Degradation of cellular waste from phagocytosis, endocytosis, and autophagy occurs through hydrolases that become activated during acidification of late endosomes and lysosomes (LELs). In our cross-sectional study, we showed diminished LEL acidification and the accumulation of surface-bound nucleosome on monocytes, dendritic cells, B cells, neutrophils, and T cells from patients with systemic lupus erythematosus (SLE). Diminished acidification and exocytosis of undegraded IgG-immune complexes were evident in active, but not inactive, disease. This was supported by our murine study in which LEL acidification was diminished, promoting exocytosis and the accumulation of cell surface IgG-immune complexes. Mechanistically, LEL dysfunction was induced by chronic PI3K activation in lupus-prone MRL/lpr mice. We also showed that on a non-autoimmune C57BL/6 background, deficiency in SHP-1 and inhibition of SHIP-1 activity were sufficient to recapitulate LEL dysfunction found in MRL/lpr mice. Non-acidic LELs were evident in the majority of patients and associated with SLEDAI arthritis, rash, and nephritis. The high frequency of LEL dysfunction in SLE suggests that it could serve as a biomarker identifying a specific disease endotype.

OBJECTIVES:Patient education is increasingly acknowledged as an important aspect of the management of systemic lupus erythematosus (SLE). The aim of the study was to develop the SLE Knowledge Assessment score (SLAKE), a digital multilingual self-assessment tool designed to quantify essential SLE knowledge. METHODS:International healthcare professionals (HCPs) and patient representatives engaged in a multi-step process to: identify essential SLE knowledge domains, select key domains via rating, and generate an item bank of 394 questions across 11 domains, which was then adapted into 19 languages. For validation, participants completed 44 questions (including 33 randomly selected), with scores calculated for total knowledge and the 11 specific domains. Statistical analyses examined associations between scores and demographic, clinical, and educational variables. RESULTS:SLAKE was used by 1182 SLE participants (1120 [94.8%] women, median age: 45 years [IQR: 35-54 years]), with a median SLE duration of 10 years (IQR: 4-20 years). The median SLAKE score was 37 (IQR: 34-40) of a maximum of 44 points while the median score across the 11 SLAKE domains ranged between 3 and 4 over a maximum of 4 points. There was a significant positive association between SLAKE score and SLE duration (p= 0.006), previous participation to a patient education course or a patient training for lupus (p< 0.0001) and the education level (p< 0.0001) but not with age (p= 0.48) or gender (p= 0.39). CONCLUSION:SLAKE is a valid, multilingual, digital self-assessment tool that effectively measures essential SLE knowledge. Its randomized question bank and domain-specific scoring enable targeted education, ultimately supporting better disease management.

Objective Medication adherence poses a challenge for young patients with systemic lupus erythematosus (SLE), who experience more active disease and damage than their older counterparts. This study aimed to quantify the rate of medication nonadherence by age and to identify differences in reasons for nonadherence between younger and older patients with SLE. Methods We collected responses to the Domains of Subjective Extent of Nonadherence (DOSE-Nonadherence)-SLE questionnaire, a clinical tool validated to measure extent of and reasons for medication nonadherence in SLE. Analysis included 336 surveys completed between February 2020 and June 2024. Proportions and odds ratios (ORs) for extent of and reasons for nonadherence were determined across age groups, and logistic regression was used to determine relationships of nonadherence with age and other covariates. Results Medication nonadherence differed significantly across age groups 18-29, 30-39, 40-49, and 50+ ( P < 0.001). For each increased year of age, self-reported nonadherence decreased by 2% ( P < 0.05). Black race and Hispanic ethnicity were also predictive of nonadherence across age groups. The < 30 age group was more likely to report nonadherence due to inability to fill medications on time (OR 3.72, 95% CI 1.53-9.02) and needing to take medicines with food (OR 2.55, 95% CI 1.06-6.13). Conclusion Younger patients reported greater extent of nonadherence, often due to logistical impediments. In addition to counseling young adults with SLE on the importance of medications, rheumatologists should, when possible, offer support to help them overcome challenges in obtaining and taking medicines. Approaches to understanding and intervening on medication nonadherence in SLE may need to be tailored by age.

