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BackgroundA Treat-to-Target approach (T2T) is broadly considered to lead to better clinical outcomes and recommended in patients with RA. However, very few studies have analyzed the effect of T2T on radiographic progression, and any such studies have provided inconsistent results.ObjectivesTo investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice leads to lower radiographic progression in RA.MethodsPatients from the multicenter RA-BIODAM cohort with ≥2 consecutive visits with radiographs available were included. In RA-BIODAM patients were enrolled as they were initiating a new csDMARD/bDMARD treatment were followed-up with the intention to benchmark and intensify treatment. The primary outcome of this analysis was the change in Sharp-van der Heijde score (SvdH, 0-448), assessed every 6 months, using average scores from 2 readers (scores with known chronological order). Following a DAS44-T2T remission strategy, which was defined at each 3-month visit, was the main variable of interest. Patients were categorized based on the proportion of visits in which T2T was followed according to our definition: very low (≤40% of the visits, low (>40%, 75%). Radiographic progression at 2 years was visualized across groups by cumulative probability plots. Per 3-month interval T2T could be followed zero, one or two times (in a total of 2 visits). Associations between the number of visits with T2T in an interval and radiographic progression, both in the same and in the subsequent 6-month interval, were analysed by generalised estimating equations, adjusted for age, gender, disease duration and country.ResultsIn total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). After 2 years, patients showed on average 2.2 (4.1) units progression (median:1 unit). Mean (SD) 2-year progression was not significantly different across categories of T2T: very low: 2.1 (2.7)-units; low: 2.8 (6.0); high: 2.4 (4.5), very high: 1.6 (2.2) (Figure 1). Meticulously following-up T2T in a 3-month interval neither reduced progression in the same 6-month interval (parameter estimates (for yes vs no): +0.15 units (95%CI: -0.04 to 0.33) for 2 vs 0 visits; and +0.08 units (-0.06;0.22) for 1 vs 0 visits) nor did it reduce progression in the subsequent 6-month interval (Table 1).Table 1.Effect of following DAS44-remission-T2T strategy on 6-month radiographic progression over 2 yearsChange in radiographic damage(regression coefficient (95% CI))N=506T2T during 3 months on radiographic progression in the same 6-month period 2 visits vs 0 followed0.15 (-0.04; 0.33) 1 visit vs 0 followed0.08 (-0.06; 0.22)T2T during 3 months on radiographic progression in the subsequent 6-month period 2 visits vs 0 followed-0.09 (-0.28; 0.10) 1 visit vs 0 followed-0.10 (-0.24; 0.05)Figure 1.Cumulative probability plot with 2-year radiographic progression according to the proportion of 3-monthly visits with T2T followedConclusionIn this daily practice cohort, more meticulously following T2T principles did not result in more reduction of radiographic progression than a somewhat more liberal attitude toward T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.AcknowledgementsBIODAM was financially supported by an unrestricted grant from AbbVieDisclosure of InterestsSofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Robert B.M. Landewé Speakers bureau: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCBDr Landewé owns Rheumatology Consultancy BV, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. Director of Imaging Rheumatology bv., Alexandre Sepriano Speakers bureau: Novartis, Consultant of: UCB, Oliver FitzGerald Speakers bureau: Biogen, Novartis, AbbVie, BMS, Pfizer, Grant/research support from: BMS, Novartis, UCB, Pfizer, Lilly, Janssen, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Orion, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, Amgen, BMS, Merck, Celgene and Novartis, Joanne Homik: None declared, Ori Elkayam Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Consultant of: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Grant/research support from: Pfizer, Abbvie, Janssen, Carter Thorne Consultant of: Abbvie, Organon, Pfizer, Sandoz, Maggie Larché Speakers bureau: AbbVie, Actelion, Amgen, BMS, Boehringer-Ingelheim, Fresenius-Kabi, Gilead, Janssen, Mallinckrodt, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi, UCB, Grant/research support from: Abbvie, BMS, Gianfranco Ferraccioli Speakers bureau: SOBI, Consultant of: Abbivie, Marina Backhaus: None declared, Gilles Boire Speakers bureau: Abbvie Canada, BMS Canada, Lilly Canada, Janssen Canada, Merck Canada, Pfizer Canada, Viatris, Consultant of: Abbvie Canada, Amgen Canada, BMS Canada, Celgene, GileadSciences, Janssen Canada, Lilly Canada, Merck Canada, Mylan Canada, Novartis Canada, Pfizer Canada, Roche Canada, Samsung Bioepis, Sanofi Canada, Teva, Grant/research support from: Lilly Canada, BMS Canada, Pfizer, Sandoz Canada, UCB Canada, Merck Canada, Novartis Canada, Roche Canada, Bernard Combe Speakers bureau: Abbvie, BMS,Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Pfizer,Roche-Chugai, Consultant of: Abbvie, Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Roche-Chugai, Grant/research support from: Pfizer, Roche-chugai, Thierry Schaeverbeke: None declared, Alain Saraux Speakers bureau: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Consultant of: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Novartis, Fresenius, Lilly, Maxime Dougados Consultant of: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Grant/research support from: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Maurizio Rossini Speakers bureau: Amgen, Abbvie, BMS, Eli-Lilly, Galapagos,MSD, Novartis, Pfizer, Sandoz, Theramex, UCB, Marcello Govoni Speakers bureau: Abbvie, Pfizer, Galapagos, BMS, Eli-Lilly, Paid instructor for: Pfizer, Consultant of: Abbvie, BMS, Novartis, Astrazeneca, Pfizer, Luigi Sinigaglia: None declared, Alain Cantagrel Speakers bureau: Abbvie, Amgen, Biogen, BMS, Janssen, Lilly France, Médac, MSD France, Nordic-Pharma, Novartis, Pfizer, Sanofi Aventis, UCB, Consultant of: BMS, Janssen, Lilly France, MSD France, Sandoz, Grant/research support from: MSD France, Novartis, Pfizer, Cornelia Allaart: None declared, Cheryl Barnabe Speakers bureau: Sanofi Genzyme, Pfizer, Fresenius Kabi, Janssen, Consultant of: Gilead, Celltrion Healthcare, Clifton Bingham Consultant of: AbbVie, BMS, Eli Lilly, Janssen, Moderna, Pfizer, Sanofi, Grant/research support from: BMS, Dirkjan van Schaardenburg: None declared, Hilde Berner Hammer Speakers bureau: AbbVie, Novartis, Lilly, Rana Dadashova: None declared, Edna Hutchings: None declared, Joel Paschke: None declared, Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer

Objectives. This study aimed to estimate the national prevalence of violence against Filipino children and youth as experienced in various forms and settings. Methods. About 3,866 young people aged 13-24 years from 172 randomly selected barangays (villages) nationwide participated in the survey. The questionnaire was self-administered, interviewer-administered, or interviewer-assisted, depending on the capability and preference of the respondent. Female respondents were interviewed or assisted by a female field assistant, while male field assistants guided the male respondents. The questionnaire was translated into seven local dialects and administered in the most comprehensible language to the respondent. Results. Overall, 80 percent of the 3,866 respondents experienced any one form of violence in the home, school, workplace, and community. More than 3 in five suffered from physical, psychological, and peer violence, while 22.4 percent were victims of sexual abuse. Ten percent were physically neglected, while a fourth felt psychologically neglected by their caregivers. More boys claimed to have been sexually abused and physically neglected, while more girls were bullied and witnessed psychological violence in the home. VAC prevalence was, however, found to be highest among LGBTQ+s compared to heterosexual males and females. Despite the high prevalence, less than 10 percent of respondents disclosed their experiences of abuse, primarily to friends and parents. About one in 10 ever sought help from a professional. Conclusion. There is a need to improve the implementation of child protection programs at the local level, where violence issues of heterosexual boys and girls and LGBTs are addressed.

Objectives. This study used a descriptive, qualitative design to explore the local understanding of child discipline and analyze the important link between parental discipline and child abuse. Methods. Focus group discussions and key informant interviews were conducted with parents, children, local leaders, and professionals in 6 rural communities in the Philippines. The respondents were asked which corrective behaviors they would consider acceptable or abusive to children by showing them a list of disciplinary acts. Results. The results showed an adequate understanding of the purpose and intent of child discipline. Children are generally disciplined to teach them good values, mold and shape their characters and equip them with a moral sense of right and wrong. Child discipline is considered already harmful if: the child sustains physical injuries and psychological pain; the disciplinary action is not commensurate to the offense committed by the child and is used frequently and repetitively, without any valid reason; when sensitive body parts such as the head are involved, and when the disciplinary action is not appropriate to the age, gender, physical and mental status of the child. Among the various types of disciplinary acts, counseling, beating or spanking, and withdrawing or reducing school allowance were considered most acceptable. Hanging, burning, and scalding were the most unacceptable or abusive disciplinary behaviors. Compared to parents, professionals, and local leaders, children were more lenient as they regarded certain inappropriate behaviors by adults as somewhat tolerable. Conclusion. Despite having an adequate understanding of the purpose and intent of child discipline, there is still a need to educate parents, children, and local leaders about when a disciplinary act becomes harmful to children. Community stakeholders should also be informed about how and where to report the abuse once it is identified.

La paraparesia espastica hereditaria es un grupo de trastornos neurodegenerativos con heterogeneidad fenotipica y genetica, caracterizados clinicamente por espasticidad y debilidad progresiva de los miembros inferiores, y en los que se describen formas de herencia autosomica dominante, autosomica recesiva y ligada al X. Actualmente hay 72 tipos descritos, de los cuales no todos tienen una mutacion causal claramente definida.

Objective: To determine associations between standardized prevalence ratios of Metabolic Syndrome (MS), High Blood Pressure (HBP), and Obesity (O) with structural factors in ecuadorian population aged 20 to 59. Methods: An ecological study was conducted through data from the Ecuador’s National Health and Nutrition Survey 2013-2014, and National Census. Standardized prevalence ratio (SPR) variability was analyzed with Poisson multiple regression models (adjusted Relative Risk). Results: The SPR variability for the three diseases was associated with non-affiliation to social security, and inversely related to lower urbanization. HBP and O were associated with functional illiteracy and higher rates of primary care physicians/1000 inhabitants. HBP and MS were related to poor housing. Conclusions: Policies of non-communicable chronic diseases control in ecological transition countries need to take structural variations into account.

Background There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. Methods RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. Results A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p p No major differences between the groups of early and established RA could be detected. Conclusions The wrist, MCP2, EDC, and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.

