Review Question - QID 214090

The red "X" in Figure A describes the interaction between TNF-alpha and its receptor. Infliximab is a human-mouse chimeric TNF-alpha monoclonal antibody that inhibits this interaction.

Disease-modifying anti-rheumatic drugs (DMARDs) have become a mainstay in the treatment of rheumatological disorders. Tumor necrosis factor-alpha (TNF) plays an important role in host defense, tumor growth control, and cell death. This signaling pathway is overactive in autoimmune disease and leads to the attack on the synovium of the host leading to the joint destruction seen in rheumatoid arthritis (RA). TNF-alpha inhibitors have emerged as a leading DMARD because of their role in minimizing cell death via this cascade. Given that these medications can make patients susceptible to malignancies and infections, patients need to be monitored closely during administration. Common TNF-alpha inhibitors include Infliximab, Adalimumab, Etanercept, and Golimumab.

Lee et al. performed a meta-analysis of TNF-alpha inhibitors (infliximab and adalimumab) to determine the risk of serious infections and malignancies for patients taking the medication for RA. The authors noted an odds ratio for malignancy of 3.3 and for serious infection of 2.0 with taking TNF-alpha inhibitors. Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of TNF-alpha inhibitors. For serious infections, the number needed to harm was 59 within a treatment period of 3 to 12 months. The authors concluded that there is evidence of a significant dose-dependent risk of serious infections and malignancies in patients with RA treated with TNF-alpha inhibitors.

Goh et al. discussed the role of TNF-alpha inhibitors on wound infection for those patients with RA undergoing elective surgery. They noted that the risk of anti-TNF-related infection is highest at the start of treatment with frequent involvement of the skin and subcutaneous tissue which could negatively influence the healing of surgical wounds. They conclude that current guidelines suggest that treatment with DMARDs should be discontinued prior to surgery but need to be reinstated promptly after surgery to avoid the risk of RA flare.

Figure A shows a schematic of the cellular process of TNF-alpha binding to its receptor and causing cell death.

Incorrect Answers:
Answer 2: Anakinra is a recombinant IL1 receptor antagonist.
Answer 3: Tocilizumab is an IL-6 receptor inhibitor.
Answer 4: Abatacept is a T-cell inhibitor that is a selective modulator of both CD80 and CD86.
Answer 5: Rituximab is a monoclonal antibody to the CD20 antigen.