Tumor Necrosis Factor Inhibitors for Immune-Mediated Inflammatory Diseases

Introduction to TNF Inhibitors

TNF-α is a proinflammatory cytokine produced by various cell types, including keratinocytes, that mediates inflammatory and immunoregulatory activities 2
TNF-α levels are elevated in affected tissues and fluids of patients with inflammatory conditions, with levels correlating with disease severity 3
The American College of Rheumatology recommends TNF inhibitors as a treatment option for patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis 1

TNF inhibitors work by binding to TNF-α, preventing its interaction with cell surface TNF receptors and thereby inhibiting its inflammatory effects 4
There are currently five FDA-approved TNF inhibitors, each with a unique structure and mechanism of TNF neutralization, including infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol 1

TNF inhibitors have been approved for the treatment of multiple inflammatory conditions, including psoriatic arthritis (PsA) 5, ankylosing spondylitis (AS) 2, and ulcerative colitis (UC) 1
The European League Against Rheumatism recommends TNF inhibitors as a first-line treatment option for patients with ankylosing spondylitis 2
All five TNF inhibitors are effective in treating rheumatoid arthritis (RA), PsA, and AS, but only infliximab, adalimumab, and golimumab are effective for inflammatory bowel disease (IBD) 1

The American Academy of Dermatology recommends tuberculosis testing before starting TNF inhibitor therapy due to the increased risk of serious infections, including tuberculosis reactivation 3
TNF inhibitors should not be used in patients with multiple sclerosis (MS) or other demyelinating diseases, or in first-degree relatives of patients with MS 3
The American Heart Association recommends caution when using TNF inhibitors in patients with congestive heart failure (CHF) due to reports of new onset and worsening of CHF 3

The American College of Obstetricians and Gynecologists recommends that women with well-controlled disease may discontinue TNF inhibitors containing an IgG1 Fc construct in the third trimester to minimize fetal exposure 7
Certolizumab can be continued throughout pregnancy due to its minimal placental transfer 7

Primary and secondary failures of TNF inhibitor therapy affect 30-50% of patients in clinical practice, particularly those with long-standing disease 1
The European League Against Rheumatism recommends considering alternative biologic DMARDs or JAK inhibitors in patients who fail TNF inhibitor therapy 8, 5

Regular monitoring for infections, particularly tuberculosis, is recommended for patients taking TNF inhibitors 3
Periodic laboratory assessments and vigilance for potential adverse effects, including injection site reactions and infusion reactions, are also recommended 7, 3