Showing papers by "Maxime Dougados published in 2017"

Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study

Abstract: Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage. Trial registration number NCT01721057; Results.

Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

Abstract: Objectives To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA). Methods An SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials. Results For GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated. For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations. Conclusions Addition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.

Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

Abstract: Objectives To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations. Methods MEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained. Results The RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or ‘spacing’ was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B). Conclusions This systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.

Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA.

Abstract: Objective The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA.

Risk factors of serious infections in patients with rheumatoid arthritis treated with tocilizumab in the French Registry REGATE.

Abstract: Objectives Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA. Methods A total of 1491 RA patients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed. Results Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data. Conclusion The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.

Can we use structural lesions seen on MRI of the sacroiliac joints reliably for the classification of patients according to the ASAS axial spondyloarthritis criteria? Data from the DESIR cohort.

Abstract: Objectives Investigating the utility of adding structural lesions seen on MRI of the sacroiliac joints to the imaging criterion of the Assessment of SpondyloArthritis (ASAS) axial SpondyloArthritis (axSpA) criteria and the utility of replacement of radiographic sacroiliitis by structural lesions on MRI. Methods Two well-calibrated readers scored MRI STIR (inflammation, MRI-SI), MRI T1-w images (structural lesions, MRI-SI-s) and radiographs of the sacroiliac joints (X-SI) of patients in the DEvenir des Spondyloarthrites Indifferenciees Recentes cohort (inflammatory back pain: ≥3 months, Results Of the 582 patients included in this analysis, 418 fulfilled the ASAS axSpA criteria, of which 127 patients were modified New York (mNY) positive and 134 and 75 were MRI-SI-s positive (E/FL≥5) for readers 1 and 2, respectively. Agreement between mNY and MRI-SI-s (E/FL≥5) was moderate (reader 1: κ: 0.39; reader 2: κ: 0.44). Using the E/FL≥5 cut-off instead of mNY classification did not change in 478 (82.1%) and 469 (80.6%) patients for readers 1 and 2, respectively. Twelve (reader 1) or ten (reader 2) patients would not be classified as axSpA if only MRI-SI-s was performed (in the scenario of replacement of mNY), while three (reader 1) or six (reader 2) patients would be additionally classified as axSpA in both scenarios (replacement of mNY and addition of MRI-SI-s). Similar results were seen for the other cut-offs (E≥3, FL≥3). Conclusions Structural lesions on MRI can be used reliably either as an addition to or as a substitute for radiographs in the ASAS axSpA classification of patients in our cohort of patients with short symptom duration.

MRI evidence of structural changes in the sacroiliac joints of patients with non-radiographic axial spondyloarthritis even in the absence of MRI inflammation.

Abstract: Studies have shown that structural lesions may be present in patients with non-radiographic axial spondyloarthritis (nr-axSpA). However, the relevance of structural lesions in these patients is unclear, particularly without signs of inflammation on magnetic resonance imaging (MRI). We assessed the presence of structural lesions at baseline on MRI in the sacroiliac joints (SIJ) of patients with nr-axSpA with and without SIJ inflammation on MRI. Bone marrow edema (BME) was assessed on short tau inversion recovery (STIR) scans from 185 patients with nr-axSpA, by two independent readers at baseline using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Structural lesions were evaluated on T1 weighted spin echo scans, with readers blinded to STIR scans, using the SPARCC MRI SIJ structural score. Disease characteristics and structural lesions were compared in patients with SIJ BME (score ≥2) and without SIJ BME (score <2). Both SIJ BME and structural lesions scores were available for 183 patients; 128/183 (69.9%) patients had SIJ BME scores ≥2 and 55/183 (30.1%) had scores <2. Frequencies of MRI structural lesions in patients with vs without SIJ BME were: erosions (45.3% vs 10.9%, P < 0.001), backfill (20.3% vs 0%, P < 0.001), fat metaplasia (10.9% vs 1.8%, P = 0.04), and ankylosis (2.3% vs 1.8%, P = ns). Significantly more patients with both SIJ BME and structural lesions were male and/or HLA-B27 positive than patients with only SIJ BME. Mean (SD) spinal scores (23 discovertebral units) were significantly higher in patients with SIJ structural lesions than without: 6.5 (11.5) vs 3.3 (5.1), respectively, P = 0.01. In patients with nr-axSpA, SIJ structural lesions, particularly erosions, may be present on MRI when radiographs are normal or inconclusive, even in patients negative for MRI SIJ inflammation. They may reflect more severe disease with greater spinal inflammation. ClinicalTrials.gov, NCT01258738 . Registered on 9 December 2010.

