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Objective To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. Methods From 2003 to 2005, 813 patients were included if they had early arthritis ( Results In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. Conclusions We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

This study was conducted in order to compare the prevalence of inflammatory posterior arch abnormalities on lumbar spine MRI between axial spondyloarthritis (axSpA) patients and low back pain (LBP) patients. Patients—axSpA patients meeting the 2009 ASAS criteria and chronic LBP patients who had a lumbar spine MRI were selected. MRI—STIR and T1 sagittal images up to T8–T9 were reviewed by two experienced rheumatologists blinded to the diagnosis and clinical data to identify inflammatory posterior arch abnormalities. Analyses—The prevalence of inflammatory posterior arch abnormalities between axSpA and LBP patients was compared. Clinical data were compared in the axSpA group depending on whether or not inflammatory posterior arch abnormalities were present. Ninety-five patients were enrolled in each group. The prevalence of all inflammatory posterior arch abnormalities was the same in the axSpA and LBP groups (58% in the SpA group versus 70% in the LBP group, p = 0.1). However, differences in terms of the prevalence of costotransverse joint arthritis, pedicle oedema above L3 and transverse and spinous process oedema were observed between the two groups (axSpA 27% versus LBP 6%, p = 0.0004). Patients with inflammatory posterior arch abnormalities in the axSpA group had a longer disease duration (11 versus 8 years, p = 0.02), higher CRP levels (median 11 versus 3 mg/l, p = 0.0002) and higher prevalence of radiographic sacroiliitis (84 versus 47%, p = 0.001) compared to patients without inflammatory posterior arch abnormalities. Costotransverse arthritis, pedicle oedema and transverse process oedema are more frequent in axSpA patients than LBP patients, on lumbar spine MRI depicting TH9-S1. • MRI pedicle oedema above L3, transverse process oedema, spinous process oedema or costotransverse arthritis is more frequently observed in axial spondyloarthritis (SpA). • SpA patients with at least one MRI inflammatory lesion on the posterior arch had higher clinical activity scores and biological inflammation. • Facet joint arthritis was more common in patients with chronic low back pain.

International audience; The 2014 French Society for Rheumatology (Société Française de Rheumatologie, SFR) recommendations about the management of rheumatoid arthritis (RA) have been updated by a task force composed of 12 expert rheumatologists, 2 patient self-help group representatives, and an occupational therapist. The material used by the task force included recent EULAR recommendations, a systematic literature review, and expert opinion. Four general principles and 15 recommendations were developed. The general principles emphasize the need for shared decision-making between the rheumatologist and the patient and for a global management program including both pharmacological and non-pharmacological treatments. The recommendations deal with the diagnostic strategy for RA, treatment targets, management organization, drug selection based on the treatment line and prognostic factors, management of remissions, and global patient management. Disease-modifying anti-rheumatic drug (DMARD) therapy should be started as early as possible. Validated composite scores should be determined at regular intervals to assess disease activity - according to the tight disease control concept - to achieve the treatment target, i.e., a remission. Methotrexate is the recommended first-line DMARD. The treatment should be optimized when methotrexate is poorly tolerated or inadequately effective. While waiting for conventional synthetic DMARDs to take effect, glucocorticoid therapy can be used, for a brief period to keep the cumulative dose low. When a sustained remission without structural progression is achieved in a patient who is not taking glucocorticoid therapy, targeted therapy de-escalation according to tight disease control principles should be considered. Patients should be periodically screened for comorbidities and their risk factors, which should be evaluated and treated.

Background To investigate the association between 12 single nucleotide polymorphisms (SNPs) located on ERAP1 and IL23R with the presence of inflammation on the sacroiliac joint (SIJ) or spinal magnetic resonance imagery (MRI) in an early onset spondyloarthritis (SpA) cohort. Methods All the patients included in the DESIR cohort with an axial SpA and available DNA at baseline were enrolled in this study (n = 645 patients) and underwent a clinical examination, CRP assay, SIJ and spinal MRI scans. Six SNPs located on ERAP1 (rs30187, rs27044, rs27434, rs17482078, rs10050860, rs2287987) and six SNPs located on IL23R (rs1004819, rs10489629, rs1343151, rs2201841, rs10889677, rs11209032) were genotyped. Univariable analyses were performed to test the association between the genotypes and SIJ and spinal MRI inflammation, as well as disease activity based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) and CRP. Results One SNP located on ERAP1 (rs27434) and haplotype CCT of ERAP1 were associated with SIJ inflammation detected by MRI, but these associations were below the Bonferroni corrected threshold of significance. However, one SNP (rs1004819) located on IL23R was associated with SIJ MRI inflammation (rs1004819: TT 42.3%, CT 40.5%, CC 26.5%, p = 0.0005). This locus was also significantly associated with Spondyloarthritis Research Consortium of Canada scores while no association with another inflammatory parameter such as BASDAI, ASDAS-CRP, CRP or Berlin MRI score was identified in this population. Conclusion One locus of the IL23R gene was associated with SIJ MRI inflammation and might be a marker of more active disease in recent onset SpA. Trial registration clinicaltrials.gov, NCTO 164 8907

Summary In order to ascertain the significance of transmembrane tumor necrosis factor (tmTNF) reverse signaling in vivo, we generated a triple transgenic mouse model (3TG, TNFR1−/−, TNFR2−/−, and tmTNFKI/KI) in which all canonical tumor necrosis factor (TNF) signaling was abolished. In bone-marrow-derived macrophages harvested from these mice, various anti-TNF biologics induced the expression of genes characteristic of alternative macrophages and also inhibited the expression of pro-inflammatory cytokines mainly through the upregulation of arginase-1. Injections of TNF inhibitors during arthritis increased pro-resolutive markers in bone marrow precursors and joint cells leading to a decrease in arthritis score. These results demonstrate that the binding of anti-TNF biologics to tmTNF results in decreased arthritis severity. Collectively, our data provide evidence for the significance of tmTNF reverse signaling in the modulation of arthritis. They suggest a complementary interpretation of anti-TNF biologics effects in the treatment of inflammatory diseases and pave the way to studies focused on new arginase-1-dependent therapeutic targets.

Background Human cytomegalovirus (HCMV) seropositivity has been associated with higher inflammation during rheumatoid arthritis (RA). However, no data are available on the impact of HCMV seropositivity on bone erosion progression during RA. Methods We selected 487 individuals of ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA. HCMV serology for these patients was determined using Architect CMV IgG assay. Baseline and 1-year central X-ray reading using modified Total Sharp Score (mTSS), Erosion Sharp Score, and joint space narrowing Sharp score were used to quantify structural damage progression. We performed univariate and multivariate analyses to investigate the association between HCMV status and bone erosion progression. Results We analyzed 273 HCMV seropositive (HCMV+) and 214 HCMV seronegative (HCMV−) RA patients. At inclusion, HCMV+ patients were less frequently ACPA+ (49.8% versus 58.9%, p p 1 point) was lower in HCMV+ patients (16.1% versus 25.2%, p = 0.0128) in comparison with HCMV−. HCMV+ status remained independently associated with lower bone erosion progression in multivariate analysis. Conclusions Our findings suggest that, independently of other confounding factors, HCMV seropositivity is associated with a lower progression of bone erosion during RA.

Objectives The aims of the Oral Status And Rheumatoid Arthritis (OSARA) cross-sectional study were to study the oral health-related quality of life and to assess the associated factors in a population of outpatients with rheumatoid arthritis in France. Methods The data were collected by five trained and standardised dentists who asked each subject the questions of a socio-demographic, behavioural and medical questionnaire, which was completed with the medical records, and performed the dental examination. Each subject filled out two self-assessment questionnaires: the Health Assessment Questionnaire and the General Oral Health Assessment Index. Results Seventy-three subjects were included. The mean age of the participants was 60.2 ± 11.9 years and 75.3% were women. For 58.3% of the subjects, their self-perceived oral health-related quality of life was described as poor. The logistic regression analysis found that a small number of teeth and marked difficulties in dressing and grooming were associated with bad oral health-related quality of life [ORa = 10.5 (1.96–56.19) and ORa = 4.3 (1.15–15.77), respectively]. Conclusions More care should be given to the prevention of dental diseases in order to improve the oral health-related quality of life of patients with rheumatoid arthritis and their self-esteem, which will already be heavily affected.

