State-of-the-art evidence in the treatment of systemic sclerosis

Nat Rev Rheumatol. 2023 Apr;19(4):212-226. doi: 10.1038/s41584-023-00909-5. Epub 2023 Feb 27.

Abstract

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and the use of organ-specific therapies, has improved, as evident from randomized clinical trials. Treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab and tocilizumab. Patients with rapidly progressive early dcSSc might be eligible for autologous haematopoietic stem cell transplantation, which can improve survival. Morbidity from interstitial lung disease and pulmonary arterial hypertension is improving with the use of proven therapies. Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease. Nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis. Pulmonary arterial hypertension is frequently treated with initial combination therapy (for example, with phosphodiesterase 5 inhibitors and endothelin receptor antagonists) and, if necessary, the addition of a prostacyclin analogue. Raynaud phenomenon and digital ulcers are treated with dihydropyridine calcium channel blockers (especially nifedipine), then phosphodiesterase 5 inhibitors or intravenous iloprost. Bosentan can reduce the development of new digital ulcers. Trial data for other manifestations are mostly lacking. Research is needed to develop targeted and highly effective treatments, best practices for organ-specific screening and early intervention, and sensitive outcome measurements.

Publication types

  • Review

MeSH terms

  • Cyclophosphamide / therapeutic use
  • Humans
  • Lung Diseases, Interstitial* / drug therapy
  • Mycophenolic Acid / therapeutic use
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Pulmonary Arterial Hypertension* / drug therapy
  • Scleroderma, Systemic* / drug therapy

Substances

  • Mycophenolic Acid
  • Phosphodiesterase 5 Inhibitors
  • Cyclophosphamide

Supplementary concepts

  • digital ulcers