Showing papers by "Maxime Dougados published in 2018"

Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force

Abstract: Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey.

Abstract: Objectives Patients with difficult-to-treat rheumatoid arthritis (RA) remain symptomatic despite treatment according to current European League Against Rheumatism (EULAR) management recommendations. These focus on early phases of the disease and pharmacological management. We aimed to identify characteristics of difficult-to-treat RA and issues to be addressed in its workup and management that are not covered by current management recommendations. Methods An international survey was conducted among rheumatologists with multiple-choice questions on disease characteristics of difficult-to-treat RA. Using open questions, additional items to be addressed and items missing in current management recommendations were identified. Results 410 respondents completed the survey: 50% selected disease activity score assessing 28 joints >3.2 OR presence of signs suggestive of active disease as characteristics of difficult-to-treat RA; 42% selected fatigue; 48% selected failure to ≥2 conventional synthetic disease-modifying antirheumatic drugs (DMARDs) AND ≥2 biological/targeted synthetic DMARDs; 89% selected inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily. Interfering comorbidities, extra-articular manifestations and polypharmacy were identified as important issues missing in current management recommendations. Conclusions There is wide variation in concepts of difficult-to-treat RA. Several important issues regarding these patients are not addressed by current EULAR recommendations.

Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers’ effectiveness in axial spondyloarthritis: results of a prospective, multicentre study

Abstract: Objective To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers’ (TNFb) response. Design Prospective observational study with two visits 3 months apart. Patients Adult patients with AxSpa initiating a TNFb. Study groups FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM. Statistical analysis Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response. Results Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups. Conclusion This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.

Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study.

Abstract: Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent and no predictive factors of patient outcome have been identified. Our objective was to investigate the modifications of intestinal microbiota composition in patients suffering from SpA three months after an anti-TNF-α treatment. We performed 16S rDNA sequencing of 38 stool samples from 19 spondyloarthritis patients before and three months after anti-TNF-α treatment onset. SpA activity was assessed at each time using ASDAS and BASDAI scores. Some modifications of the microbiota composition were observed after three months of anti-TNF-α treatment, but no specific taxon was modified, whatever the clinical response. We identified a particular taxonomic node before anti-TNF-α treatment that can predict the clinical response as a biomarker, with a higher proportion of Burkholderiales order in future responder patients. This study suggests a cross-influence between anti-TNF-α treatment and intestinal microbiota. If its results are confirmed on larger groups of patients, it may pave the way to the development of predictive tests suitable for clinical practices.

MRI for diagnosis of axial spondyloarthritis: major advance with critical limitations 'Not everything that glisters is gold (standard)'.

Abstract: Recognition of axial spondyloarthritis (SpA) remains challenging, as no unique reference standard is available to ascertain diagnosis. Imaging procedures have been used for long in the field, in particular pelvic radiography, to capture structural changes evocative of sacroiliitis, the key feature in SpA. The introduction of MRI of the sacroiliac joints (SIJs) has led to a major shift in recognition of the disorder. MRI has been shown to detect the initial inflammatory processes, in particular osteitis depicted by bone marrow oedema, even in patients having not yet developed structural lesions. In addition, MRI has revealed a previously under-recognised very early clinical phase of the disease where patients have symptomatic axial involvement, but no structural changes. However, what constitutes a 'positive MRI' in SpA remains controversial, since both sensitivity and specificity show limitations, and interpretation of MRI lesions in daily practice is critically dependent on the clinical context. There is growing evidence that integration of the assessment of structural changes on dedicated T1 weighted-sequences on MRI may enhance diagnostic utility. The performance of MRI in detecting structural lesions in the SIJs may even be superior to traditional evaluation by pelvic radiography. These findings launched a debate on imaging in SpA, whether MRI, which is advancing early recognition of disease and shows superiority to detect structural changes, should replace traditional conventional radiography of the SIJs.

An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS

Abstract: Introduction In a previous phase, 12 draft definitions for clinically important worsening in axial spondyloarthritis (axSpA) were selected, of which 3 were based on absolute changes in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP (ASDAS). The objective here was to select the best cut-off for ASDAS for clinically important worsening in axSpA for use in clinical trials and observational studies. Methods An international longitudinal prospective study evaluating stable patients with axSpA was conducted. Data necessary to calculate ASDAS were collected at two consecutive visits (spaced 7 days to 6 months). Sensitivity and specificity of the three cut-offs for change in ASDAS were tested against the patient’s subjective assessment of worsening as the external standard (ie, the patient reporting that he had worsened and felt a need for treatment intensification). Final selection was made by a consensus and voting procedure among Assessment of SpondyloArthritis International Society (ASAS) members. Results In total, 1169 patients with axSpA were analysed: 64.8% were male and had a mean age of 41.7 (SD 12.4) years. At the second visit, 127 (10.9%) patients judged their situation as worsened. Sensitivity and specificity for an increase of at least 0.6, 0.9 and 1.1 ASDAS points to detect patient-reported worsening were 0.55 (Se) and 0.91 (Sp), 0.38 (Se) and 0.96 (Sp), and 0.33 (Se) and 0.98 (Sp), respectively. The ASAS consensus was to define clinically important worsening as an increase in ASDAS of at least 0.9 points. Conclusion This data-driven ASAS consensus process resulted in an ASDAS-based cut-off value defining clinically important worsening in axSpA for use in trials.

