Rosaline van den Berg

Percentage of patients with spondyloarthritis in patients referred because of chronic back pain and performance of classification criteria: experience from the Spondyloarthritis Caught Early (SPACE) cohort

Objectives. The objectives of the study are to describe the Spondyloarthritis Caught Early (SPACE) cohort, present the performance of various SpA classification criteria and compare patients fulfilling the imaging arm with patients fulfilling the clinical arm of the Assessment of Spondyloarthritis international Society (ASAS) axSpA criteria on demographics, presence of SpA features and level of disease activity. Methods. Patients with back pain (53 months but 42 years, onset <45 years) visiting the rheumatology outpatient clinic of the Leiden University Medical Center were included in the SPACE cohort. Patients were classified according to the modified New York (mNY), ESSG, Amor and ASAS axSpA criteria. The sensitivity and specificity of criteria were tested against a rheumatologist’s diagnosis. Results. In total, 157 patients were included; 92 patients fulfilled any criteria, 11 fulfilled the mNY (sensitivity 16.9%, specificity 100%), 68 the ESSG (sensitivity 64.6%, specificity 71.7%), 48 the Amor (sensitivity 47.7%, specificity 81.5%) and 60 the ASAS axSpA criteria (sensitivity 84.6%, specificity 94.6%). Of those 60 patients, 30 fulfilled the imaging arm and 30 the clinical arm. Patients in the imaging arm are statistically significantly more often male, have a longer symptom duration and less often a positive family history for SpA than patients fulfilling the clinical arm. Patients in both arms are very similar regarding all other SpA features and level of disease activity. Conclusion. The inclusion criteria of the SPACE cohort yield the same high numbers of SpA patients compared with referral strategies like inflammatory back pain, HLA-B27+ or sacroiliitis, yet are easier to apply. The ASAS axSpA criteria outperformed the other criteria; 38.2% fulfilled the ASAS axSpA criteria. Patients fulfilling the clinical arm of the ASAS axSpA reflect a group of patients similar to those fulfilling the imaging arm.

ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the SPondyloArthritis Caught Early (SPACE)-cohort and from the Assessment of SpondyloArthritis international Society (ASAS)-cohort

Objective To compare the original Berlin algorithm for diagnosing axial Spondyloarthritis (axSpA) with two modifications in the SPondyloArthritis Caught Early (SPACE)-cohort and the Assessment of SpondyloArthritis international Society (ASAS) axSpA criteria validation (ASAS)-cohort. Methods Patients in the SPACE-cohort (back pain ≥3 months, ≤2 years, onset <45 years) and the ASAS-cohort (undiagnosed chronic back pain) were diagnosed according to three algorithms: original (inflammatory back pain (IBP) mandatory), modification 1 (IBP defined by ≥3/5 IBP-features instead of ≥4/5) and modification 2 (IBP deleted as obligatory entry criterion, added as SpA-feature). Diagnosis by rheumatologist, ASAS axSpA criteria and likelihood ratio product were used as external standards to test the performance of the algorithms. Results SPACE-cohort: Compared to the diagnosis by rheumatologist (either axSpA or no-axSpA), the original algorithm agreed in 120 patients (76.4%). Agreement decreased using modification 1 (119 patients; 75.8%), increased using modification 2 (125 patients; 79.6%). Sensitivity increased from 66.2% (original) to 72.3% (modification 1) and 78.5% (modification 2). Specificity decreased more using modification 1 (83.7% to 78.3%) than when using modification 2 (83.7% to 79.6%). ASAS-cohort: Compared to the diagnosis by rheumatologist (either axSpA or no-axSpA), the original algorithm agreed in 484 patients (70.7%). Agreement increased using modification 1 (520 patients; 75.9%) and modification 2 (548 patients; 80.0%). Sensitivity increased from 65.3% (original) to 77.9% (modification 1) and 79.6% (modification 2). Specificity decreased more using modification 1 (79.2% to 72.2%) than when using modification 2 (79.2% to 75.6%). Conclusions ASAS accepted a modified algorithm for diagnosing axSpA in which IBP is excluded as obligatory entry criterion and added as SpA-feature.

Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis

OBJECTIVE To perform a literature review as basis for the update of the Assessment in SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) treatment recommendations with biologics in AS. METHODS A literature search of all publications found in MedLine, Embase and Cochrane database between 2005 and 2009 and in the EULAR/ACR meetings between 2007 and 2009 was performed. The research evidence and strength of recommendation (SOR) for biologics were provided. RESULTS Out of 247 reports on AS treatment with biologics, 98 contained efficacy data and 25 had complete data for analysis. The treatment effect sizes (95% CI) for anti-TNF vs placebo varied between 0.34 (0.08, 0.6) and 1.5 (0.45, 2.5) for BASDAI and 0.33 (0.07, 0.59) and 2.5 (1.3, 3.7) for BASFI. The calculation of the numbers needed to treat all the different outcomes varied between 2.3 and 3.0 patients for all ASAS outcomes and between 2.7 and 6.5 patients for ASAS partial remission. Data on biologics other than anti-TNF and for TNF blockers on juvenile SpA were limited. The incidence rates of uveitis during anti-TNF treatment varied between 4.4/100 patient-years (pys) and 15.6/100 pys during placebo (P < 0.05). The incidence rates of IBD flares were significantly less during infliximab treatment (0.2/100 pys). The rate of infections was higher in patients treated with anti-TNF as compared with placebo, but there was no difference in the incidence of serious infections for treatment with anti-TNF vs placebo. CONCLUSIONS The overall evidence was very high for anti-TNF treatment (1b, SOR: A) with respect to efficacy and safety, while it was low for biologic treatment other than anti-TNF (3, SOR: C).

Agreement Between Clinical Practice and Trained Central Reading in Reading of Sacroiliac Joints on Plain Pelvic Radiographs: Results From the DESIR Cohort

To investigate the degree of agreement between local rheumatologists/radiologists and central trained readers (external standard) on the presence/absence of sacroiliitis on radiographs of the sacroiliac (SI) joints.

Performance of classification criteria for peripheral spondyloarthritis and psoriatic arthritis in the Leiden early arthritis cohort

Objectives The performance of spondyloarthritis (SpA) classification criteria is not well-established in general early arthritis cohorts. Therefore, the authors tested their performance in the Leiden Early Arthritis Clinic (EAC) cohort and assessed whether these criteria can assist rheumatologists in diagnosing patients. Methods The authors identified all SpA and psoriatic arthritis (PsA) patients in the EAC cohort according to the diagnosis of the treating rheumatologist. A control group consisting of arthritis patients with other diagnoses was matched to the SpA and PsA patients on gender, age and symptom duration. The authors assessed the fulfilment of SpA criteria in all three groups. Results Of the patients in the EAC cohort (n=2011), 7.5% was diagnosed with PsA and 3.8% with SpA. In the PsA group, the ClASsification criteria for Psoratic ARthritis (CASPAR) criteria had the highest sensitivity (88.7%). In the SpA group, the Assessment of SpondyloArthritis international Society (ASAS) peripheral SpA and European Spondylarthropathy Study Group (ESSG) criteria had the highest sensitivity (both 48.7%). Specificity of all criteria sets was good: ranging from 88.5% (ESSG) to 100% (Amor). Conclusions In early arthritis, sensitivity of SpA classification criteria is modest except for the CASPAR criteria in PsA. However, specificity of classification criteria, including the new ASAS-peripheral SpA criteria, is high.

