Can we predict kidney involvement in patients with systemic lupus erythematosus? A retrospective cohort study with independent validation.

OBJECTIVES: To discern predictive factors for incident kidney involvement in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE from the 'Attikon' Lupus cohort were monitored for lupus nephritis (LN), defined by kidney histology and/or classification criteria. Demographic and clinical characteristics at baseline were compared against patients who did not develop LN. LN-free survival curves were generated by Kaplan-Meier. A multivariate Cox proportional hazards model was used to identify independent predictors of LN. Independent validation was performed in the University of Crete Lupus registry. RESULTS: Among the 570 patients in the derivation cohort, 59 exhibited LN as their initial presentation, while an additional 66 developed LN during the follow-up period (collectively, 21.9% incidence). In the latter group, baseline factors predictive of subsequent kidney involvement were male sex (multivariable-adjusted [a]HR 4.31, 95% CI: 1.82-10.2), age of SLE diagnosis below 26 years (aHR 3.71, 95% CI: 1.84-7.48), high anti-dsDNA titre (aHR 2.48, 95% CI: 1.03-5.97) and low C3 and/or C4 (although not statistically significant, aHR 2.24, 95% CI: 0.83-6.05, p= 0.11). A combination of these factors at time of diagnosis conferred an almost 90-fold risk compared with serologically inactive, older, female patients (aHR 88.77, 95% CI : 18.75-420.41), signifying a very high-risk group. Independent validation in the Crete Lupus registry showed concordant results with the original cohort. CONCLUSION: Male sex, younger age and serologic activity at SLE diagnosis are strongly associated with subsequent kidney involvement. Vigilant surveillance and consideration of early use of disease-modifying drugs is warranted in these subsets of patients.

Residual disease activity and treatment intensification in systemic lupus erythematosus: A cross-sectional study to quantify the need for new therapies.

OBJECTIVE: The proportion of SLE patients with residual disease activity in routine settings is variable. We assessed disease activity state in patients during their most recent visit, and whether patients with residual activity were offered therapy intensification. METHODS: Cross-sectional study of consecutive lupus patients in three tertiary centers. Patients were categorized as: i) remission off-therapy, ii) remission on-therapy, iii) low disease activity, and iv) non-optimally controlled disease. Multivariable regression identified factors associated with treatment intensification and ROC analysis calculated the accuracy of SLEDAI-2K to predict this intensification. RESULTS: Three hundred and thirty-two patients were included [93.1% female, mean (SD) age 48.5 (14.7) years, median (IQR) disease duration 6.5 (12.4) years]. Mean (SD) total and clinical SLEDAI at last visit were 3.7 (3.0) and 3.0 (2.9), respectively. Although 23.2% of patients were in remission, 40.1% were categorized as non-optimally controlled disease (79.2% due to SLEDAI-2K > 4), but less than 50% of them were offered therapy intensification. Proteinuria (OR 6.78, 95% CI 2.06-22.25), arthritis (OR 5.48, 95% CI 3.20-9.40), and rash (OR 3.23, 95% CI 1.81-5.75) were associated with intensification of therapy, but the accuracy of either total or clinical SLEDAI to predict it was moderate (ROC area under the curve 0.761 and 0.779, respectively). CONCLUSIONS: About 40% of patients have evidence of residual disease activity and could qualify for novel treatments. Most treatment changes were triggered by active renal, joint, and skin disease, whereas the predictive value of SLEDAI-2K as a metric of disease activity was modest.

A prospective multicenter study assessing humoral immunogenicity and safety of the mRNA SARS-CoV-2 vaccines in Greek patients with systemic autoimmune and autoinflammatory rheumatic diseases.

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.

Left bundle branch area pacing versus conventional pacing in patients with advanced atrioventricular conduction abnormalities: a prospective cohort study.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an emerging pacing method that may prevent the deleterious effects of right ventricular pacing. The aim of this study is to compare the effects of LBBAP with right ventricular septal pacing (RVSP) in patients with advanced atrioventricular conduction abnormalities and preserved left ventricular ejection fraction. METHODS: The effect of pacing was evaluated by echocardiographic indices of dyssynchrony, including global myocardial work efficiency (GWE) and peak systolic dispersion (PSD). The primary endpoint was GWE postprocedural, at 3, 6, and 12 months after the procedure. RESULTS: Twenty patients received LBBAP and 18 RVSP. Complete follow-up was accomplished in 37 patients (97.4%) due to the death of a patient (RVSP arm) from nonrelated cause. GWE was significantly increased in the group of LBBAP compared to RVSP at all time points (90.8% in LBBAP versus 85.8% in RVSP group at 12 months, p = 0.01). PSD was numerically lower in the LBBAP arm at all time points, yet not statistically significant (56.4 msec in LBBP versus 65.1 msec in RVSP arm at 12 months, p = 0.178). The implantation time was increased (median 93 min in LBBAP versus 45 min in RVSP group, p < 0.01), along with fluoroscopy time and dose area product (DAP), in the arm of LBBAP. There were no severe perioperative acute complications in either group. CONCLUSIONS: LBBAP is an emerging and safe technique for patients with a pacing indication. Despite the longer procedural and fluoroscopy time, as well as higher DAP, LBBAP seems to offer better left ventricular synchrony compared to RVSP, according to GWE measurements.