Evaluation of Vitamin D Status in Rheumatoid Arthritis and Its Association with Disease Activity across 15 Countries: "The COMORA Study".

Abstract: The aims of this study are to evaluate vitamin D status in 1413 RA patients of COMORA study from 15 countries and to analyze relationship between patients’ RA characteristics and low levels of vitamin D. All demographic, clinical, and biological data and RA comorbidities were completed. The results showed that the average of vitamin D serum dosage was 27.3 ng/mL ± 15.1 0.1–151 . Status of vitamin D was insufficient in 54.6% and deficient in 8.5% of patients. 43% of RA patients were supplemented with vitamin D and absence of supplementation on vitamin D was related to higher prevalence of vitamin D deficiency ( ). Finally, our study shows that the status of low levels of vitamin D is common in RA in different countries and under different latitudes. Absence of supplementation on vitamin D was related to higher prevalence of vitamin D deficiency. Low levels of vitamin D were associated with patients characteristics (age, BMI, and educational level), RA (disease activity and corticosteroid dosage), and comorbidities (lung disease and osteoporosis therapy). This suggests the need for a particular therapeutic strategy to improve vitamin D status in RA patients.

Associations Between Five Important Domains of Health and the Patient Acceptable Symptom State in Rheumatoid Arthritis and Psoriatic Arthritis: A Cross-Sectional Study of 977 Patients.

Abstract: Introduction: The objective was to explore the link between a patient acceptable symptom state (PASS) and patient-perceived impact in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Patients and Methods: Cross-sectional study of unselected patients with definite RA or PsA. Pain, functional capacity, fatigue, coping and sleep disturbance were assessed by a numeric rating scale (0-10) and compared between patients in PASS or not (Cohen's effect sizes). The domains of health associated with PASS status were assessed by multivariate forward logistic regression, and PASS thresholds were determined using the 75th percentile method and ROC analyses. Results: Among 977 patients (531 RA, 446 PsA) mean age was 53.4±13.2 yrs; mean disease duration was 11.2±10.0 yrs; 637 (65.8%) were females. In all, 595 patients (60.9%) were in PASS: they had lower symptom levels, and all domains of health except sleep disturbance discriminated clearly between patients in PASS or not (effect sizes, 0.73 to 1.45 in RA and 0.82 to 1.52 in PsA). In multivariate analysis, less pain and better coping were predictive of being in PASS: odds ratio [95% confidence interval] 0.80 [0.67-0.96] and 0.63 [0.52-0.75] for pain and 0.84 [0.74-0.96] and 0.83 [0.71-0.97] for coping, in RA and PsA respectively. The cut-offs of symptom intensity (range 0-10) corresponding to PASS for the five domains of health and the two diseases were similar, i.e. around 4-5. Conclusion: In RA and PsA, PASS was associated with the five domains of health analysed, and in particular with less pain and better coping. This article is protected by copyright. All rights reserved.

Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis.

