Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Assessment and personalised advice for fatigue in systemic lupus erythematosus using an innovative digital tool: the Lupus Expert system for the Assessment of Fatigue (LEAF) study.

BACKGROUND: Fatigue is reported as the most prevalent symptom by patients with systemic lupus erythematosus (SLE). Fatigue management is complex due to its multifactorial nature. The aim of the study was to assess the usefulness of an innovative digital tool to manage fatigue in SLE, in a completely automated manner. METHODS: The «Lupus Expert System for Assessment of Fatigue¼ (LEAF) is free digital tool which measures the intensity and characteristics of fatigue and assesses disease activity, pain, insomnia, anxiety, depression, stress, fibromyalgia and physical activity using validated patient-reported instruments. Then, LEAF automatically provides personalised feedback and recommendations to cope with fatigue. RESULTS: Between May and November 2022, 1250 participants with SLE were included (95.2% women, median age 43yo (IQR: 34-51)). Significant fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue <34) was reported by 78.9% of patients. In univariate analysis, SLE participants with fatigue were more likely to be women (p=0.01), perceived their disease as more active (p<0.0001), had higher levels of pain (p<0.0001), anxiety (p<0.0001), depression (p<0.0001), insomnia (p<0.0001), stress (p<0.0001) and were more likely to screen for fibromyalgia (p<0.0001), compared with patients without significant fatigue. In multivariable analysis, parameters independently associated with fatigue were insomnia (p=0.0003), pain (p=0.002), fibromyalgia (p=0.008), self-reported active SLE (p=0.02) and stress (p=0.045). 93.2% of the participants found LEAF helpful and 92.3% would recommend it to another patient with SLE. CONCLUSION: Fatigue is commonly severe in SLE, and associated with insomnia, pain, fibromyalgia and active disease according to patients' perspective. Our study shows the usefulness of an automated digital tool to manage fatigue in SLE.

Pan American League of Associations for Rheumatology Guidelines for the Treatment of Takayasu Arteritis.

OBJECTIVE: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK). METHODS: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members. RESULTS: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible. CONCLUSION: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.

A better self-efficacy is predictive of better health-related quality of life (HRQoL) in patients with systemic lupus erythematosus: data from the Almenara Lupus Cohort.

OBJECTIVE: To determine the possible predictive value of self-efficacy on health-related quality of life (HRQoL) in patients with SLE. METHODS: Patients with SLE from the Almenara Lupus Cohort were included. Self-efficacy was ascertained with the six domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) self-efficacy for managing chronic conditions. For PROMIS domains, a score of 50 is the average for a clinical population (people with a chronic condition), a higher score indicates that the respondent has greater self-efficacy. HRQoL was ascertained with the physical and mental component summary (PCS and MCS) measures of the Short-Form 36 (SF-36). Generalised estimating equations were performed, using as outcome the PCS or MCS in the subsequent visit, and the self-efficacy domain in the previous visit; multivariable models were adjusted for possible confounders. The confounders were measured in the same visit as the self-efficacy domain. RESULTS: Two-hundred and nine patients for a total of 564 visits were included; 194 (92.8%) patients were women and mean age at diagnosis was 36.4 (14.0) years. In the multivariable models, a better PCS was predicted by a better self-efficacy for managing symptoms, managing medications and treatments and managing social interactions and general self-efficacy; a better MCS was predicted by a better self-efficacy for managing daily activities, managing symptoms, managing medications and treatments and managing social interactions. CONCLUSION: A better self-efficacy is predictive of subsequent better HRQoL, even after adjustment for possible confounders. These results should encourage clinicians to develop strategies to improve self-efficacy in patients with SLE.

Pan American League of Associations for Rheumatology Guidelines for the treatment of ANCA-associated vasculitis.

Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted. For these reasons, the Pan American League of Associations for Rheumatology developed the first ANCA-associated vasculitis treatment guidelines tailored for Latin America. A panel of local vasculitis experts generated clinically meaningful questions related to the treatment of ANCA-associated vasculitis using the Population, Intervention, Comparator, and Outcome (PICO) format. Following the Grading of Recommendations Assessment, Development, and Evaluation methodology, a team of methodologists conducted a systematic literature review. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members. 21 recommendations and two expert opinion statements for the treatment of ANCA-associated vasculitis were developed, considering the current evidence and the socioeconomic characteristics of the region. These recommendations include guidance for the use of glucocorticoids, non-glucocorticoid immunosuppressants, and plasma exchange.

Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVE: To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. METHODS: Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. RESULTS: There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). CONCLUSIONS: Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.

Severe flares are associated with a poorer health-related quality of life (HRQoL) in patients with SLE: data from the Almenara Lupus Cohort.

BACKGROUND: Flares in patients with SLE, regardless of their severity, have been associated with damage accrual. However, their impact on health-related quality of life (HRQoL) has not been fully evaluated. In fact, disease activity is only minimally associated with HRQoL. OBJECTIVE: To determine the association between flares and HRQoL. METHODS: Patients from the Almenara Lupus Cohort were included. Visits occurring between December 2015 and February 2020 were evaluated. Flares were defined as an increase on the SLE Disease Activity Index 2000 (SLEDAI-2K) of at least 4 points; severe flares were those with a final SLEDAI-2K ≥12 and mild-moderate flares all the others. HRQoL was measured using the LupusQoL. Univariable and multivariable generalised estimating regression equations were performed, adjusting for possible confounders. Confounders were determined at one visit, whereas the outcome was determined on the subsequent visit; flares were determined based on the variation of the SLEDAI-2K between these visits. RESULTS: Two hundred and seventy-seven patients were included; 256 (92.4%) were female, mean age at diagnosis was 36.0 (SD: 13.3) years and mean disease duration at baseline was 9.1 (SD: 7.1) years. Patients had mean of 4.8 (SD: 1.9) visits and a mean follow-up of 2.7 (1.1) years. Out of 1098 visits, 115 (10.5%) flares were defined, 17 were severe and 98 mild-moderate. After adjustment for possible confounders, only severe flares were associated with a poorer HRQoL in planning, pain, emotional health and fatigue. CONCLUSIONS: Severe flares, but not mild-moderate, flares are associated with poorer HRQoL.

LLDAS (lupus low disease activity state) and/or remission are associated with less damage accrual in patients with systemic lupus erythematosus from a primarily Mestizo population: data from the Almenara Lupus Cohort.

OBJECTIVE: To determine if achieving lupus low disease activity state (LLDAS) or remission prevents damage accrual in a primarily Mestizo population. METHODS: Patients with SLE from a single-centre cohort with at least two visits occurring every 6 months were included. The definitions used were the following: for remission, the 2021 Definition Of Remission In SLE; and for LLDAS, the Asia Pacific Lupus Collaboration. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and three multivariable interval-censored survival regression models were done: (1) remission versus not on remission; (2) LLDAS/remission versus active; and (3) remission and LLDAS (not on remission) versus active. Three similar multivariable models were also examined considering the duration on each state. Possible confounders included in these analyses were gender, age at diagnosis, socioeconomic status, educational level, disease duration, antimalarial use and SDI at baseline. RESULTS: Two hundred and eighty-one patients were included. Eighty-three patients (29.5%) showed increased SDI during the follow-up. In the analyses of remission, being on remission predicted a lower probability of damage (HR=0.456; 95% CI 0.256 to 0.826; p=0.010). In the analyses of LLDAS/remission, being on LLDAS/remission predicted a lower damage (HR=0.503; 95% CI 0.260 to 0.975; p=0.042). When both states were considered, remission but not LLDAS (not on remission) predicted a lower probability of damage (HR=0.423; 95% CI 0.212 to 0.846; p=0.015 and HR=0.878; 95% CI 0.369 to 2.087; p=0.768, respectively). When the duration of these states was taken into account, remission, LLDAS/remission and LLDAS not on remission were associated with a lower probability of damage accrual. CONCLUSIONS: LLDAS and/or remission were associated with a lower probability of damage accrual.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Factores asociados a infecciones serias en pacientes hospitalizados con lupus eritematoso sistémico / Factors associated with serious infections in patients hospitalized with systemic lupus erythematosus

