FRI0167 LONG TERM CLINICAL OUTCOME IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS FOLLOWED FOR MORE THAN 20 YEARS IN THREE ITALIAN TERTIARY REFERRAL CENTERS: THE MILAN SYSTEMIC LUPUS ERYTHEMATOSUS CONSORTIUM (SMILE) COHORT
Authors: M. Gerosa, G. A. Ramirez, C. Bellocchi, L. M. Argolini, L. Moroni, M. Cornalba, N. Farina, L. Dagna, R. Caporali, E. Bozzolo, L. Beretta
Journal: Annals of the Rheumatic Diseases (2020)

Background: the prognosis of Systemic lupus Erythematosus (SLE) patients has significantly improved over time, raising the need for more data about disease activity and damage accrual in the long term. Objectives: to investigate the risk of long term disease activity and to identify viable prognostic markers for disease flares in SLE patients with long standing disease Methods: data on SLE patients regularly followed at ASST PINI-CTO, Fondazione Ca’ Granda Policlinico and Ospedale San Raffaele, Milan (Milan Systemic Lupus Erythematosus Consortium, SMiLE, cohort) with disease duration ≥ 20 years, were retrospectively analyzed. Organ involvement as per the British Isles Lupus Assessment Group (BILAG) definitions was recorded along with achievement of clinical and complete remission (CR and CCR: clinical SLEDAI =0, PGA &lt;0.5 and no prednisone or immunosuppression ± negative serology) and lupus low disease activity state (LLDAS) at 15 (T15) and 20 (T20) years of follow up. Damage accrual was estimated according to the SLE International Collaborating Clinics/American College of Rheumatology damage index (SDI). Results: data from 168 patients (table 1) were available for analysis. Remission (CR+CCR) and LLDAS were achieved in 22% and 61% at T15 and 25% and 71% at T20. LLDAS was not associated with a history of involvement in any BILAG domain, but it was inversely associated with treatment with mycophenolate at any time (50 vs 23% treated vs not treated; p=0.02). SDI&gt;0 was found in 49% patients at T15 and in 71% at T20. LLDAS at T15 was associated with lower flare rates in the following five years (HR= 0.395, 95%, CI=0.239-0.653; Figure, left panel; p&lt;0.001). The risk of flaring for LLDAS was largely comparable to CCR and CR (Figure, middle panel). In the T15-T20 timeframe, 37% of patients had a flare. Patients with both low complement and anti-dsDNA positivity at T15 had an increased risk of flaring compared to serologically inactive patients (HR=2.86, 95%, CI=1.572-5.19; Figure right panel). Flaring patients were more likely to show an increase in SDI from T15 to T20 (37% vs 9% in patients with stable SDI; p&lt;0.001) Table 1. Demographic, laboratory and clinical characteristics of patients with SLE Characteristics (n=168) Demographic characteristics Female, n (%) 150 (89.3) Age at diagnosis years, median (IQR) 24 (18-32) Clinical and serological features during 15 years follow up, n (%) Musculoskeletal 140 (83) Mucocutaneous 135 (80) Constitutional 114 (68) Haematological 103 (61) Nephritis 81 (48) Cardiopulmonary 49 (29) NPSLE 31 (18) Positive anti-dsDNA 136 (81) Hypocomplementemia 136 (81) Positive antiphospholipid 73 (44) CR / CCR at T15 13 (8) / 23 (14) CR / CCR at T20 17 (10) / 25 (15) Conclusion: LLDAS is common in SLE patients with long disease duration although up to 37% of patients with 15-year disease duration may experience a flare during the following 5 years. The flare risk increases with failure to attain LLDAS at T15 and with active serology. Late flares associate with damage accrual. References: [1]Aringer M, Ann Rheum Dis. 2019; Franklin K, Ann Rheum Dis 2019 Table 2. therapy during the 20 year follow up Therapy (ever) % Prednisone 83 Hydroxychloroquine 91 Mycophenolate mofetil 33 Azathioprine 50 Methotrexate 23 Cyclophosphamide 36 Fig 1: risk of flare according to disease activity Disclosure of Interests: Maria Gerosa: None declared, Giuseppe Alvise Ramirez: None declared, Chiara Bellocchi: None declared, Lorenza Maria Argolini: None declared, Luca Moroni: None declared, Martina Cornalba: None declared, Nicola Farina: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp &amp; Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Enrica Bozzolo: None declared, Lorenzo Beretta Grant/research support from: Pfizer