In one study Dr. Kavanaugh coauthored, about half of RA patients who received methotrexate and adalimumab had their disease go into remission after two years, making them twice as likely to be symptom-free as other patients given either of the drugs alone. What’s more, X-rays showed that patients receiving the tandem of drugs also experienced less joint deterioration.

Research also indicates that methotrexate combines effectively with newer biologic agents, such as abatacept (Orencia) and rituximab (Rituxan).

A Long Record of Safety

Methotrexate is widely regarded as one of the safest of all arthritis drugs, though it carries some potential downsides. Gastrointestinal symptoms such as nausea and vomiting are the most frequent side effects linked to the drug. About one in 10 patients experience a “post-dosing reaction” – sometimes called “methotrexate fog” – soon after taking the medication, which is administered once a week (whether injected or taken orally).

“It’s hard to quantify, but some people just don’t feel good the day after they take methotrexate,” says Dr. Kavanaugh. Patients who have this reaction complain of fatigue and malaise, though these side effects usually only last a day or so.

Other possible side effects include hair loss, swollen and tender gums, headaches, drowsiness, and dizziness. Most physicians recommend taking 1 milligram of folic acid daily, which can help to offset these problems. Certain people, notably women who are or may become pregnant, should not take methotrexate. Learn more about methotrexate side effects here.

Injectable methotrexate is just one of many prescription drugs used to treat a variety of medical conditions that has gone on short supply in recent years due to a complex web of economic and regulatory factors. Last October, President Barack Obama issued an executive order that gave the FDA greater authority to take actions that could help to prevent drug shortages, while Congress is considering legislation that would give the agency more power to ensure that needed medications don’t disappear.

“It’s a big issue,” says Dr. Kavanaugh. “This shortage didn’t seem to affect a lot of our patients. But I hope it doesn’t happen again.”