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Objective: Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone., Methods: Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability (κ) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement (κ) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models., Results: In exercises I, II, and III, mNY κ were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant κ increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not (κ = 0.00, 95% CI -0.10 to 0.10; P = 0.99)., Conclusion: Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.

Objective: (1) To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR ( Devenir des Spondylarthropathies Indifférenciées Récentes ) cohort., Methods: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers' assessments., Results: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients ( P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively., Conclusion: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738, NCT01648907]., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: Radiography is still used worldwide for the detection of sacroiliitis in juvenile spondyloarthritis (JSpA), despite its low sensitivity and reliability. We aimed to define unequivocal evidence of sacroiliitis on pelvic radiography in skeletally immature youth for use in classification criteria when magnetic resonance imaging (MRI) is unavailable., Methods: Subjects were a retrospective cohort of juvenile patients with spondyloarthritis with a radiograph and MRI as part of a diagnostic evaluation for axial disease. Six musculoskeletal imaging experts underwent an iterative consensus process to define unequivocal sacroiliitis on radiography in skeletally immature youth. Radiographs were graded using the modified New York (mNY) criteria and the unequivocal sacroiliitis criteria. Interrater agreement was assessed with the Fleiss [Formula: see text] statistic. Specificity, area under the receiver operator characteristic curve (AUROC), and sensitivity of the 2 measures were tested using 2 MRI reference standards., Results: A total of 112 subjects, with a median age of 14.9 (range 6.7-20.1) years, were included. The Fleiss [Formula: see text] was fair for the mNY criteria (0.54, 95% CI 0.42-0.67) and the unequivocal sacroiliitis criteria (0.58, 95% CI 0.46-0.69). The unequivocal sacroiliitis criteria achieved > 90% specificity using both MRI reference standards. Sensitivity (59.26 and 57.14 vs 44.83 and 43.33) and AUROC (0.76 and 0.76 vs 0.71 and 0.71) were higher, for both reference standards, for the unequivocal sacroiliitis in youth definition than for the mNY criteria, respectively., Conclusion: In this study, we propose the first consensus-derived definition to our knowledge of unequivocal sacroiliitis by radiography in skeletally immature youth. This definition achieved excellent specificity and had higher AUROC and sensitivity values than the mNY criteria using both MRI reference standards. This definition has applicability to the JSpA axial disease classification imaging criterion when MRI is unavailable., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings., Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score., Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively., Conclusion: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).

Objective: To develop a whole-body magnetic resonance imaging (MRI) scoring system for peripheral arthritis and enthesitis., Methods: After consensus on definitions/locations of MRI pathologies, 4 multireader exercises were performed. Eighty-three joints were scored 0-3 separately for synovitis and osteitis, and 33 entheses 0-3 separately for soft tissue inflammation and osteitis., Results: In the last exercise, reliability was moderate-good for musculoskeletal radiologists and rheumatologists with previously demonstrated good scoring proficiency. Median pairwise single-measure/average-measure ICC were 0.67/0.80 for status scores and 0.69/0.82 for change scores; κ ranged 0.35-0.77., Conclusion: Whole-body MRI scoring of peripheral arthritis and enthesitis is reliable, which encourages further testing and refinement in clinical trials.

Objective: To develop and validate an enthesitis magnetic resonance imaging (MRI) scoring system for spondyloarthritis/psoriatic arthritis, using the heel as model., Methods: Consensus definitions of key pathologies and 3 heel enthesitis multireader scoring exercises were done, separated by discussion, training, and calibration., Results: Definitions for bone and soft tissue pathologies were agreed. In the final exercise, median pairwise single-measures intraclass correlation coefficients (ICC; patient-level) for entheseal inflammation status/change scores were 0.83/0.82 for all readers. For radiologists and selected rheumatologists, ICC were 0.91/0.84 and quadratic-weighted κ (lesion-level) 0.57-0.91/0.45-0.81., Conclusion: The proposed definitions and Heel Enthesitis Scoring System (HEMRIS) are reliable among trained readers and promising for clinical trials.

