Methotrexate Use in Rheumatoid Arthritis with Interstitial Lung Disease

General Considerations

The American College of Rheumatology conditionally recommends methotrexate over alternative DMARDs for patients with rheumatoid arthritis who have mild and stable interstitial lung disease, with moderate-to-high disease activity 1, 2
Methotrexate is not associated with progression of existing interstitial lung disease, according to observational data 3, 4

Patients with preexisting lung disease should be informed of their potentially increased risk of methotrexate pneumonitis prior to initiating treatment 1
The recommendation for methotrexate use in rheumatoid arthritis with interstitial lung disease is conditional, as some clinicians and patients may prefer alternative options due to the risk of lung toxicity 1, 2

When starting methotrexate, laboratory tests such as ALT, creatinine, and CBC should be performed every 1-1.5 months until a stable dose is reached, and every 1-3 months thereafter 5, 6
Clinical assessment for side effects and risk factors should be performed at each visit 5
Methotrexate should be stopped if there is concern for methotrexate pneumonitis, and some experts would stop it if interstitial lung disease developed while on methotrexate 3, 4

Oral methotrexate should be started at 10-15 mg/week, with escalation of 5 mg every 2-4 weeks up to 20-30 mg/week, depending on clinical response and tolerability 5, 7
Prescription of at least 5 mg folic acid per week with methotrexate therapy is strongly recommended to reduce side effects 5, 6, 7

The 2023 ACR/CHEST guideline conditionally recommends against leflunomide, methotrexate, TNF inhibitors, and abatacept as first-line interstitial lung disease treatment options for patients with rheumatoid arthritis 3, 4
Methotrexate may be continued in patients with interstitial lung disease who are receiving it for extrapulmonary manifestations of rheumatoid arthritis 3, 4

Methotrexate has an important role as an anchor treatment in rheumatoid arthritis, with a lack of alternatives with similar efficacy and/or superior long-term safety profiles 1, 2
The benefits of methotrexate in controlling rheumatoid arthritis disease activity may outweigh the potential risks in patients with mild and stable interstitial lung disease 1, 2

Methotrexate should not be automatically excluded as a treatment option for all rheumatoid arthritis patients with interstitial lung disease, as evidence suggests it may be safely used in those with mild and stable disease 1, 2
Distinguish between methotrexate pneumonitis and progression of underlying interstitial lung disease, as they require different management approaches 3, 4