Background:ESPOIR is a longitudinal prospective cohort of adults with possible early RA (ClinicalTrials.gov: NCT03666091). Patients were referred by rheumatologists and general practitioners to one of the 14 regional centers in France. The objective and design of the cohort are described elsewhere (1). Patients received standard of care by their rheumatologists and were followed without predefined therapeutic strategiesObjectives:To report the current 10-year outcome of patients with early rheumatoid arthritis (RA) in the ESPOIR cohort, and predictors of outcome.Methods:From 2003 to 2005, 813 patients were included if they had early arthritis (< 6 months) with a high probability of RA developing and had never been prescribed disease modifying anti-rheumatic drugs (DMARDs). Multivariate logistic regression analysis was used to evaluate predictors of outcome.Results:In total, 521 (64.1%) RA patients were followed up for 10 years and 35 (4.3%) died, which appears similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174/521 (33.4%) received at least one biologic DMARD, 13.6 and 23.4% within 2 and 5 years. At year 10 (Table), mean DAS28 ESR was 2.5 ± 1.3; 273 (52.4%) patients were in DAS28 remission, 39.7% in CDAI remission, 40.1% in DAS28 sustained remission, and 14.1% in drug-free remission. Disability was well controlled overtime (Figure) and half of the patients achieved a HAQ Disability Index < 0.5; the SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 ± 17.9. A total of 82 (16.5%) patients required joint surgery including arthroplasty or arthrodesis in only 6.5% of the cases. A substantial number of patients showed new comorbidities, mainly cardiovascular or metabolic diseases over 10 years. Finally, positivity for anti-citrullinated protein antibodies was confirmed as a robust predictor of long-term outcome in patients with early RA.Table 1.Outcome in ESPOIR cohort and 1993 cohort at 10 yearsESPOIR cohort n=5211993 cohort n=112DAS28 ESR2.5 ± 1.3DAS44-2.2 ± 0.9SDAI7.5 ± 8.7CDAI6.8 ±8.3DAS28 ESR remission (n (%)273 (52.4)CDAI remission207 (39.7)DAS28 sustained remission, n (%)209 (40.1)DAS28 drug-free remission, n (%)75 (14.1)DAS28 ESR LDA336 (64.5)Rheumatoid nodules39 (7.5)Sicca syndrome314 (60.3)Patient global assessment24.0 ± 24.0HAQ DI score0.5 ± 0.60.75 ± 0.71HAQ DI < 0.5, n (%)280 (54.5)SF36 MCS46.7 ± 10.5SF36 PCS44.6 ± 9.2Pain (mm, VAS)16.6 ± 20.6Fatigue (mm, VAS)31.4 ± 27.023.2 ± 23.0ESR (mm/hr)14.4 ± 13.818.4 ± 16.5CRP level (mg/l)6.4 ± 16.59.3 ± 11.7Normal CRP (< 5 mg/l), n (%)336 (67.6)Total mSharp score*13.8 ± 19.635.4 ± 46.1Erosion score4.9 ± 9.418.4 ± 26.5)Joint narrowing score8.9 ± 12.132.1 ±23.2Joint surgery82 (16.5)26 (23.2)Joint arthroplasty/arthrodesis34 (6.5)20 (17.9)Data are mean (SD)DAS28, disease activity in 28 joints; HAQ DI, Health Assessment Questionnaire Disability Index; SF36 MCS, Medial Outcomes Study 36-item Short Form mental component summary; SF36 PCS, Medical Outcomes Study 36-item Short Form physical component summary; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analog scale; CDAI, Clinical Disease Activity Index; SDAI, Simple Disease Activity Index; *van der Heijde-modified Total Sharp scoreFigure 1.Health Assessment Questionnaire Disability Index (HAQ-DI) over 10 years Data are mean (SD).Conclusion:We report a very mild 10-year outcome of a large inception cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of early RA patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients than previously.References:[1]Combe B et al. Jt Bone Spine Rev Rhum. 2007;74:440–5Acknowledgements:We thank MC Boissier, G Falgaronne and F. Lioté for help in patient recruitment. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the cohort study. Two additional grants from INSERM supported part of the biological database. The French Society of Rheumatology, Abbvie, Pfizer, Lilly and more recently Fresenius and Biogen supported the ESPOIR cohort.Disclosure of Interests:Bernard Combe Speakers bureau: AbbVie; BMS; Gilead; Lilly; Merck; Pfizer; Roche-Chugai;, Consultant of: AbbVie; BMS; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Fresenius, Novartis, Pfizer, and Roche-Chugai., Nathalie Rincheval: None declared, Francis Berenbaum Speakers bureau: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Patrick BOUMIER: None declared, Alain Cantagrel Speakers bureau: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Consultant of: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Grant/research support from: Abbvie, Fresenius, MSD France, Novartis, Pfizer, and UCB, Philippe Dieudé Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Consultant of: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer., Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Bruno Fautrel Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD and Pfizer, René-Marc Flipo Speakers bureau: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Consultant of: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Grant/research support from: Abbvie, Janssen, Novartis, Pfizer and Roche-Chugai, Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Grant/research support from: Abbvie, Biogen, MSD, Pfizer, Xavier Mariette Speakers bureau: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Consultant of: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Grant/research support from: Servier, Alain Saraux Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Grant/research support from: Roche-Chugai, Thierry Schaeverbeke Speakers bureau: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Consultant of: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Grant/research support from: Pfizer, AbbVie, BMS, Roche, UCB, Astra, MSD, Rigel, AB-sciences, Jean Sibilia Speakers bureau: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Consultant of: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Grant/research support from: AbbVie, Lilly, Pfizer, Roche, Olivier VITTECOQ Speakers bureau: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Grant/research support from: Novartis, Pfizer, Merck, and Bristol-Myers Squibb, Jean-Pierre Daures: None declared

Highlights • The SFR selected the most critical questions Rheumatologists must contend in the management of their patients with rheumatic diseases during COVID-19 pandemic • A group of 10 experts from SFR and CRI boards proposed responses based on the current knowledge of May 2020. • In most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. • If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms., Background: Rheumatologists must contend with COVID-19 pandemic in the management of their patients and many questions have been raised on the use of both anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARD). The French Society of Rheumatology (SFR) selected the most critical ones to the daily practice of a rheumatologist and a group of 10 experts from SFR and Club Rheumatism and Inflammation (CRI) boards proposed responses based on the current knowledge of May 2020. Basic procedure: Following the availability of the first 18 questions and statements, 1400 individuals consulted the frequently asked questions between the March 31, 2020 and April 12, 2020. As a result, 16 additional questions were forwarded to the SFR, and answered by the board. An additional round of review by email and video conference was organized, which included updates of the previous statements. The scientific relevance of 5 of the questions led to their inclusion in this document. Each response received a final assessment on a scale of 0–10 with 0 meaning no agreement whatsoever and 10 being in complete agreement. The mean values of these votes for each question are presented as the levels of agreement (LoA) at the end of each response. This document was last updated on April 17, 2020. Main findings: Based on current scientific literature already published, in most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms. Only, some signals suggest that people taking an immunosuppressive dose of corticosteroid therapy are at greater risk of developing severe COVID-19. Intra-articular injections of glucocorticoids are allowed when there is no reasonable therapeutic alternative, and providing that precautions to protect the patient and the practitioner from viral contamination are adopted, included appropriate information to the patient. Principal conclusions: Currently available data on managing patients with rheumatic diseases during the COVID-19 pandemic are reassuring and support continuing or initiating symptomatic as well as specific treatments of these diseases, the main target of their management remaining their appropriate control, even during this pandemic.

International audience; Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or smallfibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and nonpharmacological treatments.

Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02–1.19), smoking (OR 1.32, 95% CI 1.08–1.63) and high number of tender joints (OR 1.03, 95% CI 1.02–1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50–0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.Conclusion.Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 ResultsIn total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).ConclusionIn daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

Objective.The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.Methods.Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score.Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor–positive or anticitrullinated protein antibody–positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively.Conclusion.The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956)

Abatacept retention rates were evaluated in the French cohort in the prospective ACTION study (2010-2013), which included patients with moderate-to-severe rheumatoid arthritis managed in everyday clinical practice and started on intravenous abatacept therapy.Two-year abatacept retention rates were evaluated in 455 patients classified according to treatment line, body mass index (BMI), and status for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA).After 2 years, the overall abatacept retention rate was 44%. The retention rate was non-significantly higher in the patients with vs. without a history of unresponsiveness to at least one biologic (48.1% vs. 41.8%, respectively). No significant retention rate differences were found across BMI categories (444 patients;25, 45.5%; ≥25 to30, 48.9%; and ≥30, 36.6%). Neither were any significant differences demonstrated according to RF and ACPA status (RF+ and ACPA+, 45.7%; RF+ or ACPA+, 43.8%; and FR- and ACPA-, 39.1%).The 44% 2-year retention rate in the French ACTION cohort supports the usefulness of abatacept therapy. In this study, retention was not associated with treatment line, BMI, or antibody status.

Background and objective Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis. Patients and methods Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes. Results One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07–5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year. Conclusion Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms. Trial registration ClinicalTrials.gov: NCT03666091. Registered September 11, 2018.

Key Points Question Is receipt of tumor necrosis factor (TNF) inhibitor monotherapy at the time of COVID-19 diagnosis associated with adverse COVID-19 outcomes compared with other treatment regimens among patients with immune-mediated inflammatory diseases (IMIDs)? Findings In this cohort study of 6077 patients with IMIDs and COVID-19, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, or Janus kinase inhibitor monotherapy were each associated with significantly higher odds of hospitalization or death compared with TNF inhibitor monotherapy. Meaning This study’s findings support the continued use of TNF inhibitor monotherapy among individuals with IMIDs during the pandemic., Importance Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19–associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures The main outcome was COVID-19–associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P, This cohort study uses data from 3 international registries to examine the association between the receipt of tumor necrosis factor monotherapy and the risk of COVID-19–associated hospitalization or death among adult patients with immune-mediated inflammatory diseases.

