M. van Oosterhout

Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheumatoid arthritis is associated with decreased synovial expression of TNFα and IL18 but not CXCL12

Background: Tumour necrosis α (TNFα) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNFα independent pathways play a role in the disease. Objectives: To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNFα independent mechanisms. Methods: 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38+ cells was studied by an immunofluorescent double labelling technique. Results: Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNFα, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38+ activated T cells were more resistant to treatment than CD38+ plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. Conclusions: Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNFα independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.

Four-month metacarpal bone mineral density loss predicts radiological joint damage progression after 1 year in patients with early rheumatoid arthritis: exploratory analyses from the IMPROVED study

Aim To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal bone mineral density (BMD) loss after 4 months predicts radiological progression after 1 year of antirheumatic treatment. Methods Metacarpal BMD was measured 4 monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in patients participating in the IMPROVED study, a clinical trial in 610 patients with recent onset RA (2010 criteria) or undifferentiated arthritis, treated according to a remission (disease activity score<1.6) steered strategy. With Sharp/van der Heijde progression ≥0.5 points after 1 year (yes/no) as dependent variable, univariate and multivariate logistic regression analyses were performed. Results Of 428 patients with DXR-BMD results and progression scores available, 28 (7%) had radiological progression after 1 year. Independent predictors for radiological progression were presence of baseline erosions (OR (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)). In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). Conclusions In early RA patients, metacarpal BMD loss after 4 months of treatment is an independent predictor of radiological progression after 1 year. In patients without baseline erosions, early metacarpal BMD loss is the main predictor of radiological progression.

OP0182 Drug Free Remission After One Year of Treatment in Patients with Early Rheumatoid Arthritis: Also Possible for ACPA Positive Patients?

Background In rheumatoid arthritis (RA) remission is a realistic treatment goal. Is tapering medication to drug free remission (DFR) possible for all patients? Objectives To assess which patients with early (rheumatoid) arthritis achieve DFR after one year (DFR1year) of early remission induction therapy. Methods By protocol of the IMPROVED study, patients who achieved remission (DAS<1.6) after 4 months (early remission, n=375) of combination therapy with methotrexate 25 mg/wk and a tapered high dose of prednisone (60 mg/day tapered in 7 weeks to 7.5 mg/day, continued up to 4 months) had to taper stepwise and finally discontinue these drugs as long as remission was maintained. Characteristics of patients achieving and not achieving DFR1year were compared and predictors of DFR were identified using logistic regression. Follow up data of 16 months were included to investigate in how many patients DFR1year was sustained for 4 more months. Results 119 patients (32%) achieved DFR1year, while 245 (65%) flared and restarted medication over time. Eleven patients had insufficient data. Of patients in DFR1year, 51 (28%) at baseline fulfilled the 1987 and 2010 classification criteria for RA, 34 (35%) only fulfilled the 2010 criteria and 20 (35%) patients had UA and fulfilled neither criteria (p=0.4). In 77 (65%) DFR1year was sustained up to 16 months. Patients in DFR1year were more often rheumatoid factor (RF) negative than patients not achieving DFR1year, (50% versus 62%, p=0.04). There were no differences in baseline DAS (2.9 (0.9) versus 3.1 (0.8), p=0.12), symptom duration (16 (8-29) versus 17 (9-32), p=0.52) or ACPA positivity (56% versus 61% respectively, p=0.27). Univariable predictors were positive RF (OR 95%CI 0.6 (0.4-0.99)) and high baseline tender joint count (TJC) (OR 95%CI 0.9 (0.9-1.0). Baseline DAS, positive ACPA, age, male sex, being classified as RA according to the 2010 ACR/EULAR criteria or short symptom duration were not predictive for DFR1year. The only independent predictor was RF negativity (OR 95%CI 0.6 (0.4-0.97, adjusted for baseline TJC). Conclusions Of 375 early (rheumatoid) arthritis patients who achieved remission after 4 months of initial combination therapy with methotrexate and prednisone, 32% maintained in remission despite having tapered and discontinued all drugs at 1 year. DFR was sustained up to 16 months in 65% of these. With this treatment strategy, presence of ACPA appears not to preclude drug discontinuation, but patients with positive RF achieved DFR after 1 year somewhat less often than RF negative patients. Disclosure of Interest None Declared

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 (≥3 months, ≤2 years, onset <45 years) 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.