Background/PurposeMycophenolate compound (MMF, to represent both mycophenolate mofetil and mycophenolic acid) is an immunosuppressant used to treat Systemic Lupus Erythematosus (SLE). Due to its teratogenicity, the FDA recommends universal mycophenolate Risk Evaluation and Mitigations Strategies (MREMS) to prevent unplanned pregnancies and minimize fetal exposure. This quality improvement initiative aimed to improve documentation of the MREMS protocol in the encounter clinic note from 0% to 75% within 14 months.MethodsThe project was conducted in an academic lupus clinic from February 2023 to May 2024, with the intervention beginning in March 2023. MREMS was recommended for adult female SLE patients aged 18-50 on MMF, excluding those with hysterectomy. Interventions included provider and nurse education, nursing algorithms for identifying eligible patients and ordering pregnancy tests, electronic health record template updates, and regular feedback. Required documentation included counseling on MMF teratogenicity and contraception, with pregnancy testing at each visit. Control charts monitored documentation of MREMS counseling and pregnancy testing, and a one-year post-implementation follow-up was completed.ResultsAmong eligible encounters (n = 89), MREMS documentation increased from 0% to an average of 24% during the first 8 months of PDSA cycles, then shifted to an average of 67% of encounters. We reached and sustained our documentation goal of 75% for the last three consecutive months. Pregnancy-test ordering rose from 0% to 63%, and contraception was documented at 98% of visits. Over the course of the intervention, no pregnancies were exposed to MMF. MREMS documentation and pregnancy screening remained above 75% of encounters 1 year after intervention.ConclusionUsing quality improvement cycles, we incorporated a two-part MREMS protocol into a busy academic lupus clinic, with improved documentation and pregnancy screening.

PV228 / #365 Poster Topic:AS23 - SLE-Diagnosis, Manifestations, & Outcomes In SLE, autoantibodies (ANAs) can promote pathogenesis by forming immune complexes (ICs) that activate complement. While antibodies to DNA (anti-DNA) are known to be associated with complement levels, the role of other ANAs in activating complement is less clear. To elucidate better serological biomarkers in the context of novel therapies to decrease immunoglobulin levels or B cells, we modeled the relationship between autoantibodies (anti-DNA, other ANAs, anti-C1q) and complement. Adult SLE patients (SLICC or ACR/EULAR criteria) were enrolled during routine clinic visits from June 2020 to June 2024. At each visit, treating rheumatologists scored the PGA and SLEDAI, medications were recorded, and autoantibodies were measured. Autoantibodies including anti-DNA, anti-RNA-binding proteins (RBPs), and anti-C1q were measured by ELISA. Complement activation was defined as (1) low C3, (2) low C4, (3) low C3 and low C4, and (4) low C3 or low C4. Potential predictors of complement activation were modeled in 4 steps: (1) anti-DNA; (2) anti-DNA, anti-RBPs (Ro-52, Ro-60, Sm, La, U1RNP, RNP-70), and anti-C1q; (3) anti-DNA, anti-RBPs, anti-C1q, and medications; and (4) anti-DNA, anti-RBPs, anti-C1q, and disease activity. To identify linear and possible nonlinear relationships between predictors and complement activation, we considered both generalized linear models (GLMs; specifically, logistic regression with LASSO regularization) and decision tree models, each with continuous predictors. Models were trained and tuned on 80% of patients and evaluated on the remaining 20%. The study included 526 visits in 257 patients (mean age 42 years; mean disease duration 13 years; 88% female; 58% Black, 29% White; 6% Hispanic). Almost one-quarter of visits had low C3 or C4; anti-DNA was positive at 40% of visits. In Lasso regression models, the presence of anti-DNA accurately predicted complement levels (AUC: 0.71-0.79; Table 1); model performance improved with the inclusion of anti-RBPs and anti-C1q (AUC: 0.73-0.84). The inclusion of medications or disease activity led to limited improvement in model performance. Across outcomes of complement activation, anti-DNA and anti-C1q were consistently associated with low complement (Figure 1). For the outcome of low C3, a 1 standard deviation increase in anti-DNA levels increased the odds of having low C3 by approximately 123%; a 1 standard deviation increase in anti-C1q levels was associated with an 82% increase in the odds of having low C3. Results were similar for low C4. The results of the decision tree models (Table 1) align with the findings from Lasso logistic regression models. For both low C3 and low C4, the decision tree consistently selected anti-DNA and anti-C1q as the primary splitting variables, further affirming their predictive power. Table 1. Model performance of serologies, medications, and disease activity to predict low complement. Figure 1. Coefficients of anti-DNA, anti-RBPs and anti-C1q on low C3 and low C4. Error bars indicate 95% confidence intervals obtained via bootstrapping (1000 resamples) the development set. These results support the important role of anti-DNA antibodies in complement activation as reflected in levels of C3 and/or C4; the effects of other ANAs in the model were less marked, perhaps reflecting a more limited ability of these antibodies to form ICs that activate complement. The association of anti-C1q with low C3 and/or C4 is consistent with a role of this antibody in activating complement and suggests the value of assaying anti-C1q in studies on therapies that can impact autoantibody levels.

