Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force.

OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE. METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus. RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals. CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.

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.

Feasibility and Utility of a Pilot Peer Education Program to Improve Patient Engagement in Lupus Clinical Trials: Implementation and Evaluation in a Multisite Model Within a Lupus Clinical Trials Network.

OBJECTIVE: To assess outcomes related to Lupus Therapeutics' Patient Advocates for Lupus Studies (LT-PALS), a peer-to-peer lupus clinical trial (LCT) education program designed to improve representation of diverse groups in LCTs. Patients with lupus and clinical trial participation experience were trained as peer educators (PALs) providing trial-agnostic education to trial-naive patients with lupus. METHODS: We used a two-arm, randomized pretest/posttest study design to evaluate outcomes related to LCT participation: knowledge, attitudes, self-efficacy, and intentions to participate in an LCT. Five academic medical centers piloted the program. The intervention group (IG) individually received peer-to-peer education sessions with trained PALs, primarily via telephone; the control group (CG) received a 3-week waiting period. We conducted within/between-group t-tests and multiple linear regressions with posttest scores as dependent variables and participation in LT-PALS as the exposure variable. RESULTS: The sample (n = 136) included 64 IG and 72 CG participants, with 67.7% identifying as Black. At posttest, IG participants had higher knowledge (P < 0.01) scores than the CG participants. Regression models controlling for participant characteristics showed higher IG posttest scores for knowledge (P < 0.001) and intentions (P < 0.05). From pretest to 3-month follow-up, IG self-efficacy scores increased (P < 0.01). About half (46.9%) of IG participants reported engagement with an LCT at 1-year follow-up. Black and Hispanic participants rated higher overall program satisfaction compared with White (P < 0.01) and non-Hispanic (P < 0.05) participants. CONCLUSION: Findings demonstrated feasibility of LT-PALS and showed promise in increasing engagement from groups underrepresented in LCTs.

Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co-Expression Patterns: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

OBJECTIVE: Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE). METHODS: During screening, patients with active, non-organ-threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI). RESULTS: In this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy-evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment-related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab-treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab-treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention-to-treat (HR 0.59, P = 0.062) populations. In obexelimab-treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expression clusters with high B cell pathway modules were associated with increased time to LOI. Obexelimab was associated with infusion reactions but was generally safe and well-tolerated. CONCLUSION: Although the primary endpoint was not reached, secondary analysis showed time to LOI was significantly increased in obexelimab-treated patients, and analysis of patient subsets defined by gene expression patterns at baseline suggests a responding subpopulation.

A Provider-Based Approach to Address Racial Disparities in Lupus Clinical Trial Participation.

OBJECTIVE: Substantial disparities exist in clinical trial participation, which is problematic in diseases such as lupus that disproportionately affect racial/ethnic minority populations. Our objective was to examine the effectiveness of an online educational course aiming to train medical providers to refer Black and Latino patients to lupus clinical trials (LCTs). METHODS: The American College of Rheumatology's Materials to Increase Minority Involvement in Clinical Trials (MIMICT) study used an online, randomized, 2-group, pretest/posttest design with medical and nursing providers of multiple specialties. We exposed intervention group participants to an education course, while the control group participants received no intervention. Controlling for the effects of participant characteristics, including specialty, and professional experience with lupus, we modeled relationships among exposure to the education course and changes in knowledge, attitudes, self-efficacy, and intentions to refer Black and Latino patients to LCTs. We also examined education course satisfaction. RESULTS: Compared to the control group, the intervention group had significantly higher posttest scores for knowledge, self-efficacy, and intentions to refer Black and Latino patients to LCTs. Both medical and nursing trained intervention group participants had significantly higher mean posttest scores for knowledge and intentions to refer compared to the medical and nursing trained control group participants. Attitude was insignificant in analysis. The online education course, which received a favorable summary score, indicated that satisfaction and intentions to refer were strongly and positively correlated. CONCLUSION: The MIMICT education course is an effective method to educate medical providers about LCTs and to improve their intentions to refer Black and Latino patients.