Magnetic resonance imaging of the sacroiliac joints in the early detection of spondyloarthritis: no added value of gadolinium compared with short tau inversion recovery sequence

OBJECTIVES To investigate the additional value of T1 fat-saturated after gadolinium (T1/Gd) compared with T1 and short tau inversion recovery (STIR) sequence in detecting active lesions of the SI joints typical of axial SpA (axSpA) in a prospective cohort study, the SpondyloArthritis Caught Early (SPACE) cohort, and to assess its influence on final MRI diagnosis of the SI joint (MRI-SIJ) based on the Assessment of Spondyloarthritis International Society (ASAS) definition of active sacroiliitis. METHODS Patients in the SPACE cohort received baseline and 3-month follow-up MRI-SIJ with coronal oblique T1, STIR and T1/Gd sequences. Bone marrow oedema (BME), capsulitis/enthesitis and synovitis and active sacroiliitis according to the ASAS definition were evaluated by three blinded readers. RESULTS A total of 127 patients received an MRI-SIJ at baseline and 67 patients also received an MRI-SIJ at 3 months follow-up since the Gd protocol was added some months after the start of the SPACE project. Twenty-five of the 127 patients (19.7%) with a baseline MRI-SIJ and 14 of 67 patients (20.6%) with a follow-up MRI-SIJ presented BME on the STIR sequence sufficient to fulfill the ASAS definition for a positive MRI-SIJ. In eight patients, additional synovitis and/or capsulitis/enthesitis was observed; however, no additional BME was visualized on T1/Gd. One patient, without clinical diagnosis of axSpA, showed synovitis as an isolated finding. CONCLUSION Synovitis and capsulitis/enthesitis are detectable with the administration of Gd. However, they are always observed in the presence of BME. Therefore T1 and STIR sequence alone are sufficient in the MRI assessment that, among others, is used for diagnosing patients with early axSpA.

Classification of axial SpA based on positive imaging (radiographs and/or MRI of the sacroiliac joints) by local rheumatologists or radiologists versus central trained readers in the DESIR cohort

Objective Investigating changes in patient classification (ASAS (Assessment of SpondyloArthritis international Society) axSpA criteria) based on evaluation of images of the sacro-iliac joints (MRI-SI and X-SI) by local and central readers. Methods The DESIR cohort included patients with inflammatory back pain (IBP; ≥3 months, but <3 years), suggestive of axSpA. Local radiologists/rheumatologists (local-reading) and two central readers (central-reading) evaluated baseline images. Agreement regarding positive MRI (pos-MRI) between central readers and between local-reading and central-reading was calculated (κs). Number of patients classified differently (ASAS criteria) by using local-reading instead of central-reading was calculated. Results Inter-reader agreement between the two central readers and between local-reading and central-reading was substantial (κ=0.73 and κ=0.70, respectively). In 89/663 MRI-SIs (13.4%) local-reading and central-reading disagreed; 38/223 patients (17.0%) with pos-MRI (local-reading) were negative by central-reading; 51/440 patients (11.6%) with neg-MRI (local-reading) were positive by central-reading. In 163/582 patients eligible for applying ASAS criteria (28.0%), local-reading and central-reading disagreed on positive imaging (MRI-SI and/or X-SI; κ=0.68). In 46/582 patients (7.9%) a different evaluation resulted in a different classification; 18/582 patients (3.1%) classified no-SpA (central-reading) were axSpA by local-reading; 28/582 patients (4.8%) classified axSpA (central-reading) were no-SpA by local-reading. Among axSpA patients (central-reading), 16/419 patients (3.8%) fulfilling imaging-arm by central-reading fulfilled clinical-arm by local-reading; 29/419 patients (6.9%) fulfilling clinical-arm by central-reading fulfilled also imaging-arm by local-reading. Conclusions In patients with recent onset IBP, trained readers and local rheumatologists/radiologists agree well on recognising a pos-MRI. While disagreeing in 28% of the patients on positive imaging (MRI-SI and/or X-SI), classification of only 7.9% of the patients changed based on a different evaluation of images, showing the ASAS axSpA criterias robustness.

Patients with chronic back pain of short duration from the SPACE cohort: which MRI structural lesions in the sacroiliac joints and inflammatory and structural lesions in the spine are most specific for axial spondyloarthritis?