Objective: There is a critical need for measures to evaluate structural progression in the pediatric sacroiliac joint (SIJ). We aimed to evaluate the construct validity and reliability of the Spondyloarthritis Research Consortium of Canada SIJ Structural Score (SSS) in children with suspected or confirmed juvenile spondyloarthritis., Methods: The SSS assesses structural lesions of the SIJ on magnetic resonance imaging (MRI) through the cartilaginous part of the joint. We conducted 3 sequential reading exercises with 6 readers (1 adult and 3 pediatric radiologists, 1 adult and 1 pediatric rheumatologist). Each exercise was preceded by a calibration module. Interobserver reliability was assessed using intraclass correlation coefficients (ICC). Prespecified acceptable reliability thresholds were ICC > 0.5 for erosion, backfill, and sclerosis, and ICC > 0.7 for ankylosis and fat metaplasia., Results: The SSS had face validity and was feasible to score in pediatric cases for all 3 reading exercises. Of the cases used in the 3 exercises, 58% were male and the median age was 14 years (range 6.8-18.7 yrs). After calibration, median ICC across all readers for each SSS component were the following: erosion 0.67 (interquartile range 0.54-0.80), backfill 0.33 (0.19-0.52), fat metaplasia 0.74 (0.62-0.85), sclerosis 0.63 (0.48-0.77), and ankylosis 0.44 (0.28-0.62). Prespecified reliability thresholds were achieved in the third exercise for erosion, sclerosis, and fat metaplasia but not for backfill or ankylosis., Conclusion: The SSS was feasible to score and had acceptable reliability for pediatric SIJ MRI evaluation. The ICC improved with additional calibration and reading exercises, even for readers with limited experience.

Objective: To assess feasibility and reliability of scoring bone marrow lesions (BML) on knee magnetic resonance imaging (MRI) in osteoarthritis using the Outcome Measures in Rheumatology Knee Inflammation MRI Scoring System (KIMRISS), with a Web-based interface and online training with real-time iterative calibration., Methods: Six readers new to the KIMRISS (3 radiologists, 3 rheumatologists) scored sagittal T2-weighted fat-saturated MRI in 20 subjects randomly selected from the Osteoarthritis Initiative data, at baseline and 1-year followup. In the KIMRISS, the reader moves a transparent overlay grid within a Web-based interface to fit bones, then clicks or touches each region containing BML per slice, to score 1 if BML is present. Regional and total scores are automatically calculated. Outcomes include the interreader intraclass correlation coefficients (ICC) and the smallest detectable change (SDC)., Results: Scoring took 3-12 min per scan and all readers rated the process as moderately to very user friendly. Despite a low BML burden (average score 2.8% of maximum possible) and small changes, interobserver reliability was moderate to high for BML status and change in the femur and tibia (ICC 0.78-0.88). Four readers also scored the patella reliably, whereas 2 readers were outliers, likely because of image artifacts. SDC of 1.5-5.6 represented 0.7% of the maximum possible score., Conclusion: We confirmed feasibility of knee BML scoring by new readers using interactive training and a Web-based touch-sensitive overlay system, finding high reliability and sensitivity to change. Further work will include adjustments to training materials regarding patellar scoring, and study in therapeutic trial datasets with higher burden of BML and larger changes.

Objective: To develop and validate a knowledge transfer (KT) module aimed at enhancing feasibility and reliability of semiquantitative assessment of bone marrow lesions (BML) and synovitis-effusion using the Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS)., Methods: Three radiologists naive to the HIMRISS method reviewed the manuscript describing the method and then scored MRI scans from 16 patients with hip OA obtained at baseline and 8 weeks after intraarticular injection of corticosteroid. Readers then reviewed a KT module comprising an instructional presentation and 8 reference DICOM (digital imaging and communications in medicine) cases scored by 3 readers with expertise in the HIMRISS method, and then used electronic overlay software to score scans from 23 patients with OA. The same format was followed with a second group of 3 readers naive to HIMRISS using a KT module revised to incorporate the overlay with a Web-based DICOM viewer to enhance feasibility. Interobserver reliability was assessed with the intraclass correlation coefficient (ICC)., Results: In both exercises, reliability for baseline scores was excellent for femoral BML, very good for acetabular BML, and good for synovitis-effusion (overall ICC = 0.91, 0.89, 0.62, respectively) even without prior calibration using the KT module. However, reliability for detecting change was substantially worse than for expert readers, especially for acetabular BML and synovitis-effusion (overall ICC = 0.59 vs 0.19, and 0.42 vs 0.25, respectively). Reliability improved for detection of change in these lesions, especially after reader calibration with the revised KT module., Conclusion: Development and validation of a systematic method for KT may enhance external validation of certain imaging instruments.