Teratogenic medication use associated with favourable odds of contraception counselling in a cohort of women with systemic lupus erythematosus at a large tertiary academic medical centre.

OBJECTIVE: SLE primarily affects women of childbearing age, who have an increased risk of pregnancy complications, especially in the setting of active disease. Contraception counselling is particularly important given the teratogenicity of some medications used for SLE treatment. Our study describes the frequency of contraception counselling provided by multiple subspecialties to women with SLE and investigates associations between teratogenic medication use and receiving contraception counselling. METHODS: This was a cross-sectional retrospective study of women (aged 15-46 years) diagnosed with SLE who were seen in various outpatient clinics at a large tertiary academic medical centre over a 2-year period. Demographic data were retrieved via the university-affiliated central data repository, and additional data, including documentation of contraception counselling, were obtained via manual chart abstraction. Univariable associations between variables and contraception counselling were assessed to produce unadjusted ORs and 95% CIs. Multivariable models were generated to evaluate independent associations between variables and contraception counselling. RESULTS: Data from 478 women (52% African American, 25% Caucasian) with SLE were included. Rheumatology was the subspecialty to document contraception counselling most frequently (57%). Nearly 80% of women received counselling from at least one subspecialty, 44% from at least two. Factors associated with having lower odds of receiving contraception counselling were older age and Caucasian race. Women on teratogenic medications (methotrexate, mycophenolate mofetil/mycophenolic acid, cyclophosphamide) had higher odds of receiving contraception counselling from at least one subspecialty (OR 2.01; 95% CI 1.23 to 3.26), from two or more subspecialties (OR 2.18; 95% CI 1.50 to 3.17), and from rheumatology (OR 1.86; 95% CI 1.27 to 2.73). CONCLUSIONS: In this study, women with SLE on teratogenic medications had higher odds of receiving contraception counselling from rheumatology and from at least two subspecialties. Multidisciplinary approaches to enhance contraception counselling should be encouraged.

Perceived Impact of the COVID-19 Pandemic on Physical Activity Among Adult Patients With Rheumatologic Disease.

OBJECTIVE: The objective of this cross-sectional study was to investigate the impact of the COVID-19 pandemic on physical activity (PA) levels of patients with rheumatic and musculoskeletal diseases (RMDs) and to examine factors associated with decreased PA. METHODS: A sample of adult patients with RMDs (n = 7,776) was identified through electronic medical records from an academic health care system in North Carolina. Invitations to participate in an online survey were sent between July 2020 and September 2020 to assess self-reported changes in PA during the COVID-19 pandemic. Descriptive statistics, age-adjusted prevalence odds ratios (PORs), and 95% confidence intervals (CIs) were computed to examine patient characteristics associated with decreased PA. RESULTS: A total of 893 eligible participants completed the survey (mean age 57.8 ± 14.9 years, 75.8% female). The most common primary diagnoses reported among participants included rheumatoid arthritis (27.3%), osteoarthritis (16.0%), and systemic lupus erythematosus (SLE) (13.0%). More than half of participants (56.8%) reported engaging in less PA since the pandemic began. Factors associated with engaging in less PA included lower self-reported general health (POR, 2.21; CI, 1.64-2.97) and a diagnosis of SLE (POR, 1.57; CI, 1.03-2.38). Comorbidities associated with decreased PA included chronic pain (POR, 1.38; CI, 1.04-1.82), depression (POR, 1.48; CI, 1.09-2.01), and hypertension (POR, 1.44; CI, 1.10-1.90). CONCLUSION: The COVID-19 pandemic has exacerbated barriers to PA in patients with RMDs. There is a critical need to provide resources, support, and multifaceted programs to encourage PA in patients with RMDs during the COVID-19 pandemic.

The Disparities in Patient Portal Use Among Patients With Rheumatic and Musculoskeletal Diseases: Retrospective Cross-sectional Study.

