CHICAGO – Despite dramatic clinical benefit, the standard treatments for ankylosing spondylitis do not appear to alter the natural history of the disease.
"We’d like to believe we’re actually doing something substantial for our patients in addition to actually relieving symptoms," said Dr. Michael H. Weisman, adding that this is an area of "hot, current controversy."
Nonsteroidal anti-inflammatory drugs, for example, are clinically very useful for treating patients with ankylosing spondylitis (AS). In a study of NSAID treatment for AS and mechanical back pain, good clinical response occurred in 75% of the AS patients, compared with only about 15% of the patients with mechanical back pain (Rev. Rhum. Engl. Ed. 1995;62:10-5), Dr. Weisman said at a symposium sponsored by the American College of Rheumatology.
The response of AS patients to NSAIDs is so good, in fact, that it can be helpful for confirming the diagnosis. A greater complete response may indicate that AS is the cause of symptoms, he said.
Another study demonstrated that 70% of AS patients who received etoricoxib had a good clinical response, compared with about 20% who received placebo (Arthritis Rheum. 2005;52:1205-15).
However, the effects of NSAIDs on radiographic progression of disease are questionable, at best, said Dr. Weisman, director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.
Although findings from one study showed that there was less radiographic progression of disease after 2 years in patients on continuous versus on-demand NSAIDs, with a mean change on the modified Stoke Ankylosing Spondylitis Spinal Score of 0.4 vs. 1.5, respectively (Arthritis Rheum. 2005;52:1756-65), most experts "take this particular study with a grain of salt," Dr. Weisman said.
That’s in part because the mean difference in dose between the continuous and on-demand patients was only 50 mg/day. It’s very difficult to believe that a difference of 50 mg in celecoxib could make a difference in actually reducing the amount of bone formation in AS, he said.
Tumor necrosis factor (TNF) blockers also provide excellent clinical benefit and are approved for use in AS. Patients experience tremendous response, perhaps to even a greater degree than do rheumatoid arthritis patients and, unlike RA patients, there appears to be no increased risk of serious infection with treatment, he noted.
In a recent meta-analysis of randomized, placebo-controlled studies of anti-TNF drugs in AS, no difference was seen in the rate of serious infections in those who received active treatment versus those who received placebo (Ann. Rheum. Dis. 2010; 69:1756-61).
However, while anti-TNF agents have the potential to alter the natural history and prognosis of AS, there is also no evidence in any studies of etanercept, infliximab, or adalimumab that treatment over 2 years inhibits radiographic progression of disease.
This is a source of frustration, Dr. Weisman said.
Disease progression in AS is generally very slow. Only about 25% of patients experience disease progression. Inflammation appears to play a role, with syndesmophytes developing significantly more frequently in vertebral corners in patients with inflammation versus those without inflammation (20% vs. 5% of patients in one study). Paradoxically, though, syndesmophytes develop more frequently in vertebral corners where inflammation has resolved than in those where it persisted after anti-TNF therapy, Dr. Weisman said.
This raises concerns about whether the control of inflammation using anti-TNF agents actually liberates bone formation in these patients, he noted.
In addition to the inflammation/syndesmophyte associations, syndesmophytes sometimes form in patients with normal x-rays or MRIs, he said.
"We really don’t know why syndesmophytes form in this disease," he added, noting that, while there has been some understanding of the fact that AS biology differs from RA biology (AS is a bone-forming disease, for example), new understanding of the biology is beginning to emerge. Perhaps this new understanding, along with the discovery of bone-related genes, will help define subsets of individual pathways that can be targeted, he suggested.
Dr. Weisman had no disclosures to report.