Efficacy of Belimumab on Different Joint and Skin Manifestations of Systemic Lupus Erythematosus: Real-Life Data from a New Multicentric, Nationwide Italian Cohort (BeRLiSS-JS 2.0)

Marisol Bracalenti,1 Margherita Zen,1 Benedetta Bianchi,2 Alessandra Bortoluzzi,3 Luisa Brussino,4 Paola Castrignanò,5 Alberto Cauli,6 Lorenzo Cavagna,7 Elisabetta Chessa,6 Emanuele Chiara,8,9 Rossella De Angelis,2 Ginevra De Marchi,10 Marco Di Carlo,2 Giacomo Emmi,9,11 Isotta Galvagni,12 Michela Gasparotto,9 Mariele Gatto,1,13 Roberto Gerli,14 Marcello Govoni,3 Alberto Lo Gullo,15 Alessia Nano,10 Simone Negrini,4 Silvia Noviello,16 Giovanni Orsolini,12 Giulia Pazzola,5 Matteo Piga,6 Luca Quartuccio,10 Maurizio Rossini,12 Carlo Salvarani,5,17 Ettore Silvagni,3 Elena Silvestri,8 Marianna Tamussin,3 Martina Tizian,1 Paola Tomietto,9 Maria Letizia Urban,8 Angelo Vacca,16 Andrea Doria,1 Luca Iaccarino1 1Department of Medicine – DIMED, University of Padova, Padova, Italy; 2Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy; 3Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 4Department of Medical Sciences, University of Torino, Torino, Italy; 5Department of Transplantology, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy; 6Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; 7Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy; 8Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 9Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 10Department of Medicine (DMED), University of Udine, Udine, Italy; 11Department of Medicine, Monash University - Melbourne, Melbourne Australia; 12Rheumatology Unit, Department of Medicine, University of Verona, Verona Italy; 13Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; 14Rheumatology Unit, Department of Medicine & Surgery, University of Perugia, Perugia, Italy; 15UOSD Papardo, Hospital of Messina, Messina, Italy; 16Guido Baccelli Internal Medicine Unit, University of Bari “Aldo Moro”, Bari, Italy; 17Rheumatology, Azienda AUSL-IRCCS di Reggio Emilia, Reggio Emilia, ItalyCorrespondence: Luca Iaccarino, Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, Padova, 35128, Italy, Tel +39 0498214391, Email [email protected]: To evaluate the effectiveness of belimumab in different joint and skin phenotypes of systemic lupus erythematosus (SLE).Methods: The BeRLiSS-JS 2.0 is a decade-long observational study including adult SLE patients from 14 Italian Centers treated with belimumab (intravenous/subcutaneous) stratified by articular (nondeforming nonerosive arthritis -NDNE-, Jaccoud’s arthropathy, Rhupus) and cutaneous phenotypes (acute -ACLE-, subacute -SCLE-, and chronic cutaneous lupus erythematosus -CCLE-, and nonspecific manifestations). Outcome variables measured every 6 months up to 36 months included Disease Activity Score-28 joints (DAS28) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores, remission rates (DAS28< 2.6; CLASI-A=0), and prednisone intake (mg/day).Results: Of 443 patients, 221 (49.9%) had NDNE, 30 (6.8%) Jaccoud’s arthropathy, 21 (4.7%) rhupus, 112 (25.3%) had ACLE, 54 (12.2%) SCLE, and 18 (4.1%) CCLE. At 6 months a significant decrease of DAS28 was observed in NDNE (p< 0.001) and by CLASI-A in ACLE and SCLE (both p< 0.001). Non-specific cutaneous manifestations did not improve significantly. CLASI-D scores remained stable over 36 months. Remission rates were higher in NDNE and ACLE patients (at 6 months: NDNE 59.6%, Jaccoud’s 18.8%, rhupus 30.3% - p=0.002; at 18 months: ACLE 75.9%, SCLE 56.4%, CCLE 33.3% - p=0.018). Daily prednisone dosage decreased in all organ-specific phenotypes, but more pronouncedly in patients with NDNE, ACLE, and SCLE. Higher baseline CLASI-A and DAS28 and CLASI-D were associated with lower remission rates.Conclusion: Treatment with belimumab was associated with reduced disease activity and increased remission especially in NDNE and ACLE patients. Glucocorticoid-sparing effect was also found.Plain Language Summary: Belimumab is known to be an effective treatment for systemic lupus erythematosus (SLE), achieving the highest level of recommendation for non-responders to hydroxychloroquine/immunosuppressive agents (1a/A), while reaching a level B for active cutaneous involvement (1a/B) in the latest EULAR recommendations. On the other hand, belimumab effectiveness across different joint and skin phenotypes of SLE had not been thoroughly evaluated. This study was necessary to understand how belimumab performs in specific SLE phenotypes, such as nondeforming nonerosive arthritis (NDNE), Jaccoud’s arthropathy, rhupus, and various cutaneous manifestations (acute, subacute, chronic, and nonspecific) by using disease specific and validated clinimetric measures, such as DAS28 and CLASI.Belimumab significantly decreased disease activity and improved remission rates especially in NDNE and acute cutaneous lupus erythematosus (ACLE) patients while also highlighting a glucocorticoid-sparing effect particularly in NDNE, ACLE, and subacute cutaneous lupus erythematosus (SCLE) patients.Therefore, these findings suggest that belimumab could be more beneficial for patients with NDNE and ACLE than other phenotypes, potentially guiding more personalized treatment approaches in clinical practice.Keywords: systemic lupus erythematosus, skin manifestations, joint manifestations, belimumab, remission