BACKGROUND: During the COVID-19 pandemic, the shift to virtual care became essential for the continued care of patients. Individuals with rheumatic and musculoskeletal diseases (RMDs) especially require frequent provider visits and close monitoring. To date, there have been limited studies examining inequities in health technology use among patients with RMDs. OBJECTIVE: Our goal was to identify characteristics associated with patient portal use before and after the COVID-19 pandemic in a convenience sample of patients with RMDs from a large academic medical center. METHODS: In this cross-sectional study, Epic electronic medical record data were queried to identify established patients of the University of North Carolina Hospitals adult rheumatology clinic between November 1, 2017, through November 30, 2019. Demographic and clinical data were collected to compare MyChart (Epic's patient portal) users with nonusers before and after the COVID-19 pandemic. MyChart activation and use were modeled using logistic regression and adjusted odds ratios, and confidence intervals were estimated. RESULTS: We identified 5075 established patients with RMDs who met the inclusion criteria. Prior to the pandemic, we found that younger age (P<.001), suburban residence (P=.05), commercial/state insurance (P<.001), military insurance (P=.05), and median income >US $50,000 (P<.001) were associated with significantly higher odds of MyChart activation. Male sex (P<.001), being of Black or African American (P<.001) or "other" race (P<.001), Spanish as a primary language (P<.001), rural residence (P=.007), Medicaid insurance (P<.001), and median income of

Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus.

BACKGROUND: Blood dendritic cell antigen 2 (BDCA2) is a receptor that is exclusively expressed on plasmacytoid dendritic cells, which are implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied. METHODS: In this phase 2 trial, we randomly assigned adults with histologically confirmed cutaneous lupus erythematosus with or without systemic manifestations in a 1:1:1:1 ratio to receive subcutaneous litifilimab (at a dose of 50, 150, or 450 mg) or placebo at weeks 0, 2, 4, 8, and 12. We used a dose-response model to assess whether there was a response across the four groups on the basis of the primary end point, which was the percent change from baseline to 16 weeks in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (CLASI-A; scores range from 0 to 70, with higher scores indicating more widespread or severe skin involvement). Safety was also assessed. RESULTS: A total of 132 participants were enrolled; 26 were assigned to the 50-mg litifilimab group, 25 to the 150-mg litifilimab group, 48 to the 450-mg litifilimab group, and 33 to the placebo group. Mean CLASI-A scores for the groups at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. The difference from placebo in the change from baseline in CLASI-A score at week 16 was -24.3 percentage points (95% confidence interval [CI] -43.7 to -4.9) in the 50-mg litifilimab group, -33.4 percentage points (95% CI, -52.7 to -14.1) in the 150-mg group, and -28.0 percentage points (95% CI, -44.6 to -11.4) in the 450-mg group. The least squares mean changes were used in the primary analysis of a best-fitting dose-response model across the three drug-dose levels and placebo, which showed a significant effect. Most of the secondary end points did not support the results of the primary analysis. Litifilimab was associated with three cases each of hypersensitivity and oral herpes infection and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the participant received the last dose of litifilimab. CONCLUSIONS: In a phase 2 trial involving participants with cutaneous lupus erythematosus, treatment with litifilimab was superior to placebo with regard to a measure of skin disease activity over a period of 16 weeks. Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.).

EMBRACE: One Small Story in Lupus-One Giant Challenge in Clinical Trials.

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post-marketing commitment to the Food and Drug Administration. The study recruited only patients who self-identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well-designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long-term support to ensure equity in the process, products, and benefits from drug development and clinical trials.

ACT for Lupus: Pilot Feasibility and Acceptability Study of a Novel Web-Based Acceptance and Commitment Therapy Program for Patients With Lupus.

