A routine visit to the drug store became frustrating and worrisome for some people with rheumatoid arthritis (RA) in recent months. That’s because injectable methotrexate, which some RA patients use to control joint pain and stiffness, was suddenly unavailable at many pharmacies. The problem: The largest maker of injectable methotrexate, Ben Venue Laboratories, was forced to shut down several plants due to manufacturing problems. As a result, the nationwide supply of this important drug dwindled, which meant some pharmacies were unable to keep it in stock.

The majority of people with RA who use methotrexate – and most patients with this form of arthritis do use the drug at some point – take an oral version, which was not affected by the recent shortage. Moreover, injectable methotrexate is once again widely available, since the Food and Drug Administration asked several other manufacturers to step up production of the drug. That was especially good news for patients with certain forms of childhood leukemia and other types of cancer, since injectable methotrexate is also used in much higher doses as life-saving chemotherapy for these diseases. However, this hiccup in the drug supply chain shined a light on the importance of methotrexate, which over the last generation has become the cornerstone of treatment for RA.

Better Than Gold?

Prior to the 1980s, patients with RA had limited treatment options. Injections of gold salts were the most commonly used therapy. However, gold salts were only modestly effective and caused a variety of side effects such as mouth sores and potentially severe skin rashes; about one in three patients couldn’t tolerate the treatments and had to stop receiving them. Eager to find better therapies for RA, some researchers chose to look backward.

Methotrexate was initially developed as a cancer drug. In the 1940s, famed physician Sidney Farber, MD, developed a theory that blocking folic acid, a form of vitamin B, would stop cancer cells from spreading and induce remission in children with acute leukemia. Farber created several folic acid antagonists, or “blockers,” including methotrexate, which proved successful and became one of the first forms of cancer chemotherapy.