FRI0514 Adding Mri of The Spine To The Asas Classification Criteria for Axial Spondyloarthritis, Redundant or Beneficial? Data from The Spondyloarthritis Caught Early (Space)-Cohort

Background The ASAS definition of a positive MRI is solely based on inflammation in the sacroiliac joints (SIJ), although spinal inflammatory lesions on MRI suggestive of axial Spondyloarthritis (axSpA) may also occur. It is not well known how often inflammation in the spine occurs in absence of inflammation in the SIJ and consequently what the utility is of including inflammation in the spine in the definition of a positive MRI. Objectives To analyze the prevalence of spinal inflammation on MRI in patients with chronic back pain (CBP) at baseline and one-year follow-up, and to evaluate the yield of adding MRI-spine as imaging criterion to the ASAS classification criteria for axial SpA. Methods The SPACE-cohort includes patients with CBP (≥3 months, ≤2 years, onset <45 years) from five participating centres in Europe. All available baseline (BL) and one-year follow-up (FU) MRI of SIJ and spine were scored by 2 well-calibrated readers. MRI-SI were scored according to the ASAS definition. Bone marrow oedema suggestive of axSpA was assessed in the entire spine and only counted if visible on ≥2 consecutive slices. To define a positive MRI-spine, two cut-off values were used: ≥3 inflammatory lesions (ASAS consensus definition) and ≥5 inflammatory lesions (defined as the best cut-off in earlier analyses). Adjudication for the ASAS definition by an experienced reader was performed in case of disagreement and all modalities were considered positive if 2/3 readers agreed. Results All patients with both MRI-spine and MRI-SIJ available at BL (n=329) and FU (n=168) were included in the analyses. At BL 43/329 (13.1%) of patients had a positive MRI-SIJ, of which 7/43 (16.3%) patients had a positive MRI-spine (ASAS consensus definition, ≥3 inflammatory lesions) and 2/43 (4.7%) if defined by ≥5 inflammatory lesions. Positive MRI-SIJ at FU was seen in 28/168 (16.7%) patients, 14 of which were also positive at BL; MRI-spine positivity was identified in 2/28 (7.1%) and 1/28 (3.6%) patients for the ASAS definition defined by ≥3 and ≥5 inflammatory lesions, respectively. In total, 4 patients had a positive MRI-spine and a negative MRI-SIJ: at BL 2 patients according to the ASAS definition of whom 1 also fulfilled the alternative definition. At FU this was 2 (different patients than at baseline) and 0 patients, respectively. Addition of MRI-spine to the classification criteria by the ASAS definition of ≥3 inflammatory lesions would lead to classification of 3 additional patients via imaging arm, with 1 patient already fulfilling the clinical arm. Conclusions In this cohort, a positive MRI-spine in the absence of sacroiliitis on MRI was rarely seen Addition of MRI-spine as an imaging criterion to the ASAS criteria had a low yield in number of classifications. Therefore, performing MRI of the spine at either baseline or one-year follow-up is of little value in patients with short duration of CBP and suspicion of axial SpA. Disclosure of Interest None declared

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.

OP0176 Five Year Outcomes of Remission Steered Treatment Including Drug Tapering Strategies in Early Arthritis Patients

