Methotrexate is not classified as a Tumor Necrosis Factor (TNF) inhibitor. These two types of medications operate through distinct mechanisms to manage inflammatory conditions. While both are used in the treatment of autoimmune diseases, their approaches to modulating the immune system differ significantly.
How Methotrexate Works
Methotrexate is a conventional synthetic disease-modifying antirheumatic drug (csDMARD), utilized for its immunosuppressive and anti-inflammatory properties. Its primary mechanism involves interfering with folate metabolism by inhibiting the enzyme dihydrofolate reductase. This reduces the synthesis of purines and pyrimidines, building blocks for DNA and RNA, slowing the proliferation of immune cells like lymphocytes.
Methotrexate also influences inflammatory pathways. It increases the release of adenosine, a potent anti-inflammatory molecule, suppressing immune cell activation and reducing inflammation. The drug also affects gene expression and cell signaling. Methotrexate is a common treatment for conditions like rheumatoid arthritis, psoriasis, and psoriatic arthritis.
How TNF Inhibitors Work
Tumor Necrosis Factor (TNF) is a cytokine that plays a central role in the body’s inflammatory and immune responses. In autoimmune diseases, an overproduction or dysregulation of TNF contributes significantly to chronic inflammation and tissue damage. TNF inhibitors are a class of biologic disease-modifying antirheumatic drugs (bDMARDs) designed to target this cytokine.
These medications work by binding to TNF, neutralizing its activity or blocking its interaction with cell surface receptors. By preventing TNF from initiating inflammatory cascades, these inhibitors reduce inflammation and slow disease progression. Examples of conditions treated with TNF inhibitors include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn’s disease.
Distinguishing Methotrexate from TNF Inhibitors
The fundamental difference between methotrexate and TNF inhibitors lies in their classification and specific mechanisms of action. Methotrexate is a conventional synthetic DMARD, meaning it is chemically synthesized and exerts broad immunosuppressive effects by interfering with cellular processes like folate metabolism.
In contrast, TNF inhibitors are biologic DMARDs, which are complex proteins manufactured using living cells. They are highly targeted therapies that specifically neutralize or block the activity of Tumor Necrosis Factor, a single, specific cytokine involved in inflammation.
Despite their distinct mechanisms, methotrexate and TNF inhibitors are frequently used together, particularly in the treatment of rheumatoid arthritis. Methotrexate often serves as a first-line therapy or an “anchor” drug, providing a foundational level of immune modulation. When used in combination with TNF inhibitors, methotrexate can enhance the efficacy of the biologic therapy and reduce the likelihood of the body developing antibodies against the TNF inhibitor, which could otherwise diminish its effectiveness over time. They target different inflammatory pathways, making their combined use complementary rather than interchangeable.