What You Need to Know About TNF Inhibitors

What they are and the differences between drugs

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Tumor necrosis factor (TNF) inhibitors, sometimes called TNF-alpha or TNFα inhibitors, are medications that help reduce the inflammatory process in the treatment of autoimmune and inflammatory conditions. These medications include Enbrel (etanercept), Remicade (infliximab), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golimumab).

TNF inhibitors are approved by U.S. Food and Drug Administration (FDA) to treat a variety of conditions, including rheumatoid arthritis (RA)s, psoriatic arthritis, inflammatory bowel disease (IBD), and ankylosing spondylitis.

Woman making skin fold on stomach and injecting medicine from syringe at home
Ivan-balvan / Getty Images

How TNF Inhibitors Work

TNF inhibitors work by blocking the activity of a protein called TNFα. This protein normally helps with important functions such as fat metabolism and blood clotting, and excess TNFa can contribute to chronic inflammation and joint damage—as is the case in RA and other autoimmune conditions.

TNF inhibitors are biologics, a class of drugs that are created from living cells. Earlier biologics were derived using rodent cells, but newer ones come from lab-created versions of human cells and are called "fully humanized." This process creates monoclonal antibodies, which are antibodies that have been cloned.

TNF inhibitors are not a first-line treatment for treating RA. They can be prescribed as a replacement for a disease-modifying anti-rheumatic drug (DMARD) that isn't working well enough, and they can also be taken along with a DMARD, such as methotrexate. Current American College of Rheumatology guidelines for RA state that after maximal methotrexate therapy, either a biologic or a synthetic DMARD JAK inhibitor, like Xeljanz (tofacitinib) should be added.

When talking to your healthcare provider about which TNF inhibitor may be right for you, you may want to consider factors such as administration, side effects, and costs.

COMPARING TNF INHIBITORS
Drug Administration Frequency (maintenance dose) Monthly Cost
(maintenance dose)
Enbrel Self-injection Every week $5,000-$9,000
Remicade Infusion Every 8 weeks $650-$1,250
+infusion cost
Humira Self-injection Every 2 weeks $5,800
Cimzia Self-injection Every 2 weeks $9,000-$14,400 
Simponi Self-injection or infusion Every 8 weeks $2,250-$3,850 +infusion costs, if applicable

All TNF inhibitors come with a boxed warning, the FDA's most serious warning, due to an increased risk of severe infection and some types of cancer.

Enbrel

Enbrel (etanercept) is a genetically engineered protein created by combining human DNA and hamster ovarian cells. In 1998, it became the first anti-TNF drug to gain FDA approval.

Administration

You take Enbrel by injecting it under your skin. It comes in an auto-injector pen, pre-filled syringes, or vials that you use to fill syringes yourself. The standard adult dose is 50 milligrams (mg) once every seven days.

For plaque psoriasis, Enbrel is started at 50 mg twice a week for three months, after which it changes to the standard schedule.

Pediatric dosage is based on weight and is 0.8 mg per kilogram (kg)—about 2.2 pounds—per week, not to exceed a maximum of 50 mg.

Side Effects and Warnings

Common side effects of Enbrel include:

Less common, but more serious side effects are:

Enbrel may also increase your risk of some serious conditions, including several types of cancer, hepatitis B, and additional autoimmune diseases. If you have heart disease, Enbrel may make it worse.

Who Shouldn't Take Enbrel

Don't start Enbrel if you have a serious infection.

Enbrel may be harmful to people with certain conditions.

This drug is not recommended for people who:

Cost

Online retail estimates for Enbrel range from about $5,000 to nearly $9,000 per month. Amgen, the manufacturer, offers a co-pay card for people with insurance and a special program that allows qualifying people without insurance to get the drug for free.

Remicade 

Remicade (infliximab) is a monoclonal antibody created with a combination of mouse and human cells. It joined Enbrel on the market after gaining FDA approval in 1999.