BackgroundWork is an important outcome for people with inflammatory arthritis (IA including PsA, RA, AxSpA) and osteoarthritis (OA). It is known that people with IA and OA are at increased risk of sick leave and have to stop working early due to ill health. In addition to being at increased risk of becoming work disabled and increased absenteeism, high levels of presenteeism (i.e. reduced productivity/limited ability to work due to ill health whilst at work) have also been reported. Several instruments exist to measure presenteeism, including single-item global measures and multi-item instruments. In some studies using single-item global instruments may be more feasible. However, available global instruments differ in concept, recall period and reference. It is important to understand which of the measures have good psychometric properties before using them in clinical studies.ObjectivesTo assess the psychometric properties of four global presenteeism instruments.MethodsPatients with IA or OA were recruited via rheumatology outpatient clinics to a large international, longitudinal observational study including 8 European countries and Canada. Participants completed a survey at baseline, 1, 2, 3, 4 wks, 2 months and 3 months. The four global measures of presenteeism included: Work Productivity and Activity Impairment Questionnaire (WPAI), Work Productivity Scale–Rheumatoid Arthritis (WPS-RA), Work Ability Index (WAI) and the Quality*Quantity questionnaire (QQtotal/10) scale. To facilitate score interpretation the WAI and QQtotal were reversed. Pain was measured using an 11-point Likert scale. Spearman correlations were calculated between the presenteeism measures and the Workplace Activity Limitations Scale (WALS), a validated multi-item measure of presenteeism, and HAQ to evaluate construct validity (validity: r r >0.50-r >0.70=high). Test-retest reliability of the 4 presenteeism scales (baseline-1wk) was measured applying ICC in patients with stable disease (i.e. same pain score at baseline and 1wk) (reliability: ICC0.75=excellent). Responsiveness during 3 months was measured comparing patients with improvement in pain score (>1 point improvement in pain score (~MCID pain)) with patients with no change or worsening in pain score. The two groups were compared applying Mann Whitney U test.ResultsThis international study included 550 patients with a mean age of 47.8 (SD 9.9) yrs and 61.4% were female. Mean (SD) disease duration since diagnosis was 10.8 (10.4) yrs and 91.2% had IA. Mean (SD) presenteeism scores at baseline were: WPAI=2.9 (2.7); WPS-RA=3.4 (2.7); WAI=2.7 (2.4); and QQtotal=3.1 (3.2). The correlations between the global measures and with WALS and HAQ were moderate to good, except for QQtotal and HAQ which was low (Table 1). In patients with the same stable pain scores at baseline-1wk (n=141) ICC scores were good to excellent, respectively: WPAI (0.771), WPS-RA (0.752), WAI (0.663), and QQtotal (0.650). An improvement in pain during the 3 month study duration was observed in 145/381 (38%) of the patients. In these patients a significant reduction in mean (SD) change presenteeism was observed for all four presenteeism scales compared to those with no change or worsening of the pain score: WPAI (-1.0 (2.37) vs 0.68 (2.40), pTable 1.WPAIWPS-RAWAIQQtotalWALSHAQWPAI-0.81640.59920.51840.62690.5592WPS-RA-0.58360.52170.60550.5669WAI-0.58660.52310.5168QQtotal-0.50250.4367ConclusionThe psychometric properties of all 4 global presenteeism scales were moderate to good, with slightly better scores for both the WPS-RA and WPAI instruments both measuring the impact of OA and IA on productivity.Disclosure of InterestsSuzanne Verstappen Consultant of: EUOSHA, Grant/research support from: AbbVie, BMS. EULAR, Annelies Boonen Speakers bureau: Abbvie / Galapagos, Consultant of: Galapagos, Sarah Wilkinson: None declared, Dorcas Beaton: None declared, Ailsa Bosworth: None declared, José Canas da Silva: None declared, Gloria Crepaldi: None declared, Sabrina Dadoun: None declared, Cathie Hofstetter: None declared, Carina Mihai Speakers bureau: Boehringer-Ingelheim, Mepha, MED Talks Switzerland, Consultant of: Boehringer-Ingelheim, Janssen, Grant/research support from: Roche, Boehringer-Ingelheim, Sofia Ramiro Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: Grant: AbbVie, Galapagos, Novartis, Pfizer, UCB, Garifallia Sakellariou Consultant of: Abbvie, BMS and Galapagos., Grant/research support from: Abbvie, BMS and Galapagos., Sandra Meisalu: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer., Diane Lacaille: None declared

BackgroundIn radiographic axial spondyloarthritis (r-axSpA) it has been hypothesized that inflammation-driven bone loss triggers bone repair at anatomically distinct sites of the same vertebra: bone loss occurring in the trabecular bone and ectopic bone formation in the periosteum1.ObjectivesTo investigate whether inflammation is associated with lower bone density (surrogate of bone loss) and subsequently, if lower bone density is associated with 2-year bone formation in r-axSpA at the same vertebra.MethodsData from the Sensitive Imaging in Ankylosing Spondylitis (SIAS), a multicentre 2-year cohort, was used. Baseline vertebral bone density was assessed by Hounsfield Units (HU) on low dose Computed Tomography (ldCT) by two independent readers (Figure 1). Baseline magnetic resonance imaging (MRI) bone marrow edema (BME) status scores, and 2-year ldCT syndesmophyte formation or growth change scores were assessed by three and two readers respectively. Inter-reader reliability was assessed for each imaging scoring by vertebra. Average of readers´ continuous scores (bone density HU) or readers´ agreement in binary scores (MRI-BME and bone formation) were used at the same vertebra (1-present in ≥1 quadrant/0-absent in all quadrants). The hypothesised associations were tested in multilevel generalised estimating equations models adjusted for confounders, the unit of analysis being the vertebra.ResultsWe analysed 1,100 vertebrae in 50 patients with r-axSpA. Intraclass correlation coefficients for HU measurements varied from 0.89 to 0.97, Fleiss Kappa values for MRI-BME were between 0.41-0.78 and Cohen´s kappa for syndesmophyte formation/growth change scores varied from 0.36 to 0.74. Bone density HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at the thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant association was found between inflammation (MRI-BME) and lower bone density (regression coefficient=-51; 95% CI:-63;-39) (Table 1A). Bone density was not associated with 2-year syndesmophyte formation or growth (adjOR 1.00; 95% CI:0.99;1.00) (Table 1B).Table 1.Relationships between (A) baseline MRI detected spinal inflammation (MRI-BME) and bone density, and (B) baseline bone density and ldCT bone formation after two years, at the same vertebra.A.Independent variablesBone density (Hounsfield Units)Univariable analysisMultivariable analysisReg coeff. (95% CI)Adj Reg coeff. (95% CI)N = 910 to 985N = 985MRI-BME (presence)-51 (-63 to -39)-51 (-63 to -39)Age (years)-1 (-2 to 1)-1 (-2 to 1)Gender (male)21 (-20 to 63)16 (-24 to 57)TNFi treatment (yes)26 (-7 to 59)27 (-6 to 61)Baseline syndesmophytes (presence)*-42 (-54 to -30)-B.Independent variablesSyndesmophyte formation or growth§Univariable analysisMultivariable analysisOR (95% CI)AdjOR (95% CI)N = 672 to 691N = 672Bone density (HU)1.00 (0.99 to 1.00)1.00 (0.99 to 1.00)Age (years)1.02 (0.99 to 1.06)1.02 (0.98 to 1.05)Gender (male)0.44 (0.13 to 1.52)0.56 (0.15 to 2.06)Smoking (current)0.89 (0.40 to 1.97)1.02 (0.42 to 2.44)Treatment with TNFi (yes)1.34 (0.56 to 3.21)1.30 (0.43 to 3.90)MRI-BME (presence)2.03 (1.23 to 3.71)1.73 (1.06 to 3.34)Baseline syndesmophytes (presence)*2.84 (1.83 to 4.41)-*Multicollinearity with MRI-BME. § Absolute agreement of readers.adjOR - adjusted odds ratio; CI-confidence interval; BME - bone marrow edema; HU - Hounsfield units; ldCT - low dose computed tomography; MRI - magnetic resonance imaging; TNFi – Tumour necrosis factor inhibitors. Statistical significance highlighted in bold.ConclusionWhile in r-axSpA vertebral inflammation associates with low vertebral bone density, lower vertebral bone density itself does not increase the risk for ectopic bone formation at the same vertebra.References[1]Lories RJ. Best Pract Res Clin Rheumatol. 2018 Jun;32(3):331–41.AcknowledgementsTo the Dutch Rheumatism Association for funding SIAS study.Disclosure of InterestsMary Lucy Marques: None declared, Nuno Pereira da Silva: None declared, Désirée van der Heijde Consultant of: AbbVie, Gilead, Glaxo-Smith-Kline, Lilly, Novartis, UCB Pharma, Rosalinde Stal: None declared, Xenofon Baraliakos: None declared, Juergen Braun: None declared, Monique Reijnierse: None declared, Caroline Bastiaenen: None declared, Floris A. van Gaalen: None declared, Sofia Ramiro: None declared

BackgroundCurrent knowledge on the health status of patients (pts.) with axial spondyloarthritis (axSpA) mainly focusses on physical function and disease activity. Using a generic measure for physical- or mental health (SF36), a hierarchical relationship between disease activity, spinal damage, spinal mobility, physical function and overall health has been demonstrated in pts. with radiographic axSpA (r-axSpA) 1. Disease-specific global functioning and health can be assessed in pts. with axSpA using the ASAS Health Index (ASAS HI), which encompasses physical function, as well as aspects of emotional and social functioning and aspects of activity and participation.ObjectivesTo build a structural model that visualizes interrelationships of different patient- and disease characteristics with global functioning and health in pts. with early axSpA.MethodsData of pts. with axSpA from the DESIR cohort was analyzed, which included information on socio-demographics (age, BMI), disease activity (ASDAS), physical function (BASFI), spinal mobility (BASMI), structural damage (mSASSS), disease-specific global functioning (ASAS HI), and comorbidity count. Information on patient- and disease characteristics was retrieved from the visit performed 72 months after inclusion, which was the first time point of ASAS HI collection. A Bayesian network (BN) was used to obtain insight of the underlying structural model. BNs are probabilistic graphical models consisting of “nodes” (representing specific variables) joined by “edges” (lines representing directions of effects). They are capable of capturing complex relationships between variables and allow the incorporation of existing (prior) knowledge from previous studies.ResultsThe DESIR cohort contained data from 582 pts. at month 72, of whom 398 had data for ASAS HI. Descriptive information of these pts. is shown in Table 1. The mean ASAS HI was 5.7 (range: 0 - 16). Applying existing cut-offs for ASAS HI, 51% had ‘good’ global functioning (ASAS HI ≥5), 40% had ‘moderate’ global functioning (5< ASAS HI Table 1.Patient and disease characteristics at month 72N = 398Gender (male), N (%)181 (45%)Age (years)40.7 (8.7)Symptom duration (years)7.5 (0.9)BMI (kg/m2)25.0 (4.6)ASDAS2.0 (1.0)BASFI (0–10)2.3 (2.1)BASMI (0–10)2.5 (1.0)mSASSS (0-72)1.0 (3.6)ASAS HI (0-17)5.7 (3.9)good global functioning: ASAS HI ≤5, N (%)201 (51%)moderate global functioning: 5< ASAS HI 160 (40%)bad global functioning: ASAS HI ≥12, N (%)37 (9%)Comorbidity count1.4 (0.7)Figure 1.Structural model on interrelationships of different patient- and disease characteristics with global functioning and health (ASAS HI) in patients with early axSpAConclusionThe BN-analysis approach, that combines prior knowledge and measured data, serves to better understand the construct of global functioning and health in pts. with early axSpA. Our model shows that global functioning (ASAS-HI) is determined both by patient-reported physical function (BASFI) and by disease activity (ASDAS), which confirms the hierarchical model once proposed by Machado et al. The observed directional relationship between ASAS HI and comorbidity count is counterintuitive and requires further investigation.References[1]Machado P, ARD 2011.Disclosure of InterestsImke Redeker: None declared, Robert B.M. Landewé Speakers bureau: AbbVie, BMS, GSK Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, GSK Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Désirée van der Heijde Speakers bureau: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Annelies Boonen Speakers bureau: Abbvie / Galapagos, Consultant of: Galapagos, Grant/research support from: Abbvie, Maxime Dougados: None declared, Juergen Braun Speakers bureau: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer und UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer und UCB, Grant/research support from: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer und UCB, Uta Kiltz Speakers bureau: AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Biogen, Fresenius, Amgen, Hexal, Novartis, Pfizer

16S rNRA sequencing from the "Diet shapes evolution of a keystone member of the gut microbiota".