Association of Comorbidities in Spondyloarthritis With Poor Function, Work Disability, and Quality of Life : Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study

Abstract: Objective Comorbidities add to the burden of disease and its complexity, and may prevent the achievement of treat-to-target goals. The objective of this study was to study the relationship between comorbidities and key disease outcomes in Spondyloarthritis, namely function, work ability and quality of life. Methods Patients from the multi-national (22 countries), cross-sectional ASAS-COMOSPA study were included in the analysis provided they fulfilled the ASAS criteria. Data on comorbidities based on both self- and physician-report were collected through questionnaires and were subsequently used to compute the Rheumatic Disease Comorbidity Index (RDCI). Univariable and multivariable (adjusted for relevant confounders) multilevel (with country as a random effect) linear or logistic (as appropriate) regression analyses were conducted to investigate the relationship between the RDCI and: (1) functional ability; (2) work ability; (3) quality of life. Results In total, 3370 of 3984 (85%) patients recruited fulfilled the ASAS criteria: 66% were male, mean (SD) age was 43 (14) years, mean (SD) disease duration was 8.4 (9.5) years and mean (SD) RDCI was 0.7 (1.1). At least one comorbidity was reported in 51% of patients; 9% had ≥3 comorbidities. RDCI was independently associated with higher BASFI (β=0.37;95%CI [0.30,0.43]); lower EuroQol five dimensions questionnaire (EQ5D:β=-0.03; [-0.04,-0.02]); less work employment (OR=0.83; [0.76,0.91]); higher absenteeism (β=1.18; [1.04,1.34]) and higher presenteeism (β=1.42; [1.26,1.61]). Conclusion Comorbidities in SpA adversely influence physical function, work ability and quality of life and are important to take into account in daily clinical practice. This article is protected by copyright. All rights reserved.

Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis.

Abstract: Objective To compare 2 years of radiographic sacroiliac joint (SIJ) changes in patients with recent onset axial spondyloarthritis (axSpA) receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). Methods Endpoints were changes at week 104 per the modified New York (mNY) grading system in total SIJ score (primary endpoint) and net percentage of patients with progression defined three ways. Treatment effect was analysed with and without adjustment for baseline covariates. Results At 104 weeks, total SIJ score improved in the etanercept group (n=154, adjusted least-squares mean change: –0.14) and worsened in the control group (n=182, change: 0.08). The adjusted difference between groups (etanercept minus control) was –0.22 (95% CI –0.38 to –0.06), p=0.008. The net percentage of patients with progression was significantly lower in the etanercept versus the control group for two of three binary endpoints: –1.9% versus 1.6% (adjusted difference for etanercept minus control: –4.7%,95% CI –9.9 to 0.5, p=0.07) for change in mNY criteria; –1.9% versus 7.8% (adjusted difference: –18.2%,95% CI –30.9 to –5.6, p=0.005) for change ≥1 grade in ≥1 SIJ; and –0.6% versus 6.7% (adjusted difference: –16.4%,95% CI –27.9 to –5.0, p=0.005) for change ≥1 grade in ≥1 SIJ, with shift from 0 to 1 or 1 to 0 considered no change. Conclusion Despite the slow radiographic SIJ progression rate over 2 years in axSpA, this study suggests a lower rate of progression in the SIJ with etanercept than without anti-tumour necrosis factor therapy. Trial registration numbers NCT01258738, NCT01648907; Post-results.

Methods to improve medication adherence in patients with chronic inflammatory rheumatic diseases: a systematic literature review.

Abstract: Objective Lack of adherence to treatment is frequent in chronic inflammatory rheumatic diseases and is associated with poorer outcomes. The objective of this study was to describe and evaluate interventions that have been proposed to enhance medication adherence in these conditions. Methods A systematic literature review was performed in Pubmed, Cochrane, Embase and clinicaltrials.gov databases completed by the rheumatology meeting (ACR, EULAR and SFR) abstracts from last 2 years. All studies in English or French evaluating an intervention to improve medication adherence in chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondyloarthritis (SpA), crystal related diseases, connective tissue diseases, vasculitis and Still’s disease) were included. Interventions on adherence were collected and classified in five modalities (educational, behavioural, cognitive behavioural, multicomponent interventions or others). Results 1325 abstracts were identified and 22 studies were finally included (18 studies in RA (72%), 4 studies in systemic lupus erythematosus (16%), 2 studies in SpA (8%) and 1 study in gout (4%)). On 13 randomised controlled trials (RCT) (1535 patients), only 5 were positive (774 patients). Educational interventions were the most represented and had the highest level of evidence: 8/13 RCT (62%, 1017 patients) and 4/8 were positive (50%). In these studies, each patient was individually informed or educated by different actors (physicians, pharmacists, nurses and so on). Supports and contents of these educational interventions were heterogenous. Conclusion Despite the importance of medication adherence in chronic inflammatory rheumatic disorders, evidence on interventions to improve medication adherence is scarce.

