ACUTE AND SUBACUTE SKIN MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS ARE ASSOCIATED WITH AN EARLIER RESPONSE TO BELIMUMAB THAN THE CHRONIC PHENOTYPE: PRELIMINARY DATA FROM THE NEW NATION-WIDE COHORT OF BELIMUMAB IN REAL LIFE SETTING STUDY—NEW JOINT AND SKIN (BERLISS-NEJS)

Background: The efficacy of belimumab in reducing disease activity in Systemic Lupus Eythematosus (SLE) has been extensively explored across clinical trials and real-life studies (1, 2). However, few studies have evaluated its efficacy upon stratification for different skin and joint phenotypes. Objectives: To assess potential disparity in efficacy of belimumab on different skin and joint manifestations from a multicentre nation-wide cohort (BeRLiSS). Methods: Adult SLE patients treated with belimumab (intravenous 10 mg/kg monthly or subcutaneous 200 mg weekly) included in the pre-existing BeRLiSS cohort (1, 2) were retrospectively analysed. Participating centres were asked to enrich the old BeRLiSS database with these new variables: skin (acute, subacute, chronic, skin vasculitis, alopecia/lupus hair, livedo reticularis, ulcer/chilblain) and joint involvement (non-deforming non-erosive arthritis – NDNE -, Jaccoud’s arthropathy, and rhupus). These different subtypes were assessed for variation in DAS28, CLASI-A (Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity), SRI-4 (SLE responder Index-4) and SLEDAI-2K scores at baseline, 12 and 24 months. Parametric and non-parametric tests were used as appropriate. Results: A total of 312 patients was recruited, 284 females and 28 males, F:M ratio 9.9:1, mean age at diagnosis 29.1±12.7 years, mean treatment duration 52.2±38.0 months. At belimumab initiation 213 patients with joint manifestations (68.3%) were identified: 174 NDNE (55.8%), 22 Jaccoud’s arthropathy (7.1%) and 17 rhupus (5.5%). Skin manifestations were found in 167 patients (53.5%): 88 acute (28.2%), 46 subacute (14.7%), and 11 chronic (3.5%) phenotype, 38 skin vasculitis (12.2%), 17 livedo reticularis (5.4%), 62 alopecia/lupus hair (19.7%) and 46 ulcer/chilblain (14.7%). Achievement of response as measured by SRI-4 was significant in patients with either articular or cutaneous manifestations, albeit independent of joint (p = 0.75; p = 0.63) and skin subtype (p = 0.24; p= 0.37) at 12 and 24 months, respectively. Similarly, SLEDAI-2K reduction was significant in both groups (p < 0.001), regardless of joint (p=0.80) and skin phenotype (p=0.14). Organ-specific measures such as DAS28 and CLASI-A decreased from baseline at 12 and 24 months across all phenotypes (Table 1 and 2). A statistically significant decrease in DAS28 from baseline at 12 and 24 months was observed for NDNE (baseline-12 months: p < 0.001; baseline-24 months: p < 0.001), Jaccoud’s arthropathy (baseline-12 months: p = 0.015; baseline-24 months: p = 0.006) and rhupus (baseline-12 months: p = 0.034; baseline-24 months: p = 0.045). However, by ANOVA rhupus did not show improvement, possibly due to insufficient sample size. Comparison of CLASI-A variation from baseline at 12 and 24 months for the acute (baseline-12 months: p = 0.001; baseline-24 months: p < 0.001) and subacute subtype (baseline-12 months: p < 0.001; baseline-24 months p < 0.001) resulted to be significant. On the other hand, for the chronic subtype it only appeared to become significant at 24 months (p = 0.033). Variation of CLASI-A was not significant among different timepoints in patients with SLE-nonspecific skin manifestations. Conclusion: In our cohort of SLE patients, belimumab was effective in patients with joint and skin manifestations with no significant difference in DAS28, SRI-4 or SLEDAI-2K variation across the various joint involvement subtypes. On the other hand, the acute and subacute skin phenotypes were associated with an earlier response to belimumab on CLASI-A than the chronic phenotype. Finally, a clear response to belimumab was not found in patients with SLE-nonspecific skin manifestations alone. REFERENCES: [1] Zen M, et al. J Pers Med. 2023;13(4):691. [2] Gatto M, et al. Arthritis Rheumatol. 2020;72(8):1314-1324. Acknowledgements: NIL. Disclosure of Interests: Luca Iaccarino LI received honoraria (speaker fee) from GSK., Marisol Bracalenti: None declared, Margherita Zen MZ received honoraria (speaker fee) from GSK., Martina Tizian: None declared, Elena Ruffato: None declared, Alberto Cauli: None declared, Rossella De Angelis: None declared, Roberto Gerli: None declared, Marcello Govoni: None declared, Renato Lo Gullo: None declared, Simone Negrini: None declared, Luca Quartuccio: None declared, Carlo Salvarani: None declared, Angelo Vacca: None declared, Andrea Doria AD received honoraria (speaker fee) from GSK. DOI: 10.1136/annrheumdis-2024-eular.5657 Keywords: Skin, Biological DMARD, Observational studies/ registry, Real-world evidence Citation: , volume 83, supplement 1, year 2024, page 1010Session: Systemic lupus erythematosus (Poster View)

Skin, Biological DMARD, Observational studies/ registry, Real-world evidence