Fa van Gaalen

Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair

Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria.

Signal intensity loss of the intervertebral discs in the cervical spine of young patients on fluid sensitive sequences.

ObjectiveTo evaluate the signal intensity (SI) of the intervertebral discs of the cervical spine on magnetic resonance (MR) fluid sensitive sequences, and correlate this to secondary signs of degeneration on MR and radiographs as well as to age.Material and methodsA total of 265 patients aged ≥16 with back pain (≥3-months, <2-year, onset <45-years) from the SPondyloArthritis Caught Early (SPACE) cohort were included. Sagittal 1.5xa0T MR images and lateral radiographs of the cervical spine were independently evaluated by two readers for: SI of the intervertebral discs using a grading system based of Pfirrmann (grade 1 normal/bright SI; 2 inhomogeneous/bright SI; 3 inhomogeneous/mildly decreased SI; 4 inhomogeneous/markedly decreased SI; 5 signal void), disc herniation and Modic changes (MRI) and disc space narrowing, osteophytes and sclerosis (radiograph). Readers were blinded for clinical information. Descriptive statistics were used for characteristics and prevalence of findings, and regression analysis was used for age and grades.ResultsOf 265 patients (36xa0% male, mean age 30), 221 (83xa0%) patients had 1 to 6 discs (median 4) with decreased SI. Of 1,590 discs, 737 (46xa0%) were grade 1; 711 (45xa0%) grade 2; 133 (8xa0%) grade 3; 8 (1xa0%) grade 4 and 1 (0xa0%) grade 5. Secondary signs of degeneration were rare and seen predominantly in C5–C7 and appear to be related to signal loss grade 3 and 4.ConclusionLow signal intensity of intervertebral discs in absence of secondary degenerative signs in the cervical spine on fluid sensitive MR images might be pre-existing and part of the natural course.

Presence of multiple spondyloarthritis (SpA) features is important but not sufficient for a diagnosis of axial spondyloarthritis: data from the SPondyloArthritis Caught Early (SPACE) cohort

Objectives Concerns have been raised about overdiagnosis of axial spondyloarthritis (axSpA). We investigated whether patients with chronic back pain (CBP) of short duration and multiple SpA features are always diagnosed with axSpA by the rheumatologist, and to what extent fulfilment of the Assessment of SpondyloArthritis International Society (ASAS) axSpA criteria is associated with an axSpA diagnosis. Methods Baseline data from 500 patients from the SPondyloArthritis Caught Early cohort which includes patients with CBP (≥3u2005months, ≤2u2005years, onset <45u2005years) were analysed. All patients underwent full diagnostic workup including MRI of the sacroiliac joints (MRI-SI) and radiograph of sacroiliac joints (X-SI). For each patient, the total number of SpA features excluding sacroiliac imaging and human leucocyte antigen B27 (HLA-B27) status was calculated. Results Before sacroiliac imaging and HLA-B27 testing, 32% of patients had ≤1 SpA feature, 29% had 2 SpA features, 16% had 3 SpA features and 24% had ≥4 SpA features. A diagnosis of axSpA was made in 250 (50%) of the patients: 24% with ≤1 SpA feature, 43% with 2 SpA features, 62% with 3 SpA features and 85% with ≥4 SpA features. Of the 230 patients with a positive ASAS classification 40 (17.4%) did not have a diagnosis of axSpA. HLA-B27 positivity (OR 5.6; 95% CI 3.7 to 8.3) and any (MRI-SI and/or X-SI) positive imaging (OR 34.3; 95% CI 17.3 to 67.7) were strong determinants of an axSpA diagnosis. Conclusions In this cohort of patients with CBP, neither the presence of numerous SpA features nor fulfilment of the ASAS classification criteria did automatically lead to a diagnosis axSpA. Positive imaging was considered particularly important in making a diagnosis of axSpA.

Are Additional Tests Needed to Rule Out Axial Spondyloarthritis in Patients Ages 16–45 Years With Short‐Duration Chronic Back Pain and Maximally One Spondyloarthritis Feature?

