What is it?
Etanercept is classified as an immunosuppressive anti-rheumatic drug. It is used for several auto-immune diseases, including Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis, and Ankylosing Spondylitis.
How does it work?
It acts by blocking a chemical in the body called Tumor Necrosis Factor Alpha (TNF-α)
TNF-α is a protein chemical produced by certain types of white blood cells. It regulates inflammation. Basically, its presence tends to increase inflammation.
It does this in several ways. One effect it has is to increase the transportation of other white blood cells to the sight of inflammation. It also attaches to receptors on the surfaces of other cells and has effects such as causing them to release other chemicals called cytokines that also have a pro-inflammatory effect. Additionally, it can lead to destruction of tissues by leading to degrading of proteins that hold them together.
This is just skimming the surface of all the stuff that TNF-α does. In a nutshell, this is powerful stuff and plays a big role in your body’s defense systems. It is what drives that inflammatory response that fights off all sorts of nasties like bacteria and viruses and funguses.
Without TNF-α, we’d be in deep trouble because we’d be a whole heck of a lot more susceptible to all these invaders. Like most things in life however, too much TNF-α can cause some serious problems. If you have too much TNF-α activity, then you can get an overly abundant immune response. This can cause serious and destructive inflammation.
How does the body prevent this? Well, it produces protein chemicals known as soluble TNF-α receptors. These proteins float around in the body and attach to TNF-α and inactivate it. If TNF-α is the gas peddle for inflammation, think of these soluble TNF-α receptor proteins as the brakes.
It seems that some folks however, don’t have enough of these soluble receptors, so the TNF-α gets to run unchecked. This can cause serious troubles for them and lead to what are known as auto-immune diseases. As the name auto-immune suggests, this is when the body is recognized as foreign and attacked by its own immune system. Too much TNF-α can lead to the diseases listed above (Psoriasis, Rheumatoid Arthritis, etc), and is thought to be involved with a bunch of other diseases, in which it is thought that over-activity of the bodies immune system is involved.
Etanercept is a man-made protein that essentially does the same job as the natural soluble TNF-α receptors. Etanercept is created using recombinant DNA technology. It’s made using Chinese Hamster Ovary Cells (probably more info than you really wanted to know, but I thought it was a cool bit of trivia).
Unlike the body’s natural soluble TNF-α receptor proteins, Etanercept has a significantly longer half-life. In other words, its effect lasts longer than the natural stuff, so it is more effective at slowing down the TNF-α activity.
Using our car analogy again, if natural TNF-α receptor proteins are like old drum brakes, Etanercept is like modern disk brakes.
How is Etanercept available?
Etanercept is currently sold in the U.S. and in the U.K. under the brand name Enbrel.
It was originally marketed as a freeze dried powder that the patient needed to add sterile water to in order to dissolve it. It would then be drawn up by the patient in a syringe for subcutaneous injection. After it came to market however, it soon became obvious that a lot of the patients this medicine is intended for, people with severe arthritis of the hands, were having a great deal of difficulty with all this. Therefore, in addition to the freeze dried powder form, Enbrel is now also available in pre-filled syringes as well as a pen-shaped auto-injector.
What is the normal dose?
The normal dose for this medicine, as for many medicines, varies somewhat depending on the individual patient and the condition being treated.
For most indications, the normal adult dose is either 25mg injected subcutaneously twice weekly (3-4 days apart), or as a single 50mg dose given once a week.
For Adult Plaque Psoriasis, there is typically a starting dose of 50mg subcutaneously twice a week for 3 months. After this initial 3 months, it is then reduced to a maintenance dose of 50mg once a week.
Etanercept is approved for use in children age 4-17 years, with Juvenal Rheumatoid Arthritis (JRA). The dose is based upon the child’s weight. For kids weighing less than 31 kg (68 pounds), the dose is 0.8mg per kilogram (0.37mg per pound), with a maximum dose of 50mg. For kids weighing greater than 31 kg, the dose is 50mg.
Are there any side effects?
As with all medicines, the answer is “Yes.”
Etanercept can have some extremely serious side effects, including death. Fortunately, these serious side effects are relatively rare.
The most common side effects are discomfort at the injection sites, including reddening, pain, itching and swelling which may last for 3-5 days. Usually as a person continues to take the medicine, these problems become less and less pronounced.
Also, some folks will experience headaches and/or increased rates of upper respiratory infections (colds).
As mentioned above, there can also be some rare, though quite serious side effects. Most of these seem to be related to Etanercept’s effects on decreasing the activity of TNF-α.