Objective: Semiquantitative arthritis scoring assesses disease burden by scoring presence/extent of features such as bone marrow lesion (BML) or effusion in multiple anatomic regions at a joint. An image overlay clarifying region borders may enhance feasibility and reliability of these scoring systems. To be scalable for use in large clinical trials, systematic computer-based user training is desirable. We developed an overlay and user training module for magnetic resonance imaging (MRI)-based scoring of hip osteoarthritis (OA)., Methods: We designed a semitransparent 2-dimensional image overlay applied to individual MRI slices to facilitate hip OA scoring [HIMRISS (Hip Inflammation MRI Scoring System)], initially using freeware and then in a customized HTML Web browser environment. We developed a systematic knowledge translation package including instructional presentation, fully scored expert consensus cases, and video tutorials for training in the use of these scoring systems with the overlays. Three musculoskeletal radiologists who had not used this scoring system before each performed a scoring exercise with no overlay, then repeated this with overlays after completing the training module. Based on postexercise interviews and a reader survey, we identified and corrected problems in the module. The entire training process was then repeated using 3 new readers., Results: Overlays were considered useful, particularly when integrated into a Web browser. The knowledge translation module was considered conceptually valuable, but as initially implemented was too lengthy and not sufficiently interactive., Conclusion: Semitransparent image overlays and standardized knowledge translation modules for reader training show promise to facilitate reader calibration using MRI-based scoring systems. Based on our experience, knowledge translation modules should emphasize close feedback evaluating performance and reader time efficiency.

Objective: There is an unmet need for reliable assessment of structural progression in the sacroiliac joints (SIJ) of patients with spondyloarthritis (SpA), but radiography is unreliable and lacks responsiveness. We aimed to develop and validate a new scoring method for structural lesions based on magnetic resonance imaging (MRI), the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ Structural Score (SSS)., Methods: The SSS method for assessment of structural lesions is based on T1-weighted spin echo MRI, validated lesion definitions, slice selection according to well-defined anatomical principles, and dichotomous scoring (lesion present/absent) of 5 consecutive slices through the cartilaginous portion of the joint. Scoring ranges are fat metaplasia (0-40), erosion (0-40), backfill (0-20), and ankylosis (0-20). We progressively conducted 3 validation exercises with 2-4 readers on baseline, and either 2-year (exercises 1 and 2) or 1-year (exercise 3) scans from 147 patients with SpA assessed blinded to timepoint. Interobserver reliability was assessed by intraclass correlation coefficient (ICC) and smallest detectable change (SDC)., Results: Interobserver reliability for status score was good to excellent for ankylosis (ICC 0.79-0.98), consistently good for fat metaplasia (ICC 0.71-0.78), moderate to good for erosion (ICC 0.58-0.62), and fair to good for backfill (ICC 0.35-0.66). Reliability for change scores was moderate to good for all structural lesions despite the relatively small changes in scores, and was highest for fat metaplasia when both ICC and SDC values were compared., Conclusion: The new SPARCC MRI SSS method can detect structural changes in the SIJ with acceptable reliability over a 1-2-year timeframe, and should be further validated in patients with SpA.

