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How Effective is Methotrexate for Osteoarthritis of Hand with Synovitis?

Methotrexate for Osteoarthritis

A recent study evaluated methotrexate for osteoarthritis of the hand with active synovitis. The study found methotrexate effective in reducing swelling, and pain, and improving functional status.

Key points of the study:

  • Hand osteoarthritis with synovitis is a typical inflammatory condition associated with pain, and effective therapies for this condition are limited.
  • A new study was a double-blind, randomized, placebo-controlled trial conducted across multiple sites in Australia. It involved participants aged 40-75 years with hand osteoarthritis and synovitis.
  • Participants were randomly assigned to receive either methotrexate (20 mg) or an identical placebo orally once weekly for 6 months.
  • Researchers found that treatment with methotrexate resulted in a moderate reduction in pain.

Methotrexate for Osteoarthritis:

methotrexate for osteoarthritis of hand

Osteoarthritis (OA) is a degenerative joint disease. It commonly affects older people above 55 years of age.

However, osteoarthritis may also develop in younger individuals as well. 30% of the patients develop osteoarthritis below 40 years of age.

Patients with osteoarthritis commonly have pain in the large joints such as the knees, hips, and shoulders[Ref].

However, small joints of the fingers including distal interphalangeal joints are also frequently affected, contrary to Rheumatoid arthritis in which the distal joints are frequently spared.

The American College of Rheumatology Defined Hand Osteoarthritis [Ref]:

Presence of hand pain/ or stiffness plus any 3 of the following:

1. Fewer than three swollen metacarpophalangeal joints
2. Hard enlargement of two or more distal interphalangeal joints
3. Deformity of at least one of the ten selected joints (second and third distal interphalangeal joints, first carpometacarpal joints, and second and third proximal interphalangeal joints)
4. Hard tissue enlargement of two or more of the ten selected joints

This criterion is 94% sensitive and 87% specific. Thus, only about 6% of patients with hand osteoarthritis are missed using this clinical criteria. 13% of the patients may be falsely labeled as having hand osteoarthritis. 

The treatment of osteoarthritis should be aimed to control pain as well as to prevent disability.

Preventing disability with DMARDs (disease-modifying anti-rheumatic drugs) has not been evaluated in patients with osteoarthritis.

A recent study published in The Lancet found that using a 20 mg dose of methotrexate for six months resulted in a moderate reduction in pain for people with hand osteoarthritis and synovitis.

The lead researcher, Professor Flavia Cicuttini, who leads the Musculoskeletal Unit at Monash University and serves as the Head of Rheumatology at The Alfred, explained that the study had highlighted the significance of inflammation in hand osteoarthritis and the potential advantages of focusing on individuals with painful hand osteoarthritis.

This suggests that methotrexate could play a role in managing hand osteoarthritis with an inflammatory condition, which could be clinically significant.


Methotrexate for Osteoarthritis: Study Findings and Interpretation

The research involved participants aged 40 to 75. All subjects were clinically diagnosed with hand osteoarthritis and synovitis (inflammation of the joint).

Subjects were recruited from different cities in Australia and assigned to an intervention group and a placebo group randomly.

One group received methotrexate 20mg while the other received a similar fake treatment, and the goal was to find out if methotrexate could potentially lower joint pain in hand OA patients.

All participants took the medications daily for 6 months. Their pain was measured using the visual analog scale (VAS), where they rated it on a 100-mm line.

Following six months of treatment, the individuals who received methotrexate exhibited a more substantial decrease in pain, with an average pain reduction of -15.2 mm, in contrast to the placebo group, which had an average reduction of -7.7 mm.

This implies that methotrexate could be beneficial in the treatment of hand osteoarthritis accompanied by inflammation.

Adverse events, or unwanted side effects, were noted in both groups, with a slightly higher occurrence in the methotrexate group (62%) compared to the placebo group (60%).


Safety and Adverse Effects of Methotrexate for Osteoarthritis of the Hand with Synovitis:

methotrexate for osteoarthritis of hands

Methotrexate is commonly used to treat Rheumatoid Arthritis. It is usually given in a dose of 7.5 mg to 10 mg weekly up to a maximum dose of 25 mg weekly.

It is also given in combination with other biological drugs such as Tofacitinib and Etanercept.

However, since Rheumatoid arthritis is an inflammatory disease, the use of DMARDs such as methotrexate seems logical.

With the study cited above, methotrexate may be given a trial in patients with osteoarthritis refractory to treatment, especially those with hand osteoarthritis associated with active synovitis.

Methotrexate has a very favorable safety profile when given in low doses as recommended (7.5 mg to 25 mg weekly. However, it does have some side effects.

The common adverse effects of methotrexate are nausea, vomiting, mucosal ulcers, and loss of appetite.

Most side effects of methotrexate mimic those of folate deficiency and can be treated by taking a folic acid supplementation.

Such symptoms include anemia, hair fall, mouth ulcers, fatigue, headache, shortness of breath, dizziness, and bone marrow suppression [Ref].

This medication is strictly contraindicated in pregnancy, which is why females of reproductive age need to be made aware of its consequences.

Methotrexate can affect liver functions and may result in fibrosis and cirrhosis of the liver when taken for a longer duration.

It can also cause pulmonary fibrosis and restrictive lung disease. Patients may develop shortness of breath and exercise intolerance.


The Need for Further Research

There has been a significant amount of research done on hand OA in the past [Ref]

Obesity and being overweight are commonly related to osteoarthritis. However, hand osteoarthritis has little correlation with obesity.

Nevertheless, we need more studies that analyze the effect of methotrexate on lowering pain sensations in hand OA.

Trials are also needed to address the following gray areas:

  • Whether methotrexate treatment is safe and effective beyond 6 months of therapy or not?
  • Will patients with knee, hip, shoulder, and spine osteoarthritis benefit from Methotrexate or not?
  • Can Methotrexate prevent joint damage and disability or not?

In addition, other DMARDs should also be evaluated in patients with osteoarthritis and active synovitis.


The bottom line

People above 60 are more susceptible to joint inflammations and arthritis, which is why more research is needed to explore possible treatments for arthritis.

The recent study has opened up the gates for further analysis and review of the long-term effects of methotrexate.

Other possible treatments, like non-pharmacological methods, including exercises, need to be explored as well.

Furthermore, the study faced a few limitations as the researchers originally planned to evaluate the effect of methotrexate on pain reduction and improved radiographic progression at 2 years but couldn’t due to COVID-19.

So, a large-scale study without any significant limitations will contribute greatly to improving a hand OA patient’s life quality.


What do you think?

Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

I love my family, my profession, my blog, nature, hiking, and simple life. Read more about me, my family, and my qualifications

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