BackgroundIn early RA, the benefit of treatment with b-/tsDMARDs on work participation (WP), a top-three social role in RA, has seldom been studied.ObjectivesTo review the effect of treatment with b-/tsDMARDs on employment status (ES), presenteeism and sick leave (SL), in patients with early RA.MethodsA systematic literature review (SLR) was conducted in key electronic databases up to October 2021, to include RCTs assessing the effect of treatment with b-/tsDMARDs vs any comparator on ES, presenteeism and SL in patients with RA (≤ 3y). Two reviewers independently identified eligible studies and extracted data. Random-effects meta-analysis was only performed if ≥3 studies were conducted in comparable populations, assessing WP outcome similarly. Statistical heterogeneity was assessed with I2.ResultsFrom 7129 records (65 full-text articles screened), 11 RCTs were included in the SLR (7 in csDMARD naïve patients; 2 in inadequate responder to csDMARDs; 1 bDMARD tapering after initial combination with MTX, and 1 strategy study). Large heterogeneity was found across WP outcomes, measurement instruments, interventions and comparators (Table 1), which together with insufficient data reporting hampered meta-analysis of most outcomes. For ES, to allow meta-analysis, all outcomes were converted to employment loss, for which individual study Odds ratios (OR) were computed. The pooled OR of 4 studies with 779 patients treated with adalimumab, infliximab or baricitinib (Figure 1) showed a lower likelihood of employment loss at weeks 56 to 104 in those treated with MTX+b/tsDMARDs compared to MTX+PBO (OR: 0.65; 95% CI:0.43-0.99). For presenteeism and SL, 33/40 (83%) between-group comparisons showed improvement in favour of b-/tsDMARDs, but an effect size was reported or possible to compute for only 12 comparisons, of which 8 (67%) were statistically significant.Table 1.Overview of between-group resultsAuthor, year Study nameIntervention (I) Comparator (C)AssessedOutcomeInstrumentFollow-up(weeks)Favours intervention(+ yes; - no) $csDMARD naïveSmolen 2006ASPIREIFX+MTXESSCMI‡54+*PBO+MTXSL+*Bejarano 2008ADA+MTXESWeekly diaries‡56+*PBO+MTXSL+*Anis 2009COMETETN+MTXSLSCMI‡52+*MTXvan den Hout 2009BeStI: IFX+MTXSLSCSI‡10456w: + I vs C1/2C1: seq. monotherapyPresVAS (0-100)104w: + I vs C1 | +* I vsC2: step-up comb. Therapy + IFXC3C3: initial comb. Therapy + IFXvan Vollenhoven 2010PREMIERI1: ADA+MTXESSCMI‡104+* I1 vs C | + I2 vs CI2: ADA+PBOPres+* I1 vs C | + I2 vs CC: PBO+MTXSL+** I1 vs C | +** I2 vs CEmery 2016OPTIMAPROWDADA+MTXESWPAI-RA24-26OPTIMA & PROWD +PBO+MTXPresOPTIMA +*SLOPTIMA -Wiland 2016PRIZEI: ETN25/MTXPresWPAI-RA11739W & 65 W: + I vs C1/239W & 65 W: + I vs C1/2C1: PBO+MTXSLC2: PBO+PBOSchiff 2017RA-BEGIN¶I1: BARI+MTXPresWPAI-RA5224w: + I1/2 vs CI2: BARI+PBOSL52w: + I2 vs CC: PBO+MTX24w: + I1/2 vs C52w: + I2 vs CStrand 2021SELECT-EARLY¶I1: UPA 30Overall work impairmentWPAI-RA12+ I1/2 vs CI2: UPA 15C: MTXcsDMARD Inadequate respondersEriksson 2015SwefotIFX + MTXSLRegistry7 y+csDMARD + MTXFleischmann 2016AMPLE¶ABA+MTXPresWPAI-RA10424, 56 & 104w: +ADA+MTXSL24 & 104w: +SCMI – self composed multiple items; SCSI – self composed single item; WPAI – Work Productivity Activity Impairment questionnaire; *p ≤ 0.05 **p ≤ 0.001 vs C; ‡ non-validated instrument; $ when > 1 I/C or time-point, between-group comparisons and time-points are presented if I vs C differences were observed; ¶ insufficient data reporting to compute effect sizes.ConclusionA protective effect against employment loss was observed in patients with early RA treated with MTX+b-/tsDMARDs compared to MTX monotherapy. The methodological heterogeneity and insufficient reporting hampers clear conclusions regarding the beneficial effects of b-/tsDMARDs on presenteeism and SL. Efforts to uniformize future studies with WP as outcome by following recently developed points to consider are crucial1.References[1]Boonen A, et al. Ann Rheum Dis. 2021; 80:1116-1123.Disclosure of InterestsMary Lucy Marques: None declared, Alessia Alunno: None declared, Louise Falzon: None declared, Annelies Boonen Speakers bureau: Abbvie /Galapagos, Consultant of: Galapagos, Grant/research support from: Abbvie, Sofia Ramiro: None declared.

BackgroundAssessing local vertebral bone loss in radiographic axial spondyloarthritis (r-axSpA) poses challenges, namely because Dual-energy X-ray absorptiometry (DXA) only allows assessment of lumbar vertebrae. The measurement of Computed Tomography (CT) vertebral Hounsfield Units (HU) has been shown to correlate with vertebral bone density as measured by DXA in trauma patients. We have recently reported the excellent reliability of low dose CT (ldCT) HU measurements from C3 to L5 in patients with r-axSpA1; however, HU change scores have never been studied.ObjectivesTo describe ldCT HU change scores and their inter-reader reliability per vertebra in patients with r-axSpA over 2 years.MethodsWe used spine ldCT scans of r-axSpA patients included in the multicenter 2-year Sensitive Imaging in Ankylosing Spondylitis (SIAS) study. A standardized protocol and automatic exposure control calibration in ldCT imaging acquisition were used. Baseline and 2-year ldCT scans were independently assessed by two trained readers. The HU measurements were performed as described in Figure 1. Mean (standard deviation, SD) for the change-from-baseline scores were provided by reader, together with the respective mean differences (SD). Inter-reader reliability for the change scores was assessed using intraclass correlation coefficients (ICC) absolute agreement, applying two-way random effect models. Agreement was assessed using the smallest detectable change (SDC = 1.96 x SDdifference /(√2*√k); SDdifference is the SD of the differences in change scores between the two readers, and k=2 readers) and Bland-Altman plots. The percentage of vertebrae in which readers agreed on the direction of the change (positive vs negative) and on change scores > |SDC|were also computed.ResultsWhole spine ldCT scans from 49 r-axSpA patients (mean age of 49 (SD 10) years; 88% male and 84% HLA-B27 positive) were included. In total, 1,053 vertebrae were assessed by both readers. The HU mean change values varied from -23 to 28 and -23 to 29 for reader 1 and 2, respectively – Table 1. More vertebrae showed a positive change in the cervical spine compared with the thoracic and lumbar spine. Inter-reader reliability was excellent (ICC: 0.91 to 0.99). SDC varied from 4 to 7, mean and median of 5. Bland-Altman plots showed homoscedasticity throughout the whole spine, with negligible systematic error between the readers. The two readers agreed on the direction of the change score in 88-96% of vertebrae, and agreement on change scores > |SDC| was obtained in 64-96% of the vertebrae.Table 1.Change scores for both readers, mean differences and intraclass correlation coefficients (ICC) from C3 to L5Vertebra§Mean change (SD)Mean Difference (SD)Change > 5 #Change < -5 #Change >|5| #ICCReader 1Reader 2C318 (56)17 (56)0.2 (5.0)5532870.97C418 (53)17 (52)0.3 (5.5)5932910.98C528 (70)29 (70)-0.7 (5.0)6132930.99C623 (62)23 (62)0.4 (5.8)5039890.99C7-3 (60)-2 (59)-0.7 (6.9)4049890.98T1-6 (87)-6 (88)0.6 (5.0)4749960.98T23 (45)3 (45)0.7 (4.0)4145860.97T31 (43)2 (43)0.6 (4.4)2935640.95T4-2 (48)-1 (47)0.2 (5.3)3945840.94T50.02 (48)-0.3 (48)0.3 (5.1)3945840.91T6-3 (44)-3 (45)-0.1 (4.6)3545800.95T7-4 (43)-4 (43)-0.1 (4.5)2951800.99T8-1 (38)-1 (40)0.1 (4.6)3545800.98T9-9 (50)-9 (50)0.02 (5.4)2259810.99T100.2 (59)1 (59)-0.4 (5.2)3339720.96T11-8 (53)-7 (53)-0.6 (4.3)3543780.94T12-23 (59)-23 (60)-0.3 (4.4)3553880.99L1-9 (33)-7 (33)-1.9 (6.3)2741680.97L21 (46)2 (45)-1.1 (4.6)2941700.98L3-4 (35)-2 (34)-1.2 (6.3)2439630.92L4-2 (24)1 (22)-1.5 (5.4)3137680.91L58 (43)9 (43)-1.0 (6.0)4733800.97§ C3-C7: n=44; T1-L5: n=49# % of vertebrae in which both readers agreed on a change score > smallest detectable change.ConclusionLdCT measurement of HU is a reliable method to assess changes in bone density at each vertebra from C3 to L5. This methodology can aid the study of bone loss in r-axSpA, a disease affecting the whole spine.References[1]Marques ML, et al. Arthritis Rheumatol. 2021; 73 (suppl 10).AcknowledgementsTo the Dutch Rheumatism Association for funding SIAS study.Disclosure of InterestsMary Lucy Marques: None declared, Nuno Pereira da Silva: None declared, Désirée van der Heijde Consultant of: AbbVie, Gilead, Glaxo-Smith-Kline, Lilly, Novartis, UCB Pharma, Monique Reijnierse: None declared, Juergen Braun: None declared, Xenofon Baraliakos: None declared, Floris A. van Gaalen: None declared, Sofia Ramiro: None declared