Modification of structural lesions on MRI of the sacroiliac joints by etanercept in the EMBARK trial: a 12-week randomised placebo-controlled trial in patients with non-radiographic axial spondyloarthritis

Abstract: Objective To evaluate the impact on structural lesions observed on MRI in the sacroiliac joints (SIJ) at 12 weeks in patients with non-radiographic axial spondyloarthritis (nr-axSpA) receiving etanercept or placebo in EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in nr-axSpA, a 104 week study). Methods Patients were randomised to double-blind etanercept 50 mg/week or placebo for 12 weeks. Structural lesions at baseline and 12 weeks were scored by two independent readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score (SSS) on T1-weighted MRI. Change in SPARCC SSS and correlation with improvement in clinical outcomes was evaluated. Results MRI scans from 185 patients (etanercept, n=88; placebo, n=97) were reviewed. At baseline, there were no significant differences in mean SPARCC SSS between etanercept and placebo. From baseline to 12 weeks, change in mean SPARCC SSS was significantly greater for etanercept than placebo for erosion (–0.57 vs –0.08, respectively, adjusted p value=0.017) and backfill (0.36 vs 0.06, adjusted p value=0.022). A treatment difference was also present for the subgroup of patients with SIJ inflammation on MRI (SPARCC bone marrow oedema ≥2): erosion: –0.81 versus –0.13 for etanercept versus placebo, respectively, p=0.007; backfill: 0.48 versus 0.08, respectively, p=0.032. Decrease in erosion and increase in backfill correlated with improvement in more clinical outcomes for etanercept than placebo. Conclusion Treatment with etanercept was associated with significantly greater reduction in erosions and increase in backfill at 12 weeks compared with placebo, consistent with a very early reparative response to antitumour necrosis factor therapy. The impact on disease progression in spondyloarthritis should be studied further. Trial registration number NCT01258738; Post-results.

Imaging Findings Suggestive of Axial Spondyloarthritis in Diffuse Idiopathic Skeletal Hyperostosis

Abstract: Objective To describe the magnetic resonance imaging (MRI) findings in diffuse idiopathic skeletal hyperostosis (DISH) patients and to assess the proportion of DISH patients whose MRI findings would fulfill the Assessment of Spondyloarthritis International Society (ASAS) criteria for a positive MRI of axial spondyloarthritis (SpA). Methods This study involved all DISH patients who had a spine or sacroiliac (SI) joint MRI performed between January 2009 and December 2014. Sociodemographic and clinical data were collected. Available radiographs and MRI were analyzed and blindly scored by an experienced reader, using the Spondyloarthritis Research Consortium of Canada (SPARCC) scores for both spine and SI joint MRI. Results A total of 53 symptomatic DISH patients was included in the analysis. The mean ± SD SPARCC score of the spine was 18.3 ± 23.4. Thirty-five patients (67.3%) had at least 1 fatty corner. Thirty patients (57.7%) met the ASAS definition of a spine MRI suggestive of axial SpA, but only 6 patients (15.8%) with an available SI joint MRI had sacroiliitis according to ASAS criteria. Only 1 patient (3.3%) had ≥3 erosions on the SI joint. Conclusion Inflammatory lesions of the spine are common on the MRI of symptomatic DISH patients, and more than half fulfilled the ASAS criteria for a spine MRI suggestive of axial SpA. However, only a few patients met the ASAS definition of active sacroiliitis, suggesting that MRI of the SI joint but not of the spine might allow the differential diagnosis of DISH versus axial SpA in the elderly.

Inequity in biological DMARD prescription for spondyloarthritis across the globe: results from the ASAS-COMOSPA study

Abstract: Objectives The value of biological disease-modifying antirheumatic drugs (bDMARDs) in spondyloarthritis (SpA) is well recognised, but global access to these treatments can be limited due to high costs and other factors. This study explores country variation in the use of bDMARDs in SpA in relation to country-level socioeconomic factors. Methods Patients fulfilling the Assessment in SpondyloArthritis International Society (ASAS) SpA criteria in the multinational, cross-sectional ASAS Comorbidities in Spondyloarthritis study were studied. Current use of bDMARDs or conventional synthetic DMARDs (csDMARDs) was investigated in separate models, with multilevel logistic regression analysis, taking the country level into account. Contribution of socioeconomic factors, including country health expenditures, gross domestic product and human development index as independent country-level factors, was explored individually, in models adjusted for sociodemographic as well as clinical variables. Results In total, 3370 patients from 22 countries were included (mean (SD) age 43 (14) years; 66% male; 88% axial disease). Across countries, 1275 (38%) patients were bDMARD users. Crude mean bDMARD use varied between 5% (China) to 74% (Belgium). After adjustment for relevant sociodemographic and clinical variables, important variation in bDMARD use across countries remained (P Conclusions There remains important residual variation across countries in bDMARD uptake of patients with SpA followed in specialised SpA centres. This is independent of well-known factors for bDMARD use such as clinical and country-level socioeconomic factors.