Introduction Although biotherapy has greatly improved the prognosis of RA many patients have still recourse to an orthopaedic surgery. The current recommendation for scheduled surgery is to discontinue administration of the biological agent two to six weeks before surgery. Reinitiating anti-TNF therapy is proposed when the patient has healed. We wanted to know whether patients treated with anti-TNFα were exposed to an infectious risk undergoing a surgical procedure and if discontinuation of anti-TNFα therapy altered the risk of surgical infection. Methods We conducted a systematic review of the literature in PubMed, Embase and Cochrane until March 2014. We selected studies that reported post-operative infections by comparing patients treated with anti-TNFα to patients treated with csDMARD without biological treatment, or patients who continued anti-TNFα therapy to the patients who discontinued treatment prior to surgery. Results A first meta-analysis of 12 studies evaluating postoperative infection risk in patients treated with anti-TNFα showed that the postoperative infection risk doubled (RR = 1.81 [1.31–2.50]). Seven studies were grouped into a second meta-analysis to evaluate the benefit of the preventive discontinuation of anti-TNFα. Discontinuation of treatment did not alter the post-operative infection risk significantly: RR = 0.69 [0.39–1.21]. Conclusion This study showed that patients treated with anti-TNFα were more at risk of post-operative infection undergoing orthopaedic surgery. Preventive discontinuation of anti-TNFα does not seem to change this risk.

International audience; Introduction: Adipose-derived mesenchymal stem cells (ADSC) have been shown to have remarkable immune-modulating effects. However, their efficacy in clinical trials has yet to be fully demonstrated. This could be due to a lack of a proper inflammatory environment in vivo that primes ADSC. Here, we define how the articular microenvironment of rheumatoid arthritis (RA) patients modulates the therapeutic efficiency of ADSC. Methods: Synovial fluids (SF) were collected from 8 RA patients, 2 Spondyloarthritis patients and one control synovial fluid from a patient undergoing traumatic-related surgery. SF inflammatory status was determined by routine analysis and quantification of pro-inflammatory cytokines. ADSC were first treated with SF and ADSC proliferation and gene expression of immunomodulatory factors was evaluated. In order to determine the mechanisms underlying the effect of SF on ADSC, tumor necrosis factor (TNF), interleukin-6 (IL-6), and NF-κB neutralization assays were performed. To evaluate the effect of SF on ADSC functions, ADSC were pre-treated with SF and then co-cultured with either macrophages or T cells. The modulation of their phenotype was assessed by flow cytometry. Results: Pro-inflammatory RASF maintained the proliferative capacity of ADSC and upregulated the gene expression of cyclooxygenase-2 (COX2), indoleamine-1,2-dioxygenase (IDO), interleukin-6 (IL-6), tumor-necrosis factor stimulated gene 6 (TSG6), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and programmed death-ligand 1 (PD-L1), all factors involved in ADSC immunomodulatory potential. The RASF-induced gene expression was mainly mediated by TNF alone or in combination with IL-6 and signaled through the NF-κB pathway. Conditioning ADSC with pro-inflammatory RASF enhanced their ability to induce CD4+Foxp3+CD25high regulatory T cells (Tregs) and inhibit pro-inflammatory markers CD40 and CD80 in activated macrophages. Conclusions: Inflammatory synovial fluids from RA patients had the capacity to modulate ADSC response, to induce Tregs and modulate the phenotype of macrophages. The clinical use of ADSC in affected joints should take into account the influence of the local articular environment on their potential. Having a sufficient pro-inflammatory microenvironment will determine whether optimal immunoregulatory response should be expected. Direct ADSC intra-articular delivery to patients could be a potential strategy to properly prime their immunomodulatory potential and enhance their clinical benefits.

Background: Dietary long-chain polyunsaturated fatty acids (PUFAs) of the n3 and n6 families are involved in immune homeostasis and can contribute to modulate inflammatory processes. Dietary intake of n3PUFA (by either supplementation or fish consumption) has been inversely associated with RA incidence in different populations. Some evidence suggests that, in subject at high risk of developing rheumatoid arthritis (RA), high erythrocyte membrane content in long-chain n3-PUFA is associated with lower ACPA prevalence and progression to RA. While long-chain n6PUFA are considered mainly proinflammatory, some, like gamma-linolenic acid (GLA), are endowed with anti-inflammatory activity, and the erythrocyte content in n6 linoleic acid was inversely associated with the development of RA in a nested-case control study. No study hitherto evaluated the longitudinal association between individual PUFA profile and disease activity in early RA. Objectives: To characterize serum profiles of PUFA and to determine their association with baseline variables and with 6-month disease activity in a cohort of patients with early RA. Methods: Serum PUFAs were quantified by gas chromatography-mass spectrometry (GC/MS) in 594 patients with early RA at the time of recruitment in the French Etude et Suivi des POlyarthrites Indifferenciees Recentes (ESPOIR) cohort. Principal component analysis on 19 serum fatty acids with 14 to 22 carbon atoms allowed to determine 3 orthogonal patterns of baseline serum PUFA. Pattern 1 included high proportions of short-chain fatty acids, pattern 2 was high in n3 long-chain PUFA (EPA et DHA), pattern 3 was rich in n6 long-chain fatty acids (among which, GLA had the highest concentration). Patients were stratified in tertiles according to how much the fitted into each pattern, with tertile 1 meaning lowest and tertile 3 highest fitting into the pattern. The association of PUFA patterns with baseline variables was tested in univariate analysis. The association with 6-month disease activity (with high disease activity defined as DAS28>5.1) was tested in multivariable analysis after adjustment on baseline CRP, corticosteroid and/or NSAIDs use, socioeconomic status, ACPA and RF positivity, traditional and biologic DMARDs treatment between 0 and 6 months after inclusion. Results: In baseline univariate analysis, pattern 1 was associated with high BMI, active smoking and with non-Caucasian origin. Profile 2 was associated with higher socioeconomic status and inversely associated with DAS28 and CRP. Profile 3 was associated with ACPA positivity and higher baseline CRP. In multivariate analysis, fitting into pattern 2 and 3 was associated with lower odds of having active disease after 6 months (OR for tertile 3 vs. tertile 1: 0.49 (95% CI 0.25 to 0.97, p Conclusion: In a cohort of early RA patients, we could identify a high serum long-chain n3PUFA profile associated with low disease activity between 0 and 6 months of follow-up in the cohort. This is consistent with a presumed immunomodulatory action of n3PUFA. Despite the baseline association with disease severity features, like ACPA positivity and high CRP, a high serum long-chain n6PUFA profile is also associated with 6-month lower disease activity, possibly due to the presence of high concentrations of GLA in this profile. Disclosure of Interests: Johanna Sigaux Speakers bureau: celgene, Camille de Brauer Buscail: None declared, Chantal Julia: None declared, Rene Marc Flipo: None declared, Alain Cantagrel: None declared, Bernard Bannwarth: None declared, Francois Laporte: None declared, marie-Christophe Boissier Grant/research support from: Pfizer MSD, Speakers bureau: Pfizer Lilly Biogen, Luca Semerano Grant/research support from: pfizer, Speakers bureau: pfizer, roche, msd.

To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Objectives To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Methods Using the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. Results Among 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients’ median age was 36 years (range 6–78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3–12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2–16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. Conclusion In France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD. journal article 2019 06 2018 09 28 imported

Background: Having demonstrated bioequivalence and similar efficacy, safety and immunogenicity as the originator, SB4 is approved in the EU as an ETN biosimilar. There is limited evidence on outcomes of transition from originator to biosimilar in a multi-country real-world setting. Objectives: To provide real-world evidence on outcomes of transition from ETN to SB4 in routine clinical practice at EU sites. Methods: Eligible patients had RA or axSpA and had initiated SB4 in routine clinical practice following a minimum of 6 months treatment with a stable dose of originator ETN, at clinics in France, Germany, Italy, and Spain. Data were captured from patient records prospectively and/or retrospectively for 6 months following transition. Outcome measures include clinical characteristics, disease scores (DAS-28 for RA, BASDAI for axSpA) and clinical management. Results: Analysis of 533 eligible patients (347 RA, 186 axSpA) demonstrated no clinically significant difference in disease score from baseline to 6 months post-transition; mean individual change was 0.0 (95% CI -0.1, 0.1) and 0.0 (95% CI -0.3, 0.2) at 6 months post-transition in RA and axSpA subjects respectively. Regarding dose regimen, 73.5% and 63.4% of RA and axSpA subjects transitioned from ETN 50mg QW to SB4 50mg QW; by 6 months post-transition, 73.5% and 63.4% of subjects were receiving SB4 50mg QW. Conclusion: Patients with stable RA or axSpA who transitioned from originator ETN to SB4 maintained clinical response at 6 months post-transition. Most patients transitioned to the same dose regimen of biosimilar as they had received for the originator, remaining largely unchanged at 6 months, supporting ease and effectiveness of transition. Biogen International GmbH sponsored and funded this study. Disclosure of Interests: Klaus Krueger: None declared, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Alain Cantagrel Grant/research support from: Abbvie, Chugai, MSD, Pfizer, UCB, Consultant for: BMS, Chugai, Janssen, Lilly France, Medac, MSD France, Novartis, Pfizer, Roche, Sandoz, Sanofi Aventis, UCB, Speakers bureau: Abbvie, Biogen, BMS, Celgene, Chugai, Janssen, Lilly France, MSD France, Nordic-Pharma, Novartis, Pfizer, Roche, Sanofi, UCB, Abad Hernandez: None declared, Ulrich Freudensprung Shareholder of: Biogen, Employee of: Biogen, Mourad Farouk Rezk Shareholder of: Biogen, Employee of: Biogen, Janet Addison Shareholder of: Biogen, Employee of: Biogen