Objective: To compare the utility of radiography and magnetic resonance imaging (MRI) for the diagnosis of juvenile-onset spondyloarthritis in pediatric patients presenting with low back and/or sacroiliac (SI) pain of potentially inflammatory etiology., Methods: Radiographs and MRI studies of the SI joints in 26 patients with juvenile spondyloarthritis (JSpA) and 35 controls were assessed independently by 2 radiologists, with discrepancies arbitrated by a third. Radiographs and MRI were blinded and read in separate batches in random order., Results: Erosion was common and was the most useful diagnostic feature on radiography [positive likelihood ratio (LR) = 3.5] and was especially diagnostic of SpA on MRI (LR = 6.7). Subchondral sclerosis was common but was the least specific feature for both modalities. Joint space narrowing had some utility on radiography (LR = 2.0) and MRI (LR = 2.7) but was uncommon and had poor reader reliability. Bone marrow edema (LR = 3.1) and subarticular fat infiltration (LR = 4.5), detectable only on MRI, were both useful features. Global diagnostic impression of MRI (LR = 9.4) had very high utility for the diagnosis of JSpA, exceeding radiography (LR = 4.4) because of superior specificity. In addition, global diagnosis of SpA is much more reliably made on MRI (κ = 0.80) compared to radiography (κ = 0.30)., Conclusion: Specificity and reliability of MRI of the SI joints are superior to radiography for the diagnosis of juvenile-onset SpA and, where available, MRI should replace radiography as the first line of investigation.

Objective: As a wider variety of therapeutic options for osteoarthritis (OA) becomes available, there is an increasing need to objectively evaluate disease severity on magnetic resonance imaging (MRI). This is more technically challenging at the hip than at the knee, and as a result, few systematic scoring systems exist. The OMERACT (Outcome Measures in Rheumatology) filter of truth, discrimination, and feasibility can be used to validate image-based scoring systems. Our objective was (1) to review the imaging features relevant to the assessment of severity and progression of hip OA; and (2) to review currently used methods to grade these features in existing hip OA scoring systems., Methods: A systematic literature review was conducted. MEDLINE keyword search was performed for features of arthropathy (such as hip + bone marrow edema or lesion, synovitis, cyst, effusion, cartilage, etc.) and scoring system (hip + OA + MRI + score or grade), with a secondary manual search for additional references in the retrieved publications., Results: Findings relevant to the severity of hip OA include imaging markers associated with inflammation (bone marrow lesion, synovitis, effusion), structural damage (cartilage loss, osteophytes, subchondral cysts, labral tears), and predisposing geometric factors (hip dysplasia, femoral-acetabular impingement). Two approaches to the semiquantitative assessment of hip OA are represented by Hip OA MRI Scoring System (HOAMS), a comprehensive whole organ assessment of nearly all findings, and the Hip Inflammation MRI Scoring System (HIMRISS), which selectively scores only active lesions (bone marrow lesion, synovitis/effusion). Validation is presently confined to limited assessment of reliability., Conclusion: Two methods for semiquantitative assessment of hip OA on MRI have been described and validation according to the OMERACT Filter is limited to evaluation of reliability.

Objective: Development of a validated magnetic resonance image (MRI) scoring system is essential in hip OA because radiographs are insensitive to change. We assessed the feasibility and reliability of 2 previously developed scoring methods: (1) the Hip Inflammation MRI Scoring System (HIMRISS) and (2) the Hip Osteoarthritis MRI Scoring System (HOAMS)., Methods: Six readers (3 radiologists, 3 rheumatologists) participated in 2 reading exercises. In Reading Exercise 1, MRI of the hip of 20 subjects were read at a single time point followed by further standardization of methodology. In Reading Exercise 2, MRI of the hip of 18 subjects from a randomized controlled trial, assessed at 2 timepoints, and 27 subjects from a cross-sectional study were read for HIMRISS and HOAMS bone marrow lesions (BML) and synovitis. Reliability was assessed using intraclass correlation coefficient (ICC) and kappa statistics., Results: Both methods were considered feasible. For Reading 1, HIMRISS ICC were 0.52, 0.61, 0.70, and 0.58 for femoral BML, acetabular BML, effusion, and total scores, respectively; and for HOAMS, summed BML and synovitis ICC were 0.52 and 0.46, respectively. For Reading 2, HIMRISS and HOAMS ICC for BML and synovitis-effusion improved substantially. Interobserver reliability for change scores was 0.81 and 0.71 for HIMRISS femoral and HOAMS summed BML, respectively. Responsiveness and discrimination was moderate to high for synovitis-effusion. Significant associations were noted between BML or synovitis scores and Western Ontario and McMaster Universities Osteoarthritis Index pain scores for baseline values (p ≤ 0.001)., Conclusion: The BML and synovitis-effusion components of both HIMRISS and HOAMS scoring systems are feasible and reliable, and should be validated further.

