What is the most common treatment for systemic sclerosis?

Most Common Treatment for Systemic Sclerosis

Mycophenolate mofetil (MMF) is the most common first-line treatment for systemic sclerosis, particularly for skin manifestations and interstitial lung disease. 1

Treatment Approach Based on Disease Manifestations

Skin Manifestations

• First-line: Mycophenolate mofetil (MMF)

  • Chosen primarily because it provides benefits for both skin and interstitial lung disease 1
  • Skin improvement occurs in approximately 72% of patients treated with MMF 1

• Alternative first-line/second-line:

  • Methotrexate (15-25 mg weekly)
    • Between-group difference of approximately 5 points in modified Rodnan skin score (mRSS) compared to placebo 1
    • Higher doses (up to 25 mg weekly) are now commonly prescribed 1

• For worsening or severe skin disease:

  • Rituximab (anti-CD20)
  • Tocilizumab (anti-IL-6)
  • Cyclophosphamide (oral or IV)
  • Autologous hematopoietic stem cell transplantation (AHSCT) in eligible patients 1

Interstitial Lung Disease (ILD)

• First-line: Mycophenolate mofetil

  • Has surpassed cyclophosphamide as initial treatment for SSc-ILD 1

• For progressive fibrotic ILD:

  • Add nintedanib (anti-fibrotic therapy) 1
  • Possibly pirfenidone 1

• For severe or rapidly progressive ILD:

  • Cyclophosphamide 1
  • Consider rituximab 1

Raynaud's Phenomenon and Digital Ulcers

• First-line: Dihydropyridine calcium channel blockers (especially nifedipine) 1, 2

• Second-line:

  • Phosphodiesterase-5 inhibitors 1, 2
  • IV iloprost (for severe cases) 1, 2

• For prevention of digital ulcers:

  • Bosentan (endothelin receptor antagonist) can reduce development of new digital ulcers 1

Pulmonary Arterial Hypertension (PAH)

• Initial treatment: Combination therapy with:

  • Phosphodiesterase-5 inhibitors and
  • Endothelin receptor antagonists 1, 2

• For severe or progressive PAH:

  • Add prostacyclin analogues 1, 2

Disease-Modifying Treatments

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

• Reserved for carefully selected patients with early diffuse cutaneous SSc at high risk of mortality 1
• Candidates include those with:
  • Very high skin scores (mRSS)
  • Moderate skin involvement with worsening ILD 1
• Can improve survival but carries significant treatment-related risks 1

Treatment Selection Considerations

Diffuse Cutaneous SSc vs. Limited Cutaneous SSc

• Treatment is more aggressive for diffuse cutaneous SSc (dcSSc)
• Appropriate treatment for early limited cutaneous SSc is less well-defined 1
• Recent trend shows increased and earlier use of immunosuppressants in dcSSc patients 3

Antibody Status

• Anti-topoisomerase 1 (anti-Scl-70) antibodies are associated with higher risk of ILD 1
• Autoantibody status is a consistent predictor of immunosuppressive therapy needs 3

Common Pitfalls and Caveats

1. Delayed treatment initiation: Early intervention is crucial, particularly for ILD and skin manifestations in dcSSc.

2. Inadequate monitoring: Regular screening for organ complications is essential (particularly for ILD and PAH).

3. Suboptimal dosing: Higher doses of methotrexate (up to 25 mg weekly) may be more effective than previously studied lower doses 1.

4. Limited access to biologics: Many prescribers have restricted access to tocilizumab and rituximab, which may limit treatment options 1.

5. Treatment discontinuation risks: Abrupt discontinuation of cyclophosphamide can lead to progression of restrictive lung disease after one year 1.

6. Weak treatment effects: Most treatments for skin disease have only modest effects, highlighting the need for new treatment approaches or combination therapies 1.