Administration

Remicade is given as an infusion at a healthcare provider's office, hospital, or clinic. It's delivered slowly through an intravenous (IV, in a vein) line, which usually takes two hours or longer.

After your first infusion, you'll get another in two weeks, another four weeks later, and then go on a maintenance schedule of infusions every eight weeks. It can be given as frequently as every 4 weeks for patients that have an incomplete response.

Your healthcare provider will determine the proper dosage for your infusions.

Side Effects & Warnings

Common side effects of Remicade include:

  • Infusion site reactions
  • Headache
  • Nausea
  • Runny mose
  • White patches in the mouth
  • Flushing
  • Yeast infections (women)

In rare cases, more serious side effects have been reported, such as:

  • Stomach pain
  • Chest pain
  • Dizziness or fainting
  • Dark urine
  • Infection
  • Irregular heartbeat
  • Bloody stools
  • Seizures
  • Shortness of breath

Who Shouldn't Take Remicade

If you have any of the following conditions, you may not be a good candidate for Remicade:

Also, let your healthcare provider know if you've had any recent vaccinations.

Cost

Online estimates for a single dose of Remicade range from $1,300 to $2,500, plus the cost of the infusion procedure itself. The manufacturer, Janssen, offers programs to help you cover the costs, whether or not you're insured.

Humira 

Humira (adalimumab), approved in 2002, was the first fully-humanized monoclonal antibody.

Administration

You inject yourself under the skin with Humira. It's available in a pre-filled syringe or injector pen.

For most uses, the standard dosage of Humira is 40 mg every two weeks, but this can vary by condition. If you are not adequately improving, your healthcare provider may increase the frequency of your dose to once a week.

For some conditions, you'll start with a higher and/or more frequent initial dose, then transition to the standard dose that's recommended for your condition.

Pediatric doses of Humira vary by weight, with different ranges for different conditions.

Side Effects & Warnings

Common Humira side effects include:

  • Headache
  • Infections
  • Injection site reactions (usually mild)
  • Nausea
  • Back pain

More serious reactions include:

Who Shouldn't Take Humira

If you have a demyelinating disease, such as multiple sclerosis, Humira might make it worse.

You shouldn't start Humira if you have an active infection or have a high risk of infection due to uncontrolled diabetes or other health problems.

This drug isn't recommended during pregnancy or lactation.

As with all TNF inhibitors, you should not take Humira if you have cancer.

Cost

Online estimates for Humira costs are around $5,800 dollars per month (two doses). Manufacturer AbbVie offers programs to help you pay for the drug.

Cimzia

Cimzia (certolizumab pegol) is a fully-humanized monoclonal antibody approved in 2008.

Administration

Cimzia is a self-injected drug that typically starts out with an initial dose that's higher than the maintenance dose.

For most indications, you start out with two separate injections of 200 mg each. You take the same amount two weeks later and two weeks after that. Your maintenance dose will then be either 200 mg every 14 days or 400 mg every 28 days.

Side Effects & Warnings

Common side effects of Cimzia include:

  • Upper respiratory tract infection
  • Rash
  • Urinary tract infections
  • Injection site reactions
  • Headache
  • Back pain

Less often, the drug may cause severe side effects, including:

  • Demyelinating disease (new onset)
  • Heart failure
  • Lupus-like syndrome
  • Reactivation of hepatitis B infection
  • Reactivation of tuberculosis infection
  • Shortness of breath
  • Dizziness or fainting
  • Rash that worsens in the sun
  • Problems with vision
  • Joint pain
  • Loss of appetite

Who Shouldn't Take Cimzia

Certain conditions could make this drug more dangerous for you.

You and your healthcare provider will need to discuss the pros and cons of Cimzia if you have:

  • Diabetes
  • HIV/AIDS
  • Other conditions that impair the immune system

You may need to delay starting Cimzia if you recently had a live vaccine.

Cost

Online estimates for Cimzia range from around $4,500 to $7,200 for a single 200-mg dosage. UBC, the manufacturer, offers programs to help cover the cost.

