Enbrel vs. Humira: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Enbrel and Humira are two brand-name medications used for rheumatoid arthritis, juvenile idiopathic arthritis, plaque psoriasis, and various other inflammatory autoimmune diseases. They can help reduce joint damage and improve signs and symptoms of these conditions. 

Humira—but not Enbrel—can also be used for inflammatory bowel disease (IBD, which includes Crohn’s disease and ulcerative colitis), hidradenitis suppurativa, and uveitis. 

Humira is made by AbbVie and has been the world’s top-selling drug since 2012. Enbrel is made by Amgen, and is number 11 on the top-selling drug list. 

Enbrel and Humira are both approved by the U.S. Food and Drug Administration (FDA). These drugs are known as biologics, and are monoclonal antibodies. Enbrel and Humira are categorized in a drug class called tumor necrosis factor blockers (TNF blockers). TNF blockers work by blocking the activity of tumor necrosis factor (TNF). TNF is a substance in the body that causes inflammation. TNF blockers, also known as TNF inhibitors, suppress the immune system, and block the activity of TNF. 

Although Enbrel and Humira are both TNF blockers, they are not exactly the same. Continue reading below to learn more about Enbrel and Humira. 

What are the main differences between Enbrel vs. Humira

Enbrel and Humira are both TNF blockers. Enbrel contains the ingredient etanercept. It is available as various single-dose prefilled injections. Enbrel is given subcutaneously (under the skin of the thigh, stomach, or outer upper arm). After proper training, Enbrel can be self-injected by the patient, or administered by a caregiver.

Humira contains the ingredient adalimumab and is available as a pen injection or a prefilled syringe injection. Humira is administered subcutaneously, under the skin of the thigh or stomach. Humira can be self-injected by the patient, or administered by a caregiver, after proper training. 

Currently, both drugs are available in the brand-name version only. Biologic drugs, such as Enbrel and Humira, do not have exact generic equivalents; instead, the brand-name drug is referred to as the reference product, and the biosimilar is highly similar to the reference product. Some biosimilars have been approved for Enbrel and Humira, but are not available yet. 

Conditions treated by Enbrel and Humira

Enbrel is approved for the treatment of:

• Rheumatoid arthritis (in adults with moderately to severely active disease; can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs, or DMARDs)
• Juvenile idiopathic arthritis (JIA) in adults and children ages 2 years and older with moderate to severely active JIA 
• Psoriatic arthritis in adults (alone or in combination with methotrexate)
• Ankylosing spondylitis in adults
• Moderate to severe chronic plaque psoriasis in adults and children 4 years and older

Humira is approved for the treatment of: 

• Moderate to severe Crohn’s disease in adults and children 6 years and older who have not adequately responded to conventional therapy
• Moderate to severe ulcerative colitis in adults and children 5 years and older who have not adequately responded to conventional therapy
• Rheumatoid arthritis (in adults with moderately to severely active disease; in combination with methotrexate or other DMARDs)
• Psoriatic arthritis in adults (alone or in combination with non-biologic DMARDs)
• Ankylosing spondylitis in adults
• Moderate to severe chronic plaque psoriasis in adults
• Juvenile idiopathic arthritis (JIA) in adults and children ages 2 years and older with moderately to severely active JIA (alone or in combination with methotrexate)
• Hidradenitis suppurativa in moderate to severe cases in adults and children ages 12 years and older
• Uveitis in adults and children ages 2 years and older

Enbrel or Humira is usually taken together with other medications for the condition being treated. For example, an adult with moderate rheumatoid arthritis may also take methotrexate, folic acid, corticosteroids, and/or nonsteroidal anti-inflammatory drugs (NSAIDs), in addition to the TNF blocker. 

Is Enbrel or Humira more effective?

Although both drugs have undergone the required testing for safety and efficacy, there is very little data comparing the two drugs. 

When considering Enbrel vs Humira, one important factor is the reason for use. Either drug can be used for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, or juvenile idiopathic arthritis. However, only Humira can be used for Crohn’s disease, ulcerative colitis, hidradenitis suppurativa, or uveitis. 

Another factor may include insurance coverage. Patient preference and comfort can also play a role in drug selection. One small study showed that Humira was considered by patients to be more convenient, but had more stinging and burning associated with injection; however, at six months, patients reported similar outcomes with either drug. However, this study only looked at under 300 patients. 

