Keeping knees up the research agenda
Published on 07 October 2013
Jane Tadman reports on the latest clinical trials looking at new ways of treating osteoarthritis of the knee. As our £1.8m research project looking at the effects of altering gait and posture produces some practical results, an exciting new trial looking at the effectiveness of methotrexate in treating this common condition is about to start recruiting.
1. The ROAM (Research into Osteoarthritis in Manchester) Project
When world-renowned knee osteoarthritis expert Professor David Felson was awarded a five-year special strategic award by Arthritis Research UK in 2009, he promised a radical new approach to treating the condition that affects six million people in the UK.
Rather than testing the effectiveness of certain treatments in generalised knee osteoarthritis, he and his team at the Universities of Manchester and Salford specifically targeted three groups of patients with three distinctly different types of knee osteoarthritis in three clinical separate trials. The emphasis was very much on correcting gait and posture, and changing ways of walking in order to reduce pain.
The last edition of Arthritis Today reported the outcome of one of the trials and the success of a knee brace in treating a type of osteoarthritis that affects the kneecap – also known as patellofemoral osteoarthritis.
A second, on-going study is looking at the effectiveness of steroid injections in the type of osteoarthritis that causes swelling in the knee.
And a third trial, run by Dr Richard Jones, senior lecturer in clinical biomechanics at the University of Salford, looked at medial osteoarthritis, the most common type, affecting the inside of the knee joint between the femur and the tibia . It’s a painful condition that restricts daily life in those affected.
This trial studied the effectiveness of two types of orthotic (a device that provides support or adjust the mechanical function of a joint, also called an orthosis, an insole or an insert) and two types of shoe. It used 3D gait analysis to look at how the knee moves and why it moves in a particular way, and also looked at the hip, ankle and foot.
The theory was that because of the way we walk, we have constant loading on the inside of the knee, which is linked to the progression of osteoarthritis. And if this could be altered, the progression of disease could be affected.
While the results of this trial are still in the pipeline, early findings have revealed that the orthotic may prevent the development of osteoarthritis or its progression in the opposite knee, with at least one of the insoles helping reduce pain in some of the patients.
And it has certainly been beneficial for one man, 76-year-old Peter Street.
The previously fit pensioner thought his active days were over when he developed painful arthritis in his right knee. But since taking part in the trial he has found a new lease of life.
Mr Street used to cycle 30 miles twice a week, regularly went for long hikes including the Pennine Way, and was a ski-ing fanatic who had enjoyed alpine holidays for the past 50 years.
That all came to an abrupt end with a diagnosis of osteoarthritis in his knee. “The arthritis came on came on very quickly and I was completely incapacitated,” explained Mr Street.
However, since volunteering to take part in the trial, the result has been remarkable. “I’d only been wearing the orthotic for a month before I realised it was working: it was amazing,” he said. “It made a tremendous difference in terms of pain relief.”
Not only did the pain in his knee reduce almost immediately after starting to wear the insoles, but Mr Street was also able to go on a ski-ing trip which he never thought would be possible. Two years on, he is still wearing the orthotic, and still swearing by it.
Arthritis Today will update readers on the full outcome of the trial when it is published in a journal.
A second orthotic trial
On the back of this study, Dr Jones is now recruiting for another, related clinical trial. It is very much a fine-tuning exercise looking at individuals who respond well to wearing orthotics.
Researchers are now recruiting up to 60 people to test wedge orthotics, which could reduce load on the knee joint by correcting the way they walk, and hopefully reduce pain.
Local people aged between 40 and 85 who join the study are asked to walk and climb stairs barefoot and wearing two different orthotics in their shoes, and their gait and foot pressure analysed. If individuals are found to biomechanically respond to the treatment, they will then attend three further gait analysis assessments over a 16-week period. A number of orthotics which have been designed to potentially lower the loads in the knee joint will be put through their paces.
Dr Jones and his team believe that these orthotics could be extremely popular, effective and inexpensive interventions for osteoarthritis of the knee - if they can find out which individuals and which orthotics have the best results.
