The usual drug treatments for osteoarthritis are anti-inflammatory painkillers, often topped up with cortisone injections. And for more than a year this is what Susan Dawson was given, but it made little difference. Susan, a school learning ‘mentor’ from Liversedge, West Yorks, has osteoarthritis in all her joints – it started in her elbows in 2007, but she quickly developed it in her shoulders, hips, fingers and knees and she could soon walk only with a stick.
Then Susan, who is married with a son and daughter in their 30s, was prescribed a new drug in a six-month pilot study by Arthritis Research UK and the University of Leeds.
After taking the drug for three months the swelling in her knees went down markedly and the pain reduced. She was also able to walk without the stick – before and after scans and measurements of the knees showed a remarkable improvement in the inflammation.
‘I couldn’t believe it,’ she says. ‘The drug made a huge difference. I was very grateful, as I’d been in so much pain.’
The drug Susan was given was methotrexate – a chemotherapy drug which is also licensed for treating rheumatoid arthritis, an autoimmune condition that affects around 400,000 people in the UK, causing inflammation of the joints.
In rheumatoid arthritis, the drug helps to reduce the inflammation by reducing the activity of the immune system – around half of those with rheumatoid arthritis take methotrexate.
Osteoarthritis is a degenerative joint disease where the cartilage, which cushions the joints, wears away.
Both conditions can lead to inflammation – pain, swelling and stiffness – in the joints. The thinking behind the pilot study was that if methotrexate works in reducing inflammation, it would help osteoarthritis, too.
Osteoarthritis is typically managed with weight loss and muscle-strengthening exercises (to help provide support for the joint). Current drug options include cortisone injections and anti-inflammatories.
But patients often live with severe pain and have difficulty carrying out their normal day-to-day activities, says Philip Conaghan, professor of musculoskeletal medicine at the University of Leeds and lead researcher on the pilot study.
‘There is an urgent need to find better ways of managing their pain,’ he says. The pilot study suggested methotrexate could possibly answer that need.
It found that 37 per cent of the 30 patients with knee osteoarthritis who took methotrexate had a significant (40 per cent) reduction in their pain (there was no placebo group as a comparison). About 10 per cent (four people) had increased pain.
The results also suggested that inflammation plays a role in the pain of osteoarthritis, something that hasn’t been clear before.
Before she joined the pilot study in 2009, Susan had been in excruciating pain. Just over a year earlier, she’d noticed her knees were clicking when she walked, then the right one gave way completely.
‘I didn’t hurt myself, but all I could think of was how I was going to manage on the Nile cruise my husband, Stephen, and I were set to go on a month later,’ she says.
Her GP prescribed anti-inflammatories and the knee improved enough for her to be able to hobble around without support – and take the cruise – but the following year her left knee gave way in the school playground.
‘I was terrified it was going to keep happening and that I’d keep falling over,’ says Susan.
She was put on different anti-inflammatories and signed off work for three-and-a-half weeks. ‘I couldn’t walk at all and the pain was terrible,’ she says.
After seeing a number of specialists at her local hospital, Susan was referred to Chapel Allerton Hospital, where Professor Conaghan invited her to take part in the trial.
‘The anti-inflammatories and cortisone injections just weren’t working and I felt so bad I’d have turned to anything,’ she says.
Susan was prescribed eight 2.5mg tablets of methotrexate once a week, gradually increased to 6.5mg – this is the standard dose for rheumatoid arthritis.
She also had to take folic acid to reduce the nausea and mouth ulcers that are sometimes associated with taking the drug.
Then, three months after she’d started the treatment, Susan noticed a significant change – the swelling in her knees had gone down and she wasn’t in so much pain. ‘I felt so much better,’ she says.
She improved so much that when the trial finished Professor Conaghan gave permission for her to keep taking the drug. She was given three-monthly blood tests to check for possible major side-effects such as liver damage. As Professor Conaghan explains: ‘Changes in liver function tests are seen in about 10 per cent of people taking methotrexate.
‘These changes are reversible, but we routinely monitor the blood readings and reduce or stop the drug if we see any changes. Liver damage is extremely rare.
‘One of the advantages of methotrexate is that we know there are a large number of people being treated for rheumatoid arthritis who have been able to stay on it for years.’
This means doctors already know about the effects of the drug’s use, should it become available to osteoarthritis patients.
Most trials of osteoarthritis drugs, on the other hand, usually last only three months, says Professor Conaghan.
‘Yet most people have the disease for 20 to 30 years,’ he says. ‘Taken over long periods, anti-inflammatory drugs such as diclofenac and ibuprofen can have serious side-effects such as heart attack, stroke and stomach bleeds, which is why they are prescribed only in the lowest doses for the shortest amount of time. They are not very practical for chronic conditions.’
Early next year Arthritis Research UK and the University of Leeds will be carrying out a larger clinical trial to test the effectiveness of methotrexate compared with a placebo.
Professor Alan Silman, medical director of Arthritis Research UK, which is funding the research, said: ‘Many people with osteoarthritis complain their joints are swollen and tender, suggesting there is inflammation which is damaging the joint.
‘Stopping that inflammation early could halt the continuing damage many patients suffer.’
Meanwhile, Susan, who is no longer on the drug, has had no more flare-ups of her osteo-arthritis and any pain is manageable with ibuprofen.
However, she is careful and avoids doing too much or walking long distances.
Her biggest bugbear is not being able to wear high heels any more as they puts pressure on her knees.
‘But that’s a small price to pay for being able to get around,’ she says.