Tumor necrosis factor (TNF) inhibitors were the first biologics approved by the U.S. Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis (RA). This class of medications helps to stop or reduce inflammation in autoimmune diseases such as RA, inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), psoriatic arthritis, plaque psoriasis, and ankylosing spondylitis.

RA is an autoimmune disease that causes a person’s immune system to attack healthy cells in their body. The joints are most commonly affected, causing painful swelling due to joint damage. Fortunately, disease-modifying antirheumatic drugs (DMARDs) such as TNF inhibitors can help slow disease progression and improve the quality of life for people living with RA.

The Connection Between Tumor Necrosis Factor and Rheumatoid Arthritis

Tumor necrosis factor is a molecule in the body that has multiple functions related to the immune system. It is involved in different processes through which the immune system creates inflammation. Normally, TNF supports the immune system in fighting off infections and disease.

In people with RA, the immune system mistakenly targets healthy cells and tissues. It also produces inflammatory cytokines, or chemical messengers that cause pain and inflammation at the site of disease — the lining of the joints in people with RA. This process creates RA symptoms like pain, swelling, and stiffness in the affected joints. Higher levels of TNF in the body also contribute to long-lasting inflammation in people with RA.

How Do TNF Inhibitors Help RA Symptoms?

In response to the understanding of how TNF contributes to RA and its symptoms, scientists have studied two ways of inhibiting TNF to help treat RA. These include constructs called monoclonal anti-TNF antibodies and soluble TNF receptors. Both work by connecting to TNF-alpha cells in the body and limiting their ability to signal inflammatory pathways — a process that aims to prevent inflammation caused by TNF activity.

TNF Inhibitors as RA Treatment

There are three main classes of drugs that can help treat RA — corticosteroids (including prednisone), nonsteroidal anti-inflammatory drugs (NSAIDs), and DMARDs. TNF inhibitors fall under the DMARD class of drugs. The purpose of DMARDs is to reduce RA disease activity and bothersome symptoms like chronic pain.

TNF inhibitors can be expensive and may have side effects. Due to these factors, methotrexate, another DMARD, is usually prescribed as the first treatment for mild or moderate RA. If methotrexate doesn’t work well to treat someone’s RA, doctors may consider having them switch to a TNF inhibitor.

TNF inhibitors can be used alone in the treatment of RA, or they may be used in combination with other drugs like corticosteroids, or other DMARDs like methotrexate, sulfasalazine, leflunomide, or hydroxychloroquine. Your rheumatologist will work with you to test and find the best treatment for your RA.

How Do You Take TNF Inhibitors?

There are currently five different TNF inhibitors approved to treat RA. Depending on the drug, the medicine is given as an injection under the skin (subcutaneous) or as an infusion into a vein (intravenously). Infusions must be performed in a doctor's office, and subcutaneous injections can be performed at home.

Here are the five FDA-approved TNF inhibitors and how they’re taken:

• Etanercept (Enbrel) — Subcutaneous injection
• Infliximab (Remicade) — Intravenous infusion
• Adalimumab (Humira) — Subcutaneous injection
• Golimumab (Simponi) — Either an infusion or as a subcutaneous injection
• Certolizumab pegol (Cimzia) — Subcutaneous injection

TNF Inhibitor Injections

Subcutaneous injections like Enbrel shots can be given in either the thigh or the abdomen. You can give them to yourself or have a trusted friend or family member help you with the injection. Do not inject the medicine in the same location each time because this can cause skin reactions (called injection-site reactions).

For instructions and advice about giving yourself injections, talk to your doctor or pharmacist. You can also consult the pamphlet that comes with the medication. Many drug manufacturers offer instructional videos on their websites, which show you the step-by-step process of giving yourself an injection.

TNF Inhibitor Infusions

TNF inhibitor infusion therapy is usually administered at an infusion center or a doctor’s office. The process of infusing the medication might take up to four hours.

The frequency of infusions or injections varies based on what your health care provider prescribes. The usual range is every one to four weeks. People who are starting TNF inhibitors generally begin to see a change in their symptoms after three months.

