2084: Efficacy and Safety of a Step-down Regimen of Low Dosage of Glucocorticoids Combined with Early Administration of Synthetic or Biologic Immunosuppressants in Anti-synthetase Syndrome: A Pilot Study
No financial relationships with ineligible companies to disclose
Edoardo Conticini1, Paolo Cameli1, Silvia Grazzini1, Miriana d'Alessandro1, Laura Bergantini1, Brunetta Porcelli1, Maria Antonietta Mazzei1, Luca Cantarini1, Elena Bargagli1 and Bruno Frediani2, 1Università di Siena, Siena, Italy, 2Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy Background/Purpose: Anti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of anti-aminoacyl-transfer-RNA synthetase antibodies (ARS) and the involvement of muscles, skin, joints, and lungs. Despite increasing interest and evidence, optimal clinical management remains unclear due to a lack of randomized control trials. This study aims to evaluate the efficacy and safety of a treatment regimen involving early co-administration of glucocorticoids and immunosuppressants, with rapid prednisone tapering. Methods: We prospectively enrolled patients referred to our multidisciplinary “Myositis Clinic” with a diagnosis of ASS. Clinical, serological, instrumental and medications data were collected at baseline and at 6 and 12 months follow-up. According to treatment protocol, patients were treated with traditional synthetic immunosuppressants or rituximab (RTX) depending on clinical manifestations. Prednisone (PDN) was gradually tapered and eventually discontinued within 6 or 12 months. Results: A total of twenty-seven subjects were enrolled: arthritis, myositis and ILD were assessed in 9, 16 and 18 patients, respectively, and all of them had an active disease. RTX was administered after methotrexate (MTX) in 4 cases of refractory joint involvement and co-administration of a second immunosuppressant was necessary in 2 patients. When muscle involvement was present, first-line therapy was MTX, followed by mycophenolate mofetil (MMF) or RTX, which allowed to achieve low disease activity or remission, respectively. Eight ILD-patients were treated with MMF and switched to RTX in 5 cases of inefficacy, but all patients were in clinical remission at the end of follow-up. At 12 months, 12 patients discontinued PDN. Conclusion: This study is the first to prospectively report on the efficacy and safety of a stepwise, steroid-sparing treatment ASS encompassing various domains. MTX, as well as other synthetic immunosuppressants, showed limited efficacy in ASS-related arthritis, while RTX emerged as a promising option. This study recommends early RTX use in case of arthritis, suggesting it as a pivotal treatment for ILD too, and raises questions regarding maintenance therapy and treatment-free remission.
Induction scheme for the treatment of ASS. Legend: ILD: interstitial lung disease; PDN: prednisone.
Mean glucocorticoids dosage at baseline and during follow-up. Legend: PDN: prednisone; SD standard deviation.
Lung function tests at baseline and during follow-up. Legend: DLCO: diffusing capacity for carbon monoxide; FEV1: forced expiration; FVC: forced vital capacity; SD standard deviation.
E. Conticini: None; P. Cameli: None; S. Grazzini: None; M. d'Alessandro: None; L. Bergantini: None; B. Porcelli: None; M. Mazzei: None; L. Cantarini: None; E. Bargagli: None; B. Frediani: None.