Immunogenicity & biologics

This information outlines the relevance of immunogenicity in the context of treatment with biologics.

Biologics are a new class of drugs which are derived from human proteins. Though engineered molecules, biologics are closely related to substances naturally made by your body’s immune system. This in contrast to conventional medicines, which are more chemical by nature. 

By interfering in the immune system, some biologics are for instance able to interrupt the inflammatory cycle, characteristic for various inflammatory diseases such as rheumatoid arthritis and certain bowel- and skin diseases. In addition, (other) biologics are more and more frequently applied for cancer treatment.

The immune system

The immune system is a collection of mechanisms which protects your body by identifying and killing foreign agents like pathogens such as bacteria, viruses, fungi, and tumor cells. It is present in the entire body and ranges from physical barriers such as skin and mucosa, to an elaborate and dynamic network of many types of proteins such as antibodies, cells, organs and tissues. Most immune cells are white blood cells, of which the so-called T- and B-lymphocytes are critical for destroying pathogens and controlling the immune response. The immune system is regulated by cytokines, such as Tumor necrosis factor-α (TNF-α). These are messenger molecules which act as communicators between cells. TNF-α is an example of such a cytokine. Inflammatory diseases are usually caused by or accompanied with an imbalance of the immune system.  

How biologics work

Some biologics are specifically designed to counter the immune system imbalance by targeting overactive immune cells in the body. They attack immune cells directly, like rituximab, which binds to the CD20 molecule on the surface of B-lymphocytes. This leads to the removal of those cells, which decreases inflammatory processes. Rituximab is also used for treatment of cancer of B-lymphocytes. 

Other biologics are directed against cytokines like TNF-α, which is produced in excess amounts in people suffering from rheumatoid arthritis, psoriasis and Crohn’s disease. This overproduction mediates inflammation in joints, skin and bowel respectively. Well-known TNF-α inhibitors such as infliximab, adalimumab and etanercept have lead to marked improvement of disease symptoms and have reduced damage in for example joints of rheumatic patients. 

Side effects of biologics

The most common side effects seen with injectable biologics are skin reactions. These reactions, occurring in less then 30% of patients, include localized rash, burning or itching at the side of injection. When given intraveneously, infusion reactions such as: upper respiratory tract infections, headache, nausea, coughing and diarrhoea can occur. A significant adverse effect of TNF-α inhibitors is the enlarged risk of infections such as fungal infections, pneumonia, shingles (herpes zoster) and tuberculosis. Therefore, TNF-α inhibitors are not administered to patients who have an infection. Your specialist will check you up for that. Before therapy starts, patients are tested for TB, as an old or dormant infection may flare up by the use of anti-TNF biologics. 

Immune respons against biologics

Biologics have shown to be very successful, however patients can develop an inhibitory response against these drugs. Though biologics resemble human proteins they remain engineered molecules. In some patients treated with biologics the immune system therefore identifies those biologics as foreign entities and gets triggered. The subsequent immune response leads to the production of antibodies, which bind and eliminate the biologic. Depending on the amount of antibodies produced the biologic is removed from the blood to a greater or lesser extend. The more biologic is removed the lower its concentration in the blood and the lesser it is able to do its task (inhibit TNF-α or remove B-lymfocytes). This results in a less effective treatment. In short: high levels of antibody, low levels of biologic, low drug efficacy. Antibody formation can also lead to side effects such as infusion reactions. 

Does your treatment have effect?

If the biologic you are using does not seem to work it is advisable to consult your physician or specialist. He/she is able to determine whether treatment with a biologic is successful. Usually your doctor will combine information on your well-being with a fixed list of observations and standard lab values, resulting in an overall score. For rheumatoid arthritis the so called “DAS28 score” might be used. 

This score includes: 

  • the number of swollen and tender joints, assessed in 28 joints
  • the Erythrocyte Sedimentation Rate (ESR), a marker for inflammation, measured in blood
  • the patient’s general health 

The DAS28 provides you with a number on a scale from 0 to 10, indicating the current activity of the rheumatoid arthritis of the patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. In the US the American College of Rheumatology uses the so called ACR criteria to classify reumatoid arthritis. Scores used for other diseases are for instance the PASI-score (Psoriasis Area Severity Index) and the BASDAI for Bechterew’s disease.