AN OBSERVATIONAL MULTICENTER STUDY COMPARING THE EFFECTIVENESS BETWEEN TNF INHIBITORS AND APREMILAST ON ORAL ULCERS OF BEHCET’S DISEASE

G. Lopalco, V. Venerito, L. Cantarini, G. Emmi, G. Espinosa, M. Mosca, A. Cauli, M. Piga, R. Talarico, G. M. Lledó, J. Sota, C. Fabiani, F. Bello, I. Mattioli, L. M. Argolini, F. DI Cianni, R. Caporali, F. IannoneBari, Department of Precision and Rigenerative Medicine and Ionian Area (DiMePRe-J), Bari, Italy Bari, Department of Precision and Rigenerative Medicine and Ionian Area (DiMePRe-J), Bari, Italy University of Siena, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Siena, Italy University of Florence, Department of Experimental and Clinical Medicine, Florence, Italy University of Barcelona, Department of Autoimmune Diseases, Hospital Clínic, Carrer de Villarroe, Barcelona, Spain University of Pisa, Azienda Ospedaliero Universitaria Pisana and Department of Clinical and Experimental Medicine, Pisa, Italy University of Cagliari, Department of Medical Sciences and Public Health, Cagliari, Italy University of Milan, Department of Clinical Sciences and Community Health, Research Center for Pediatric and Adult Rheumatic Diseases, Milan, Italy  Background Recurrent oral and genital ulcers are the most nagging clinical manifestations of Behcet’s disease (BD) and colchicine should be used first for the treatment and prevention of ulcers relapse. In contrast, TNF-α inhibitors (TNFi) are helpful in resistant cases, leading to a rapid improvement of mucosal lesions [1]. More recently, the phosphodiesterase-4 inhibitor apremilast was evaluated in two RCTs showing a significant improvement of oral ulcers compared to placebo [2, 3]. Moreover, several observational studies also investigated the effectiveness of apremilast in BD patients with mucosal ulcers [4]. Objectives To date, there are no comparative data about the effectiveness between TNFi and apremilast in mucocutaneous involvement of BD. The present study aims to compare the effectiveness between TNFi and apremilast on oral ulcers of BD. Methods Data on patients classified as BD (according to International Criteria for BD and International Study Group criteria) who underwent apremilast or TNFi for refractory oral ulcers from March 2017 to January 2022 in 7 tertiary rheumatology centers (6 Italian and 1 Spanish) were retrospectively analyzed. Retrieved data including demographics and clinical characteristics were collected. We also recorded the presence of active oral aphtosis at either baseline, 3-month and 6-month follow-up as well as the occurrence of oral ulcers during the intervals between visits. Patients on TNFi were considered controls for nearest-neighbour propensity score (PS-)-matching (neighbours for replacement matching, minimum 1, maximum 4). PS is an epidemiological tool used for the adjustment of non-randomized longitudinal studies. It is a conditional probability of being exposed to a disease given an asset of covariates. In brief, this was carried out using the patients’ age, disease duration and gender, with a selected calliper of 0.2. Chi-square test was used to test difference between proportions of patients with active aphtosis in both groups at different follow-up times. Results Among 159 patients with BD on TNFi or apremilast, the matching algorithm retrieved 84 patients. More in detail, 26 patients in the apremilast group and 58 patients in TNFi group. All had active aphtosis at treatment start. Clinical ad demographic characteristics of patients at baseline are reported in Table 1 and Figure 1 and 2. Concerning proportion of patients with active oral aphtosis, no difference was observed either at 3-month (p=0.60) and 6-month (p=0.66) follow-up visits (Figure 2). Consistently, the rate of flares in the time intervals between visits was not different between groups (46.15% vs 37.93% from month 0 to 3, p=0.47; 34.62% vs 34.48% from month 3 to 6, p=0.99). Conclusion The main limitations of our study are the small sample size and the short-term follow-up. Nevertheless, we provide evidence that apremilast and TNFi show similar effectiveness, inducing a meaningful and early benefit in BD patients with refractory oral ulcers. Table 1. Apremilast TNF-α inhibitors Av.Obs. Av.Obs Female, n(%) 26 17(65.38) 58 30 (51.72) Age at diagnosis, mean (SD) 26 31.15(14.05) 58 26.60(12.39) Age at baseline, mean (SD) 26 28.34(14.57) 58 40.84 (12.73) Disease Duration, mean (SD) 26 7.19 (8.24) 58 4.24(5.35) csDMARDs combotherapy, n(%) 26 7(26.92) 58 37(63.79) Current bDMARD/tsDMARD treatment line, median (IQR) 26 1 (1-2) 58 1(1-2) Figure 1. Image/graph: References Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018 Jun;77(6):808-818. Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behçet’s syndrome—a phase 2, placebo-controlled study. N Engl J Med. 2015 Apr 16;372(16):1510-8. Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of Apremilast for Oral Ulcers in Behçet’sBehçet’s Syndrome. N Engl J Med. 2019 Nov 14;381(20):1918-1928. Lopalco G, Venerito V, Leccese P, et al. Real-world effectiveness of apremilast in multirefractory mucosal involvement of Behçet’sBehçet’s disease. Ann Rheum Dis. 2019 Dec;78(12):1736-1737. Acknowledgements: NIL. Disclosure of Interests None Declared. Keywords: Behcet’s disease DOI: 10.1136/annrheumdis-2023-eular.3185Citation: , volume 82, supplement 1, year 2023, page 1151Session: Other orphan diseases (Poster View)