Abstract: Objectives To evaluate the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis (RA) and an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. Methods In this phase III study, patients were randomised 1:1:1 to placebo (N=228), baricitinib 2 mg once daily (QD, N=229) or baricitinib 4 mg QD (N=227). PROs included the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient9s Global Assessment of Disease Activity (PtGA), patient9s assessment of pain, measures from patient electronic daily diaries (duration and severity of morning joint stiffness (MJS), Worst Tiredness, Worst Joint Pain), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), SF-36, EuroQol 5-D index scores and visual analogue scales (VAS) and the Work Productivity and Activity Impairment Questionnaire-RA. The primary time point for the study was week 12. Treatment comparisons were assessed with logistic regression for categorical measures and analysis of covariance for continuous variables. Results Statistically significant improvements were observed for both baricitinib groups versus placebo in HAQ-DI, PtGA, pain, daily diary measures, EuroQoL index scores and SF-36 physical component score at week 12 and for those measures when assessed at week 24. Baricitinib 2 mg and baricitinib 4 mg were statistically significantly improved versus placebo for the EuroQoL VAS and FACIT-F, respectively, at week 24. Conclusions Baricitinib 2 or 4 mg provided significant improvement versus placebo in PROs across different domains of RA, including physical function, MJS, fatigue, pain and quality of life. Trial registration number NCT01721057; Results.

Large country differences in work outcomes in patients with RA - an analysis in the multinational study COMORA

Abstract: We aimed to explore whether country of residence or specific country characteristics are associated with work outcomes in rheumatoid arthritis (RA). Data from the 17 countries participating in the Comorbidities in RA (COMORA) study were used. Work outcomes were measured by the Work Productivity and Activity Impairment Questionnaire, addressing employment (yes/no), absenteeism (percentage of time; 3 categories) and presenteeism (percentage of at-work productivity restrictions; 4 categories). Contribution of country of residence, gross domestic product (GDP), Human Development Index (HDI), unemployment rate, social protection expenditures (SPE) or world region to work outcomes was investigated in adjusted (ordered) logistic regressions. The patients (n = 2395) were younger than 60 years; mean age 48 (SD 9.2) years, 1972 (84%) female and 1065 (45%) employed. Large country differences were found. Taking the country with the best work outcome as reference, Moroccan patients had the lowest odds of being employed (OR 0.2 (95% CI 0.1; 0.3) vs. Germany) and highest odds of absenteeism (OR 13.2 (3.6; 48.3) vs. Japan). Patients in Taiwan had the highest odds of presenteeism (OR 13.0 (5.5; 30.9) vs. Venezuela). All country indices except SPE were associated with work outcomes. For example, patients in low-GDP countries had lower odds of employment (OR 0.6 (0.5; 0.8)), higher odds of absenteeism (OR 2.8 (2.0; 4.1)), but lower odds of presenteeism (OR 0.5 (0.4; 0.7)) compared to higher-GDP countries. Substantial differences in work outcomes among patients with RA were observed between countries. Lower economic wealth and human development of countries were associated with worse employment and higher absenteeism, but lower presenteeism.

Prevalence and risk factors of low bone mineral density in spondyloarthritis and prevalence of vertebral fractures

Abstract: Investigate the prevalence and risk factors of low bone mineral density (BMD) in patients with axial spondyloarthritis as well as investigating the prevalence of vertebral fractures. Patients underwent BMD measurements with dual-energy X-ray absorptiometry (DXA) in the anterior-posterior lumbar spine, lateral spine and hip. We screened for vertebral fractures using vertebral fracture assessment, and then checked for syndesmophytes on the VFA images. Sociodemographic and clinical variables were collected. A total of 89 patients (41,6% female) took part in the study with a mean age of 44 ± 14 years and disease duration 10.2 ± 10.6 years. According to World Health Organization (WHO) criteria, 48,3% of patients displayed osteopenia and 6,7% osteoporosis. In the subgroup of women who underwent measurement at all sites including the lateral spine, the prevalence of osteopenia was 39.3% in the anterior-posterior spine, 32.1% in the lateral spine, and 64.3% with all sites together. VFA led to the diagnosis of at least one vertebral fracture in 6.2% of patients. On VFA, syndesmophytes were found in 24.3% of patients. The variables associated in multivariate analyses with low BMD in different measurement sites were low body mass index (BMI), a high physician’s global assessment score, a high Bath Ankylosing Spondylitis Functional Index (BASFI) score and female gender. Our study found a high prevalence (around 50%) of low BMD in SpA. Conversely, the prevalence of osteoporosis (6.7% according to WHO criteria) and vertebral fractures (6.2%) was lower than generally reported in the literature. While lateral spine BMD measurement did little to improve the detection of osteopenia in women, the sample size was not large enough to enable us to draw definite conclusions.

