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.

Finding the Role of Anifrolumab in the New Paradigm of Systemic Lupus Erythematosus Treatment.

The article by Tani et al, "Anifrolumab in Refractory Systemic Lupus Erythematosus: A Real-World, Multicenter Study,"1 evaluates the efficacy of anifrolumab (ANI) in patients with systemic lupus erythematosus (SLE) who failed to respond to other treatments, including biologics.There are many unmet needs in the treatment of SLE. Despite recent advances, remission and low disease activity (LDA) rates remain suboptimal; therefore, some patients with SLE are at high risk of developing endstage renal disease, organ damage, drug-related toxicities-particularly related to the prolonged use of glucocorticoids (GCs)-and premature mortality.2-4.

A 12-month follow-up study of patients with systemic lupus erythematosus after immunization against SARS-CoV-2.

OBJECTIVE: To identify all post-BNT162b2 vaccination (BioNTech and Pfizer) events during the ensuing 12 months in patients with systemic lupus erythematosus (SLE) from the Immuno-Rheumatology Department at Cayetano Heredia Hospital's cohort, Lima, Perú. METHODS: A 12-month follow-up study was conducted from the first dose of immunization with the BNT162b2 vaccine, which was given between May and June 2021, to SLE patients from this cohort. RESULTS: The initial population was constituted by 100 patients (100 patients received the 1st dose, 90 the 2nd dose, and 85 the 3rd dose of this vaccine); 33 patients presented a SLE reactivation (flare), 9% (9/100) post 1st dose, 26.6% (24/90) post 2nd dose, and 16.4% (14/85) post 3rd dose. The most common types of flare were articular (26) and renal (14) with 5/33 (15.1%) requiring hospitalization for flare management. A negative association with flare occurrence was found between the use of hydroxychloroquine RR 0.43 (0.21-0.85) and the opposite was the case for azathioprine RR 2.70 (1.39-5.25). During follow-up, 26 patients developed SARS-CoV-2 infection of whom three required hospitalization, one of whom died. CONCLUSIONS: 33 of 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, presented SLE flares (47 episodes in total); 5 of these patients required in-hospital management and all fully recovered; 26 patients had SARS-CoV-2 infection; three required hospitalization, one died.

Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Predictors of first hospitalization due to disease activity and infections in systemic lupus erythematosus patients.

OBJECTIVES: To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS: The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS: 1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS: The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.

Unveiling the Link Between Antiphospholipid Antibodies and Cognitive Dysfunction in the Almenara Lupus Cohort.

OBJECTIVE: Cognitive dysfunction is a prevalent manifestation of systemic lupus erythematosus (SLE). There is evidence for the role of antiphospholipid (aPL) antibodies on its etiopathogenesis. Our objective was to identify the association between aPL antibodies and cognitive dysfunction in SLE patients. METHODS: This cross-sectional study included 135 patients evaluated from March 2015 to October 2017 at one center. Cognitive deficit was measured using the NEUROPSI test. Disease activity and damage were ascertained using the SLEDAI-2K (SLE Disease Activity Index 2000) and the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), respectively; aPL antibodies were measured by enzyme-linked immunosorbent assay. The association between cognitive dysfunction and aPL antibodies was evaluated using univariable and multivariable linear regression models adjusted for age, sex, education, socioeconomic status, disease duration, SLEDAI-2K, SDI, mean current dose of prednisone, time of exposure to glucocorticoids, and drug use (immunosuppressants, hydroxychloroquine, aspirin, and warfarin). RESULTS: One hundred thirty-one patients (97.1%) were women; their mean (SD) age was 46.6 (12.5) years; 59 patients (43.7%) had positivity for at least 1 aPL antibody. IgM anticardiolipin (aCL) was positive in 24.5%, IgG in 13.5%, IgM aß2GP1 in 16.8%, IgG anti-ß2 glycoprotein in 24.6%, and the lupus anticoagulant in 5.3%. Ninety patients (66.7%) had some cognitive dysfunction. In the univariable analysis, a significant correlation between the NEUROPSI score and IgM aCL antibodies was found (B = -20.87 [SE, 3.2]; p < 0.001), which remained significant in the multivariable model (B = -13.89 [SE, 3.14]; p < 0.001). CONCLUSIONS: IgM aCL antibodies are associated with cognitive dysfunction in patients with SLE. Larger and longitudinal studies are needed to assess the impact of these findings.

