Enbrel (Etanercept) for Rheumatoid Arthritis – all your questions answered

Enbrel for Rheumatoid Arthritis


Etanercept (Enbrel®) is one of the most common “biologic” medications that we use for patients suffering from moderate to severe Rheumatoid Arthritis. This is a medication that we use for patients that failed other therapies like disease modifying drugs (DMARDs) or non-steroidal inflammatory (NSAIDs) medications. Education is key in understanding the benefits but also the risk of using this medication. Thus, I discuss with my patients in detail and here are the most common questions that I answer for my patients.

  • What is Etanercept/ Enbrel?
  • What is the effect of Enbrel in Rheumatoid Arthritis patients?
  • Is Enbrel a pill or an injectable medication?
  • What tests are needed before starting Enbrel?
  • Can Enbrel be combined with other medications such as biologics?
  • What are the most common side effects?
  • Can Enbrel increase the risk of infections and how common are the SEVERE infections?
  • How can I decrease and prevent infections?
  • Can Enbrel increase the risk of cancer?
  • Is Enbrel safe for patients with heart failure?
  • What vaccines are recommended before starting Enbrel?
  • Is  Enbrel safe for pregnancy?

What is Etanercept / Enbrel?

Etanercept, sold under the brand name Enbrel, is a medication from the TNF-alpha inhibitors class. It is prescribed to patients with moderate to severe cases of  rheumatoid arthritis. Enbrel, like Humira/ adalimumab, is a recombinant monoclonal antibody. It binds to the human tumor necrosis factor alpha (TNF-alpha) receptor. TNF-alpha is a well-known molecule that causes inflammation in our body.

What is the effect of Enbrel on Rheumatoid Arthritis patients?

Patients with Rheumatoid Arthritis have high levels of inflammation. Inflammation may be present systemic (affecting many organs) or in the joints. Treatment of rheumatoid arthritis with Etanercept (Enbrel) works to reduce signs/ symptoms, inhibit the progression of structural joint damage, and improve physical function. Enbrel interferes with TNF-alpha molecules that can be found in high levels in the synovial fluid of patients suffering from Rheumatoid Arthritis.

Is Enbrel a pill or an injectable medication?

Enbrel is a self-administered injectable medication usually taken by a 50 mg injectable pen or syringe weekly. It may be given in the thigh or abdomen area. It is recommended that you rotate the site of the injection whenever you give yourself the injection. You should leave it at room temperature for about 15- 30 minutes before use, but do not remove the cap or cover during this time. Do not use it if the solution is discolored. Do not administer on areas of skin that are red, bruised, hard, or have scars.

Enbrel Pen for Rheumatoid Arthritis

What tests are needed before starting Enbrel?

Before starting therapy with Etanercept (Enbrel), it is crucial to screen for latent tuberculosis and hepatitis B/hepatitis C. You will also need other tests like CBC with differential, complete metabolic panel, and HIV screening in high-risk patients. Laboratory tests are also needed during therapy with Enbrel. Discuss with your physician how frequently you need testing.

Tests to monitor for Enbrel Therapy

Can Enbrel be combined with other medications, such as biologics?

Enbrel can be combined with other disease-modifying anti-rheumatic drugs (e.g methotrexate, leflunomide, sulfasalazine and hydroxychloroquine). However,  it is not recommended to be associated with other TNF- alpha inhibitors or biologics due to the increased risk of infections.

What are the most common side effects of Enbrel ?

Here are listed the most common side effects reported by patients on Etanercept (Enbrel):

  • Skin rash
  • Positive ANA titer
  • Antibody development
  • Infections (upper respiratory infections such as sinusitis)
  • Injection site reaction 
  • Nervous system symptoms such as headache and torso pain
  • Cardiovascular complications such as acute myocardial infarction, cardiac arrhythmia, chest pain, and palpitations 
  • Gastrointestinal issues such as abdominal pain
  • Hypersensitivity reaction
  • Back pain
  • Alopecia

Can Enbrel increase the risk of infections? 

Enbrel puts patients at an increased risk of developing severe infections, mainly if used in combination with other drugs that lower your immune system (e.g methotrexate; corticosteroids). The risk is about 4-5%.

Infections include active tuberculosis, the reactivation of latent tuberculosis, invasive fungal infections, or other bacterial and viral infections (herpes zoster, hepatitis B). If you get an infection you should stop the medication and call your physician immediately.

How can I decrease and prevent infections?

I recommend getting up to date with all immunizations (e.g. flu vaccine, pneumococcal vaccine, COVID-19 vaccine, Herpes Zoster vaccine)   to all my patients prior to starting therapy, unless they have contraindications. However, I recommend against getting any LIVE vaccines during therapy with Enbrel.

Can Enbrel increase the risk of cancer?

Lymphoma and other malignancies are rare, but they have been reported in patients taking TNF-alpha inhibitors like Enbrel ( e.g. lymphoma and non-melanoma skin cancers). However the risk of getting a malignancy on this medication is still under debate.

Is Enbrel safe for patients with heart failure?

Patients on TNF- alpha inhibitors rarely may develop new-onset or worsen heart failure. Thus, if you suffer from cardiac disease, disclose this to your physician, as you will need a complete cardiac evaluation before starting this therapy.

What vaccines are recommended before starting Enbrel?

Being up to date with all immunizations is recommended before starting Enbrel. Live vaccines should not be given concurrently to Enbrel. Inactivated vaccines should be given at least 2 weeks prior to initiation of therapy and patients who are vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2-3 months after therapy is complete.

Is Enbrel safe for pregnancy?

The risk of using Enbrel during pregnancy is considered moderate to low. No adverse maternal or fetal effects risks have been observed following Etanercept exposure during pregnancy. If you remain pregnant on this medication, contact your physician. It is considered safe to continue therapy until 32 weeks of pregnancy. TNF-alpha inhibitors are considered safe with breastfeeding. 

This medication information is limited. Patients should use it as a tool better to understand the medication’s role in disease treatment. It is not supposed to be comprehensive and does NOT include all information about a diagnosis, treatment, medication, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a physician. 


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