Objectives To investigate the extent and performance of MRI lesions in the sacroiliac joint (MRI-SI) and spine (MRI-spine) in patients with suspected axial spondyloarthritis (axSpA). Methods MRI-SI/spine of patients with chronic back pain (onset <45 years) in the SPondyloArthritis Caught Early (SPACE) cohort were scored by two well-trained readers for inflammation, fatty lesions, erosions, sclerosis/ankylosis and syndesmophytes. MRI performances were tested against the Assessment of Spondyloarthritis international Society (ASAS) axSpA criteria (positive: imaging-arm+ or clinical-arm+; negative: possible axSpA (few spondyloarthritis (SpA) features present) or no SpA). Arbitrary cut-off levels for MRI lesions were set to assure at least 95% specificity (tested in the no SpA group). Results In total 126 patients were ASAS criteria positive (73 imaging-arm+ (22 by modified New York criteria (mNY)+; 51 by MRI+mNY−); 53 clinical-arm+) and 161 were ASAS criteria negative (89 possible axSpA and 72 no SpA). On MRI-SI (n=287), at least three fatty lesions (or at least three erosions) were seen in 45.5 (63.6)% of mNY+ patients, 15.7 (47.1)% of MRI+mNY− patients and 15.1 (13.2)% of clinical-arm+ patients versus 3.4 (6.7)% of possible axSpA patients and 2.8 (4.2)% of no SpA patients. A combined rule (at least five fatty lesions and/or erosions) performed equally well. Sclerosis and ankylosis were too rare to analyse. On MRI-spine (n=284), at least five inflammatory lesions (or at least five fatty lesions) were seen in 27.3 (18.2)% of mNY+ patients, 13.7 (21.6)% of MRI+mNY− patients and 3.8 (1.9)% of clinical-arm+ patients versus 4.5 (6.7)% of possible SpA patients and 2.9 (4.3)% of no SpA patients. Conclusions The presence of (1) at least five fatty lesions and/or erosions on MRI-SI, (2) at least five inflammatory lesions or (3) at least five fatty lesions on MRI-spine allows an acceptable discrimination of axSpA and no SpA, while assuring >95% specificity.

Rate and Predisposing Factors for Sacroiliac Joint Radiographic Progression After a Two-Year Follow-up Period in Recent-Onset Spondyloarthritis

To evaluate the rate of radiographic structural progression in the sacroiliac (SI) joints in patients with radiographic or nonradiographic axial spondyloarthritis (SpA), and to determine factors predisposing to such progression, over 2 years.

Sacroiliac radiographic progression in recent onset axial spondyloarthritis: the 5-year data of the DESIR cohort

Objective To estimate sacroiliac joint radiographic (X-SIJ) progression in patients with axial spondyloarthritis (axSpA) and to evaluate the effects of inflammation on MRI (MRI-SIJ) on X-SIJ progression. Methods X-SIJ and MRI-SIJ at baseline and after 2 and 5 years in patients with recent onset axSpA from the DESIR cohort were scored by three central readers. Progression was defined as (1) the shift from non-radiographic (nr) to radiographic (r) sacroiliitis (by modified New York (mNY) criteria) or alternative criteria, (2) a change of at least one grade or (3) a change of at least one grade but ignoring a change from grade 0 to 1. The effects of baseline inflammation on MRI-SIJ on 5-year X-SIJ damage (mNY) were tested by generalised estimating equations. Results In 416 patients with pairs of baseline and 5-year X-SIJ present, net progression occurred in 5.1% (1), 13.0% (2) and 10.3% (3) respectively, regarding a shift from nr-axSpA to r-axSpA (1), a change of at least one grade (2) or a change of at least one grade but ignoring a change from grade 0 to 1 (3). Baseline MRI-SIJ predicted structural damage after 5 years in human leukocyte antigen-B27 (HLA-B27) positive (OR 5.39 (95% CI 3.25 to 8.94)) and in HLA-B27 negative (OR 2.16 (95% CI 1.04 to 4.51)) patients. Conclusions Five-year progression of X-SIJ damage in patients with recent onset axSpA is limited but present beyond measurement error. Baseline MRI-SIJ inflammation drives 5-year radiographic changes.