Symposium 3

Abstract

Systemic sclerosis (SSc) remains a refractory condition with poor functional and survival outcomes. This is attributable primarily to the extremely diverse clinical course and distribution of organ involvement. The pathogenesis of SSc includes microangiopathy and chronic inflammation, leading to accumulation of extracellular matrix and resultant irreversible fibrosis resulting in distortion of the normal tissue architecture. This pathogenic process is analogous to that observed in rheumatoid arthritis, in which persistent synovitis leads to articular cartilage and bone destruction, resulting in functional impairment due to joint deformity. Therefore, successful experiences in developing treatment strategies in patients with rheumatoid arthritis can also be applied to SSc. These include early diagnosis and intervention, treat-to-target strategy aiming at achievement of clinical remission or low-disease activity, prediction of disease progression and prognosis, and disease modification by pharmacologic treatment. Immunosuppressants targeting lymphocytes, including mycophenolate mofetil and cyclophosphamide, have been the mainstream of the treatment of SSc, based on treatment evidence showing prevention of decline in forced vital capacity, promotion of improving modified Rodnan skin thickness score, and improved patient-reported outcomes. However, survival benefit has not been shown in long-term follow-up of patients treated with non-specific immunosuppressants. Recently, drugs targeting a variety of molecules involved in the pathologic process of SSc, such as tocilizumab and nintedanib, have been shown to prevent progression of certain organ involvement in clinical trials, resulting in expanding treatment options. Implementation of those potential disease-modifying therapies in management of SSc requires adequate assessment of disease activity and treatment goal setting. In addition, clinical characteristics that predict the progression of organ manifestations, such as skin sclerosis and interstitial lung disease, need to be identified as prognosis factors. Like other rheumatic diseases, early interventions have been shown to be more effective than delayed intervention. This lecture features current standings and challenges of treat-to-target strategy in SSc patients.