OBJECTIVE: Acceptance and commitment therapy (ACT) has demonstrated effectiveness in addressing symptoms of anxiety and depression, frequently experienced by patients with systemic lupus erythematosus (SLE). The goal of this pilot study was to develop and assess the feasibility and acceptability of a novel web-based ACT skills training program tailored for patients with lupus: ACT for Lupus. The program served as a complementary approach to support the management of symptoms and stressors during the COVID-19 pandemic. METHODS: This study employed a single-group pretest-posttest design. Participants with a diagnosis of SLE were primarily recruited through an institutional healthcare system between November 25, 2020 and December 17, 2020 and through an online national lupus organization listserv. Participants were invited to attend two 1-hour webinars delivered over a 2-week period. Educational ACT-based content was tailored for patients with lupus and delivered by an experienced clinical psychologist specializing in ACT. Surveys assessed patient-reported outcomes of anxiety, depression, and quality of life and evaluated program feedback, usability, and satisfaction. RESULTS: A total of 83 participants submitted the baseline survey, with 21 participants designated as study completers. The program was well received by participants, who reported feasibility and acceptability of the intervention, as reflected by high usability ratings. Participants reported favorable experiences with the program. Feedback included suggestions to include additional lupus-tailored content, increase the range and scope of sessions and activities, and improve program flexibility and availability to avoid scheduling conflicts. CONCLUSION: This study provides preliminary evidence for an adapted, ACT-based virtual skills training program as a feasible and acceptable intervention to support the well-being of patients with lupus.

Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies.

Non-White people are more likely to develop systemic lupus erythematosus (SLE) yet are underrepresented in SLE clinical trials. The efficacy and safety of drugs may be influenced by ancestry, and ancestrally diverse study populations are necessary to optimize treatments across the full spectrum of patients. However, barriers to entry into clinical trials are amplified in non-White populations. To address these issues, a conference was held in Bethesda, Maryland, from October 15-16, 2019, entitled "Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies: Overcoming the Barriers." Conference participants included people with lupus, lupus physicians, lupus clinical trialists, treatment developers from biotechnology, social scientists, patient advocacy groups, and US government representatives (The Office of Minority Health, Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration). For all these groups, the organizers of the conference purposefully included people of non-White ancestry. Decreased participation of non-White SLE patients in clinical research was evaluated through historical, societal, experiential, and pragmatic perspectives, and several interventional programs to increase non-White patient participation in SLE and non-SLE research were described and discussed. The presentations and discussions highlighted the need for changes at the societal, institutional, research team, referring physician, and patient education levels to achieve equitable ancestral representation in SLE clinical studies.

Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus.

OBJECTIVE: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified Black race. METHODS: EMBRACE (GSK Study BEL115471; ClinicalTrials.gov identifier: NCT01632241) was a 52-week multicenter, double-blind, placebo-controlled trial in adults of self-identified Black race with active SLE who received monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26-week open-label extension phase included patients who completed the double-blind phase. The primary end point of the study was SLE Responder Index (SRI) response rate at week 52 with modified proteinuria scoring adapted from the SLE Disease Activity Index 2000 (SLEDAI-2K) (SRI-SLEDAI-2K). Key secondary end points included SRI response rate at week 52, time to first severe SLE flare, and reductions in prednisone dose. RESULTS: The modified intent-to-treat population comprised 448 patients, of whom 96.9% were women and the mean ± SD age was 38.8 ± 11.42 years. The primary end point (improvement in the SRI-SLEDAI-2K response rate at week 52) was not achieved (belimumab 48.7%, placebo 41.6%; odds ratio 1.40 [95% confidence interval 0.93, 2.11], P = 0.1068); however, numerical improvements favoring belimumab were observed, in which the SRI-SLEDAI-2K response rates were higher in those who received belimumab compared with those who received placebo, especially in patients with SLE who had high disease activity or renal manifestations at baseline. The safety profile of belimumab was generally consistent with that observed in previous SLE trials. Adverse events were the primary reasons for double-blind phase withdrawals (belimumab 5.4%, placebo 6.7%). CONCLUSION: The primary end point of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry.

Association of Lupus Nephritis Histopathologic Classification With Venous Thromboembolism-Modification by Age at Biopsy.