Career situation of first and presenting author Post-doctoral fellow. Introduction Anti-TNF agents are widely used in rheumatoid arthritis (RA). Their effect on inflammation results from the neutralization of soluble TNF (sTNF), but also supposedly from the induction of reverse signaling through their binding to membrane TNF (tmTNF). Despite possible clinical relevance, reverse signaling has been described only in vitro but has not been proven in vivo. Objectives In this study we aim to demonstrate for the first time the existence of tmTNF reverse signaling in vivo and its importance in anti-TNF response during arthritis. Methods Triple transgenic mouse model (3TG), KO for TNFR1/TNFR2 and KI for tmTNF, thus secreting no sTNF was developed. To analyze reverse signaling, mice were injected either with etanercept (ETA, 10 mg/kg), an anti-mouse TNF antibody (MP6-XT22, rat IgG1, 10 mg/kg) or an anti-human IL17 antibody (secukinumab, SEC, 10 mg/kg) as a control. Daily clinical evaluation of K/BxN serum induced-arthritis was performed in 3TG as well as WT mice. Polarization of bone marrow-derived macrophages (BMDM) and cytokine production from non-arthritic WT and 3TG mice under the action of anti-TNF in vitro was evaluated by RT-qPCR, CBA and ELISA. Results In vivo, the administration of anti-TNF (ETA or MP6-XT22) decreased arthritic scores in WT mice (p=0.005) as well as in 3TG mice (p Conclusions Our work provides in vivo evidence for the involvement of reverse signaling in the anti-TNF-mediated modulation of arthritis. Reverse signaling is expected to result in the modulation of macrophage polarization from an inflammatory to an alternative functional phenotype in arthritic mice. Our data prompt us to consider new interpretation of the effects of anti-TNF in the treatment of RA. Disclosure of Interest None declared.

Author(s): Deodhar, Atul; Gensler, Lianne S; Sieper, Joachim; Clark, Michael; Calderon, Cesar; Wang, Yuhua; Zhou, Yiying; Leu, Jocelyn H; Campbell, Kim; Sweet, Kristen; Harrison, Diane D; Hsia, Elizabeth C; van der Heijde, Desiree | Abstract: ObjectiveTo evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo-controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti-tumor necrosis factor [anti-TNF]-naive patients and patients with inadequate response or intolerance to anti-TNF, respectively); study 3 patients had nonradiographic axial SpA.MethodsIn all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo-treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3.ResultsFor study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies.ConclusionIn these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications.

BACKGROUND Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identify patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice. OBJECTIVE To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis. METHODS After the literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012 and 2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques. RESULTS One hundred and sixty-eight patients were recruited, of whom nine were excluded for known PsA and 21 did not attend the rheumatologist consultation. Of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained four independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged

Citrullination, carbamylation and oxidation are posttranslational modifications of proteins that produce neoepitopes. Rheumatoid arthritis (RA) is an autoimmune disease of which one distinctive feature is the development of B-cell-mediated immunity against these neoepitopes. Antibodies to citrullinated proteins (ACPAs) were identified nearly two decades ago and are now widely used in clinical practice. The identification of additional citrullinated proteins as potential autoantibody targets has suggested new pathophysiological hypotheses and prompted studies of potential associations with disease severity or specific disease patterns. Carbamylation is a nonenzymatic posttranslational modification that produces homocitrullines, against which newly identified autoantibodies different from ACPAs have been found in over 15% of patients with RA. Finally, the development of antibodies to oxidized type II collagen reflects immunization against collagen modified by oxidation in relation to intraarticular oxidative stress. These new autoantibodies are both sensitive and specific and may therefore serve as early disease markers and as useful tools for therapeutic monitoring.

ObjectiveThe objective was to investigate the short-term risk of major adverse cardiovascular events (MACEs) or congestive heart failure (CHF) in patients with psoriatic arthritis (PsA) or psoriasis initiating a biological therapy.MethodsScreening for the study was carried out using MEDLINE, Cochrane and Embase, from the inception of the database to December 2017. Randomised controlled trials (RCTs) of anti-tumour necrosis factor (TNF), anti-interleukin (IL)12/23, anti-IL23 and anti-IL17 agents for the treatment of PsA or psoriasis were included. Two investigators independently extracted MACEs or CHF data reported during the placebo-controlled phase. The primary outcome measures were the incidence of MACEs or CHF.ResultsOf 753 references screened, 62 articles were selected, and 12 articles were added by manual searches. Accordingly 77 RCTs were included in the meta-analysis (MA) (10 174 patient-years (P-Y)). No significant difference was observed in MACE incidences in patients receiving anti-TNF, anti-IL12/23, anti-IL23 or anti-IL17 agents in comparison to the placebo. However, 10 MACEs were observed in the anti-IL12/23 group (1150 P-Y) compared with 1 in the placebo group (652 P-Y), with 0.01 −0.00 to 0.02 event/P-Y risk difference, which is not statistically significant. This trend was not observed in the anti-IL23 group. No significant difference was observed in CHF incidence in patients receiving biological agents in comparison to placebo.ConclusionThis MA of 77 RCTs did not reveal any significant change in the short-term risk of MACE or CHF in patients with PsA or psoriasis initiating a biological therapy.

Background Rhupus, a combination of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus, is a rare entity. Existing epidemiological and therapeutic data are limited. Objectives The aim of this study was to describe the therapeutic impact and safety of three biologic therapies: Rituximab, Tocilizumab and Abatacept in a french Rhupus cohort. Methods We have set up a transverse observational retrospective and multi-centric study. To be included in the cohort, patients had to present an overlap syndrome fulfilling criterias for rheumatoid arthritis and lupus, and to be treated at least by one of these three therapies. Enrollment has been made with a file available on the CRI website and the analysis of the French RA registers (AIR, REGATE and ORA). Primary endpoint was the median time in therapeutic maintenance for each biological agent. Results Forty patients from fifteen rheumatologic centres were included. The main demographic data for these patients are given in table 1. Thirty of them received a treatment with Rituximab, twelve with Tocilizumab and seven with Abatacept. Nine patients received 2 biologics at two different times of the disease. The medians of therapeutic maintenance were 82 months with Rituximab, 48 with Tocilizumab and 55 with Abatacept. The detailed analysis of clinical and biologic parameters revealed differences in effectiveness between therapies: corticosteroid doses decreased more in Rituximab group, VAS activity decreased more in Abatacept group, CRP decreased more in Tocilizumab group. Safety of biologics was similar to the data in literature for RA patients. Conclusions This study provides original data on the effectiveness and safety of non-TNF biologics, mostly rituximab, in a large cohort of patients with rhupus. We have not enough patients treated with Tocilizumab and Abatacept to conclude but the therapeutic maintenance of Rituximab in Rhupus is similar to the one usually observed in RA. Disclosure of Interest None declared

Background Recently, EULAR updated the rheumatoid arthritis (RA) management recommendations.1 2 In 2018, the French Society of Rheumatology (SFR) updated their recommendations regarding the management of RA.3 This gave us the opportunity to compare the recommendations. Objectives To update the 2014 French recommendations for the management of RA and to compare them to the EULAR recommendations. Methods The SFR approach was based on the literature and on expert opinion. A systematic literature review (SLR) was performed by 2 fellows, collecting data to answer 11 questions. The previous (2014) recommendations were updated by a committee including 11 rheumatologists, 2 patients and 1 healthcare professional, during a 1 day meeting in January 2018. The recommendations were compared to the recently issued EULAR recommendations.1 2 Results The SLR included 137 papers. The consensus process led to 4 overarching principles and 15 recommendations. The overarching principles emphasise the need for shared decisions between the rheumatologists and the patient and the importance of a global approach of RA including pharmaceutical and non-pharmacological management. The recommendations address the diagnostic phase of RA, early initiation of disease-modifying antirheumatic drugs (DMARDs) and the usefulness of regular disease activity assessments through validated composite indices with a target of clinical remission or low disease activity. As first strategy, the expert committee recommends methotrexate (MTX). In case of intolerance or inadequate response to MTX, treatment must be optimised. If unfavourable prognostic markers are present, adding a targeted treatment (either biologic or synthetic) can be proposed, at best in combination with MTX; if not, switching to another conventional synthetic DMARD (csDMARD) or combined csDMARDs therapy can be proposed. While waiting for csDMARDs efficacy, short term (less than 6 months) glucocorticoids (GC) can be proposed. Second-line and further treatments and management of remission are also addressed, as well as the importance of managing comorbidities and of non-pharmacological measures. Conclusions These recommendations are designed to improve the management of RA and are concordant with the recent EULAR recommendations on several items. Main differences concern the place of GC and of combined csDMARD therapy, as well as additional points on diagnosis, non-pharmacological measures, comorbidities and the importance of a global approach. References [1] Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis2017;76(6):960–77. [2] Combe B, Landewe R, Daien CI, et al. 2016update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis2017;76(6):948–59. [3] Gaujoux-Viala C, Gossec L, Cantagrel A, et al. Recommendations of the French Society for Rheumatology for managing rheumatoid arthritis. Jt Bone Spine Rev Rhum2014;81(4):287–97. Disclosure of Interest None declared

ObjectivesTo assess the risk of losing remission, low disease activity (LDA) or radiographic progression in the case of (1) discontinuing or (2) tapering doses of biological disease-modifying antirheumatic drugs (bDMARDs) compared with continuation of the initial treatment regimen in rheumatoid arthritis (RA) patients with remission or LDA.Materials and methodsA systematic literature analysis was carried out through May 2017 on the PubMed, Embase, Cochrane and international congress databases, selecting controlled trials comparing bDMARDs discontinuation/tapering versus continuation in RA patients with remission or LDA. The meta-analysis assessed the risk ratio (RR) and 95% CI of losing remission or LDA and the risk of radiographic progression after (1) discontinuing and (2) tapering doses of bDMARDs versus continuing the initial treatment.ResultsThe meta-analysis comparing bDMARDs discontinuation versus continuation performed on nine trials showed an increased risk of losing remission (RR (95% CI)=1.97(1.43 to 2.73), PConclusionDiscontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographic progression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographic progression, even though there is an increased risk of losing remission.