Prevalence of degenerative changes and overlap with spondyloarthritis-associated lesions in the spine of patients from the DESIR cohort.

Abstract: Objectives To describe the prevalence of degenerative changes on MRI and conventional radiographs of the spine in a young population with suspicion of axial spondyloarthritis (axSpA) and assess whether it is possible to discriminate between degenerative changes and lesions associated with axSpA. Methods Whole spine MRI and cervical and lumbar radiographs of patients ≥18 years with chronic back pain (≥3 months, ≤3 years, onset Results In 456/648 (70.4%) patients (46.8% men, mean age 33.6), degenerative lesions were found with similar percentages in patients with no axSpA and with axSpA (72.4% and 69.2%, p=0.45). Modic changes were found more often in patients with no axSpA (29/239, 12.1%) versus patients with axSpA (19/409, 4.6%, p=0.01). Other lesions were evenly distributed. Overlap was minimal in 19 patients (3.0%) and 32/14 674 (0.2%) VUs for SpA reader 1 and in 23 patients (3.6%) and 34/14 674 VUs (0.2%) for SpA reader 2. Conclusion The prevalence of degeneration is high in an early inflammatory back pain cohort. Discrimination between degeneration and axSpA lesions is very well possible with little overlap between degenerative and axSpA readings.

Comorbidities in spondyloarthritis including psoriatic arthritis.

Abstract: Comorbidities in spondyloarthritis (SpA) including psoriatic arthritis have to be differentiated to the concept of clinical features of SpA (e.g., uveitis, psoriasis, and inflammatory bowel disease). In addition to atherosclerosis-related cardiovascular diseases, the most frequent comorbidities in SpA are osteoporosis, fibromyalgia, and depression. Moreover, the current available drug therapies (e.g., NSAIDs, corticosteroids, and biologics) might increase the risk of some comorbidities such as infections and gastrointestinal disorders. Awareness about these comorbidities is crucial to improve their screening and management. For this purpose, any systematic periodical review should integrate a program (ideally internationally standardized) focused on comorbidities.

Vitamin D status in spondyloarthritis: results of the ASAS-COMOSPA international study

Abstract: OBJECTIVES Spondyloarthritis (SpA) encompasses both bone production and bone loss, and the latter is particularly linked to inflammation. Vitamin D deficiency has been associated with several inflammatory conditions (i.e. cardiovascular disease, rheumatoid arthritis), but it has been poorly evaluated in SpA patients. We aimed to a) describe the prevalence of vitamin D deficiency in SpA patients worldwide; b) compare SpA patients with and without vitamin D deficiency in terms of disease phenotype, activity severity and comorbidities. METHODS This is an ancillary study of the ASAS-COMOSPA study initiative, an international cross-sectional study of patients with SpA. Demographics, patients' phenotype, disease activity/severity measures and comorbidities were assessed. Serum 25-hydroxyvitamin D (25OHD) deficiency was defined as <20 ng/mL (<50 nmol/L). STATISTICAL ANALYSIS a) prevalence of vitamin D deficiency; b) comparison of the disease presentation/activity/severity and comorbidities in the group of patients with and without vitamin D deficiency by bi-variable and multivariable analysis. RESULTS Vitamin D deficiency was observed in 527(51.2%) of the 1030 patients with available data who were not receiving any supplementation. Vitamin D deficiency was independently associated with the presence of radiographic sacroiliitis (OR=2.1 [95%CI1.3; 3.3]) and a 25OHD measured in winter and spring (OR=1.88 [95%CI 1.2; 2.9]). No independent association between vitamin D deficiency and comorbidities was found. CONCLUSIONS This study suggests that vitamin D deficiency is common in SpA worldwide and is associated with season but also with more severe forms of SpA.

A randomised, double-blind, placebo-controlled study assessing the efficacy of high doses of vitamin D on functional disability in patients with rheumatoid arthritis.