Effects of Long-Term Etanercept Treatment on Clinical Outcomes and Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: 104-Week Results From a Randomized, Placebo-Controlled Study.

Abstract: Objective To evaluate the long-term clinical and imaging efficacy of etanercept in patients with early, active nonradiographic axial spondyloarthritis (SpA). Methods Adult patients who satisfied the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA (but not the modified New York radiographic criteria), with symptom duration >3 months to Results Of 215 randomized patients (etanercept: n = 106; placebo: n = 109), 205 entered the study (etanercept/etanercept: n = 100; placebo/etanercept: n = 105) and 169 completed the open-label period (etanercept/etanercept: n = 83; placebo/etanercept: n = 86). At week 104, 61 of 81 (75%), 49 of 81 (61%), 48 of 80 (60%), and 57 of 81 (70%) patients who received etanercept throughout the trial achieved ASAS20, ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and Bath Ankylosing Spondylitis Disease Activity Index criteria for 50% improvement (BASDAI 50) scores, respectively (observed). From baseline to week 104, continued improvements in clinical outcomes (ASDAS-C-reactive protein: -1.5 and -1.7; BASDAI: -3.3 and -3.8 [last observation carried forward]), and SPARCC MRI scores (sacroiliac joint: -6.0 and -3.4; spinal: -2.1 and -0.8 [observed]) were seen in patients receiving etanercept/etanercept and placebo/etanercept. During the study, 8% in the etanercept/etanercept group and 7% in the placebo/etanercept group had serious adverse events; no new safety signals were seen. Conclusion Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement in clinical and imaging outcomes that were sustained through 104 weeks of etanercept treatment.

Evaluation of whether extremely high enthesitis or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores suggest fibromyalgia and confound the anti-TNF response in early non-radiographic axial spondyloarthritis.

Abstract: OBJECTIVES Differentiating between pain from spondyloarthritis (SpA) and pain from fibromyalgia is challenging. We evaluated patients with non-radiographic axial SpA (nr-axSpA) to determine the percentage of patients with extremely high enthesitis and/or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, the relationship between extreme scores and depression, and the effect of extreme scores on treatment outcomes with etanercept. METHODS Patients with nr-axSpA received double-blind etanercept 50 mg or placebo weekly and were divided into those who did vs did not have extreme scores at baseline. Extreme scores were defined as the highest quintile for enthesitis score (≥6), and/or scores ≥8 on three of five BASDAI items (excluding morning stiffness duration). Depression was assessed with the Hospital Anxiety and Depression Scale, depression subscale (HADS-D) and medication use. Week 12 outcomes included Assessment of SpondyloArthritis (ASAS) 40 and ASAS partial remission. RESULTS At baseline, 35/213 (16.4%) patients met extreme enthesitis criteria, 31 (14.6%) met extreme BASDAI criteria, 12 (5.6%) met both, and 135 (63.4%) met neither. More patients with extreme scores than without met the HADS-D definition of depression: 35/68 (51.5%) vs. 27/118 (22.9%), p<0.0001. For patients with vs. without extreme scores who received etanercept, no significant difference existed in week 12 ASAS 40: 13/41 (31.7%) vs. 21/60 (35.0%), respectively, or ASAS partial remission: 8/41 (19.5%) vs. 19/60 (31.7%). CONCLUSIONS Extreme enthesitis and/or BASDAI scores were associated with measurements of depression, but did not affect week 12 ASAS 40 or ASAS partial remission.

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort

Abstract: Background Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. Objective To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. Methods Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. Results Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. Conclusion Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.