Simponi

Simponi (golimumab) is a fully-humanized monoclonal antibody. The FDA granted it approval in 2009.

Administration

Simponi is self-injected under the skin. For most conditions, the standard dose is 50 mg once a month. For ulcerative colitis, there's a higher initial dose and a maintenance dose of 100 mg every eight weeks.

A different formulation of this drug, Simponi Aria, is given as an infusion at a healthcare provider's office, hospital, or clinic. After the first infusion, you'll get a dose every eight weeks thereafter. Each infusion should last about 30 minutes.

Side Effects & Warnings

Common side effects of Simponi include:

  • Upper respiratory tract infection
  • Injection site reactions
  • Viral infections (e.g., cold sores, influenza)

More serious complications of the drug include:

  • Reactivation of tuberculosis infection
  • Reactivation of hepatitis B infection
  • Increased risk of some types of cancer
  • Low blood count
  • Heart failure
  • Multiple sclerosis
  • Guillain-Barré syndrome
  • Liver disease
  • Psoriasis
  • Lupus-like syndrome
  • Joint pain
  • Vision changes
  • Sensitivity to the sun
  • Chest pain
  • Shortness of breath

You shouldn't get live vaccines while taking Simponi.

Who Shouldn't Take Simponi

You shouldn't start taking Simponi while you have an active infection.

You should carefully weigh the pros and cons of this drug with your healthcare provider if you've previously had hepatitis B or have recently had a live vaccine.

Cost

Online cost estimates for Simponi range from about $4,500 to $7,700. Janssen, the manufacturer, has a program designed to help you pay for the medication.

Saving Money on TNF Inhibitors

In addition to exploring pharmaceutical company programs for offsetting patients' drug costs, your healthcare provider or a hospital social worker may be able to guide you to other resources that can help you afford your medication(s).

Biosimilars

Biosimilar drugs are based on biologics and are determined by the FDA to have no clinically meaningful differences from the original drug, which is called a reference product. You can recognize a drug as a biosimilar if you see a four-letter suffix at the end of its name.

Biosimilars are typically less expensive than biologics. A pharmacy can't substitute a biosimilar for the reference product. If you want the biosimilar, you have to get a prescription specifically for it.

If you've been prescribed a biologic but would rather take a biosimilar for financial or other reasons, you'll need to get a whole new prescription for it. Speak with your healthcare provider.

BIOLOGIC AVAILABLE BIOSIMILARS 
Enbrel Erelzi (etanercept-szzs) •Eticovo (etanercept-ykro)
Remicade •Avasola (infliximab-axxq) •Inflectra (infliximab-dyyb) •Ixifi (infliximab-qbtx) •Renflexis (infliximab-abda)
Humira •Abrilada (adalimumab-afzb) •Amjevita (adalmimumab-atto) •Cyltezo (adalimumab-adbm) •Hadlima (adalimumab-bwwd) •Hulio (adalimumab-fkjp) •Hyrimoz (adalimumab-adaz)
Cimzia None
Simponi None
12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  5. National Institutes of Health, U.S. National Library of Medicine: MedlinePlus. Infliximab injection.

  6. U.S. Food and Drug Administration: FDA AccessData. Humira: Highlights of prescribing information and Full prescribing information.

  7. National Institutes of Health, U.S. National Library of Medicine: MedlinePlus. Adalimumab injection.

  8. Sator P. Safety and tolerability of adalimumab for the treatment of psoriasis: a review summarizing 15 years of real-life experienceTher Adv Chronic Dis. 2018;9(8):147–158. doi:10.1177/2040622318772705

  9. U.S. Food and Drug Administration: FDA AccessData. Cimzia: Highlights of prescribing information and Full prescribing information.

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  12. National Institutes of Health, U.S. National Library of Medicine: MedlinePlus. Golimumab injection.

Additional Reading
Carol Eustice

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.