsets of previously reported patients with inactive SLE and idiopathic fibromyalgia (FM) and also identified subsets of patients with active SLE with a greater frequency of severe fatigue. CONCLUSION: Gene co-expression analysis successfully identified unique transcriptional patterns that segregate type 1 SLE from type 2 SLE and further identified type 2 molecular features in patients with inactive SLE or FM and with active SLE with severe fatigue.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Pregnancy Outcomes in Patients With Interstitial Lung Disease.

OBJECTIVE: Women with interstitial lung disease (ILD) are recommended to avoid pregnancy based on limited data. This study seeks to determine maternal and pregnancy outcomes in the largest-to-date cohort of patients with ILD. METHODS: Medical records in the Duke University Health System were reviewed for pregnancies in patients with a diagnosis of ILD with underlying autoimmune disease. Pregnancies were classified as having very severe, severe, mild-moderate, or normal lung function based on pulmonary function tests (PFTs). Adverse pregnancy outcomes (APOs) were defined using the Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus and Antiphospholipid Syndrome APO (PROMISSE-APO) and Severe PROMISSE-APO criteria. RESULTS: Among 86 pregnancies in 60 women, 85% women were Black, 71% had sarcoidosis, and 29% had connective tissue disease (CTD)-associated ILD (CTD-ILD). Of the pregnancies with available PFTs (n = 59), 12% had very severe ILD, 25% had severe ILD, 51% had mild-moderate ILD, and 12% had normal lung function. PROMISSE-APOs occurred in 32% of pregnancies, including all pregnancies with very severe ILD (P = 0.02 across severity groups), 56% of pregnancies with CTD-ILD, and 23% with sarcoidosis (P = 0.02). Severe PROMISSE-APOs occurred in 15% of pregnancies, including 60% with very severe ILD and 28% with CTD-ILD. There were no maternal deaths. One woman required an intensive care hospital stay during pregnancy. Three women had volume overload after delivery that resolved with medical management. Seven women received oxygen during delivery, although none were intubated. CONCLUSION: Although APOs were common in women with very severe ILD and underlying CTD, overall maternal morbidity and mortality were low. These data suggest women with ILD may be able to safely attempt pregnancy.