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.

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.

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).

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.

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.

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.

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.

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.

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.

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

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

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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

The use of patient-reported outcome measures to classify type 1 and 2 systemic lupus erythematosus activity.

OBJECTIVE: We developed a model that categorizes systemic lupus erythematosus (SLE) activity into two dimensions: Type 1 SLE consists of inflammatory activity, including arthritis, nephritis, and rashes; Type 2 SLE includes fatigue, myalgia, mood disturbance, and cognitive dysfunction. Patient-reported outcome (PRO) measures have received attention as a way to capture symptomatology of SLE. The objective of this study was to explore the use of existing PRO measures to classify Type 1 and 2 SLE activity. METHODS: Systemic lupus erythematosus patients completed three questionnaires: Systemic Lupus Activity Questionnaire (SLAQ), Polysymptomatic Distress Scale (PSD), and Patient Health Questionnaire (PHQ-2). SLE Disease Activity Index (SLEDAI) and physician global assessments (PGA; 0-3) for Type 1 and Type 2 activity were also recorded. High Type 1 SLE activity was defined as cSLEDAI ≥4 (scored without labs), SLEDAI ≥6, active nephritis, or Type 1 PGA ≥1.0. High Type 2 SLE activity was defined as Type 2 PGA ≥1.0. Patients with both high Type 1 and 2 activity were defined as Mixed SLE, and patients with low Type 1 and 2 activity were defined as Minimal SLE. Data were reduced with a factor analysis. Using a reduced set of 13 variables, multinomial logistic regression models estimated the probability of Minimal, Type 1, Type 2, and Mixed SLE classification. RESULTS: The study included 208 patients with SLE. The model accurately predicted the clinician-based Type 1 and 2 SLE classification in 63% of patients; 73% of patients had their Type 1 SLE activity accurately predicted; and 83% had their Type 2 SLE activity accurately predicted. Performance varied by group: 87% of Minimal patients were correctly predicted to be in the Minimal SLE group, yet only about one-third of patients in the Type 1 group were correctly predicted to be in the Type 1 group. CONCLUSIONS: Our findings indicate Type 2 SLE activity can be identified by patient-reported data. The use of PROs was not as accurate at predicting Type 1 activity. These findings highlight the challenges of using PROs to categorize and classify SLE symptoms since some manifestations of Type 1 activity (e.g., nephritis) may be essentially clinically silent while other Type 1 manifestations may cause severe symptoms.

Association of Health Literacy and Numeracy With Lupus Knowledge and the Creation of the Lupus Knowledge Assessment Test.

OBJECTIVE: Limited health literacy and numeracy are associated with worse patient-reported outcomes and higher disease activity in systemic lupus erythematosus (SLE), but which factors may mediate this association is unknown. We sought to determine the association of health literacy and numeracy with SLE knowledge. METHODS: Patients with SLE were recruited from an academic center clinic. Participants completed validated assessments of health literacy (Newest Vital Sign [NVS]; n = 96) and numeracy (Numeracy Understanding in Medicine Instrument, Short Version [S-NUMI]; n = 85). They also completed the Lupus Knowledge Assessment Test (LKAT), which consists of 4 questions assessing SLE knowledge that were determined through consensus expert opinion for their wide applicability and importance related to self-management of the disease. Descriptive statistics and multivariable logistic regression modeling were used to analyze the results. RESULTS: In our SLE cohort (n = 125), 33% (32/96) had limited health literacy and 76% (65/85) had limited numeracy. The majority correctly identified that hydroxychloroquine prevented SLE flares (91%); however, only 23% of participants correctly answered a numeracy question assessing which urine protein to creatinine (UPC) ratio was > 1000 mg/g. The mean LKAT score was 2.7 out of 4.0. Limited health literacy, but not numeracy, was associated with lower knowledge about SLE as measured by the LKAT, even after adjusting for education. CONCLUSION: Patients with SLE with limited health literacy had lower knowledge about SLE. The LKAT could be further refined and/or used as a screening tool to identify patients with knowledge gaps. Further work is needed to improve patients' understanding of proteinuria and investigate whether literacy-sensitive education can improve care.

Intermittent and Persistent Type 2 lupus: patient perspectives on two distinct patterns of Type 2 SLE symptoms.