Objective: To explore whether morphological features of fat infiltration (FI) on sacroiliac joint (SIJ) magnetic resonance imaging (MRI) contribute to diagnostic utility in 2 inception cohorts of patients with nonradiographic axial spondyloarthritis (nr-axSpA)., Methods: Four blinded readers assessed SIJ MRI in 2 cohorts (A/B) of 157 consecutive patients with back pain who were ≤ 50 years old, and in 20 healthy controls. Patients were classified according to clinical examination and pelvic radiography as having nr-axSpA (n = 51), ankylosing spondylitis (n = 34), or nonspecific back pain (n = 72). Readers recorded FI, bone marrow edema (BME), and erosion, predefined morphological features of FI (distinct border, homogeneity, subchondral location), and anatomical distribution of SIJ FI. The proportion of SIJ quadrants affected by FI and frequencies of various SIJ FI features were analyzed descriptively. We calculated positive/negative likelihood ratios (LR) to estimate the diagnostic utility of various features of FI, with and without associated BME, and erosion., Results: Of the patients with nr-axSpA in cohorts A/B, 45.0%/48.4% had FI in ≥ 2 SIJ quadrants. Of those, 25.0%/22.6% and 20.0%/25.8% showed FI with distinct border or homogeneous pattern, respectively, and 50% to 100% of those patients displayed concomitant BME or erosion. FI per se in ≥ 2 SIJ quadrants had no diagnostic utility (LR+ 1.62/1.91). FI with distinct border (LR+ 8.29/2.13) or homogeneity (LR+ 6.24/3.78) demonstrated small to moderate diagnostic utility., Conclusion: SIJ FI per se was not of clinical utility in recognition of nr-axSpA. Distinct border or homogeneity of FI on SIJ MRI showed small to moderate diagnostic utility in nr-axSpA, but were strongly associated with concomitant BME or erosion, highlighting the contextual interpretation of SIJ MRI.

Objective: To define the minimally important change (MIC) in the SpondyloArthritis Research Consortium of Canada (SPARCC) spine and sacroiliac (SI) joint magnetic resonance imaging (MRI) indices in patients with ankylosing spondylitis., Methods: MRI scans were performed during a placebo-controlled trial of adalimumab (no. NCT00195819). Two independent readers, blinded to treatment and sequence, determined SPARCC scores for the spine and SI joints and a global evaluation of change (GEC; "much worse," "worse," "no change," "better," or "much better"; categories other than "no change" were pooled together as "change") between baseline-Week 12, baseline-Week 52, and Weeks 12-52. Mean absolute changes in SPARCC scores (95% CI) were calculated for each interval, treatment group, and GEC. Receiver-operating characteristic (ROC) curves were used to identify the MIC. Relationships of MIC to clinical responses were examined., Results: Reader agreement on GEC evaluations was > 70%. Changes in SPARCC scores were generally comparable between time intervals and treatment groups for "change" and "no change" categories and were combined for each category; change in score was significantly associated with GEC of "change" (area under ROC curves: spine 0.839; SI joints 0.960). ROC curves peaked at values of 5.0 for the spine and 2.5 for SI joints. Placebo-treated patients achieving > 2.5 unit improvement in SI joint score had significantly better clinical responses than placebo-treated patients who did not achieve such improvement. MRI and clinical responses were uncoupled in adalimumab-treated patients., Conclusion: We propose that changes of 5.0 for the spine and 2.5 for SI joints define the MIC for the SPARCC MRI indices.

