What medication is used for systemic sclerosis with lung involvement?

October 14, 2025 •

3 min read

Interstitial lung disease (ILD) is a leading cause of death in people with systemic sclerosis (SSc), affecting up to 65% of patients. This condition leads to inflammation and fibrosis, or scarring, of the lungs. Thankfully, a range of therapies, including new FDA-approved options, now exist to slow disease progression and manage symptoms for systemic sclerosis with lung involvement.

Quick Summary

Several medications are used to treat systemic sclerosis with lung involvement, including immunosuppressants such as mycophenolate mofetil and targeted therapies like the antifibrotic drug nintedanib and the biologic tocilizumab. Treatment choice depends on disease severity and progression.

Key Points

Mycophenolate Mofetil (MMF) is First-Line: MMF is a recommended initial therapy for SSc-ILD due to its efficacy and better tolerability.
Nintedanib is an FDA-Approved Antifibrotic: Approved for SSc-ILD, nintedanib slows the decline in pulmonary function and can be used alone or combined with immunosuppressants.
Tocilizumab is an FDA-Approved Biologic: This biologic agent targets the IL-6 pathway and is approved to slow lung function decline in SSc-ILD, particularly for patients with early, inflammatory disease.
Combination Therapy is an Option: Combining an immunosuppressant like mycophenolate with an antifibrotic like nintedanib may benefit patients with progressive or more advanced disease.
Monitoring is Key: Regular PFTs and HRCT are essential for tracking disease and assessing treatment response.
Cyclophosphamide for Severe Cases: This potent immunosuppressant is reserved for rapidly progressive SSc-ILD due to its toxicity risk.
Alternative Treatments for End-Stage Disease: AHSCT or lung transplantation are options for severe, refractory cases.
Treatment Choice Depends on Disease State: Medication regimens are chosen based on factors like disease severity, activity level, and progression rate.

Understanding Systemic Sclerosis with Lung Involvement

Systemic sclerosis (SSc), commonly known as scleroderma, is a chronic, progressive autoimmune disease that causes widespread fibrosis, or thickening and scarring of connective tissues. When this scarring affects the lungs, it is called systemic sclerosis-associated interstitial lung disease (SSc-ILD). SSc-ILD can severely compromise lung function, leading to respiratory failure and a high mortality rate. Management aims to control inflammation and slow down the fibrotic process to preserve lung function.

Immunosuppressants: Modulating the Immune Response

Traditional immunosuppressive therapies have been foundational in treating SSc-ILD by targeting the immune system overactivity that drives inflammation.

Mycophenolate Mofetil (MMF): MMF is widely recommended as a first-line treatment for SSc-ILD due to its efficacy and better safety profile compared to older options like cyclophosphamide. It inhibits lymphocyte proliferation and has shown effectiveness for long-term disease stabilization and preserving pulmonary function.
Cyclophosphamide (CYC): A potent immunosuppressant, cyclophosphamide is often used for patients with rapidly progressing SSc-ILD. Its use is limited by a less favorable side effect profile.
Rituximab (RTX): This monoclonal antibody targets B-cells. It's a second-line therapy for patients who progress despite treatment with mycophenolate and has shown comparable effectiveness to cyclophosphamide with fewer adverse events.

Targeted Therapies: Blocking Fibrotic Pathways

Newer, targeted therapies address the fibrotic component of SSc-ILD.

Nintedanib: This antifibrotic medication is FDA-approved to slow the rate of decline in pulmonary function for SSc-ILD patients. It blocks multiple signaling pathways involved in fibrosis. Studies like the SENSCIS trial showed it reduced the rate of FVC decline. It may be combined with immunosuppressants.
Tocilizumab: Also FDA-approved for SSc-ILD, this biologic agent blocks the interleukin-6 (IL-6) receptor, an inflammatory cytokine that drives fibrosis in SSc. Clinical trials suggest it helps preserve lung function.

