Struggling to cope with chronic pain and waking up to six times a night, Annie Icke wondered if there was a better treatment for her symptoms than the steroids her GP had been prescribing for eight years.
He has polymyalgia rheumatica (PMR), an inflammatory autoimmune disease that primarily affects the muscles and joints of the shoulders, hips, neck and wrists, causing painful stiffness.
PMR is estimated to affect around 200,000 people over the age of 50. While a family history of the disease increases the risk, it can be triggered by infections, including some strains of influenza and pneumonia.
Annie developed it after a bout of flu that affected her neck, hips, shoulders and wrists. “It was like I’d had a fit,” recalls the 78-year-old retired personal assistant who lives with her husband Paul, 68, a retired IT consultant, in Gloucestershire.
Annie Icke has polymyalgia rheumatica (PMR), an inflammatory autoimmune disease.
Although steroid medication helped, its well-documented side effects took their toll.
“In my case, these included anxiety and crying, loss of muscle tone and damage to my shoulder tendons, bowel problems (diarrhea and constipation), insomnia (due to side effects) and terrible nightmares,” says Annie.
“And yet, every time I tried to stop taking them (I tried at least twice), my symptoms would flare up and cause me excruciating pain. I was trapped.”
But the good news is that there is a new, more effective option than steroids for patients like Annie: a biweekly treatment that appears to offer better pain relief and reduce the number of flare-ups.
The drug sarilumab (brand name Kevzara) is already approved for rheumatoid arthritis, where it works by blocking the effects of an inflammatory protein called interleukin-6.
Now, new data from a UK trial suggests it may reduce the number of relapses in patients with PMR.
Furthermore, it could mean that PMR patients can stop taking steroids without suffering the significant withdrawal symptoms that many experience.
PMR is also one of the most common reasons steroids are prescribed long-term, accounting for more than one in five (22 per cent) of all steroid prescriptions, according to the National Institute for Health and Care Excellence (NICE).
The symptoms can be dramatic and crippling, says Bhaskar Dasgupta, professor of rheumatology at University Hospital Southend. “It’s not just any pain – it usually starts suddenly and causes intense pain in the shoulders and upper arms, and is so debilitating that you can’t turn over, get out of bed, get dressed, reach for anything – not even sit on the toilet,” he says. “Two-thirds of PMR patients also suffer from pain in the buttocks and thighs.”
While steroids such as prednisolone tablets relieve symptoms, they can also lead to weight gain and a “moon face”, although Annie managed to avoid this.
Most patients with PMR have to take steroids for about 18 months, as controlling the underlying inflammation is a long process.
NICE guidelines state that most patients will need a further two years to taper off the standard dose of 15mg a day (Annie was on a higher daily dose of 20mg), but one in four are still taking it after four years. Possible long-term side effects of steroid medication include: increased risk of infections, thinning of the skin, bone fractures, high blood pressure, cataracts and glaucoma.
According to Professor Dasgupta, about half of patients relapse when they try to reduce the dose. “Polymyalgia rheumatica is an undertreated and neglected disease,” he says.
“In addition, prednisolone is not satisfactory for patients with recurrent symptoms and can have long-term side effects. Patients may experience relapses while tapering off the dose, and these relapses currently have few treatment options.”
One such option is methotrexate, a chemotherapy drug that suppresses an overactive immune system, or leflunomide, a daily pill with a similar effect.
But recent research led by Professor Dasgupta, published in the New England Journal of Medicine, suggests that sarilumab may provide an alternative.
In the one-year trial, 118 patients taking steroids received twice-monthly injections of sarilumab plus steroids, or steroids alone.
Both groups had their existing steroid doses gradually reduced, over 14 weeks for the sarilumab group and 12 months for the steroid group, as they did not have the benefit of a second medication.
Sarilumab drug could reduce the number of relapses in patients with PMR
At the end of the trial, 28 percent of the group taking sarilumab had maintained remission of pain and stiffness, compared with 10 percent of those taking steroids.
And while 57 percent of patients receiving steroids relapsed within a few months, only 24 percent of the sarilumab group did.
Professor Dasgupta said: “This is an exciting development that has the potential to improve treatment options for patients with recurrent PMR who are trying to come off steroid medication.”
Although sarilumab also has side effects (including lower white blood cell counts, joint pain, diarrhoea and infections), Professor Dasgupta says these are less debilitating than the side effects associated with steroids.
Sarilumab is not currently approved to treat PMR in the UK, but NICE may consider approving it next year.
Annie’s symptoms came on suddenly, disrupting her sleep and leaving her exhausted. “Paul had to massage my knees and legs in the morning so I could get out of bed,” she recalls. “I couldn’t climb the stairs without him or get dressed without help. Just weeks earlier I had been leading a very active life – gardening, decorating, walking and enjoying pleasant holidays.”
At first, Annie attributed the problem to the lingering effects of a recent bout of flu. But when her symptoms worsened, she went to her GP. Blood tests showed she had elevated inflammatory markers which, together with her history of symptoms, led to the diagnosis of PMR.
She was prescribed steroids. “They worked to relieve the pain, but they also made me anxious and emotional,” Annie says. “I must have driven Paul crazy with my crying.”
‘He had to retire early and become my carer as there were many things I couldn’t do for myself.
‘I also developed cataracts, which may be related to the steroids, I started bruising easily because my skin had become so thin, and I had very bad sleeping problems.’
Annie was referred to several specialists and received numerous drug treatments over the years.
“Methotrexate made my hair fall out in clumps, so I stopped taking it,” she recalls. “And later I tried azathioprine, which also reduces inflammation, but I developed liver function problems.” Finally, in 2016, Annie read about Professor Dasgupta’s research into new treatments and booked a private appointment.
In addition to PMR, she was diagnosed with a related condition called giant cell arteritis (GCA), “which I didn’t know about,” she says. GCA causes inflammation of blood vessels, including the aorta, the largest blood vessel in the body that carries blood away from the heart. It affects up to 30 percent of people with PMR.
If left untreated, GCA can cause stroke and blindness as arteries become swollen and damaged, restricting blood flow to the brain and eyes.
“It was a lot to take in,” Annie says. “But Professor Dasgupta explained to me that there were other effective drugs I could try, which was a relief.” In 2016, she took part in a trial of a drug called sirukumab (which works in a similar way to sarilumab). Her symptoms improved, but the trial was stopped after the US drug regulator raised safety concerns about the higher number of deaths compared to a placebo group.
Undaunted, in 2019 Annie began taking tocilizumab, an immunosuppressant drug that works in a similar way and which she injects herself every ten days: she was recently also prescribed another immunosuppressant, leflunomide, in daily tablets.
Her steroid dose has now been reduced to 4mg a day and her symptoms have greatly improved. Annie says: “I am now back to gardening, walking and decorating. I want other people to know that they don’t have to take steroids – there are newer treatments available for PMR that can really improve your quality of life.”