Nav: Home

Study investigates rates of adverse events for common rheumatoid arthritis drug

February 17, 2020

Methotrexate is a common drug with a long history; for the past 40 years, it's been used to treat a range of diseases. Today it is the most commonly used drug for systemic rheumatic diseases worldwide and is the first drug a physician will prescribe for a patient with rheumatoid arthritis. But despite its use by millions of people, there is not robust data on the rates of the side effects of the drug. Observational studies have suggested that methotrexate may elevate a person's risk of a variety of adverse events, including liver toxicity, anemia and difficulty in breathing, but the magnitude of risk was unknown. Taking advantage of data from the Cardiovascular Inflammation Reduction Trial (CIRT), a randomized double-blind, placebo-controlled trial, investigators from Brigham and Women's Hospital have been able to far more accurately determine rates of adverse events for people taking methotrexate, finding small-to-moderate elevations in risks for skin cancer, gastrointestinal, infectious, lung, and blood adverse events. Results are published in Annals of Internal Medicine.

"Methotrexate is a cornerstone drug for a variety of inflammatory diseases, especially for rheumatoid arthritis," said Daniel Solomon, MD, MPH, a rheumatologist in the Division of Rheumatology, Inflammation and Immunology at the Brigham. "Over the decades, we've learned about the side effects but only from small studies. Questions for both physicians and patients have lingered about the drug's safety. Our study offers a detailed side-effect profile that I think will help us prescribe methotrexate in an informed way."

Solomon and his colleagues looked at data on 4,786 participants from CIRT who were randomized to receive low-dose methotrexate with folate or a placebo. Of 2,391 subjects who received methotrexate, 87 percent experienced an adverse event of interest compared to 81.5 percent of those who were randomized to placebo.

According to Solomon, the team's most surprising finding was a doubling of risk of skin cancer for participants taking methotrexate (53 incidents of skin cancer versus 26 for placebo). This result may be particularly important because patients with psoriatic arthritis -- a form of arthritis that affects people with psoriasis -- are already at increased risk of skin cancer.

Gastrointestinal, infectious, pulmonary and hematologic adverse events were also elevated, but the increased risk was mild to moderate. As anticipated, the team also saw an increase in liver test abnormalities and five cases of cirrhosis in the methotrexate arm versus zero in the placebo arm. The authors note that CIRT participants did not have rheumatoid arthritis or other rheumatic diseases and it is possible, although unlikely, that adverse event rates may vary outside of the CIRT population.

"We now have real numbers we can share with patients when talking about side effects," said Solomon. "We definitely wouldn't suggest this drug is too dangerous to give. But having a clear side-effect profile allows us to give it with eyes wide open and better balances the risks and benefits of an age-old drug."
-end-
This work was supported by the National Institutes of Health (NIH R01 HL119718, NIH U01 HL101422, and U01 HL101389).

Paper cited: Solomon, DH et al. "Adverse Effects of Low Dose Methotrexate in a Randomized Double-Blind Placebo-Controlled Trial: Adjudicated Results from the Cardiovascular Inflammation Reduction Trial" Annals of Internal Medicine DOI: 10.7326/M19-3369

Brigham and Women's Hospital

Related Rheumatoid Arthritis Articles:

New pieces added to the molecular puzzle of rheumatoid arthritis
researchers have revealed new details about how joint inflammation evolves in rheumatoid arthritis, and the cells that prolong the inflammatory attack.
Thermal cameras effective in detecting rheumatoid arthritis
A new study, published today in Scientific Reports, highlights that thermal imaging has the potential to become an important method to assess Rheumatoid Arthritis.
Rheumatoid arthritis -- can its onset be delayed or prevented?
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that leads to significant health issues as well as high treatment costs.
Disease burden in osteoarthritis is similar to rheumatoid arthritis
Osteoarthritis (OA) has traditionally been viewed as a highly prevalent but milder condition when compared with rheumatoid arthritis (RA), and some may believe that it is part of a normal aging process requiring acceptance, not treatment.
Prospect of a new treatment for rheumatoid arthritis
An international research group led by Charité -- Universitätsmedizin Berlin has completed testing a new drug to treat rheumatoid arthritis.
Can rare lymphocytes combat rheumatoid arthritis?
Immunologists at Friedrich-Alexander-Universität Erlangen-Nürnberg have demonstrated that ILC2, a group of rare lymphoid cells, play a key role in the development of inflammatory arthritis.
How environmental pollutants and genetics work together in rheumatoid arthritis
New research documents how chemicals and a certain gene activate an enzyme to increase the risk and severity of RA and bone destruction.
Rheumatoid arthritis meets precision medicine
Scientists are bringing precision medicine to rheumatoid arthritis for the first time by using genetic profiling of joint tissue to see which drugs will work for which patients, reports a new multi-site study.
Causes of death in rheumatoid arthritis patients
Mortality rates were increased for patients with rheumatoid arthritis relative to the general population across all causes of death in a recent Arthritis Care & Research analysis.
Menopause found to worsen symptoms of rheumatoid arthritis
A recent study published in Rheumatology suggests that women with rheumatoid arthritis suffer a greater decline in physical function following menopause.
More Rheumatoid Arthritis News and Rheumatoid Arthritis Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.