International audience; Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16–0.61), p = 0.001). No association was found with any of the other SNPs tested.

Introduction Adipose-derived mesenchymal stem cells (ADSC) are currently considered as a potential innovative therapy for rheumatoid arthritis (RA) due to their immune-modulating properties. It has been well established that ADSC exert an immune-regulating response when exposed to an inflammatory environment through the secretion of soluble mediators and cell-cell contact mechanisms. Several molecules are implicated in ADSC-mediated immunomodulation such as PGE2, IDO, IL-6, TGF-β and TSG6. However, while ADSC have shown remarkable results in vitro and in animal models, their efficacy in clinical applications has yet to be fully elucidated. Objectives Considering the diversity of the local inflammatory microenvironment in the joints of RA patients and to further explore the behaviour of ADSC within their microenvironment, we aimed to study the effect of synovial fluid (SF) collected from patients with RA on ADSC proliferation and immune-modulating properties. Methods ADSC isolated from 6 healthy subjects were cultured for 24 hours in the presence or absence of RASF (diluted to 5%) obtained from 10 different RA patients or a control SF obtained from a patient undergoing non-inflammatory rheumatism related surgery. ADSC proliferation was assessed by an MTT colorimetric assay. After SF treatment, ADSC were harvested for RNA extraction and subsequent RT-qPCR to quantify the gene expression of COX2, IL6, IDO, TSG6, TGF-β. To evaluate the inflammatory status of SF, pro-inflammatory cytokines present in SF were first identified using an antibody-based membrane array and then quantified by ELISA or CBA. Results RASF differentially affected the proliferation of ADSC with 2 out of 10 inducing ADSC proliferation whilst the remaining inhibited proliferation. Gene expression of COX2, IDO, IL-6, TSG6 and TGF-β was simultaneously induced in only 4 of the 10 RASF included in this study. We thus investigated if these four RASF had any particular inflammatory signature that could explain their effect on ADSC. Higher concentrations of one or more of the following markers IL-6, TNFα, MCP1, ICAM1, IL1ra were detected in these SF compared to others, which correlates with a more potent pro-inflammatory environment. Conversely, RASF that had no effect on ADSC gene expression presented a less inflammatory profile. Recombinant cytokines and neutralisation assays are underway to determine which specific molecules mediated the SF effect on ADSC. Conclusions Proper licensing of ADSC to an anti-inflammatory phenotype is usually done in vitro by stimulation with high concentrations of pro-inflammatory cytokines which do not necessarily reflect the concentrations present in the synovial fluid. This study sheds further light on how ADSC respond to local inflammatory stimuli in order to better direct their immunomodulatory ability and efficacy in clinical therapy. Acknowledgements *N. Alaaeddine and J.-L. Davignon are joint senior authors Disclosure of interest None declared

International audience; Objective: The aim was to evaluate the incidence of serious infusion-related reactions (SIRRs) in RA treated by non-TNF-targeted biologics. Methods: We analysed data from three independent prospective registers, namely autoimmunity and rituximab, Orencia (abatacept) and RA (ORA) and Registry RoAcTEmra (tocilizumab), promoted by the French Society of Rheumatology and including patients with RA. SIRRs were defined by an occurrence during or within 24 h of an infusion and requiring discontinuation of treatment. Characteristics of patients with SIRRs were extracted from the electronic database. Results: Among the 4145 patients, SIRRs occurred in 100 patients: 56 patients with the rituximab cohort (2.8% or 0.7/100 patient-years), 15 with the abatacept cohort (1.5% or 0.6/100 patient-years) and 29 with tocilizumab (1.9% or 1/100 patient-years). No fatal SIRR occurred. A previous mild infusion reaction to non-TNF-targeted biologics was observed in a quarter of patients with SIRRs. After pooled multivariate analysis, positive anti-CCP was associated with a higher risk of SIRR (odds ratio = 2.5; 95% CI: 1.01, 6.17). Absence of concomitant treatment with a synthetic DMARD tended to be associated with a higher risk of SIRR (odds ratio = 1.67; 95% CI: 1.00, 2.86). Conclusion: In daily practice, SIRRs are slightly more frequent than in clinical trials and rarely life threatening. In common practice, serological status (anti-CCP positivity) and absence of concomitant treatment with a synthetic DMARD increase the risk of SIRR.

International audience; INTRODUCTION: Sanoia is an online interactive electronic e-health platform developed to allow patient self-assessment and self-monitoring. The objective was to assess in rheumatoid arthritis (RA) patients, the efficacy on patient-physician interactions, of giving access to Sanoia.METHODS: In this French, multi-center, 12-months randomized controlled trial (CarNET: NCT02200068), patients with RA and internet access were randomized to: access without incentives to the Sanoia platform after minimal training, or usual care. The primary outcome was the change from baseline in patient-physician interactions, by the patient-reported Perceived Efficacy in Patient-Physician Interactions (PEPPI-5) questionnaire. The number of accesses to Sanoia was recorded and satisfaction with the platform was assessed through a 0-10 numeric rating scale. Analyses were in intention to treat (ITT), on SAS.RESULTS: Of 320 RA patients (159 Sanoia versus 161 usual care), mean (standard deviation) age was 57.0 (12.7) years, mean (SD) disease duration was 14.6 (11.1) years, 216 (67.5%) were taking a biologic and 253 (79.1%) were female. Mean (SD) PEPPI scores at baseline and 12 months were 38.6 (8.2) and 39.2 (8.0) (delta=+0.60 [5.52]) versus 39.7 (7.3) and 38.8 (8.0) (delta=-0.91 [6.08]) in the Sanoia and control group, respectively (P=0.01). Although mean satisfaction with the platform was very high (1.46 [1.52]), 41 patients (25.7%) never accessed Sanoia.CONCLUSION: Giving RA patients access to the interactive Sanoia e-health platform led to a small improvement in patient-perceived patient-physician interactions. A disjunction between patient satisfaction and access to the platform was noted. E-Health platforms are promising in RA.

Introduction An understanding of real-world predictors of abatacept retention is limited. We analysed retention rates and predictors of abatacept retention in biologic-naïve and biologic-failure patients in a 12-month interim analysis of the 2-yearAbataCepTIn rOutiNe clinical practice (ACTION) study. Methods ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. In this 12-month interim analysis, crude abatacept retention rates, predictors of retention and European League Against Rheumatism (EULAR) response were evaluated in both biologic-naïve and biologic-failure patients. Retention by rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) status was also assessed, in patients with or without baseline radiographic erosions, and by body mass index (BMI). Results Overall, 2350/2364 enrolled patients were evaluable (674 biologic naїve; 1676 biologic failure). Baseline characteristics were largely similar in biologic-naïve and biologic-failure groups. Crude retention rates (95% CI) at 12 months were significantly higher in biologic-naїve (78.1%(74.7% to 81.2%)) versus biologic-failure patients (69.9%(67.6% to 72.1%); P

Objective To investigate the possible link between Porphyromonas gingivalis infection and rheumatoid arthritis (RA), according to antibody profile, genetic and environmental factors, and RA severity. Methods For assessing P gingivalis infection, serum levels of antibodies directed against P gingivalis lipopolysaccharide were measured in 694 patients with early RA who were not exposed to steroids or disease-modifying antirheumatic drugs. Anti–P gingivalis antibody titers were compared between patients with early RA and various control groups, and according to various patient characteristics. Results Anti–P gingivalis antibody titers did not significantly differ between patients with RA and controls and did not significantly differ with anti–citrullinated protein antibody (ACPA), rheumatoid factor (RF), or HLA shared epitope status. Anti–P gingivalis antibody titers were significantly higher among patients who had never smoked compared to patients who had ever smoked (P = 0.0049). Among nonsmokers, high anti–P gingivalis antibody levels were associated with a higher prevalence of erosive change (47.5% versus 33.3% with modified Sharp/van der Heijde score erosion subscale ≥1; P = 0.0135). Conclusion In this large early RA cohort, we did not detect any association of anti–P gingivalis antibodies with RA or with ACPA status. These results suggest that the association of periodontitis and RA could be linked to bacterial species other than P gingivalis or to a mechanism other than citrullination. Nevertheless, we found higher anti–P gingivalis antibody titers in nonsmokers. In addition, in this population of nonsmokers, high anti–P gingivalis antibody titers were associated with more severe disease. We hypothesize that the role of tobacco in RA pathogenesis is so high that the effect of P gingivalis could be revealed only in a population not exposed to tobacco.

