Compare and contrast Enbrel and Humira, two injectable medications for rheumatoid arthritis (RA).

If you have rheumatoid arthritis (RA), you’re all too familiar with the kind of pain and joint stiffness that can make even getting out of bed in the morning hard to manage.

Enbrel and Humira are two drugs that might help. Take a look at what these drugs do and how they stack up against each other.

Enbrel (Etanercept) and Humira (adalimumab) are prescription biologic drugs used to treat RA.

Both drugs are tumor necrosis factor (TNF)-alpha inhibitors. TNF-alpha is a protein made by your immune system. It contributes to inflammation and joint damage.

Enbrel and Humira are tumor necrosis factor (TNF) inhibitors. In this case, they block the action of the TNF-alpha, which allows them to decrease damage from abnormal inflammation.

The current 2021 American College of Rheumatology (ACR) guidelines do not recommend TNF-alpha inhibitors as a first-line therapy for RA. Instead, they recommend starting treatment with methotrexate, which is a disease-modifying anti-rheumatic drug (DMARD).

Besides RA, the Food and Drug Administration (FDA) has also approved Enbrel and Humira to treat:

In addition, Humira treats:

Enbrel and Humira work in the same way to treat RA, and many of their features are the same.

The ACR 2021 guidelines don’t express a preference for one TNF-alpha inhibitor over the other due to a lack of convincing evidence that one is more effective than the other.

Some people benefit from switching to a different TNF-alpha inhibitor if the first doesn’t work. Still, most doctors would recommend switching to a different RA drug instead.

The following table highlights the features of these two drugs:

Enbrel
manufacturer information		Humira
manufacturer information
What’s the generic name of this drug?etanerceptadalimumab
Is a generic version available?nono
Is a biosimilar version available in the U.S.?noyes
Amjevita or adalimumab-atto
What form does this drug come in?under-the-skin (SQ) injectable solutionSQ injectable solution
What strengths does this drug come in?• 25-mg/0.5 mL and 50-mg/mL single-dose prefilled syringes

• 50-mg/mL single-dose prefilled SureClick autoinjector

• 25-mg/0.5 mL single-dose vial

• 25 mg lyophilized powder in a multiple-dose vial for reconstitution

• 50-mg/mL single-dose prefilled Enbrel Mini cartridge for use with AutoTouch autoinjector		• 80-mg/0.8 mL, 40-mg/0.8 mL, 40-mg/0.4 mL single-dose prefilled pen

• 80-mg/0.8 mL, 40-mg/0.8 mL, 40-mg/0.4 mL, 20-mg/0.4 mL, 20-mg/0.2 mL, 10-mg/0.2 mL, 10-mg/0.1 mL single-use prefilled glass syringe

• 40-mg/0.8 mL single-use glass vial (institutional use only)
How often is this drug usually taken?once per week (initially twice weekly for some conditions)once per week or once every other week

You may find that the Enbrel AutoTouch or SureClick Autoinjector and Humira prefilled pens are easier and more convenient to use than single-dose vials and prefilled syringes. They require fewer steps.

People will typically see some improvement with either drug after two to three doses. Yet, an adequate trial of the drugs is about 3 months to see the full benefit.

How each person responds to either drug will vary.

Enbrel and Humira are stored the same way, except for the length of time they can be stored at room temperature.

Both should be kept in the original carton to protect them from light or physical damage. Other storage tips are seen below:

  • Keep the drug in a refrigerator at a temperature between 36°F and 46°F (2°C and 8°C).
  • Don’t freeze the drug or use it if it has been frozen and thawed.
  • Do not shake the product.
  • If traveling, keep the drug at room temperature (68–77°F or 20–25°C) and:
    • Protect the drug from light and humidity.
    • After 14 days at room temperature for Humira, throw the drug away. Do not put it back in the refrigerator.
    • After 30 days at room temperature for Enbrel SureClick pens and AutoTouch Mini cartridges, throw the drug away. Do not put it back in the refrigerator.

Enbrel and Humira are only available as brand-name drugs, not generics, and they cost about the same.

