Baseline Severity of Sacroiliitis and Extensive Fat Metaplasia Predicts the Progression of Backfill at the Sacroiliac Joint in Patients With Axial Spondyloarthritis.

Fat metaplasia in an erosion cavity, also known as backfill, is an essential intermediary in new bone formation in axial spondyloarthritis (axSpA) patients; however, the predictors of backfill progression are unknown. This longitudinal study aimed to assess the predictors of backfill progression in axSpA patients on magnetic resonance imaging (MRI). Clinical and MRI data were collected at baseline and follow-up in 52 axSpA patients. Backfill progression was defined as the new or increased T1 hyperintensity within the SI joint space. Logistic regression analyses were performed to identify the predictors of the backfill progression. A total of 19 patients had "backfill" at baseline and 30 patients exhibited the backfill progression after follow-up. The mean disease duration and SPARCC scores at baseline were significantly different between patients with and without backfill progression (P<0.001, P=0.003, respectively). Patients with backfill progression had a higher frequency of backfill at baseline, a higher SSS score of fat metaplasia, and a higher SSS score of backfill than those without (P=0.001, P<0.001, and P=0.002, respectively). A higher fat fraction value in the fat metaplasia area at the baseline was more frequent in patients with, than without, backfill progression (P=0.019). In the univariate logistic regression analyses, a higher SPARCC score for inflammation and a higher SSS score for fat metaplasia at baseline were associated with backfill progression. Severity of sacroiliitis and extensive fat metaplasia at baseline are predictors of the backfill progression in axSpA patients.

Zhang Y ，Guo Z ，Wang L ，Zhan Y ，Qu J ，Lei X ... -  《Frontiers in Immunology》

Evaluation of active inflammation, chronic structural damage, and response to treatment of sacroiliitis in axial spondyloarthritis using the Spondyloarthritis research consortium of Canada scoring system.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease affecting the spine and sacroiliac joints. To investigate whether there are differences in inflammatory and chronic structural damages, as assessed by a semiquantitative MRI scoring method, between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) patients with active inflammation at baseline, and to evaluate the treatment response in these patients after 3 months of tumor necrosis factor-alpha (TNF-α) inhibitor treatment. Fifty-eight axSpA patients with active inflammation were included in the study. The patients were divided into nr-axSpA group and AS group. MRI examinations of the sacroiliac joints were performed before and after treatment. Inflammatory and structural damages in these patients were assessed using the established Spondyloarthritis Research Consortium of Canada (SPARCC) inflammation and sacroiliac joint structural (SSS) scoring methods, which are two MRI-based scoring methods. The SPARCC score, SSS score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were compared between the two groups. At baseline, SPARCC scores for patients in the nr-axSpA and AS groups did not differ significantly (P > 0.05); however, SSS scores for fat metaplasia, erosion, and backfill for patients in the AS group were significantly higher (P < 0.001). Compared with baseline, SPARCC scores were significantly decreased in both groups after treatment (P < 0.001); however, after treatment, no statistically significant difference was found regarding SPARCC scores between the AS and nr-axSpA groups. Compared with baseline, a significant increase in the SSS scores for fat metaplasia and backfill (P < 0.001) and a significant decrease in the SSS scores for erosion (P < 0.001) were observed in all axSpA patients. Changes in the SPARCC score was inversely correlated with the changes in the SSS score for fat metaplasia (r = - 0.634, P < 0.001). Changes in the SSS score for backfill were positively correlated with the changes in the SSS score for fat metaplasia (r = 0.277, P < 0.05) and inversely correlated with those for erosion (r = - 0.443, P < 0.001). The SPARCC and SSS scoring systems can be used to assess inflammatory and chronic structural damages as well as treatment responses in patients with axSpA. More severe structural damages were seen in AS patients. TNF-α inhibitor treatment for 3 months could effectively reduce inflammation in axSpA patients.

Zhang Y ，Guo Z ，Zhan Y ，Qu J ，Lei X ... -  《BMC MUSCULOSKELETAL DISORDERS》

Development and Validation of 3 Preliminary MRI Sacroiliac Joint Composite Structural Damage Scores in a 5-year Longitudinal Axial Spondyloarthritis Study.