What Are the Common Side Effects of TNF Inhibitors?

Because TNF plays a role in the functioning of the immune system, TNF inhibitors present the risk of mild to severe side effects.

Infections are the most significant side effect when taking a TNF inhibitor. Bacterial, viral, and fungal infections are possible because the reduction in TNF activity reduces a person’s ability to fight infections.

There is also an increased risk of serious infections in people taking multiple immunosuppressive drugs, such as TNF inhibitors and methotrexate. If a person develops a severe infection while taking a TNF inhibitor, the medication is usually stopped until they fully recover from the infection.

Other common side effects from TNF inhibitors include:

• Headaches
• Rashes and skin redness or discoloration (common at the injection site)
• Anemia (a decreased production of healthy red blood cells, which causes fatigue and weakness)
• Gastrointestinal issues (diarrhea, nausea, or abdominal pain)
• Respiratory issues (cough, pharyngitis, sinusitis, or respiratory tract infections)

Potential for Serious Side Effects

When taking TNF inhibitors, more serious side effects are possible. TNF inhibitors should not be used in people with severe congestive heart failure. Past studies have shown an increased risk of death in people living with both RA and congestive heart failure when they took TNF inhibitors. The medication may be given to people with mild congestive heart failure, but it should be carefully monitored.

Another serious but rare side effect of TNF inhibitors is the development of lupus-like symptoms, including rashes, low platelet counts (thrombocytopenia), low white blood cell counts (leukopenia), or hemolytic anemia (low red blood cells). However, these symptoms usually go away after a person has stopped taking the drug for weeks or months.

There is also concern regarding the risk of malignancies (tumors) with TNF inhibitor use. Because TNF plays a role in cancer cell death, there is an increased risk of developing cancer while taking a TNF inhibitor. There is a possible connection between taking TNF inhibitors and developing lymphoma or nonmelanoma skin cancers. Annual skin exams are beneficial for people taking TNF inhibitors.

If you experience serious or bothersome side effects from taking a TNF inhibitor, your doctor may prescribe you a different TNF inhibitor. Talk to your doctor about your concerns regarding the side effects of these medications.

What To Know Before Starting TNF Inhibitors

Before prescribing a TNF inhibitor, your doctor will evaluate your medical history and screen you for certain conditions. Certain preexisting medical conditions or infections might not make you a good candidate for using TNF inhibitors.

Existing Infections and TNF Inhibitors

TNF inhibitors increase your risk of infection, and they can also aggravate existing infections. Doctors need to understand if a person has any existing infections before recommending a TNF inhibitor. You’ll likely be screened for the following before being prescribed a TNF inhibitor:

• Tuberculosis
• Hepatitis B and hepatitis C
• HIV
• Varicella-zoster virus (which causes chicken pox and shingles)

If you have any of these infections, your doctor will typically try to treat the infection before recommending you start a TNF inhibitor.

Pregnancy and TNF Inhibitors

Another important consideration before starting a TNF inhibitor is whether you’re pregnant or breastfeeding. There have not been any controlled trials to determine if TNF inhibitors are safe for women who are pregnant or breastfeeding. This class of medications is generally not prescribed for women who are pregnant unless there is a strong indication that the benefits outweigh the potential risks.

Vaccines and TNF Inhibitors

Once you start taking a TNF inhibitor, talk with your health care provider before getting any vaccines. Certain types of vaccines, such as live vaccines, should be avoided. Also, be sure to tell your health care provider if you develop a high fever while you are taking a TNF inhibitor, as this may be a sign of an infection.

Remember that an effective treatment plan is a collaborative effort between you and your rheumatologist. Don’t hesitate to ask your doctor questions about taking TNF inhibitors to treat your RA symptoms.

Talk With Others Who Understand

On myRAteam, the social network for people with rheumatoid arthritis and their loved ones, more than 193,000 members come together to ask questions, give advice, and share their stories with others who understand life with rheumatoid arthritis.

Have you taken TNF inhibitors or are you thinking of taking them for your rheumatoid arthritis? What has your experience been? Please share your story in the comments below — or start a conversation or ask a question by posting on your Activities page.