Active substance/effect

Most biologics are proteins. There are different generations of biologics and therefore also of TNF-α inhibitors. The generations differ from the production.

The ending of the name tells how much mouse protein is still present in the active ingredients. With the ending -omab there is 100%, with the ending -ximab there is still 25% mouse protein, with the ending -zumab there is still 5-10% and with the ending -umab there is none. This plays a role in the tolerability of the drugs.

Furthermore, the TNF-α inhibitors can act in different ways. They can intercept TNF-α and thus prevent it from binding to its receptor. As a result, certain processes in the cell that would lead to a destructive immune reaction do not take place.

Another possibility is that the TNF-α inhibitor blocks the binding site of TNF-α to the receptor. The drug then acts as a so-called antagonist. It is also possible that TNF-α inhibitors act as so-called fusion proteins.

These are also called decoy receptors. Decoy receptors are receptors that bind ligands but do not transmit signals. The TNF-α decoy receptors are soluble receptors that intercept TNF-α before it has reached its original target.

As a result, there is no longer a signal and the growth of the destructive immune cells is slowed down. The commercial preparation Enbrel® contains the active ingredient Etanercept. This is a so-called decoy receptor or fusion protein.

Enbrel® is used in particular for rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthritis and so-called spondylarthritis. Psoriatic arthritis is a special form of psoriasis that is associated with joint pain. Enbrel® acts as a TNF-α inhibitor in these diseases, and to some extent in other autoimmune diseases.

However, Enbrel® is not effective in Crohn’s disease. As a rule, it is applied subcutaneously once a week with 50 mg or twice a week with 25 mg. The active ingredient Infliximab is found, for example, in the commercial preparation Remicade®.

Infliximab is a chimeric monoclonal antibody that inhibits the activity of TNF-α. Since it is a chimeric monoclonal antibody, the main scaffold is made of human parts and the antigen binding sites (25%) are made of mouse protein. This means that the efficacy is higher than with so-called murine monoclonal antibodies, which consist of 100% mouse protein, and lower compared to humanised (5-10% mouse protein) or human monoclonal antibodies (0% mouse protein).

Accordingly, the risk of allergy and intolerance is lower than with murine monoclonal antibodies and higher than with humanised or human antibodies. Remicade® is used in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other autoimmune diseases. In contrast to Etanercept, the active ingredient Infliximab is also effective in Crohn’s disease. Depending on the disease, the dosage is 3-5 mg per kg body weight.