In axial spondyloarthritis (axSpA), sacroiliac joint (SIJ) erosion is often followed by fat metaplasia in an erosion cavity (backfill), and subsequently ankylosis. We aimed to combine the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score for erosion, backfill, and ankylosis into 3 versions of a novel preliminary axSpA magnetic resonance imaging (MRI) SIJ Composite Structural Damage Score (CSDS) and to test these. Thirty-three patients with axSpA, followed for 5 years after initiation of tumor necrosis factor inhibitor, had MRIs of the SIJs at baseline, and yearly thereafter. Three versions of CSDS were calculated based on different weightings of erosion, backfill, and ankylosis: (1) equal weighting: CSDSequal = (erosion × 0.5) + backfill + ankylosis; (2) advanced stages weighting more: CSDSstepwise = (erosion × 1) + (backfill × 4) + (ankylosis × 6); and (3) advanced stages overruling earlier stages ("hierarchical") with "<" meaning "overruled by": CSDShierarchical = (erosion × 1) < (backfill × 4) < (ankylosis × 6). At baseline, all CSDS correlated positively with SPARCC fat and ankylosis scores and modified New York radiography grading, and negatively with the Bath Ankylosing Spondylitis Disease Index and SPARCC SIJ inflammation scores. CSDSstepwise and CSDShierarchical (not CSDSequal) correlated positively with symptom duration and the Bath Ankylosing Spondylitis Metrology Index, and closer with SPARCC ankylosis score and modified New York radiography grading than CSDSequal. The adjusted annual progression rate for CSDSstepwise and CSDShierarchical (not CSDSequal) was higher the first year compared with fourth year (P = 0.04 and P = 0.01). Standardized response mean (baseline to Week 46) was moderate for CSDShierarchical (0.64) and CSDSstepwise (0.59) and small for CSDSequal (0.25). Particularly CSDSstepwise and CSDShierarchical showed construct validity and responsiveness, encouraging further validation in larger clinical trials. The potential clinical implication is assessment of SIJ damage progression by 1 composite score.

Wetterslev M ，Østergaard M ，Sørensen IJ ，Weber U ，Loft AG ，Kollerup G ，Juul L ，Thamsborg G ，Madsen OR ，Møller JM ，Pedersen SJ ... -  《-》

Effects of ixekizumab treatment on structural changes in the sacroiliac joint: MRI assessments at 16 weeks in patients with non-radiographic axial spondyloarthritis.

There is limited understanding regarding the inhibition of structural damage in the sacroiliac joint of patients with non-radiographic axial spondyloarthritis. This study evaluated the effect of the interleukin-17A inhibitor ixekizumab versus placebo on structural lesions in the sacroiliac joints as assessed by MRI at week 16 in patients with non-radiographic axial spondyloarthritis from the COAST-X study. COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly allocated to placebo or double-blind ixekizumab 80 mg every 4 weeks (Q4W) or 2 weeks (Q2W), with an 80 mg or 160 mg starting dose. We report a post-hoc analysis of 266 patients with available MRI scans from baseline and week 16. MRI scans were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural score (SSS) method independently by two masked readers. Treatment comparisons used analysis of covariance based on observed cases. Correlations were evaluated among changes in SPARCC SSS for erosion, fat lesions, and backfill, and between changes in SPARCC SSS and sacroiliac joint inflammation scores and clinical measures. COAST-X was registered with ClinicalTrials.gov, NCT02757352. Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled to the COAST-X study. 290 (96%) of 303 participants completed the week 16 visit (95 in the ixekizumab Q4W group, 98 in the ixekizumab Q2W group, and 97 in the placebo group), and MRI scans were available for 266 patients at baseline and week 16 (85 in the ixekizumab Q4W group, 91 in the ixekizumab Q2W group, and 90 in the placebo group). Changes from baseline to week 16 in mean SPARCC SSS for erosion were -0·39 for ixekizumab Q4W (p=0·003 vs placebo), -0·40 for ixekizumab Q2W (p=0·002), and 0·16 for placebo; for fat lesions: 0·16 for ixekizumab Q4W (p=0·013), 0·10 for ixekizumab Q2W (p=0·067), and -0·04 for placebo; and for backfill: 0·21 for ixekizumab Q4W (p=0·011), 0·22 for ixekizumab Q2W (p=0·006), and -0·10 for placebo. Ankylosis did not change. Effects of ixekizumab versus placebo on structural changes were most pronounced in patients with baseline inflammation in the sacroiliac joints. Changes from baseline at week 16 in erosion, fat lesions, and backfill were correlated. Although the clinical relevance is not yet clear, patients with non-radiographic axial spondyloarthritis receiving ixekizumab had significant reductions in erosions and increases in fat lesions and backfill in the sacroiliac joints versus placebo at week 16, suggesting an early repair process with ixekizumab treatment. Eli Lilly and Company.

Maksymowych WP ，Baraliakos X ，Lambert RG ，Landewé R ，Sandoval D ，Carlier H ，Lisse J ，Li X ，Hojnik M ，Østergaard M ... -  《Lancet Rheumatology》

Tumor necrosis factor inhibitor therapy but not standard therapy is associated with resolution of erosion in the sacroiliac joints of patients with axial spondyloarthritis.

Pedersen SJ ，Wichuk S ，Chiowchanwisawakit P ，Lambert RG ，Maksymowych WP ... -  《-》