Yet Another Study Finds Methotrexate Moderates Osteoarthritis Pain

In a study of 144 patients with primary knee osteoarthritis (OA), researchers at the University of Alexandria, Egypt, found that methotrexate was a therapeutic option for the treatment of pain and inflammation.

From the endpoint of pain, analog scores decreased significantly with methotrexate from 66.7 mm to 40.5 mm at 28 weeks, according to Diana Swift, writing for MedPage Today. This compared with placebo’s 66.5 mm to 51.7 mm, for a mean change from baseline of -26.2 versus -14.8.

“Methotrexate may be a therapeutic option in the treatment of pain and inflammation related to knee osteoarthritis, ” wrote Anna Abou-Raya, Ph.D., in Annals of the Rheumatic Diseases. “Certainly there is an unmet need for more effective treatments for OA, and there has been increasing evidence that there is some degree of inflammation involved in the pathogenesis of osteoarthritis.”

Kelly Weselman, M.D., of Atlanta, Georgia, who was not involved with the study, told MedPage Today, “Using methotrexate to treat osteoarthritis is certainly a novel approach.”

Methotrexate (MTX), formerly known as amethopterin, is an antimetabolite and antifolate drug.

It is most commonly used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid via dihydrofolate reductase.

Methotrexate began to replace the more toxic antifolate aminopterin starting in the 1950s. The drug was originally synthesized by the Indian biochemist Yellapragada Subbarow and clinically developed by the American pediatrician Sidney Farber. It is on the World Health Organization’s List of Essential Medicines, a list of the most important medications needed in a basic health system.

It is often used as a disease-modifying treatment for some autoimmune diseases, including rheumatoid arthritis, juvenile dermatomyositis, psoriasis, psoriatic arthritis, lupus, sarcoidosis, Crohn’s disease, eczema and many forms of vasculitis.

Although originally designed as chemotherapy drug (using high doses), in low doses methotrexate is a generally safe and well tolerated drug in the treatment of certain autoimmune diseases. Because of its effectiveness, low-dose methotrexate is now first-line therapy for the treatment of rheumatoid arthritis.

Weekly doses are beneficial for 12 to 52 weeks duration therapy, although discontinuation rates are as high as 16% due to adverse effects. Although methotrexate for autoimmune diseases is taken in lower doses than it is for cancer, side effects such as hair loss, nausea, headaches, and skin pigmentation are still common. Use of methotrexate together with NSAIDS is safe, if adequate monitoring is done.

Not everyone is responsive to treatment with methotrexate, but multiple studies and reviews showed that the majority of people receiving methotrexate for up to one year had less pain, functioned better, had fewer swollen and tender joints, and had less disease activity overall as reported by themselves and their doctors. X-rays also showed that the progress of the disease slowed or stopped in many people receiving methotrexate, with the progression being completely halted in about 30% of those receiving the drug. Those individuals with rheumatoid arthritis treated with methotrexate have been found to have a lower risk of cardiovascular events such as myocardial infarctions (heart attacks) and strokes. It has also been used for multiple sclerosis.

Swift reported that at 28 weeks, the investigators observed a clinically relevant reduction in the intervention group for the three outcomes of pain, physical function, and activities-of-daily-life scores.

“Improvement in WOMAC scores, which reflect function, were particularly striking in patients receiving methotrexate compared with those receiving placebo, ” Abou-Raya and her colleagues wrote.

Despite the encouraging results of the study the researchers remain cautious. While there are indications that methotrexate may decrease pain and improve function, the researchers are aware that the findings are limited by the relatively small number of patients involved in the study and the short duration of the follow-up.