The Lupus Foundation of America-Rapid Evaluation of Activity in Lupus Clinician-Reported Outcome Predicts Damage in Patients With Systemic Lupus Erythematosus. Data From the Almenara Lupus Cohort.

OBJECTIVE: To evaluate the predictive value of the LFA-REAL ClinRO (Lupus Foundation of America Rapid Evaluation of Activity in Lupus clinician-reported outcome) on damage accrual in systemic lupus erythematosus patients. METHODS: Data from a prevalent lupus cohort were used. The LFA-REAL ClinRO includes 9 domains: mucocutaneous (global and 3 subdomains), musculoskeletal (global and 2 subdomains), cardiorespiratory, neuropsychiatric, renal, hematological, constitutional, vasculitis, and other (it allows for other or rare manifestations). For each domain, a 0- to 100-mm visual analog scale is used, and global domains are included except for the mucocutaneous and musculoskeletal domains where the subdomains are included; it allows for 3 manifestations under "other," so the score ranges from 0 to 1400 (sum of 14 in the visual analog scale). Damage was assessed with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index. Generalized estimating equations were performed, being the outcome the increase in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index; confounders from the previous visit were included; adjusted multivariable models were done. Incidence rate ratios per 10-unit increase in the LFA-REAL ClinRO were reported. Similar models were performed to evaluate the impact of the SLEDAI-2K (SLE Disease Activity Index) and physician global assessment on damage to determine which measure would better predict damage accrual. RESULTS: Three-hundred thirty-one patients and 1425 visits were included, 1.9 (SD 1.2) years of follow-up. Disease duration at baseline was 10.7 (7.4) years. The mean LFA-REAL ClinRO was 18.2 (SD 30.7). During the follow-up visits, 63 (17.9%) patients accrued damage once; 4 (1.1%) accrued damage twice. The LFA-REAL ClinRO was predictive of damage accrual even after adjustment for possible confounders (incidence rate ratio 1.10 (95% confidence interval 1.04-1.16; p < 0.001). Similar results were obtained using the SLEDAI-2K and the physician global assessment. CONCLUSION: The LFA-REAL ClinRO is predictive of damage accrual, even after adjusting for possible confounders.

Rituximab as Treatment for Lupus Nephritis: Data From the Peruvian ALMENARA Lupus Cohort.

OBJECTIVE: The aim of this study was to evaluate the response to rituximab (RTX) as treatment for lupus nephritis (LN) in a Latin American Lupus cohort. METHODS: The medical records from LN patients from a single-center cohort spanning between January 2012 and December 2020 were reviewed. Demographic factors (age at diagnosis and baseline, gender), disease duration, previous and concomitant treatments, serum creatinine, and 24-hour proteinuria (24-HP) levels at baseline, and 6th and 12th months were obtained. Complete response (CR) or responder status was defined according to the LUNAR, AURORA-1, and BLISS-LN trials. RESULTS: Thirty-six patients received RTX as induction treatment; 32 (88.9%) were women. Their age at baseline and disease duration were 32.6 (11.7) and 7.6 (6.5) years, respectively. The time between renal biopsy and RTX use was 2.64 (4.41) years. At baseline, serum creatinine and 24-HP levels were 1.5 (1.5) mg/dL and 3.4 (2.8) g, respectively. At months 6 and 12, serum creatinine levels were 1.6 (1.6) and 1.6 (1.5) mg/dL, and 24-HP were 2.2 (2.2) and 1.6 (1.5) g, respectively. According to LUNAR and AURORA-1 criteria, CR at 6th and 12th months were 6/34 (17.6%) and 8/30 (26.7%) and 6/34 (17.6%) and 7/31 (22.6%) patients, respectively. According to BLISS-LN criteria, responders at 6th and 12th months were 9/34 (26.5%) and 10/31 (32.3%) patients, respectively. CONCLUSIONS: CR and responder status were reached in less than one third of LN patients treated with RTX, regardless of the criteria used to define them. However, serum creatinine levels did not increase, and there was a decrease in proteinuria levels during the follow-up.

