A diagnosis of inflammatory arthritis is life changing, but is no longer a life sentence, explains Prof Anne Barton

The past and present are two very different places when it comes to the impact of many medical conditions, including inflammatory arthritis.

Inflammatory arthritis is a term that is used to cover a range of conditions in which joint inflammation is the main feature. It includes rheumatoid arthritis, psoriatic arthritis, childhood arthritis, ankylosing spondylitis and reactive arthritis.

Joint inflammation causes pain, swelling, stiffness and they may look red or feel warm to touch. If left untreated, inflammation can cause damage to the joints resulting in restricted movement and leading to disability.

When I first started my training in rheumatology in 1995, outpatient clinics were full of people in wheelchairs and the hospital had a dedicated ward for those with inflammatory arthritis.

The good news is that the situation has improved dramatically over the past couple of decades.

A look at the past

Up until the 1950s, the treatment for inflammatory arthritis was bedrest, anti-inflammatory drugs such as aspirin, and splinting to try to keep the joints in the correct alignment.

In 1950, the Nobel Prize was awarded for the discovery of steroids, which were dramatic in the way they controlled inflammation. It soon became clear, however, that steroids can cause long-term side effects such as increasing the risk of fractures, diabetes and heart disease.

Other medications, such as gold injections and penicillamine tablets were available but due to the risk of serious side-effects, were only used in people with severe active disease. Surgery was used widely to replace damaged joints and was seen as an important treatment for people with inflammatory arthritis.

The positive change in the outlook for people with inflammatory arthritis came about in the 1980s.

First, research began to show that treating inflammation early, preferably within the first six months of symptoms, prevents joint damage and disability up to 20 years later. This finding produced a sea-change in the way clinicians recommended treatments; therapy was started sooner following diagnosis.

Second, clinical trials showed that treatments such as methotrexate were effective at controlling inflammation. And combinations of treatments (for example methotrexate plus sulfasalazine plus hydroxychloroquine) could be even more effective, especially in people with severe and active disease. We still use these medications today and they are good at controlling joint inflammation in most people.

Game changer

There was still a minority of patients in whom the treatments available did not control inflammation. The next major advance for them was the discovery of biologic drugs in the late 1990s.

Research had shown that inflammation in rheumatoid arthritis was driven by high levels of a substance in the body called tumour necrosis factor (TNF). A pharmaceutical company developed an inhibitor to TNF, called infliximab. This is essentially an antibody that blocks TNF binding to its receptors, which in turn prevents activation of the inflammatory pathways.

TNF was initially developed to treat sepsis (infection) but didn’t work. When it was tried in people with rheumatoid arthritis, the results were dramatic. Other pharmaceutical companies developed different ways to block TNF, and TNF inhibitors remain the most popular biologic therapy for patients with inflammatory arthritis.

Companies also developed drugs to target other parts of the inflammatory pathway in rheumatoid arthritis including B cells, T cell inhibitor receptors and inflammatory molecules such as interleukin 6.

All the biologic drugs need to be given as injections or infusions as they would be broken down in the stomach if taken as tablets.

Most recently, inhibitors of a key inflammatory pathway (JAK/STAT pathway) have been developed that can be taken as tablets.

Buoyed by the success of treatments in rheumatoid arthritis, many of the drugs were trialled for other forms of inflammatory arthritis and some, but not all, work across conditions. For ankylosing spondylitis and psoriatic arthritis, biologic drugs targeting the interleukin 17 and 23 pathways are now available, which work for those conditions but not in rheumatoid arthritis.

Current challenges

Several challenges remain.

First, for each drug option, we still can’t tell if the drug will work for a particular person. Each option fails to control inflammation in around four out of 10 patients, so it remains a trial-and-error approach to finding the treatment that works and suits a particular person.

Some people develop side-effects and we can’t predict who will experience those. Researchers at the NIHR Manchester Biomedical Research Centre are focusing on identifying measures in the blood that could help match the right treatments to the right patients.

Second, whilst we are much better at controlling inflammation in most people, there remain a very small number for whom none of the current options work, so there is still a need to identify new treatments.

Third, fatigue remains an issue that many patients face. The treatments available can help symptoms such as fatigue, but were not specifically developed to do so. If fatigue is caused by inflammation, they should help but if there are other causes for the fatigue, they may not.

Fourth, we know that drug treatment alone is not enough to keep people healthy. Exercise and maintaining muscle tone and strength remains an important part of management.

The treatment landscape has changed dramatically and there are a range of potential therapies available. But these treatments are not cures. They control inflammation but need to be taken long-term.

The future

Researchers at the Centre for Genetics and Genomics Versus Arthritis in Manchester are working to understand the genes and pathways involved in these conditions because it is now possible to change genes to reduce the risk of developing diseases. At some point, it may be possible to truly cure inflammatory arthritis but that remains a long time off. In the meantime, the range of treatment options available mean that more patients can live full lives, remain in work and have a better quality of life.

The diagnosis of inflammatory arthritis is definitely no longer a life-sentence but a condition that can be managed through a combination of drug treatment and a healthy lifestyle.

First published January 2023

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