NIHR | Manchester Biomedical Research Centre

Rheumatoid Arthritis and predicting the future – Dr Stephanie Ling speaks to Arthritis Digest

Arthritis Digest is a magazine for people with arthritis that highlights the latest relevant research and reviews topical issues. Continuing regular contributions from our BRC Musculoskeletal theme researchers, Dr Stephanie Ling, Clinical Research Fellow at Manchester Royal Infirmary, discusses working with rheumatoid arthritis patients through research to improve biologic treatments.

A rheumatoid arthritis diagnosis today has vastly different implications than it did in the past. That’s because we have a deeper understanding of the condition and have developed much better medication – including biologics – to control it. But there is still further to go. We know biologics change lives. Yet they work better for some people than others, and some biologics don’t work on some people at all. Why?

The backstory

Rheumatoid arthritis is a long-term condition that affects people’s joints, as well as their whole bodies. It is caused by patients’ own immune systems attacking structures in their bodies, such as their joints. While there is no cure, we can keep rheumatoid arthritis under control with medication and prevent the immune system from attacking and damaging the joints.

Image shows Dr Stephanie Ling, Clinical Research Fellow

People with more active rheumatoid arthritis can be treated with drugs called biologics, of which there are several different types. Biologics are drugs that are based on naturally-occurring proteins that are found in the blood, and help an over-active immune system behave more like it should.

Our work at the Centre for Genetics and Genomics Versus Arthritis focuses on choosing the right drug for the right person, whilst walking the tightrope of balancing arthritis control with over-treatment. It is important to avoid over-treatment, as biologics can cause side-effects, such as infections and rashes.

Previous findings by our research group have shown that after receiving a biologic, the amount of that drug detected in the blood varies both with time and between different patients. This matters, as people with lower levels of the drug in their blood are less likely to respond to treatment and have their rheumatoid arthritis under control.

We are interested in what is causing this variation in drug levels, and how well people therefore respond to treatment. Could it be because of conditions in the body (such as an increased level of inflammation) when the drug is first started? Could it be because of an individual’s genetic makeup?

Breaking new ground

We are studying levels of naturally-occurring proteins in the blood of people who are first starting treatment with a biologic. Proteins in the blood can bind to drugs and reduce their effectiveness. This could explain why different people respond differently after being given the same dose of a drug.

The work is part of a much larger research project called the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, in which we are relating an individual’s genetic makeup back to our findings. Could changes in protein or drug levels be affected by a person’s genetics? Can we use this to predict who will respond better to each drug?

One of our patient partners, Sharon Blackall, who is 58 years-old and from Manchester, explains her motivation for taking part in this research, and what it entailed.

Image shows lupus patient Sharon Blackall

Sharon Blackall

Sharon's story

When Dr Ling explained her research to me, I was immediately keen to get involved. My rheumatoid arthritis diagnosis came out of the blue almost six years ago, although I shouldn’t have been surprised. My father suffered terribly with rheumatoid arthritis from an early age, leading to hospitalisation in London in his mid-twenties, and his aunt was wheelchair-bound with the same disease.

The genetic research at the heart of Dr Ling’s study immediately drew me in. What was the hereditary connection between my rheumatoid arthritis, my father’s, and his aunt’s? Was there something in my own genetic makeup that predisposed me to the disease?

As a mother, I was concerned about the possibility of one my daughters succumbing to the condition in the future, especially as it appears longstanding in my genetic line. I could already see minor ailments affecting them the way that I had once suffered. Recurrent bouts of ulcers, chest infections, tonsillitis and so on. All common childhood complaints perhaps, but also possibly signals that could suggest a compromised immune system, which is at the heart of a rheumatoid arthritis diagnosis.

At the same time, I could clearly see that my own rheumatoid arthritis prognosis and the effects of the disease upon my daily life were greatly improved from my father’s and his aunt’s experiences. I think this is primarily due to the improved understanding of the condition and treatments available, through research conducted over the years by clinicians such as Dr Ling. How could I not help with her research when my daughters, nephew or future grandchildren might one day be the beneficiaries?

Part of the team

Dr Ling and the team based at the NIHR Manchester Clinical Research Facility (CRF) at the Manchester Royal Infirmary (part of Manchester University NHS Foundation Trust) made the whole process very easy.

After an initial consultation in clinic to take bloods and complete the necessary forms (quick and straightforward), Dr Ling visited me at home a few weeks later. We timed this visit to coincide with my training session to learn how to self-administer my new biologic treatment (Benepali) which I was moving on to from synthetic DMARDS. This was probably the lengthiest session as there needed to be a specific amount of time between administering the drug and having more bloods taken. The session gave me the opportunity to discuss rheumatoid arthritis and quiz Dr Ling about her research – an insightful bonus.

Further short sessions in clinic spread across several months followed the home visit. I tried to coincide these with my regular hospital appointment schedule, which was easily accommodated, and I was reimbursed for any travel expenses, so was never out of pocket. It was a painless process throughout.

Taking control

An unexpected outcome was how empowering it felt to actively participate in the research process. The experience has shifted my perspective from feeling that rheumatoid arthritis was something awful that was happening to me, to a more positive sense that I was making a difference.

Rheumatoid arthritis didn’t have total control over me anymore; I had the opportunity to fight back! As a result, I have contributed to other research projects.

I volunteer as a public contributor through the Social Responsibility and Public Engagement Team based in the Faculty of Biology, Medicine and Health at The University of Manchester. Through this, I hope to strengthen my engagement with rheumatoid arthritis research, and share my experiences of the processes, benefits and outcomes of research to a wider audience.

Rheumatoid arthritis research needs people like me – people like you. My experiences have been positive and rewarding and I urge anyone asked to participate in a research study to seriously consider it. Future knowledge and improved treatments may depend on you.

What this means for people with arthritis

Medical research, with the generous participation of people affected, is essential to improving the lives of people with rheumatoid arthritis, now and in the future. We are currently studying if we can change the spacing between doses of biologics. Biologics are given at a set dose and a set time between each dose, and people usually give these to themselves in the form of injections, like insulin for people with diabetes.

Our research aims to predict the frequency and dose of biologics that each individual needs, by first measuring levels of each drug in the blood of study participants like Sharon. We will then use this information to build a computer model to predict what might happen by changing how often these drugs are given to patients.

For example, for people not receiving a high-enough dose to control their symptoms, increasing the dose should improve this, resulting in fewer appointments. This would hopefully improve the person’s experience and reduce demand on the NHS.

If an individual responds well to one of these drugs, it may be possible to treat them with less frequent injections. This will minimise the risk of side-effects and reduce the burden on the NHS.

As alluded to earlier, someone may have characteristics that will make certain types of biologics ineffective, such as protein levels or their genetics. In that case, they would be better treated with an alternative drug available for treating rheumatoid arthritis.

Biologics are prescribed in many long-term conditions, not just rheumatoid arthritis. This means our findings could allow people with a range of conditions (including psoriatic arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease) to be treated more effectively.

The end game

In the future we hope to be able to tailor each individual’s treatment for their benefit, leading to improved quality of life, fewer flare-ups and fewer hospital visits. Our aim is to achieve these improvements as quickly as possible in every patient, to reduce all the associated symptoms (such as pain and fatigue) of uncontrolled rheumatoid arthritis.

At the same time, the financial and time pressure on the NHS will be reduced, freeing up capacity that will benefit people elsewhere in the healthcare system. None of this would be possible without the altruistic and essential participation in research of people with arthritis. We need your help, to help others like you, both now, and in the future.