New research profiles side-effects linked to methotrexate

07 February 2022

New research led by University of Manchester and NIHR Manchester Biomedical Research Centre (BRC) scientists has profiled the side effects of methotrexate. This is a common drug used to treat arthritis and other autoimmune diseases.

What is the aim of the study?

The researchers hope their findings published in the journal Rheumatology will ease the concerns of patients before starting treatment. Often people don’t have much knowledge of the drug, including its impact and side effects.

Though the study is unable to conclude if the drug causes the side effects they report in arthritis patients, the associations give them and their doctors valuable information to discuss together. This can help decisions about how best to manage treatments for individuals.

How was the research carried out?

The team evaluated data of 1,069 patients who participated in the Rheumatoid Arthritis Medication Study (RAMS) from 38 hospitals across the UK, including in Greater Manchester. The patients were recruited to the study before starting methotrexate treatment and were followed up for one year.

At six and 12-months, 957 patients (89.5per cent) and 902 patients (84.4per cent) were still taking the drug orally, respectively.

What common side effects were reported?

Side effects were common among patients over the first year of methotrexate, though most were not serious.

Overall, 77.5% experienced at least one side effect during the 12 months: 250 reported only one, 169 reported two, and the others reported three or more.

Of the side effects associated with taking the drug:

  • 42% were gastrointestinal, including nausea (31%) and diarrhoea (15%).
  • 39.6% were generalised, including fatigue (29%).
  • 28.6% were neurological, including headaches (19 per cent) and dizziness (12%).
  • 26.0 per cent were mucocutaneous, including alopecia (9 per cent), and mouth ulcers (12 per cent).

Why is this study important?

Lead researcher of the RAMS study, Dr Suzanne Verstappen is a Reader in musculoskeletal epidemiology at The University of Manchester and a researcher for Manchester BRC’s Adult Inflammatory Arthritis research programme.

She said: “Methotrexate has transformed the treatment of inflammatory arthritis and improved the lives of almost two million people worldwide.

“But worrying about side effects could stop patients from using this important drug or reduce sticking to the treatment."

How can the data help patients make informed choices?

PhD researcher Ahmad Sherbini from The University of Manchester, said:

“Using the data in this study, patients can make informed decisions whether to start this drug and potentially increasing adherence to treatment.”

“It can also help identifying patients with higher risk of side effects who require frequent monitoring and additional GP visits. Ultimately and with further studies, treatment can be tailored to patients, and better resource utilisation can be achieved.”

A look to the future

We know that finding effective and tolerated treatments for arthritis can be a process of trial and error.

We want healthcare to take a precision medicine approach using biological data and also taking account a person’s experience to understand how that may affect their treatment.

Over the next four years we will invest in research like this, which helps understand how a person will respond to medicines.

Natalie Carter, Head of research engagement, Versus Arthritis said:

“Research like this is vitally important. It means that people with arthritis are better informed on the medications being suggested and can support them when navigating a sometimes confusing and complicated treatment regime, especially when first diagnosed.

“With a better understanding on the types of side effects caused by medication, people with arthritis can have productive conversations with their rheumatology team about what is working, and how they can tailor that treatment to get the best possible result in managing their condition.”

Help and support