OBJECTIVE: We have developed a new conceptual model to characterise the signs and symptoms of SLE: the Type 1 and 2 SLE Model. Within the original model, Type 1 SLE consists of inflammatory manifestations like arthritis, nephritis and rashes; Type 2 SLE includes symptoms of fatigue, myalgia, mood disturbance and cognitive dysfunction. Through in-depth interviews, we explored how the Type 1 and 2 SLE Model fits within the lived experience of patients with SLE, with a focus on the connection between Type 1 and Type 2 SLE symptoms. METHODS: Semistructured in-depth interviews were conducted among adult participants meeting 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria for SLE. Participants were purposefully selected for age, race, sex and nephritis history. All interviews were audio-recorded and transcribed. Data were analysed through episode profile and thematic analysis. RESULTS: Through interviews with 42 patients with SLE, two patterns of Type 2 SLE emerged: Intermittent (n=18) and Persistent (n=24). Participants with Intermittent Type 2 SLE described feeling generally well when Type 1 is inactive; these participants were younger and had more internal SLE manifestations. Participants with Persistent Type 2 described always experiencing Type 2 symptoms despite inactive Type 1, although the severity may fluctuate. Participants with Persistent Type 2 SLE experienced traditional lupus symptoms of joint pain, hair loss and rash, but less often had severe organ system involvement. CONCLUSIONS: By listening to the stories of our patients, we found two underlying patterns of Type 2 SLE: Intermittent Type 2 symptoms that resolve in synchrony with Type 1 inflammatory symptoms, and Persistent Type 2 symptoms that continue despite remission of Type 1 symptoms.

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

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

The Categorization of Pain in Systemic Lupus Erythematosus.

Systemic lupus erythematous is a systemic autoimmune disease that can cause severe pain and impair quality of life. Pain in lupus can arise from a variety of mechanisms and is usually assessed in terms of activity and damage. In contrast, categorization of symptoms as type 1 and type 2 manifestations encompasses a broader array of symptoms, including widespread pain, fatigue, and depression that may track together. The categorization of symptoms as type 1 and type 2 manifestations can facilitate communication between patient and provider as well as provide a framework to address more fully the complex symptoms experienced by patients.

Hydroxychloroquine and COVID-19: a Rheumatologist's Take on the Lessons Learned.

PURPOSE OF REVIEW: Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy against the novel SARS-CoV-2 virus. This review describes the history, mechanisms, pharmacokinetics, therapeutic applications, and safety profile of hydroxychloroquine as an immunomodulatory and antiviral agent. It also summarizes the major studies that launched and assessed the use of hydroxychloroquine against COVID-19 infection. RECENT FINDINGS: More recent literature calls into question the long-held dogma that endolysosomal alkalinization is the primary mode of action of hydroxychloroquine. Ongoing uncertainty about the multiple potential mechanisms contributing to the therapeutic effect of hydroxychloroquine in rheumatic and viral disease led to a natural avenue for exploration in the treatment of COVID-19. Taken as a whole, the literature does not support utilizing hydroxychloroquine to treat or prevent infection from the SARS-CoV-2 virus. This is, at least in part, due to the wide variability in hydroxychloroquine pharmacokinetics between patients and difficulty achieving adequate target tissue concentrations of hydroxychloroquine without encountering unacceptable toxicities. Hydroxychloroquine continues to be a routinely prescribed, well-tolerated, effective, and low-cost treatment for rheumatic disease. Its therapeutic versatility has led to frequent repurposing for other conditions, most recently as an investigative treatment against the SARS-CoV-2 virus. Despite overall negative findings, the intense study of hydroxychloroquine against COVID-19 infection has enhanced our overall understanding of how hydroxychloroquine operates in autoimmune disease and beyond.

Using Clinical Characteristics and Patient-Reported Outcome Measures to Categorize Systemic Lupus Erythematosus Subtypes.

OBJECTIVE: The type 1 and type 2 systemic lupus erythematosus (SLE) categorization system was recently proposed to validate the patients' perspective of disease and to capture a more comprehensive spectrum of symptoms. The objective of this study was to characterize the clinical manifestations of SLE subtypes and to determine the correlation between the patient- and physician-reported measures used in the model. METHODS: This was a cross-sectional study of patients with SLE in a university clinic. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and 2011 American College of Rheumatology fibromyalgia (FM) criteria. Active SLE was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥6, clinical SLEDAI score ≥4, or active lupus nephritis. We identified 4 groups: type 1 SLE (active SLE without FM), type 2 SLE (inactive SLE with FM), mixed SLE (active SLE with FM), and minimal SLE (inactive SLE without FM). RESULTS: In this cohort of 212 patients (92% female, mean age 45 years), 30% had type 1 SLE, 8% had type 2 SLE, 13% had mixed SLE, and 49% had minimal SLE. Regardless of SLE disease activity, patients with FM (21%), reported higher SLAQ scores, patient global assessment scores, and self-reported lupus flare that resulted in discordance between patient- and physician-reported measures. CONCLUSION: Fatigue, widespread pain, sleep dysfunction, and mood disorders are common symptoms in SLE. Identifying these symptoms as type 2 SLE may be a method to improve patient communication and understanding. The level of type 2 SLE impacts patients' perception of disease and self-reported symptoms. The SLAQ may need to be reinterpreted based on the FM severity scale.