Background The window of opportunity hypothesis suggests that early initiation of treatment targeted at remission in early arthritis patients may avoid chronicity of inflammation and may result in early drug-free remission (DFR). Objectives To assess clinical outcomes of induction therapy followed by 5 years DAS-remission targeted therapy including rapid drug tapering strategies in early arthritis patients. Methods The IMPROVED study included 610 early rheumatoid arthritis (RA, 2010 criteria) or undifferentiated arthritis (UA) patients starting with methotrexate (MTX) and tapered high dose of prednisone. Patients in early DAS-remission (ER) (disease activity score (DAS)<1.6 after 4 months) stopped prednisone and if remission persisted at t=8 months also MTX. Patients not in ER (DAS≥1.6) were randomized to MTX+sulfasalazine+hydroxychloroquine+low dose prednisone (arm 1) or MTX+adalimumab (arm 2), 50 patients were not randomized and were treated “outside of protocol” (OP). Four monthly treatment adjustments aimed at DAS<1.6; if DAS<1.6 taper/stop medication and if DAS≥1.6 restart/intensify medication. Percentages of patients in (drug free) DAS-remission after 5 years were compared between RA and UA patients and the different treatment strategies. Logistic regression analysis was used to identify predictive factors of DAS-remission and DFR after 5 years. Results After 5 years mean±SD DAS decreased and functional ability improved in all treatment groups without differences between arm 1 and 2. 295/610 (48%) patients were in DAS-remission: 220/387 (57%) in the ER group, 31/83 (37%) in arm 1, 29/78 (37%) in arm 2 (p=0.768 arm 1 vs arm 2) and 15/50 (30%) in OP. 134/610 (22%) patients were in DFR: 105/387 (27%) in the ER group, 9/83 (11%) in arm 1, 12/78 (15%) in arm 2 (p=0.374 arm 1 vs arm 2) and 8/50 (16%) in OP. DAS-remission was achieved in similar percentages in RA and UA patients and autoantibody positive (+) vs negative (−) patients. More UA than RA patients were in DFR at year 5 (33% vs 19%, p<0.001), and the same was true for anti-citrullinated protein antibodies (ACPA)− vs ACPA+ patients (31% vs 15%, p<0.001) and rheumatoid factor (RF)− vs RF+ positive patients (28% vs 17%, p<0.001). Between anti-carbamylated antibodies (anti-CarP)+ and − patients there was no difference in DFR rates. Predictors of DAS-remission were age (OR 0.97 (95% CI 0.96–0.99)), symptom duration (0.99 (0.98–0.99)), baseline tender joint count (0.95 (0.90–1.00)) and achieving ER (1.95 (1.23–3.10)) (figure). Predictors of DFR were symptom duration (0.99 (0.97–1.00) and ER (2.67 (1.48–4.84)). ACPA+ was mostly associated with less DFR. Conclusions After 5 years of DAS-remission steered treatment, 48% of early RA and UA patients were in DAS-remission and 22% in DFR. Remission results were better for patients who achieved ER and who had a shorter symptom duration. Remission results were similar for RA and UA patients, randomization arms and autoantibody status, but more UA than RA patients and more autoantibody? than + patients were in DFR. Disclosure of Interest G. Akdemir: None declared, L. Heimans: None declared, R. J. Goekoop: None declared, M. van Oosterhout: None declared, J. B. Harbers: None declared, C. Bijkerk: None declared, G. M. Steup-Beekman: None declared, L. Lard: None declared, P. B. J. de Sonnaville: None declared, B. A. M. Grillet: None declared, T. W. J. Huizinga: None declared, C. F. Allaart Grant/research support from: Year 1 of the IMPROVED study was sponsored by Abbott.

OP0085 Does The Presence of Multiple SpA-Features in Patients with Chronic Back Pain Always Lead To Diagnosis of Axial Spondyloarthritis?

Background The number of clinical SpA-features plays an important role in the Assessment of SpondyloArthritis international Society (ASAS) modified Berlin algorithm for the diagnostic work-up of patients (pts) with a suspicion of axial SpA (axSpA). Objectives To investigate whether all pts with short duration chronic back pain (CBP) and multiple SpA-features are always diagnosed as axSpA by the rheumatologist and to describe the features of these patients. Methods The SPondyloArthritis Caught Early (SPACE)-cohort includes CBP pts (≥3 months, ≤2 years, onset <45 years) from various European rheumatology centres. Baseline data were used for the analyses. Following a fixed protocol all pts underwent a full diagnostic work-up consisting of performance of MRI and radiographs of sacroiliac joints (MRI-SI and X-SI), acute phase reactants, HLA-B27 testing, and assessment of other SpA-features (inflammatory back pain (IBP), good response to NSAIDs, family history for SpA, peripheral arthritis, dactylitis, enthesitis, uveitis, inflammatory bowel disease (IBD), and psoriasis). Local radiologists or rheumatologists from the different centres interpreted MRI-SI and X-SI on presence of sacroiliitis (yes/no) using global assessment as part of routine clinical practice. Total number of SpA-features was calculated excluding sacroiliac imaging and HLA-B27 status. The treating rheumatologist provided clinical diagnosis of pts and the ASAS-criteria for axSpA were used for classification. Results A total of 522 pts were analysed in this study: before sacroiliac imaging and HLA-B27 testing 164/522 (31.4%) pts had no or 1 SpA-feature, 148/522 (28.4%) pts had 2 SpA-features, 85/522 (16.3%) pts had 3 SpA-features, and 125/522 (23.9%) pts had ≥4 SpA-features respectively. IBP, good response to NSAIDs, and positive family history for SpA were most common in all subgroups (0 or 1 feature: 26.8%, 8.5%, and 16.5% of pts; 2 features: 72.3%, 34.5%, 39.9%; 3 features: 87.1%, 60.0%, 54.1%; ≥4 features: 94.4%, 83.2%, 68.0% respectively). Of the pts with 2 and 3 SpA-features with negative X-SI 20/132 (15.2%) and 9/78 (11.5%) did not have axSpA diagnosis despite being HLA-B27+ (Figure 1). All pts with ≥4 SpA-features and X-SI+ (n=28) were diagnosed with axSpA. In contrast to what would be expected by following the modified Berlin algorithm for pts with ≥4 SpA-features, 18/94 pts (19.1%) with negative imaging (of which 4 HLA-B27+), were not diagnosed with axSpA by their rheumatologist. Multivariate regression analysis of presence of SpA-features identified MRI-SI+ (OR 41.7;95%CI 17.3.1–100.5), X-SI+ (OR 31.5;95%CI 3.1–321.0), HLA-B27+ (OR 4.7;95%CI 2.5–8.6), uveitis (OR 4.3;95%CI 1.5–12.7), IBP (OR 2.5;95%CI 1.4–4.7), heel enthesitis (OR 5.5;95%CI 2.7–11.4), IBD (OR 3.2;95%CI 1.2–8.8), elevated CRP/ESR (OR 2.7;95%CI 1.4–5.3), and psoriasis (OR 2.5;95%CI 1.0–6.0) as significant independent predictors of axSpA diagnosis. Conclusions In this cohort of pts with CBP having numerous SpA-features did not automatically lead to a clinical axSpA diagnosis but positive imaging was the main driving factor to diagnosis of axSpA. Disclosure of Interest None declared