Objective: To test the hypothesis that in patients with ankylosing spondylitis (AS) a vertebral corner inflammatory lesion (CIL) visible on magnetic resonance imaging (MRI) that completely resolves following treatment with anti-tumor necrosis factor-α (TNF-α) agents is more likely to develop into a de novo syndesmophyte visible on a radiograph as compared to a vertebral corner with no CIL., Methods: Fifty patients with AS, who had MRI at baseline and at followup (mean 19.2 months), and spinal radiography at baseline and after 2 years, were followed prospectively. A persistent CIL was defined as being present on both MRI, while a resolved CIL was defined as present at baseline MRI and completely disappeared at followup MRI. Two readers read the MRI independently, and analyses were done for areas with agreement (concordant reads) and for individual reads., Results: For patients receiving anti-TNF therapy (n = 23), new syndesmophytes developed more frequently from vertebral corners where a CIL had completely resolved on followup MRI (42.9% on concordant reads) as compared to vertebral corners where no CIL was demonstrable on either the baseline or followup MRI (2.4%; p < 0.0001). Results from individual readers showed similar differences. For patients receiving standard treatment (n = 27), the same pattern, although nonsignificant, was observed (20% vs 3.3%; p = 0.16) on concordant reads, as well as on individual reads., Conclusion: Our study of AS spines documents that MRI findings predict new bone formation on radiograph. Demonstration of an increased likelihood of developing new bone following resolution of inflammation after anti-TNF therapy supports the theory that TNF-α acts as a brake on new bone formation. Because the number of new syndesmophytes was low, further study is necessary to make firm conclusions.

Objective: To evaluate the influence of low-dose infliximab (IFX) on spinal inflammation scored by magnetic resonance imaging (MRI). The dose recommended for rheumatoid arthritis (3 mg/kg) is also clinically effective for ankylosing spondylitis (AS), although effects on spinal inflammation as defined by MRI have yet to be described in a placebo-controlled trial., Methods: In a 12-week double-blind period, patients were randomized 1:1 to receive either IFX 3 mg/kg at 0, 2, and 6 weeks, or placebo. Spinal inflammation in discovertebral units (DVU) was measured by the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Index at baseline and 12 weeks by 3 readers blinded to timepoint and treatment allocation. We also compared reliability and discrimination of the SPARCC MRI index based on evaluation of the entire spine (23 DVU score) compared to assessment of only the 6 most severely affected DVU (6 DVU score)., Results: At Week 12, patients treated with IFX experienced mean reductions of 55.1% and 57.2% in the 6 DVU and 23 DVU SPARCC scores, respectively, compared with a mean increase of 5.8% and decrease of 3.4% in 6 DVU and 23 DVU scores, respectively, for patients taking placebo (p < 0.001). A large treatment effect (Guyatt's effect size >or= 1.7) and high reliability was evident and comparable between 6 DVU and 23 DVU scoring methods., Conclusion: Treatment with low-dose IFX leads to a large treatment effect on spinal inflammation as measured by MRI. Scoring for inflammation of only the most severely affected regions of the spine by MRI is comparable to assessment of the entire spine.

Magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the spine is increasingly important in the assessment of inflammatory activity and structural damage in clinical trials with patients with ankylosing spondylitis (AS). We investigated inter-reader reliability and sensitivity to change of several scoring systems to assess disease activity and change in disease activity in patients with AS. Twenty sets of consecutive MRI, derived from a randomized clinical trial comparing an active drug with placebo and selected on the basis of the presence of activity at baseline, were presented electronically to 7 experienced readers from different countries (Europe, Canada). Readers scored the MRI by 3 different methods including: a global score (grading activity per SI joint); a more comprehensive global score (grading activity per SI joint per quadrant); and a detailed scoring system [Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system], which scores 6 images, divided into quadrants, with additional scores for "depth" and "intensity." A fourth and a fifth scoring system were constructed afterwards. The fourth method included the SPARCC score minus the additional scores for "depth" and "intensity," and the fifth method included the SPARCC slice with the maximum score. Inter-reader reliability was investigated by calculating intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs. Sensitivity to change was investigated by calculating standardized response means (SRM) on change scores that were made positive. Overall inter-reader ICC per method were between 0.47 and 0.58 for scoring status, and between 0.40 and 0.53 for scoring change. ICC per possible reader pairs showed much more fluctuation per method, with lowest observed values close to zero (no agreement) and highest observed values over 0.80 (excellent agreement). In general, agreement of status scores was somewhat better than agreement of change scores, and agreement of the comprehensive SPARCC scoring system was somewhat better than agreement of the more condensed systems. Sensitivity to change differed per reader, but in general was somewhat better for the comprehensive SPARCC system. This experiment under "real life," far from optimal conditions demonstrates the feasibility of scoring exercises for method comparison, provides evidence for the reliability and sensitivity to change of scoring systems to be used in assessing activity of SI joints in clinical trials, and sets the conditions for further validation research in this field.

Objective: Infliximab, a neutralizing antibody to tumor necrosis factor-alpha, appears to be effective therapy in ankylosing spondylitis (AS), although treatment is costly and serious infections are an increasing concern. We investigated the efficacy and tolerability of infliximab in a prospective observational inception cohort of patients with nonsteroidal antiinflammatory drug-refractory AS seen in both university and community based practice. We also used a lower dose, 3 mg/kg, than has been evaluated to date in AS., Methods: We included all consecutive patients with AS starting infliximab therapy 3 mg/kg i.v. at 0, 2, and 6 weeks and q 2 months between April 2000 and October 2001. Data were systematically collected at baseline, 14 weeks, and 1 year, or at withdrawal, and included demographic characteristics, Bath AS indexes (BASDAI, BASFI, BASGI, BASMI), adverse events, and reasons for withdrawal. Laboratory measures included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum matrix metalloproteinases (MMP) 1 and 3, and serum human cartilage glycoprotein-39 (YLK-40). The first 6 consecutive patients were also studied by several magnetic resonance sequences, including dynamic MRI with gadolinium augmentation of affected joints. Maximal rate of augmentation was determined at baseline and 84 days. Analysis was by intention-to-treat., Results: Twenty-one patients (m:f = 17:4), mean age 42.5 years (range 24-66), mean disease duration 13.8 years (range 3-26), were studied: 13 had active peripheral synovitis at baseline. Mean followup was 47.5 weeks (range 10-77). Four patients withdrew, 2 for serious adverse events (septic osteomyelitis and severe hypersensitivity after 3 and 2 infusions, respectively), one for lack of efficacy, and one lost to followup. Three patients required an increased dose to 5 mg/kg after 14 weeks. Efficacy data were available on 17 patients at 14 weeks; mean BASDAI improved significantly from baseline (6.2) to 14 weeks (2.8) (p < 0.001), with 10 patients (58.8%) showing at least 50% improvement (range 0-99.6%). Significant reduction in mean BASFI (43.4%; p < 0.001), BASGI (44%; p = 0.001), ESR (55%; p < 0.001), and CRP (63.5%; p = 0.01) was evident. Complete remission of peripheral joint disease was seen in 5 of 11 (45.4%) patients evaluated at 14 weeks and maximal rate of MRI defined gadolinium augmentation was significantly decreased (p = 0.04). Reductions in serum YKL-40 and MMP-1 and 3 were nonsignificant, but significant correlations were observed between changes in BASDAI, ESR, CRP, and changes in serum levels of MMP-3 and YKL-40 (p < 0.005 to p < 0.05). Followup data on 8 patients completing 1 year of therapy revealed continued efficacy at a dose of 3 mg/kg every 8 weeks., Conclusion: Infliximab appears to be effective and well tolerated for both axial and peripheral joint disease in AS even at lower doses than those examined to date. Suppression of markers of cartilage degradation/turnover commensurate with reductions in clinical and laboratory measures of disease activity suggests that these markers should be further validated as surrogates for structural damage in AS. Controlled trials are warranted to further assess the potential of this agent in ameliorating structural damage.