When to consider starting Nintedanib (Ofev) in a patient with diffuse type scleroderma and interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern, who has been on Mycophenolate Mofetil (MMF) for 6 months and still shows residual changes on high-resolution computed tomography (HRCT)?

When to Start Nintedanib (Ofev) in SSc-ILD with Residual Changes After 6 Months of MMF

You should start nintedanib now if there is documented progression of ILD (decline in FVC ≥5-10% predicted, worsening respiratory symptoms, or increased fibrosis on HRCT), as the 2023 ACR/CHEST guidelines conditionally recommend nintedanib for SSc-ILD progression despite first-line immunosuppressive therapy. 1

Defining Disease Progression

The key decision point is whether your patient has progressive ILD versus stable disease with residual changes:

• Progressive ILD is defined as: 1

  • FVC decline ≥10% predicted within 24 months, OR
  • FVC decline 5-10% predicted PLUS worsening respiratory symptoms or increased fibrosis on HRCT, OR
  • Worsening respiratory symptoms AND increased fibrosis on HRCT

• "Residual changes" alone on HRCT does not equal progression - you must compare the current HRCT to baseline to determine if fibrosis has increased 1

Treatment Algorithm for Your Patient

If Progression is Documented:

Add nintedanib 150 mg twice daily to the existing MMF regimen 1, 2, 3

• The SENSCIS trial demonstrated that nintedanib reduced FVC decline in SSc-ILD patients already taking MMF (annual decline -40.2 mL/year with nintedanib+MMF vs -66.5 mL/year with placebo+MMF) 3

• The treatment effect was consistent regardless of concomitant MMF use, with no heterogeneity detected between subgroups 3

• Expert consensus supports adding nintedanib to MMF in patients with progressive fibrotic ILD despite immunosuppressive therapy 4

If No Clear Progression:

Continue MMF alone and monitor closely 1

• The 2023 ACR/CHEST guidelines conditionally recommend against adding nintedanib to mycophenolate in patients without evidence of ILD progression 1

• Repeat PFTs every 3-6 months and HRCT within 6 months to detect early progression 1

• The first 3 years after diagnosis are critical for identifying progressive disease 1

Alternative Options if Progression is Documented:

If nintedanib is not tolerated or contraindicated, consider: 1

• Rituximab (conditionally recommended for SSc-ILD progression)
• Tocilizumab (conditionally recommended for SSc-ILD progression)
• Cyclophosphamide (conditionally recommended for SSc-ILD progression)
• Switching from MMF to one of these agents rather than adding nintedanib

Critical Monitoring and Management:

Before Starting Nintedanib:

• Check baseline liver function tests 2, 5
• Counsel patient about diarrhea (occurs in 76% of patients on nintedanib+MMF) 3

After Starting Nintedanib:

• Monitor liver enzymes monthly for 3 months, then every 3 months 5, 6
• Start at 150 mg twice daily; reduce to 100 mg twice daily if diarrhea or other GI side effects are intolerable 2, 6
• Continue monitoring PFTs every 3-6 months to assess treatment response 1

Important Caveats:

• Nintedanib slows progression but does not reverse existing fibrosis - residual changes on HRCT will persist 2, 6

• Strongly avoid glucocorticoids in SSc-ILD due to increased risk of scleroderma renal crisis, particularly at doses >15 mg/day prednisone equivalent 1

• The combination of nintedanib + MMF is safe based on SENSCIS trial data, with adverse event profiles similar between subgroups 3

• Consider early lung transplant referral if disease continues to progress despite combination therapy 1