Reforming rheumatoid arthritis treatment:
a step in the right direction

By Elizabeth McAdam
CRUK London Research Institute, UK

This summary was awarded 2nd place for Access to Understanding 2014

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There is good news for rheumatoid arthritis sufferers: scientists are a step closer to predicting which patients will benefit the most from a particular type of drug using just a urine sample.

Imagine being in pain whilst carrying out routine, daily tasks such as opening a door, reaching for something in the cupboard, or writing. On top of this, imagine that this pain often comes on quickly and intensively, but not being able to predict when this will happen. This is what thousands of people with rheumatoid arthritis have to cope with every day.

Usually, the cells of your immune system protect your body from invasion by harmful viruses and bacteria, acting as your body’s army. Rheumatoid arthritis occurs when some of these immune cells start to attack your own cells, specifically in the healthy tissue around your joints. This results in the affected joint and surrounding area becoming swollen, painful and stiff. These symptoms often intensify very quickly and without warning, resulting in severe discomfort for the person concerned. What causes these sudden ‘flares’ and the onset of the disease in general is still largely a mystery.

There are currently several different types of drugs available to treat the symptoms of rheumatoid arthritis. Unfortunately, it can take a period of trial and error to find out which drug works the best to reduce symptoms in each patient. Doctors and scientists are currently trying to find out why some drugs work very well in some people, but not in others. This research is important as it will ensure that in the future, patients are more likely to be given a drug that works the best for them; wasting less time than trying treatments by trial and error.

TNF-alpha inhibitors are a group of drugs currently used to treat moderate to severe rheumatoid arthritis. TNF-alpha is one of the proteins responsible for creating the swelling and pain in joints affected by rheumatoid arthritis. These drugs block the TNF-alpha protein, and so in turn reduce the symptoms associated with rheumatoid arthritis. They work very well in reducing symptoms in some patients, but do not work for many others. This latest research reveals a potential way to identify which people with rheumatoid arthritis are most likely to respond well to the TNF-alpha inhibitor drugs, by looking at their urine.

The researchers decided to see if they could find any differences in the amounts of certain molecules in the urine of rheumatoid arthritis patients who responded well to the TNF-alpha inhibitors, compared to the urine of those who did not respond well. They chose to look at the patients’ urine as a similar approach has already been successful with other diseases. Obtaining a urine sample is also very quick, easy and not intrusive to the patient.

Sixteen rheumatoid arthritis patients were chosen to participate in the study. They each gave a urine sample before commencing treatment with one of two TNF-alpha inhibitor drugs, which continued for one year. After this time, a doctor assessed the patients and decided, based on their symptoms, who had responded well and who had not. At the same time, scientists analysed the urine samples the patients had given at the beginning of the study. They did this using a technique called nuclear magnetic resonance spectroscopy. This takes advantage of the notion that different molecules behave differently when they come into contact with a magnetic field. When a magnetic field was applied to the urine samples, all the different molecules in the urine separated and a machine identified exactly which molecules were present, and in what amounts.

Three different computer programs analysed the results to make sure the final conclusions were accurate. In the patients who responded well to the TNF-alpha inhibitor drugs, all three computer programs agreed that these patients had more histamine, glutamine and xanthurenic acid molecules in their urine, but less ethanolamine molecules, compared to those who did not respond well. These findings mean that, if this test was used in the future, a doctor could take a urine sample from a rheumatoid arthritis patient to help him or her decide if the TNF-alpha inhibitor drugs are likely to ease the symptoms of the patient.

This study was small, so the next step is to test these findings on a larger group of rheumatoid arthritis patients. These initial findings are exciting though, and not just for those patients who are most likely to benefit from the TNF-alpha inhibitors. For patients where the drugs are not likely to work, this will be known quickly, and an alternative can be suggested instead. This means that each patient is more likely to receive a treatment that helps his or her symptoms as quickly as possible; something which is invaluable.

This article describes the research published in:

Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis (2013) S. R. Kapoor, A. Filer, M. A. Fitzpatrick, B. A. Fisher, P. C. Taylor, C. D. Buckley, I. B. McInnes, K. Raza, S. P. Young Arthritis & Rheumatology 65(6), 1448-1456
http://EuropePMC.org/articles/PMC3715109

This article was selected for inclusion in the competition by Arthritis Research UK.