Joint Damage and Low Lean Body Mass in a Cohort of Peruvian Patients With Rheumatoid Arthritis.

OBJECTIVES: To determine the association between radiologic joint damage (JD) and a lower lean body mass (LBM) in rheumatoid arthritis (RA) patients. METHODS: A cross-sectional study from a single center established RA cohort. JD and appendicular LBM (arms and legs) were measured with the Sharp/van der Heijde (SvdH) score and dual x-ray absorptiometry expressed as kg/m 2 , respectively. A univariable analysis was used to determine the association between JD an LBM; then, a multivariable regression model was performed to evaluate the persistence of this association, adjusted by age, gender, disease duration, socioeconomic status (by the Graffar method), tobacco use, anticitrullinated protein antibody levels, Disease Activity Score in 28 joints for RA with erythrocyte sedimentation rate, glucocorticoid use (as prednisone equivalent), disease-modifying antirheumatic drug use, body mass index, and disability (by the multidimensional Health Assessment Questionnaire). RESULTS: Two hundred forty-seven patients were included; the average (SD) age was 63.0 (12.8) years, disease duration 20 (15.00) years, the total SvdH was 66 (86.75), and the aLBM was 13.6 (3.82) kg/m 2 . In the univariable analysis, a lower appendicular LBM was associated with higher SvdH score on the female population, in terms of the total ( B = -8.6, p < 0.01), bone erosion (-4.4, p < 0.01), and joint space narrowing (-4.2, p < 0.01) scores; this correlation remained in the multivariable analysis in terms of total SvdH ( B = -9.5, p < 0.01), bone erosion (-5.2, p < 0.01), and joint space narrowing (-4.3, p < 0.01). CONCLUSIONS: A lower LBM in female patients was associated with more severe JD independently of other variables examined. Strategies aimed at preserving LBM could have a favorable impact on the course of disease.

Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes.

OBJECTIVES: A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes. METHODS: Demographic, clinical and serological data from 805 patients with SLE obtained within 15 months of diagnosis and at 3-year and 5-year follow-up were included. For each visit, sera were assessed for 29 antinuclear antibodies (ANA) immunofluorescence patterns and 20 autoantibodies. K-means clustering on principal component analysis-transformed longitudinal autoantibody profiles identified discrete phenotypic clusters. One-way analysis of variance compared cluster enrolment demographics and clinical outcomes at 10-year follow-up. Cox proportional hazards model estimated the HR for survival adjusting for age of disease onset. RESULTS: Cluster 1 (n=137, high frequency of anti-Smith, anti-U1RNP, AC-5 (large nuclear speckled pattern) and high ANA titres) had the highest cumulative disease activity and immunosuppressants/biologics use at year 10. Cluster 2 (n=376, low anti-double stranded DNA (dsDNA) and ANA titres) had the lowest disease activity, frequency of lupus nephritis and immunosuppressants/biologics use. Cluster 3 (n=80, highest frequency of all five antiphospholipid antibodies) had the highest frequency of seizures and hypocomplementaemia. Cluster 4 (n=212) also had high disease activity and was characterised by multiple autoantibody reactivity including to antihistone, anti-dsDNA, antiribosomal P, anti-Sjögren syndrome antigen A or Ro60, anti-Sjögren syndrome antigen B or La, anti-Ro52/Tripartite Motif Protein 21, antiproliferating cell nuclear antigen and anticentromere B). Clusters 1 (adjusted HR 2.60 (95% CI 1.12 to 6.05), p=0.03) and 3 (adjusted HR 2.87 (95% CI 1.22 to 6.74), p=0.02) had lower survival compared with cluster 2. CONCLUSION: Four discrete SLE patient longitudinal autoantibody clusters were predictive of long-term disease activity, organ involvement, treatment requirements and mortality risk.