New Treatments for Rheumatoid Arthritis
Up until recently doctors have been working somewhat in the dark when treating this common and disabling condition.
This is because we had little understanding of the underlying reasons for the condition and so could not target treatments to the causes of the disease.
Rheumatoid arthritis is a common and very troublesome disease. It affects one in a hundred people in the UK, causing a reduction in life expectancy comparable to Non-Hodgkin’s Lymphoma or three artery Coronary Heart Disease. So it’s an important condition and the cause of significant pain, distress, disability and some shortening of life.
The important change over the last few years is that a revolution in the understanding of the underlying mechanisms for the disease has occurred. This, along with new and powerful drugs, has enabled rheumatologists to directly target the disease processes. The results have been startlingly good.
Inflammation - The Scientific Basis
This is complicated. As part of the immune response, white blood cells (WBCs) take in proteins and break them down into peptides. With these the WBCs form structures called Major Histocompatibility Complexes (MHCs) on their surfaces. T-lymphocytes recognise these MHC and peptide combinations and secrete cytokines. Cytokines are chemical messages from one cell to another and can be thought of as local hormones.
Cytokines Influence Inflammation
Cytokines are chemicals with low molecular weights and act as inter-cell messengers. They are essential for the ability to develop immunity. Some cytokines increase inflammation in the tissues, others decrease it and it is the balance between the two which determines the state of inflammation in the person.
Tissue necrosis factor alpha (TNF Alpha) is one of the most powerful increasers of inflammation in rheumatoid joints. High levels of this chemical have been found in RA joints and the levels of TNF Alpha relate well to the levels of pain the individual is suffering from. This indicates that the TNF levels are an important indicator of what is going on in inflamed joints, as well as being significantly responsible for causing the inflammation.
TNF makes cells produce more cytokines and this can increase the inflammation greatly. Anyone who has had a severely inflamed joint (just one is enough) knows just how bad that can be.
Once the importance of TNF was realised, the drug companies worked to develop drugs which would inhibit the production of TNF. Available at the moment are Infliximab, Adelinimab and Etanercept. This are either given intravenously or injected just under the skin. There is no oral treatment for these compounds yet.
Many cells have TNF Alpha receptors on their surfaces, areas which accept TNF Alpha chemicals produced by other cells and which causes the receptor cells to become inflamed. In the same way, many cells produce TNF Alpha. The drugs capture and bind the TNF Alpha molecules and prevent the receptors from receiving them, thus reducing the inflammation in the cells.
Good results from TNF Blockers
The results of previous treatments for rheumatoid arthritis were really not that good. On average only 52% were 20% better within one year and 35% better within ten years. By 5 years from the start of treatment, 64-78% of people had stopped taking their treatments.
The results of treatment by TNF blockers are MUCH better. Doctors can now seriously talk about inducing remission (stopping the disease activity) in rheumatoid arthritis for the first time.
The State Of The Art
TNF Alpha is a pro-inflammatory (promotes inflammation) cytokine for which there are now highly effective inhibitors available. In ankylosing spondylitis the results are good too, with an especial improvement in low back pain at night, a very useful property of these drugs. They might also have a role to play in sciatica, migraine and complex regional pain syndrome, but it is not clear yet how useful they will be.