Would it be reasonable to add mycophenolate to tocilizumab (Interleukin-6 receptor antagonist) in a patient with diffuse scleroderma and positive PM/SCL (Polymyositis/Scleroderma) antibodies, who has developed a typical NSIP (Nonspecific Interstitial Pneumonia) pattern on CT scan?

Adding Mycophenolate to Tocilizumab for Diffuse Scleroderma with NSIP Pattern

Yes, adding mycophenolate to tocilizumab is reasonable and supported by current guidelines for this patient with diffuse scleroderma who has developed NSIP pattern ILD on CT. 1

Rationale for Combination Therapy

The 2023 ACR/CHEST guidelines specifically address this clinical scenario and support your proposed approach:

• Tocilizumab was studied primarily in early SSc-ILD, not as monotherapy for established ILD with NSIP pattern 1
• Mycophenolate is conditionally recommended as a first-line treatment option for SSc-ILD and is specifically recommended when switching therapy for ILD progression 1
• Some panelists explicitly add rituximab to mycophenolate for SSc-ILD, establishing precedent for combination immunosuppressive approaches in this disease 1

Clinical Context Supporting This Decision

Your patient has several features that favor adding mycophenolate:

• PM/Scl antibody positivity is associated with ILD risk and often responds to immunosuppression 1
• NSIP pattern on CT specifically responds well to mycophenolate-based therapy 2, 3, 4
• Diffuse cutaneous involvement suggests more aggressive disease requiring robust immunosuppression 5

Evidence for Mycophenolate in SSc-ILD with NSIP

Mycophenolate has the strongest evidence base for SSc-ILD treatment:

• The American Thoracic Society recommends mycophenolate as the primary treatment for SSc-ILD (not just suggests) 6
• Early treatment with mycophenolate in clinically evident SSc-ILD improves DLCO and FVC within 4-6 months 7
• Combination of rituximab and mycophenolate was superior to mycophenolate alone in ILD with NSIP pattern, demonstrating that combination approaches can be beneficial 3

Practical Implementation

Dosing and monitoring:

• Start mycophenolate at 1000-1500 mg twice daily (target 2g daily) 2, 8
• Monitor CBC every 2-4 months for cytopenias 2, 8
• Perform baseline and periodic liver function tests 2
• Continue tocilizumab at current dose (typically 162 mg subcutaneously weekly) 1

Assessment of response:

• Obtain baseline pulmonary function tests (FVC and DLCO) 2, 8
• Repeat PFTs every 3-6 months to assess for stabilization or improvement 8
• Consider repeat HRCT at 6-12 months if clinically indicated 2

Critical Pitfalls to Avoid

Do not add or continue long-term glucocorticoids for this patient's ILD—the ACR/CHEST guideline has a strong recommendation against glucocorticoids in SSc-ILD due to moderate-certainty evidence of scleroderma renal crisis risk 1

Monitor for infections carefully given dual immunosuppression—the combination of rituximab and mycophenolate showed increased viral infections in one trial, though your patient is on tocilizumab rather than rituximab 3

Ensure PJP prophylaxis with trimethoprim-sulfamethoxazole given combination immunosuppression 1

Alternative Considerations if Progression Occurs

If ILD progresses despite tocilizumab plus mycophenolate:

• Rituximab can be added to or substituted for one agent, with evidence for FVC stabilization in SSc-ILD 1, 6
• Nintedanib may be added, particularly if progressive fibrosing features develop on HRCT 1
• Cyclophosphamide remains an option despite toxicity concerns 1, 6

The combination you propose is guideline-concordant, evidence-based, and addresses the specific pathology (NSIP pattern) that has emerged in your patient. 1, 2