To investigate whether HLA–B27 testing and imaging of the sacroiliac joints are needed in patients with ≤1 spondyloarthritis (SpA) feature, referred to a secondary care setting, after medical history collection, clinical examination, and measurement of acute phase reactants.

Prevalence and clinical significance of lumbosacral transitional vertebra (LSTV) in a young back pain population with suspected axial spondyloarthritis: results of the SPondyloArthritis Caught Early (SPACE) cohort

ObjectiveTo determine in a cohort of young patients with suspected axial spondyloarthritis (axSpA), the prevalence of lumbosacral transitional vertebra (LSTV), its association with local bone marrow edema (BME) and lumbar spine degeneration, and the potential relationship with MRI findings and clinical signs of axSpA.Materials and methodsBaseline imaging studies and clinical information of patients from the SPondyloArthritis Caught Early-cohort (back pain ≥3xa0months, ≤2xa0years, onset <45xa0years) were used. Two independent readers assessed all patients for LSTV on radiography, and BME-like and degenerative changes on MRI. Patients with and without LSTV were compared with regard to the prevalence of MRI findings and the results of clinical assessment using Chi-squared test or t test.ResultsOf 273 patients (35.1% male, mean age 30.0), 68 (25%) patients showed an LSTV, without statistical significant difference between patients with and without axSpA (pu2009=u20090.327). Local sacral BME was present in 9 out of 68 (13%) patients with LSTV and absent in patients without LSTV (pu2009<u20090.001). Visual analogue scale (VAS) pain score and spinal mobility assessments were comparable.ConclusionsLSTV is of low clinical relevance in the early diagnosis of axSpA. There is no difference between patients with and without LSTV regarding the prevalence of axSpA, pain and spinal mobility, and a BME-like pattern at the pseudoarticulation does not reach the SI joints.

KIR3DL1 and KIR3DL2 gene copy number variation in axial spondyloarthritis

Axial spondyloarthritis (axSpA), including the subgroup ankylosing spondylitis (AS) is strongly genetically determined. HLA-B27 is the strongest known risk factor (1) and in recent years genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) have yielded new genetic risk factors for AS (2). However, it is thought that HLA-B27 and the SNPs discovered in GWAS only account for a small part of the total genetic risk for AS. In order to fully understand the origin of axSpA, a complete risk analysis is required. We therefore performed a pilot study to determine the genetic risk of known binding partners of HLA-B27. Human leukocyte antigen (HLA) class I molecules constitute natural ligands for a number of killer immunoglobulin-like receptors (KIRs), which are expressed by natural killer (NK) cells and a subset of T-cells. KIRs are involved in the regulation of the cytotoxic activity of these cells. The HLA-B27 molecule is known to be recognized by KIR3DL1 and KIR3DL2 (3), and binding of HLA-B27 to KIR3DL2 activates Th17 cells in AS (4). The KIR locus is subject to genetic variation, which is because of gene polymorphisms and gene copy number variation (CNV), as we have previously shown (5). Although KIR genes and polymorphisms have been studied in SpA, nothing is known of gene CNV in relation to this disease. In this study, we investigated the distribution of KIRs and their CNV in a panel of Caucasian AS and early axSpA patients [from the Leiden Early Arthritis cohort (EAC) and Spondyloarthritis Caught Early (SPACE) cohort, respectively] (6, 7) (Table 1). All patients fulfill the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria (8). An unusual characteristic of the AS patients in the EAC was the low percentage of inflammatory back pain (IBP) according to ASAS expert criteria. Information on IBP was retrieved from patient files and at the time of inclusion of patients in the EAC, the ASAS IBP criteria had not been published.We observed that the ‘pain at night’ feature was not commonly used in clinical practice which has likely led to a lower percentage of IBP-positive patients in the EAC cohort. Consistent with this explanation is that a much higher percentage of more than 80% of AS patients had IBP according to the Calin criteria, which is consistent with other cohorts (9).

Is it useful to repeat MRI of the sacroiliac joints after three months or one year in the diagnostic process of patients with chronic back pain suspected of axial spondyloarthritis

To investigate the value of repeated magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in diagnosing chronic back pain patients in whom axial spondyloarthritis (SpA) is suspected and to examine determinants of positive MRI findings in SI joints.

