What treatment options are available for patients with a high Modified Rodnan Skin Score (MRSS) indicating significant skin involvement in scleroderma?

Treatment Options for High Modified Rodnan Skin Score (MRSS) in Scleroderma

Mycophenolate mofetil (MMF) should be considered as the first-line treatment for patients with high Modified Rodnan Skin Score (MRSS) indicating significant skin involvement in scleroderma. 1

First-Line Treatment Options

Mycophenolate Mofetil (MMF)

• Most commonly used first-line drug for skin manifestations in diffuse cutaneous systemic sclerosis (dcSSc) 1
• Post-hoc analyses from the Scleroderma Lung Study II showed significant improvement in MRSS from baseline to 24 months (-4.90,95% CI -6.4 to -3.4) 1
• Better safety profile compared to cyclophosphamide with significantly fewer cases of leukopenia (4 vs 30 patients) 1
• Additional benefit: Positive effects on interstitial lung disease (ILD), which commonly co-exists with skin fibrosis 1

Methotrexate

• Alternative first-line treatment or second-line after MMF 1
• Studies showed a between-group difference of approximately 5 points in MRSS compared to placebo 1
• Higher doses (up to 25 mg weekly) are often prescribed, though optimal dosing is not definitively established 1

Second-Line Treatment Options

Rituximab

• Strong evidence from a double-blind RCT in Japan showing significant improvement in MRSS at 24 weeks compared to placebo (-6.30 vs +2.14; difference -8.44) 1
• Recommended by EULAR for treatment of skin fibrosis in SSc 1
• Consider when patients fail to respond to first-line therapies 1

Cyclophosphamide

• In Scleroderma Lung Study I, one year of oral cyclophosphamide resulted in a between-group difference in MRSS of 3 points versus placebo 1
• In Scleroderma Lung Study II, showed improvement in MRSS of -5.35 over 24 months 1
• 78% of patients showed improvement of ≥5 units in MRSS 1
• Caution: Higher risk of adverse effects including leukopenia compared to MMF 1

Tocilizumab

• May be considered specifically for early, inflammatory dcSSc 1
• Phase 2 trial showed a trend toward benefit with change in MRSS at 48 weeks of -6.33 vs -2.77 in placebo group 1
• Phase 3 trial showed modest improvement (-6.14 vs -4.41 for placebo) 1

Advanced Treatment Option

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

• Most dramatic effect on skin fibrosis with between-group differences in MRSS of approximately 10 points 1
• Associated with 20-point reduction in MRSS in the ASTIS trial 1
• Consider for patients with rapidly progressive early dcSSc who have failed other therapies 1
• Important caveat: 5-10% treatment-related mortality risk, requiring careful patient selection 1

Monitoring and Assessment

• MRSS is the gold standard for measuring dermal skin thickness in scleroderma 2
• Skin improvement (decrease in MRSS) correlates with overall disease improvement, better function, and improved quality of life 3
• A decrease of ≥5 points or ≥25% in MRSS is considered clinically meaningful improvement 3
• Regular assessment of MRSS is essential to monitor treatment response

Treatment Algorithm

1. Initial Assessment:

   • Confirm high MRSS (significant skin involvement)
   • Assess for concurrent organ involvement, especially ILD

2. First-line Treatment:

   • If ILD is present or suspected: Start MMF
   • If minimal/no ILD concern: Consider either MMF or methotrexate

3. Monitoring Response:

   • Assess MRSS every 3-6 months
   • Target improvement of ≥5 points or ≥25% in MRSS

4. If Inadequate Response after 6-12 months:

   • Switch to alternative first-line agent or
   • Add/switch to second-line therapy (rituximab, tocilizumab, or cyclophosphamide)

5. For Severe Progressive Disease Despite Treatment:

   • Consider AHSCT in eligible patients at experienced centers

Important Considerations

• Skin involvement in scleroderma is associated with more severe internal organ manifestations and poorer prognosis 2
• Early intervention is crucial as most treatments show better efficacy in early inflammatory disease
• Most treatments for skin disease have only modest effects; combination therapy may be needed in resistant cases 1
• Regular assessment of other organ systems is essential as skin improvement may not always correlate with improvement in all organs