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Methotrexate (MTX) has long been used to treat rheumatic conditions, especially rheumatoid arthritis (RA), because of its ability to reduce immune system overactivity and help lower inflammation. Methotrexate is also frequently prescribed to patients with psoriatic arthritis (PsA) and severe psoriasis. This disease-modifying anti-rheumatic drug (DMARD) usually works well, though it’s sometimes best when combined with another medication like a biologic. Yet as with all medications, there are side effects to consider.

One well-known side effect of methotrexate is that it may cause liver damage. Long-term use sometimes leads to elevated liver enzyme levels, fibrosis (scarring of the liver), and in rare cases cirrhosis (severe scarring). This potential side effect doesn’t mean that methotrexate isn’t safe for most people, but liver function is something that your doctor needs to monitor regularly to ensure the drug is safe for you.

While anyone taking methotrexate might develop a liver problem, rheumatologists at the University of Pennsylvania Perelman School of Medicine wanted to find out if the risk might be greater for those with psoriasis or PsA compared to patients with rheumatoid arthritis. According to their research, it’s possible.

Their study, which was published in the Journal of the American Academy of Dermatology, analyzed the data of a large group of Danish patients who had psoriasis, PsA, or RA and used methotrexate between 1997 and 2015. The researchers sorted the patients by their diagnosis, as well as by the degree of impact the drug had on their liver: mild liver disease, moderate-to-severe liver disease (which includes fibrosis), cirrhosis, and cirrhosis-related hospitalization.

According to their findings, rheumatoid arthritis patients using methotrexate were the least likely to experience liver complications. “Compared with patients with RA, patients with [psoriasis] were 1.6 to 3.4 times more likely to develop at least one of the liver disease outcomes, whereas those with PsA were 1.3 to 1.6 times more likely to develop mild liver disease and cirrhosis after adjusting for demographics, smoking, alcohol use, comorbidities, and methotrexate dose,” they wrote.

It’s not clear why psoriasis and PsA patients were more apt to have liver problems compared to those with RA, so more research in this area is needed.

The biggest takeaway for anyone using methotrexate is to follow your doctor’s instructions and get regular liver function tests as directed. Read more here about how doctors monitor methotrexate use in those with inflammatory arthritis.

Given these new findings, psoriasis and psoriatic arthritis patients might want to be even more vigilant and ask their prescriber if they ought to have a new type of blood test (such as FibroSure) and/or a liver ultrasound like FibroScan to check for early-stage liver scarring so they can catch it before it progresses, lead author Joel Gelfand, MD, Director, Psoriasis and Phototherapy Treatment Center at Penn Medicine, said in an email. “These screening tests are especially important in patients with additional risk factors for liver disease, such as those who are obese, have diabetes or metabolic syndrome, or drink alcohol regularly,” he noted.

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Forrand RL. Liver disease may be more common in patients on methotrexate for psoriatic disease. Healio. March 22, 2021. https://www.healio.com/news/dermatology/20210322/liver-disease-may-be-more-common-in-patients-on-methotrexate-for-psoriatic-disease.

Gelfand JM, et al. Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: A population-based study. Journal of the American Academy of Dermatology. February 16, 2021. doi: https://doi.org/10.1016/j.jaad.2021.02.019.

Hannoodee M, et al. Methotrexate. StatPearls. March 7, 2021. https://www.ncbi.nlm.nih.gov/books/NBK556114/.

Interview with Joel Gelfand, MD, Director, Psoriasis and Phototherapy Treatment Center at Penn Medicine