Inflammatory and structural changes in vertebral bodies and posterior elements of the spine in axial spondyloarthritis: construct validity, responsiveness and discriminatory ability of the anatomy-based CANDEN scoring system in a randomised placebo-controlled trial

Abstract

Background: The Canada-Denmark (CANDEN) definitions of spinal MRI lesions allow a detailed anatomy-based evaluation of inflammatory and structural lesions in vertebral bodies and posterior elements of the spine in patients with axial spondyloarthritis (axSpA). The objective was to examine the reliability, responsiveness and discrimination of scores for spinal inflammation, fat, bone erosion and new bone formation based on the CANDEN system and to describe patterns of inflammatory and structural lesions and their temporal development.

Methods: 49 patients with axSpA from an investigator-initiated, randomised, placebo-controlled trial of adalimumab underwent spinal MRI at weeks 0/6/24/48. MR images were scored according to the CANDEN system and the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Total scores, and various subscores, were created by summing individual lesion scores.

Results: The CANDEN spine inflammation score had high responsiveness, similar to the SPARCC MRI spine index (Guyatt's responsiveness index 1.88 and 1.67, respectively), and discriminated between adalimumab and placebo treatment already at 6 weeks' follow-up (P=0.03). Anterior/posterior corner inflammation subscores showed similar responsiveness. Inter-reader reliability for the CANDEN spine inflammation and fat scores was good to very good for status and change scores (intraclass correlation coefficient (ICC)=0.71-0.92). Reliability for CANDEN new bone formation and erosion scores was good to very good for status scores (ICC=0.61-0.75) but, due to minimal progression, poor for change scores (ICC≤0.40).

Conclusions: The CANDEN spine inflammation score showed good responsiveness, discrimination between active treatment and placebo and reliability. The CANDEN spine structural scores had good cross-sectional reliability, but longer studies are needed to investigate their sensitivity to change.

Trial registration number: NCT01029847; Results.

Keywords: inflammation; magnetic resonance imaging; outcomes research; spondylarthritis.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1

(A) User interface used for scoring of sagittal images according to the Canada-Denmark scoring system. Twenty-three discovertebral units (DVUs) are assessed. Fat lesions are scored in a similar way as inflammatory lesions, except that the posterior elements (FIL, SP, ST and TP/R) are not assessed for fat lesions. Fat lesions follow the principles of inflammation, except that posterior elements are not assessed. aCIL, anterior corner inflammatory lesion; NIL, non-corner inflammatory lesion; pCIL, posterior corner inflammatory lesion; FIL, facet joint inflammatory lesion; SP, spinous process inflammatory lesion; ST, soft tissue inflammatory lesion; aLIL, anterior lateral inflammatory lesion; pLIL, posterior lateral inflammatory lesion; TP/R, transverse process/rib; aCOBE, anterior corner bone erosion; pCOBE posterior corner bone erosion; NOBE, non-corner bone erosion; aCANK, anterior corner ankylosis; pCANK, posterior corner ankylosis; NANK, non-corner ankylosis; aCOS, anterior corner spur; pCOS, posterior corner spur; NOS, non-corner spur; FANK, facet joint ankylosis. (B) Axial view of inflammatory lesions. Note that as sagittal images are used for scoring, the boundaries illustrated in axial view may vary a few millimeters depending on the exact placement of the sagittal slices, when following the definition of central and lateral slices.

Figure 2

The distribution at baseline of inflammatory and structural lesions across vertebral bodies and posterior elements at each level from C2/C3 to L5/S1. Bars represent the number of patients with lesion by type and anatomical location. BME, bone marrow oedema; ERO, erosion; FAT, fat lesion; NBF, new bone formation (ankylosis/bone spur); PE, posterior elements; VB, vertebral body.

Figure 3

Mean values of CANDEN spine inflammation score and for vertebral body and posterior elements subscores, bars represent the SEM; as observed (n=49, 47, 42, 39). For comparison, change in SPARCC MRI spine index (23-DVU) is also shown. P values for difference between group at week 6 were calculated in post hoc secondary analyses by ANCOVA. Bar plots show changes from baseline to week 6 with P values for the difference between change values at week 6 calculated by Mann-Whitney U tests with continuity correction (per protocol); as observed (n=47). MRI scores were the average of the two readers. CANDEN,Canada-Denmark; DVU, discovertebral unit; SPARCC, Spondyloarthritis Research Consortium of Canada.