- To monitor your tumor necrosis factor (TNF) inhibitor therapy, to determine if your TNF inhibitor level is adequate, if your TNF inhibitor dose needs to be adjusted, or another therapy needs to be considered
- To detect TNF inhibitor antibodies that can interfere with the effectiveness of TNF inhibitor therapy
Tumor Necrosis Factor (TNF) Inhibitors and TNF Inhibitor Antibodies
A blood sample drawn from a vein
None, but the timing of the sample for testing is important. Your blood should be drawn just before your next dose of TNF inhibitor.
Tumor necrosis factor (TNF) inhibitors are a type of therapy that targets tumor necrosis factor (TNF). TNF inhibitors are manufactured immune proteins called monoclonal antibodies (Mab for short). These monoclonal antibodies attach to TNF and limit its activity and its effect on the body. TNF inhibitor therapy is prescribed to treat autoimmune conditions, such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA).
Tumor necrosis factor (once called tumor necrosis factor alpha) is a normal part of your immune system. It is a protein that promotes inflammation and fever when your body is fighting anything that the immune system perceives as foreign or "non-self", such as bacteria or viruses. Inflammation plays a role in helping the body to heal from an injury or infection. In healthy people, the immune response is regulated, so inflammation does not become excessive.
If you have an autoimmune disease, your immune system fails to distinguish between "self" and "non-self" and mistakenly targets your own cells and tissues in an autoimmune reaction. This attack can cause excess inflammation, leading to signs and symptoms that periodically flare up and die down. Some autoimmune complications are serious enough to require medical treatment and can result in progressive and/or permanent tissue damage.
TNF is typically elevated in inflammatory autoimmune disorders such as IBD and RA. TNF promotes inflammation, which can increase the severity, complications, and damage associated with these disorders. This makes TNF a good target for drug therapies to treat inflammatory autoimmune conditions.
TNF inhibitor therapy is prescribed to decrease inflammation and allow damaged tissues to heal. It can alleviate symptoms, prevent complications, and help autoimmune disorders go into remission. TNF inhibitor therapy is primarily used when you have an active inflammatory autoimmune disorder, with moderate to severe symptoms, that is not responding well to other treatments. TNF inhibitor therapy usually involves an initial series of infusions (into your vein) or injections (under your skin), and then periodic infusions or injections every few weeks.
TNF inhibitors may be used to treat conditions such as:
- IBD (which includes Crohn disease and ulcerative colitis)
- Psoriatic arthritis
- Ankylosing spondylitis
- Plaque psoriasis
The first TNF inhibitor to be developed was infliximab, about 20 years ago. It is still being used, but other TNF inhibitors have been introduced, such as:
Not everyone is helped by TNF inhibitor therapy. As many as 30% of people will not respond at all (primary nonresponse). Up to 50% will need to discontinue therapy, either because they initially respond but then stop (secondary nonresponse) or because they have adverse events.
Nonresponse to therapy is thought to be caused by a variety of factors, including:
- There is not enough medication in your body to sustain a response. This can happen because the dose was not large enough or your body cleared the drug too quickly. This can occur both initially and after you have been receiving the medication for a while.
- Your body develops antibodies against the TNF inhibitor (TNF inhibitor antibodies). This can occur at any time after the few weeks of starting therapy. The TNF inhibitor antibodies can make TNF inhibitor therapy less effective, for example by blocking the drug from binding to TNF. TNF inhibitor antibodies may be present in low levels that some studies suggest can be overcome by giving a higher dose of TNF inhibitor, or they may be present in sufficient quantity to prevent TNF inhibitor therapy from being effective.
- No identified cause—the TNF inhibitor therapy is not effective for your condition, even if there is enough drug present and no TNF inhibitor antibody.
Because some people do not respond to TNF inhibitor therapy, testing may be performed to determine the cause. This testing can include two separate tests:
- One test measures the level or activity of the TNF inhibitor that you are receiving to help determine whether the dose is adequate.
- Another test detects and measures the quantity or neutralizing ability of the TNF inhibitor antibodies that may have developed and that make the treatment less effective.
