ANIFROLUMAB IN REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS: A REAL-LIFE, MULTICENTER STUDY

F. Trentin, C. Tani, A. Cauli, F. Ceccarelli, F. Ciccia, F. Conti, L. Coladonato, L. Dagna, G. De Marchi, G. Emmi, S. Fasano, M. Gatto, L. Moroni, F. Riccio, M. Piga, M. Zen, M. MoscaUniversity of Pisa, Italy., Rheumatology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy AOU and University of Cagliari, Rheumatology Unit, Department of Medical Sciences and Public Health, CAGLIARI, Italy, Cagliari, Italy Sapienza Università di Roma, Reumatologia, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Roma, Italy University of Campania Luigi Vanvitelli, Rheumatology Unit, Department of Precision Medicine, Napoli, Italy University of Bari, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Bari, Italy Università Vita-Salute San Raffaele, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Milan, Italy IRCCS Ospedale San Raffaele, Milan, Italy., Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Milan, Italy Academic Hospital “Santa Maria della Misericordia”, ASUFC, Division of Rheumatology, Department of Medicine, Udine, Italy, Udine, Italy University of Florence, Department of Experimental and Clinical Medicine, Florence, Italy University of Padova, Rheumatology Unit, Department of Medicine DIMED, Italy, Italy  Background Anifrolumab (ANI) is a monoclonal antibody to the type I interferon receptor recently approved by EMA as an add-on therapy for the treatment of moderate to severe SLE. As of this writing, real world data on its use are still lacking. Objectives To depict the clinical phenotype of refractory SLE patients treated with ANI. To evaluate short-term effectiveness and safety of ANI in clinical practice. Methods Multicenter prospective cohort study on adult patients with SLE treated with ANI for compassionate use. Demographic data, clinical and treatment history, and SLICC Damage Index (SDI) were retrieved from clinical charts. SLEDAI-2K, SLE-DAS, daily prednisone dose, number of tender (Tj) and swollen (Sj) joints, Cutaneous LE Disease area and severity index (CLASI-A), and Physician Global Assessment (PGA) were recorded at baseline, 1, 3, and 6 months of follow-up. Remission (according to 2021 DORIS definition) and low disease activity (according to LLDAS definition) were assessed at 6 months. Adverse events (AE) were recorded at each visit. Results 20 patients (90% female, 90% Caucasian, median age 48 (range 24-68), median disease duration 12 (4-27) years from 9 referral centers were included. 100% of patients had a history of articular involvement, 95% of skin rash, 50% of hematological involvement, 30% of nephritis, 25% of serositis, and 10% of neuropsychiatric involvement. Fifteen percent had a concomitant antiphospholipid syndrome and 10% Sjogren’s syndrome. At baseline, 65% had an SDI>0 (median 2, 1-5). The median number of previous immunosuppressive therapies was 4 (1-7), while the median cumulative dose of prednisone was 10.3 g (5-90). Reasons for adding ANI to treatment were persistently active disease (83.3%) or disease flare (16.7%). Main active manifestations were: muco-cutaneous (70%), articular (40%), and hematological (25%). Concomitant therapies were glucocorticoids in 94.1% (pred-eq median daily dose 7.5 mg, range 0-25), conventional DMARD in 84% (31% mycophenolate, 16% azathioprine, 32% methotrexate, 5% cyclosporine), and hydroxychloroquine in 74% of cases. At 1 month after starting ANI, a significant decrease in all the activity indices was recorded: mean±SD SLEDAI from 7.6±4.2 at baseline to 6.1±3.5 (p=0.02), CLASI-A from 8.8±9.7 to 3.6±5.2 (p=0.01), and PGA from 1.3±0.5 to 1±0.5, (p=0.005), SLE-DAS from 9.6 ±6.5 to 6.8 ±5.2 (p=0.04), SJ from 1.6 ±0.6 to 0.5±0.2 (p=0.02). The improvement was maintained trough the 6 months of follow-up. A reduction in the mean daily dose of glucocorticoids was observed at all time points, but statistical significance was not reached (Table 1). LLDAS and remission were achieved by 75% of patients at 6 months of follow-up. One patient discontinued treatment after 2 infusions due to a lack of response. Nine AE were recorded, mainly mild viral infections including one herpes zoster reactivation. Only one AE (thromboembolism) led to treatment discontinuation. Conclusion ANI demonstrated a rapid efficacy on skin manifestation, arthritis, and overall disease activity in patients with SLE refractory to the standard of care. The good safety profile is also confirmed in this real-world analysis. References van Vollenhoven RF, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus Sci Med. 2021 Franklyn K, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Table 1. Mean ±SDMedian (range) Baseline At 1 month At 3 months At 6 months SLEDAI-2K 7.2±4.36 (1-18) 6.1±3.56 (2-14) 4.5 ± 2.95 (0-10) 1±0.81 (0-2) SLE-DAS 9.4±6.15.96 (4.45-27.4) 7.1±5.45.5 (3.5-21) 4.3 ± 3.73.5 (0.37-14) 0.9±0.60.85 (0.37-1.5) CLASI-A 9.3±9.87 (0-27) 3.6±5.22 (0-17) 3.2 ±5.11 (0-17) 0.5±10 (0-2) Tj 3.8±4.72 (0-15) 4.6±4.83 (0-14) 3 ± 4.90 (0-15) 7.5±11.92.5 (0-25) Sj 1.2±20 (0-6) 0.6± 0.80 (0-2) 0.3±0.60 (0-2) 00 PGA 1.3±0.41 (1-2) 1±0.51 (0-2) 0.8±0.60.7 (0-2) 0.3±0.20.4 (0-0.5) Prednisone daily dose (mg) 8.2± 5.37.5 (0-25) 8±66.25 (0-25) 6.7 ± 3.26.25 (0-12.5) 5±4.15 (0-10) LLDAS n° (%) 3 (75%) Remission n° (%) 3 (75%) Acknowledgements AstraZeneca for providing the drug. Disclosure of Interests Francesca Trentin: None declared, Chiara Tani: None declared, Alberto Cauli: None declared, Fulvia Ceccarelli: None declared, Francesco Ciccia: None declared, Fabrizio Conti: None declared, Laura Coladonato: None declared, Lorenzo Dagna: None declared, Ginevra De Marchi: None declared, Giacomo Emmi: None declared, SERENA FASANO: None declared, Mariele Gatto: None declared, Luca Moroni: None declared, Flavia Riccio: None declared, Matteo Piga: None declared, Margherita Zen Speakers bureau: GSK., Marta Mosca Speakers bureau: Dr Mosca personal fees from AstraZeneca, GSK, and Lilly outside the submitted work. Keywords: bDMARD, Systemic lupus erythematosus, Real-world evidence DOI: 10.1136/annrheumdis-2023-eular.3552Citation: , volume 82, supplement 1, year 2023, page 1476Session: SLE, Sjön’s and APS - treatment (Publication only)