Efficacy of belimumab on specific and nonspecific skin manifestations of systemic lupus erythematosus; results from a multicentric, nationwide cohort of patients treated in a real-world setting (BeRLiSS-Skin)

Background: The efficacy of belimumab in SLE has been extensively proved, both in randomized controlled trials, and real-life observational studies. However, there are no studies in which patients were stratified by subtype of skin manifestations. Aim of the study: The aim of this study was to evaluate potential differences in clinical response to Belimumab among patients with distinct cutaneous subtypes. Specifically, the study assessed disparities related to two subtypes of skin disease: specific and non-specific skin manifestations. Another endpoint of the study was to determine, especially among specific manifestations, whether there was a different response to Belimumab in terms of both the magnitude and timing of response. A secondary endpoint was to determine if the daily dose of prednisone decreases differently among the various cutaneous subtypes of SLE. Materials and Methods: The study was conducted retrospectively from 2013 to 2024, following patients from the initiation of Belimumab and involving a nationwide cohort of patients with SLE, all treated in lupus clinics. All adult patients treated with Belimumab (intravenous 10 mg/kg or subcutaneous 200 mg weekly) who had active skin and joint manifestations were included in the study (BeRLiSS-neJS). However, only patients with active skin manifestations were analysed in this study (BeRLiSS-Skin). The Italian lupus clinics which participate to the study were asked to complete a dedicated database for consistent remote data collection. Skin-related information was collected by sorting it into subtypes (ACLE, SCLE, CCLE, cutaneous vasculitis, alopecia/lupus hair, livedo reticularis). Patient response to belimumab was assessed using variation of CLASI-A and CLASI-D scores every 6 months from the start of belimumab treatment. Achievement of CLASI-A remission was defined as CLASI-A=0 and was tested at baseline, 6, 12, 24, 30, 36 months of follow-up. Both parametric and non-parametric tests were appropriately used for analysis. Results: The study included patients with active cutaneous SLE from 14 Italian centres, with a mean follow-up period of 31.6 ± 20.8 months. Mean age at diagnosis was 29.9±13.2 years. At belimumab initiation 242 patients (54,6%) had skin involvement of which: 112 acute (46,3%), 54 subacute (22,3%) and 18 chronic (7.4%), 48 cutaneous vasculitis (19.8%), 23 livedo reticularis (9.5%), 79 alopecia/lupus hair (32,6%). CLASI-A score decreased from baseline at 12, 24, and 36 months in all phenotypes. A statistically significant decrease in CLASI-A from baseline was observed as early as 6 months for the acute (p<0.001) and subacute phenotype (p<0.001), as late as 12 months for the chronic one (0-6 months p=0.297, 0-12 months p=0.003) and as late as 18 months for livedo reticularis (0-12 months p=0,066, 0-18 months p=0,027). No significant decrease in CLASI-A was found for the other nonspecific skin manifestations of SLE. The variation of CLASI-D showed stability at 36 months compared to baseline for all specific skin phenotypes (p=0.508 for acute, p=1.000 for subacute, p=0.770 for chronic). Among all skin phenotypes, including both specific and non-specific manifestations, no significant decrease emerged in terms of CLASI-D improvement (p=0.089). Moreover, remission tested with CLASI-A was more frequent in patients with acute than subacute and chronic phenotype at 18, 24 and 36 months. Finally, this study also demonstrated that the GCs sparing effect of belimumab especially for patients with acute and subacute lupus, whereas for the chronic subtype, and non-specific SLE the variation in daily PDN intake did not yield significant results. Conclusions: belimumab was effective at reducing cutaneous activity. CLASI-A reduction was achieved later in CCLE patients than those with ACLE and SCLE. CLASI-D demonstrated stability at 36 months in all phenotypes. ACLE had the best GCs dose reduction.