What are the newer drugs for treating systemic sclerosis?

Newer Drugs for Systemic Sclerosis Treatment

The most effective newer drugs for systemic sclerosis include nintedanib, tocilizumab, and rituximab, which target different pathological mechanisms of the disease and have shown significant benefits for specific organ manifestations. 1, 2

Key Newer Medications by Organ System

For Interstitial Lung Disease (ILD)

1. Nintedanib

   • Anti-fibrotic therapy with level 1A evidence and strength of recommendation A
   • Indicated for SSc-ILD, can be used alone or in combination with mycophenolate mofetil (MMF)
   • Slows the rate of decline in pulmonary function 1
   • Dosage: 150mg twice daily (can be reduced to 100mg twice daily if not tolerated)

2. Tocilizumab

   • IL-6 receptor antagonist with level 1B evidence and strength of recommendation B
   • FDA-approved specifically for slowing the rate of decline in pulmonary function in SSc-ILD 2
   • Demonstrated preservation of forced vital capacity (FVC) in clinical trials 3
   • Dosage: 162mg subcutaneously weekly or 4-8mg/kg intravenously monthly

3. Rituximab

   • Anti-CD20 B-cell depleting therapy with level 1A evidence for ILD 1
   • Particularly effective for patients with early, inflammatory disease
   • Shown to stabilize or improve lung function in multiple studies 4
   • Dosage: Two intravenous infusions 2 weeks apart, then one infusion every 6 months

For Skin Fibrosis

1. Rituximab

   • Level 1A evidence for treatment of skin fibrosis 1
   • Demonstrated significant reduction in modified Rodnan Skin Score (mRSS) in randomized controlled trials
   • In the DESIRES trial, showed absolute change in mRSS of -6.30 vs +2.14 in placebo group (p<0.0001) 4
   • Particularly effective in early diffuse cutaneous SSc 5

2. Tocilizumab

   • Level 1B evidence with strength of recommendation C for skin fibrosis 1
   • May be considered specifically for early, inflammatory diffuse cutaneous SSc
   • Shows beneficial effects on global composite measures 3

Treatment Algorithm Based on Organ Involvement

For SSc-ILD:

1. First-line: MMF (2-3g daily)
2. For progressive disease despite MMF:
   • Add nintedanib (150mg twice daily)
   • OR switch to/add tocilizumab (162mg SC weekly)
   • OR switch to/add rituximab (two IV infusions 2 weeks apart, then every 6 months)
3. For severe or rapidly progressive ILD:
   • Consider cyclophosphamide (IV 600mg/m²) followed by maintenance with MMF
   • Consider autologous hematopoietic stem cell transplantation (AHSCT) in selected patients with early diffuse disease and poor prognosis 1

For Skin Fibrosis:

1. First-line: MMF or methotrexate
2. For inadequate response or severe disease:
   • Rituximab (particularly effective in early diffuse disease)
   • Tocilizumab (for early inflammatory diffuse cutaneous SSc)
   • Cyclophosphamide (for concurrent severe ILD)

Clinical Pearls and Pitfalls

• Important consideration: Treatment selection should be guided by the predominant organ involvement and disease subtype (diffuse vs. limited cutaneous SSc) 6

• Common pitfall: Delayed initiation of therapy can lead to irreversible organ damage, particularly in rapidly progressive diffuse cutaneous SSc 6

• Monitoring requirement: Regular assessment of pulmonary function tests is essential when using these newer therapies, as early detection of stabilization or improvement guides treatment decisions

• Caution: Rituximab and tocilizumab are immunosuppressive and require appropriate screening for infections prior to initiation

• Treatment duration: These newer therapies typically require long-term administration, as treatment discontinuation can lead to disease progression, particularly for ILD 6

• Combination approach: For severe or progressive disease, combining anti-fibrotic therapy (nintedanib) with immunosuppressive therapy (MMF) may provide additive benefits 1

The evidence supporting these newer therapies represents a significant advancement in SSc treatment, moving beyond traditional immunosuppressants to more targeted approaches addressing specific pathogenic mechanisms of the disease.