BackgroundRegular physical activity is recommended for all patients in the ASAS/EULAR recommendations for the management of axial spondyloarthritis (axSpA). However, there is a lack of outcome measures that assess the amount and type of physical activity in patients with axSpA. For this matter, the modified Short QUestionnaire to Assess Health enhancing physical activity (mSQUASH) was developed and validated, originally in Dutch1.ObjectivesTo translate and cross-culturally adapt the mSQUASH into Spanish and to test the equivalence of the translated version in patients with axSpA.MethodsThe mSQUASH was translated into Spanish and then back-translated into Dutch, following forward-backward procedure as described by Beaton2 (Figure 1). Two bi-lingual translators (native speakers for European Spanish) produced independent forward translations of the item content, response options, and instructions of the mSQUASH into Spanish. Both versions were harmonized in a meeting among the Spanish translators, a methodologist and a rheumatologist into a consensual version. Another translator (native speaker for Dutch), blinded for the original version, back translated the synthesized version into Dutch. An expert committee, including all translators, one methodologist and a rheumatologist, reached consensus on discrepancies, ensuring equivalence between the Dutch and Spanish versions, and developed a pre-final version of the Spanish mSQUASH. The field test with cognitive debriefing involved a sample of 10 patients with axSpA covering the full spectrum of the disease -radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA)- with different gender, age, disease duration, and educational background. Each patient was interviewed to check understandability, interpretation and cultural relevance of the translation.Figure 1.Cross-cultural adaptation of the mSQUASHResultsThe translation process of the mSQUASH was completed without major complications following the forward-backward procedure. The first translation needed several iterations due to small discrepancies in the wording. Back-translation was performed without difficulties, and the expert committee agreed upon a final version of the questionnaire. A total of 10 patients with axSpA participated in the field test (Table 1). Seven were male, mean age (SD) was 38.9 (14.4) years; 6 patients had r-axSpA, 9 were HLA-B27+. Cognitive debriefing showed the Spanish questionnaire to be, relevant, understandable and comprehensive. The preliminary version was accepted with minor modifications. As a result of the interviews, minor spelling errors were corrected, and the wording of the response categories was homogenized (“despacio/ligero”). Besides, the term “colegio”- translated literally from the Dutch “school”- was found not comprehensive enough to reflect possibilities on education (i.e. it does not include university), so it was adapted to “el lugar de estudio”.Table 1.Patients’ characteristics#GenderAgeWorking statusEducationaxSpA subtypeDisease durationHLA-B27DrugBASDAI1Male63WorkingUniversityr-axSpA35 y+NSAIDs2.32Male24StudentSecondaryr-axSpA6 y+NSAIDs03Male37WorkingUniversityr-axSpA5 y+ADA2.54Male66RetiredUniversityr-axSpA23 y+IFN3.15Male29WorkingUniversityr-axSpA11 y+ADA06Female26WorkingUniversitynr-axSpA2 y+NSAIDs-7Male24StudentUniversitynr-axSpA1 y+ETA4.58Male35WorkingUniversityr-axSpA12 y+GOL09Female40WorkingSecondarynr-axSpA4 y+NSAIDs-10Female45UnemployedPrimarynr-axSpA9 y-GOL8.2ConclusionThe resulting Spanish version of the mSQUASH showed good linguistic and face validity according to the field test, revealing potential for use in both clinical practice and research settings. In order to conclude the cross-cultural adaptation of the mSQUASH into Spanish, the next step is the assessment of psychometric properties of the Spanish version.References[1]Beaton DE, et al. Spine. 2000; 25:3186-91[2]Carbo et al. Semin Arthritis Rheum. 2021; 51:719-27Disclosure of InterestsDiego Benavent Speakers bureau: Jannsen, Roche, Grant/research support from: Novartis, Andrea Jochems: None declared, DORA PASCUAL-SALCEDO Speakers bureau: Pfizer, Menarini, Takeda, Abvvie., Grant/research support from: Pfizer, Menarini, Takeda, Abvvie., Gijs Jochems: None declared, Chamaida Plasencia Speakers bureau: Pfizer, Abbvie, Lilly, Sandoz, Sanofi, Biogen, Roche and Novartis, Grant/research support from: Pfizer and Abbvie, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Suzanne Arends: None declared, Anneke Spoorenberg Consultant of: AbbVie, Novartis, Pfizer; UCB, Lilly, Grant/research support from: AbbVie, Pfizer, Alejandro Balsa Speakers bureau: Pfizer, Abbvie, Lilly, Galapagos, BMS, Sandoz, Nordic Pharma, Gebro, Roche, Sanofi, UCB, Consultant of: Pfizer, Abbvie, Lilly, Galapagos, BMS, Nordic Pharma, Sanofi, UCB, Grant/research support from: Pfizer, Abbvie, BMS, Nordic Pharma, Gebro, Roche, UCB, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie and Novartis

BackgroundThe Short Questionnaire to Assess Health-enhancing physical activity (SQUASH) is a validated tool measuring the duration, frequency, and intensity of physical activity. The modified version of the SQUASH (mSQUASH) has been developed, in collaboration between spondyloarthritis (SpA) experts and axial (ax)SpA patients, to better address the needs of these patients in the assessment physical activity (1).ObjectivesTo translate and cross-cultural adapt the mSQUASH into Turkish as well as its cognitive debriefing to test the conceptual equivalence of the translated version among patients with axSpA.MethodsThe mSQUASH was translated into Turkish by 2 bilingual translators, native speakers of Turkish one from medical (informed) and the other is without medical background (uninformed). The consensus on forward-translation was reached by the team included two rheumatologist (GA and LK) and the translators. Backward-translation into Dutch was performed by 2 bilingual translators, native speakers of Dutch and who were blinded to the original mSQUASH version. After the review of the Turkish version by an expert committee that included translators, two patients and the research team a pre-final version was prepared. This version was used in a field-test with cognitive debriefing and involved a sample of 10 axSpA patients (7 radiographic- and 3 non-radiographic axSpA patients) with variation in gender, age, disease duration, and educational background. The final Turkish mSQUASH version was reached after the patients were interviewed to check understandability, interpretation and cultural relevance of the translation. The whole process was performed according to the Beaton method (Figure 1) (2).Figure 1.Flow-chart of the translation and cross-cultural adaptation processResultsAfter the forward-backward translation process, small incompatibilities were resolved during the expert committee meeting. For example: `Ander transport (heen en terug)` was translated as `Diğer hedeflere (gidip gelmek)`. The meaning in English is `Other transport (round trip)’. This item questions the way of going to other places and the discrepancy raised whether to use `transportation` or the `target` as the title. To make it culturally adaptable consensus reached to use a word equivalent to `the target` which is semantically equal to the Dutch version. A total of 10 patients with axSpA [7 females, mean (SD) age of 38 (10)] participated in the field test. Mean (SD) time to complete the mSQUASH was 6.1 (2.4) minutes. Cognitive debriefing showed that items of the mSQUASH are clear, relevant, understandable, and easy to complete. None of the patients indicate any important aspect of physical activity that is missing from the questionnaire items. During the cognitive debriefing, 2 patients suggested a change in the wording of one item to make it more suitable to the Turkish culture. This item inquires after sport activities and patients raised the concern that the example activities, ice-skating, tennis, handball are not culturally suitable. According to their comments these items were replaced by other examples such as football.ConclusionThe final Turkish version of the mSQUASH showed acceptable linguistic validity and can be used in both clinical practice and for research purposes. However, to implement the Turkish version of the mSQUASH, further assessment of its psychometric properties (validity and reliability) is needed.References[1]Carbo MJ, et al. Semin Arthritis Rheum. 2021 Aug;51(4):719-727.[2]Beaton DE, et al.. Spine (Phila Pa 1976). 2000 Dec 15;25(24):3186-91Disclosure of InterestsGizem Ayan: None declared, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Fernando M Pimentel-Santos Speakers bureau: Abbvie, Novartis, UCB, Tecnimed, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Tecnimed, UCB, Grant/research support from: Abbvie, Janssen, Novartis, Anneke Spoorenberg Speakers bureau: AbbVie, Novartis Pharma, Pfizer, UCB Pharma, Lilly, Consultant of: AbbVie, Novartis Pharma, Pfizer, UCB Pharma, Lilly, Grant/research support from: AbbVie, Novartis Pharma, Pfizer, Suzanne Arends: None declared, Levent Kiliç: None declared

BackgroundSo far, no consensus has been reached on a definition of early SpA. The ASAS-SPEAR (SPondyloarthritis EARly definition) project aims to develop a consensual definition. Therefore, it is important to know whether treatment earlier in the disease course compared to treatment of established disease leads to better outcomes in axSpA.ObjectivesTo summarize the evidence on the relationship between symptom duration or the presence of radiographic damage and clinical response in patients with axSpA treated with NSAIDs, bDMARDs or tsDMARDs.MethodsA SLR was conducted using Medline, EMBASE and the Cochrane Library (April 28, 2021), supplemented by hand-searches in the FDA website. Randomized controlled trials (RCTs) and cohort studies in patients with axSpA addressing the impact of symptom duration or disease duration and presence of radiographic damage on treatment response (to NSAIDs, b/tsDMARDs) were included. Based on a cut-off of symptom/disease duration or the absence/presence of radiographic damage, groups of ‘early’ and ‘established’ disease were compared. Treatment outcomes were measures of disease activity, function or quality of life.Two reviewers independently identified eligible studies and extracted the data, including the risk of bias (RoB) assessment. For categorical outcomes we calculated relative risk (RR), relative risk ratio (RRR) and number needed to treat (NNT), and differences in differences (DID) for continuous outcomes.ResultsFrom the 8769 articles retrieved, 23 were included and 3 added by hand-search, most of them with low RoB. Nineteen studies (9 RCTs) compared groups based on symptom (n=6)/disease duration (n=13) and 7 studies (4 RCTs) based comparisons on absence/presence of radiographic damage in posthoc analyses.When early axSpA was defined by symptom duration in RCTs (n=4), in patients with nr-axSpA, early treatment was associated with higher RR and RRR and lower NNT for ASAS40 in two studies (Table 1); a third study showed that patients achieving ASDAS-ID and ASAS-PR had shorter symptom duration than those not achieving this. Lastly, in one study including patients with axSpA patients, no difference in treatment response was observed based on symptom duration. In most of the cohort studies using a definition based on symptom/disease duration (n=10), no association was found between symptom/disease duration and treatment response (n=8). Only in one cohort study, disease duration was a significant predictor of quality of life, and in another cohort study, it was a predictor of functional improvement.Table 1.Assessment of treatment response in RCTs based on symptom durationStudyPopulationEarly vs established (years)RR (early vs established)RRR (95%IC)NNTs (early vs established)ASAS20Landewé 2014axSpA1.5 vs 1.50.96 (0.53-1.73)5.5 vs 4.8ASAS40Sieper 2012nr-axSpA8.2 vs 1.65.24 (1.12-24.41)2.4 vs 9.1Kay 2019nr-axSpA5.0 vs 3.31.52 (0.60-3.87)2.1 vs 3.93.6 vs 3.51.01 (0.46-2.20)2.1 vs 2.9ASDAS-MIKay 2019nr-axSpA5.1 vs 6.50.78 (0.19-3.16)2.7 vs 4.97.1 vs 6.41.11 (0.34-3.66)2.1 vs 3.0StudyPopulationSymptom durationp valueRespondersNon respondersASDAS-IDSieper 2019nr-axSpA6.1±6.28.3±8.1ASAS-PRSieper 2019nr-axSpA5.3±5.78.0±7.8Cell coloursIn favor of early diseaseIn favor of establish diseaseNon significantWhen early axSpA was defined based on disease duration or the presence of radiographic damage, there was no significant difference in response to treatment between early and established axSpA.ConclusionStudies addressing treatment response based on symptom duration or radiographic damage in axSpA are scarce.When defining early axSpA based on symptom duration, in nr-axSpA, treatment with bDMARDs may lead to better outcomes compared to established axSpA whereas in axSpA there is no difference in response to treatment between early and established disease.When early axSpA is defined based on disease duration or radiographic damage, no differences in response to treatment are found between early and established disease.AcknowledgementsThe Assessment of Spondyloarthritis international Society (ASAS) supported Diego Benavent financially for this work.Disclosure of InterestsDafne Capelusnik Speakers bureau: Bristol Myers Squibb, Pfizer, Grant/research support from: Pfizer, Diego Benavent Speakers bureau: Janssen, Roche, Grant/research support from: Novartis, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB PharmaDirector of Imaging Rheumatology bv., Robert Landewé Consultant of: AbbVie, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, and Pfizer, Astrid van Tubergen Consultant of: Novartis, Galapagos, Grant/research support from: Pfizer, UCB, Novartis, Louise Falzon: None declared, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Novartis, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB

BackgroundCoping with Rheumatic Stressors (CORS) is a valid and reliable instrument that measures eight coping strategies directed at pain, limitations and dependency as the most prominent chronic stressors of Rheumatoid Arthritis (RA) (1). This questionnaire has also been used in axial Spondyloarthritis (ax-SpA) previously (2).ObjectivesTo describe the translation and cross-cultural adaptation process of the CORS into Turkish as well as its cognitive debriefing to test the conceptual equivalence of the translated version among patients with RA, radiographic (r) and non-radiographic (nr) axSpA.MethodsThe CORS was firstly translated into Turkish (by 2 bilingual translators who are native speaker for Turkish) and then back-translated into Dutch (by 2 bilingual translators who are native speaker for Dutch) following the Beaton’s method (Figure 1) (3). Back-translation procedure was done totally blinded to the original version. After the review of the Turkish version by an expert committee that included translators, two patients and the research team, a consensus was reached on the pre-final version. Using the pre-final version, the field test with cognitive debriefing involved a sample of 10 RA and 10 axSpA patients with different gender, age, disease duration, and educational background. After some small changes resulting from the feedback from patients the final version was obtained.Figure 1.Flow-chart of the translation and cross-cultural adaptation processResultsThe CORS was translated into Turkish following the forward-backward procedure. Minor incompatibilities arose from the translation process of CORS which have been easily resolved by the expert committee meetings. For example, `Ik concentreer me op iets anders` was translated as `Başka seylere odaklanirim` which is in English `I concentrate on something else`. The discrepancy was raised whether to use a word equivalent `to concentrate` or `to focus` and decision was made to use `to focus` while there was no exact Turkish word of `to concentrate`. A total of 10 patients with RA [9 females, mean (SD) age of 49 (13)] and 10 patients with axSpA [7 females, mean (SD) age of 38 (10), r-AxSpA, n=7, nr-AxSpA, n= 3] participated in the field test. Mean (SD) time to complete the CORS was 8.3 (3.4) minutes. Cognitive debriefing showed that items of the CORS are clear, relevant, understandable, and easy to complete. Cognitive debriefing revealed that the wording of one item had to be changed to provide better understanding (Section B, item 22 the word `stop` in Dutch and `stop` in English which was translated as `durdurmak` in Turkish changed to `sonlandirmak`.ConclusionThe final Turkish version of the CORS showed acceptable linguistic validity and can be used in both clinical practice and for research purposes, in patients with RA and in patients with axSpA. However, to implement Turkish-CORS, further assessment is ongoing to test its psychometric properties (validity and reliability).References[1]van Lankveld W, et al. Br J Rheumatol. 1994;33(11):1067-73.[2]Boonen A, et al. Ann Rheum Dis. 2004;63(10):1264-8.[3]Beaton DE, et al. Spine (Phila Pa 1976). 2000 Dec 15;25(24):3186-91Disclosure of InterestsGizem Ayan: None declared, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Fernando M Pimentel-Santos Speakers bureau: Abbvie, Novartis, UCB, Tecnimed, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Tecnimed, UCB, Grant/research support from: AbbVie, Janssen, Novartis, Wim van Lankveld: None declared, Levent Kiliç: None declared

BackgroundThere is no international consensus on an optimal ultrasound scoring system in patients with rheumatoid arthritis (RA) yet.ObjectivesTo assess the musculoskeletal ultrasound score on seven joints (‘US7 score’) (1) for the identification of the most frequently pathologic and responsive joint regions during 3 and 6 months of therapy in order to optimize the score. Furthermore, to evaluate the impact of disease duration on the performance of the score.MethodsRA patients were recruited from 54 German rheumatology centers when starting or changing DMARD therapy. Patients were assessed by the US7 score in greyscale (GS) and power Doppler (PD) at baseline, after 3 and 6 months. The frequency of pathologic joint/tendon regions and their responsiveness to therapy were assessed including the comparison of palmar vs. dorsal regions.Differences between the palmar and the dorsal sides were analyzed using Chi-square test, the gradings of the US-joint inflammation were compared between baseline, 3 months, and 6 months by Friedman test with Dunn test as post-hoc test.We used standard response mean to determine the responsiveness of possible reduced scores and linear regression to assess the amount of information retained from the original score. Analyses were also performed separately for early and established RA.ResultsA total of 435 patients (n=138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons out of 7 joints were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p≤0.003 in GS/PD).The dorsal vs. palmar side of the wrist by GS/PD (pConclusionThe wrist, MCP2, EDC and ECU tendons were most frequently pathologic and responsive to therapy, representing an optimized score for monitoring of RA patients for both early and established RA and should therefore be included in comprehensive scores for monitoring RA patients.References[1]Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009;61(9):1194-201.AcknowledgementsWe thank Gabriela Schmittat for logistical support in the study.Disclosure of InterestsAnnika Franziska Podewski: None declared, Anne-Marie Glimm: None declared, Imma Fischer: None declared, George Bruyn: None declared, Petra Hanova: None declared, Hilde Berner Hammer Speakers bureau: Paid speaker for Lilly, Novartis and AbbVie, Employee of: Advisory board for AbbVie, Anna-Birgitte Aga Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer and UCB, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer and UCB, Espen A Haavardsholm: None declared, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Gerd Rüdiger Burmester: None declared, Marina Backhaus Speakers bureau: Speaker fee from AbbVie, BMS, Galapagos, UCB, Novartis, Sarah Ohrndorf: None declared

BackgroundIxekizumab (IXE), a monoclonal antibody that selectively targets interleukin IL-17A, has shown efficacy in patients with radiographic axial spondyloarthritis (r-axSpA). Spinal pain, in particular spinal pain at night (SP-N), is a major contributor to the patient burden of r-axSpA.ObjectivesTo assess SP-N improvement in patients up to week (W) 52 and to determine the association of SP-N improvement in patients treated with IXE with other patient-reported outcomes (PROs) at W16 and with reaching ASDAS LDA at W52.MethodsThe Phase III COAST-V (NCT02696785) trial investigated the efficacy of IXE in 341 patients with r-axSpA and were biological disease-modifying anti-rheumatic drug (bDMARD)-naïve. Patients were randomised to IXE every 2W (IXEQ2W), IXE every 4W (IXEQ4W), adalimumab (ADA) or placebo (PBO) up to W16. Only approved dose IXEQ4W data are presented here. SP-N was measured at each visit using a numeric rating scale (NRS) (0-10). A clinically relevant improvement in SP-N was defined as >2 point improvement from baseline. Differences in baseline variables between those achieving versus not achieving >2 improvement in SP-N were tested using Fisher’s exact test (binary variables) and analysis of variance (ANOVA; continuous variables). Associations of SP-N improvement with PROs (BASFI, Fatigue Severity NRS, Jenkins Sleep Evaluation Questionnaire (JSEQ), SF-36 PCS) at W16, and ASDAS LDA at W52 were tested using analysis of covariance (ANCOVA; continuous variables) and logistic regression (binary variables). Missing values were imputed using non-responder imputation, and modified baseline observation carried forward.ResultsA greater proportion of patients achieved >2 improvement in SP-N with IXE treatment compared to PBO at W16 (63.0% vs. 32.2%, p 2 improvement in SP-N (63%) at W16 were younger, more frequently positive for HLA-B27 and had higher disease activity at baseline compared to those that did not achieve >2 improvement (Table 1). Achieving >2 improvement in SP-N was associated with improvement in PROs including BASFI, Fatigue Severity, JSEQ and SF-36 PCS at W16 and with achieving ASDAS2 improvement in SP-N (Table 1).Table 1.Baseline demographics, clinical characteristics, and PROs of IXE treated patients achieving vs. not achieving >2 improvement in SP-N at W16.Achieved >2 Improvement in SP-N at W16Yes (n=51)No (n=30)Baseline CharacteristicsAge, yrs38.6 (11.4)*44.9 (12.4)Positive for HLA-B27, n (%)50.0 (98.0)*25.0 (83.3)CRP (mg/L)14.9 (14.9)*7.6 (8.4)ASDAS3.9 (0.8)*3.5 (0.6)Spinal Pain at Night7.4 (1.3)*6.4 (1.4)PROsBaselineW16 CFBBaselineW16 CFBBASFI6.1 (1.9)-3.4 (2.2)***6.0 (1.6)-0.7 (1.5)Fatigue Severity NRS6.9 (1.7)-3.5 (2.6)***6.3 (1.6)-0.7 (2.0)JSEQ7.1 (5.4)-3.2 (4.2)***7.2 (5.2)-0.1 (2.7)SF-36 PCS32.8 (7.7)10.9 (7.7)***36.1 (6.7)2.0 (6.5)ASDAS 34 (66.7)**9 (33.3)Values represent mean (SD) unless otherwise stated. *p2 improvement in SP-N.HLA-B27; Human Leukocyte antigen-B27, CRP; C-reactive protein, ASDAS; Ankylosing Spondylitis Disease Activity Score, CFB; change from baseline, BASFI; Bath Ankylosing Spondylitis Functional Index, NRS; Numeric Rating Score, JSEQ; Jenkins Sleep Evaluation Questionnaire, SF-36 PCS; Short-Form 36 physical component score.Figure 1.Patients achieving meaningful spinal pain at night improvement through W52.ConclusionIXE improved SP-N for patients with r-axSpA not previously treated with bDMARDs. Improvements in SP-N were associated with improvements in disease activity, function, fatigue and quality of life.Disclosure of InterestsSofia Ramiro Speakers bureau: Eli Lilly and Company, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly and Company, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Pfizer, Novartis, UCB, Cédric Lukas Speakers bureau: AbbVie, Amgen, Novartis, Pfizer, Galapagos, Consultant of: AbbVie, BMS, Chugai, Roche, Eli Lilly and Cmpany, MSD, Novartis, Pfizer, Amgen, Grant/research support from: Roche, Pfizer, Novartis, Eli Lilly and Company, Michael J. Nissen Speakers bureau: Eli Lilly and Company, Janssen, Novartis, Consultant of: AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Yves Schymura Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Khai Ng Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andrew Bradley Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Gabriel Doridot Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Antoni Chan Speakers bureau: Novartis, AbbVie, Amgen, UCB, Janssen, Celgene, Biogen, Consultant of: Novartis, Eli Lilly and Company, Janssen, Amgen, UCB, AbbVie, James Cheng-Chung Wei Consultant of: tsh biopharma, Abbvie, BMS, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer, Sanofi-Aventis, UCB pharma, Grant/research support from: AbbVie, BMS, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB pharma

BackgroundThe term “early spondyloarthritis (SpA)” has been frequently used to refer to the first phase of the disease, however, no standardized definition on “early” has been established. The ASAS-SPEAR (SPondyloarthritis EARly definition) project aims at developing a consensual definition on what is meant by “early SpA”. In order to inform the ASAS-SPEAR working group, it is highly relevant to assess the current meaning of “early SpA” in the literature.ObjectivesTo identify all possible definitions of “early SpA” employed in the literature, including “early axial SpA (axSpA)” and “early peripheral SpA (pSpA)”.MethodsA systematic literature review was conducted in Medline, EMBASE and the Cochrane Library (through April 28th, 2021). The eligibility criteria were studies with any design, in adults that included any mention of “early SpA” or its subtypes in the title or abstract. Two reviewers independently identified eligible studies and extracted data, including the literal definition of early SpA used in each of them. The proportion of studies reporting a definition was calculated, and the different definitions were assessed, including the core of the definition: whether they were based on symptom duration, disease duration, radiographic damage, a combination of them or any other aspects, and their boundaries.ResultsOut of 9,651 titles identified, 355 publications reporting data from 186 studies were included (291 full papers, 64 conference abstracts). Among them, 217 (61%) were cohort studies, 72 (20%) were reviews and 46 (13%) were clinical trials. Over time, an increasing number of publications on early SpA were identified: Table 1.Top 3 candidate definitions for “early SpA” and subtypesCore of the definitionNumber of studies, n (%)SpA (n= 35)nr-axSpA10 (29%)< 2 years duration10 (29%)< 1 year duration6 (17%)AxSpA (n=38)< 5 years duration12 (34%)< 3 years duration9 (24%)nr-axSpA duration8 (21%)AS/r-axSpA (n=38)9 (24%)nr-axSpA7 (18%)< 2 years duration6 (16%)nr-axSpA (n=4)nr-axSpA2 (50%)< 1 year & nr-axSpA1 (25%)< 5 years & nr-axSpA1 (25%)pSpA (n=1)< 12 weeks duration1 (100%)“Duration” refers to symptom duration or disease duration.Figure 1.Number of studies stratified by the core of the definition.ConclusionOver time, the term “early SpA” and its subtypes are increasingly used. Despite addressing early SpA, more than one third of the studies did not include a clear definition of the term. The studies reporting a definition of early SpA showed a large heterogeneity, with two out of three of them based on the duration of symptoms or disease. These results emphasize the need for a standardised definition of early SpA.AcknowledgementsThe Assessment of Spondyloarthritis international Society (ASAS) supported Diego Benavent financially for this work.Disclosure of InterestsDiego Benavent Speakers bureau: Jannsen, Roche, Grant/research support from: Novartis., Dafne Capelusnik Speakers bureau: Bristol Myers Squibb, Pfizer, Grant/research support from: Pfizer, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma., Employee of: Director of Imaging Rheumatology bv., Robert B.M. Landewé Consultant of: AbbVie, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, and Pfizer, Astrid van Tubergen Consultant of: Novartis, Galapagos, Grant/research support from: Pfizer, UCB, Novartis, Louise Falzon: None declared, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: Abbvie and Novartis

