Title:Molecular and Cellular Pathways as Treatment Targets for Biologic Therapies in Systemic Sclerosis
Volume: 22
Issue: 16
Author(s): Theodoros Dimitroulas, Dimitrios Daoussis, Alexandros Garyfallos, Petros P. Sfikakis and George D. Kitas
Affiliation:
关键词:
系统性硬化，纤维化，生物治疗，利妥昔单抗，托珠单抗。
摘要: Recent advances have shed light on the complex pathogenic processes that underlie the development
and progression of Systemic Sclerosis (SSc) but management of the disease remains problematic
and curative treatment is not available. Better understanding of the underlying pathology has
enabled novel therapeutic approaches to be investigated, as therapies in rheumatology are becoming increasingly disease/
organ-specific, targeting unique biological networks and signalling pathways. The pathophysiologic and clinical
pleiomorphism of SSc however, represents a major barrier to conducting large well-controlled studies for the evaluation
of non-selective immunosuppressive and novel highly selective agents. Therapeutic biologic strategies targeting inflammatory
or profibrotic cytokines and lymphocyte activation proved to be efficacious in other systemic rheumatic diseases
but have demonstrated contradictory results in SSc. Blocking of tumour necrosis factor alpha and interleukin-6 may improve
SSc-associated arthritis, while depletion of B-cells may have benefits for skin and lung fibrosis, but randomized
studies are needed. In this review we critically appraise available data for the treatment of SSc focusing on immunologic
and antifibrotic strategies. Attenuation of the fibrotic process remains an unmet goal but the potential to prevent damage
by promoting tissue repair has been shown in preclinical studies. Translation of these findings into clinical practice will
hopefully establish new therapeutic options and improve prognosis of these patients, for which our therapeutic armamentarium
remains poor.
