In the 1990s, researchers made a huge step in understanding our immune system, and the first targeted treatments, called “biologics,” entered the market to treat patients with Rheumatoid Arthritis. Biologics have dramatically changed the disease prognosis as they were able to decrease pain, inflammation, and joint deformities and slow down the disease progression. Although they cannot cure Rheumatoid Arthritis, they are beneficial in many cases. Despite these benefits, there are some important things that people should know before starting therapy with biologics.
What are “Biologics” and how do they work?
Biologics are sophisticated therapies designed to target molecules causing inflammation in our body (e.g., TNF-alpha, IL-6, IL-1, etc). They are also called “monoclonal antibodies” that have been designed to block either receptors on the cells that produce inflammation or to block inflammatory molecules that are floating in our blood or in the joints’ space.
Let me give you an example: TNF-alpha is a molecule known to cause inflammation and can be present floating in the blood, the fluid in the joints, or on the immune system cells. Researchers have designed medications like TNF-alpha inhibitors (e.g., adalimumab, etanercept) that will block the activity of the TNF alpha molecule and, thus, will decrease inflammation.
What are the most common classes of biologics used for Rheumatoid Arthritis?
The most common classes of Biologics were designed to block one or multiple molecules that will produce inflammation. For patients with Rheumatoid Arthritis, here are the classes of medications that we currently use
- TNF-alpha inhibitors will inhibit TNF-alpha molecules (e.g., Adalimumab/ Humira, Etanercept/Enbrel, Golimumab/Simponi, Certolizumab/ Cimzia, Infliximab/ Remicade, etc.).
- IL-6 inhibitors will inhibit IL-6 molecules (e.g., Tocilizumab/ Actemra and Sarilumab/ Kevzara)
- CTLA-4 inhibitors (Abatacept/ Orencia)
- Janus kinase (JAK) inhibitors (e.g., Tofacitinib/Xeljanz, Baricitinib/Olumniant, Upadacitinib/Rinvoq). They act on the nucleus of immune cells, thus inhibiting the production of multiple proteins, and causing inflammation simultaneously.
Important things to know before you start therapy with Biologics
1- What are the laboratory tests required before starting Biologics therapy?
Before starting Biologics therapy, it is crucial to have specific laboratory tests obtained. These medications can lower your immune system, and that can cause reactivation of an infection like Tuberculosis. If you do have latent Tuberculosis, you need to be treated or start on treatment for Tuberculosis before you start on a “biologic” therapy.
The laboratory test required must include
- Cell counts
- Renal and hepatic function
- Markers of inflammation
- Test for Tuberculosis (TB status)
- Hepatitis B and Hepatitis C
Patients with evidence of Hepatitis B require monitoring of the viral loads while treated with these drugs. In patients with Hepatitis C, it is preferred to have treatment for hepatitis C before starting on a biologic medication.
2- What vaccines are required before starting Biologics therapy?
Vaccination is essential before starting therapy with biologics. Since these medications can potentially decrease your ability to fight infections, you should get up to date on vaccines to protect you from flu, COVID-19 infection, shingles, or pneumonia. Certain drugs, like JAK inhibitors, may increase your risk of developing shingles. Before you get other types of vaccines, ask your doctor, as certain live vaccines might not be appropriate.
3- How to react if you develop an infection while taking Biologics medication?
Based on the latest research, the risk of developing infection is higher in the first 6 to 12 months of therapy, especially for TNF-alpha inhibitors. Upper respiratory infections like sinusitis, otitis, or bronchitis can happen. There is also an increased risk of shingles, especially in patients taking glucocorticoids along with biologics or JAK inhibitors. Severe infections are rare but also possible. If you develop an infection or signs of infections (rash or redness and pain to the site of the injection, fever, chills, night sweats, cough, etc), stop taking the biologic medication and immediately contact your doctor. Once the infection is treated and cleared, you may resume treatment, but only after discussing it with your doctor.
4- Biologics can be given as intravenous infusions or self-injectables.
Discuss with your doctor which type of biologics is appropriate for your case. In some patients, intravenous infusion is preferred. If you’re going to get an infusion, make sure you schedule enough time to receive the medication, have someone to accompany you, especially for the first infusions, and drink plenty of water in advance. If you are getting an injection, make sure you understand how to store the drug and how to use the pen/injection. Leave the pen/ injection at room temperature 15- 30 minutes before use, but do not remove the cap or cover. Do not use it if the solution is discolored. Always inject in an area of clean and intact skin. It is recommended that you rotate the site of the injection whenever you give yourself the injection. If you develop redness in the injection area, contact your doctor immediately.
5- Biologics can be combined with other medications.
Therapy with biologics is usually started in addition to other medications used for Rheumatoid Arthritis, like DMARDs (disease-modifying anti-rheumatic drugs like methotrexate, leflunomide) or even other non-steroidal anti-inflammatory medications (e.g., ibuprofen, naproxen, meloxicam).
6- Don’t stop other medications when you start Biologics therapy.
Discuss with your doctor before stopping any medication. If you feel great, in time, your doctor may consider stopping other medications and leave you just on the biologic therapy.
7- Discuss your history of cancers with your doctor.
If you have a recent history of cancer, especially in the last five years, you should tell your doctor. Some biologics, like TNF-alpha inhibitors, are contraindicated in people with a recent history of cancers. In addition, there are some reports about an increased risk of developing cancers like lymphoma or skin cancers in people using biologics, but this is still under debate. Carrying a disease like Rheumatoid Arthritis will increase your risk of cancer due to ongoing inflammation.
However, the risk of cancers should not stop you from considering therapy with biologics. Every year, you should get skin cancer screening by a dermatologist as a precaution, as there were some studies suggesting an increased risk of skin cancer in patients treated with TNF-alpha inhibitors.
8- Are biologics safe in people with heart disease?
Yes, biologics are generally safe in people with heart disease. A special consideration needs to be paid to TNF-alpha inhibitors and JAK inhibitors. Patients with heart failure taking TNF-alpha inhibitors rarely may develop new-onset or worsening of this condition. Patients with a previous history of heart disease like myocardial infarction, stroke, or pulmonary thrombosis need to avoid using JAK inhibitors.
Thus, if you suffer from a cardiac disease, you should disclose this to your physician, who will order a complete cardiac evaluation before starting you on this therapy.
9- Are biologics safe in pregnancy?
Certain biologics, like TNF-alpha inhibitors, are considered relatively safe for pregnancy. No risks of adverse maternal or fetal effects have been observed following TNF-alpha inhibitors like adalimumab (Humira) or Certolizumab (Cimzia) exposure during pregnancy. However, the data that we have regarding the use of other biologics is very limited, so it is crucial to contact your physician immediately if you remain pregnant and discuss your therapy options.
10- Biologics need time to work
Do not expect that you will feel better overnight. Usually, it takes 4 to even six months to see the effect of this drug. Many patients feel better gradually, and they notice improvement in pain, stiffness, and swelling in a few months.
Special Considerations and Personalized Treatment
Treatment with biologics should be discussed in depth before with a rheumatologist who specializes in Rheumatoid Arthritis and can tailor the therapy based on your needs. At Rheumatologist on Call, we offer an integrative approach specifically tailored for Rheumatoid Arthritis patients. Our method combines personalized treatment plans, including education on nutrition, physical therapy sessions, and mindfulness techniques, all designed to be a 1:1 approach between patients and the physician.