There are two ways the tests can be ordered. One way is that both tests can be done at the same time. The other way is the TNF inhibitor level or activity is measured first and then the TNF inhibitor antibody test is only performed if the TNF inhibitor level or activity is low (but not if it is high).
TNF inhibitor testing is considered therapeutic drug monitoring (TDM) because it can help to tailor your dose, to ensure the medication is in your body long enough at a level that is effective in treating your condition.
How is the test used?
This testing may be used to monitor your TNF inhibitor therapy. It is not typically done when you are on TNF inhibitor therapy and are responding well to it. If you are not responding well to your treatment, you might have one or both of the following tests:
- TNF inhibitor level or activity testing is used to help determine whether the dose you receive is adequate for you, to help adjust the dose if necessary, and/or to determine the need to change to another therapy.
- TNF inhibitor antibody testing is used to help determine why you are not responding to therapy. This test may be performed at the same time as the TNF inhibitor level or activity test, or sometimes it is only performed if the TNF inhibitor level or activity is low (but not if it is high).
When is it ordered?
TNF inhibitor testing is ordered when you experience a flare up of your autoimmune condition or you are failing to respond to TNF inhibitor therapy. Testing is typically done just before your next dose, when the level of the therapy should be at its lowest. This is called a trough level.
If testing leads to an adjustment of your dose, then the test may be ordered again to recheck TNF inhibitor levels or activity on the new dose.
Testing may sometimes be ordered when you have a partial response to the start of therapy, when you have an adverse reaction to the TNF inhibitor infusion or injection, and sometimes with a primary nonresponse (you do not respond to the drug when first introduced).
What do the results mean?
The table below summarizes the meaning of some results that may be seen:
TNF Inhibitor Level or Activity TNF Inhibitor Antibody Likely Interpretation Not detected or low Not detected There is not enough drug. Your healthcare practitioner may consider increasing your dose or shortening the time between doses. Not detected or low Detected You have developed an antibody to the TNF inhibitor that is likely interfering with therapy. Your healthcare practitioner may consider prescribing a different TNF inhibitor or different therapy. In some cases, your healthcare practitioner may try increasing your dose. Adequate or high Not detected There is enough TNF inhibitor, but you are not responding to it. Your healthcare practitioner may consider a different type of therapy. Adequate or high Detected You have developed an antibody to the TNF inhibitor that is likely interfering with therapy. Your healthcare practitioner may consider prescribing a different TNF inhibitor or different therapy.
Note: There are no exact rules for what TNF inhibitor levels and activity should be. However, a 2017 guideline from the American Gastroenterological Association suggested minimum trough levels for TNF inhibitor therapies. For example, the guideline suggested a trough level of infliximab be greater than 5 micrograms per milliliter (mcg/mL).
Is there a reason to test a "peak" sample when my TNF inhibitor should be at its highest level, or a random sample (neither peak nor trough)?
Can I have my test performed in my healthcare practitioner’s office?
How long will it take for results?
It depends on the lab performing the testing. The tests may be completed within a day or so if testing is done at a local laboratory. If your sample is sent to a reference lab for testing, it may take a few days for results to be available.
Are the two tests always done together?
Once I have developed TNF inhibitor antibodies, will they go away?
In most cases, these antibodies persist for as long as you receive that TNF inhibitor therapy. While antibody levels may decrease between doses or drop to undetectable levels if you are switched to a different therapy, the antibodies will usually come back if you are given another dose and/or started on the therapy again.
Can TNF inhibitor therapy cure my autoimmune disorder?
Do I need to tell other healthcare practitioners that I am on TNF inhibitor therapy?
Yes, this is important information for them to have as it may affect other treatment decisions. An example of this is that you should not get any live vaccines while receiving TNF inhibitor therapy, and neither should your newborn if you are on TNF inhibitor therapy during pregnancy. Additionally, your healthcare practitioner should be notified because the therapy suppresses your immune system, increasing your risk of infections, such as COVID-19 and tuberculosis.
If I develop antibodies to one type of TNF inhibitor therapy, and I am switched to a different one, will I develop antibodies to the second TNF inhibitor?