Abstract: OBJECTIVES: To evaluate the short-term efficacy of vitamin D (cholecalciferol) supplementation on functional disability in RA patients. METHODS: 1) Patients: RA (ACR 1987 revised criteria) in non-remission (DAS28 >2.6) whose treatment was not expected to be changed over a 3-month period following inclusion and presenting with vitD deficits (serum 25OHD <30ng/mL). 2) Study design: prospective randomised placebo-controlled trial (NCT02243800). 3) Study arms: either vitD ampoules (cholecalciferol 100,000IU) or placebo. 4) Outcome measures: primary: improvement in patients' functional disability using the Health Assessment questionnaire (HAQ); secondary: improvement in DAS28ESR, DAS28CRP, ESR, CRP, RAID score, fatigue (EVA and FACIT), and SF36. RESULTS: Overall, 59 patients were included, 83.1% females, aged 59.8±10.9 years on average, with RA for 17.0±9.7 years. Thirty patients received placebo and 29 vitD. At 6 months, HAQ scores tended to be increased in the placebo group (+0.08±0.25), while slightly numerically decreased in the vitD group (-0.03±0.23) (p=0.11). After adjusting for age, gender, season, and initial vitD status, the between-group difference achieved statistically significance (p=0.046). After adjusting for age, gender, season, and initial vitD status, there was no significant difference in the secondary criteria between the 2 groups except for ESR and CRP (p=0.002 and 0.04, respectively). CONCLUSIONS: In this randomised, double-blind, placebo-controlled clinical trial in patients with RA and VitD deficiency, high doses of cholecalciferol resulted in a statistically significant improvement in functional disability at month 6, which, however, was clinically not relevant.

Work participation in spondyloarthritis across countries: analysis from the ASAS-COMOSPA study

Abstract: Objectives To explore the role of individual and country level socioeconomic (SE) factors on employment, absenteeism and presenteeism in patients with spondyloarthritis (SpA) across 22 countries worldwide. Methods Patients with a clinical diagnosis of SpA fulfilling the ASAS classification criteria and in working age (≤65 years) from COMOSPA were included. Outcomes of interest were employment status, absenteeism and presenteeism, assessed by the Work Productivity and Activity Impairment Specific General Health questionnaire. Three multivariable models were built (one per outcome) using mixed-effects binomial (for work status) or ordinal regressions (for absenteeism and presenteeism), with country as random effect. The contribution of SE factors at the individual-level (eg, gender, education, marital status) and country-level (healthcare expenditure (HCE) per capita, Human Development Index (HDI) and gross domestic product per capita) SE factors, independent of clinical factors, was assessed. Results In total, 3114 patients with SpA were included of which 1943 (62%) were employed. Physical function and comorbidities were related to all work outcomes in expected directions and disease activity also with absenteeism and presenteeism. Higher education (OR 4.2 (95% CI 3.1 to 5.6)) or living in a country with higher HCE (OR 2.3 (1.5 to 3.6)) or HDI (OR 1.9 (1.2 to 3.3)) was positively associated with being employed. Higher disease activity was associated with higher odds for absenteeism (OR 1.5 (1.3 to 1.7)) and presenteeism (OR 2.1 (1.8 to 2.4)). No significant association between individual-level and country-level SE factors and absenteeism or presenteeism was found. Conclusions Higher education level and higher country SE welfare are associated with a higher likelihood of keeping patients with SpA employed. Absenteeism and presenteeism are only associated with clinical but not with individual-level or country-level SE factors.

Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients.

Abstract: The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤ 1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA > 1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N = 731, French ESPOIR cohort) or established RA (N = 236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p = 0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.

LB0001 Dual neutralisation of il-17a and il-17f with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study