INTRODUCTION:In the type 1 and 2 SLE model, inflammation mediates type 1 manifestations, but its role in type 2 manifestations (eg, fatigue, myalgias, mood disturbance, cognitive dysfunction) is less clear. Therapeutic hydroxychloroquine (HCQ) levels reduce type 1 activity, but their relationship with type 2 activity is unknown. Exploring this relationship may illuminate type 2 SLE pathophysiology. METHODS:We measured whole blood HCQ levels using liquid chromatography-mass spectrometry, categorising them as underexposure (<200 ng/mL), subtherapeutic (200 to <750 ng/mL) or therapeutic (≥750 ng/mL). We measured type 1 SLE activity using the type 1 Physician Global Assessment (PGA) and Systemic Lupus Erythematosus Disease Activity Index and type 2 SLE activity using the type 2 PGA and patient-reported polysymptomatic distress scores. Patients were categorised into minimal (low type 1 and type 2), type 1 (high type 1 and low type 2), type 2 (low type 1 and high type 2) and mixed activity (high type 1 and type 2) groups. We analysed relationships between HCQ levels and type 1 and type 2 SLE activities. RESULTS:Among 154 patients (median age 43, 90% women, 63% Black race, 7% Hispanic ethnicity) across 297 visits, HCQ levels were underexposed at 41 (14%) visits, subtherapeutic at 76 (26%) and therapeutic at 180 (61%) visits. Patients had minimal activity at 102 visits (34%), type 1 activity at 33 (11%), type 2 activity at 85 (29%) and mixed activity at 77 (26%) visits.Underexposed HCQ levels were independently associated with higher type 1 (OR 2.33, 95% CI 1.23 to 4.44) and type 2 activities (OR 1.80, 95% CI 1.07 to 3.04). Mixed activity most strongly associated with Underexposed HCQ levels (OR 3.4-10.3, p<0.05). CONCLUSIONS:Low HCQ levels are associated with increased type 1 and type 2 SLE activities, particularly for the mixed activity group, suggesting that immunologic activity may contribute to type 2 symptoms in some patients.

