Introduction: Anti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of antiaminoacyl-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. Materials and 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. Conclusions: 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.

Conticini, E., Cameli, P., Grazzini, S., D'Alessandro, M., Bergantini, L., Porcelli, B., et al. (2024). 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. SEMINARS IN ARTHRITIS AND RHEUMATISM, 69 [10.1016/j.semarthrit.2024.152560].

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

Conticini, Edoardo;Cameli, Paolo
;
Grazzini, Silvia;d'Alessandro, Miriana;Bergantini, Laura;Porcelli, Brunetta;Mazzei, Maria Antonietta;Cantarini, Luca;Bargagli, Elena;Frediani, Bruno
2024-01-01

Abstract

Introduction: Anti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of antiaminoacyl-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. Materials and 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. Conclusions: 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.
2024
Conticini, E., Cameli, P., Grazzini, S., D'Alessandro, M., Bergantini, L., Porcelli, B., et al. (2024). 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. SEMINARS IN ARTHRITIS AND RHEUMATISM, 69 [10.1016/j.semarthrit.2024.152560].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1276449