Abstract: Background Dual neutralisation of IL-17F, in addition to IL-17A, reduces inflammation 1 to a greater extent than inhibition of IL-17A alone in disease–relevant cell models. Bimekizumab, a monoclonal antibody that potently and selectively neutralises both IL-17A and IL-17F, provided rapid and substantial clinical improvements in studies evaluating patients with psoriasis 2 and psoriatic arthritis. 1 Objectives Assess 12 week efficacy and safety of bimekizumab in patients with active AS; the primary objective was to assess the ASAS40 dose-response relationship at Week 12. Methods In this ongoing 48 week study (NCT02963506: double blind to Week 12 then dose blind to Week 48), 303 patients with active (BASDAI ≥4; spinal pain ≥4 [0–10 numerical rating scale]) AS, fulfilling the modified New York criteria, were randomised 1:1:1:1:1 to receive subcutaneous bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo Q4W, for 12 weeks. Prior exposure to 1 anti-TNF therapy was permitted. The primary endpoint was ASAS40 response rate at Week 12. Secondary endpoints (ASAS20 and ASAS5/6 response rate and change from baseline in BASDAI and ASDAS-CRP at Week 12) and safety were also assessed. Results Overall, 297 (98.0%) patients completed the 12 week double-blind period. The majority of patients were male (84.5%) with a mean (SD) age of 42.2 (11.8) and median (min, max) symptom duration of 13.3 (0.3, 48.2) years; baseline characteristics were similar among treatment groups (median [min, max] hs-CRP: 12.1 [0.3, 130.6] mg/L; mean [SD] BASDAI: 6.5 [1.4]; ASDAS-CRP: 3.9 [0.8]; prior anti-TNF exposure: 11.2%). At Week 12, there was a significant (p 0.05, all comparisons). Compared with placebo, greater reductions from baseline were achieved with bimekizumab for both BASDAI (figure 1) and ASDAS-CRP (LS mean [SE] change from baseline: 16 mg: −1.0 [0.15]; 64 mg: −1.6 [0.15]; 160 mg: −1.4 [0.16]; 320 mg: −1.5 [0.16]; placebo: −0.4 [0.16]; p Conclusions The primary and key secondary objectives were achieved; dual neutralisation of IL-17A and IL-17F with bimekizumab provided clinically meaningful improvements in disease outcome measures. No new safety signals were observed versus previous studies. 1 2 References [1] Glatt. Ann Rheum Dis2018;77:523–532. [2] Glatt. Br J Clin Pharmacol2017;83:991–1001. Acknowledgements Study funded by UCB Pharma. The authors acknowledge K Alexander of iMed Comms, an Ashfield Company, for medical writing support funded by UCB Pharma in accordance with GPP3. Disclosure of Interest D. van der Heijde Consultant for: AbbVie; Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, Employee of: Director of Imaging Rheumatology BV, L. S. Gensler Grant/research support from: AbbVie, Amgen, UCB, Consultant for: Novartis, Lilly, Janssen, A. Deodhar Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, X. Baraliakos Grant/research support from: Abbvie, Pfizer, MSD, UCB, Novartis, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB, D. Poddubnyy Grant/research support from: Abbvie, MSD, Novartis, Consultant for: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, UCB, M. K. Farmer Employee of: UCB Pharma, D. Baeten Employee of: UCB Pharma, T. Kumke Employee of: UCB Pharma, M. Oortgiesen Shareholder of: UCB Pharma, Employee of: UCB Pharma, M. Dougados Grant/research support from: UCB, Lilly, Pfizer, AbbVie, Merck, Consultant for: UCB, Lilly, Pfizer, AbbVie, Merck

Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis: Post hoc analyses of overall and Japanese results from two phase 3 clinical trials

Abstract: Objective: To examine patient-reported outcomes (PROs) in patients with different rheumatoid arthritis (RA) disease activity levels and identify residual symptoms.Methods: Post hoc analyses of overall and Japanese data from two randomized controlled trials including RA patients with previous inadequate responses to methotrexate (NCT01710358) or no/minimal previous disease-modifying antirheumatic drug treatment (NCT01711359) (sponsor: Eli Lilly and Company). Week 24 assessments were disease activity (Simplified Disease Activity Index, Disease Activity Score/Disease Activity Score 28 joints-erythrocyte sedimentation rate) and PROs (pain visual analog scale [VAS], morning joint stiffness [MJS], Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, and Medical Outcomes Study Short Form 36 Health Survey Physical and Mental Component Scores).Results: Patients achieving remission/low disease activity (LDA) at Week 24 had larger/significant improvement...

Uncovering the heterogeneity of disease impact in axial spondyloarthritis: bivariate trajectories of disease activity and quality of life

Abstract: Objective The goal of managing axial spondyloarthritis (axSpA) is to improve and maintain patients’ health-related quality of life (HRQoL), mainly through targeting towards low disease activity. Here, we aim to gain insight into the joint evolution of HRQoL and disease activity by identifying and characterising latent subgroups of patients with longstanding disease displaying similar trajectories throughout 8 years of follow-up. Methods Data from Outcome in Ankylosing Spondylitis (AS) International Study (n=161) and Groningen Leeuwarden AS cohort (n=264) were used. Biennially, HRQoL was assessed by AS Quality of Life (ASQoL) and disease activity by AS Disease Activity Score—C reactive protein (ASDAS-CRP). Bivariate trajectories of these outcomes were estimated by group-based trajectory modelling. Next, trajectories were profiled by comparing the latent groups with respect to baseline factors using analysis of variance and χ² test. Results Five bivariate trajectories were distinguished, in which ASQoL and ASDAS-CRP were tightly linked: (t1) low impact of disease; (t2) moderate impact; (t3) high impact with major improvement; (t4) high impact with some improvement; (t5) very high impact. Profiling revealed, for example, that (t1) was characterised by male gender and Human Leucocyte Antigen B27 positivity; (t3) by younger age, shorter symptom duration and biological intake and (t5) by the highest proportion of females. Conclusions We identified five bivariate trajectories of HRQoL and disease activity demonstrating a clear mutual relationship. The profiles revealed that both individual-related and disease-related features define the type of disease course in respect to HRQoL and disease activity in axSpA. This may provide clinicians insight into the differences among patients and help in the management of the disease.

