Is subcutaneous methotrexate safe in patients with rheumatoid arthritis?

This study investigated if subcutaneous methotrexate (MTX-sc; Otrexup) is safe and well tolerated in patients with rheumatoid arthritis (RA). They found that MTX-sc is safe and well-tolerated in these patients.

Rheumatoid arthritis (RA) is a chronic condition. It is caused by painful inflammation in the joints. Drugs that reduce inflammation are used to treat RA. They are called disease-modifying anti-rheumatic drugs (DMARDs). The first-line treatment for RA is methotrexate (MTX). MTX targets several pathways involved in inflammation. This reduces the production of inflammatory chemicals. It also reduces the number of inflammatory cells in the joints.

MTX is usually taken orally as a tablet. Oral MTX can have negative effects on the gastrointestinal (GI) system (stomach and gut). These include vomiting and diarrhea. Administering MTX in a different way might avoid these side effects. Subcutaneous (sc) administration involves an injection under the skin. MTX is available in a formulation for sc administration (MTX-sc). It is unclear if MTX-sc is safe and well tolerated in patients with RA.

This study included 3042 patients with RA treated with MTX. 2093 patients took MTX oral (MTX-o) and 949 took MTX-sc. The main outcome of the study was safety. Treatment continuation was used to measured effectiveness. 

Reduced neutrophil count was the most common side effect (61%). Neutrophils are a type of white blood cell. Elevated liver enzymes were also common (39%). Slightly higher rates of reduced neutrophils and elevated liver enzymes were seen in the MTX-sc group compared to the MTX-o group. 

Patients on lower doses of MTX-sc were more likely to continue with treatment than in the MTX-o group. Significantly fewer patients stopped treatment due to GI side effects in the MTX-sc group. This was similar in patients taking MTX-sc alone or combined with biologic drugs. 

The authors concluded MTX-sc is safe and well-tolerated in patients with RA.

This study did not compare disease activity data. This means it is unclear if MTX-sc is similarly effective compared to MTX-o. A controlled study is needed. 

If you have any concerns regarding RA management, please discuss this with your doctor.