Rheumatoid arthritis (RA) is a complex autoimmune disease that requires consistent, long-term management. For many patients, methotrexate remains a cornerstone of treatment due to its ability to control inflammation and slow disease progression. However, recent research highlights an often-overlooked factor that could be interfering with treatment success: gastrointestinal health.

A new study has revealed that acid reflux and other stomach issues may negatively impact methotrexate use and overall RA outcomes. For individuals living with RA—especially those struggling with GI side effects—this is a critical connection to understand.

Methotrexate: A Powerful Treatment With Potential Side Effects

Methotrexate is one of the most widely prescribed disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis. When taken consistently at therapeutic doses, it can significantly reduce joint pain, stiffness, and long-term damage.

However, methotrexate is also known for its potential side effects, particularly in the digestive system. These may include:

• Nausea

• Indigestion

• Abdominal discomfort

• Acid reflux (GERD)

• Loss of appetite

For some patients, these side effects are more than just unpleasant—they can interfere with treatment adherence.

New Study Highlights a Gut-Joint Connection

A recent study published in a rheumatology journal examined RA patients who were prescribed methotrexate and also experienced significant gastrointestinal symptoms, particularly acid reflux. The findings were notable:

• Patients with more severe acid reflux symptoms were more likely to have higher disease activity scores, meaning their RA was less controlled.

• These patients also tended to receive lower doses of methotrexate, often due to intolerance or side effects.

• Overall, treatment outcomes were poorer, with less improvement in symptoms and function.

This suggests that gastrointestinal symptoms may not only be side effects of treatment—they may also limit the effectiveness of RA therapy by reducing how consistently and how much medication patients can take.

Why Digestive Health Matters in RA Management

Stomach discomfort, reflux, and nausea can discourage patients from sticking to their treatment plans. In some cases, methotrexate is taken inconsistently or discontinued altogether, often without a suitable replacement. This leads to higher inflammation levels, more pain, and an increased risk of joint damage.

In addition, emerging research suggests a more direct biological connection between gut health and immune regulation. Known as the gut-joint axis, this link recognizes that inflammation in the digestive tract can influence systemic immune activity—including the type that drives RA.

The Gut-Joint Relationship Includes:

• Alterations in gut microbiota (the balance of good and bad bacteria)

• Chronic inflammation in the gastrointestinal lining

• Medication absorption issues

• Immune system activation from digestive distress

Because RA is an autoimmune condition, any additional source of immune stress—such as gut inflammation—can contribute to disease flares or reduce response to treatment.

Practical Steps for Managing GI Symptoms and Staying on Track

If you’re living with RA and struggling with acid reflux or other stomach issues, here are some steps to discuss with your healthcare provider:

1. Adjust Medication Form or Dosage

Some patients tolerate injectable methotrexate better than the oral version. Your rheumatologist may also recommend dose adjustments or anti-nausea medications to make treatment more manageable.

2. Manage Acid Reflux Actively

Lifestyle strategies—such as avoiding trigger foods (like caffeine, spicy meals, or acidic drinks), eating smaller meals, and elevating the head during sleep—can help reduce reflux symptoms. Over-the-counter or prescription medications like proton pump inhibitors (PPIs) may also be helpful.

3. Consider Folate Supplementation

Methotrexate can reduce folic acid levels, which may worsen GI side effects. Taking a folic acid supplement (as recommended by your provider) can often ease nausea and protect against other side effects.

4. Talk to a Gastroenterologist

If symptoms persist or interfere with treatment, your care team may refer you to a specialist to assess for conditions like GERD, ulcers, or gastritis.

Whole-Body Health Supports Joint Health

RA management is not just about controlling joint inflammation—it’s about supporting overall well-being. This includes recognizing that digestive health plays a role in how medications are tolerated and how effectively they work.