As I touched on in my last post about Biologics, one cool thing about these meds is that we are blocking specific “biological” pathways that we know produce inflammation, i.e., TNF, Interleukin (aka IL), B cells, and T cells.

Studies have shown three key cytokines that are responsible for the inflammation and destruction of bone and cartilage in the autoimmune rheumatic conditions. These three cytokines include TNF, IL-1, and IL-6.

Why do some respond to one Biologic and not the other?

Fact is, we don’t really know why. Unfortunately, we don’t have the test that tells us, “Mrs. Smith, you would do best with drug X.” So, although we know that the inflammation of these conditions is largely driven by TNF and Interleukin, we don’t know what med is best for one person in particular.

One thing to know is that although several medications can block the same inflammatory pathway, the actual construction of the medications are unique and different from one another, and perhaps that’s why we see the varied responses.

General adverse events of Biologics: What we have to remember about all the medication commercials we see is that, by law, for every 30 seconds of benefit a drug professes on a commercial, they HAVE to provide 30 seconds of risk.

Medication Form: The vast majority of Biologics DO NOT come as a pill. Many of these medications only come as ‘self inject.’ In other words, they come in a pen or a syringe, and we, the patient, inject ourselves in the belly or leg (like an epi pen or a diabetic shot) anywhere from once a week to once a month.

Many of them can be self injected OR given as an intravenous infusion (such as Orencia, Actemra, or Benlysta, for example) and some are only given as an infusion (such as Remicade, Simponi Aria, or Rituxan)

Cost: Yes, they are all VERY expensive. As a general rule, if you have Medicare only, the likelihood of getting a biologic covered through insurance is low. If you have Medicare and a supplement, the most likely Biologic that will be covered is an IV (intravenous) medication. And,if you have commercial insurance, they will tell us what you can and can’t get.

Potential adverse injection site and IV reactions:

1.Injection Site Reactions:
– typically 50% of people, usually lasts 3 to 5 days
– usually stops after 3 months of continued use
– improved with pre-medicating with an anti-histamine such as Benadryl
– typically not a reason to stop treatment unless persistent
– Enbrel and Cimzia have less reported injection site reactions

2. IV (intravenous) Reactions:
Remicade / Simponi Aria are TNF blockers that are given as an IV (Intravenous) infusion: A few unique potential adverse events with these meds include low blood pressure, headache, nausea, and shortness of breath.

Side notes:
1.If you have more than three drug allergies or have had an infusion reaction before, it is best to pre-medicate before the infusion with an anti-histamine, aspirin, and perhaps a steroid.

2. Also, if you are not responding to the current Remicade dose, it’s best to shorten the interval between infusion rather than increase the dose.

Potential Adverse Events / Risk of most Biologics:

The overall risk is about 3-5% and is 2-3 times higher than just being on an older med such as Methotrexate, Sulfasalazine, Arava, or Imuran.

Pneumonia is most common infection an is more common in first 6 months of use

Risk from infection following surgery is reduced if holding Biologic prior to surgery:
1 1/2 weeks for Enbrel
4-5 weeks for Humira and Remicade
6 weeks for Simponi / Simponi Aria and Cimzia

Tuberculosis (TB):
ALL TNF meds can cause an inactive TB infection to become active again. Risk of reactivating TB with a TNF med is 10 times greater then other meds.Typically occurs within the first 6-12 months
Can take TNF blockers after 2-4 weeks of Isoniazid (INH) and after 2 months for active tuberculosis treatment if they are needed.

Hepatitis B (Hep B):
ALL TNF meds can cause reactivation of viral Hepatitis B infection. If Hep B is resolved, risk of reactivation is less than 2%.
If chronic Hep B either avoid TNF or wait 2-4 weeks after starting Hep B treatment.

Hepatitis C (Hep C):
TNF meds can be used with Hepatitis C but need to have liver function tests and Hepatitis C viral level in blood checked often.

Fungal Infections:
ALL TNF meds can increase risk of fungal infections such as Histoplasmosis. They can also increase risk of Shingles and other infections that are unique to being “immunocompromised.”

The primary cancer risk is lymphoma, but studies have shown that the risk may not be any greater than the baseline increased risk a person with RA or another autoimmune rheumatic condition already has.

There is no increased risk for development of solid tumors (such as breast, lung, or colon cancer, for example).

Lymphoma risk is greatest in children receiving TNF meds.

General consensus is to wait 3-5 years to use Biologics in a person who has had cancer.

TNF medications, in particular, should not be used in a person with a history of optic neuritis or multiple sclerosis.

Heart Failure:
TNF meds should not be used if you have Class 3 or 4 heart failure.



Actemra (blocks Interleukin 6)
Watch your liver enzymes, lipid (cholesterol) panels and perforations of the GI tract
No increase risk of malignancy, heart failure, or nerve issues

Stelara (blocks Interleukin 12 and 23)
IL 12 and 23 are important to prevent mycobacterial and salmonella infections so blocking these might pose an increased risk of these infections.

Xeljantz (a JAK inhibitor – blocks tyrosine kinase)
Can increase lipids (cholesterol)
Might have increased risk of blood clots in people wh have had previous clots
Also, slight increase risk of Shingles compared to other Biologics

Benlysta (blocks B cells)
Only Biologic specifically designed for Lupus

Orencia (blocks T cells)
Infections (namely the ‘opportunistic’ infections such as Histoplasmosis) is less common than with other Biologics

Overall, most of us Rheumys do like using the Biologics.

So what’s the advantage of a ‘Biologic’ compared to the older medications such as Methotrexate?
In general, the advantage comes from blocking specific inflammatory pathways and therefor, greater control (or suppression) of inflammation and subsequent damage to the joints and organs.

What’s the greatest disadvantage of the Biologics?
Infection—especially atypical infections such as fungal infections and reactivation of Hepatitis B and Tuberculosis.
Cost—thousands a month…really??? Yes, really.

Typically, if you do not respond in three months with one of these medications, then it might be time to try a different one.

I hope this helps and thanks for the read! Today and every day, let’s always remember to live our value one choice at a time.