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

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

The impact of rural residency on the expression and outcome of systemic lupus erythematosus: data from a multiethnic Latin American cohort

Objective: The objective of this paper is to examine the role of place of residency in the expression and outcomes of systemic lupus erythematosus (SLE) in a multi-ethnic Latin American cohort. Patients and methods: SLE patients (<two years of diagnosis) from 34 centers constitute this cohort. Residency was dichotomized into rural and urban, cut-off: 10,000 inhabitants. Socio-demographic, clinical/laboratory and mortality rates were compared between them using descriptive tests. The influence of place of residency on disease activity at diagnosis and renal disease was examined by multivariable regression analyses. Results: Of 1426 patients, 122 (8.6%) were rural residents. Their median ages (onset, diagnosis) were 23.5 and 25.5 years; 85 (69.7%) patients were Mestizos, 28 (22.9%) Caucasians and 9 (7.4%) were African-Latin Americans. Rural residents were more frequently younger at diagnosis, Mestizo and uninsured; they also had fewer years of education and lower socioeconomic status, exhibited hypertension and renal disease more frequently, and had higher levels of disease activity at diagnosis; they used methotrexate, cyclophosphamide pulses and hemodialysis more frequently than urban patients. Disease activity over time, renal damage, overall damage and the proportion of deceased patients were comparable in rural and urban patients. In multivariable analyses, rural residency was associated with high levels of disease activity at diagnosis (OR 1.65, 95% CI 1.06-2.57) and renal disease occurrence (OR 1.77, 95% CI 1.00-3.11). Conclusions: Rural residency associates with Mestizo ethnicity, lower socioeconomic status and renal disease occurrence. It also plays a role in disease activity at diagnosis and kidney involvement but not on the other end-points examined. Lupus (2012) 21, 1397-1404.211313971404Federico Wilhelm Agricola Foundation ResearchNational Institute of Arthritis and Musculoskeletal and Skin Diseases [P01 AR49084]STELLAR (Supporting Training Efforts in Lupus for Latin American Rheumatologists) ProgramRheuminations Inc.Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS)-Beca de Formacio i Contractacio de Personal InvestigadorNational Institute of Arthritis and Musculoskeletal and Skin Diseases [P01 AR49084

Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus.

The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: Data from a Latin American cohort

Objectives The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. Methods Systemic lupus erythematosus (SLE) patients (n=1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. Results Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (+/- SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p=0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR 3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50-0.99). Conclusions Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.229899907Federico Wilhelm Agricola Foundation Research (BAPE)National Institute of Arthritis and Musculoskeletal and Skin Diseases [P01 AR49084]STELLAR (Supporting Training Efforts in Lupus for Latin American Rheumatologists) ProgramRheuminations IncInstitut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS)-Beca de Formacio i Contractacio de Personal Investigador (GPE)FONDECYT [1110395]National Institute of Arthritis and Musculoskeletal and Skin Diseases [P01 AR49084]FONDECYT [1110395