THU0748-HPR Recommendations on physical therapy prescription for axial spondyloarthritis in the netherlands

Background In national and international guidelines physical therapy, comprising exercise interventions and education, is recommended as a required treatment modality for the optimal treatment of axial spondyloarthritis (axSpA). [1–3]. However, specific details regarding referral for physical therapy and optimal content and dose of exercise interventions are lacking. Research showed large variation in the content of exercise therapy in axSpA patients, which reflects suboptimal care [4]. Objectives To develop practice recommendations on indications for referral, content, dose and safety aspects of exercise therapy for axSpA patients based on scientific evidence, expert opinion and patient values. The ultimate aim is improving the quality of exercise therapy care for people with axSpA. Methods The recommendations are based on scientific evidence, expert opinion and patient values and were formulated following a combination of literature review and three expert-group meetings (consisting of patients, rheumatologists, physical and exercise therapists, policy makers, scientists and special interest groups). In three consecutive expert-meetings clinically relevant questions, draft recommendations based on systematic literature reviews, and final recommendations including level of agreement were generated. Lastly, a field consultation among physical and exercise therapists, rheumatologists, scientists and special interest groups will be scheduled and an implementation strategy, comprising of an information intervention and directives, will be developed. Results In the first expert-group meeting 18 clinically relevant questions were formulated, on: indication and referral, assessment, content of treatment, evaluation and safety. In addition to recently published systematic reviews, additional literature reviews concerned assessment, safety and the dosage of exercise therapy. Related to the clinical questions, a framework for the therapeutic process and 12 draft recommendations were developed and discussed in the second meeting. In the third and last meeting the 12 recommendations regarding the delivery of physical therapy and exercise interventions were set and the level of agreement was determined. Conclusions The expert-meetings and literature searches led to 12 practice recommendations and a clear starting point for the development of the implementation strategy. Twelve practice recommendations regarding the delivery of physical therapy for patients with axSpA were developed, based on scientific evidence, expert opinion patient values. The field testing and development and execution of a dissemination and implementation strategy will be done in 2017. References Dagfinrud H, et al. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev. 2008. van der Heijde D, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017. Steeringgroup recommendations Spondyloartritis, Dutch Rheumatology Association, Guidelines for diagnosis and treatment of axial Spondyloartrtis, 2014. Van der Giesen et al. Use and content of physical and (group)exercise therapy for people with axial spondylarthritis, NVR congress, posterpresentation, 2016. Acknowledgements The Dutch Arthritis Foundation financially supported this project. Disclosure of Interest None declared

OP0314-PARE Group Exercise Therapy in Ankylosing Spondylitis (AS): The Patients' Perspective