INTRODUCTION: Lupus nephritis (LN) is an independent risk factor for venous thromboembolism (VTE). The risk of VTE has not been analyzed by International Society of Nephrology/Renal Pathology Society or World Health Organization LN class. Study goals were to measure VTE incidence in an LN patient cohort, to evaluate associations between VTE and LN class, and to investigate factors modifying associations between VTE and LN class. METHODS: A retrospective analysis was performed using Glomerular Disease Collaborative Network data. Image-confirmed VTE was compared between patients with any LN class V lesion and patients with only LN class III or IV. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Effect modification was assessed between main effect and covariates. RESULTS: Our cohort consisted of 534 LN patients, 310 (58%) with class III/IV and 224 (42%) with class V with or without class III/IV, including 106 with class V alone. The VTE incidence was 62 of 534 (11.6%). The odds of VTE were not significantly different between patients with class III/IV and class V in adjusted analyses (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.45-1.48). An age interaction was observed (P = 0.009), with increased odds of VTE with class III/IV diagnosed at a younger age (2.75, 0.90-8.41 estimated at age 16 years) and decreased odds with class III/IV diagnosed at an older age (0.23, 0.07-0.72 estimated at age 46 years), compared to class V. CONCLUSIONS: The VTE incidence was similar among patients with LN classes III/IV and V, suggesting that VTE risk is not limited to class V-related nephrotic syndrome and that age may modulate LN class-specific VTE risk.

Pilot study of an internet-based pain coping skills training program for patients with systemic Lupus Erythematosus.

BACKGROUND: Patients with Systemic Lupus Erythematosus (SLE) often experience pain and other symptoms that negatively impact quality of life. Interventions that enhance the use of behavioral and cognitive coping strategies may lead to improved outcomes among patients with SLE. Pain coping skills training (PCST) programs have been shown to improve outcomes among patients with other rheumatic conditions, but there have been no trials of PCST among patients with SLE. This study was a preliminary assessment of the feasibility and efficacy of painTRAINER, an automated, internet-based PCST program, among patients with SLE. METHODS: Participants (n = 60) with SLE from one health care system were randomly assigned with equal allocation to painTRAINER or a wait list control group. PainTRAINER involves 8 modules; participants were instructed to complete one module weekly, along with practice activities for each cognitive or behavioral coping skill. Outcome measures were assessed at baseline and 9-week follow-up, including the Pain Catastrophizing Scale, PROMIS Subscales (Pain Interference, Physical Function, Sleep Disturbance, Anxiety, Depression, Fatigue and Participation), and the LupusPRO questionnaire. Mean changes in outcomes from baseline to follow up and Cohen's d effect sizes were computed. RESULTS: Effect sizes for the painTRAINER group (relative to the wait list group) were small, with changes being greatest for the PROMIS Depression score (d = - 0.32). Among those randomized to the painTRAINER group, 50% accessed the program ("painTRAINER users"). Most of those who did not access the program stated that they did not receive instructions via email. Effect sizes for "painTRAINER users" (relative to wait list) were larger than for the whole painTRAINER group: Pain Catastrophizing d = - 0.60, PROMIS Pain Interference d = - 0.3., PROMIS Depression d = - 0.44, LupusPRO Health-Related Quality of Life d = 0.30. CONCLUSIONS: PainTRAINER users reported meaningful improvements in multiple physical and psychological outcomes, supporting the potential of PCST programs to benefit individuals with SLE. However, strategies are needed to improve engagement with the program and tailor content to comprehensively address key SLE symptoms and challenges. TRIAL REGISTRATION: NCT03933839 , May 1, 2019.

Mortality and adverse events of special interest with intravenous belimumab for adults with active, autoantibody-positive systemic lupus erythematosus (BASE): a multicentre, double-blind, randomised, placebo-controlled, phase 4 trial.