Is the current ASAS expert definition of a positive family history useful in identifying axial spondyloarthritis? Results from the SPACE and DESIR cohorts

Abstract: The Assessment of SpondyloArthritis international Society (ASAS) definition of a positive family history (PFH) of spondyloarthritis (SpA) includes the following diseases in first- or second-degree relatives: ankylosing spondylitis (AS), acute anterior uveitis (AAU), reactive arthritis (ReA), inflammatory bowel disease (IBD), and psoriasis. However, it is not known if a PFH for each of these diseases contributes to making a diagnosis of axSpA, sacroiliitis on imaging, or fulfilling the ASAS criteria in patients presenting with chronic back pain (CBP). Therefore, the aim of this study was to assess which SpA diseases in family members are associated with human leukocyte antigen B27 (HLA-B27) and axial spondyloarthritis (axSpA) in CBP patients. CBP patients suspected of axSpA from the SPACE (n = 438) and the DESIR (n = 647) cohort were asked about the presence of SpA diseases in first- or second-degree relatives (AS, AAU, ReA, IBD, and psoriasis). The associations between a PFH and HLA-B27, sacroiliitis on imaging (magnetic resonance imaging (MRI) or radiographs), axSpA diagnosis, and ASAS classification in CBP patients were assessed. In the SPACE and the DESIR cohort, a PFH of AS (odds ratio (OR) 5.9 (95% confidence interval (CI) 3.5–9.9), and OR 3.3 (95% CI 2.1–5.2)) and a PFH of AAU (OR 9.8 (95% CI 3.3–28.9) and OR 21.6 (95% CI 2.9–160.1)) were significantly associated with presence of HLA-B27. Furthermore, in both cohorts a PFH of AS and a PFH of AAU were positively associated with fulfilment of the ASAS criteria, but not with sacroiliitis on imaging. In SPACE but not in DESIR a PFH of AAU was positively associated with axSpA diagnosis. In both cohorts a PFH of ReA, IBD, or psoriasis was not positively associated with HLA-B27 positivity, sacroiliitis on imaging, axSpA diagnosis, or meeting the ASAS criteria for axSpA. In our cohorts, a PFH of AS or AAU is useful for case-finding of axSpA as this is correlated with HLA-B27 carriership. However, as a PFH of ReA, IBD, or psoriasis does not contribute to identifying axSpA in CBP patients, these data suggest that the widely used ASAS definition of a PFH of SpA should be updated. Trial registration number, NCT01648907 . Registered on 20 July 2012.

Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis.

Abstract: Background The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 ( IRF5 and IRF7 ), tyrosine kinase 2 ( TYK2 ), signal transducer and activator of transcription 4 ( STAT4 ) and osteopontin ( SPP1 ). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). Methods Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. Results The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34×10 −6 , OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%. Conclusion Our results support the contribution of the IRF5 , SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24.

Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib

Abstract: Patients with rheumatoid arthritis (RA) have a high prevalence of comorbidities.1 This post-hoc analysis investigated the effect of select comorbidities (depression, osteoporosis, hepatic, cardiovascular or pulmonary disorders) on the efficacy and safety of baricitinib 4 mg once daily in patients with moderate-to-severe active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Data from the placebo-controlled periods of five baricitinib studies2–6 were pooled for baricitinib 4 mg; data for baricitinib 2 mg were not analysed due to low (n=302) patient numbers. Additional data for all baricitinib-treated patients with a median exposure of 2 years were derived from an ongoing open-label, long-term extension (LTE) study that included patients from phase II and III studies (RA-BEYOND; NCT01885078).7 Efficacy outcomes were evaluated at week 12 (vs placebo). Interaction of comorbidity-by-treatment was analysed using logistic regression or analysis of covariance. Safety observations up to week 16 (vs placebo) and during the LTE were summarised by the Medical Dictionary for Regulatory Activities preferred term. Data from 1684 patients (803, baricitinib 4 mg; 881, placebo) from the placebo-controlled periods were analysed. The mean (SD) age was 52.7 (12.1) years, with only 38 (2.3%) patients aged ≥75 years; most patients (1506, 89.4%) were receiving background methotrexate, alone or in combination with another csDMARD. The numbers of patients receiving placebo and baricitinib 4 mg combined (with or without each comorbidity, respectively) were 133/1551 for depression, 247/1437 for osteoporosis, 424/1260 for hepatic disorders, 731/953 for cardiovascular disorders, and 166/1518 for pulmonary disorders. Demographic and clinical characteristics within each comorbidity subgroup were similar between patients randomised to baricitinib or placebo. Higher …

Flare in axial spondyloarthritis: investigation of meaningful changes in symptomatic outcome measures.