BackgroundThere is growing evidence revealing that females report worse patient-reported outcomes compared to males in axial spondyloarthritis (axSpA). However, in which precise outcomes there is a meaningful difference across gender and whether this also occurs in patients with peripheral spondyloarthritis (pSpA) and psoriatic arthritis (PsA) is not fully understood.ObjectivesTo investigate the influence of gender on disease outcomes in patients with SpA, including axSpA, pSpA and PsA, in a worldwide setting.MethodsData from 4185 patients with axSpA, pSpA or PsA from the ASAS-PerSpA study were analysed. The ASAS-PerSpA is a cross-sectional study that recruited consecutive patients with SpA (according to their rheumatologist) from 24 countries. Associations between gender and disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), C-reactive protein (CRP)], function [Bath Ankylosing Spondylitis Functional Index (BASFI)], and overall health [ASAS-Health Index (ASAS HI), European Quality of Life Five Dimension (EQ-5D)] were investigated. Multilevel (country) univariable and multivariable linear mixed models were used. Interactions between gender and disease phenotype (SpA, pSpA and PsA) were analysed, and if relevant, models were stratified by disease subtype. Models were adjusted for relevant confounders (Table 1).Table 1.Multivariable multilevel model by disease phenotypeOutcomeDeterminant of interestDisease phenotypeAxSpApSpAPsAASDAS +Gender (female vs male)0.02 (-0.07, 0.11)0.36 (0.15, 0.58)0.25 (0.12, 0.38)BASDAI *0.39 (0.20, 0.58)1.22 (0.77, 1.69)0.88 (0.59, 1.16)BASFI -0.01 (-0.14, 0.17)0.30 (-0.12, 0.71)0.46 (0.20, 0.72)CRP^-1.36 (-3.17, 0.44)ASAS-HI#0.90 (0.70, 1.10)EQ-5D°-0.02(-0.03, -0.01)All models are adjusted by age, gender and education.+Also adjusted for marital status, BMI, smoking, axial involvement, peripheral arthritis, enthesitis, fibromyalgia, NSAIDs, steroids, csDMARDs, bDMARDs* Also adjusted for marital status, BMI, smoking, axial involvement, peripheral arthritis, enthesitis, psoriasis, fibromyalgia, NSAIDs, bDMARDs- Also adjusted for marital status, BMI, ASDAS, radiographic damage, fibromyalgia, NSAIDs, bDMARDs^ Also adjusted for marital status, BMI, radiographic damage, concomitant NSAIDs, steroids, csDMARDs# Also adjusted for smoking, ASDAS, BASFI, peripheral arthritis, enthesitis, fibromyalgia° Also adjusted for BMI, smoking, ASDAS, BASFI, radiographic damage, HLA-B27, enthesitis, fibromyalgiaResults are expressed in β (95% CI). Estimates with pResultsIn total, 4185 patients were included, of which 2719, 1033 and 433 had a diagnosis of axSpA (mean age 42 years, 32% female), PsA (mean age 52 years, 52% female) and pSpA (mean age 44 years, 53% female), respectively. A significant interaction between gender and disease phenotype was found for ASDAS, BASDAI and BASFI. Multivariable models for each outcome are shown in Table 1 (stratified by disease phenotype). While being female independently contributed to higher BASDAI across the three disease phenotypes (though with varying magnitude), female gender was only associated with higher ASDAS in pSpA [β (95% CI): 0.36 (0.15, 0.58)] and PsA [0.25 (0.12, 0.38)] but not in axSpA [0.016 (-0.07, 0.11)]. Female gender was associated with higher BASFI in PsA [0.46 (0.20, 0.72)]. No associations were observed between gender and CRP levels. Female gender was associated with higher ASAS-HI [0.90 (0.70, 1.10)] and EQ5D [-0.02 (-0.03, -0.01)], without significant differences across disease phenotype.ConclusionFemale gender was associated with less favorable outcomes across the SpA spectrum, except for CRP in which there were no differences between gender. While female gender influenced BASDAI across disease phenotypes, ASDAS was not associated with gender in axSpA. These results suggests that ASDAS should be the preferred instrument in clinical practice both for females and males with axSpA.AcknowledgementsWe would like to thank all ASAS-perSpA investigators and members of the scientific committee.Disclosure of InterestsDiego Benavent Speakers bureau: Janssen, Roche, Grant/research support from: Novartis, Dafne Capelusnik Speakers bureau: Bristol Myers Squibb, Pfizer, Grant/research support from: Pfizer, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Anna Moltó Consultant of: Abbvie, UCB, Novartis, Gilead, Pfizer, Lilly y Janssen, Grant/research support from: UCB, Clementina López-Medina Speakers bureau: Lilly, Novartis, Janssen, UCB and Abbvie, Maxime Dougados: None declared, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie and Novartis

BackgroundWork participation (WP) is a top priority for people with RA and a determinant of patients’ quality of life. Therefore, assessing the effect of interventions on WP outcomes is important.ObjectivesTo review the effect of b/tsDMARDs on employment status (ES), sick leave (SL) and presenteeism in patients with longstanding RA.MethodsA systematic literature review up to October 2021 was conducted using the PICOT framework (Figure 1). Two researchers independently screened abstracts, then full texts were reviewed to determine eligibility. Data from eligible articles were extracted. Heterogeneity and insufficient reporting of data precluded meta-analysis.ResultsWe included 42 studies:16 randomized controlled trials (RCT) and 26 longitudinal observational studies (OBS). All studies were conducted with background therapy with csDMARDs; 33 (78%) in csDMARD-IR patients. RCTs provided short-term data only (≤24 weeks (w)) which have limited relevance for WP outcome domains such as ES1. OBS reported long-term data (≤ 5 years), albeit imposing challenges due to lack of random allocation to interventions and often lack of a comparator. Regarding ES, 6 RCTs and 4 OBS did not report significant differences in bDMARD-treated patients vs background csDMARDs. For SL (19 studies), 1 RCT showed that etanercept significantly reduced RA-related SL up to 12-16w; however, one OBS showed no such effect on the long-term. Conflicting results were obtained by 2 RCTs on baricitinib. Most compounds assessed in the 12 OBS without comparator reported improvement in SL up to 104w. For presenteeism (11 studies; Table 1), 4 RCTs showed that etanercept, golimumab, certolizumab pegol, baricitinib and peficitinib were superior to PBO+csDMARDs up to 12w. Two H2H studies assessing sarilumab and baricitinib vs adalimumab observed comparable presenteeism in all treatment arms at 12-16w.Table 1.Overview of presenteeism from RCTs and OBS with a comparator in csDMARD-IR patientsAuthorYearInstrumentRecall periodIntervention (I)¶Comparator (C)¶N employed/N totalEffect sizeFrom the articleComputed SMD (95% CI)Bae2013WPAI-GH7 dI: ETNC: csDMARDNR/197NR/103% improvement49.623.6-0.24 (-0.5; -0)Bingham2014Self-composed single item4 wI: GOLC: PBONR/395NR/197Mean Δ (SD)–2.4 (2.8)–0.7 (4.5)-Emery2017WPAI-RA7 dI: BARI 2mgI: BARI 4mgC: PBO88/22976/22790/228LSM Δ from BL (95% CI)−14 (−20 to −8)−16 (−22 to −11)−8 (−13 to −2)-Keystone 2017WPAI-RA7 dI: BARIC: PBO199/487206/488LSM Δ from BL (95% CI)-18 (-22, -15)-10 (-13, -6)-Kavanaugh 2009WPS-RA1 mI: CZP 200 mgI: CZP 400 mgC: PBO132/393139/39069/199NR-0.09 (-0.3; 0.1)-0.17 (-0.3; -0)Kavanaugh 2009WPS-RA1 mI: CZP 200 mgI: CZP 400 mgC: PBO101/24695/24649/127NR-0.11 (-0.3; 0.1)-0.11 (-0.3; 0.1)Strand2018WPS-RA1 mI: SARIC: ADA78/184185LSM Δ from BL (SE)-3.74 (0.5)-3.50 (0.5)-Kaeley2018WPAI-RA7 dI: ADA + MTX 7.5mgC: ADA + MTX 20mgNR/154NR/155NR0.20 (-0.03-0.4)Tanaka2021†WPAI7 dI: PEF100mg ± csDMARDsI: PEF150mg ± csDMARDsC: PBO60/10453/10250/102Mean Δ−12.2−18.73.6-Tanaka2021WPAI7 dI: PEF100mg ± MTXI. PEF150mg ± MTXC: PBO ± MTX83/174101/17499/170Mean Δ−11.6−16.9−2.7-Tanaka2018 & 2020*WPAI 7 daysI: TCZC: csDMARDs167/377160/347Mean Δ-17.7-17.2-*OBS WPAI, work productivity and activity index; WPS, work productivity survey; GH, global health; NR, not reported; LSM, least mean square; BL, baseline; CI, confidence interval; SE, standard error; SMD, standardized mean difference; d, days; w, weeks; m, month. ¶Added to background therapy with csDMARDs unless otherwise stated.ConclusionShort-term data from RCTs with background therapy with csDMARDs showed adding b/tsDMARDs was more effective than PBO in improving presenteeism. However, data on SL are conflicting and the positive results come from OBS without comparator. Future studies should consider existing guidance on the assessment of WP outcome domains to allow pooling and meta-analysis1.References[1]Boonen A, et al. Ann Rheum Dis. 2021;80:1116-23.Disclosure of InterestsAlessia Alunno: None declared, Mary Lucy Marques: None declared, Louise Falzon: None declared, Sofia Ramiro: None declared, Annelies Boonen Speakers bureau: Abbvie, Galapagos, Consultant of: Galapagos, Grant/research support from: Abbvie