IntroductionBlack patients with systemic lupus erythematosus (SLE) have lower medication adherence than White patients, contributing to worse health outcomes. However, racial differences in reasons for nonadherence and beliefs about medications are not well understood.MethodsWe conducted a cross-sectional analysis of Black and White patients with SLE who completed the Beliefs about Medicines Questionnaire and the SLE-specific Domains of Subjective Extent of Nonadherence survey. We compared scores by race and by adherence level within each racial group.ResultsAmong 123 patients (52% Black, 48% White), adherence was lower in Black patients (44% vs 64%, p = .02). Black patients reported greater concerns about SLE medications and medication overuse and harm than White patients. Nonadherent Black patients reported weaker beliefs in SLE medication necessity and greater concerns about medication overuse and harm than adherent Black patients. Reasons for nonadherence reported by Black patients but not White patients included feeling well (45%), concerns about future fertility (14%), and doubts about their doctors and medicines (8%).ConclusionNonadherence among Black patients was uniquely associated with stronger concerns about medication overuse and harm and weaker beliefs that SLE medicines were necessary, potentially reflecting medical mistrust that may drive skipping doses when feeling well or when concerns arise. These insights can help clinicians more astutely probe and address each patient's needs to enhance medication adherence and SLE management.

PV233 / #350 Poster Topic:AS23 - SLE-Diagnosis, Manifestations, & Outcomes In SLE, early childhood trauma and adverse childhood experiences have been associated with chronic pain, fatigue, depression, self-reported flares and incident SLE. In this study we evaluated the frequency and impact of abusive and non-abusive trauma on quality of life in SLE. This study involved adult SLE patients (2012 SLICC or 2019 ACR/EULAR criteria) from August 2023 to April 2024. Patients completed the LupusPRO; FACIT-fatigue scale; PROMIS measures for pain intensity, pain interference, self-efficacy, and psychological stress; and the Trauma History Screen. Additional trauma questions regarding emotional abuse and pregnancy loss or abortion were added. Abusive trauma was defined as physical, sexual, and emotional trauma as an adult or child. Patients were divided into 3 groups: abusive trauma, non-abusive trauma, and no trauma. Differences across groups were analyzed by Fisher’s exact test or ANOVA. In this cohort of 262 SLE patients (92% female, mean age 44 years, mean disease duration 15 years, 60% self-reported Black), the vast majority experienced at least 1 traumatic event (85%) with almost half suffering abusive trauma. Trauma was more common among women, with abusive trauma occurring almost exclusively in women. Education attainment was similar across groups, however a greater number of patients with abusive trauma had an annual income less than $50,000. There was a progressive increase in fatigue, pain intensity, and pain interference across the 3 groups with the highest scores in those with abusive trauma (Table 1). More than half of patients with abusive trauma reported moderate to severe levels of fatigue, pain intensity and interference in social and daily activities. Likewise, patients with trauma reported significantly more psychological stress and lower self-efficacy for managing symptoms and medications than those without trauma. When evaluating the relationship of trauma across LupusPRO, patients with abusive trauma had lower scores for sleep, physical and emotional health, pain, fatigue, cognition, body image, effects from lupus medications indicating worse health-related quality of life in these domains (Figure 1). Finally, scores for coping, desires and goals, and support system were worse in patients with abusive trauma. Table 1. Influence of trauma on pain, fatigue, self-efficacy and stress Figure 1. Influence of trauma on LupusPRO health and non-health related quality of life Many patients with lupus have suffered trauma, including abusive trauma, throughout their lives and experience reduced quality of life across multiple health and non-health domains. Further, the data suggest that abusive trauma can impact the burden and severity of lupus symptoms as well the ability to manage symptoms and medications. Incorporating a trauma-informed approach to care may therefore be important in developing and delivering treatment to improve quality of life in SLE.

