Welcome to the CORA 2023
Interactive Program

Background and Aims

We aimed to determine the effect of the use of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with active systemic lupus erythematosus (SLE).

Methods

We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia (NEA) clinical trials of belimumab (N=3225), that included seropositive, active SLE patients with no active severe lupus nephritis (LN). Participants were allocated to receive intravenous (IV) belimumab 1 mg/kg (N=559), IV belimumab 10 mg/kg (N=1033), subcutaneous (SC) belimumab 200 mg (N=556) or placebo (N=1077) in addition to standard therapy. The outcome of the present analysis was development of renal flares, defined according to the analysis plan within the BLISS programme. The hazard of renal flare was assessed with adjusted Cox regression models.

Results

In total, 192 patients developed a renal flare after a median of 197 days. In multivariable Cox regression analysis, use of AMA was associated with a lower risk of renal flares (HR: 0.64; 95% CI: 0.54–0.96; p=0.026). Compared with placebo, the risk of renal flares was lower among patients receiving IV belimumab 1 mg/kg (HR: 0.44; 95% CI: 0.25–0.79; p=0.006) and IV belimumab 10 mg/kg (HR: 0.63; 95% CI: 0.45–0.87; p=0.005), but not SC belimumab 200 mg (HR: 0.90; 95% CI: 0.57–1.42; p=0.648).

Conclusions

Belimumab and AMA prevent against renal flares in patients with active, seropositive SLE but no ongoing severe renal involvement. The prominent effect of low-dose belimumab motivates the investigation of the efficacy of intermediate doses of belimumab.

Background and Aims

Updated data regarding SLE epidemiology in Europe are few, and information from Italy is scanty. We aimed at estimating the incidence and prevalence of SLE in northeastern Italy over the period 2012–2020.

Methods

A retrospective population-based study was conducted in Veneto Region (4,900,000 people) using the Population Registry, an administrative health database where all residents are recorded, which was linked with healthcare copayment exemption database and hospital discharge records. Between 2012 and 2020, SLE cases were defined by a healthcare copayment exemption for SLE (national registry code 028) or any hospital diagnosis of SLE (ICD-9-CM 710.0), whichever came first. Standardized incidence and prevalence were reported by age and gender, and trends during the follow-up were analyzed through Poisson regression models.

Results

We identified 4,283 SLE patients (85% female), with 1,092 incident cases. Across the study period, SLE standardized point prevalence significantly increased from 66.7 (95% CI 64.3-69.0) to 72.9 per 100,000 residents (70.5-75.3, annual increase 1.1%, p<0.0001). SLE incidence was 2.8 per 100,000 (95% CI 2.6-2.9), with a significant difference between females (4.5, 4.3-4.8) and males (0.9, 0.8-1.0, p<0.001), and with a 8% annual decline (p<0.0001). The highest incidence was observed in women aged 30-39 (8.40, 7.31-9.65). The female-to-male incidence rate ratio overall was 5.00 (4.25-5.87; p<0.0001), with a peak in the 30-39 age group (10.4, 6.58-16.87).

Conclusions

Over the last decade SLE prevalence has increased, while incidence has stably declined. In view of the introduction of new high-cost drugs, a clear definition of the epidemiology of SLE is crucial for all healthcare stakeholders.

Background and Aims

IL-17/ IL-23 axis seems to have a role in lupus nephritis (LN). The aim of this study is to evaluate the prognostic factors in a cohort of patient with LN focusing on the impact of IL-17/IL 23 axis on renal outcome

Methods

84 patients with active LN at disease onset or at renal flare were enrolled. Clinical data were collected at baseline and at 6(T6),12(T12),24(T24) months and at the last follow-up(FU). Renal biopsies were evaluated according to ISN/RPS classification. Active interstitial infiltrate (IF) was assessed using the BANFF score. Baseline IL-17 and IL-23 serum levels were assessed in 37 patients

Results

The results of univariate and multivariate analysis for each outcome considered showed that IF>5% and antiphospholipid antibodies positivity (APL+) were associated with worse renal outcomes. IF was associated to not reaching early remission in both univariate analysis (p<0,01) and multivariate analysis (OR 0.12(0.04-0.37)), and to chronic damage (p= 0,01), no persistent remission (p= 0,02), proteinuria (p <0,01), in the univariate analysis. APL+ was associated to less early remission achievement in both univariate analysis (p= 0,03) and multivariate analysis (OR 0.36(0.11-1.37)) as well as to chronic damage in univariate analysis (p= 0,04) and multivariate analysis (OR 0.77 (0.39-15.16)). Higher IL-23 serum level was associated with persistent proteinuria (p<0,01) and chronic damage (p=0.05)

Conclusions

IF and APL+ represent in this study the strongest predictors of worse renal outcome. A higher IL-23 serum level seems to be a negative prognostic factor suggesting a possible role of IL-17/IL- 23axis as a biomarker of more aggressive LN

Background and Aims

BLyS inhibition following belimumab therapy is associated with circulating B-cell and short-lived plasmacells reduction. Aim of the study:characterize B-cell phenotype in SLE patients at baseline and after anti-BlyS treatment.

Methods

Fifty-four active SLE patients (49 females, mean age 40.6±13.2years, disease duration 12.3±9.0years, SLEDAI-2K 6.6±3.1) who received belimumab were enrolled. Phenotyping of peripheral blood B-cells (using as phenotypic markers IgD,CD38,CD27) was performed at six(T6) and twelve(T12)months by flow cytometry.