The Prevalence of Renal Impairment in Patients with Spondyloarthritis: Results from the International ASAS-COMOSPA Study

Abstract: Objective. To assess the prevalence and association of renal dysfunction in patients with spondyloarthritis (SpA). Methods. The ASAS-COMOSPA (Assessment of Spondyloarthritis international Society-COMOrbidities in SPondyloArthritis) was an international study (22 participating countries from 4 continents) investigating comorbidities in SpA. Renal function was assessed based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease equation. SpA characteristics and risk factors for renal impairment were collected. Nonsteroidal antiinflammatory drug (NSAID) use was assessed based on current intake (last 3 mos). Results. Of the 3984 patients recruited, 2098 (52.6%) were analyzed after excluding outliers and patients with no available eGFR measurement [male sex: 63.5%; age: 45.3 yrs; disease duration: 8.6 years; HLA-B27+: 73.1%; Bath Ankylosing Spondylitis Activity Index (BASDAI): 3.6/10]. Overall, 153 patients (5.2%, mean age: 53.6 yrs) exhibited an eGFR 60 yrs: OR 6.2), HLA-B27 positivity (OR 0.51), and CRP (OR 1.3) remained significantly associated with eGFR Conclusion. Renal impairment was associated with age, HLA-B27 positivity, and inflammation, though not with CV risk factors, disease severity, or NSAID intake in patients with SpA.

Immunogenicity and persistence of a prime-boost re-vaccination strategy for pneumococcal vaccines in patients with rheumatoid arthritis

Abstract: Objectives: Patients with rheumatoid arthritis (RA) are at an increased risk of Pneumococcal infections. Immunogenicity and persistence of a prime-boost revaccination strategy using 13-valent/23-valent anti-pneumococcal vaccines was evaluated in patients with RA treated by Methotrexate (MTX) and anti-TNF. Method: Twenty-four patients with RA received one dose of PCV13 (Prevenar13®; Pfizer) followed two months later by one dose of PPV23 (Pneumovax®, Merck). Concentrations of IgG specific for 7 serotypes common to both vaccines and 3 uncommon serotypes, included only in the PPV23 were measured by ELISA and Opsonophagocytic Assay (OPA) at baseline and after 4, 12 and 24 months post-vaccine. Results: Similar percentages of protection were found at 4 months (63% vs. 55%), 12 months (54% vs. 50%) and 24 months (52% vs. 55%) for the 7 common and 3 uncommon serotypes when antibody titers were assayed by ELISA. Based on functional antibody measurements by OPA, a decrease of protected patients was observed 24 months after vaccine with only 19% of patients protected compared to 29% at baseline. Conclusion: Although the combined pneumococcal revaccination strategy induces good protection in the short term in RA patients, this protection does not persist beyond two years with levels of functional antibody decreasing below pre-vaccine levels. We did not observe a higher efficacy of the conjugate vaccine compared to the polysaccharide vaccine. Our results clearly question the advantage of the prime-boost strategy as it highlight the possible hyporesponse induced by PPV23 against the immune response elicited by the primo-injection of the PCV13 vaccine.

Sick leave and its predictors in ankylosing spondylitis: long-term results from the Outcome in Ankylosing Spondylitis International Study.

Abstract: Objective To investigate the occurrence of ankylosing spondylitis (AS)-related sick leave (SL) over 6 12 years and explore factors predicting first and recurrent SL. Methods Data from employed patients from the Outcome in Ankylosing Spondylitis International Study were used. At each visit, patients indicated the occurrence of SL (yes/no) in the previous inter-assessment period. Cox regressions predicted a first episode of SL. Generalised estimating equations (GEE) explored the association between SL and (time-lagged) predictors. To investigate whether SL predicts new SL, SL in the first year was included as covariate in a separate analysis. Results 139 patients (76% males, mean (SD) age 38.7 (10.0) years) were at risk for SL for an average period of 7.9 years, of whom 88 (63%) reported any SL. In both the Cox baseline predictors model (HR (95% CI)) and the time-varying GEE models (OR (95% CI)), AS Disease Activity Score (1.67, 1.23 to 2.28 (HR); 1.48, 1.07 to 2.03 (OR)); Bath AS Disease Activity Index (1.33, 1.18 to 1.51 (HR); 1.31, 1.15 to 1.49 (OR)), Bath AS Functional Index (1.17, 1.02 to 1.34 (HR); 1.31, 1.16 to 1.47 (OR)) and comorbidity at baseline (GEE only, 1.52, 1.00 to 2.29 (OR)) were associated with SL in separate models, but only in patients with low educational attainment. SL in the first year was an independent predictor of SL over time (OR: 2.62 to 8.37 in different models, all p Conclusion Disease activity and physical function predicted first and recurrent SL, but only in patients with low educational attainment. Prior SL results in future SL, and SL should therefore be a signal for support to prevent future adverse work outcome.

Can power Doppler ultrasound of the entheses help in classifying recent axial spondyloarthritis? Data from the DESIR cohort.