Objectives Diagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc. Methods A systematic literature search was performed using PubMed and Cochrane databases’ publications between 1999 and March 2017. Search terms were: “systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor OR cohort OR value diagnostic)”. In a first step, we selected cohorts with > 50 SSc patients with ACPA identification, for ACPA frequency determination. In a second step, we included studies that analysed clinical profiles according to ACPA status. Meta-analyses were performed when at least two studies were available. Results First, we identified 13 observational studies with a total of 1231 SSc patients. The mean prevalence of ACPA in SSc was 9.2%. Secondly, we identified nine studies reporting clinical aspects according to ACPA status. Our meta-analyses showed a significant association between ACPA positivity and the presence of arthritis (odds ratio (OR) = 22.48 [10.71–47.21]), joint erosions seen on X-rays (OR = 14.79 [6.38–34.28]), pulmonary fibrosis (OR = 2.75 [1.21–6.24]), oesophagus involvement (OR = 2.72 [1.05–7.07]), and diffuse skin involvement (OR = 2.21 [1.21–4.03]). Conclusions The prevalence of ACPA in scleroderma is 9.2%. Our meta-analysis shows an increased risk for erosive arthritis, pulmonary fibrosis, oesophagus involvement and diffuse skin involvement, in patients with ACPA-positive SSc. ACPA should be systematically included in SSc assessment.

Objective To assess the effectiveness of exercise programs on disease activity and function in ankylosing spondylitis (AS) by a systematic review and meta-analysis of randomized controlled trials (RCTs). Data Sources Medline via PubMed and Cochrane Library. Study Selection Reports of RCTs examining the effectiveness of exercise programs for AS published up to May 2017. Data Extraction Outcomes were evolution of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after the completion of exercise programs. Modalities of exercise were compared and the use of biologic therapy was reported. Data Synthesis After screening 190 abstracts, we selected 26 reports for detailed evaluation and finally investigated 8 trials that assessed a home-based exercise program (2/8), swimming (1/8), Pilates training (1/8), or supervised exercises (4/8), for a total of 331 patients with AS. Four trials included patients receiving antitumor necrosis factor therapy. All trials except one showed a decrease in BASDAI and BASFI with exercise. The weighted mean difference was −0.90 (95% confidence interval, −1.52 to −0.27; I 2 =69%; P =.005) for the BASDAI and −0.72 (95% confidence interval, −1.03 to −0.40; I 2 =0%; P Conclusions Despite the small number of patients and the heterogeneity of exercise programs in the RCTs included in this meta-analysis, its results support the potential of exercise programs to improve disease activity and body function in AS.

Background Disability, alteration in quality of life and fatigue are frequently reported in spondyloarthritis (SpA). Anti-TNF demonstrated clinical efficacy in SpA. However efficacy on patient-reported outcomes (PROs) may differ from medical assessment. Objectives To assess the impact of anti-TNF on quality of life, disability and fatigue reported by SpA patients. Methods Design: systematic review and meta-analysis of the literature. Data sources: two authors (SL and YD) independently screened PubMed-Medline, Cochrane library and EMBASE databases until November 2016. Key words: (“Patient reported” OR “quality of life” OR fatigue OR FACIT) AND (spondyloarthritis OR “psoriatic arthritis” OR “ankylosing spondylitis”) AND (anti-TNF OR certolizumab OR etanercept OR adalimumab OR infliximab OR golimumab). Articles selection: randomized controlled trials (RCTs), published in English, assessing efficacy of anti-TNF on PROs, in ankylosing spondylitis (AS), psoriatic arthritis (PsA) or SpA according to the ASAS criteria. Data collected: fatigue assessed by FACIT score, quality of life assessed by Short Form 36 (SF36) mental and physical component or by Health AssessementQuestionnary Disability Index (HAQ). Data analysis: Article quality was evaluated by the JADAD scale. For SF36 and HAQ outcomes, pooled variations at 12 and 24 weeks were computed by meta-analysis. Heterogeneity was measured by I2 index. Results Of the 604 articles identified, 37 references were eligible for systematic review and 13 for meta-analysis. Our systematic review identified 10 RCTs concerning AS, 20 concerning PsA and 7 concerning axial SpA. However due to the heterogeneity in available statistical data, references eligible for meta-analysis were mainly related to PsA. HAQ assessment was available for a meta-analysis in 8 studies. HAQ was significantly improved at 12 and 24 weeks with anti-TNF. The impact on HAQ variation at week 24 was -0.29 points [95% CI: -0.37, -0.22]. Heterogeneity was important (I2 =57%; see figure). Ten studieswere eligible for a meta-analysis of anti-TNF effect on SF36 mental form. An improvement was observed at 12 and 24 weeks, although superior at 24 weeks. The effect at week 24 was 2.78 [95% CI: 1.87 - 3.68], without heterogeneity (I2 =0%; see figure). Twelve studies were eligible for a meta-analysis of anti-TNF effect on SF36 physical form. We observed a similar and significant improvement at 12 and 24 weeks. The effect at week 24 was 6.74 [95% CI: 5.34 – 8.13], with an important heterogeneity (I2 =84%; see figure) Fatigue was evaluated in 3 studies. Adalimumab induced a significant improvement in FACIT score at 12 and 24 weeks in one study. Two studies using different scores (Fatigue Assessment Scale, BASDAI fatigue item) to assess certolizumab effect highlighted similar findings: an early improvement in fatigue at week 12, remaining significant and stable at week 24. Conclusions Anti-TNFs agents significantly improve disability, quality of life and fatigue in patients with PsA. Acknowledgements Abbvie France pharmaceutical company provided logistic support by organizing a meta-analysis methods workshop, but played no further role in the project. Disclosure of Interest None declared

Background Tocilizumab (TCZ) as monotherapy (Mono) is nowadays a standard treatment in rheumatoid arthritis (RA) for patients in whom methotrexate (MTX) is inappropriate1. Objectives To describe factors influencing the use of TCZ in Mono or in combination with DMARDs (Combo) in real-life practice in RA patients (pts). Methods Analysis: pooled data of 3 prospective, multicentre, observational studies (PEPS n=610, Spare-1 n=307, Act-solo n=577). Patients: RA pts requiring TCZ treatment according to their physician. Treatment: TCZ as prescribed in real life. Endpoint: Evaluation of factors influencing the use of TCZ in Mono or in Combo. Data collected: demographic characteristics, past medical history, RA characteristics and history including previous RA treatments, TCZ treatment strategy (Mono or Combo). Statistical analysis: Pts fulfilling inclusion and non-inclusion criteria and with ≥1 TCZ infusion were analyzed. 1- descriptive analysis 2- Univariate and multivariate analysis to determine factors influencing the use of TCZ in Mono. Variables with more than 20% of missing data were excluded from the multivariate model. Results 1494 pts (3 studies) were analysed at inclusion. Pts9 characteristics: 56% of the pts were >55 years old, 79.6% female, mean RA duration 11.1±9.3 years, 83.0% positive for rheumatoid factors and/or ACPA, 77.3% with erosive disease on X-rays, mean ESR 29.9±23.1mm, mean CRP 19.9±26.2 mg/l mean DAS 28-ESR 5.21±1.22, mean HAQ-DI 1.56±0.68, and mean pain VAS 61.5±23.2. Past RA treatment included csDMARDs in 98.5% and biologics in 77.8% (median=2 [1–6]). TCZ was initiated as Mono in 36.4% of pts and in Combo in 63.6%, with MTX in 83.3% of Combo pts (mean dose 15.7±4.4mg/week). Corticosteroids were used in 74% of pts (mean dose 10±7mg/day). Variables associated with a TCZ prescription in Mono were age (≥65 years), number of previous bDMARD, use/dose of steroids, ESR/CRP values, VAS global activity (physician and pt), pain VAS and HAQ-DI. In the multivariate analysis, variables associated with a TCZ prescription in Mono were age ≥65 years (OR=1.71 [1.30 - 2.24], p Conclusions This pooled analysis suggests that physicians preferably prescribe TCZ alone in older patients, heavily treated before, with higher inflammatory markers and higher pain VAS. This use might be explained by physicians9 reluctance to prescribe the association in frailer patients and complementary data on comorbidity factors will be analysed to support this hypothesis. References JS. Smolen et al, Ann Rheum Dis doi:10.1136/annrheumdis-2013–204573. Disclosure of Interest A. Saraux: None declared, A. Cantagrel: None declared, B. Combe Consultant for: Chugai Pharma France, R.-M. Flipo Consultant for: Chugai Pharma France, I. Idier Employee of: Chugai Pharma France, C. Baffie Employee of: Altizem for Roche SAS, J. Tebib: None declared

