Does Methotrexate Improve Osteoarthritis Pain?

Jenny A. Van Amburgh, PharmD, BCACP, CDE


February 18, 2015


Can methotrexate be used for osteoarthritis?

Response from Jenny A. Van Amburgh, PharmD, BCACP, CDE
Assistant Dean of Academic Affairs; Clinical Professor, School of Pharmacy, Northeastern University; Director, Clinical Pharmacy Services & Residency Program, Harbor Health Services, Inc., Boston, Massachusetts

Affecting nearly 27 million adults in the United States, osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain in the knees, hands, spine, or hips.[1,2]Rheumatoid arthritis (RA), in contrast, is an autoimmune disease leading to damage of the synovial membranes, which causes generally symmetric swelling and pain typically in smaller joints, such as feet and hands.[3]

Currently, there is no cure for OA or RA; therefore, treatment options for both focus on managing symptoms to improve a patient's quality of life. Standard treatment for OA includes acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management.[4] In contrast, treatment for RA consists of NSAIDs in conjunction with disease-modifying antirheumatic drugs (DMARDs).[5]DMARDs slow the progression of joint damage and disability associated with RA; they are not intended merely for use as pain management.[3,5]

Methotrexate (MTX), the most common initial DMARD used in RA, has been a mainstay of treatment since in the 1980s.[5,6] The exact mechanism by which MTX alleviates the symptoms of RA is unknown; however, it is hypothesized to reduce proinflammatory biological markers in the body and promote anti-inflammatory activity.[6,7]

Some small studies have shown promise for use of MTX in knee OA. Wenham and colleagues' open-label pilot study[8] evaluated 30 participants with OA who received MTX up to 20 mg/week for 24 weeks; of those participants, 43% reported ≥ 30% reduction in knee pain according to a visual analog scale.

More recently, Abou-Raya and colleagues[9] conducted a randomized, placebo-controlled study demonstrating a reduction in knee OA pain associated with the use of up to 25 mg/week of MTX for 28 weeks. They found a statistically significant mean difference between the treatment arms of 11.4% for the knee OA pain score on the visual analog scale. In addition, they found a reduction in synovitis (clinically and on ultrasonography) in the MTX group at 28 weeks.

Both of these studies show that MTX can reduce symptoms of pain in knee OA, which is encouraging, because this may indicate MTX may reduce inflammation associated with OA. However, the use of MTX does not come without adverse effects, ranging from mild (gastrointestinal disturbances, alopecia) to severe (hepatoxicity).[7] In addition, it is important to highlight that in both studies, the majority of participants (53%-88%) were taking concomitant NSAIDs, acetaminophen, or opioid medications in addition to MTX.[8,9]

Large, randomized, placebo-controlled trials with substantial efficacy and safety outcomes need to be published in order to strongly recommend the use of MTX for knee OA in clinical practice guidelines.

Acknowledgment: The author wishes to acknowledge the assistance of Amy Thein, PharmD, RPh; Josephine Aranda, PharmD, RPh; and Lisa Cillessen, PharmD, RPh, PGY1 Residents, at Northeastern University—School of Pharmacy, in collaboration with Federally Qualified Health Centers & the Program of All-Inclusive Care for the Elderly, Boston, Massachusetts.


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