SAN ANTONIO, Texas—Although patients with ankylosing spondylitis who respond to tumor necrosis factor-alpha (TNF-alpha)-blocking therapy will have a higher activity index on magnetic resonance imaging (MRI) than nonresponders, a team of German researchers reported that they were surprised that the difference between the 2 patient groups was not more marked.¹

"We thought that MRI and the extent of active inflammatory changes might be a predictor of response to TNF-blocking therapy," said Martin Rudwaleit, MD, a Rheumatologist and Assistant Professor of Medicine at the Charité Benjamin Franklin Campus of the University Hospital in Berlin, Germany, who presented the findings here at the annual meeting of the American College of Rheumatology. "When we compared responders and nonresponders, the mean activity score of responders was significantly higher, but just barely so."

Therefore, the investigators suspect that other issues may be confounding the scores of nonresponders, he said. For example, they may have both acute inflammatory lesions, the marker of response that was measured, and destructive changes that impede their response to treatment. "We'll be looking at nonresponders in ongoing studies," said Dr. Rudwaleit, the study's principal investigator.

In previous studies, Dr. Rudwaleit and his investigative team had identified 3 factors that predicted response to TNF-blocking therapy: short disease duration, functional status as defined by the Bath Ankylosing Spondylitis Functional Index (BASFI), and elevated C-reactive protein (CRP) as main factors predicting a major clinical response to TNF blockers.² However, they also wanted to know whether acute inflammatory lesions as depicted by MRI would also be a predictor.

The German researchers reviewed the records of 99 ankylosing spondylitis patients who had participated in 2 placebo-controlled randomized trials; 69 had been in a trial involving infliximab, and 30 from a trial of etanercept. The investigators defined a major clinical response as a 50% improvement over the baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), after they had been treated for 12 weeks with either drug.

The investigators reviewed MRI scans for 63 patients; of these, they had MRIs of the spine from 52 patients, scans of the sacroilial joints from 43, and MRIs from both locations in 32 patients. They scored the presence and extent of acute inflammatory lesions in the spine by calculating the extent of bone marrow edema, with or without concomitant erosions, in each vertebral unit, and used a scale of 0 to 3. They scored the iliac and sacral part of each sacroilial joint on a scale of 0 to 3, also, with 0 indicating no inflammation and 3 indicating severe inflammation.

Among the 29 BASDAI 50 responders, 20 (69%) had acute inflammatory lesions in the spine compared to 14 (70%) of the 20 nonresponders. Such lesions were also found in the sacroilial joints of 18 of the 26 responders (69%) and in eight of the 14 nonresponders (57%).

The investigators also found trends for more inflammatory lesions in the spine among responders compared to nonresponders, with responders having an average of 5.4 lesions and nonresponders having an average of 4.1 lesions (P = 0.36). Responders averaged 2.6 such lesions in the sacroilial joints compared to an average of 1.6 in nonresponders (P = 0.19).

When the investigators analyzed the results for the 32 patients for whom they had MRIs for both areas, 87% had detectable acute inflammatory lesions in either area. Such lesions were found in 94% of responders and 77% of nonresponders (P = 0.2). Responders had an average of 5.4 lesions in the spine compared to an average of 4.4 in non-responders (P = 0.9). There were an average of 3.2 lesions in the sacroilial joints of responders, compared to an average of 1.5 in nonresponders (P = 0.85).

References:

Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to TNF-alpha blockers in ankylosing spondylitis. Ann Rheum Dis. 2004; 63:665-670.

Braun J, Baraliakos X, Golder W, Brandt J, Rudwaleit M, Listing J, Bollow M, Sieper J, Van Der Heijde D. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum. 2003;48:1126-1136.