PV207 / #177 Poster Topic:AS23 - SLE-Diagnosis, Manifestations, & Outcomes Our prior qualitative work demonstrated there are at least 2 distinct subgroups of Type 2 SLE; one is related to active inflammation (Intermittent Type 2 SLE) and another can be present regardless of inflammation (Persistent Type 2 SLE). The objective of this study was to utilize longitudinal measures of Type 1 and Type 2 SLE activity to characterize these Type 2 SLE subgroups. SLE patients meeting SLICC or ACR criteria were enrolled in a university lupus registry. At each clinic visit, participants completed the Polysymptomatic Distress Scale (PSD), and rheumatologists completed disease activity measures, including the SLEDAI and Physician Global Assessments (PGA) for both Type 1 and Type 2 SLE activity. Patients seen between May 2023 and April 2024 were invited to participate in a substudy that included the FACIT-fatigue scale; PROMIS measures for pain intensity, pain interference, self-efficacy, and psychological stress; and the Trauma History Screen. Only patients who participated in the substudy and had ≥3 visits in the registry were included in the analysis. High Type 1 SLE activity was defined as clinical SLEDAI ≥4, SLEDAI ≥6, active lupus nephritis or PGA ≥1. High Type 2 SLE activity was defined as Type 2 PGA ≥1 or PSD ≥8. Patients who had high Type 1 SLE activity at <30% of visits and high Type 2 SLE activity at ≥50% of visits were classified as Persistent Type 2 SLE. Patients who had fluctuating Type 2 SLE activity were classified as Intermittent Type 2 SLE. Patients who never had high Type 2 SLE activity during follow-up (n=13) were excluded from the analysis. Differences in characteristics between the 2 groups were estimated by t-tests and Fisher’s exact tests. The analysis included 183 patients (mean age 45 years, 92% female, 60% Black); 26% of patients had Persistent Type 2 SLE. Demographics were similar between the 2 groups (Table 1). Patients with Persistent Type 2 SLE were more likely to have experienced abusive trauma. While patients with Intermittent Type 2 SLE had higher Type 1 SLE activity over time, approximately half of patients in each group had a history of lupus nephritis, and there were no differences between groups in historical use of prednisone, DMARDs, or biologics. Patients in the Persistent Type 2 SLE group were more likely to have been prescribed a Type 2 SLE medication and to have been prescribed more Type 2 SLE medications over time. By definition, patients with Persistent Type 2 SLE had higher PSD scores during follow-up, yet patients with Intermittent Type 2 SLE still had mild to moderate PSD scores, on average, during follow-up. There were similar self-efficacy scores for managing medications between groups, yet patients with Persistent Type 2 SLE had lower self-efficacy for managing symptoms; they also had worse scores for FACIT-fatigue, PROMIS pain intensity, and pain interference. Table 1. Cohort characteristics. One in 4 patients met our study definition for Persistent Type 2 SLE. Despite having taken on average 4 different medications to treat Type 2 SLE symptoms, patients with Persistent Type 2 SLE continued to have a high burden of pain, fatigue, depression, and brain fog, demonstrating a need for better treatment approaches. Several psychosocial stressors could predispose or perpetuate Persistent Type 2, and future work will evaluate these triggers to better understand the etiology and target solutions for these symptoms.

