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

• Published in: Seminars in arthritis and rheumatism Vol. 69; p. 152560
• Main Authors: Conticini, Edoardo, Cameli, Paolo, Grazzini, Silvia, d'Alessandro, Miriana, Bergantini, Laura, Porcelli, Brunetta, Mazzei, Maria Antonietta, Cantarini, Luca, Bargagli, Elena, Frediani, Bruno
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2024
• Subjects: Adult; Aged; Anti-synthethase syndrome; Arthritis; Drug Tapering; Drug Therapy, Combination; Female; Glucocorticoids; Glucocorticoids - administration & dosage; Glucocorticoids - therapeutic use; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - therapeutic use; Interstitial lung disease; Male; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Middle Aged; Myositis; Myositis - drug therapy; Pilot Projects; Prednisone - administration & dosage; Prednisone - therapeutic use; Prospective Studies; Rituximab; Rituximab - administration & dosage; Rituximab - adverse effects; Rituximab - therapeutic use; Treatment Outcome; Rituximab; Myositis; Arthritis; Anti-synthethase syndrome; Glucocorticoids; Interstitial lung disease
• ISSN: 0049-0172; 1532-866X; 1532-866X
• DOI: 10.1016/j.semarthrit.2024.152560

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. 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. 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. 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.