Novel whole-body magnetic resonance imaging response and remission criteria document diminished inflammation during golimumab treatment in axial spondyloarthritis.

OBJECTIVES: To investigate criteria for treatment response and remission in patients with axial SpA as assessed by whole-body magnetic resonance imaging (WB-MRI) of axial and peripheral joints and entheses during treatment with golimumab. METHODS: We performed an investigator-initiated cohort study of 53 patients who underwent WB-MRI at weeks 0, 4, 16 and 52 after initiation of golimumab. Images were assessed according to the Spondyloarthritis Research Consortium of Canada MRI SI joint inflammation index, Canada-Denmark MRI spine inflammation score and the MRI peripheral joints and entheses inflammation index. RESULTS: At weeks 4, 16 and 52, WB-MRI demonstrated an at least 50% reduction of MRI inflammation of the sacroiliac joints in 16, 29 and 32 (30%, 55% and 60%) patients, of the spine in 20, 30 and 31 (38%, 57% and 58%) patients and of peripheral joints and entheses in 8, 17 and 15 (15%, 32% and 28%) patients, respectively. The BASDAI50 response was achieved by 29, 31 and 31 (55%, 58% and 58%) patients, while ASDAS clinically important improvement (ASDAS-CII) was achieved by 37, 40 and 34 (70%, 75% and 64%) patients. WB-MRI remission criteria for spine, sacroiliac joints and peripheral joints and entheses were explored; total WB-MRI remission was attained by 2, 6 and 3 (4%, 11% and 6%) patients. At week 16, among 35 patients with an at least 50% reduction in the MRI Axial Inflammation Index (sacroiliac joint and spine inflammation), 29 (83%) achieved BASDAI50 and 35 (100%) achieved ASDAS-CII; among 16 patients with MRI axial inflammation non-response, 14 (88%) were BASDAI50 non-responders and 11 (69%) did not achieve ASDAS-CII. CONCLUSION: WB-MRI demonstrated a significant reduction of inflammation in both the spine, sacroiliac joints and peripheral joints and entheses during golimumab treatment. Few patients achieved total WB-MRI remission. Combining spinal and sacroiliac joint inflammation in an MRI Axial Inflammation Index increased the ability to capture response. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02011386.

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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Test-retest repeatability of the apparent diffusion coefficient in sacroiliac joint MRI in patients with axial spondyloarthritis and healthy individuals.

BACKGROUND: The apparent diffusion coefficient (ADC) may be used as a biomarker to diagnose axial spondyloarthritis (axSpA) and monitor therapeutic response. PURPOSE: To measure the repeatability of the ADC in healthy individuals and in patients with axSpA with and without active sacroiliitis in a test-retest set-up, and to correlate ADC to conventional magnetic resonance imaging (MRI) bone marrow edema (BME) scores and clinical findings. MATERIAL AND METHODS: A total of 25 patients with axSpA and 24 sex- and age-matched healthy individuals were prospectively examined with MRI twice within 10 days. Short tau inversion recovery (STIR), T1-weighted and diffusion-weighted imaging sequences were performed. Mono-exponential ADC maps were based on four b-values: 0; 50; 500; and 800. Inter-study repeatability and intra-reader reproducibility were investigated in subgroups, as were associations with conventional MRI and clinical findings. RESULTS: The inter-study repeatability for the median ADC was moderate for all individuals (intraclass correlation coefficient [ICC] 0.66); it was good in patients with axSpA (ICC 0.79) and poor in healthy individuals (ICC 0.27). Significant differences in ADC were found between women and men (P = 0.03), and between patients with versus without BME on STIR (P = 0.01). ADC was associated with an MRI BME score and with age in women. CONCLUSION: ADC seems to be a repeatable parameter in patients with axSpA but not in healthy individuals. ADC is correlated with MRI sacroiliac joint BME score and with age in women.

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.

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.

Whole-body Magnetic Resonance Imaging in Axial Spondyloarthritis: Reduction of Sacroiliac, Spinal, and Entheseal Inflammation in a Placebo-controlled Trial of Adalimumab.

OBJECTIVE: To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA). METHODS: An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6. RESULTS: The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients. CONCLUSION: ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.

Reproducibility of the Bath Ankylosing Spondylitis Indices of disease activity (BASDAI), functional status (BASFI) and overall well-being (BAS-G) in anti-tumour necrosis factor-treated spondyloarthropathy patients.

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Function Index (BASFI) and the Bath Ankylosing Spondylitis Global Score (BAS-G) (ranges 0-10) have gained widespread in use as self-reported measures of disease activity, functional impairment and overall well-being in patients with ankylosing spondylitis and other spondyloarthropathies (SpA). In Denmark, BASDAI, BASFI and BAS-G are systematically used to monitor treatment response in patients treated with tumour necrosis factor (TNF) inhibitors. The purpose of the present study was to examine the reproducibility of the indices in anti-TNF-treated SpA patients already familiar with the use of the indices. Testing was performed twice on two different days (median interval 7 days, range 4-10 days) under standardised conditions in 26 out-clinic patients (median age 39 years, range 22-56 years). Limits of agreement were calculated as the 95% likely range for the difference between paired scores. Test-retest results were significantly intercorrelated with r (s) = 0.90 for BASDAI, 0.92 for BASFI and 0.74 for BAS-G. Limits of agreement for BASDAI, BASFI and BAS-G were +/-1.8, +/-1.4 and +/-3.2, respectively. Reproducibility as expressed as the mean of individual standard deviations was significantly poorer for BAS-G than for BASDAI and BASFI (p < 0.01). Internal consistency reliability and construct validity of BASDAI and BASFI were acceptable. In conclusion, in a sample of anti-TNF-treated patients experienced with the use of BASDAI, BASFI and BAS-G, random measurement errors of the scores were not negligible. The finding should be considered when monitoring anti-TNF treatment in daily clinical practice.