Products
TNF-α inhibitors are commercially available as injectable and infusion preparations. Infliximab (Remicade) was the first agent from this group to be approved in 1998, and in many countries in 1999. Biosimilars of some representatives are now available. Others will follow in the next few years. This article refers to biologics. Small molecules can also have an effect on TNF-α, such as thalidomide and lenalidomide.
Structure and properties
TNF-α inhibitors are biologics with high affinity and selectivity for TNF-α. With two exceptions, they are monoclonal antibodies. Certolizumab pegol is a pegylated Fab fragment of a monoclonal antibody. Etanercept – from , intercept – is a fusion protein that contains the binding domain of TNF receptor-2 and acts as a “false receptor.” The drugs are produced by biotechnological methods.
Effects
TNF-α inhibitors (ATC L04AB) have anti-inflammatory and immunosuppressive properties. The effects are based on the binding and neutralization of tumor necrosis factor-α (TNF-α). TNF-α is a proinflammatory cytokine that plays an important role in inflammatory processes and in the immune system and induces other cytokines. The active ingredients have a long half-life. TNF-α is a transmembrane protein consisting of 233 amino acids. The enzyme TACE (TNF-α-Converting Enzyme) additionally forms the soluble TNF-α from this protein. Both forms are active as trimers. The inhibitors bind to both proteins.
Indications
Not all drugs are approved for all of the following indications:
- Rheumatoid arthritis
- Psoriatic arthritis
- Juvenile idiopathic arthritis
- Bechterew’s disease (ankylosing spondylitis)
- Axial spondyloarthritis without radiographic evidence.
- Crohn’s disease
- Ulcerative colitis
- Plaque psoriasis
- Hidradenitis suppurativa (acne inversa)
- Uveitis
Dosage
According to the professional information. The drugs are usually injected as a subcutaneous injection. Infliximab is administered as an intravenous infusion. Prefilled syringes and pens are available of most products. Because of the long half-life, the dosing interval is, for example, 2, 4, 6, or 8 weeks. Pretreatment or combination with methotrexate is prescribed for individual agents.
Agents
The following agents have regulatory approval:
- Adalimumab (Humira)
- Certolizumab pegol (Cimzia)
- Etanercept (Enbrel)
- Golimumab (Simponi)
- Infliximab (Remicade)
The originals are listed in parentheses. There are also biosimilars on the market.
Contraindications
Contraindications include (selection):
- Hypersensitivity
- Active tuberculosis or other serious infections such as sepsis and opportunistic infections
- Moderate to severe congestive heart failure
For complete precautions, see the drug label.
Interactions
Co-administration of similar biologics such as anakinra or abatacept is not recommended because of a higher risk of infection. Live vaccines should not be given during therapy.
Adverse effects
The most common potential adverse effects include injection site reactions, headache, skin rash, gastrointestinal upset, and infectious disease. One serious side effect is reactivation of latent tuberculosis.
