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Causality: well established
Causality assessment · Causality: well established
Methotrexate and Pneumonitis / pulmonary fibrosis: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Methotrexate ↔ Pneumonitis / pulmonary fibrosis
n=3,464 co-reports · PRR 10.9 · ROR 11.0
Methotrexate can cause a hypersensitivity-type pneumonitis and, less often, chronic pulmonary fibrosis — a rare but serious effect that can occur at any dose and at any time during therapy, including the first months. It is the reason new breathlessness or dry cough in a patient on methotrexate is investigated promptly and the drug stopped. The 3,464 co-reports (PRR 10.9) reflect both the real effect and methotrexate's very large treated population.
Regulatory basis: methotrexate prescribing information (acute pneumonitis and pulmonary fibrosis warning). Established methotrexate-lung-toxicity literature.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Lung injury develops during therapy and may improve after withdrawal |
| Strength | met | PRR 11 on a large co-report count |
| Consistency | met | Reproduced across rheumatology case series |
| Specificity | met | A recognised methotrexate effect, uncommon with most other drugs |
| Biological gradient | partial | Not clearly dose-related; can occur early |
| Plausibility | met | An immune/hypersensitivity reaction in the lung is the proposed mechanism |
| Coherence | met | Coheres with the labelled advice to investigate new respiratory symptoms |
| Experiment | partial | Dechallenge (withdrawal) is essential and often helps; no randomized trial |
| Analogy | met | Analogous to pneumonitis from other DMARDs (leflunomide, TNF inhibitors) |
This page's own qualitative read, not an automated/citation-gated assessment.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for methotrexate captured drug-induced pneumonitis or pulmonary fibrosis as a coded event; the reaction is rare and identified in clinical practice rather than in trial AE tables.