Oral TNF Inhibitors for Treatment
Currently, there are no oral TNF inhibitors available for treatment of inflammatory conditions. 1
Available TNF Inhibitors and Administration Routes
All currently approved TNF inhibitors are administered parenterally (either intravenously or subcutaneously) 1:
- Infliximab - intravenous administration
- Adalimumab - subcutaneous administration
- Etanercept - subcutaneous administration
- Golimumab - subcutaneous administration
- Certolizumab pegol - subcutaneous administration
These medications are monoclonal antibodies or fragments of monoclonal antibodies that cannot be effectively administered orally due to their protein structure and molecular size 1, 2
The protein structure of TNF inhibitors would be degraded by digestive enzymes if administered orally, preventing them from reaching systemic circulation in their active form 3, 4
Current Treatment Approaches Without Oral Options
For conditions requiring TNF inhibition (such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease), patients must use injectable or infusion therapies 1
In psoriatic arthritis treatment algorithms, TNF inhibitors are recommended for patients who fail to respond to at least one DMARD therapy, but all options require parenteral administration 1, 5
For axial manifestations of psoriatic arthritis, TNF inhibitors are particularly important as traditional oral DMARDs (methotrexate, leflunomide, sulfasalazine) have not been shown to be effective 1, 6
Research Directions
There has been interest in developing oral, small-molecule inhibitors that could regulate TNF-alpha biology, which would potentially replace injectable therapies or provide better disease control when used alone or in combination with existing therapies 3
Research has focused on developing oral small molecules that could affect TNF signaling pathways rather than directly binding to TNF itself 3, 4
The development of oral TNF inhibitors would potentially improve medication adherence, which is an important factor in maintaining the benefits of anti-TNF therapy 2, 7
Alternative Oral Options for Inflammatory Conditions
For patients who prefer oral therapy, JAK inhibitors (such as tofacitinib) are available oral options for some inflammatory conditions, though they work through different mechanisms than TNF inhibitors 1
Phosphodiesterase-4 (PDE4) inhibitors like apremilast represent another class of oral medications for certain inflammatory conditions, though they also work through different mechanisms than TNF inhibitors 5
Traditional oral DMARDs (methotrexate, leflunomide, sulfasalazine) remain important treatment options for peripheral arthritis but have limitations in treating axial disease and other manifestations 1, 5
Clinical Implications
Patients who cannot or prefer not to use injectable medications must consider alternative mechanisms of action rather than TNF inhibition 1
The lack of oral TNF inhibitors represents an unmet need in the treatment of inflammatory conditions, particularly for patients with needle phobia or difficulty with self-injection 3, 2
When selecting therapy for inflammatory conditions, the route of administration remains an important consideration that may impact adherence and patient preference 2, 7