New thinking on methotrexate: don’t delay treatment due to fears of ILD

A team of UK rheumatologists has urged clinicians to not delay treatment with methotrexate in rheumatoid arthritis because of fears over lung injury.

In fact, use of methotrexate in a treat-to-target approach in patients with progressive disease may prevent the development of interstitial lung disease (ILD) developing, they conclude.

Dr Elena Nikiphorou, a clinical researcher and consultant rheumatologist at King’s College London, told the limbic that they wanted to address this controversial topic by reviewing the existing evidence with a focus on clinical trial and observational data.

Analysis of clinical trial data shows that there is no clear evidence that methotrexate is causatively related to ILD in rheumatoid arthritis patients. Lung problems that do occur are more likely to be infectious in nature highlighting the importance of taking actions like pneumococcal vaccination, she said.

The review, published in Rheumatology, also found that more recent studies have shown methotrexate-related pneumonitis to be far less common than previously thought with a meta-analysis showing an absolute risk of 0.3%.

In addition, evidence from ‘real-world’ observational studies suggests that there is, in fact, no clear association between methotrexate as a direct cause of development of ILD, she added.

“Some evidence actually suggests the opposite,” said Dr Nikiphorou. “It suggests that there is a delay in ILD onset in those treated with methotrexate. What you see is that methotrexate is actually associated with better survival.”

The review authors do stress that clinicians still need to exercise caution in treating and monitoring patients with pre-existing lung disease who do seem to be at increased risk of methotrexate-related pneumonitis.

It may be that the more recent evidence tells a different story because we are better at differentiating between different types of lung disease, Dr Nikiphorou explained.

“We tackle an important misconception here,” she said. “Methotrexate should not be delayed because of fears of a potential link with ILD because in fact it could stop it. The evidence is showing almost the contrary to what was thought.”

“There has been a generalised nervousness around this, myself included, but the evidence is becoming clearer in recent years and this is why we wanted to do the review and share key messages with fellow rheumatologists.”

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