Old medications and new targeted therapies in systemic sclerosis

Abstract

SSc is a multiorgan disease with significant morbidity that is associated with poor health-related quality of life. Treatment of this condition is often organ based and non-curative. However, there are newer, potentially disease-modifying therapies available to treat certain aspects of the disease. This review focuses on old and new therapies in the management of SSc in clinical practice.

Keywords: Raynaud’s phenomenon; digital ulcers; immunosuppressive therapy; interstitial lung disease; pulmonary arterial hypertension; renal crisis; skin fibrosis; systemic sclerosis; treatment.

Fig. 1

Treatment recommendations in SSc Expert consensus and a growing evidence base underpin the management of SSc, as shown schematically with focus on individual organ systems and current approaches used in practice. MSK: musculoskeletal; ILD: interstitial lung disease; PAH: pulmonary arterial hypertension; RCT: randomized controlled trial; ERA: endothelin receptor antagonist; PDE-5i: phosphodiesterase-5 inhibitor; sGC: soluble guanylate cyclase; CCBs: calcium channel blockers; ARB: angiotensin receptor blocker; DU: digital ulcer; SRC: scleroderma renal crisis; ACEi: angiotensin converting enzyme inhibitor.

Fig. 2

Current management of digital vasculopathy in SSc Treatment approaches may target individual pathological processes in SSc and include agents that are undergoing clinical evaluation or may have potential. Anti-fibrotic strategies are currently less developed than vascular or immunological candidate therapies. *If indicated. MRA: magnetic resonance angiography; CCB: calcium channel blocker; ARB: angiotensin receptor blocker. Modified from the Royal Free Hospital protocol.

Fig. 3

Potential novel therapies in SSc Digital ischaemia underlies important complications of systemic sclerosis and is amenable to multifaceted treatment including an increasing number of potentially disease-modifying agents that may work through a combination of vasodilator, anti-infective or structural vascular mechanisms. ET_A: endothelin A; ET_B: endothelin B; IP: prostacyclin; CD20: cluster of differentiation 20; CTLA4: cytotoxic T lymphocyte antigen 4; c-ABL: Abelson murine leukaemia viral oncogene; c-KIT: stem cell factor; CTGF: connective tissue growth factor; FGF: fibroblast growth factor; LPA: lysophosphatidic acid receptor; CB2: cannabinoid receptor 2; HT: 5-hydroxytryptamine receptor.