From the Guidelines
Azathioprine is a conditionally recommended first-line treatment option for interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases, including those with non-specific interstitial pneumonia (NSIP). When considering azathioprine for ILD treatment, particularly in the context of NSIP, it's essential to weigh the benefits and risks, as outlined in the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases 1. Key points to consider include:
- The dosing regimen, which typically starts at 50 mg daily and can be titrated up to 2-3 mg/kg/day based on patient tolerance and response.
- The importance of thiopurine methyltransferase (TPMT) enzyme testing before initiating azathioprine to assess for genetic deficiency that could increase toxicity risk.
- Regular monitoring, including complete blood counts, liver function tests, and kidney function tests, initially every 1-2 weeks and then every 1-3 months once on a stable dose.
- Potential side effects, such as bone marrow suppression, hepatotoxicity, increased infection risk, and gastrointestinal disturbances, and the need for patients to report any signs of infection, unusual bleeding or bruising, or jaundice immediately. Azathioprine's mechanism of action in NSIP involves suppressing T-cell function and reducing inflammation in lung tissue, making it a valuable option when corticosteroids alone are insufficient or to facilitate steroid dose reduction 1.
From the Research
Azathioprine in ILD NSIP
- Azathioprine is used as an immunosuppressive agent in the treatment of interstitial lung disease (ILD), including non-specific interstitial pneumonia (NSIP) 2, 3.
- The treatment of ILD, particularly NSIP, is not well established, but azathioprine has been reported as an alternative to cyclophosphamide 2.
- In patients with fibrotic connective tissue disease-associated interstitial lung disease, azathioprine has been shown to be associated with pulmonary function stability over time, with a marginal improvement 4.
- However, a significant minority of patients may not tolerate azathioprine due to non-respiratory side effects 4.
- Azathioprine hypersensitivity syndrome is a rare but potentially life-threatening condition that can occur in patients treated with azathioprine, and clinicians should be aware of this possibility 5.
Treatment Approaches
- Immunomodulatory agents, including azathioprine, are the cornerstone of therapy for ILDs other than idiopathic pulmonary fibrosis (IPF) 3.
- The choice of immunomodulatory agent depends on the specific ILD and the patient's underlying condition 3.
- Azathioprine can be used in combination with other immunosuppressive agents, such as mycophenolate mofetil, to treat ILD 4.
Idiopathic NSIP
- Idiopathic NSIP is a rare diagnosis that requires exclusion of other possible causes, including connective tissue disease and toxins 6.
- Patients with idiopathic NSIP typically present with dyspnea, cough, and constitutional symptoms, and have a female predominance 6.
- Treatment of idiopathic NSIP is generally instituted in the form of immunosuppression, although the prognosis is favorable compared to idiopathic pulmonary fibrosis 6.