Scleroderma Medication

Updated: Mar 01, 2023
  • Author: Abhishek Nandan, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication Summary

Pharmacologic therapy consists principally of treatment directed toward complications of the disease and providing symptomatic relief. Nintedanib and tocilizumab are approved by the US Food and Drug Administration to slow the rate of decline in pulmonary function in adults with interstitial lung disease associated with scleroderma.



Class Summary

These agents are used to treat inflammatory complications (eg, myositis, pneumonitis).

Prednisone (Deltasone, Rayos, Prednisone Intensol, Sterapred, Sterapred DS)

Prednisone is an immunosuppresant used for treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing inflammatory cell activity. Prednisone is inactive and must be metabolized to prednisolone. Metabolism may be impaired in patients with liver disease. High dose corticosteroids (e.g.- prednisone >20mg) should be avoided in systemic sclerosis because it increases the risk of renal crisis.


Immunosuppressive agents

Class Summary

These agents inhibit key steps in immune reactions.

Azathioprine (Azasan, Imuran)

Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA and RNA. It may decrease proliferation of immune cells, which results in lower autoimmune activity.

Methotrexate (Trexall, Rheumatrex, Otrexup, Rasuvo)

Methotrexate is an antimetabolite that inhibits DNA synthesis and cell division in malignant cells. It may suppress the immune system. Methotrexate use in systemic sclerosis should be avoided in severe or active interstitial lung disease.

Cyclophosphamide (Cytoxan)

Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth and proliferation of normal and neoplastic cells.

Mycophenolate (CellCept, Myfortic, MMF)

Mycophenolate is a potent selective, noncompetitive, and reversible inhibitor of purine synthesis. It has cytostatic effects on lymphocytes. It may suppress the immune system.

Rituximab (Rituxan)

Rituximab is a potent immunosuppressive drug that acts by causing a selective depletion of B lymphocytes. Rituximab was initially approved for treatment of certain hematologic malignancies. However, owing to its potent immunosuppressive effects, its use in the therapy of autoimmune diseases, including systemic sclerosis, is expanding rapidly.

Tocilizumab (Actemra)

Tocilizumab is indicated for treatment of interstitial lung disease in systemic sclerosis that is refractory or highly progressive.


Tyrosine Kinase Inhibitors

Class Summary

Nintedanib is a tyrosine kinase inhibitor that targets growth factors (eg, vascular endothelial growth factor receptor [VEGFR], fibroblast growth factor receptor [FGFR], platelet-derived growth factor receptor [PDGFR] 1-3, colony-stimulating factor 1 receptor [CSFIR]) that are implicated in the pathogenesis of interstitial lung diseases.

Nintedanib (Ofev)

Indicated to slow the rate of decline in pulmonary function in patients who have interstitial lung disease associated with scleroderma.


Endothelin receptor antagonist

Class Summary

These agents bind to endothelin receptors present in endothelium and vascular smooth muscle cells. The effect can result in vasodilation.

Bosentan (Tracleer)

Bosentan is a dual endothelin A and B receptor antagonist for treatment of pulmonary arterial hypertension. It decreases both pulmonary and systemic vascular resistance and increases cardiac output without increasing heart rate

Ambrisentan (Letairis)

Ambrisentan is an endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with World Health Organization (WHO) class II or III symptoms. It improves exercise ability and decreases progression of clinical symptoms. Ambrisentan inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to significant increase in cardiac index associated with significant reduction in pulmonary artery pressure, pulmonary vascular resistance, and mean right atrial pressure.

Because of the risks of hepatic injury and teratogenic potential, this agent is available only through the Letairis Education and Access Program (LEAP). Prescribers and pharmacies must register with LEAP in order to prescribe and dispense. For more information, see or call (866) 664-LEAP (5327).

Macitentan (Opsumit)

Macitentan is a novel agent acting as dual endothelin receptor-1(ETA and ETB) antagonist with sustained receptor-binding properties. It has been approved by the FDA for the treatment of pulmonary hypertension. Studies assessing its efficacy and safety in ischemic digital ulcers secondary to Raynaud phenomenon is systemic sclerosis are under way.


PAH, PDE-5 Inhibitors

Class Summary

These agents may increase vasodilation in the pulmonary vascular bed.

Tadalafil (Adcirca)

Tadalafil is aphosphodiesterase type-5 inhibitor indicated for improving and increasing exercise capacity in patients with World Health Organization (WHO) class I pulmonary arterial hypertension. It increases cyclic guanosine monophosphate (cGMP), which is the final mediator in the nitric-oxide pathway. Tadalafil has been shown to improve systemic sclerosis associated pulmonary hypertension and Raynaud phenomenon. Tadalafil has an extended half-life and therefore can be administered once daily without compromising its effectiveness.

Sildenafil (Revatio)

Sildenafil promotes selective smooth muscle relaxation in lung vasculature, possibly by inhibiting phosphodiesterase type 5. This effect results in subsequent reduction of pulmonary artery pressure and increase in cardiac output.

Sildenafil has been shown to be effective in reducing pulmonary artery pressure in systemic sclerosis associated pulmonary hypertension. Because of its potent peripheral vasculature vasodilatory effects it has also been used for treatment of severe Raynaud phenomenon with digital ulcers. However, owing to the short duration of its vasodilatory effects, sildenafil has to be administered several times per day.


Chelating agents

Class Summary

These agents may improve the fibrotic aspects of systemic sclerosis.

Penicillamine (Cuprimine, Depen)

Penicillamine inhibits the formation of mature collagen crosslinks, rendering un-crosslinked molecules more susceptible to proteolytic degradation. The inhibition of collagen crosslink formation very likely causes a marked decrease in tissue stiffness, an important profibrotic mechanism.