**Question:** All are TNF–α antagonists used in rheumatoid arthritis except:

A. Infliximab
B. Adalimumab
C. Golimumab
D. Certolizumab

**Core Concept:** TNF-α (tumor necrosis factor-alpha) is a pro-inflammatory cytokine that plays a significant role in the pathogenesis of rheumatoid arthritis (RA). TNF-α antagonists are medications that block the effects of TNF-α and are used in the treatment of RA.

**Why the Correct Answer is Right:** Certolizumab is a TNF-α antagonist used in the treatment of RA. However, it is different from the other options in terms of its structure and mode of action. Certolizumab is a humanized monoclonal antibody that binds specifically to soluble TNF-α, preventing its interaction with cell surface receptors. This results in decreased inflammation and improvement in RA symptoms.

**Why Each Wrong Option is Incorrect:**

A. Infliximab: A monoclonal antibody that binds to both soluble and membrane-bound TNF-α, preventing its interaction with cell surface receptors. Infliximab is a more potent TNF-α antagonist compared to certolizumab, which might make it more effective but also more prone to adverse reactions due to its broader binding spectrum.

B. Adalimumab: A fully human monoclonal antibody that binds to soluble TNF-α, preventing its interaction with cell surface receptors. Similar to infliximab, adalimumab is a potent TNF-α antagonist, but with no significant differences in efficacy or safety compared to certolizumab.

C. Etanercept: A soluble TNF-α receptor fusion protein that acts as a decoy receptor, binding to TNF-α and neutralizing its effects. Etanercept is a different therapeutic approach compared to monoclonal antibodies (infliximab, adalimumab, and certolizumab) which directly bind to TNF-α, but shares a common mechanism of action with these drugs, targeting TNF-α in RA treatment.

D. Golimumab: A monoclonal antibody that binds to soluble TNF-α, preventing its interaction with cell surface receptors. Golimumab is a potent TNF-α antagonist and shares a similar mechanism of action with the other TNF-α antagonists, targeting soluble TNF-α in RA treatment.

**Clinical Pearl:** TNF-α blockade is a crucial component in the treatment of rheumatoid arthritis, as it reduces inflammation and improves disease activity. The choice of TNF-α antagonist depends on factors such as patient characteristics, treatment history, and access to specific medications. Rheumatologists usually consider these factors while selecting an appropriate TNF-α antagonist for an individual patient.