Is Rituximab (rituximab) a suitable treatment option for a patient with a history of interstitial lung disease (ILD) experiencing a flare, particularly those with autoimmune conditions such as rheumatoid arthritis (RA) or scleroderma?

Rituximab for ILD Flare in Autoimmune Disease

Rituximab is a conditionally recommended and highly appropriate treatment option for patients with autoimmune-associated interstitial lung disease experiencing a flare, particularly in rheumatoid arthritis, systemic sclerosis, and inflammatory myopathies. 1

First-Line Treatment Context

For patients with systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), rituximab is conditionally recommended as a first-line treatment option alongside mycophenolate, cyclophosphamide, and azathioprine. 1 The 2023 ACR/CHEST guidelines specifically support rituximab across multiple autoimmune conditions including:

• Rheumatoid arthritis-ILD: Rituximab is a preferred first-line option, particularly when active inflammatory arthritis coexists 1, 2
• Systemic sclerosis-ILD: Four trials and observational studies demonstrate FVC stabilization or improvement 1
• Inflammatory myopathies (IIM-ILD): Evidence supports rituximab for both initial and progressive disease 1
• Mixed connective tissue disease (MCTD-ILD): Conditionally recommended as first-line therapy 1
• Sjögren's disease-ILD: Included as a treatment option 1

Management of ILD Progression/Flare

When ILD progresses despite first-line therapy (representing a "flare"), rituximab is conditionally recommended as a second-line treatment option if not already used initially. 1 The guidelines explicitly state that some clinicians add rituximab to mycophenolate for progressive SSc-ILD and IIM-ILD, while others switch to rituximab monotherapy depending on patient risk factors 1

Key Decision Points for Progressive Disease:

• Switch vs. Add Strategy: If the patient is on mycophenolate and experiencing progression, you can either switch to rituximab or add rituximab to the existing regimen 1
• Cyclophosphamide is typically not combined with other therapies, whereas rituximab may be used individually or in combination 1
• Short-term glucocorticoids (≤3 months) may be useful as a bridge when switching therapy during a flare 1

Rapidly Progressive ILD (Severe Flares)

For rapidly progressive ILD representing a severe flare, rituximab is conditionally recommended as a first-line option, with strong preference for upfront combination therapy over monotherapy. 1

The management algorithm for rapidly progressive disease includes:

• Pulse IV methylprednisolone as initial therapy 1
• Rituximab and cyclophosphamide are recommended over IVIG, though IVIG may be preferred if high infection concern exists 1
• Double or triple therapy is recommended over monotherapy for rapidly progressive cases 1
• Additional options to combine include: mycophenolate, calcineurin inhibitors, JAK inhibitors, and IVIG 1

Critical Caveat for Systemic Sclerosis:

In rare SSc patients with rapidly progressive ILD, there was no consensus on glucocorticoid use due to scleroderma renal crisis risk; if used, close monitoring for renal crisis is mandatory 1

Evidence Supporting Rituximab in ILD Flares

The mechanistic rationale is strong: Four trials and observational studies in SSc, RA, and IIM demonstrate that rituximab results in FVC improvement or stabilization 1, which directly addresses the pathophysiology of an ILD flare. Rituximab may be particularly preferred when:

• Inflammatory arthritis is active (addresses both pulmonary and articular disease) 1, 2
• Myositis is present (dual benefit for muscle and lung involvement) 1
• Sjögren neuropathy exists (treats multiple manifestations) 1

Safety Considerations and Monitoring

The Voting Panel expressed caution regarding infection risk, cost, and impact on vaccine immunogenicity 1, which are particularly relevant during acute flares when patients may be on multiple immunosuppressants.

Monitoring Requirements During Treatment:

• Pulmonary function tests (FVC and DLCO) every 3-6 months to objectively assess flare resolution 2, 3
• High-resolution CT at baseline and annually or with significant PFT changes 2, 3
• Complete blood count every 2-4 months for immunosuppression monitoring 2, 3

Common Pitfalls to Avoid

• Do not discontinue effective rituximab therapy based solely on insurance criteria when clinical response is documented and guidelines support use 2
• Avoid long-term glucocorticoid dependence for ILD flare management given substantial adverse effects without proven long-term efficacy 1, 3
• Do not use methotrexate for SARD-ILD treatment (though it may be appropriate for extrapulmonary manifestations) 2
• Recognize that treatment hierarchy should not be mandated by insurers; clinicians must retain latitude to prescribe based on individual patient factors 2

Disease-Specific Nuances

For RA-ILD with active inflammatory features experiencing a flare, rituximab may be chosen over mycophenolate as the preferred agent 2, representing a departure from the general preference for mycophenolate as first-line therapy across other SARD-ILD conditions.

For progressive RA-ILD despite rituximab, pirfenidone is conditionally recommended as add-on therapy 1, 3, whereas this recommendation does not extend to other SARD-ILD types 1.