BackgroundRheumatic diseases substantially affect the lives of patients, with complex associations between disease severity and self-perceived health status. In this regard, the Coping with Rheumatic Stressors (CORS) questionnaire was developed to measure how patients with rheumatoid arthritis cope with stressors such as pain or dependence. There is no validated instrument to measure coping in axial spondyloarthritis (axSpA) and therefore the adaptation of the CORS would be of great value.ObjectivesTo cross-culturally adapt the CORS into Spanish and to test the conceptual equivalence of the translated version in patients with axSpA.MethodsA translation of the CORS into Spanish was performed, followed by a back-translation into Dutch, following forward-backward procedure as described by Beaton1(Figure 1). Two bi-lingual translators (native speakers for Spanish), one of them informed of the content of the questionnaire and the other not informed, produced independent forward translations of the item content, response options, and instructions of the CORS into Spanish. Both versions were harmonized in a consensual version. Another translator (native speaker for Dutch), not informed of the concepts used in the questionnaire, back translated the synthesized version into Dutch. An expert committee including all translators, one methodologist and a rheumatologist, held a meeting and reached consensus on discrepancies to develop a pre-final version of the Spanish CORS. The field test with cognitive debriefing involved a sample of 10 patients with axSpA covering the full spectrum of the disease and with different sociodemographic backgrounds.Figure 1.Cross-cultural adaptation of the CORSResultsThe translation process of the CORS was completed following the forward-backward procedure, after discussion of the discrepancies throughout the process. The first translation was done without major complications. However, several discrepancies appeared in the back-translation, in which there were minor modifications in the wording in one response option (“muchas veces” to “muy a menudo”) and 15 questionnaire items. As an example, “Ik ga de deur uit”, literally meaning “I go out by the door”, was initially translated as such (“salgo por la puerta”); however, it conceptually represents “I go away”, and it was adapted like this (“me voy a la calle”). Thus, a pre-final consensus version of the CORS was agreed by the expert committee. This pre-final version was field tested in 10 patients with axSpA: mean age (SD) was 38.9 (14.4) years, 7 patients were male, 6 had radiographic axSpA, and 9 were HLA-B27+. The Spanish questionnaire appeared clear and understandable to all patients. However, some minor modifications were proposed in some items (Table 1). As a result of the cognitive debriefing, two changes were implemented (one instruction and one item), whereas two other suggestions did not lead to any change due to minor wording discrepancies with similar conceptual equivalence. The final version of the Spanish CORS is shown at shorturl.at/cimC6.Table 1.Cognitive debriefing queries and decisions from the expert committeeOriginal Dutch itemSpanish translation pre-final# Patient queriesQueriesFinal version(….) aan te geven hoe vaak u het beschreven gedrag uitvoert.(…) indique cuán a menudo usted ha llevado a cabo dicho comportamiento.1Literal discrepancies(…) indique la frecuencia con que usted ha tenido dicho comportamiento.Ik rust op tijd uitMe voy a tiempo a descansar1Literal discrepanciesNo changesIk probeer er het beste van te makenIntento aprovechar al máximo1Literal discrepanciesNo changesIk houd rekening met anderenTengo en cuenta a los demás2Meaning doubtsTengo en consideración a los que me ayudan/cuidanConclusionThe Spanish version of the CORS showed good cross-cultural validity and good face validity in patients with axSpA according to the field test. Before the Spanish CORS is implemented, further validation is in progress to test the psychometric properties of the instrument.References[1]Beaton DE, et al. Spine. 2000; 25:3186-91Disclosure of InterestsDiego Benavent Speakers bureau: Jannsen, Roche, Grant/research support from: Novartis, Andrea Jochems: None declared, DORA PASCUAL-SALCEDO Speakers bureau: Pfizer, Menarini, Takeda, Abvvie., Grant/research support from: Pfizer, Menarini, Takeda, Abvvie., Gijs Jochems: None declared, Chamaida Plasencia Speakers bureau: Pfizer, Abvvie, Lilly, Sandoz, Sanofi, Biogen, Roche, Novartis., Grant/research support from: Pfizer, Abvvie., Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UC, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Wim van Lankveld: None declared, Alejandro Balsa Speakers bureau: Pfizer, Abbvie, Lilly, Galapagos, BMS, Sandoz, Nordic Pharma, Gebro, Roche, Sanofi, UCB, Consultant of: Pfizer, Abbvie, Lilly, Galapagos, BMS, Nordic Pharma, Sanofi, UCB, Grant/research support from: Pfizer, Abbvie, BMS, Nordic Pharma, Gebro, Roche, UCB, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie and Novartis

BackgroundIn axial spondyloarthritis (axSpA), an alternative ASDAS (altASDAS) was developed to be used when Patient Global Assessment (PGA) is unavailable. AltASDAS replaces PGA with BASDAI total score and has so far only been internally validated [1].ObjectivesTo test the psychometric properties of altASDAS in an external cohort, according to the OMERACT filter 2.0 (truth, discrimination; feasibility was evaluated in our previous work).MethodsCohorts from the COAST trial programme of ixekizumab (COAST-V,-W,-X;primary endpoint: 16-week), enrolling radiographic/non-radiographic axSpA (r-/nr-axSpA) patients, were pooled. AltASDAS was calculated for all evaluations. Truth was assessed by: 1) agreement with original-ASDAS, as a continuous score and as a categorical variable (disease activity-DA-states), with intraclass correlation coefficients (ICC) and weighted Kappa respectively; 2) Bland & Altman plots with mean difference (MD) and 95% limits of agreement (LoA) 3) comparison of Pearson correlations of altASDAS and original-ASDAS with other constructs. Discrimination was tested by 1) the ability of altASDAS to distinguish high/low DA states according to an external anchor (nocturnal pain>6 indicating high DA) 2) agreement (kappa) with original-ASDAS in major/clinically important-improvement (MI/CII) achievement at 16-weeks 3) comparison of number of patients reaching MI/CII in the treatment versus placebo arm at 16-weeks, according to original and altASDAS (higher Chi-square=better discrimination).Results958 patients were included, 70% males, mean age 42.7 years, 68% r-axSpA. Truth: 1) agreement with original-ASDAS: ICC=0.97 (95%CI:0.93-0.99), kappa=0.84 (0.83-0.85) 2) MD with original-ASDAS: 0.14; 95% LoA -0.56 to 0.28 3) correlation coefficients of altASDAS with related constructs were within a pre-specified 0.3-wide band around those between original-ASDAS and the same construct (Table 1 a). Discrimination altASDAS discriminated between DA states (Table 1 b) and in sensitivity to change (Kappa with original-ASDAS for MI=0.87 95%CI:0.83-0.91; for CII=0.93; 95%CI:0.90-0.95) and Table 1 e cTable 1.Psychometric properties of alternative Ankylosing Spondylitis Disease Activity Score (altASDAS)a) Truth: correlations with constructs related to disease activityData expressed as correlation coefficient rFunction (BASFI)Quality of Life (MCS)Quality of life (PCS)Overall functioning and health (ASAS HI)Original-ASDAS0.58-0.11-0.480.35altASDAS0.57-0.11-0.470.35b) Discrimination: disease activity statesAnchor to define disease activity: Nocturnal pain (NRS 0-10)NRS >6 Mean ASDAS (SD)NRS ≤ 6 Mean ASDAS (SD)SMDOriginal-ASDAS3.99 (0.76)2.61 (0.86)-1.68altASDAS3.87 (0.83)2.46 (0.96)-1.57c) Discrimination: sensitivity to changeTreatment N (%)Placebo N (%)Chi-squareN° of patients628272-Original-ASDAS MI151 (24)12 (4)49.3altASDAS-MI167 (26)13 (5)56.4Original-ASDAS CII342 (54)62 (23)76.9altASDAS-CII350 (56)64 (23)79.2BASFI: Bath Ankylosing Spondylitis Functional Index, MCS and PCS: mental and physical component summary of Short-Form 36; ASAS HI: ASAS Health Index; NRS: Numerical rating scale; SD: standard deviation; SMD: standardised mean differences; MI and CII: Major and Clinically Important ImprovementConclusionAltASDAS was shown to be truthful and discriminative in an external cohort and as such has been fully validated and can be used in cases when PGA is unavailable.References[1]Ortolan A et al. Rheumatology (Oxford). 2021;60:638-48.AcknowledgementsThe authors wish to thank Lilly for providing data of the trials COAST-V, (NCT02696785), COAST-W (NCT02696798) and COAST-X (NCT02757352).Disclosure of InterestsAugusta Ortolan Grant/research support from: 2020 New Horizon Fellowship, Sofia Ramiro Consultant of: Consultancy/speaking fees from AbbVie, Eli Lilly, MSD, Novartis, UCB, Sanofi, Grant/research support from: Research grant from MSD, Désirée van der Heijde Consultant of: Consulting fees AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, Employee of: Pharma Director of Imaging Rheumatology bv

BackgroundA definition for clinically important worsening (CIW) of axSpA has been proposed by ASAS: i.e. an increase of ≥0.9 points of ASDAS. However, it is unknown how this definition performs in an early axSpA cohort.ObjectivesTo determine the prevalence of CIW in a population of early axSpA, as well as the association between the occurrence of CIW and the presence of concomitant signs of inflammation; finally, to determine whether MRI inflammation was predictive of a future CIW.Methods708 patients with early axSpA from the French DESIR cohort were included in the analysis. Patients were followed every 6 months for the first 2 years and annually thereafter. All patients had an MRI of spine and sacroiliac joints at baseline, but only patients from the APHP centers performed those at 2 and 5 years. Prevalence of CIW was calculated during the 5 years of follow-up in the cohort. The association between CIW and concomitant objective signs of inflammation (such as swollen joint count) was assessed over time using mixed models adjusted for sociodemographic and other clinical covariates. CIW predictive factors including the predictive capacity of MRI inflammation (measured by SPARCC at SIJ and spine) and MRI structural damage (defined by presence of ≥5 structural lesions of SI joints or spine) on the occurrence of a future CIW (time-lagged models) were evaluated.ResultsTotal number of CIW was 378 in 5 years with 42.8% (303/708) of patients presenting at least one CIW during the follow-up. There were no significant sociodemographic or clinical differences at inclusion between patients with at least one episode of CIW and those without CIW during follow-up.In the association models, concomitant tender joint count (OR 1.02, CI95%[1.00; 1.03]) and ASAS-NSAID score last week (OR 1.00, CI95%[1.00; 1.01]) were significantly associated with CIW over time. Presence of MRI-SIJ inflammation (OR (per SPARCC point) 1.02, CI95%[1.01; 1.04]) and MRI-SIJ structural damage (OR 2.74, CI95%[1.27; 5.93]) were predictive of future (next visit) occurrence of CIW.ConclusionPatients with CIW according to the ASAS definition had significantly more objective signs of inflammation concomitantly but also over time. These data support the construct validity of this definition of CIW in an early axSpA population. MRI-SIJ inflammation and structural damage may have a predictive role in the subsequent occurrence of CIW.References[1]Molto A, et al. Ann Rheum Dis. 2018Table 1.Effect of MRI lesions on the future development of CIWVariablesOR [95%CI]Visit1.01 [0.98; 1.04]Sex (Women)1.55 [0.71; 3.36]Age0.99 [0.95; 1.04]Marital status (Single)0.64 [0.30; 1.37]Education (University or equivalent)0.89 [0.41; 1.94]White collar workers vs blue collars0.52 [0.19; 1.46]HLA B27 status1.15 [0.57; 2.32]Symptoms duration1.43 [1.00; 2.05]Enthesitis score1.00 [0.92; 1.08]Tender joint count1.02 [0.98; 1.06]Swollen joint count0.81 [0.39; 1.70]ASAS NSAID score last week1.01 [1.00; 1.01]csDMARD intake last 6 months0.76 [0.20; 2.80]TNF last 6 months0.78 [0.37; 1.63]Lag SPARCC-SIJ1.02 [1.00; 1.04]Lag SPARCC-spine0.98 [0.95; 1.02]AcknowledgementsThis project was conducted thanks to an ASAS grant.Disclosure of InterestsFaten Hamitouche Grant/research support from: ASAS (Assessment in SpondyloArthritis International Society) grant, Sushmithadev Kumaradev: None declared, Désirée van der Heijde Consultant of: Consulting fees AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Employee of: Director of Imaging Rheumatology bv., Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Alexandre Sepriano Speakers bureau: Novartis, Consultant of: UCB, Anna Moltó Consultant of: Abbvie, BMS, Novartis, UCB, Pfizer, Lilly, Grant/research support from: UCB

