Is There a Disconnect Between Spinal Inflammation and Bony Ankylosis in Ankylosing Spondylitis?
Background:
Despite improvements in clinical signs and symptoms, preliminary evidence has suggested that TNF inhibitor use may not be able to prevent progressive bony ankylosis in ankylosing spondylitis (AS). This preliminary evidence is based on findings presented at EULAR last year (link to ) exploring the effect of one TNF inhibitor, etanercept, on radiographic progression over 2 years. These findings suggest, but have yet to prove, that there may be a disconnect between inflammation and ankylosis in AS. This pair of related abstracts explores both sides of the issue. In the first, Braun et al use magnetic resonance imaging (MRI) to assess the effect of treatment with the TNF inhibitor infliximab on spinal inflammation in AS patients. In the second, van der Heijde et al investigate short-term radiographic progression in AS patients treated with infliximab.
OP0044. Sustained Reduction in Spinal Inflammation in Patients with Ankylosing Spondylitis after Treatment with Infliximab
Authors: Braun, Landewe, Hermann, Deodhar, Baker, Han, Xu, Williamson, van der Heijde
Methods:
Patients enrolled in a 24 week randomized clinical trial of infliximab 5 mg/kg vs. placebo (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT)) had gadolinium-enhanced MRI scans of the spine performed at baseline (pre-treatment) and at 24 and 102 weeks. Infliximab doses were increased in patients with continued clinical symptoms. Placebo subjects crossed over to active treatment at 24 weeks. MRI scans were analyzed using the Ankylosing Spondylitis Spinal MRI Activity (ASspiMRI-a) score by two independent radiologists blinded to treatment allocation and sequence of the scans.
Results:
201 patients were randomized to infliximab and 78 to placebo. The average ASspiMRI-a score was 5.91 ± 6.58 in the infliximab treated patients and 6.21 ± 7.95 in the placebo treated patients. After 24 weeks of therapy, ASspiMRI-a scores decreased by an average of 4.44 ± 6.16 points in infliximab treated subjects compared to increasing an average of 0.38 ± 3.97 points in placebo treated subjects (p<0.001). After 102 weeks, when placebo treated subjects had crossed over to active treatment with infliximab for 24 weeks, there was no difference between mean change scores from baseline between subjects initially treated with placebo and those receiving infliximab for 102 weeks (-4.89 ± 6.85 vs. -4.87 ± 6.42, respectively; p=0.983)
Conclusions:
Compared to placebo treated patients, infliximab treatment was associated with a marked reduction in spinal inflammation by MRI.
OP0111. Radiographic Progression in Patients with Ankylosing Spondylitis after 2 Years of Treatment not Inhibited with Infliximab
Authors: van der Heijde, Landewe, Deodar, Baker, Han, Xu, Williamson, Houben, Baraliakos, Braun
Methods:
Infliximab treated patients enrolled in the ASSERT trial (described above) who received infliximab for 102 weeks were compared to AS patients enrolled in the Outcome in AS International Study (OASIS) who did not receive TNF inhibitors. Radiographs of the spine at baseline (pretreatment) and after 102 weeks were compared using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with X-ray assessors blinded to treatment allocation and sequence of the scans.
Results:
201 infliximab treated patients enrolled in ASSERT were matched to 70 patients from the OASIS cohort. After 2 years, mSASSS scores increased an average of 0.9 ± 2.6 points in infliximab treated subjects compared to 1.2 ± 3.9 points in the matched OASIS cohort subjects (p=0.683). There was no difference when the entire unmatched OASIS cohort was compared, or after adjustment for baseline NSAID use.
Conclusions:
Despite clinical improvements by MRI, infliximab treatment was not associated with a significant reduction in radiographic progression over two years in AS.
Editorial Comment:
The possibility that TNF inhibitors may improve spinal inflammation but have no impact on bony ankylosis is a discouraging concept, but one that is not unique to rheumatology. Other rheumatic diseases, such as scleroderma, demonstrate a disconnect between inflammation and aberrant healing. In AS the counterpart to the aberrant dermal fibrosis of scleroderma is represented by bony overgrowth in the spine leading to ankylosis. However, these results remain preliminary and it is much too early to give up on the possibility that, either with prolonged exposure or early aggressive treatment, TNF inhibitors may be capable of inhibiting bony ankylosis in AS. As AS is a disease of decades, two year radiographic data is probably too early to firmly base any lasting conclusions. It is encouraging to see such profound and rapid suppression of spinal inflammation using a sensitive means of detection. In particular, these results suggest that maximal suppression of spinal inflammation with infliximab occurs by 24 weeks and appears to be maintained at that level, at least through 2 years, with continued exposure.