Results

In the whole cohort a reduction of CD19^pos[T0:11.1±6.1% vs T6:6.4±3.4%,p<0.01;T12:4.2±3.4%,p<0.01] and CD19^posIgD^posCD27^neg[T0:55.8±28.7% vs T6:34.9±22.2%,p<0.01;T12:30.0±19.4%,p=0.04] and an increase of CD19^posIgD^negCD27^pos[T0:21.0±20.2% vs T6:37.5±21.4%,p<0.01;T12:42.2±21.7%,p=0.02] after therapy was observed. Stratifying patients based on organ involvement, a reduction of CD19^pos[T0:10.7±4.6% vs T6:6.8±2.4%,p=0.03;T12:4.5±3.5%,p=0.03] and CD19^posIgD^posCD27^neg[T0:61.0±24.6% vs T6:38.9±17.5%,p<0.01;T12:36.9±16.0%,p=0.03] in patients with mild organ involvement and an increase of CD19^posIgD^negCD27^posin both subgroups [(severe T0:24.1±25.0% vs T6:44.9±27.4%,p=0.01) (mild T0:18.9±18.3 vs T6:31.2±12.7%,p<0.01)] was found. Evaluating the B-cell subsets according to the treatment response, a reduction of CD19^posIgD^posCD27^neg at T6 [(responders T0:55.4±29.3 vs T6:32.3±19.9,p<0.01) (no-responders T0:63.1±41.3% vs T6:41.4±33.5%,p=0.05)] and an increase of CD19^posIgD^negCD27^pos[(responders T0:22.4±21.2% vs T6:39.6±19.4%,p<0.01) (no-responders T0:20.6±26.1% vs T6:38.6±35.3%,p<0.05) was observed in both groups. ROC curve analysis of IgD^negCD27^possubset identified a cut-off of 9.94% [AUC(95% CIs:0.761:(0.566-0.957),p=0.023) ] associated with response at T6. Moreover, having an IgD^negCD27^posrate ≥9.94% [OR:4.5(95%CIs:0.9-17.2)] and the presence of anti-dsDNA antibodies at baseline [OR:5.2(95%CIs:1.2-22.1)], identified patients who achieved early response within T6 from therapy initiation

Conclusions

Anti-BLyS therapy significantly impacts on the B-cell subpopulations in SLE in relation with the distinct organ involvement. Moreover, baseline immunological features and IgD^negCD27^posB-cell subset rate are novel putative biomarkers of response to anti-BLyS therapy in SLE.

Background and Aims

To investigate rates and predictors of cutaneous response to belimumab in patients with systemic lupus erythematosus (SLE) skin manifestations by using CLASI.

Methods

We included patients with SLE cutaneous manifestations from the BeRLiSS cohort. The outcome was evaluated by CLASI=0 (skin remission) and CLASI20, 50, 70, defined by a decrease of at least 20%, 50% and 70% at 6, 12, 24, 36 and 48 months. Baseline predictors were evaluated by logistic regression analysis.

Results

In the analysis were included 147 patients with SLE skin manifestations. Percentages of patients achieving the different outcomes at different time points are reported in the Figure.

Low complement at baseline was associated with CLASI50 at 12-month (p=0.017) and low complement at 12 months with CLASI70 at 24-month (p=0.002).

CLASI70 at 12-month was also associated with CLASI=0 at 36-months (p=0.030). There was a trend for association between number of flares in the first 24-month and CLASI=0 at 36-month (p=0.061) and CLASI50 at 24-months (p=0.086). The number of flares after the first 12 months of follow-up was positively associated with CLASI70 at 24-months (p=0.011).

Smoking was a negative predictor of CLASI50 at 12 months (p=0.026) and CLASI70 at 24 months (p=0.031). CLASI damage score>0 and disease duration at baseline were negatively associated with CLASI=0 at 36 months (p=0.031, p=0.036 respectively).

Conclusions

In belimumab-treated patients with SLE-related skin manifestations, best response was found in patients with low complement and relapsing remitting pattern of disease activity. As already known, smoking is negatively associated with cutaneous response.

Background and Aims

Various immune cells and cytokines are involved in the pathogenesis of SLE. Continuous immune activation results in production of large amounts of inflammatory cytokines leading to local inflammation and tissue damage. Th-10, a subset of T helper cells, known to produce IL-10 contributes in disease pathogenesis by stimulating B cells to produce antibodies. IL-10, is a pleiotropic cytokine, which exerts both anti-inflammatory and pro-inflammatory effects.

Our study aimed to measure circulating Th-10 levels and serum levels of IL-10 in SLE patients and to find their correlation with the SLE disease activity index.

Methods

The study was a hospital based cross-sectional case control study with patients of SLE(n=60) and healthy controls(n=30). Detection of T helper 17 cells(Th 17) was done by measurement of combined expression of CD45, CD3, CD4 , CCR 6 and IL-17 and IL-10 using Beckman Coulter Navios using the monoclonal antibodies conjugated with different fluorescent dyes.

Results

Flowcytometric expression of Th17 was significantly(p=0.04) higher among patients 2(1.80) in comparison to controls 1.19(1.35). Statistically significant(p=0.04) increase in the expression of Th 10 cells was found among cases 1.90(7.31) when compared to controls 1.07(2.02). Similar change was observed in active and inactive cases.Expression of Th17, Th10 IL-17 and IL-10 level was significantly higher in cases of nephritis when compared to those without nephritis.

Conclusions

Study concluded the pro-inflammatory role of IL-17 and IL-10. Expression of T helper 17(Th17) cells, was a subset of CD4+ T helper cells was increased and considered to contribute to inflammation related damage through IL-17 production.