PV097a / #117 Poster Topic:AS11 - Epidemiology and Public Health Adverse social drivers of health (SDoH) in systemic lupus erythematosus (SLE) are associated with worse health outcomes and quality of life. The aim of this initiative was to provide support to SLE patients with SDoH needs. To respect patient autonomy, financial support was given as $100 cash to spend as they deemed best. Herein, we report the clinical characteristics of those who received financial support as well as the patient and staff perspective of the program. Adult Duke Lupus Clinic (DLC) patients are screened annually for SDoH insecurities. From January 2024 to October 2024, SLE patients were with food and/or transportation insecurity by routine SDoH screening, lupus nephritis patients with federally funded (Medicare and/or Medicaid) or no insurance, and patients with a SDoH need as determined by the treating clinician’s discretion qualified for financial support. These patients were offered 1) $100 cash at the end of visit 2) a referral to NCCare360, a statewide community social support program, and 3) a referral to DukeWell, an internal healthcare navigation program. After the visit, patients completed an anonymous survey on barriers to healthcare and experience with the program. Feedback was obtained from the clinic team. The clinical and demographic data of participants in the Duke Lupus Registry (DLR) who did and did not receive cash assistance were analyzed. Cash was distributed to 101 DLC patients; 27 patients received cash at more than 1 visit. Of the 276 DLR patients seen during this time, 74 patients (26%) received cash assistance and underwent analysis. There was no difference in age, disease duration, gender, and Hispanic ethnicity between participants who had identified SDoH barriers and those who did not (Table 1). However, patients with identified SDoH barriers were more likely to have lower educational attainment, federally funded insurance or no health insurance, and a low annual income. Nearly half of patients with an identified SDoH barrier reported food insecurity and over a quarter reported transportation insecurity. Nearly three-quarters identified difficulty paying for a variety of basic needs such as food, housing, medical care, and heating. Participants with an identified SDoH barrier were more likely to have a history of brain fog, fatigue, waking unrefreshed, and anxiety in the previous 18 months. Over three-quarters of patients completed the anonymous survey. Over half of patients had never worked with a case manager or social worker. The most frequently reported barriers to managing and accessing healthcare included the cost of food (55%), cost of utilities (45%), and cost of medications (43%). Feedback from patients was overwhelmingly positive (Table 2), with patients frequently sharing emotions such as “grateful” or “blessed.” Quotes from the clinical team highlight the profound, positive impact of the program, with team members noting how the cash assistance has addressed tangible needs of patients with SLE. Table 1. Demographics and Disease Manifestations Table 2. Patient and clinical team quotes about the cash assistance program. A financial support program was implemented to address SDoH needs that are identified upon routine clinic screening. A range of SDoH needs and financial difficulty affording food, utilities, and medications are not uncommon in SLE. Those with SDoH needs experienced a greater burden of fatigue, pain, and mental health suggesting a connection between social, environmental, and physical health. Patients and the clinical team expressed gratitude and appreciation for program. Sustainable programs that screen and address SDoH could impact disparities in lupus outcomes.

Systemic autoimmune rheumatic diseases (SARDs) consist of a broad range of immune-mediated multisystem diseases. They are chronic, incurable illnesses that often present in early to mid-life and can be associated with a high symptom burden, disability, and early mortality. Treatment guidelines for similar chronic, life-limiting conditions with uncertain disease courses now recommend palliative care (PC) assessment at the time of diagnosis. Recently, the first rheumatology treatment guidelines to recommend PC were also published. Integration of PC into rheumatology offers an opportunity to improve quality of life and deliver better goal-concordant care for people with severe rheumatic disease. This article provides 10 tips to guide PC clinicians when caring for people with rheumatic diseases.

ObjectiveHealth literacy is an important social determinant of health, with limited health literacy associated with worse health outcomes. This study examined the associations between limited health literacy with patient‐reported outcomes and disease activity/damage among 267 Black women with active systemic lupus erythematosus (SLE) enrolled in the Peer Approaches to Lupus Self‐Management (PALS) program.MethodsThe three‐item Chew Health Literacy Screening was used to dichotomize those reporting in the “limited” range on any item with outcomes compared via generalized linear models. Baseline surveys and assessments obtained at study entry as part of the PALS study were used. Primary outcomes included disease activity and lupus damage; other secondary outcomes included patient activation, self‐efficacy, physician/patient communication, and quality of life.ResultsThe study included 267 Black women with SLE. In covariate‐adjusted analyses, participants with limited health literacy (88 [33%]) were more likely to have lower patient activation (Patient Activation Measure P < 0.0001), lower self‐efficacy (Lupus Self‐Efficacy P < 0.0001), higher lupus damage (self‐administered Brief Index of Lupus Damage P = .016), higher disease activity (Systemic Lupus Activity Questionnaire symptom severity P = 0.006), and worse physician/patient communication (patient‐centered care P < 0.0001) compared to those with adequate health literacy. Those with limited health literacy also reported worse lupus quality of life (P = 0.0004) and greater levels of stress (Perceived Stress Scale‐4 P < 0.0001) and were 2.4 times more likely to have probable major depression (Patient Health Questionnaire Depression Scale‐8 of ≥10 P = 0.004) and probable anxiety disorder (General Anxiety Disorder‐7 of ≥10 P = 0.007) compared to those with adequate health literacy.ConclusionBlack women with SLE and limited health literacy have worse clinical outcomes and represent a particularly vulnerable population with significantly disparate health outcomes. These findings suggest health literacy and complexities of managing SLE may impair clinical care in multiple domains, ultimately contributing to higher disease activity and death/damage, and are important to address in clinical care and future interventions in patients with SLE.

