In rheumatoid arthritis, if prednisone and methotrexate fail, the next step is a drug that blocks the effects of which cytokine?

• A. IL-6
• B. IFN-gamma
• C. IL-1
• D. TNF-alpha

Answer: (D)

The main idea is that after standard therapies like prednisone and methotrexate, rheumatoid arthritis is often treated with a biologic drug that dampens a key inflammatory signal driving joint damage. TNF-alpha is a central proinflammatory cytokine in RA; it promotes inflammatory cell activation, expression of adhesion molecules, and the destruction of cartilage and bone through pannus formation. Blocking TNF-alpha with drugs such as etanercept, infliximab, or adalimumab reduces this inflammatory cascade, leading to symptom relief and slowed joint damage. While other cytokines like IL-1, IL-6, or IFN-gamma also contribute to RA, TNF-alpha inhibitors have historically been the standard next step after MTX failure due to their robust effect on disease activity.