Abstract L11 : A Randomised Controlled Trial of Infliximab shows clinical and MRI efficacy in patients with HLA B27 positive very early ankylosing spondylitis
Authors
N Barkham, H Keen, L Coates, P O'Connor, E Hensor, A Fraser, L Cawkwell, D McGonagle, P Emery.
Purpose:
Patients with inflammatory back pain who are HLA B27 with positive MRI findings are predicted to progress to AS in more than 90% of cases without treatment. The current diagnostic criteria for AS relies on plain film sacroiliitis, which can take 10 years to develop. The benefits of treatment of AS in the preradiographic phase have not been established. The objective of this study was to assess the effects of infliximab on MRI changes of the spine and sacroiliac joints.
Methods:
HLA-B27 positive patients with inflammatory back pain positive underwent MRI scanning of the spine and sacroiliac joints. 40 patients within 3 years of onset of symptoms were recruited if edema could be detected at the sacroiliac joints. In double-blinded, placebo-controlled fashion, patients were randomized equally to infusions of placebo or infliximab 5 mg/kg at 0, 2, 6 and 12 weeks. Concomitant NSAIDS at a stable dose was permitted for the duration of the study. T1 and fat-suppressed T2 MRI scans of the spine and sacroiliac joints (subdivided into 8 regions) were performed at baseline and 16 weeks. Paired scoring was performed for each lesion using a semi-quantitative scale. The primary endpoint was change in MRI score from baseline to week 16. Clinical assessments were included as secondary endpoints.
Results:
Forty of 49 patients with early inflammatory back pain and HLA B27 had bone edema on MRI and were randomized. Twenty patients received infliximab, 20 placebo. The mean age was 28.8 years (SD 7.5), mean symptom duration was 15.3 months (SD 8.8), NSAID use was 90%, and 75% of patients were male. There were no statistically significant differences between the baseline characteristics of the 2 groups. Primary and secondary endpoints are described in the table. Compared to the placebo group, significant improvements in MRI and clinical endpoints were observed in the infliximab group (Table). Overall, infliximab was well tolerated, and no patients discontinued due to adverse events.
|
All patients (baseline) |
Infliximab |
Placebo |
P-value |
Total MRI score of sacroiliac joints, mean (95% CI) |
5.1 |
-2.0 (-6.25, -0) |
0(-2 ,- 1.5) |
0.033† |
Patients with spinal lesions, N (%) |
9 (22.5%) |
60% resolved |
25% resolved |
|
Sacroiliac MRI lesions resolving, N (%) |
- |
47 (62.7) |
20(29.4) |
0.001† |
New SI lesions on MRI, N (%) |
- |
1(1.2) |
11 (12) |
0.004† |
HAQ, median (IQR) |
0.88 (0.5,-1.25) |
-0.44 (-0.93, -0.13) |
-0.13 (-0.38, 0.00) |
0.065 |
ASQoL, median (IQR) |
10.5 (8.0,13.0) |
-6.18 (-10.0, -2.25) |
-1.00 (-4.50, 0.75) |
0.009† |
BASFI, mean (SD) |
4.26 (1.71) |
-2.70 (2.36) |
-0.47 (2.25) |
0.004† |
*BASDAI, mean (SD) |
5.81 (1.46) |
-3.41 (2.53) |
-0.75 (2.42) |
0.002† |
*BASDAI50, N (%) |
- |
12 (60.0) |
3 (15) |
0.006† |
**ASAS partial remission, N (%) |
- |
10 (55.6) |
2 (10) |
0.009† |
**ASAS20, N (%) |
- |
14 (77.8) |
5 (31.3) |
0.006† |
**ASAS50, N (%) |
- |
11 (61.1) |
3 (18.8) |
0.012† |
**ASAS70, N (%) |
|
10 (55.6) |
2 (12.5) |
0.009† |
* N=38 (P=18, I=20)
**N = 34 (P=16, I=18)
Conclusion:
Infliximab was effective for very early inflammatory back pain by providing a rapid reducing MRI radiographic lesions and measures of clinical efficacy.
Editorial Comment:
As with the Adalimumab study above (Abstract 753) patients with early pre-plain radiographic AS showed improvements in signs and symptoms over 16 weeks with infliximab at a dose of 5 mg/kg. This study also demonstrated a regression of spinal and sacroiliac lesions on MRI as well as fewer new lesions in patients receiving infliximab compared with placebo. It remains to be seen whether these MRI changes will correlate with a slowing of the rate of plain radiographic ankylosis. However, because of the robustness of the clinical response seen with the TNF antagonists, continuing a study of patients treated with placebo for a prolonged period of time to demonstrate differences in ankylosis as an endpoint wiill be increasingly difficult from an ethical perspective, given that the plain radiographic changes may take years to develop. If changing the course of MRI detectable edema however can be correlated with a slowing of ankylosis, then TNF antagonsism may represent true “disease-modifying” therapy in AS as in RA. Additional studies of infliximab in AS were reviewed at EULAR 2007.