Comparison of Key Medications for SSc-ILD


Feature	Mycophenolate Mofetil (MMF)	Nintedanib	Tocilizumab	Cyclophosphamide (CYC)
Drug Class	Immunosuppressant	Antifibrotic (Tyrosine Kinase Inhibitor)	Biologic (IL-6 Receptor Blocker)	Immunosuppressant
Administration	Oral tablets	Oral capsules	Subcutaneous injection or IV infusion	Oral or IV infusion
Mechanism	Inhibits lymphocyte proliferation.	Blocks multiple pathways involved in fibrosis.	Blocks inflammatory cytokine IL-6.	Potent cytotoxic agent.
FDA Approval for SSc-ILD	Recommended as first-line but not FDA-approved for SSc-ILD.	Yes (2019).	Yes (2021).	Recommended conditionally, but not FDA-approved.
Typical Use	First-line therapy for ongoing management.	Add-on for progressive disease or as monotherapy in stable disease.	Initial therapy for high-risk, early-stage disease with inflammation.	Rapidly progressive disease or treatment failure.
Primary Goal	Stabilize and preserve lung function.	Slow the rate of lung function decline.	Preserve lung function, especially in early, inflammatory disease.	Suppress acute inflammatory activity.
Notable Side Effects	Gastrointestinal upset, myelosuppression.	Diarrhea, nausea, liver enzyme elevation.	Infections, injection site reactions.	High toxicity risk, including myelosuppression, bladder issues.

Sequential and Combination Therapy

Treatment plans for SSc-ILD are individualized. Combination therapy, such as nintedanib with mycophenolate, may be used for more severe or progressive disease. Regular monitoring with pulmonary function tests (PFTs) and HRCT is crucial.

Other and Investigational Treatments

Autologous Hematopoietic Stem Cell Transplantation (AHSCT): This intensive procedure is for select patients with severe, rapidly progressing SSc but carries significant risks.
Lung Transplantation: An option for end-stage lung disease unresponsive to other treatments.
Emerging Therapies: Research continues into novel agents and clinical trials are ongoing.

Conclusion

Management of SSc-ILD has advanced with targeted therapies like nintedanib and tocilizumab alongside immunosuppressants like mycophenolate mofetil. Treatment is tailored based on disease severity and progression. A multidisciplinary approach is essential for proper management. Ongoing research aims to further improve outcomes.

Frequently Asked Questions

Mycophenolate mofetil (MMF) is widely recommended as the initial treatment of choice for many patients with SSc-ILD due to its strong evidence base and favorable safety profile. Other options may be considered depending on the patient's specific presentation.

Nintedanib can be used as monotherapy, particularly in patients with stable disease or those who cannot tolerate immunosuppressants. However, it may also be combined with an immunosuppressant, such as mycophenolate mofetil, especially in patients with progressive disease, to provide a stronger antifibrotic and immunosuppressive effect.

Tocilizumab is a biologic medication that targets and blocks the interleukin-6 (IL-6) receptor. By inhibiting IL-6 signaling, tocilizumab reduces inflammation and plays a key role in preventing the excessive fibrosis that damages the lungs in SSc-ILD.

The most common adverse events associated with nintedanib include diarrhea, nausea, vomiting, and elevated liver enzymes. Gastrointestinal side effects are particularly notable in SSc-ILD patients, but they can often be managed with dose adjustments or other medications.

Cyclophosphamide is typically reserved for patients with more severe or rapidly progressive SSc-ILD due to its greater toxicity. It is often used for a limited duration to achieve a rapid immunosuppressive effect, after which patients may transition to a maintenance therapy like mycophenolate mofetil.

Some patients may see stabilization or even modest improvement in lung function with treatment, especially if started early in the disease course. However, treatment primarily aims to slow the rate of decline and prevent further damage, as lung scarring (fibrosis) is largely irreversible.

AHSCT is a very aggressive therapy considered for a small, select group of patients with severe, rapidly progressive SSc-ILD that is unresponsive to other treatments. It aims to reset the immune system, but it involves significant risks and is not a routine procedure.