It has been long understood and well accepted that inflammation and structural damage are tightly connected in rheumatoid arthritis and that the degree of structural damage will be controlled if the inflammation is controlled.
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Explore This IssueOctober 2010
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Eric M. Ruderman, MD, associate professor of medicine at Northwestern University Feinberg School of Medicine in Chicago, moderated the session on the apparent disconnect between inflammation and disease progression in ankylosing spondylitis (AS) at the 2009 ACR/ARHP Annual Scientific Meeting in Philadelphia.
“Once TNF [tumor necrosis factor] blockers entered the arena, the link between inflammation and what was occurring structurally was found not to be so tight. Even though we are treating the symptoms, we may not in the long run be having any impact on the structural outcome of the disease,” he said.
A chronic inflammatory disease, AS preferentially affects the axial structure, with peripheral arthritis and extraarticular manifestations common. Inflammation of the enthesis is also common, with insertion of bone into tendons and ligaments, Dr. Ruderman said.
Effect of TNF Agonist Therapy
Desiree M.F.M. van der Heijde, MD, PhD, professor of rheumatology at Leiden University Medical Center in Leiden, The Netherlands, reviewed recent research that has investigated the efficacy of TNF blockers on progression of structural damage in AS. One trial used etanercept therapy; another, infliximab; and the third, adalimumab. In the trial with etanercept, Davis et al showed a sustained response in improvement of signs and symptoms of AS in patients receiving twice weekly doses of the agent.1 The Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) trial examined efficacy of infliximab versus placebo and found that the therapy decreased spinal inflammation as assessed by MRI.2
The two-year results of the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in Ankylosing Spondylitis (ATLAS) trial showed that adalimumab reduced the signs and symptoms of AS and induced partial remission for up to two years. As with etancercept and infliximab, the agent improved patient quality of life.3
Dr. van der Heijde reviewed results of two-year follow-up studies that compared radiographic progression between patients enrolled in those trials and those enrolled in the Outcome Assessments in Ankylosing Spondylitis International Study (OASIS). The OASIS trial began in 1996 at four European centers and is a longitudinal observational study. Patient use of nonsteroidal antiinflammatory drugs was comparable in all trials.
One of these follow-up studies compared progression in structural damage between patients enrolled in either the Canadian AS study or the ATLAS trial and those in the OASIS cohort. In the Canadian AS study and in ATLAS, patients had been treated with the TNF blocker adalimumab; patients in the OASIS trial had not received a TNF blocker. Radiographic progression in the spine at baseline and at two years was measured using the modified Stoke AS Spine Score (mSASSS) method.
Once TNF blockers entered the arena, the link between inflammation and what was occurring structurally was found not to be so tight. Even though we are treating the symptoms, we may not in the long run be having any impact on the structural outcome of the disease.
—Eric M. Ruderman, MD