People with osteoarthritis of the knee living in the Salford and Manchester area who would like to find out more about the trial can contact the trial team for further information on 0161 306 0545/0547/0549.
2. The PROMOTE (pragmatic, double-blind, randomised, placebo-controlled trial of methotrexate to treat osteoarthritis of the knee) trial
Methotrexate has been the gold-standard treatment for mild to moderate rheumatoid arthritis for decades, working by damping down the over-activity of the immune system which causes inflammation in the joints.
Until very recently, it had never been used to treat osteoarthritis, which is a completely different condition.
According to Professor Philip Conaghan from the University of Leeds, recent studies have suggested that inflammation is also important in causing pain in osteoarthritis. He and colleagues already performed a pilot study which showed that 37% of patients with knee osteoarthritis who took methotrexate had a 40% reduction in their pain.
Now Professor Conaghan is being funded by Arthritis Research UK to run a multi-centre clinical trial of methotrexate in 160 people with knee osteoarthritis.
“Current drug treatments for knee osteoarthritis are limited in that they have significant side-effects and aren’t suitable for many people,” explained Professor Conaghan, a nationally recognised osteoarthritis expert. “As a result, people with osteoarthritis often live with severe pain and have significant difficulty in carrying out their normal day-to-day activities. There is therefore an urgent need to find new and better ways of managing their pain.”
The Leeds team at Chapel Allerton Hospital will now carry out a full clinical trial of methotrexate on people with moderate to severe osteoarthritis of the knee, who are not getting benefit from traditional treatments such as painkillers. Half of those recruited will take methotrexate for 12 months and the other half will take a placebo tablet. All patients will have an MRI image taken of their knee, and fill in questionnaires every three months.
The study is about to start recruiting in 15 centres around the UK.
Arthritis Today will keep readers up to date with the PROMOTE trial. To find out more, contact Sarah Hogg, trial coordinator on 0113 392 4990 or email@example.com
A new Boots knee osteoarthritis orthotic
One of the orthotics tested in the two above-mentioned clinical trials, called a lateral wedge orthotic, is now available to buy in Boots, specifically for people with medial knee osteoarthritis. Developed by a spin-off company of Salford University, Salford Insole, after years of research - some of which was funded by Arthritis Research UK, - the Knee Arthritis Orthotic combines an arch insole in a lateral wedge which stops the foot moving about in the shoe, and prevents any possible ankle pain.
They are available through the NHS hospital trusts as medical devices, but making them commercially available opens up access to a lot more people with knee osteoarthritis who are treated by their GP.
• The Boots Knee Arthritis Orthotic, which has on-pack information about Arthritis Research UK, is available from Boots, priced £34.99. You may need to check with the pharmacist whether the orthotic is appropriate for your condition, as it is designed solely for people with media osteoarthritis, which affects the inside of the knee.
Susan Dawson, from Liversedge, near Wakefield, has osteoarthritis in all her joints but her knees are worst affected. She had tried painkillers, steroid injections and physiotherapy before taking part in Professor Conaghan’s pilot trial of methotrexate.
It worked very well for her and she noticed a pronounced difference. After three months, the swelling in her knees went down.
Susan, aged 57, says: “I couldn’t believe the difference it made and there was a huge improvement in the before and after scans. I was really, really grateful. I didn’t have any side-effects, my bloods were always fine; the only thing I found at the beginning was that I felt sick with it at first and had a few mouth ulcers for a short time.”
Susan was on the trial for 12 months, and when it ended, continued to take methotrexate for a further two years on a named-patient basis before slowly being weaned off the drug. She currently manages her condition with occasional ibuprofen and ibuprofen gel, and still feels better than before she went onto methotrexate.
Medication, muscle-strengthening, increased activity and devices such as walking sticks may all aid in controlling painful symptoms, and not all people with osteoarthritis will require joint replacements. The number of people affected has increased two-to-four fold over the past 50 years as the population has aged and become more obese – which are the two major risk factors for developing osteoarthritis. The condition accounts for more than a third of chronic moderate to severe pain in the UK.