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HomeBlogRheumatoid arthritis: immunologists explore pathways from chronic condition to cure

Rheumatoid arthritis: immunologists explore pathways from chronic condition to cure

By: Medix Team
Rheumatoid arthritis: immunologists explore pathways from chronic condition to cure

Rheumatoid arthritis drugs are being used to treat Covid-19 patients. Will the pandemic deepen our understanding of the world’s most common autoimmune disease, helping scientists to find ways to prevent it rather than manage the symptoms?

In 2020, it didn’t really matter whether someone was a trained scientist or an armchair one. Everyone ended up being rapidly immersed in the inner workings of the human immune system whether they wanted to be or not.

 

A majority of people had never heard of B-cells or T-cells before, let alone what they do. Now most of us have at least a basic understanding of the role they play within the immune system, fending off external pathogens like the Covid-19 virus.

 

We also now know what can happen when the immune system goes haywire and turns against us, potentially inflicting terrible damage on one organ after another as it tries to get rid of the Covid-19 virus. So far, the most effective treatments against this inflammatory cytokine storm are drugs that have long been used to manage autoimmune conditions like rheumatoid arthritis, type-1 diabetes and inflammatory bowel disease.

 

These are diseases, which are caused by friendly fire when the immune system gets “confused” and starts attacking healthy tissue thinking there’s a pathogen it needs to get rid of by generating antibodies. The most common one is rheumatoid arthritis, when the immune system mistakenly sends antibodies into the lining between the joints known as the synovium.

 

The resulting inflammation causes the synovium to swell. When it recedes (temporarily, unless the condition is diagnosed quickly), the synovium can no longer hold the joints securely in place. Chemicals released by this inflammatory response also cause collateral damage to the bones and surrounding tissues such as cartilage and tendons.

 

Sufferers experience pain, redness, swelling and stiffness. Rheumatoid arthritis impacts up to 1% of the world’s population and is two to three times more likely to affect women than men. It typically comes on quickly and at a much younger age than osteoarthritis, which is generally caused by age-related wear and tear.

 

As yet, there’s no known cure. Unless it is managed properly, it can turn into a debilitating and chronic illness.

 

The pain causes many sufferers to give up work. It also triggers mental health issues in nearly a fifth of cases and raises the risk of other potentially lethal inflammatory conditions ranging from heart disease to strokes.

 

Scientists still don’t know exactly why the immune system misfires. Consequently, most existing treatments either target the inflammation to control the pain, or try to prevent further damage by minimising flare-ups.

 

Steroids are one of the first lines of attack to reduce the inflammation. They’ve been used to treat rheumatoid arthritis since 1948 when a 29-year old woman was injected with a then experimental drug at the Mayo Clinic in the US.  Two days and two injections later, she felt well enough to be discharged and went on a three-hour shopping spree.

 

Over the past year, a steroid called dexamethasone has also become the frontline drug to dampen Covid-related inflammation. At the end of 2020, scientists discovered that it was even more potent when administered in conjunction with a second rheumatoid arthritis drug called tocilizumab.

 

This type of drug is called a biologic. These are antibodies, similar to ones, which the human immune system produces naturally to fight off bacteria and viruses. But they’re "custom-designed" to target immune system components like B-cells, T-cells and specific chemokines (signalling proteins).

 

Biologics have revolutionised rheumatoid arthritis treatment over the past two decades by controlling the autoimmune response.

 

Tocilizumab was authorised by the US Food & Drug Administration (FDA) in 2010. It generates an antibody that blocks a cell receptor called interleukin 6 (IL-6). This receptor acts like a flag for the immune system, telling it send in the troops, far too many of them, causing inflammation. 

 

The problem with steroids and biologics is that there are side effects. Biologics are also expensive, which puts them out of reach of patients in many developing countries

 

But more importantly, dialling down the immune system is a short-term fix. Over the longer-term, doing so heightens the risk of other diseases and infections.

 

So scientists want to understand what causes rheumatoid arthritis in the first place. If they can understand its origin and disease pathway, then they stand a much better chance of developing drugs that prevent it while leaving the rest of the immune system to carry on as normal.

 

Late last year, a group of academics published an article in the Lancet expanding on the potential for immunotherapy - harnessing the immune system to extend remission, or even prevent progression. They noted that while immunotherapy is being increasingly used to treat a number of cancers, research is still at a much earlier stage for autoimmune diseases.

 

However, in recent years there have been a number of studies examining why some cancer patients develop rheumatoid arthritis after being treated with immunotherapy drugs. One silver lining of this is that scientists are now actively evaluating cancer patients at risk of rheumatoid arthritis. Traditionally, doctors were only able to start unravelling how rheumatoid arthritis developed once sufferers showed symptoms.

 

potential peptide-based vaccine is also under investigation, although this is still at a very early stage too. One area of research is a vaccine that suppresses a certain type of T-cell.

 

These are T-cells that over-stimulate the immune system to produce antibodies because they cannot distinguish between “good” self-antigens (normal cellular processes) and “bad” non-self antigens (external pathogens like viruses). When the body is functioning normally, T-cells go through a vetting process when they’re maturing in the lymph nodes and a chemical process kills off overaggressive ones before they’re fully formed.

 

However, this process doesn’t work as well in people who develop autoimmune diseases. In early February, Pfizer entered into an R&D and licensing agreement with a Belgian biotech company called Imcyse to develop a drug to try and address this.

 

Immunotherapy offers the prospect that one day there may be a cure for rheumatoid arthritis. What scientists learn from Covid-19 may well help to speed this up.

 

Over the past 40 years, treatments have also come a long way.  Significant deformities are far more rare. Fewer patients are confined to a wheelchair in crippling pain.

 

But rheumatoid arthritis remains a disease that needs to be managed. Vigilance pays. It’s a disease that benefits from a swift visit to the doctor at the first sign of symptoms because there are drugs that can arrest further damage and enable sufferers to lead productive lives. 



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