Kamen, Diane L.

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.

Abstract Objective The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus. Methods We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019–2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical personnel surveys to examine the perceived lupus PtDA appropriateness, acceptability, feasibility, success, and permanence, at 4 months, 12 months and 24 months post-PtDA implementation. Results Among the sites, the clinical personnels’ (n = 184) baseline ORIC commitment and efficacy scores (a 0–5 scale, higher = better) ranged from 3.5 to 4.2, and 3.4 to 4.4, respectively; the TLPSS scores (a 0–7 scale, higher = better) were 3.9–5.5 for internal learning, 3.7–5.6 for external learning, and 4.3–5.5 for psychological safety. The penetration (primary outcome) among 15 geographically diverse US rheumatology clinics ranged from 3% to 44%. We found that the total number of providers in the clinic was positively associated with higher penetration. Clinical personnel–perceived lupus PtDA outcomes were optimal at 4 months (all scale scores ranged from 1 to 5, higher = better): (i) appropriateness, 3.43 (s.d. 0.86); (ii) acceptability, 3.53 (s.d. 0.83); (iii) feasibility, 3.44 (s.d. 0.71); (iv) success, 3.41 (s.d. 0.73); and (v) permanence, 3.22 (s.d. 0.74). Conclusion We implemented a lupus PtDA with varied success rates during the COVID pandemic; more providers were associated with higher clinic penetration. Clinical personnel perceived high lupus PtDA appropriateness, acceptability, feasibility, success, and permanence that persisted up to 24 months. Trial Registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03735238.

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.

ObjectiveSystemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE.MethodsPreviously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow‐up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE‐specific portion of the Connective Tissue Disease Screening Questionnaire (SLE‐CSQ). Serum and plasma samples were tested for the presence of lupus‐associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition.ResultsOf the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow‐up (mean time to follow‐up 6.4 years). Relatives who transitioned to SLE displayed more lupus‐associated autoantibody specificities and higher SLE‐CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow‐up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon‐associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin‐10 (P ≤ 0.03). GEE analyses revealed that baseline SLE‐CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03).ConclusionPreclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high‐risk relatives for rheumatology referral and potential enrollment in prevention trials.

Objective Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end‐stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene ( APOL1 ) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk. Methods APOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN‐ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression. Results Ninety percent of the SLE patients were female. The mean ± SD age at SLE diagnosis was significantly lower in LN‐ESRD cases than in SLE non‐nephropathy controls (27.3 ± 10.9 years versus 39.5 ± 12.2 years). The mean ± SD time from SLE diagnosis to development of LN‐ESRD in cases was 7.3 ± 7.2 years. The G1/G2 risk alleles were strongly associated with SLE‐ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 × 10 −9 ), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 × 10 −6 ). The age‐, sex‐, and admixture‐adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was ∼2 years earlier among individuals with APOL1 risk genotypes ( P = 0.01). Conclusion APOL1 G1/G2 alleles strongly impact the risk of LN‐ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN‐ESRD in African Americans.