The healthcare provider will also refer to guidelines for treatment, such as the 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. These guidelines recommend first trying methotrexate alone, before adding a TNF blocker. This is because many patients will improve on methotrexate alone, without the additional risks for serious reactions—as well as high costs—associated with TNF blockers. However, the guidelines note that some patients do prefer a more aggressive approach with both methotrexate and a TNF blocker.

The most effective medication for a patient should only be determined by the healthcare provider, who will consider the patient’s medical condition(s), history, and medications they may already be taking that could interact with Enbrel or Humira, as well as the patient’s response to treatment.

Coverage and cost comparison of Enbrel vs. Humira

Enbrel and Humira are often filled through a specialty pharmacy, but in some cases, may be filled at your local pharmacy. 

The out-of-pocket cost of Enbrel at your pharmacy could be $8,000 or more. Use a free SingleCare card to lower the price to $5,645 for a box of prefilled syringes.

The out-of-pocket cost of Humira could be $6,800 or more. Using a free SingleCare discount card can lower the price to approximately $5,600 for a box of prefilled syringes.  

Contact your prescription drug insurance plan or Medicare prescription drug plan for up-to-date cover information on Enbrel or Humira. Your insurance plan can also advise you on where you should fill your prescription for Enbrel or Humira. 

Common side effects of Enbrel vs. Humira

The most common side effects of Enbrel are infections, injection site reactions, and diarrhea.

Common Humira side effects include upper respiratory infections, sinus infections, injection site reactions, headaches, and rash. 

This is not a full list of side effects. Other side effects may occur. Consult your healthcare professional for a full list of side effects. Read the warning section below for further information on some of the serious side effects/reactions of Enbrel and Humira. 

Source: Enbrel (DailyMed), Humira (DailyMed)

Drug interactions of Enbrel vs. Humira

Enbrel or Humira should not be combined with other biologic products used to treat the same conditions, due to an increase in serious infections and other complications that could arise. Examples of interacting drugs include anakinra, abatacept, or tocilizumab. 

People taking Enbrel or Humira should not receive live vaccines. 

Patients taking cyclophosphamide should not take Enbrel. 

Humira can interact with drugs that have a narrow therapeutic index. A narrow therapeutic index means that the drug has a very small window between being safe and being dangerous. Examples of these drugs include Coumadin (warfarin), cyclosporine, and theophylline. Enbrel interacts with cyclosporine, as well.

This is not a full list of drug interactions. Other drug interactions may occur. Before you take Enbrel or Humira, tell your healthcare professional about all of the medications you take, including Rx and OTC drugs, vitamins, and supplements. 

Warnings of Enbrel and Humira

Enbrel and Humira have a black box warning. This is the strongest warning required by the FDA. The black box warning states:

• Enbrel or Humira can increase the risk of serious infections. This is because they suppress the immune system. These infections may include tuberculosis (TB), bacterial sepsis, and invasive fungal infections, and can lead to hospitalization or death. 
• Enbrel or Humira should not be started when the patient has an active infection. If a patient develops a serious infection during treatment, Enbrel or Humira should be discontinued. 
• Before a patient starts taking Enbrel or Humira, a TB test should be performed. If the test is positive, TB treatment should begin before Enbrel or Humira is started. During Enbrel or Humira treatment, patients should be monitored for TB and other infections. 
• Lymphoma and various other cancers, some of which have been fatal, have occurred in children and adolescent patients treated with TNF blockers such as Enbrel or Humira.

Other warnings for both Enbrel and Humira:

• Hepatitis B virus reactivation: TNF blockers, including Enbrel or Humira, can reactivate hepatitis B virus (HBV) in people who are chronic carriers. In some cases, HBV reactivation combined with TNF treatment (and often with other immunosuppressants) has caused death. Patients should be tested for HBV before starting Enbrel or Humira. 
• Liver toxicity: TNF blockers can cause severe liver problems, and liver function should be monitored. Symptoms of liver problems, such as fatigue, stomach pain, and yellowing of the skin and whites of the eyes, require immediate medical attention. 
• Heart failure: TNF blockers can cause a higher risk of heart failure, or a worsening of heart failure. The use of a TNF blocker in people with heart failure is determined on an individual basis. Patients with heart failure should consult their healthcare provider before taking Enbrel or Humira. 
• Hypersensitivity: Enbrel or Humira can cause serious allergic reactions. Symptoms of hives, difficulty breathing, low blood pressure, or swelling around the face, lips, tongue, or throat, require emergency medical attention. 
• Hematologic reactions: Enbrel or Humira can cause life-threatening or fatal blood problems. These may include low white blood cell counts, low platelet counts, and pancytopenia. Patients should seek emergency medical attention if symptoms of infection occur. Symptoms may include fever, bruising, bleeding, or pale skin. 
• Neurologic reactions: TNF blockers can cause central nervous system (CNS) problems such as seizures, multiple sclerosis, or Guillain-Barré syndrome. TNF blockers should be used cautiously in people with CNS conditions. 
• Live vaccines: Vaccinations should be up to date before starting treatment with Enbrel or Humira. Live vaccines (such as measles, mumps, rubella or MMR, polio, rotavirus, typhoid, yellow fever, or chickenpox) should not be administered to a patient who is taking a TNF blocker, because serious infection could result. Live attenuated bacteria, such as BCG bladder instillation for cancer treatment, could also cause infection, and should not be given with a TNF blocker. Patients taking Enbrel or Humira should avoid people who are sick, and should call their healthcare provider for guidance if they are exposed to chickenpox or measles.

Frequently asked questions about Enbrel vs. Humira

What is Enbrel?

Enbrel is a TNF blocker that is given by subcutaneous injection (injection under the skin of the thigh, abdomen, or outer upper arm). Enbrel contains the ingredient etanercept. It is used to treat rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and juvenile idiopathic arthritis.

What is Humira?

Humira is a TNF blocker that is given by subcutaneous injection (injection under the skin of the thigh or abdomen). Humira contains the ingredient adalimumab. It is used to treat Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, juvenile idiopathic arthritis, hidradenitis suppurativa, and uveitis.

Are Enbrel and Humira the same?

Enbrel and Humira are both TNF blockers and can be used for many of the same conditions. However, Humira can also be used for several conditions that Enbrel cannot be used for (such as Crohn’s disease, ulcerative colitis, hidradenitis suppurativa, and uveitis). Enbrel and Humira also have other similarities and differences, as outlined in the information above. Other drugs in the TNF blocker class you may have heard of include Remicade (infliximab), Cimzia (certolizumab pegol), and Simponi (golimumab).

Is Enbrel or Humira better?

While either drug can help improve symptoms, there are many factors to consider, such as the condition being treated, insurance coverage, medical guidelines, and patient preference. The healthcare provider can take all of the factors into consideration to decide which drug is more appropriate for treatment.

Can I use Enbrel or Humira while pregnant?

Women who are pregnant or planning to become pregnant should consult their healthcare provider before using Enbrel or Humira. Women who already take Enbrel or Humira and find out they are pregnant should contact their provider. 

The use of Enbrel or Humira is generally considered safe while breastfeeding, as long as approved by the healthcare provider. 

Can I use Enbrel or Humira with alcohol?

When taking Enbrel or Humira, it is safest to avoid alcohol. Chronic alcohol use can cause inflammation, which is the reaction that Enbrel or Humira is trying to suppress. Also, TNF blockers such as Enbrel or Humira can increase the risk of liver problems, and alcohol can also cause liver damage. Also, people who take Enbrel or Humira usually take other medications for their conditions that can interact with alcohol, or cause liver damage or stomach bleeding. 

Does Enbrel cause weight gain?

Weight gain is not a side effect of Enbrel. Patients taking Enbrel who notice an increase in weight may have another serious complication such as heart failure, which can occur with Enbrel treatment and can cause rapid weight gain. Patients who experience weight changes should consult their healthcare professional for medical advice.

Who should not take Enbrel?

Enbrel should not be used in people who are allergic to etanercept or any of the components of Enbrel. Enbrel also should not be used in patients with sepsis. 

Enbrel also should only be used cautiously in various patient populations, such as older adults (>65 years old), patients with uncontrolled diabetes, patients who are at risk of infection or cancer, and patients with heart failure. 

Does Enbrel cause hair loss?

Generally, Enbrel is not associated with hair loss. Hair loss, or alopecia, is not listed as a side effect in the prescribing information for Enbrel. However, there may be cases where hair loss does occur in people who take TNF blockers. Usually, the hair loss can be attributed to another drug the patient is taking along with Enbrel, such as methotrexate or leflunomide.