BACKGROUND: Belimumab is approved for the treatment of active systemic lupus erythematosus (SLE). Although clinical trials showed a favourable benefit-risk profile, numerical differences in the incidence of mortality and adverse events of special interest (AESIs) have been reported. We assessed the frequency of these events in patients with SLE receiving belimumab or placebo plus standard therapy. METHODS: BASE was a double-blind, randomised, placebo-controlled, phase 4 trial done in 33 countries. Adults with active SLE were randomly assigned (1:1) to receive intravenous belimumab (10 mg/kg) or placebo, plus standard therapy, for 48 weeks. The primary endpoints were incidences of all-cause mortality and AESIs during the on-treatment period (first-to-last study drug dose + 28 days). Safety analyses were done in the as-treated population (patients grouped by actual treatment received >50% of the time). This study was registered with ClinicalTrials.gov (NCT01705977). FINDINGS: Between Nov 27, 2012, and July 28, 2017, we randomly assigned 4018 patients. The as-treated population included 2002 patients in the belimumab group versus 2001 in the placebo group. Ten (0·50%) patients in the belimumab group died versus eight (0·40%) in the placebo group (difference 0·10%, 95% CI -0·31 to 0·51). Incidences were similar in the belimumab and placebo groups for serious infections (75 [3·75%] of 2002 vs 82 [4·10%] of 2001; difference -0·35%, 95% CI -1·55 to 0·85), opportunistic infections and other infections of interest (36 [1·80%] vs 50 [2·50%]; -0·70%, -1·60 to 0·20), non-melanoma skin cancers (4 [0·20%] vs 3 [0·15%]; 0·05%, -0·21 to 0·31) and other malignancies (5 [0·25%] vs 5 [0·25%]; 0·00%, -0·31 to 0·31). A higher proportion of patients in the belimumab group than in the placebo group had infusion and hypersensitivity reactions (8 [0·40%] vs 2 [0·10%]; 0·30%, -0·01 to 0·61), serious depression (7 [0·35%] vs 1 [0·05%]; 0·30%, 0·02 to 0·58), treatment-emergent suicidality (28 [1·42%] of 1972 patients vs 23 [1·16%] of 1986; 0·26%, -0·44 to 0·96), and sponsor-adjudicated serious suicide or self-injury (15 [0·75%] of 1972 patients vs 5 [0·25%] of 1986; post hoc difference 0·50%, 0·06 to 0·94). INTERPRETATION: In line with previously published data, incidences of all-cause mortality and AESIs were similar in patients given belimumab and placebo, except for serious infusion or hypersensitivity reactions, serious depression, treatment-emergent suicidality, and sponsor-adjudicated serious suicide or self-injury events. FUNDING: GSK.

Rise and Fall: Hydroxychloroquine and COVID-19 Global Trends: Interest, Political Influence, and Potential Implications.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to rapid research and reporting on potential preventatives and treatments for the disease, including the drug hydroxychloroquine (HCQ). Despite a lack of robust evidence to support the use of HCQ for treatment of COVID-19, it was publicly endorsed and received widespread media coverage and public interest. The purpose of this report is to describe and contextualize the surges in public interest, demand, and adoption of HCQ for treatment of COVID-19 and outline implications for future public health policy and practice. METHODS: Using national and global events and Google Trends data as a measure of public interest, we describe the timeline and trends in the emergence of, interest in, and adoption of HCQ as a treatment of COVID-19. We additionally review reports on public demand for HCQ for treatment of COVID-19 and impacts on medication access among patients with indicated uses. RESULTS: Public interest and demand for HCQ surged in the United States and globally following endorsements from public officials and enaction of policies to facilitate off-label use of HCQ for treatment of COVID-19. Surges in demand for HCQ led to multiple documented shortages and barriers to accessing HCQ treatment for patients with indicated uses for HCQ. Although there have been reversals in policies to support HCQ use for treatment of COVID-19 in some regions, others have continued or expanded recommended uses. CONCLUSION: Insights from the global response to HCQ and COVID-19 can be used to inform prudent decision-making in the future to prevent premature action and promote informed and equitable responses to promote public health.

Quantification of citrullinated histones: Development of an improved assay to reliably quantify nucleosomal H3Cit in human plasma.