ObjectiveSystemic 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.MethodsWe 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.ResultsForty-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.ConclusionPatients 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.

Disclosures AME, JLR, MEBC: Exagen, Immunovant Funding Duke CTSA grant (UL1TR002553) Background The Type 1 & 2 SLE Model encompass symptoms classically attributed to inflammation, including arthritis, rash, serositis and nephritis (Type 1 SLE), and symptoms of fatigue, widespread pain, mood disturbance, and brain fog (Type 2 SLE). Our preliminary data suggest there are at least two distinct sub-types of Type 2 SLE, one related to active inflammation and another that exists regardless of inflammation. The objective of this study was to use longitudinal measures of Type 1 and Type 2 SLE activity to identify subgroups of Type 2 SLE. Methods SLE patients meeting Systemic Lupus Collaborating Clinics (SLICC) criteria with ≥2 visits at a university rheumatology clinic over a 36-month period between February 2018 and August 2022 were included. At each visit, rheumatologists scored Type 1 and 2 SLE activity separately by Physician's Global Assessments (PGA), visual analog scales of 0–3 (0=no activity, 3=severe activity). Growth mixture models derived classes of patients based on their Type 1 and Type 2 PGA trajectories, and posterior probabilities assigned patients to the class with the highest probability. Patients were then classified according to their classes of Type 1 and Type 2 PGA trajectories into different 'groups'. Clinical and demographic characteristics were compared across groups. Results We included 297 patients with 2,011 visits. The best model fit of trajectories for both the Type 1 and Type 2 PGA included three classes. When patients were grouped according to their Type 1 and Type 2 PGA classes, the majority (73%) fell into one of four groups: 29% had low Type 1 and Type 2 activity (Minimal); 19% had constant high Type 2 but low Type 1 activity (Type 2); 7% had constant high Type 1 but low Type 2 activity (Type 1); and 18% had constant high Type 1 and Type 2 activity (Mixed). The remaining 27% of patients had variable Type 1 and Type 2 changes over time that did not fit into a distinct group (figure 1). Patients in the Type 2 SLE group were older and more likely to be on disability (table 1). While the SLEDAI and Type 1 PGA scores were similar between the Type 1 and Mixed groups, the disease manifestations were somewhat different, with more nephritis in the Type 1 group and higher LFA-REAL Musculoskeletal PGA scores in the Mixed group. While overall Type 2 PGA scores were similar for those in the Type 2 and Mixed groups, there was more depression, pain, and symptom severity among those in the Mixed group. In a descriptive analysis to determine if Type 1 and Type 2 PGA changed concordantly, 39% of patients had Type 1 and Type 2 SLE PGAs that consistently changed together. Conclusion We identified four main longitudinal subgroups of patient trajectories. Supporting our prior qualitative work, we found changes in Type 1 and Type 2 occurred together in almost 40% of patients. Future work is needed to understand the underlying etiology of each subgroup, allowing us to target these groups with appropriate medical and non-medical treatments.