Abstract: OBJECTIVES To assess symptomatic outcomes associated with flare after discontinuation of non-steroidal anti-inflammatory drugs (NSAIDs) in axial spondyloarthritis (axSpA). METHODS Patients with NSAID-refractory axSpA discontinued NSAIDs, restarted if symptoms recurred, and self-recorded Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). 75th percentiles were calculated for changes in BASDAI total and components from NSAID discontinuation to resumption. RESULTS 75th percentiles for absolute/relative changes: BASDAI total (0-10)=1.5/28%; fatigue=2.0/25%; spinal pain=2.0/33%; joint pain/swelling=2.0/50%; enthesitis=2.0/43%; morning stiffness=1.5/27%. CONCLUSIONS No single score threshold applied but absolute change ≥2 or relative change ≥30% indicated symptomatic deterioration for most BASDAI components.

Low incidence of vertebral fractures in early spondyloarthritis: 5-year prospective data of the DESIR cohort

Abstract: Objectives An increased risk of vertebral fractures (VFs) has been reported in spondyloarthritis (SpA). Our hypothesis is that the prevalence of VFs is lower than reported in previous studies, especially in early SpA. This study aimed at assessing the incidence of radiographical VFs over 5 years in early axial SpA. Methods The DESIR (DEvenir des Spondylarthropathies Indifferenciees Recentes) cohort, which included patients with inflammatory back pain highly suggestive of axial SpA, is the basis of this study. All radiographs of the DESIR cohort had been assessed at a central facility, by one investigator specialised in the field of the diagnosis of VFs according to Genant’s method. We assessed the prevalence and incidence of VFs and vertebral deformities at baseline and over 5 years. Results Five-year X-rays were available for 432 patients (mean age 34.3±8.7 years, 53% women). Diagnosis of VF was doubtful and needed adjudication for 19 patients (4.4%). 13 patients had prevalent VFs (3.0%) which were located at the thoracic spine (12 were grade 1). At 5 years, five patients had an incident VF (1.15%); seven vertebrae were fractured, mostly located at the thoracic spine (n=6/7), and of grade 1 (n=6/7). Conclusion In the DESIR cohort, a population of early SpA, we found a low prevalence and incidence of VFs (3.0% and 1.15 %), respectively. This confirms our hypothesis that the actual prevalence and incidence of VFvertebral fracture in SpA is lower than that reported in the previous studies.

Assessment of typical SpA lesions on MRI of the spine: do local readers and central readers agree in the DESIR-cohort at baseline?

Abstract: Comparing local reading (LocR) with central reading (CentR) of typical spondyloarhritis lesions including bone marrow edema (BME) and structural lesions on magnetic resonance imaging of the spine (MRI-spine), in patients with inflammatory back pain (IBP; ≥3 months, <3 years) Baseline data of 667 patients, age 18-50 years, from the Devenir des Spondylarthopathies Indifferenciees Recentes (DESIR)-cohort were used Two trained central readers scored anterior and posterior corner BME, fatty lesions, erosions and syndesmophytes on MRI-spine Presences of lesions, based on average scores, were used for CentR A local radiologist and/or rheumatologist scored MRI-spine on presence/doubt/absence of 'inflammation' and 'structural lesions' Agreement between central readers and readings was calculated (Cohen's kappa: κ) Agreement between central readers was moderate (BME κ = 055, fatty lesions κ = 050) to slight (erosions κ = 012, syndesmophytes κ = 019) Agreement between LocR and CentR was κ = 032 (BME) and κ = 013 (structural lesions) In 78/160 patients (488%) LocR were in doubt while CentR scored BME lesions, for structural lesions this was 178% (28/157 patients) Agreement between 2 central readers for scoring spondyloarhritis-like lesions on MRI-spine was moderate but better compared to LocR and CentR agreement LocR often doubt about the presence of MRI-spine lesions while central trained readers score lesions

Psychometric properties of sleep and coping numeric rating scales in rheumatoid arthritis: a subanalysis of an etanercept trial.