Background Interactive, online electronic (e)-health services with patient-reported outcome measure (PROM)-based instruments may be helpful for patients (pts). Sanoia is a secure, independent e- and mobile (m)-health platform developed to allow pt self-assessment, storage of questions to ask physicians, and self-monitoring of disease status. The platform offers a dedicated set of scores, PROMs and information about different diseases, including rheumatoid arthritis (RA). Objectives To characterise pts with RA who chose to access e-health services regularly over a 12-month (mo) period. Methods Post-hoc analysis of CarNET (NCT02200068): a French, multicentre, 12-mo randomised controlled trial. Pts with RA were randomised to: access to Sanoia (30-min training via the telephone with no further incentive to access the platform) or usual care (normal internet use without access to Sanoia). The Sanoia group pts used a home-based e-Case Report Form to record frequency of Sanoia access, satisfaction with the platform (0–10 scale; 0=completely satisfied, 10=not satisfied), and barriers to use (from a pre-specified list). Baseline pt characteristics associated with more frequent use (above the median) were analysed by univariate and multivariate logistic regression. Results 159 RA pts were randomised to the Sanoia arm: mean±SD age was 56.1±13.1 years, disease duration was 15.0±11.5 years and 132 (83.0%) of pts were female. Mean DAS28 was 2.7±1.2 with 57.2% of pts in remission; 115 (72.3%) were taking a biologic; 23.3% had attended therapeutic education sessions; 15.7% were members of pt associations; and 53.5% had participated in university-level studies. Overall, 41 pts (25.7%) never accessed Sanoia and 81 (50.9%) accessed the platform at least twice; median=2, mean±SD=4.4±11.3 connections/pt over the 12 mos. 54 pts (34.0%) used Sanoia for ≥2 mos with a noticeable investigator effect (0.3±0.2, 0–1 scale). Mean satisfaction with the platform was very high (1.5±1.5), with 90% scoring satisfaction ≤3. One barrier was expressed in 11.8% of cases: “the platform is not useful for me since I am in remission”. In multivariate analysis, the only variable associated with greater usage of Sanoia was being a member of a pt association: odds ratio [95% CI]=1.44 [1.17–1.77]. Conclusions A quarter of pts who participated in this trial to assess e-health did not access the platform whereas half accessed the platform at least twice. Pts expressed high satisfaction and the only barrier was lower usefulness when in remission. e-Health is a promising tool for self-management in RA. The impact of offering additional services should also be explored in a further study. Acknowledgements This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical Consulting. Disclosure of Interest L. Gossec Grant/research support from: UCB Pharma, Lilly, Consultant for: AbbVie, BMS, Celgene, Janssen, Novartis, MSD, UCB, A. Cantagrel: None declared, M. Soubrier: None declared, J. M. Joubert Employee of: UCB Pharma, W. Czarlewski Employee of: UCB Pharma, B. Combe Grant/research support from: Merck Pfizer Inc, Roche-Chugai, Consultant for: Merck, Pfizer, Roche-Chugai, UCB Pharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Speakers bureau: Merck, Pfizer, Roche-Chugai, UCB Pharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, J. M. Berthelot: None declared, D. Wendling: None declared, E. Dernis: None declared, L. Grange: None declared, C. Beauvais Speakers bureau: UCB Pharma, A. Perdriger: None declared, H. Nataf: None declared, M. Dougados Grant/research support from: UCB Pharma, AbbVie, Pfizer, Lilly, Merck, Novartis, H. Servy Shareholder of: Sanoia platform operating company: e-health services, Employee of: Sanoia

Background Antidrug antibodies (ADAb) seem to be associated with a loss of response in immune-mediated inflammatory diseases (1) and in psoriatic arthritis (2). Objectives To assess the effect of ADAb on clinical response in patients with spondyloarthritis (SpA) treated with anti-TNF drugs. Methods We conducted a systematic literature review of controlled trials and observational studies assessing the effect of ADAb on response to anti-TNF drugs (Adalimumab (ADL), Certolizumab (CTZ), Etanercept (ETA), Golimumab (GOL) and Infliximab (INF)) in patients with axial or peripheral SpA. Databases analysed were PubMed, the Cochrane library, and ACR/EULAR meeting abstracts, until January 2017. A meta-analysis was performed using the inverse variance approach and statistical heterogeneity was assessed with the Cochran Q-test and I 2 values. A statistical threshold of 5% was considered as significant. Results Over 1,387 publications screened, 7 studies were selected for meta-analysis (3–9). These studies were observational studies (n=6) or controlled trial (n=1); involved patients with axial or peripheral SpA (n=6) or psoriatic arthritis (n=1); included treatments with ADL (n=4), ETA (n=1), INF and INF biosimilar (n=2), or various anti-TNF drugs (n=1). ADAb rates varied between anti-TNF drugs: 0% for ETA, 13.6–31.4% for ADL, 0–28.9% for INF. Patients with ADAb were less often responders than patients without ADAb in 6 studies, more often responders in one study, while the risk ratio (RR) for response was not assessable in one study due to the absence of ADAb. The weighted pooled RR (95% CI) for response to anti-TNF drugs was 0.73 (0.54–0.98) in ADAb+ in comparison with ADAb- patients (p=0.04) (see figure). There were trends towards more infusion reactions and lower serum drug levels in patients with ADAb (data not shown). Conclusions According to the results of this meta-analysis, ADAb positivity is associated with a lower rate of response to anti-TNF agents in patients with SpA. References The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis, Garces.S and al, ARD 2014; 72:1947–1955. The comparative immunogenicity of biologic therapy and it9s clinical releavance in psoriatic arthritis: a systematic review of the literature, Balsa.A and al, ACR 2016, Abstract number 1691. Disclosure of Interest None declared

Background Macrophages contribute to the rheumatoid arthritis (RA) pathogenesis. They can display various states of activation or “ polarization ”, characterized by distinct functions in inflammation, and reversibility depending on their environment [1]. M1 polarization corresponds to the “classical”, pro-inflammatory activation as identified in RA. M2 “alternative” polarizations display pro-resolving or wound-healing properties. Data concerning the effects of RA biological drugs (bDMARDs) on macrophage polarization are scarce. Objectives To assess in vitro modulation of macrophage polarization by RA bDMARDs. Methods Blood monocytes from 14 healthy donors were positively sorted by CD14+ magnetic selection. Macrophages were Derived from Monocytes (MDM) by 5 days of culture in the presence of MCSF, and activated or not for 24h as M1 pro-inflammatory MDM (by LPS + IFNγ) or as M2 alternative MDM (by IL10 or IL4). MDM were cultured with or without bDMARDs. We evaluated 2 anti-TNF agents (etanercept (ETA), adalimumab (ADA)), 1 anti-IL6R agent (tocilizumab (TCZ)), and 1 anti-CD20 agent (rituximab (RTX)) used as control monoclonal antibody. bDMARDs effects were assessed separately on differentiation and activation phases by flow cytometric analysis of membrane markers. Functional aspects of polarization were assessed by analysis of cytokine production in supernatants (cytometric bead array) and phagocytosis (flow cytometry). MDM cultured in the presence of bDMARDs were compared to untreated MDM by a Wilcoxon matched pairs test. Results We first validated membranous polarization markers in our culture model: CD40 and CD80 as M1 (LPS + IFNγ) markers; CD16, CD163 and CD64 as M2 (IL10) markers, CD206 and CD200R as M2 (IL4) markers. Anti-TNF significantly modulated surface polarization markers of MDM obtained after differentiation. CD40 decreased with both anti-TNFs. CD16 increased with ADA, whereas opposite effects on CD64, decrease with ETA, increase with ADA, were observed. CD206 increased with ADA. CD200R increased with both anti-TNF. We observed a significant increase in CD64 with TCZ. RTX induced no modulation except an increase in CD64. Concerning the effect of bDMARDs on M1 activation (M1 MDM) shown in Figure, anti-TNF agents induced a significant decrease in M1 markers and a significant modulation in M2 (IL10) markers. We observed a decrease in CD40 and CD80, an increase in CD16, CD163, a decrease in CD64 with ETA and an increase with ADA. TCZ induced a slight but significant decrease in CD40 and an increase in CD64. RTX only affected CD64 as observed for differentiation. In M2 (IL4) et M2 (IL10) activated MDM, anti-TNF agents induced a similar trend toward M2 (IL10) phenotype. Anti-TNF agents led to a significant decrease in TNFα, IL6, IL12 and IL10 levels measured in cell culture supernatant after M1 MDM. TCZ mainly affected IL6 and TNFα productions. No significant effect was observed with RTX. Phagocytosis was superior in M2 (IL10) and M2 (IL4) activated MDM than in M1 MDM. Anti-TNF agents but not TCZ or RTX induced an increase of phagocytosis in M1 MDM. Conclusions Anti-TNF agents upregulate M2 alternative pro-resolving markers and downregulate M1 inflammatory markers in macrophages. Our results need to be extended by transcriptional analysis and evaluated in RA patients. References Martinez FO and Gordon S, F1000Prime Reports 2014, 6:13. Disclosure of Interest Y. Degboe Grant/research support from: Societe Francaise de Rhumatologie, B. Rauwel: None declared, M. Baron: None declared, J.-F. Boyer: None declared, A. Cantagrel: None declared, A. Constantin: None declared, J.-L. Davignon: None declared

