TNF Inhibitors: A Comprehensive Guide to This Anti-Inflammatory Drug Class
Key takeaways:
Tumor necrosis factor (TNF) inhibitors are injectable biologic medications that treat autoimmune disorders. They help lessen inflammation and improve symptoms in people living with rheumatoid arthritis, Crohn’s disease, psoriasis, and more.
Humira (adalimumab), Remicade (infliximab), and Enbrel (etanercept) are all TNF inhibitors. Cimzia (certolizumab pegol) and Simponi (golimumab) are too. Your personal preferences, medical history, and insurance coverage status will determine which medication you take.
Humira biosimilars and Remicade biosimilars are also available. They’re lower-cost alternatives that are expected to deliver the same benefits as Humira and Remicade. Think of them as generic versions of brand-name medications.
Table of contents
Your immune system is an intricate and fascinating network that protects your body against infection and injury. It’s designed to fight off outsiders like bacteria, viruses, and fungi that threaten your health.
But sometimes, this defense system can work a bit too hard. Autoimmune disorders develop when your immune system attacks your body's healthy tissues by mistake. This creates excess inflammation. And in turn, this contributes to chronic pain, discomfort, and swelling.
Tumor necrosis factor (TNF) inhibitors are a class of biologic drugs that treat inflammatory health conditions like these. They work by blocking inflammation-causing TNF proteins in different areas of the body. They’ve been around for over 20 years, with biosimilars becoming available more recently.
Below, we offer a comprehensive overview of TNF inhibitors and their role in treating autoimmune disorders.
What are TNF inhibitors?
TNF inhibitors are prescription-only medications that block TNF, a protein in your body that can contribute to inflammation. They’re given as intravenous (IV) infusions or subcutaneous (under the skin) injections. IV infusions are administered at a healthcare facility. But you can generally give subcutaneous injections to yourself.
TNF inhibitors are also generally considered specialty medications.
Read more like this
Explore these related articles, suggested for readers like you.
What health conditions do TNF inhibitors treat?
TNF inhibitors treat several inflammatory health conditions. Each medication has its own list of FDA-approved uses. Between them, they can treat:
Full list of FDA-approved TNF inhibitors
There are currently five TNF inhibitors that are available for use. They are:
Humira (adalimumab)
Remicade (infliximab)
Enbrel (etanercept)
Cimzia (certolizumab pegol)
Simponi (golimumab)
The FDA has also approved biosimilars to Humira, Remicade, and Enbrel. Biosimilars are lower-cost medications that are very similar to their original (“reference”) biologic. However, only Humira biosimilars and Remicade biosimilars are actually available for use. Enbrel biosimilars likely won’t be available until 2029 due to patent limitations.
The FDA hasn’t approved any biosimilars for Cimzia and Simponi yet. But due to expiring patents, Cimzia biosimilars and Simponi biosimilars may be approved and released in the near future.
How do TNF inhibitors work?
TNF is an important part of your body’s normal immune response. It’s a naturally occurring protein in the body. In fact, it’s one of the first molecules to appear in your bloodstream after an injury or infection.
However, too much TNF can be harmful. If there’s too much TNF, it may lead to excessive inflammation or an inflammatory health condition.
For example, in rheumatoid arthritis, chronic inflammation occurs in the joints. This causes painful swelling. In psoriasis, high levels of TNF help form inflamed, itchy plaques on the skin.
TNF inhibitors help change this, as they lower the amount of TNF in your body over time. This then helps to relieve inflammation and many of the symptoms that go along with it. They’re meant to provide long-term relief and lower the risk of disease progression.
Are TNF inhibitors common first-choice treatment options?
TNF inhibitors are effective, but they’re generally not the first-choice treatment option. This is especially true if your symptoms are mild. They are a better choice when your symptoms are moderate to severe, or when other options haven’t worked.
There are a few reasons TNF inhibitors aren’t a first choice, including:
The potential for serious side effects
The high price tag, especially if your insurance doesn’t cover them, you have a high copay, or don’t have insurance
The inconvenience caused by receiving the IV infusions at a clinic or hospital
Your healthcare provider can help you choose the best medication for you based on your symptoms, personal preferences, and treatment history.
What are the risks and side effects of TNF inhibitors?
TNF inhibitors are well tolerated for many people. But some side effects are possible. Common TNF inhibitor side effects include:
Pain or swelling at the injection site
Increased risk of infection
Headache
Nausea
Cough
Many of these side effects go away quickly. But others, such as the risk of infection, can be more serious. Your provider may adjust your dose based on your response to the medication or if you have side effects.
Serious TNF inhibitor side effects
TNF inhibitors have a couple of boxed warnings, the FDA’s most serious medication warning.
While rare, there’s an increased risk of developing a life-threatening infection while receiving a TNF inhibitor. Tuberculosis (TB), bacterial sepsis, and fungal infections have been reported on some occasions. There’s also a small, but elevated risk of developing lymphoma or skin cancer.
Routine testing and monitoring can typically catch these issues before they become a larger problem. Your provider will test you for TB before starting treatment. They should continue to track for signs of infection throughout treatment. But make sure to look after yourself too. If you’re experiencing a side effect that feels worrisome, reach out to your care team right away.
What are the best alternatives to TNF inhibitors?
Your healthcare provider may recommend a different medication before trying a TNF inhibitor.
If your symptoms are relatively mild or infrequent, corticosteroids, such as prednisone, or nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), may do the trick. But if your symptoms are more frequent or longer-lasting, disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (Trexall) and sulfasalazine (Azulfidine), may be better choices.
Another option is trying a biologic that works differently from TNF inhibitors. Interleukin antagonists, such as Stelara (ustekinumab), and integrin antagonists, such as Entyvio (vedolizumab), are both possible alternatives, among others.
The bottom line
There are several different TNF inhibitors available to treat autoimmune disorders. Common ones include Humira (adalimumab), Remicade (infliximab), and Enbrel (etanercept). Cimzia (certolizumab pegol) and Simponi (golimumab) are also helpful for many people. Lower-cost Humira and Remicade biosimilars are available, too.
When deciding if you’d benefit from a TNF inhibitor or another medication, your healthcare provider will consider your preferences, treatment history, and insurance coverage status to determine the best treatment option for you.
Why trust our experts?
References
D’Arcy, M. E., et al. (2021). Tumor necrosis factor inhibitors and the risk of cancer among older Americans with rheumatoid arthritis. Cancer Epidemiology, Biomarkers & Prevention.
Generics and Biosimilars Initiative. (2017). Biosimilars of certolizumab pegol.
Gerriets, V., et al. (2023). Tumor necrosis factor inhibitors.
GlobalData. (2023). Alvotech’s AVT05 emerges as leading contender for Simponi biosimilar in rheumatoid arthritis, says GlobalData.
Jang, D. I., et al. (2021). The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. International Journal of Molecular Sciences.
Jeremias, S. (2023). Stelara and Enbrel chosen for IRA price negotiation. The Center for Biosimilars.
Kim Chan, K. (2023). Tumor necrosis factor (TNF) inhibitors. American College of Rheumatology.
Melsheimer, R., et al. (2019). Remicade (infliximab): 20 years of contributions to science and medicine. Biologics: Targets and Therapy.
Monaco, C., et al. (2014). Anti-TNF therapy: Past, present and future. International Immunology.
Rath, L., et al. (2022). What happens when an anti-TNF fails for RA. Arthritis Foundation.
