In 2007, Toronto stock broker Andrew Turner was enjoying the prime of his life. The 35-year-old father of three was a serious runner, swimmer and cyclist, a model of physical fitness. The exercise regimen, however, took a toll: X-rays revealed not only a bulging disc, but something more sinister – a fusion of his pelvis's sacroiliac joint, and a distinct rounding of the vertebrae.
Both form part of the classic signature of ankylosing spondylitis (AS), a form of spinal arthritis that often spreads to other joints.
AS attracts less attention than other auto-immune disorders, such as lupus or rheumatoid arthritis, but it affects one in 200 Canadians – about 200,000 in total – principally men between 15 and 40. (Men are three times more likely to be stricken as women.) Typically, new bone spurs – such as those visible on Turner's X-rays – fuse with the spine, leaving victims permanently bent and chronically in pain.
A subsequent blood test confirmed that Turner was carrying HLA B27, the distinctive genetic marker for AS. Recently, scientists have concluded that at least 20 separate genes may be involved in AS and determine its progress.
Initially, Turner's case seemed mild. But two years later, minor surgery on his left knee caused the disease to spring horribly to life. His immune system went into overdrive, inflaming knees, ankles, wrists, hips and rib cage. He had trouble getting out of bed. He could not straighten his left leg.
"I couldn't sneeze without keeling over," Turner recalls. Every week, he upped the dosage of over-the-counter anti-inflammatory drugs. Lethargic, he slept 16 hours a day, grew deeply depressed and took a leave of absence from his job. He feared he faced years of acute pain and functional disability.
Then, four months after the surgery, Turner's wife injected him with 50 mg of Enbrel (etanercept), a relatively new anti-inflammatory drug that doctors prescribe when less potent medications fail. The effect was miraculous. Two weeks later, he was downhill skiing; the following March, he ran a five-kilometre race.
Now, for the first time, a three-year international research study of 335 patients – led by Toronto Western Hospital rheumatologist Dr. Nigil Haroon – has shown that Turner's case was not an anomaly.
Because it frequently presents as intermittent back pain, AS often takes eight to 10 years to identify. What the study showed is that early pharmaceutical intervention with Enbrel or its clones not only relieve symptoms of the disease; they appear to arrest its progression.
Enbrel and several similar biologic drugs, including Humira, Simponi and Remicade, are known as TNF-inhibitors. They work by blocking the action of the so-called tumour necrosis factor (TNF) in the blood, which precipitates inflammation and joint damage. TNF is also implicated in a range of other immune-system diseases, among them Crohn's, ulcerative colitis, rheumatoid and psoriatic arthritis.
According to Haroon's study, published recently in the medical journal Arthritis and Rheumatism, patients on TNF-inhibitors were 70-per-cent less likely to deteriorate than those taking other medications. Those who waited 10 years or more to begin such treatment were far less likely to respond.
"Before this paper," says Haroon, "either you went undiagnosed for years, or the GP did not take it seriously, because there was no treatment except over-the-counter anti-inflammatories. Now, we know that treatment with biologics makes a difference."
"We believe this study will change the landscape of AS," says Haroon's colleague, University Health Network senior scientist Dr. Robert Inman, who runs the largest AS patient clinic in Canada. "Until now, there's been a kind of therapeutic nihilism among general practitioners."
It is precisely that inertia, Inman concludes, that must now be addressed by educating GPs, sports-medicine doctors, chiropractors, physiotherapists and others about the importance of early diagnosis.
About 25 per cent of all AS patients respond well to ordinary analgesics like Motrin, says Inman. Among those who need something stronger, about 70 per cent will be able to control symptoms with biologics like Enbrel.
AS has long been considered an auto-immune disorder, but only recently has that categorization been formally confirmed – by a second study at Toronto Western Hospital. Research conducted by Dr. Florence Tsui, a senior scientist working with Inman, shows that AS patients carry so-called autoantibody complexes, which disable proteins that prevent abnormal bone formation.
Equally interesting, says Tsui, is that "more than half of AS patients also have subclinical gut inflammation, and about 10 per cent have both AS and intestinal bowel disease. It's not yet perfectly understood, but there's a clear connection between ankylosing spondylitis and IBD."
Her research, Tsui says, holds the possibility of developing a simple, fast and much cheaper blood test to identify telltale autoantibodies and to facilitate rapid diagnosis.
Meanwhile, four years after he began biologics therapy, Andrew Turner is training for Ironman competitions. "I plan to do four," he says, "and, since I now have another child, I'll give the finishing medal to each of my kids as a reminder that their dad did all this to prove that his illness did not stop him from doing anything."
Editor's note: The headline has been changed from a previously published version of this story.
Editor's Note: An earlier online version of this story incorrectly stated that the injection of Enbrel (etanercept) was 50 millilitres. The correct dosage was 50 milligrams.