RESUMEN Introducción. En pacientes con lupus eritematoso sistémico (LES) existe incremento de infecciones debido a la propia enfermedad, al uso de inmunosupresores y corticoides. Objetivo. Identificar los factores asociados a infecciones serias en pacientes lúpicos en un hospital de referencia nacional. Estudio retrospectivo, analítico, de casos y controles en el Servicio de Reumatología del Hospital Nacional Guillermo Almenara Irigoyen, Lima, Perú. Métodos. Se analizó el registro de pacientes hospitalizados en el periodo de estudio, los casos fueron pacientes en los que se demostró la etiología de la primera infección durante su hospitalización. Los controles fueron pacientes lúpicos hospitalizados sin infecciones en el mismo periodo de estudio. Se analizaron variables asociadas al desarrollo de infecciones. Resultados. 61 pacientes de 390 hospitalizados desarrollaron infecciones durante su hospitalización. 48 desarrollaron 1 solo evento infeccioso (en 40 se demostró etiología). Los casos tuvieron mayor actividad, daño y comorbilidad en comparación con los controles. En el análisis univariado, el salario (p=0,031), el uso de inmunosupresores a la admisión (previo: p=0,004 y actual: p=0,004), el uso de glucocorticoides (<30 días: p=0,015 y >30-360 días: p=0,028), la actividad (p=0,029) y el daño (p=0,026) producido por la enfermedad, y el tiempo de hospitalización (p=0,045) tuvieron asociación estadísticamente significativa. En el análisis multivariado, los días de hospitalización se asociaron al desarrollo de infecciones. Conclusiones. Existió asociación entre días de hospitalización y el desarrollo de infecciones serias en pacientes lúpicos durante el periodo de estudio.

ABSTRACT Introduction. Lupus patients have an increased risk of developing infections due to the disease, use of immunosuppressants and corticosteroids. Objective. To identify the associated factors for serious infections in lupus patients in a national referral hospital. Retrospective, analytical, case-control study in the Rheumatology Service of the Guillermo Almenara Irigoyen National Hospital, Lima, Peru. Methods. The registry of hospitalized patients in the study period was analyzed, the cases were patients in whom the etiology of the first infection developed their hospitalization. Controls were hospitalized lupus patients without infections in the same study period. Variables predisposing to the development of infections were analyzed. Results. 61 patients out of 390 hospitalized developed infections during their hospitalization. 48 developed 1 only infectious event (in 40 an etiology developed). The cases had higher damage, activity and comorbidity compared to the controls. In the univariate analysis, salary (p = 0.031), use of immunosuppressants upon admission (previous: p = 0.004 and current: p = 0.004), use of glucocorticoids (<30 days: p = 0.015 and> 30-360 days: p = 0.028), activity (p = 0.029) and damage (p = 0.026) produced by the disease and length of hospitalization (p = 0.045), had a statistically significant association. In the multivariate analysis, the days of hospitalization were associated with the development of infections. Conclusions. There is an association between days of hospitalization and the development of serious infections in lupus patients in the study period.

Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies.

OBJECTIVE: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. METHODS: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. RESULTS: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. CONCLUSIONS: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.

Guía de práctica clínica para el tratamiento farmacológico inicial de nefritis lúpica en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the initial pharmacological treatment of lupus nephritis in the Peruvian Social Security (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el tratamiento farmacológico inicial nefritis lúpica en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para tratamiento farmacológico inicial de adultos con nefritis lúpica clase I a V no refractarios en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios en PubMed durante el 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. Se evaluó la certeza de evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos antes de su aprobación. Resultados: La GPC abordó 6 preguntas clínicas, divididas en 2 temas: tratamiento inicial de la fase de inducción y mantenimiento. En base a dichas preguntas se formularon 11 recomendaciones (todas condicionales), 22 puntos de buena práctica clínica, y 2 flujogramas. Conclusión: Se emitieron recomendaciones basadas en evidencia para el manejo de pacientes con esta patología.

