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The Tumor-Necrosis-Factor Alpha (TNF-a) Blockers: An Overview

by Chris Miller | Posted on 04/18/2013


Overview

The Tumor-Necrosis-Factor alpha (TNF-a) blockers are biologic medications that have been shown to be highly effective in treating not only the arthritis of the joints but the spinal arthritis associated with ankylosing spondylitis (AS) and related diseases.

As of this writing, there are four anti-TNF therapies used in the US that have an indication from the Food and Drug Administration (FDA) to treat AS and other diseases in the spondyloarthritis family (presented in order of initial FDA approval):

Enbrel (etanercept) - Originally approved in 1998 for rheumatoid arthritis (RA), Enbrel is self-injected and normally administered 1-2 times weekly. It has received indications for use in the following conditions:

  • Ankylosing Spondylitis
  • Psoriatic Arthritis
  • Rheumatoid Arthritis
  • Juvenile Idiopathic Arthritis
  • Plaque Psoriasis

Remicade (Infliximab) - Approved in 1999 initially for RA. Remicade is given by infusion - through an IV drip - thus one must visit a doctor's office or infusion clinic to receive the medication. The infusion can take around 2 hours. The infusion cycle varies per individual, but is commonly done every 6-8 weeks. It has been approved by the FDA for the following conditions:

  • Ankylosing Spondylitis
  • Psoriatic Arthritis
  • Crohn's Disease
  • Ulcerative Colitis
  • Rheumatoid Arthritis
  • Plaque Psoriasis

Humira (adalimumab) - Humira was given its first indication in 2002 for RA. Humira is self-injected and normally administered 2-4 times each month. It has received approval for use in the following conditions:

  • Ankylosing Spondylitis
  • Psoriatic Arthritis
  • Crohn's Disease
  • Ulcerative Colitis
  • Rheumatoid Arthritis
  • Juvenile Idiopathic Arthritis
  • Plaque Psoriasis

Simponi (golimumab) - Approved in 2009 for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Simponi is the newest TNF-a blocker to become available. Simponi is self-injected and administered once each month. It has received approval for use in the following conditions:

  • Ankylosing Spondylitis
  • Psoriatic Arthritis
  • Rheumatoid Arthritis

Quick Reference Table

Trade Name Generic or
Brand Name
Dose Frequency Total Dose (Range) Route of Administration
Enbrel Etanercept 25-50 mg 1-2 times/week 50 mg/week Subcutaneous injection
Remicade Infliximab 3-6 mg/kg Given at variable intervals NA Intravenous
Humira Adalimumab 40 mg 2-4 times/month NA Subcutaneous injection
Simponi Golimumab 50 mg 1 time/month NA Subcutaneous injection

How do anti-TNF therapies work?

Each of the above mentioned medications target and attempt to block TNF-alpha in the body. TNF-alpha is a cytokine involved in the inflammatory process. Excess amounts of TNF-alpha have been associated with various forms of inflammatory arthritis.

The National Institutes of Health describes cytokines as follows: "Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to coordinate appropriate immune responses."

It should be noted that each TNF-a inhibitor works in a slightly different manner within the body to block TNF-a. Thus, if one does not have a positive effect in a particular individual, a different one might.

What are the Potential Side Effects?

The most serious known side effect of the TNF-a blockers is an increased frequency of infections, especially tuberculosis. Thus, a TB test is usually required before starting any of the TNF therapies.

Fungal infections have also been reported, such as pulmonary and disseminated histoplasmosis, coccidioidomycosis, and blastomycosis.

A very rare possible complication is increased frequency of cancer, especially of the blood (leukemia) or of the lymphatic system (lymphoma). However, this has not been fully substantiated.

In an April 1, 2013 article titled, "TNF Inhibitors: Safer than we thought," Rheumatologist Dr. Irwin Lim states that, "The good news is that there has been no definite signal, after a decade of widespread use, in patients all over the world, of an increase in incidence of solid cancers. By that I mean breast cancer, colon cancer, etc.

"Lymphoma was always a worry. Patients with rheumatoid arthritis already have a higher risk of lymphoma...To date, there has been no increase in lymphoma seen in patients on TNF inhibitor therapy."

Dr. Lim adds, however, that rheumatologists should remain vigilant regarding side effects.

Please also see the following sites for important, additional safety information:

The Problem of Cost

Depending on individual insurance coverage and medical plans, the cost of TNF-a inhibitors can vary greatly, and co-pays can be quite high. That is one of the drawbacks to this class of drugs that impedes patient access to them.

Here's a list of assistance programs that can help with the cost of medications, co-pays, and other healthcare needs.

Resources & Further Reading



About the writer: Chris Miller is the Director of Programs at the Spondylitis Association of America and is Editor-in-Chief of SAA's news magazine, Spondylitis Plus. He has been at SAA for nine years.



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