BackgroundPresence of vertebral corner inflammation (VCI) increases the likelihood of a new syndesmophyte in the same vertebral corner (VC) in patients with r-axSpA. It was suggested that subsequent vertebral corner fat deposition (VCFD) partially explains this effect. However, this has not been formally tested.ObjectivesTo determine how much of the effect of VCI on the development of new syndesmophytes is explained by new VCFD.MethodsTwo datasets (SIAS cohort, ASSERT clinical trial) were analyzed. Patients with r-axSpA were assessed at baseline (T0), an intermediate visit (T1) (SIAS: 1 year; ASSERT: 24 weeks) and the end of follow-up (T2) (SIAS: 2 years; ASSERT: 102 weeks). Syndesmophytes were assessed on whole spine low dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 and considered present if seen by 2 of 2 readers. VCI (T0) and VCFD (T0 and T1) on spinal MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). VCs with VCFD or a syndesmophyte at baseline were excluded. We used the counterfactual approach1 to decompose the total effect of VCI at T0 (binary exposure) on the formation of a new syndesmophyte in the same VC at T2 (binary outcome) into the effect that is explained (natural indirect effect, NIE) and the effect that is not explained (natural direct effect, NDE) by new VCFD (binary mediator) at T1. Because there was no interaction between the exposure and mediator (p=0.88 for SIAS; p=0.82 for ASSERT), the average NIE (aNIE) and average NDE (aNDE) are reported. The aNIE, aNDE and total effect, expressed as absolute increase in risk, were estimated in R using the ‘mediation’ package, which takes into account the 2-level structure of the data (VCs nested within patients).ResultsIn total, 49 patients (2,667 corners) in SIAS and 168 patients (2,918 corners) in ASSERT were included. A new syndesmophyte occurred at T2 in 124/2,667 (5%) corners in SIAS and 91/2,918 (3%) corners in ASSERT (Table 1). New VCFD at T1 was also uncommon (SIAS: 4%; ASSERT: 2%), but occurred more often in corners with (SIAS: 12%; ASSERT: 18%) than without VCI at T0 (SIAS: 3%; ASSERT: 1%). Applying the mediation formula, in SIAS, the presence of VCI at T0 increased the probability of a new syndesmophyte in the same VC at T2 by 9.3% [total effect (95% CI)=9.3% (4.5; 15.0)]. There was only a 0.2% increase in this probability that was mediated by the formation of new VCFDs at T1 [aNIE=0.2% (-0.4; 1.0)]. In contrast, 9.1% of the increase in probability remained unexplained [aNDE=9.1 (4.3; 15.0)]. This means that only 2% (0.2/9.3) of the total effect of VCI on the formation of new syndesmophytes was explained by new VCFD [% mediated=2.0% (-4.1; 13)]. In ASSERT, the total effect was somewhat lower than in SIAS [total effect=7.3% (2.0; 16.0)], and again the aNIE was small [aNIE=0.8% (-0.2; 3.0)], and the aNDE composed most of the total effect [aNDE=6.5% (1.3; 14.0)]. The proportion of the total effect explained by VCFD (0.8/7.3=10% (-3.1;44)) was larger than in SIAS but still non-significant.Table 1.Marginal and conditional probabilitiesSIASVCI T0New VCFD T1New SYND T2nP (SYND|VCI, VCFD)P(VCFD|VCI)0002302P (SYND|0,0) =90/2392= 0.038P(VCFD|0) = 74/2466=0.0300019001070P (SYND|0,1) =4/74 = 0.0540114100152P (SYND|1,0) = 25/177 = 0.141P(VCFD|1) = 24/201 =0.1191012511019P (SYND|1,1) = 5/24 = 0.2081115ASSERTVCI T0New VCFD T1New SYND T2nP (SYND|VCI, VCFD)P(VCFD|VCI)0002660P (SYND|0,0) = 76/2736= 0.028P(VCFD|0) = 35/2771 =0.0130017601034P (SYND|0,1) =1/35= 0.0290111100112P (SYND|1,0) = 9/121= 0.074P(VCFD|1) = 26/147 =0.177101911021P (SYND|1,1) = 5/26 = 0.1921115VCI, vertebral corner inflammation; VCFD, vertebral corner fat deposition; Synd, syndesmophytes; T0, baseline; T1, intermediate visit; T2, end of follow-up; n, number of vertebral corners; P, probabilityConclusionIn these two datasets we see that VCI only infrequently leads to syndesmophyte formation via visible VCFD.References[1]Pearl, The mediation formula, 2011Figure 1.The pathways under study. VCI, vertebral corner inflammation; VCFD, vertebral corner fat depositionDisclosure of InterestsRosalinde Stal: None declared, Alexandre Sepriano Speakers bureau: Novartis, Consultant of: UCB, Sofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVi, Galapagos, MSD, Novartis, Pfizer, UCB, Floris A. van Gaalen Consultant of: Novartis, MSD, AbbVie, Bristol Myers Squibb, Eli Lilly, Grant/research support from: Stichting vrienden van Sole Mio, Stichting ASAS, Jacobus Stichting, Novartis, UCB, Pedro Machado Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Xenofon Baraliakos: None declared, Rosaline van den Berg: None declared, Monique Reijnierse Grant/research support from: reader for ASAS CLASSIC study, Juergen Braun: None declared, Robert B.M. Landewé Consultant of: AbbVie, Amgen, BMS, GSK, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Gilead, Glaxo-Smith-Kline, Lilly, Novartis, UCB Pharma, Grant/research support from: Dutch Rheumatism Association

New evidence shows that host-microbiota crosstalk can be modulated via endogenous miRNAs. We have previously reported that miR-21 ablation protects against liver injury in cholestasis. In this study, we investigated the role of miR-21 in modulating the gut microbiota during cholestasis and its effects in liver dysfunction. Mice lacking miR-21 had reduced liver damage and were protected against small intestinal injury as well as from gut microbiota dysbiosis when subjected to bile duct ligation surgery. The unique microbiota profile of miR-21KO mice was characterized by an increase in Lactobacillus, a key microbiome genus for gut homeostasis. Interestingly, in vitro incubation of synthetic miR-21 directly reduced Lactobacillus load. Moreover, supplementation with Lactobacillus reuteri revealed reduced liver fibrosis in acute bile duct-ligated mice, mimicking the protective effects in miR-21 knockout mice. D-lactate, a main product of Lactobacillus, regulates gut homeostasis that may link with reduced liver fibrosis. Altogether, our results demonstrate that miR-21 promotes liver dysfunction through direct modulation of the gut microbiota and highlight the potential therapeutic effects of Lactobacillus supplementation in gut and liver homeostasis.

Most microbes live in spatially confined subpopulations. Under spatial structure conditions, the efficacy of natural selection is often reduced (relative to homogeneous conditions) due to the increased importance of genetic drift and local competition. Additionally, under spatial structure conditions, the fittest genotype may not always be the one with better access to the heterogeneous distribution of nutrients. The effect of radial expansion may be particularly relevant for the elimination of antibiotic resistance mutations, as their dynamics within bacterial populations are strongly dependent on their growth rate. Here, we use Escherichia coli to systematically compare the allele frequency of streptomycin, rifampin, and fluoroquinolone single and double resistance mutants after 24 h of coexistence with a susceptible strain under radial expansion (local competition) and homogeneous (global competition) conditions. We show that there is a significant effect of structure on the maintenance of double resistances which is not observed for single resistances. Radial expansion also facilitates the persistence of double resistances when competing against their single counterparts. Importantly, we found that spatial structure reduces the rate of compensation of the double mutant RpsL(K43T) RpoB(H526Y) and that a strongly compensatory mutation in homogeneous conditions becomes deleterious under spatial structure conditions. Overall, our results unravel the importance of spatial structure for facilitating the maintenance and accumulation of multiple resistances over time and for determining the identity of compensatory mutations.

© The Author(s). 2020 Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/.The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data., Background: To investigate whether the reason to discontinue the first TNF inhibitor (TNFi) affects the response to the second TNFi in axial spondyloarthritis (axSpA). Methods: Patients with axSpA from the Rheumatic Diseases Portuguese Register (ReumaPt), who discontinued their first TNFi and started the second TNFi between June 2008 and May 2018, were included. Response was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (ASDAS-CII), major important improvement (ASDAS-MI), low disease activity (ASDAS-LDA), and inactive disease (ASDAS-ID). The reason for discontinuation of the first TNFi was defined, according to ASDAS-CII as primary failure (no response ≤ 6 months), secondary failure (response ≤ 6 months but lost thereafter), adverse events, and others. The association between the reason for discontinuation of the first TNFi and response to the second TNFi over time was assessed in multivariable generalized equation (GEE) models. Results: In total, 193 patients were included. The reason for discontinuation of the first TNFi did not influence the response to the second TNFi, according to the ASDAS-CII. However, a difference was found with more stringent outcomes, e.g., there was a higher likelihood to achieve ASDAS-ID with the second TNFi for patients discontinuing the first TNFi due to secondary failure (OR 7.3 [95%CI 1.9; 27.7]), adverse events (OR 9.1 [2.5; 33.3]), or other reasons (OR 7.7 [1.6; 37.9]) compared to primary failure. Conclusion: Patients with axSpA with secondary failure to their first TNFi, compared to those with primary failure, have a better response to the second TNFi according to stringent outcomes., This work was supported by a research grant from Merck Sharp & Dohme Corp., a division of Merck & Co., Inc., Kenilworth, NJ, USA [IIS# 57763]. AS is supported by a doctoral grant from “Fundação para a Ciência e Tecnologia”(SFRH/BD/108246/2015)

Bacteria generally live in species-rich communities, such as the gut microbiota. Yet little is known about bacterial evolution in natural ecosystems. Here, we followed the long-term evolution of commensal Escherichia coli in the mouse gut. We observe the emergence of mutation rate polymorphism, ranging from wild-type levels to 1,000-fold higher. By combining experiments, whole-genome sequencing, and in silico simulations, we identify the molecular causes and explore the evolutionary conditions allowing these hypermutators to emerge and coexist within the microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III proofreading and catalytic subunits, which increase mutation rate by approximately 1,000-fold and stabilise hypermutator fitness, respectively. Strong mutation rate variation persists for >1,000 generations, with coexistence between lineages carrying 4 to >600 mutations. The in vivo molecular evolution pattern is consistent with fitness effects of deleterious mutations sd ≤ 10−4/generation, assuming a constant effect or exponentially distributed effects with a constant mean. Such effects are lower than typical in vitro estimates, leading to a low mutational load, an inference that is observed in in vivo and in vitro competitions. Despite large numbers of deleterious mutations, we identify multiple beneficial mutations that do not reach fixation over long periods of time. This indicates that the dynamics of beneficial mutations are not shaped by constant positive Darwinian selection but could be explained by other evolutionary mechanisms that maintain genetic diversity. Thus, microbial evolution in the gut is likely characterised by partial sweeps of beneficial mutations combined with hitchhiking of slightly deleterious mutations, which take a long time to be purged because they impose a low mutational load. The combination of these two processes could allow for the long-term maintenance of intraspecies genetic diversity, including mutation rate polymorphism. These results are consistent with the pattern of genetic polymorphism that is emerging from metagenomics studies of the human gut microbiota, suggesting that we have identified key evolutionary processes shaping the genetic composition of this community., Weak-effect deleterious mutations and negative frequency–dependent selection, acting on beneficial mutations, shape the dynamics of molecular evolution within the mouse gut microbiota.

Switching from a low-fat and high-fiber diet to a Western-style high-fat and high-sugar diet causes microbiota imbalances that underlay many pathological conditions (i.e., dysbiosis). Although the effects of dietary changes on microbiota composition and functions are well documented, their impact in gut bacterial evolution remains unexplored. We followed the emergence of mutations in Bacteroides thetaiotaomicron, a prevalent fiber-degrading microbiota member, upon colonization of the murine gut under different dietary regimens. B. thetaiotaomicron evolved rapidly in the gut and Western-style diet selected for mutations that promote degradation of mucin-derived glycans. Periodic dietary changes caused fluctuations in the frequency of such mutations and were associated with metabolic shifts, resulting in the maintenance of higher intraspecies genetic diversity compared to constant dietary regimens. These results show that dietary changes leave a genetic signature in microbiome members and suggest that B. thetaiotaomicron genetic diversity could be a biomarker for dietary differences among individuals. info:eu-repo/semantics/publishedVersion