From the Guidelines
Methotrexate is conditionally recommended over leflunomide for patients with mild and stable lung disease, but leflunomide may be preferred for those with compromised lung function or a history of interstitial lung disease, as it has a lower incidence of drug-induced lung disease 1. When comparing methotrexate and leflunomide for lung health in patients with autoimmune conditions, it is essential to consider the potential risks and benefits of each medication.
- Methotrexate can cause a serious adverse effect called methotrexate-induced pneumonitis, which occurs in approximately 1-5% of patients and can develop at any time during treatment 1.
- This pneumonitis presents as acute shortness of breath, dry cough, and fever, and can be life-threatening if not promptly recognized and treated.
- In contrast, leflunomide has a lower incidence of drug-induced lung disease, making it potentially safer for patients with pre-existing lung conditions 1. However, leflunomide is not without pulmonary risks, as it can occasionally cause interstitial lung disease, particularly in patients with risk factors such as smoking or prior lung disease.
- For patients with compromised lung function or a history of interstitial lung disease, leflunomide may be the preferred option, though close monitoring with pulmonary function tests and chest imaging is recommended for patients on either medication 1. The decision between these medications should be individualized based on the patient's specific lung health status, underlying condition being treated, and other comorbidities.
- According to the 2021 American College of Rheumatology guideline, methotrexate is conditionally recommended over alternative DMARDs, including leflunomide, for patients with mild and stable lung disease 1.
- However, the 2023 American College of Rheumatology/American College of Chest Physicians guideline conditionally recommends against leflunomide and methotrexate as first-line ILD treatment options, citing uncertain benefit and potential harm 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Comparison of Methotrexate and Leflunomide for Lung Health
- There is no direct comparison between methotrexate and leflunomide for lung health in the provided studies.
- However, the studies suggest that leflunomide can cause interstitial lung disease (ILD) and other pulmonary complications 2, 3.
- Leflunomide has been associated with an increased risk of ILD, particularly in patients with a history of ILD or methotrexate use 3.
- On the other hand, leflunomide has been shown to be effective in improving pulmonary function in patients with chronic hypersensitivity pneumonitis, especially those without significant fibrosis 4.
- Leflunomide has also been used as an alternative therapy for pulmonary and extrapulmonary sarcoidosis, with some patients showing improvement in lung function and reduction in steroid dose 5.
- Additionally, leflunomide has been linked to pulmonary hypertension, although this is a rare complication 6.
Leflunomide-Related Pulmonary Complications
- Interstitial lung disease (ILD) is a known complication of leflunomide therapy, with most patients presenting within three months of starting treatment 2.
- Pulmonary hypertension is a rare but potential complication of leflunomide use, with a median time to diagnosis of 32 months 6.
- Leflunomide can cause gastrointestinal and other adverse effects, leading to discontinuation of therapy in some patients 4, 5.
Patient Selection and Monitoring
- Patients with pre-existing ILD or a history of methotrexate use may be at increased risk of developing ILD with leflunomide therapy 3.
- Patients with significant fibrosis may not benefit from leflunomide treatment, and alternative therapies should be considered 4.
- Close monitoring of lung function and adverse effects is necessary for patients receiving leflunomide therapy 4, 5.