POS1268 LEFLUNOMIDE IS A SAFE AND EFFECTIVE DRUG IN PATIENTS WITH SJÖGREN’S SYNDROME WITH ACTIVE SYSTEMIC DISEASE
Authors: E. Fiorentini, M. Bandeira, M. Silvério-António, N. Khmelinskii, A. Damiani, L. Cometi, S. Guiducci, J. E. Fonseca, V. C Romão
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> To date, there are no approved treatments for Sjögren's disease (SjD). Leflunomide (LEF) has a pleiotropic immunosuppressive effect and was proposed as a promising drug for the management of systemic manifestations of SjD [1]. <h3>Objectives:</h3> To evaluate the efficacy and safety of LEF as an off-label treatment for patients with active systemic SjD in a real-life setting. <h3>Methods:</h3> We included patients fulfilling ACR/EULAR 2016 classification criteria for SjD treated with LEF. We collected demographic and clinical data at baseline and at last follow-up visit, including disease activity assessed by the EULAR SS Disease Activity Index (ESSDAI), patient symptoms (EULAR SjD Patient Reported Index [ESSPRI], EULAR sicca score [ESS]), complement levels and serum IgG. We compared baseline and last follow-up data using Paired T-test. P-value was considered significant at &lt;0.05. <h3>Results:</h3> We included 18 female patients with SjD who started LEF between September 2020 and October 2023, with a mean (SD) age of 52.6 (17.5) years and a mean disease duration of 6.3 (4.9) years (Table 1). Most of them had xerostomia and xeropthalmia (83.3% and 94.4% respectively), 88.9% were positive for ANA, 94.4% for anti-Ro, and 61.1% had a positive salivary gland biopsy. All patients started LEF due to systemic disease activity, with a mean ESSDAI at baseline of 6.06 (3.99). More than half of the patients (n=11, 61.1%) had moderate-to-severely active disease (ESSDAI ≥5). Active articular and biological domains were the main indications for starting LEF in 44.4% and 27.8% of cases, respectively. Glandular and skin involvement (22.2%), lymphadenopathy (16.7%), constitutional (11.1%) and hematological (5.6%) activity were also present. The starting dose of LEF was 10mg/day in 77.8% of patients, 15mg/day in 5.6%, and 20mg/day in 16.7%. Hydroxychloroquine, prednisolone, and topical substitutive therapy for sicca symptoms were common coexistent treatments. (61.1%, 61.1%, and 66.7% respectively). Mean follow-up was 11.9 (9.4) months and the daily dose of LEF at the last follow-up visit was 20mg in half of the patients (15mg: 33.3%; 10mg: 16.7%). Five patients stopped LEF after a mean of 6.2 (3.4) months due to: adverse events (alopecia n=1, gastrointestinal intolerance n=1), persistent disease activity (enrollment in clinical trial n=1, switch to rituximab n=1), and pregnancy desire (n=1). LEF was effective, significantly reducing ESSDAI (6.06 (3.99) to 3.18 (3.00); <b>p= 0.0206</b>), with 72.2% of patients achieving an ESSDAI≤3. Patient symptoms also improved, with a reduction of pain (from 6.79 (2.42) to 5.21 (3.02); <b>p=0.0297</b>) and oral dryness (from 4.92 (2.94) to 4.33 (2.87); <b>p=0.0314</b>). Of note, there was a significant decrease in IgG levels (from 1.94g/dL (0.71) to 1.65g/dL (0.55); <b>p=0.0363</b>), and 86.7% of patients presenting an IgG&lt;2.0 g/dL at last follow-up visit. <h3>Conclusion:</h3> In our experience, LEF has been a safe and effective treatment for patients with SjD and active systemic disease, particularly in improving markers of B cell hyperactivity, like serum IgG levels. This could be due to a direct suppressive effect on B cell activity, as previously reported [2]. These data suggest LEF may become a crucial drug in future management of SjD. <h3>REFERENCES:</h3> [1] E. H. M. van der Heijden <i>et al.</i>, 'Leflunomide–hydroxychloroquine combination therapy in patients with primary Sjögren's syndrome (RepurpSS-I): a placebo-controlled, double-blinded, randomised clinical trial', <i>Lancet Rheumatol</i>, vol. 2, no. 5, pp. e260–e269, May 2020, doi: 10.1016/S2665-9913(20)30057-6. [2] J. M. van Woerkom <i>et al.</i>, 'Safety and efficacy of leflunomide in primary Sjogren's syndrome: a phase II pilot study', <i>Ann Rheum Dis</i>, vol. 66, no. 8, pp. 1026–1032, Jan. 2007, doi: 10.1136/ard.2006.060905. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Elisa Fiorentini: None declared, Matilde Bandeira SPCare, Manuel Silvério-António: None declared, Nikita Khmelinskii GSK, AstraZeneca, GSK, Vifor Pharma, Abbvie, AstraZeneca, GSK, Novartis, Arianna Damiani: None declared, Laura Cometi Lilly, Serena Guiducci: None declared, Joao Eurico Fonseca: None declared, Vasco C Romão Astrazeneca, Abbvie, GSK, Janssen, Lilly, Pfizer, Sobi, Research grant: MSD, SPCare Travel Grants and scientific support: Abbvie, Lilly, Medac, Novartis, Pfizer, Roche.