Methotrexate (MTX) is one of the most common drugs used to treat Rheumatoid Arthritis (RA). It is also used to treat many other diseases, and in much higher doses it can also be used to treat cancers of certain types. Even though MTX is effective in reducing pain and joint damage and improving joint function, patients taking MTX commonly report experiencing fatigue. And it isn’t just a feeling of being tired. CreakyJoints’ Facebook community describes fatigue as “influenza without end” and “exhausted by exhaustion!”

It is no surprise that many RA patients who take MTX want to know if they can help their fatigue by stopping the medication.

To find out, we conducted a study involving 1,082 RA patients and compared levels of fatigue among those taking different combinations of MTX and biologic disease modifying antirheumatic drugs (DMARDs).

The Study: Methotrexate Use and Fatigue in Rheumatoid Arthritis Patient

RA patients from the ArthritisPower research registry participated in this study. Using the ArthritisPower web or mobile app, participants on MTX and/or biologic therapy submitted patient-reported outcomes about their fatigue, pain, and sleep via our ArthritisPower health assessment.

Questions to evaluate fatigue included:

  • In the past 7 days how much were you bothered by your fatigue on average?
  • In the past 7 days how often did you have to push yourself to get things done because of your fatigue?
  • In the past 7 days how run-down did you feel on average?

What We Learned

The symptoms of RA patients were compared across different treatments and patients taking MTX tended to have better scores of pain interference, sleep disturbance, and fatigue compared to those who were not. From these results, it appears that MTX use, especially when combined with biologic use, may be associated with better symptoms among RA patients.

Although patients taking MTX had slightly higher fatigue scores overall, the level of a patient’s RA disease activity as measured by the Routine Assessment of Patient Index Data 3 (RAPID3) seemed to make a difference. For patients in remission—with very low RAPID3 scores—those taking MTX monotherapy had the highest fatigue scores. Among patients in high disease activity, fatigue scores were similar across different treatment combinations.

In order to better understand the relationship between MTX and fatigue, we need to collect and analyze more data over time.

Why is this important for patients?

In general, patients don’t prefer MTX as their primary treatment because it is associated with other troublesome side effects (i.e., upset stomach). This study demonstrated that MTX can be an effective treatment for patients despite commonly heard patient reported experiences of bothersome side effects, such as fatigue, from the therapy.

Patients taking MTX may be tempted to discontinue treatment because of fatigue, but it’s important to recognize that the fatigue may be caused by something other than MTX. RA patients may have other conditions that could be causing the fatigue. Anemia, chronic fatigue syndrome, depression, sleep disorders and inflammation-induced fatigue are common comorbidities among RA patients and can cause chronic fatigue.

Despite the fatigue, discontinuing MTX without consulting a physician may worsen symptoms. It is important for patients to talk to their physician to help determine if the fatigue is due to MTX or some other factor.

What can patients do to manage fatigue?

Unfortunately, there is no quick remedy to eliminate chronic fatigue. Patients should work with their doctor to tailor options to their unique needs. More often than not, suggestions for dealing with fatigue fall into one of these categories:

  • Adjust medications by dose reduction or change in the class of medication
  • Find and treat underlying medical issues which may be the cause of the fatigue
  • Seek therapy and emotional help through support groups

Exercising, healthy eating, and good sleep habits can help patients overcome fatigue. It is important to eat balanced meals with a lot of fruits and vegetables. This can help patients feel energized throughout the day. Exercising increases muscle mass, strength and blood circulation, which boost energy. Exercising also leads to the production of endorphins in the brain that produce a sense of well-being and vitality. These brain chemicals also have an analgesic effect (i.e. reduce pain) and improve sleep.

Joining a support group may also be helpful. A support group can help patients cope more effectively and feel less isolated as they make connections with others facing similar challenges. Sharing feelings with others can ease the burden of fatigue and prevent depression. However, a support group shouldn’t replace your standard medical care.

Participating in Future Studies

If you are diagnosed with rheumatoid arthritis, we encourage you to participate in future studies by joining CreakyJoints’ patient research registry, ArthritisPower. As a patient-led, patient-centered initiative, our research team is committed to investigating research topics that matter most to patients.

For more information, click here to view our poster on this study.