Abstract: Early diagnosis of axial spondyloarthritis (axSpA) remains a challenge due to the lack of specificity of clinical symptoms and variable prevalence of axial imaging findings permitting a definite diagnosis. Power Doppler ultrasonography (PDUS) of the entheses has demonstrated to be a potential useful tool for the classification and diagnostic management of early SpA independently of the phenotype. Objectives To assess the classification value (sensitivity and specificity) of PDUS-defined enthesitis for identifying patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA (ASAS+) in patients with recent inflammatory back pain (IBP) (the DESIR (DEvenir des Spondylarthropathies Indifferenciees Recentes) cohort). Methods Baseline PDUS was performed at eight entheseal sites, and PDUS enthesitis was defined by the presence of vascularisation at entheseal insertion. Results 402 patients from the DESIR cohort underwent a PDUS evaluation. PDUS enthesitis was detected in 58 (14.4%) patients of whom 40 (14.2%) belonged to the ASAS+ patients and 18 (17%) to the ASAS- patients. The sensitivity of PDUS enthesitis was 13.9% and the specificity was 83.5%, with a positive predictive value of 69% and 26.8% of negative predictive value for meeting ASAS criteria for axSpA. Of the 18 ASAS- patients with positive PDUS, 59% fulfilled Amor’s criteria, 88% European Spondyloarthropathy Study Group criteria and 59% both. Conclusions In a cohort of patients with recent IBP, the prevalence of PDUS enthesitis was low (14.4%); however, its specificity for classifying patients as axSpA according to ASAS criteria was high (83.5%). PDUS enthesitis might be of additional value for classifying as patients with axSpA IBP who do not fulfil ASAS criteria.

SAT0199 Switch from innovator etanercept to biosimilar etanercept in inflammatory rheumatic diseases: the experience of cochin university hospital paris-france.

Abstract: Background: Etanercept biosimilar (bETN) is available for treatment of spondyloarthritis (SpA) and rheumatoid arthritis (RA) since 2016 in France. Data showing effectiveness and safety of bETN are still limited. Objectives: 1/To evaluate the RA and SpA patients’ and treating rheumatologists’ characteristics associated with the switch 2/To evaluate the safety and efficiency of bETN. Methods: Patients: All the patients receiving innovator etanercept for at least 3 months on October 2016 and monitored in the department of rheumatology B of Cochin hospital. Physicians: All the 9 physicians in charge of at least one patient. Study design: After information (one hour session) on the biosimilars, all the physicians were invited to propose a switch from innovator etanercept to bETN. Data collected: physicians’ characteristics, patients’ characteristics (demographics, diagnosis of the rheumatic disease, disease activity parameters). Results: Of the 435 outpatients who had received etanercept; 304 were receiving etanercept in 2016 and 183 were eligible for a potential switch (the remaining 121 patients did not attend any out-patient-clinic between October 1st 2016 and April 1st 2017). The percentage of patients who switched to bETN was 51.6% (94 patients). This switch was more frequently performed in patients monitored by older physicians (mean age: 50.4±14.3 vs 44.8±11.3, p=0.005) and by physicians with a full-time academical position (56.4 % vs 13.5 %, p The patients’ characteristics were similar: % RA (51.1% vs 44.9%), age (52.1±15 vs 50.5±15), female gender (57.4% vs 51.6%), disease duration (16.8±11.9 vs 14.8±11.3) except for the NSAID intake (28.3 % vs 12.3 %, p=0.014) and the global evaluation (25.2±19.4 vs 19.1±21.8, p=0.02) in the switchers vs non-switchers, respectively. However, no independent factors were associated with the switch in the multivariate analysis. The bETN retention rate was 83 % [0.76–0.92] after a 6 month follow-up period. The bETN was discontinued in 26 patients with the following reasons: inefficiency 13 patients, adverse event 13 patients (painful injection site n = 4, fatigue = 2, pruritus n = 2, “allergic reaction” n =1, headache n = 1, pollakiuria n = 1, dizziness n = 1, supply problem n = 1). The univariate analysis aimed at evaluating the baseline predisposing factors of bETN discontinuation overtime picked up the baseline objective sign of inflammation (defined by CRP≥6 mg/L or ESA ≥28 mm) (OR=4.18 [1.19 – 14.66] p=0.0256), p=0.002) and global disease activity score (OR = 1.57 [1.04 – 2.36], p=0.03). Nevertheless, no independent factors were associated with the switch in the multivariate analysis. There was no difference in the changes in the disease activity parameters in both the completer and ITT population. Conclusions: This study suggests that: 1/The probability to switch from etanercept innovator to bETN was mainly related to physicians’ behavior 2/Using an open design, the percentage of patients complaining of a lower efficiency and/or a worse safety profile of the biosimilar was high 3/There was no objective parameter permitting to conclude at a lower efficiency and/or a worse safety profile of the bETN in comparison to the innovator etanercept. Disclosure of Interest: None declared