Background Group exercises have been recommended for patients with AS with, some exercise classes having been instituted more than 20 years ago. Current practice may therefore not be consistent with the current needs and preferences of AS patients and new scientific insights into required components and dosage (exercises improving joint mobility, strength, cardiopulmonary fitness and neuromotor abilities) dosage (intensity x duration/repetitions, dependent on age and health status), frequency (at least 2–3 times a week). Objectives To determine to what extent patients with AS are satisfied with a long-existing group exercise programme and what their preferences are regarding the current and required features of group exercise classes. Methods A survey was administered to patients participating in a group exercise programme used in a randomised trial (1). The programme, once a week during 2.5 hours, consisted of mobility exercises, sports activities (e.g. volleyball, badminton) and hydrotherapy, addressing strength, mobility and fitness without specification of dosage, regular monitoring or home exercises. The survey investigated experiences with the dosage of the programme components (too high/too low), its subjective effects, patients preferences regarding potentially novel elements (heart rate controlled training, regular standardized assessments of mobility, physical function and activity limitations) and increased exercise frequency (in favour/not in favour/dont know). Results 43 of 48 patients (90%) returned the survey, 31 (72%) were male, their median age was 58 years (range 33–80). Overall, there were patients finding the dosage of various programme components either high/too high or low/too low and/or deserving less or more attention. The top 3 of most frequently perceived positive effect of the programme were the prevention of deterioration (74%), moving less stiff (61%) and an improved cardiopulmonary fitness (30%). Regarding potential adaptations, the majority of patients favoured implementing heart rate-guided cardio-vascular training (63%) and standardized and periodic assessments (74%), whereas a minority favoured increasing the frequency of exercise classes (23%). Satisfaction of 43 AS patients regarding a group exercise programme Patients opinions regarding programme components Exercise therapy Sports Hydrotherapy Duration too short/too long 4 (9)/3 (7) 7 (16)/4 (9) 4 (9)/1 (2) Intensity too high/not high enough 3 (7)/6 (14) 3 (7)/9 (21) 3 (7)/8 (19) Patients opinions regarding exercise modalities Muscle strength Joint mobility CP-fitness Too little attention 10 (23) 4 (9) 12 (28) Enough attention 32 (74) 37 (86) 29 (67) Too much attention 0 0 1 (2) Conclusions The variety regarding patients perception with a group exercise programme of its intensity and preferred components underlines the need for individual adaptions, according to results of regular assessments. As only a minority of patients favours group exercises more than once a week, the delivery of home-based exercises meeting minimum requirements to enhance health status in patients with AS is a future challenge. References Is group physical therapy … A randomized controlled trial. Hidding A. et al. Arthritis Care Res. 1993;6:117–25. Acknowledgement Dutch Arthritis Association, grant number: BP 14–1-161. Disclosure of Interest None declared

FRI0125 Impact of Repeating Imaging of the Sacro-Iliac Joints over One Year on the Classification According the ASAS Axial SPA Criteria of Patients

Background It is known that in axial spondyloarthritis (axSpA) inflammatory lesions on MRI of the SI joints (MRI-SI) can change over time. The usefulness of repeating imaging in the diagnostic process is unclear. Objectives To investigate how patients with short-term chronic back pain are classified by the ASAS axSpA- criteria at baseline and after 1 year follow-up, with a focus on the role of imaging. Methods Patients in the SPACE cohort (back pain: ≥3 months, ≤2 years, onset <45 years) with (suspicion of) axSpA underwent MRI and X-rays of the sacroiliac joints at baseline and 1 year follow-up. Only patients with complete MRI- and X-SI data at both baseline and year 1 were included in the analysis (n=80). MRI-SI and X-SI were scored independently by 3 well-calibrated readers according to the ASAS definition for a positive MRI and the mNY-criteria. Readers were blinded for patient characteristics and time sequence. Fulfillment of ASAS or mNY criteria was considered positive if 2/3 readers agreed. For each timepoint, patients were classified according the ASAS axSpA criteria and grouped in different arms (imaging arm: mNY+/- or MRI+/-; clinical arm, fulfillment of both arms and possible axSpA). In contrary to the normal application of the criteria, where a positive feature remains positive, we grouped patients according to the finding at one year, ignoring previous imaging findings. Results At baseline, 41/80 patients (32.8%) fulfilled the ASAS criteria (clinical arm: 22; imaging arm: 12, both arms: 7) (table). After 1 year, 3 additional patients fulfilled the criteria (2 clinical arm; 1 imaging arm). After 1 year, in 5 patients MRI-SI became positive and 1 patient fulfilled the mNY criteria. On the other hand, MRI-SI became negative after 1 year in 4 other patients. Of these patients, 3 still fulfilled the ASAS criteria (imaging arm (mNY+, n=1) or clinical arm (n=2)). Only 1 patient (classified as axSpA at baseline) would be missed if imaging would have been performed at 1 year only (due to a negative MRI). Conclusions With one year longer symptom duration, 3/39 (8%) of the possible SpA patients could be classified additionally as axSpA because of additional SpA features (5%) or positive MRI (3%), while 1/41 (2%) of the axSpA patients would not be classified due to a normal MRI. There was a switch between imaging and clinical arm in 12% of the patients. Therefore, our data show the robustness of the axSpA criteria and does not support repeating imaging after one year. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1630