Calling your prescription insurance company can give you a more specific idea about their current costs.

Many insurance providers require prior authorization from your doctor before paying for either of these drugs. Check with your insurance company or pharmacy to determine whether you need prior authorization for Enbrel or Humira.

Your pharmacy can help you with the paperwork if authorization is needed. Many pharmacies carry both Enbrel and Humira. However, to dispense them, they will need to have special pharmacy divisions. This is because both medications are considered specially drugs.

These drugs treat certain complex conditions and may have particular instructions for use and monitoring side effects. They may also need a specific kind of storage. You can call your local pharmacy to see if they have Enbrel or Humira in stock and if they can dispense them.

Biosimilars are available for both drugs. Once they become widely available, biosimilars may be more affordable than the original brand-name drug.

One Humira biosimilar, Amjevita, became available in U.S. markets in January 2023.

Seven other biosimilars of Humira have been approved by the FDA but will not be released until mid-2023:

  • Hadlima (adalimumab-bwwd)
  • Cyltezo (adalimumab-adbm)
  • Hulio (adalimumab-fkjp)
  • Hyrimoz (adalimumab-adaz)
  • Abrilada (adalimumab-afzb)
  • Idacio (adalimumab-aacf)
  • Yusimry (adalimumab-aqvh)

Additional biosimilars of Humira are pending FDA approval.

The biosimilars of Enbrel are Erelzi and Eticovo. Even so, because of Enbrel’s drug patent, they may not be available in the U.S. until 2029.

Enbrel and Humira belong to the same drug class. As a result, they have similar side effects.

Some of the more common side effects include:

More severe side effects can include:

To reduce injection site reactions, the manufacturer of Humira reformulated the product to a citrate-free formulation. Before this change, those using Humira were over three times as likely to report injection-site burning and stinging.

Lastly, a 2019 Lancet study demonstrated that TNF-alpha inhibitors did not increase the risk of primary types of cancer, such as lymphoma. However, there still may be a risk of non-melanoma skin cancer, especially squamous cell cancer.

As a result, it’s a good idea for all patients using TNF-alpha inhibitors to get a yearly skin check with a dermatologist.

Always let your doctor or pharmacist know about all medications, vitamins, or herbs you’re taking. This can help prevent possible drug interactions, which can change how your drug works.

In addition, interactions can be harmful or prevent the drugs from working well.

Using either Enbrel or Humira with the following live vaccines increases your risk of severe infection:

Since Shingrix is not a live vaccine, people needing a shingles vaccine can now get one while taking Enbrel or Humira.

Enbrel and Humira also have different interactions with separate medications. These differences may be meaningful when choosing which product to use.

Drug interactions specific to Humira include:

  • methotrexate — increases the blood level of Humira and increases the risk of infection
  • certain drugs that are processed by a liver enzyme called cytochrome p450, including warfarin (Coumadin), cyclosporine (Neoral, Sandimmune), theophylline

Drug interactions specific to Enbrel include:

Furthermore, manufacturers warn against combining Enbrel or Humira with other drugs that suppress your immune system, such as anakinra (Kineret) or abatacept (Orencia). The combination of any biologic medicines can increase the risk of serious infection.

The use of Enbrel or Humira in persons with dormant TB may result in an active TB infection. Your doctor will test you for TB before you start treatment.

If you have hepatitis B virus infection, taking Enbrel or Humira could also restart your infection. That means you could experience hepatitis B symptoms, such as:

The active infection can also lead to liver failure and death. Your doctor will test your blood to make sure you don’t have hepatitis B before you receive either of these drugs.

Enbrel and Humira are very similar drugs. They’re equally effective at relieving the symptoms of RA.

However, there are slight differences, some of which might make one more convenient or better for you.

Some drug interactions differ between Enbrel and Humira. Your doctor or pharmacist can help you decide whether drug interactions affect your choice.

Also, Humira can be taken every other week or weekly, while Enbrel can only be taken weekly.

You may also prefer specific applicators, such as a pen or autoinjector. That preference may determine which medication you choose.

Knowing more about these two drugs can help you talk with your doctor to decide whether either option is an option for you.