BACKGROUND: Recent data propose a diagnostic and prognostic capacity for citrullinated histone H3 (H3Cit), a marker of neutrophil extracellular traps (NETs), in pathologic conditions such as cancer and thrombosis. However, current research is hampered by lack of standardized assays. OBJECTIVES: We aimed to develop an assay to reliably quantify nucleosomal H3Cit in human plasma. METHODS: We assessed the common practice of in vitro enzymatically modified histone H3 as calibration standards and the specificity of available intrapeptidyl citrulline antibodies. Based on our findings, we developed and validated a novel assay to quantify nucleosomal H3Cit in human plasma. RESULTS: We show that enzymatically citrullinated H3 proteins are compromised by high enzyme-dependent lot variability as well as instability in plasma. We furthermore demonstrate that the majority of commercially available antibodies against intrapeptidyl citrulline display poor specificity for their reported target when tested against a panel of semi-synthetic nucleosomes containing distinct histone H3 citrullinations. Finally, we present a novel assay utilizing highly specific monoclonal antibodies and semi-synthetic nucleosomes containing citrulline in place of arginine at histone H3, arginine residues 2, 8, and 17 (H3R2,8,17Cit) as calibration standards. Rigorous validation of this assay shows its capacity to accurately and reliably quantify nucleosomal H3Cit levels in human plasma with clear elevations in cancer patients compared to healthy individuals. CONCLUSIONS: Our novel approach using defined nucleosome controls enables reliable quantification of H3Cit in human plasma. This assay will be broadly applicable to study the role of histone citrullination in disease and its utility as a biomarker.

Types of paraproteinemia in patients with multiple myeloma: A cross-sectional study.

OBJECTIVE: To determine the types of paraproteins in patients with multiple myeloma in a tertiary care setting. METHODS: The cross-sectional study was conducted at the Liaquat National Hospital, Karachi, from November 2015 to May 2016, and comprised patients with multiple myeloma selected using consecutive, non-probability sampling technique. Detailed history was taken and immunofixation assay was conducted to assess the type of paraproteins in the patients. Data was recorded on a proforma and analysed using SPSS 22. RESULTS: Of the 87 patients, 62(71.3%) were males and 25(28.7%) were females. The overall mean age was 57.41±10.53 years. Of the total, 52(71.3%), patients had Immunoglobulin G kappa and 61(70%) had Immunoglobulin A kappa paraprotein. CONCLUSIONS: The most common types of paraprotein was found to be Immunoglobulin G kappa followed by Immunoglobulin A kappa.

Association of Lupus Nephritis With Coronary Artery Disease by ISN/RPS Classification: Results From a Large Real-world Lupus Population.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at an increased risk for developing coronary artery disease (CAD). Several studies suggest that the presence of lupus nephritis (LN) is independently associated with CAD. The purpose of our study was to assess whether the presence of LN is independently associated with CAD in our patient population and whether this association varies by class of LN. METHODS: A retrospective cross-sectional analysis was performed using medical records of patients 18 years and older with SLE at University of North Carolina Hospitals from April 4, 2014, to December 31, 2017. Subjects were identified using International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, 10th Revision (ICD-10) codes specific for SLE. LN class was defined by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. CAD was the outcome of interest. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Our sample consisted of 3732 patients with SLE, of whom 598 (16%) had LN and 537 (14%) had CAD. When adjusting for demographics and factors associated with CAD and LN, the odds of having CAD were significantly higher for patients with SLE and LN compared with patients without LN (OR 1.47; 95% CI 1.07-2.02; P = 0.017). Controlling for these factors, class III LN (OR 1.98; 95% CI 0.95-4.12; P = 0.069) and class III/V LN (OR 2.23; 95% CI 1.09-4.62; P = 0.028) were very strongly associated with CAD in subjects with LN compared with subjects without LN. CONCLUSION: We confirm the observations of previous studies that LN is significantly associated with CAD. Our study is the first to show the association between CAD and specific classes of LN.