Citations

Objective Despite the reported clinical significance of anti-C1q immunoglobulin G autoantibodies (anti-C1q) for SLE and the development of anti-C1q commercial kits, their performance characteristics in routine patient evaluation remain poorly defined. Methods In this cross-sectional study, an unselected cohort of 107 patients with suspicion of a systemic autoimmune disease and 102 controls were included and evaluated for anti-C1q autoantibodies with three kits (Bühlmann, Orgentec and Werfen). Patients in the unselected cohort were classified as having SLE or a mimicker condition. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K and SLE patients were subclassified based on the presence of lupus nephritis (LN) (history/active). Each kit was assessed for diagnostic performance. The degree of association between anti-C1q and SLEDAI/complement levels was assessed using the Spearman correlation coefficient (rho). Between-kit agreement was evaluated using Fleiss Ƙ. Results Werfen had the best performance in discriminating patients with SLE from non-SLE (area under the curve (AUC)=0.76), whereas for the SLE versus mimicker comparison Bühlmann (AUC=0.71) and Werfen (AUC=0.71) exhibited adequate discrimination. Among patients with SLE, all kits exhibited poor discrimination of patients with history of LN versus non-renal SLE, but Orgentec displayed good discrimination for patients with active LN from non-active LN (AUC=0.74). A positive correlation was observed between anti-C1q and SLEDAI scores, whereas a negative correlation was found between anti-C1q and complement C3 and C4 across all kits. Agreement for SLE between the three kits was moderate (Ƙ=0.42). Conclusion Anti-C1q can identify patients with SLE and correlate with global and renal disease activity, highlighting their potential to function as follow-up markers in SLE. Agreement with commercial anti-C1q kits is variable. Further studies are required to harmonise anti-C1q kits for optimal routine patient evaluation.

Objective Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological diagnosis that can be associated with SLE. The clinical presentation, risk factors and outcomes of PRES in patients with SLE remain insufficiently described. Methods We conducted a multicentre cohort study at the Mayo Clinic and performed a systematic literature review (SLR) of patients with incident PRES and SLE. We described the clinical features, treatments and outcomes. Across both the cohort study and SLR, we assessed neurological sequelae, recurrence and survival. Within the cohort study, we examined PRES risk factors and discontinuation of antiseizure medications (ASMs). We used logistic regression to evaluate factors associated with neurological sequelae and Cox regression to assess predictors of recurrence. Kaplan-Meier methods estimated the rates of recurrence, survival and ASMs discontinuation. Results 550 cases (53 from the cohort study) were included, of whom 92% were female. Across both cohort and SLR, the most common symptom was seizure, occurring in 80%. PRES was the first manifestation of SLE in 13% of cases. In the adjusted analysis, older age was associated with neurological sequelae (OR 1.63 per 10-year increase; 95% CI 1.12 to 2.39). After 5 years of follow-up, 11.5% (95% CI 2.3 to 19.9%) of patients had a recurrent PRES episode. 30-day and 180-day survival following PRES was observed in 96.3% (95% CI 93.5 to 99.1%) and 93.7% (95% CI 89.8 to 97.7%) patients, respectively. In the Mayo Clinic cohort, 81% of PRES cases were attributed to hypertension in the context of lupus nephritis (LN), and by the fifth year of follow-up, 78.1% (95% CI 58.7 to 88.4%) of patients had discontinued ASMs. Conclusions In this cohort, most of the incident PRES episodes were preceded by hypertension and occurred in patients with LN. Although short-term and long-term prognoses are favourable, older patients more frequently experienced neurological sequelae.