FRI0404 Illness Perceptions and Health-Related Quality of Life in Patients with Axial Spondyloarthritis and Other Forms of Chronic Back Pain in The Space-Cohort

Background Knowledge about the impact of illness perceptions on Health-Related Quality of Life (HRQoL) in patients (pts) with axial Spondyloarthritis (axSpA) and other forms of chronic back pain (CBP) is lacking. Objectives To explore the association between illness perceptions and HRQoL in pts with short symptom duration of axSpA and other forms of CBP at baseline. Methods The Spondyloarthritis Caught Early (SPACE) study includes pts with CBP (≥3 months, ≤2 years, onset <45 years) recruited from 5 European centres. The Revised Illness Perception Questionnaire (IPQ-R) was completed at baseline. In the illness identity dimension, pts reported if they have experienced and believed that a certain symptom is CBP related. Other illness perceptions and causal dimensions used 5-point Likert scales (1 strongly disagree, 5 strongly agree). HRQoL was assessed by 36-item Short-Form (SF-36). Scale scores ranged from 0 (worst) to 100 (best). Physical (PCS) and Mental Component Summary (MCS) scores were calculated. Univariable regression models were built for each IPQ-R subscale as independent and PCS or MCS as dependent variable. The models were adjusted for age and gender and stratified in case of effect modification by gender (p<0.10). Results 315 pts were included; 123 fulfilled axSpA ASAS criteria and 192 did not fulfil the criteria. Mean age was 31.3 (SD 8.3) years, mean duration of CBP was 13.2 (SD 7.2) months and 36.5% was male. Mean PCS was 28.0 (SD 16.3) for axSpA pts and 24.9 (SD 14.4) for CBP. As the MCS was only slightly decreased compared to the general population (48.0 (SD 13.3) axSpA and 49.7 (SD 11.5) CBP pts), analyses focused on PCS. Pts reported a mean of 4.3 (axSpA) and 4.8 (CBP) symptoms to be associated with back pain. Most reported symptoms were pain and joint stiffness. All other subscales showed a mean of approximately 3, except psychological attributions, risk factors, immunity and accident (mean approximately 2). All pts attributed their complaints mostly to genetic factors. In both pts groups attribution of multiple symptoms to CBP (Figure 1;-1.8 axSpA, -2.1 CBP) was associated with lower PCS. However more dimensions showed association with PCS in axSpA (8) than CBP pts (6). In male axSpA pts belief in severe consequences (-12.1), more negative emotions towards their complaints (-9.3), and stronger belief of psychological attributions as a cause (-8.8) were associated with lower PCS. Whereas in male CBP pts stronger belief in risk factors (-8.1) and immunity as a cause (-10.0) were associated with lower PCS. More illness coherence was associated with higher PCS in male axSpA (6.2) and all CBP pts (2.8). In women consequences (-6.3, axSpA) and strong emotional representations (-4.0, CBP) were statistically significant. No gender differences were found for risk factors (-6.0) or immunity (-5.7) in axSpA and consequences (-7.9) in CBP pts. Conclusions Negative illness perceptions are associated with lower PCS of HRQoL in pts with axSpA and other forms of CBP. The impact of negative illness perceptions on PCS was more pronounced in men than in women. Disclosure of Interest None declared