As we know from the paragraphs at the beginning of this article, TNF-α plays a vital part in our body’s immune defense system. So, anything that puts the brakes on this may leave a person more susceptible to infections. This could include new infections as well as reactivation of pre-existing infections that perhaps the body has driven into dormancy.
For instance, folks who have had previous infections of tuberculosis or hepatitis-B may still have these bugs in their bodies, but their immune system has it under good control so that clinically there are no signs of active infection. If the immune system suddenly has its arms tied behind its back however, these bugs may again get out of control.
Since coming to market, there have been some other rare, but serious conditions that have been seen in patients taking this medicine. There have been cases of Central Nervous System (CNS) demyelination. What this means is that an important component of nerve cells in the CNS (the brain and spinal cord) becomes damaged and causes problems with the function of these nerves.
There have also been some folks who have developed pancytopenias (where their bone marrow quits making a normal amount of blood cells) including aplastic anemia (where the bone marrow completely stops making all blood cells).
There also appears to be a slight increase in the rate of lymphoma (a type of blood cell cancer) in folks taking this medication.
Does Etanercept bear any responsibility for these problems? Are these problems simply things that would have befallen these patients anyway, and it is just coincidence that they happened to be taking this medicine? We don’t know yet. The best answer to these questions right now appears to be “Maybe, maybe not.” Only time, and continued research will tell for sure.
Are there any interactions with other medications?
There are basically two broad classes of medications that one should be concerned about here.
The first is a particular class of vaccines known as “Live Virus” or “Modified Live Virus” vaccines.
As the name implies, these are vaccines that actually contain live viruses. They are typically viruses that have been altered in some way (hence the “Modified” part) so that they only cause a low grade infection, rather than the full blown infection that they are being given to prevent. Basically, they allow your body to gain some exposure to the bug and develop an immune response to it so that it will be ready to defeat it if you should become exposed to it in the future. Sometimes, rather than a modified version of the bad virus, we use a different virus altogether. This is usually a virus that is similar enough to the disease causing germ for the body to develop immunity to both, but is itself not a cause for serious disease. The classic example of this is the smallpox vaccine which basically involves infecting a person with the cowpox virus.
As you might have already deduced, giving Etanercept to someone who has recently been given such a vaccine, or conversely, giving such a vaccine to somebody already taking Etanercept, might cause a problem in that the vaccine might cause such a person (with an immune system weakened by Etanercept) to develop a serious infection from the vaccine.
Another concern I would have would be that with a compromised immune system, would Etanercept prevent a vaccinated person (with any kind of vaccine) from developing an immunity to the targeted disease? I don’t know the answer to this question. If someone reading this does, please shoot me an email at drsam@drsamonline.com.
The other big class of medications that are of concern if combined with Etanercept would be any other medicine designed to weaken the body’s immune response. These would include other TNF-α blockers (such as Infliximab and Adalimubab as well as Certolizumab pegol, which is a TNF-α blocker still awaiting FDA approval at the time of this writing) as well as other immune modifying drugs designed for immune mediated diseases such as Rheumatoid arthritis. This includes medications such as Kineret (Anakinra) and cyclophosphamide.
A commonly used medication in such patients, Methotrexate, CAN be used safely concurrently with Etanercept.
Bottom line here, if you are taking any medications designed to modify your body’s immune response for diseases like rheumatoid arthritis, Crohn’s disease, lupus, etc., you need to definitely discuss this with your doctor prior to taking Etanercept.
Who should NOT take this medication?
Obviously, common sense should tell you that each patient is an individual and should discuss this medication with their doctor, as there may be cases where the benefits might outweigh the risks.
That said, in general, this medication should not be used by anyone with a current infection or signs of infection or sepsis (which is a severe infection in which bacteria are in the blood stream and moving all over the body wreaking havoc).
It should obviously not be used by anyone known to be allergic to it (although this appears to be pretty darn rare).
It should be used with great caution, if at all in anyone with uncontrolled diabetes, Wegener’s granulomatosis, a history of chronic recurrent infections, a history of blood dyscrasias (which are problems with the bone not making blood cells normally), asthma, a history of CNS demyelination, a seizure disorder, congestive heart failure, the elderly, and as alluded to above, anyone taking other TNF-α blockers or other immune suppressive medications. Also, there is some evidence that this medicine might be problematic in folks who already have forms of immune suppression such as HIV patients.
Dr Sam’s bottom line: This is a powerful medication with great potential to help relieve suffering in a lot of people, but like most powerful things in life, it also has the potential to do great harm. Therefore, it needs to be used with great care and caution, and should really only be prescribed by folks who are very familiar with it.