Introduction: This article summarizes the clinical practice guideline (CPG) for initial pharmacological treatment of lupus nephritis in the Peruvian Social Security (EsSalud). Objective: To provide evidence-based clinical recommendations for initial pharmacological treatment of adults with non-refractory class I to V lupus nephritis in EsSalud. Material and Methods: A guideline development group (GDG) was formed that included medical specialists and methodologists, which formulated clinical questions. Systematic searches of systematic reviews and -when considered pertinent- primary studies were performed in PubMed during 2021. Evidence was selected to answer each of the clinical questions posed. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before approval. Results: The CPG addressed 6 clinical questions, divided into 2 topics: initial treatment of the induction phase and maintenance. Based on these questions, 11 recommendations (all conditional), 22 points of good clinical practice, and 2 flowcharts were formulated. Conclusion: Evidence-based recommendations were issued for the management of patients with this pathology.

2021 DORIS definition of remission in SLE: final recommendations from an international task force.

OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.

Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: a systematic literature review.

BACKGROUND: Remission and low disease activity (LDA) have been proposed as the treatment goals for patients with systemic lupus erythematosus (SLE). Several definitions for each have been proposed in the literature. OBJECTIVE: To assess the impact of remission/LDA according to various definitions on relevant outcomes in patients with SLE. METHODS: This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using PubMed (1946-week 2, April 2021), Cochrane library (1985-week 2, week 2, April 2021) and EMBASE (1974-week 2, April 2021). We included longitudinal and cross-sectional studies in patients with SLE reporting the impact of remission and LDA (regardless their definition) on mortality, damage accrual, flares, health-related quality of life and other outcomes (cardiovascular risk, hospitalisation and direct costs). The quality of evidence was evaluated using the Newcastle-Ottawa Scale. RESULTS: We identified 7497 articles; of them, 31 studies met the inclusion criteria and were evaluated. Some articles reported a positive association with survival, although this was not confirmed in all of them. Organ damage accrual was the most frequently reported outcome, and remission and LDA were reported as protective of this outcome (risk measures varying from 0.04 to 0.95 depending on the definition). Similarly, both states were associated with a lower probability of SLE flares, hospitalisations and a better health-related quality of life, in particular the physical domain. CONCLUSION: Remission and LDA are associated with improvement in multiple outcomes in patients with SLE, thus reinforcing their relevance in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020162724.

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. CONCLUSION: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

Understanding Risk Factors for Poor Outcomes in a Multiethnic Longitudinal Cohort: The LUMINA (Lupus in Minorities: Nature vs. Nurture) Experience (LUMINA LXXXII).

The Lupus in Minorities: Nature Vs Nurture (LUMINA) cohort has placed Hispanics on the lupus map in the United States. Texan Hispanic and African American patients experience, overall, worse outcomes than the Caucasian and Puerto Rican Hispanic patients. The genetic component of ethnicity is important early in the disease course whereas socioeconomic factors become more important subsequently. The role of hydroxychloroquine in preventing damage accrual and reducing mortality in lupus patients is a major contribution of LUMINA.

Design of an algorithm for the diagnostic approach of patients with joint pain.

BACKGROUND: Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. OBJECTIVE: To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. METHODS: Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point "joint pain" as a common symptom for the four diseases. RESULTS: Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. CONCLUSION: We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain. Key Points • We developed an algorithm with the participation of rheumatologists from 18 countries of Ibero-America, which gives a global vision of the clinical context of the patient with joint pain. • We integrated four rheumatic diseases into one tool with one common symptom: joint pain. It is a novel tool, as it is the first algorithm that will support the primary care physician in the consideration of four different rheumatic diseases. • It will improve the correct diagnosis and reduce the number of paraclinical tests requested by primary care physicians, in the management of patients with joint pain. This point was verified in a recently published study in the journal Rheumatology International (reference number 31).

Systemic lupus erythematosus: The search for the ideal biomarker.

During the last decades, there has been an increased interest in the discovery and validation of biomarkers that reliably reflect specific aspects of lupus. Although many biomarkers have been developed, few of them have been validated and used in clinical practice, but with unsatisfactory performances. Thus, there is still a need to rigorously validate many of these novel promising biomarkers in large-scale longitudinal studies and also identify better biomarkers not only for lupus diagnosis but also for monitoring and predicting upcoming flares and response to treatment. Besides serological biomarkers, urinary and cerebrospinal fluid biomarkers have emerged for assessing both renal and central nervous system involvement in systemic lupus erythematosus, respectively. Also, novel omics techniques help us to understand the molecular basis of the disease and also allow the identification of novel biomarkers which may be potentially useful for guiding new therapeutic targets.