Abstract: OBJECTIVES In rheumatoid arthritis, quality of sleep and ability to cope are important for patients; however their usefulness as outcome measures is not well established METHODS Post-hoc analysis of an open-label 12-week trial of etanercept in biologic-naive rheumatoid arthritis patients with visits at screening, baseline and over 12 weeks Outcomes measured included Disease Activity Score 28 erythrocyte sedimentation rate (DAS28), numeric rating scales for sleep, coping, patient and physician-global assessment, pain and fatigue, and modified-HAQ Reliability between screening and baseline visits by intra-class correlation, and responsiveness between baseline and 12 weeks by standardised response means were assessed for each outcome RESULTS In 108 patients, mean age 54 (standard deviation (SD) 13) years, mean disease duration 8 (SD 7) years, 75% women; disease activity was high at baseline: mean DAS28 55 (SD 08) Reliability intra-class correlation was 083[95% confidence interval: 077;088] for sleep, 081[074;087] for modified-HAQ, 080[071;086] for fatigue, 072[062;080] for physician-global assessment, 066[054;076] for coping, 065[053;075] for pain and 063[050;073] for patient-global assessment Responsiveness standardised response means was 165[132;210] for physician-global assessment, 137[109;173] for pain, 136[108;173] for patient-global assessment, 115[095;141] for fatigue, 096[070;128] for coping, 092[073;115] for sleep and 086[069;107] for modified-HAQ CONCLUSIONS Numeric rating scales assessing sleep and coping were found to be generally as reliable as 'usual' outcomes in rheumatoid arthritis Responsiveness was less high, indicating these domains of health may be less accessible to biologic treatment When assessing the patient's perspective on treatment, it is feasible and valid to measure sleep and coping by numeric rating scales

OP0248 Serious infection and associated risk factors in patients with moderate to severe rheumatoid arthritis treated with baricitinib

Abstract: Background Baricitinib (BARI) is an oral Janus Kinase (JAK)1/JAK2 inhibitor in development for patients (pts) with active rheumatoid arthritis (RA). Compared to the general population, RA pts have an increased rate of serious infection events (SIE) due to disease state and concomitant therapies.1 Objectives To evaluate the incidence rate (IR) of SIE and associated risk factors in BARI-treated pts with active RA across 8 completed studies (4 Ph3, 3 Ph2, 1 Ph1) and 1 ongoing long-term extension (LTE) study. Methods The ALL BARI RA analysis set included pts exposed to any BARI dose, with exposure up to 5 years (yrs) (Phase [Ph] 1–3 and LTE studies); the comparison with placebo (PBO) was based on 6 studies (Ph 2–3) with BARI 4 mg once daily (QD) and PBO arms up to Week (Wk) 24; dose response assessment was based on 4 studies (Ph 2–3) with both BARI 2 and 4 mg QD arms up to Wk 24. An extensive list of potential risk factors for SIE was investigated in the ALL BARI RA set using Cox models; SIE risk factors among BARI-treated pts are reported (Table). Results The most frequent SIE observed in the ALL BARI RA set (N=3492; 5133 pt-yrs (PY) of exposure [PYE] were pneumonia, herpes zoster, urinary tract infection, and cellulitis (all Conclusions SIE incidence was similar between BARI- and PBO-treated RA pts. SIE risk factors include concomitant corticosteroids, prior biologics, non-normal BMI, Asian region of enrollment, and advancing age. References Listing J et al. Rheumatology. 2013;52:53–61. Disclosure of Interest K. Winthrop Grant/research support from: Pfizer, BMS, Consultant for: Pfizer, UCB, Abbvie, Eli Lilly and Company, Amgen, BMS, M. Genovese Grant/research support from: Eli Lilly and Company, Abbvie, Astellas, Galapagos, Pfizer, Vertex, Crescendo Bioscience, Consultant for: Eli Lilly and Company, Abbvie, Astellas, Galapagos, Pfizer, Vertex, Crescendo Bioscience, M. Harigai Grant/research support from: Bristol-Myers Squibb KK, Eisai Co Ltd, Ono Pharma, Takeda Pharma Ltd, Consultant for: Eli Lilly and Company, L. Chen Employee of: Eli Lilly and Company, C. Dickson Employee of: Eli Lilly and Company, D. Hyslop Employee of: Eli Lilly and Company, A. Nishikawa Employee of: Eli Lilly Japan K.K., J. Bradley Employee of: Eli Lilly and Company, M. Dougados Grant/research support from: Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, Consultant for: Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS

SAT0163 Systematic switch from innovator infliximab to biosimilar infliximab in inflammatory rheumatic diseases in daily clinical practice: the experience of cochin hospital, paris, france

Abstract: Background Biosimilars of originator biologic therapeutics are going to change medical practices. In October 2015, the medical community of Cochin Hospital decided to systematically propose the switch from innovator infliximab to biosimilar infliximab to all treated patients. Objectives To investigate efficacy and safety of switching treatment from innovator infliximab to biosimilar infliximab. Methods This is a usual care study conducted in patients aged >18 years who agreed to switch to biosimilar infliximab, and who received at least 3 infusions of innovator infliximab prior to the switch. The primary outcome of the study was the retention rate of biosimilar infliximab at the time of the third infusion. Secondary outcomes included the factors associated with biosimilar discontinuation, the change between baseline and the last visit (July 2016) in DAS28-CRP (rheumatoid arthritis, RA), BASDAI/ASDAS (axial spondyloarthritis, axSPA) and infliximab trough levels, and the occurrence of adverse events. Results 260 patients fulfilled the inclusion criteria: 182 patients followed-up in Rheumatology (131 with axSPA, 31 with RA, and 20 with other inflammatory rheumatic diseases), 64 in Gastroenterology and 14 in Internal Medicine. The retention rate at the time of the third biosimilar infusion was 82% (149/182 patients), which was lower than the rate observed in patients with inflammatory bowel diseases or uveitis followed-up in Gastroenterology and Internal Medicine, respectively (71/78 patients, 91%). Between baseline and the last visit (mean follow-up: 34±4.5 weeks), 48/182 (26%) patients, including 36 patients with axSPA, discontinued biosimilar infliximab, mainly due to experienced inefficacy (n=47). No clinical or biological factors were associated with biosimilar discontinuation. One infusion reaction led to treatment discontinuation. No serious adverse events occurred. 43 patients restarted innovator infliximab, 2 patients switched to etanercept, 1 to abatacept and 2 maintained biological-free. In RA patients, the mean DAS28-CRP remained stable from baseline to the last visit: 3.38±1.16 to 3.08±1.08 (p=0.217). In axSpA patients, the mean BASDAI increased from 2.94±2.20 to 3.18±2.21 (p=0.046) and the mean ASDAS increased from 1.79±0.90 to 1.99±1.08 (p=0.022). In RA and axSPA, mean CRP levels at baseline (5.95±6.06 and 5.98±11.14 mg/l respectively) and the last visit (6.52±11.32 and 5.03±8.26 mg/l respectively) were not statistically different (p=0.289 and p=0.271, respectively). Mean infliximab trough levels were similar in patients with RA (3.70±5.36 vs. 3.21±4.35 μg/ml, p=0.551) and AxSPA (5.88±5.82 vs. 5.70±5.42 μg/ml, p=0.617) during follow-up. Conclusions In the majority of patients, innovator infliximab can be switched to biosimilar infliximab without changes in efficacy and safety during 34 weeks follow-up. However, 26% of patients discontinued biosimilar infliximab, mainly those with AxSPA due to a subjective increase in BASDAI or ASDAS scores, possibly explained by suggestion or attribution effects rather than pharmacological differences. Disclosure of Interest None declared