Background DAS28 is often used as a treatment decision tool in patients with rheumatoid arthritis (RA) in the daily clinic. Although different versions of DAS28 have previously been validated, and although disease activity thresholds are the same, it is not clear whether DAS28-ESR and DAS28-CRP can be used interchangeably in individual patients. Objectives The aims of our study were to examine the agreement between these two DAS28 versions in individual early RA patients in the daily clinic and to idenditify factors related to the discrepancies between disease activity levels according to these 2 scores. Methods Baseline and 6 months data from 677 patients with early RA (ACR EULAR 2010) were extracted from the French cohort of early arthritis ESPOIR (at least 2 swollen joints for less than 6 months, DMARD naive) and were used to calculate DAS28-ESR and DAS28-CRP. Disease activity levels according to the DAS thresholds and EULAR responses were assessed. Intraclass correlation coefficient [ICC] and weighted kappa (k) were calculated. The Bland-Altman method was used to examine the bias between the DAS scores and the 95% limits of agreement (LoA). Multivariate logistic regression was used to determine the patient and RA features independently associated with discrepancies between disease activity levels according to DAS28-ESR and DAS28-CRP. Results The mean value of DAS28-CRP (5.04±1.16 at M0 and 3.38±1.33 at M6) was smaller than that of mean DAS28-ESR (5.33±1.24 at M0 and 3.51±1.42 at M6). Agreement between the scores was excellent: ICC=0.93 at M0 and M6. Agreement between disease activity levels according to the 2 scores was good: k=0.70 at M0 and 0.75 at M6. Agreement between EULAR responses at M6 according to the 2 scores was good: k=0.78. At M0, the bias of DAS28-CRP was -0.28 (LoA -1.16, 0.59) and -0.14 (LoA -1.17, 0.89) at M6.There were discrepancies between disease activity levels according to the 2 scores in 122 (18.6%) patients at M0 with clear difference in moderate (88 patients for DAS28-CRP vs 29 for DAS28-ESR) and high disease activity (18 patients for DAS28-CRP vs 80 for DAS28-ESR), and in 171 (28.1%) patients at M6 with clear difference in remission (42 patients for DAS28-CRP vs 29 for DAS28-ESR) and high disease activity (9 patients for DAS28-CRP vs 32 for DAS28-ESR). At M0, presence of erosion (OR 95% CI=1.76 [1.07–2.90]), better mental component of the SF36 (OR 95% CI=2.14 [1.38–3.31]), fewer tender joint counts (TJC) and better physical component of the SF36 (PCS) (with significant interaction between TJC and PCS) were associated with discrepancies between disease activity levels according to the 2 scores. At M6, only being male (OR 95% CI=1.62 [1.09–2.41]) was associated with discrepancies. Conclusions DAS28-CRP significantly underestimated disease activity compared to DAS28-ESR. Agreement was high between the 2 scores, good for disease activity levels and EULAR responses. In the individual patient, however, the two scores may differ considerably. The scores should not be used interchangeably in the daily clinic without caution. Disclosure of Interest None declared

Background There has been growing emphasis on the importance of shared decision-making in rheumatoid arthritis (RA).1,2 Patient-physician (pt-phy) shared decision-making necessitates open and thorough discussions and good interactions. Objectives This analysis explored pt-perceived quality levels of pt-phy interactions and characteristics of pts when these interactions are described as very good by pts. Methods CarNET (NCT02200068) was a French, 12-month, multicentre randomised controlled trial to assess access to an e-health platform (Sanoia) allowing self-assessment of disease.1,2 This was a post-hoc analysis, using baseline data only. Pts had confirmed RA and were enrolled by their treating rheumatologist. Pt-perceived pt-phy interactions were assessed through the pt-reported questionnaire Perceived Efficacy in Patient-Physician Interactions (PEPPI-5)3 which consists of 5 items, each starting with “How confident are you in your ability to ...” (eg. “... know what questions to ask a doctor?”). Pts rated each item on an 11-point scale; 0=not at all confident, 10=very confident. Total PEPPI-5 scores range from 0–50; higher scores represent higher perceived self-efficacy in pt-phy interactions. Factors associated with a higher PEPPI-5 (ie. >median) were analysed by univariate and multivariate logistic regression (factors included pt demographics, phy demographics, disease characteristics and activity including pt-perceived coping [scored 0–10 in the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire; lower scores indicate better coping]). Results Of 320 RA pts (159 vs 161; Sanoia vs usual care), mean±SD age was 57.0±12.7 years, disease duration was 14.6±11.1 years and 253 (79.1%) were female. Mean DAS28 was 2.7±1.2, 54.1% were in DAS28 remission ( Conclusions Among RA pts whose disease was well controlled, pt-perceived pt-phy interactions were good. Pt-perceived coping was associated with better pt-perceived pt-phy interactions, indicating that perhaps pts who felt in control were more at ease with their phy, or vice-versa. The data did not allow us to attribute causality. These elements are important in the shared decision-making process. References www.sanoia.com. Gossec L. Arthritis Rheum 2016;68:S10. ten Klooster P. Patient Educ Couns 2012;87(1):125–30. Acknowledgements This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical Consulting. Disclosure of Interest L. Gossec Grant/research support from: UCB Pharma, Lilly, Consultant for: AbbVie, BMS, Celgene, Janssen, Novartis, MSD, UCB, C. Desthieux: None declared, A. Cantagrel: None declared, M. Soubrier: None declared, J. M. Berthelot: None declared, J. M. Joubert Employee of: UCB Pharma, B. Combe Grant/research support from: Merck Pfizer Inc, Roche-Chugai, Consultant for: Merck, Pfizer, Roche-Chugai, UCB Pharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Speakers bureau: Merck, Pfizer, Roche-Chugai, UCB Pharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, W. Czarlewski Employee of: UCB Pharma, D. Wendling: None declared, E. Dernis: None declared, L. Grange: None declared, C. Beauvais Speakers bureau: UCB Pharma, A. Perdriger: None declared, H. Nataf: None declared, M. Dougados Grant/research support from: UCB Pharma, AbbVie, Pfizer, Lilly, Merck, Novartis, H. Servy Shareholder of: Sanoia platform operating company: e-health services, Employee of: Sanoia

Background Blau Syndrome (BS) is a rare autosomal dominant inflammatory disease characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis (1). Mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 gene (mainly R334W, R334Q and L469F) have been identified in Blau syndrome (2). Despite advances in BS knowledge, patients9 functional prognosis remains uncertain, BS potentially leading to visual impairment or joint deformities. Optimal treatments have not been determinated yet. Objectives To assess the efficacy of several biologic agents in this affection Methods We conduct an observational, international, retrospective cohort of BS collecting clinical, biological and histological data. Results Among the twenty-three patients included in the cohort, 14 patients were treated by one or several lines of biologic agents, mostly by TNF blockers (80%), IL1 blockers (16%) or treatment targeting CTLA-4 (4%). Fifty-seven percent of patients achieved remission after almost two lines of treatment (1.75 lines; [0.8–2.7]). Association with csDMARDs did not significantly improved response to biologics. Considering the 3 mains symptoms independently, TNF blockers were associated with a better response in case of articular or skin features but less effective in case of ocular involvement, a clinical situation in which IL-1 targeting should be preferentially chosen. Conclusions Biologic treatments appeared to be effective in BS but additional data prospectively collected are still needed in order to define their place in the therapeutic strategy in order to minimize functional consequences. References Blau EB. Familial granulomatous arthritis, iritis, and rash. The Journal of pediatrics. 1985 Nov;107(5):689–93. PubMed PMID: 4056967. Epub 1985/11/01. eng. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nature genetics. 2001 Sep;29(1):19–20. PubMed PMID: 11528384. Epub 2001/08/31. eng. Disclosure of Interest None declared

Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors.In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295.Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4-45·2]; p0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1-39.8]; p0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported.Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab.Eli Lilly and Company.

Objectives To compare the risk of serious adverse events, serious infections and death caused by methotrexate and biological disease-modifying antirheumatic drug (bDMARD) combination therapy versus a bDMARD prescribed as monotherapy in rheumatoid arthritis (RA). Methods A systematic literature review was conducted until February 2016 in PubMed, Embase and Cochrane Library databases by selecting randomised controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy in RA. The meta-analysis compared the occurrence of (1) serious adverse events, (2) serious infections and (3) death among these groups by the Mantel-Haenszel method. Results The literature review selected 16 controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy. After meta-analysis comparing patients under monotherapy to those under combination therapy: (1) the risk of occurrence of serious adverse events was comparable in 12 trials: RR (95% CI) 0.92 (0.78 to 1.08). (2) No significant difference was observed in the risk of occurrence of serious infections in 13 trials: RR (95% CI) 1.15 (0.84 to 1.58). We noted a trend, although insignificant, towards a high risk of the occurrence of tuberculosis in 10 studies: RR (95% CI) 1.78 (0.63 to 4.99). (3) The risk of death was comparable in 12 trials: RR (95% CI) 0.73 (0.40 to 1.35). Conclusions The results showed no significant difference between the two groups, confirming that the use of methotrexate and bDMARD combination therapy in RA does not cause an increased risk of serious adverse events or serious infections or death compared with bDMARD monotherapy.

Objective: The impact of gender on the response and tolerance to abatacept was assessed in a large prospective cohort during 2 years of follow-up. Methods: From the 1017 patients included in the Orencia and Rheumatoid Arthritis registry, disease activity was assessed at baseline, 6, 12 and 24 months. The relationship between the European League Against Rheumatism (EULAR) response, Disease Activity Score 28 (DAS28) remission, rate of adverse events and gender was explored in multivariate analysis. Results: 990 patients, 79.3%female, with at least one follow-up visit were analysed. At baseline, women had longer disease duration, higher disease activity and more often received antitumour necrosis factor (TNF) drugs. The remission was not different between men and women during the follow-up after adjustment on age, disease duration and activity, rheumatoid factor and anti-cyclic citrullinated pyeptide (CCP) positivity, and current disease-modifying antirheumatic drugs (DMARDs), previous TNF blockers and corticosteroids use. The proportion of men and women achieving EULAR good-or-moderate response at any endpoints was similar (52.4% vs 55.5%), as well as time to achieving EULAR response (5.4+/-4.9 vs 5.6+/-5.2 months). Moderate EULAR response was more frequent in women at 6 months (OR=1.80, p=0.02) but was no longer significant at 12 or 24 months. During the follow-up, the DAS28, the tender joint count score and the patient global assessment remained higher in women (p=0.001, 0.04 and 0.06, respectively). Drug retention and safety were comparable. Conclusion: In this large daily practice cohort of established rheumatoid arthritis treated with abatacept, women achieved similar remission and EULAR response than men despite higher disease activity and tender joint count during the treatment course.