• Hand osteoarthritis is a condition that can cause joint pain and swelling, making it harder for people to go about their daily lives.
• Research is ongoing about how to best treat hand osteoarthritis.
• Data from a recent study found that methotrexate—a common treatment for other arthritis types—may help treat hand osteoarthritis and inflammation of the synovial membrane.

People use their hands daily to accomplish tasks and go about their lives. When the joints in the hand become stiff and rigid to move, it can be debilitating and hard to function. This can be the case for people who have hand osteoarthritis. Researchers are interested in understanding the most effective treatment options for people with hand osteoarthritis.

A recent study published in The Lancet examined how well the drug methotrexate may help treat hand osteoarthritis.

The study found that participants who received methotrexate over six months had moderate pain improvement.

The results indicate that methotrexate, which is helpful in treating other types of arthritis such as psoriatic or rheumatoid arthritis, may benefit people with hand osteoarthritis and inflammation.

Osteoarthritis is a condition that affects the joints of the body. One of the most common places it happens is in the hands. People with osteoarthritis in their hands may report trouble with movement, swelling of the joints, and pain. The joint swelling or synovitis can be particularly troubling.

Dr.Fiona E. Watt, a reader in rheumatology, honorary consultant rheumatologist, UKRI Future Leaders Fellow, and part of the Osteoarthritis Research Group, Department of Immunology and Inflammation, Imperial College London, who was not involved in the study, explained to Medical News Today:

“Hand osteoarthritis is the [most common] form of arthritis affecting the hands—it is usually associated with some inflammation of the lining of the joint, also known as synovial inflammation (synovitis) although this may not be present all the time, or at all stages in the condition.”

Pain with osteoarthritis

“Those with multiple joints affected by synovial inflammation are more likely to have significant symptoms like higher levels of hand pain and stiffness. They are also more likely to get progressive damage or ‘erosive’ osteoarthritis, which is linked to deteriorating hand function over time.”
— Dr. Fiona E. Watt

Hand osteoarthritis and associated joint swelling can be difficult to manage and treat. The current study’s authors wanted to see if the medication methotrexate may be useful in helping with pain relief among people with hand osteoarthritis and synovitis. Methotrexate is a common treatment for other types of arthritis, like rheumatoid arthritis.

Professor Philip Conaghan,director of the NIHR Leeds Biomedical Research Centre in the U.K., and arthritis expert, who was also not involved in the study, explained to MNT why this drug is not usually considered as first-line treatment for osteoarthritis:

“Methotrexate is the [most common] drug used around the world for treating immune-mediated inflammatory arthritis such as rheumatoid arthritis or psoriatic arthritis. It has multiple anti-inflammatory actions. Because the inflammation in osteoarthritis is not primarily driven by the immune system, it has not been clear if methotrexate would work in osteoarthritis.”

Study author Professor Flavia Cicuttini, the head of the musculoskeletal unit at Monash University and the head of rheumatology at Alfred Hospital, explained the difficulty surrounding treatment options for hand osteoarthritis.

“Hand osteoarthritis is a disabling condition that causes pain and affects function, impeding daily activities such as dressing and eating. It can significantly reduce quality of life,” she told MNT.

Lack of treatments for osteoarthritis

“At the moment, if a person goes to the doctor with hand osteoarthritis, treatments are very limited and do not work well. Often, patients are told there is nothing much doctors can offer them except pain relief with paracetamol or anti-inflammatory medications such as Naprosyn or Celebrex.”
— Prof. Flavia Cicuttini

To look at the effectiveness of methotrexate in improving pain in people with hand osteoarthritis with synovitis, researchers conducted the current study.

The study was a double-blind, randomized, placebo-controlled trial. The researchers included 97 participants in their analysis. Of this number, 50 participants received methotrexate, and 47 received the placebo. Participants took either the placebo or methotrexate weekly for six months.

All participants had hand osteoarthritis and synovitis in at least one joint, as confirmed by MRI. They excluded participants who had other types of arthritis and certain conditions like cancer and hepatitis B.

In addition to their study participation, participants also got their typical care from their health practitioners. They took folic acid on any other day of the week that they weren’t taking methotrexate, as this can help with methotrexate side effects.

The methotrexate group had a slightly higher body mass index than the placebo group. Other than this, the groups were very similar.

Researchers found that the methotrexate group had a higher level of pain and stiffness reduction than the placebo group.

There were some reported adverse events in both groups, which could have been related to study medications. However, overall, methotrexate was well-tolerated.

“The main finding of this study is that methotrexate, a medication that is commonly used often used worldwide for conditions such as rheumatoid arthritis, works for hand osteoarthritis with inflammation. The results of our study support a potential role for methotrexate in the management of hand osteoarthritis and inflammation and provide clinicians with a safe treatment option for this common type of hand osteoarthritis.”
— Prof. Flavia Cicuttini

Prof. Conaghan further commented with his thoughts on the study:

“There is a believable mechanism for the benefit seen in this study, and generally, the study is well designed. For example, it was good to see people were excluded if they had blood test indicators of rheumatoid arthritis.”

The nature of this study allows for tight control and a low risk of bias. Regardless, researchers still acknowledge some potential limitations.

First, the intervention period only lasted six months. Thus, future studies could include longer follow-up time. There was some missing data from some participants, indicating the need for studies with even larger sample sizes. The researchers did not look at how methotrexate affected structural progression.

The researchers encountered a study pause due to the COVID-19 lockdowns. They were unable to collect data on the primary outcome from certain participants. They could not establish how methotrexate affected tender swollen joint count.

It’s further possible that the effects of the methotrexate were underestimated among some participants. There was a low risk of memory bias among participants. The research also included more women than men.

Prof. Cicuttini noted that they needed conduct further trials “to establish whether the effect of methotrexate extends longer than six months, for how long we need to treat patients, and whether methotrexate reduces joint damage in patients with hand osteoarthritis and associated inflammation.”

Dr. Watts offered the following words of caution about using methotrexate for hand osteoarthritis in clinical practice:

“There are some practical considerations, too before this drug enters routine practice. The trial participants all had hand MRIs, not something we would do currently in usual practice. MRI is expensive and cheaper alternatives would probably need to be tested.”

Dr. Watts and Prof. Conaghan both noted that using methotrexate needed regular monitoring.

“Methotrexate is a drug which requires blood test safety monitoring for the duration of therapy, so before this type of treatment was implemented, we would need appropriate pathways of care to be established and funded in the NHS and other healthcare systems—these do not currently exist for this form of arthritis. The next step would be testing whether this drug is effective in practice, alongside or in addition to other standard treatments and this will be a really important next step,” said Dr. Watts.

“[B]ecause osteoarthritis is such a common problem, and because methotrexate requires monitoring, including regular blood tests (meaning more work for health systems), I think we will need a second trial to verify the findings in the Wang study before there is a big change in clinical practice,” said Prof. Conaghan.

Finally, Prof. Philip Conaghan reports that he also presented positive results for a methotrexate trial for knee osteoarthritis at an OARSI World Congress on Osteoarthritis meeting several years ago. However, the full results of that study have yet to appear in print.