TNF Inhibitors and How they help stop inflammation

Tumor necrosis factor (i-TNF) α inhibitors occupy a leading position in the treatment of rheumatoid arthritis (RA) and other inflammatory arthropathies. Drugs directed against tumor necrosis factor-alpha have revolutionized the treatment of chronic inflammatory diseases. Paradoxically, they can provoke the development of de novo autoimmune diseases. ETC does not belong to the class of monoclonal antibodies (mAbs) and has a different mechanism of action. It is an artificial dimeric hybrid protein molecule (fusion protein), including a receptor for TNF, connected to the Fc fragment of human Ig1. ETC can block not only TNFα but also lymphotoxin α. ETC contains only a protein identical to that of humans.

Efficacy of TNF Inhibitors

In terms of anti-inflammatory efficacy, all TNF-α are approximately the same. Registry data show that the risk of discontinuation of i-TNFα therapy in the first 2–3 years is quite high, while there is a tendency to increase the frequency of discontinuation due to loss of effect. It has been established that the risk of discontinuation of therapy due to both insufficient efficacy and adverse events (AEs) is minimal for ETC and maximal for INF. Since ETC is a hybrid molecule and contains fewer potentially immunogenic epitopes than mAbs, the detection rate of antibodies to the drug (ATP) is noticeably lower.

Crohn Disease

is a chronic inflammatory disease that primarily affects the gastrointestinal (GI) tract. Any part of the gastrointestinal tract from the oral cavity to the anal canal (anus) can be involved in the process. The disease can manifest itself at any age, but in most cases occurs in people aged 20 to 40 years.

Clinical Researches

The study included 17,018 patients with autoimmune diseases who received TNF-alpha inhibitors (most used infliximab, etanercept, and adalimumab) and 63,308 individuals who did not receive drugs. Patients treated with etanercept have been shown to have a 2-fold increased risk of developing Crohn’s disease and ulcerative colitis during therapy. Many TNF inhibitors have been approved by the FDA. Your doctor will help you find the one that is available and best for you:

• Infliximab (Remicade, Remsima)
• Adalimumab (Humira)
• Golimumab (Simponi)

TNF inhibitors are antibodies produced in the laboratory from human or animal tissue. (Your body makes antibodies to fight infections.) Once they enter your bloodstream, they trigger a reaction in your immune system that blocks inflammation. Your immune system produces a substance called tumor necrosis factor (TNF). Normally, your body maintains a stable level of TNF. But if you have an autoimmune disease, like RA, something will go wrong. You start making too much TNF and this leads to inflammation. Inflammation that gets out of control can wreak havoc on your body. You may have pain, swelling, or feeling unwell. These drugs block the action of TNF. Most people feel better 2–4 weeks after the first dose. After 3–6 months, your symptoms may improve even further.

Infliximab (Remicade, Remsima)

This is a medical product, monoclonal antibodies to TNF-α. A specific immunosuppressive drug that selectively suppresses autoimmune reactions due to specific binding to one of the immune cytokines — the so-called “tumor necrosis factor type alpha”, TNF-α. Known under the brand name Remicade. Infliximab is an artificially synthesized antibody. The original antibodies were isolated in mice, but in humans, mouse proteins elicit an immune response, so common domains in mouse antibody genes have been replaced with similar human domains for use in humans. Since the genetic code of the resulting antibodies is a combination of mouse and human DNA, they are called “chimeric monoclonal antibodies”.

Adalimumab (Humira)

This is a medical product sold under the brand name Humira. The drug is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriasis, suppurative adenitis, uveitis, and juvenile idiopathic arthritis. Usually, the use of the drug is recommended only for people who have refused other treatments. It is administered by injection under the skin. Adalimumab is a selective immunosuppressant. It is a recombinant monoclonal antibody whose peptide sequence is identical to human lgG1. It is included in the WHO Model List of Essential Medicines, a list of essential medicines compiled by the World Health Organization. It is available as a biosimilar drug.

Golimumab (Simponi)

These are human monoclonal antibodies of the IgG1κ class, which are produced by a mouse hybridoma cell line using recombinant DNA technology. Golimumab had an effective modulating effect on the levels of inflammatory markers and indicators of bone metabolism in patients with various diseases. Patients should be closely monitored for infections before starting golimumab, during therapy, and for 5 months after the end of therapy. In the event of severe infections or sepsis, therapy should be discontinued.

Conclusion

Your doctor will likely test you for tuberculosis and hepatitis B before you start taking a TNF inhibitor to make sure you don’t have either, even if you don’t know it. Medicines can make the effects of these infections worse. If you need antibiotics to treat an infection, you may need to stop taking the TNF inhibitor until the infection clears up. This is rare, but you may also be at a higher risk of getting cancer if you take TNF inhibitors, including lymphoma or skin cancer. Some people may experience severe brain reactions. People with heart failure or multiple sclerosis should not take these drugs.