Objective To assess the impact of renal replacement therapy in people with lupus nephritis (LN)–associated end‐stage kidney disease (ESKD) and support the development of the 2024 American College of Rheumatology LN treatment guidelines. Methods We conducted a systematic literature review and meta‐analysis to address three Population, Intervention, Comparison, and Outcome (PICO) questions related to renal replacement therapy for ESKD due to LN, including comparisons of kidney transplant versus dialysis, hemodialysis versus peritoneal dialysis, and preemptive kidney transplant versus no preemptive kidney transplant. Outcomes of interest included mortality, cardiovascular (CV) events, infections, lupus flares, disease‐related damage, graft failure, and quality of life. We conducted a meta‐analysis and analyzed hazard ratios for time‐to‐event analyses and risk ratios for dichotomous outcomes, as well as absolute risk estimates. Results Sixteen comparative observational studies addressed at least one of the three PICO questions. Kidney transplant was found to reduce the risks of all‐cause mortality, CV mortality, infection‐related mortality, and CV events compared with dialysis (high certainty). Dialysis modality (peritoneal vs hemodialysis) was not associated with mortality (high certainty) or with other outcomes of infection, CV complications, and systemic lupus erythematosus flares (low certainty). Preemptive kidney transplant was associated with lower risks of graft failure and mortality (low certainty). Conclusion This systematic review identified improved outcomes with kidney transplant versus dialysis for people with LN‐associated ESKD and potential benefits of preemptive kidney transplant. This evidence supports the use of kidney transplant as a preferred renal replacement therapy for people with LN‐ESKD.

Objective To provide evidence‐based and expert guidance for the treatment and management of non‐renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline. Methods Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present recommendations and ungraded, consensus‐based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE‐related morbidity and mortality, and minimize medication‐related toxicities. Conclusion This guideline presents direction regarding treatment and management of SLE and provides a foundation for well‐informed, shared clinician–patient decision‐making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.

Objective To provide evidence‐based and expert guidance for the treatment and management of non‐renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline. Methods Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present recommendations and ungraded, consensus‐based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE‐related morbidity and mortality, and minimize medication‐related toxicities. Conclusion This guideline presents direction regarding treatment and management of SLE and provides a foundation for well‐informed, shared clinician–patient decision‐making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.

ObjectiveThe objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis.MethodsThe Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation.ResultsWe present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response.ConclusionThis guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

Objective The objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis. Methods The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response. Conclusion This guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

Objective The 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria score (≥20 points) has been associated with poor outcomes. We aimed to evaluate its utility as a predictor for mortality and hospitalisation and to derive and validate an ominosity score based on the SLE classification criteria set. Methods Incident patients with SLE in a population-based cohort were included. The association between the 2019 EULAR/ACR SLE score and mortality and hospitalisation was assessed using Cox regression adjusted for age, sex and calendar year. An ominosity score for mortality was developed based on the SLE criteria set. The least absolute shrinkage and selection operator method was used to estimate model coefficients. Concordance and calibration were assessed by cross-validation and by plotting the observed event rates against the deciles of predicted probabilities. Results Among 374 patients with incident SLE, a EULAR/ACR score ≥20 points was not associated with an increased risk of mortality (HR 1.17, 95% CI 0.67 to 2.03) or first hospitalisation (HR 1.14, 95% CI 0.79 to 1.64) compared with a score ≤19 points. The derived ominosity score for mortality included age, sex, thrombocytopaenia, neuropsychiatric manifestations, subacute cutaneous or discoid lupus, non-scarring alopecia, inflammatory arthritis, renal involvement, antiphospholipid antibodies and hypocomplementaemia. This model demonstrated a concordance=0.76 with adequate calibration. Age and sex were the main predictors, as seen in the model including just age, sex and year (concordance=0.77). Conclusion The 2019 EULAR/ACR SLE criteria score was not associated with mortality and hospitalisation. The derived ominosity score for mortality presented good prediction for mortality but was not better than age and sex alone.

ObjectiveWe aimed to characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE‐specialized care.MethodsWe included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE‐specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays.ResultsThe study included 373 patients with SLE. The median time to access SLE‐specialized care was 1.1 (95% confidence interval [CI] 0.9–1.5) months, time to diagnosis was 30.6 (95% CI 18.9–48.1) months, and time to treatment initiation was 4.7 (95% CI 3.9–8.4) months. Approximately 25% of patients (93 out of 373) experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE‐related encounter (fewer than two SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, whereas hematologic (odds ratio [OR] 1.71, 95% CI 1.03–2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46–14.88) were associated with delays. Delays were associated with damage at first access to SLE‐specialized care (SDI ≥1; 30% vs 7%, P < 0.001).ConclusionPatients follow a heterogeneous pathway to receive care. One‐fourth of patients experienced delays accessing SLE‐specialized care, which was associated with disease‐related damage. Fewer manifestations, hematologic manifestations, or antiphospholipid antibodies were associated with delays.image