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ObjectiveThe aim of the present study was to investigate whether the relationship between sex and clinical outcomes in early rheumatoid arthritis (RA) varies by autoantibody status.MethodsTwo inception cohorts of consecutive patients with early RA (ie, symptom duration ≤ 12 months) in the southern region of Sweden were investigated. Patients were stratified by anticitrullinated peptide antibody (ACPA) status. The primary outcome was remission (Disease Activity Score in 28 joints [DAS28] < 2.6) at 12 months. Secondary outcomes were remission at 6 months and European Alliance of Associations for Rheumatology good response at 6 and 12 months compared to baseline. In logistic regression models, which were adjusted for age, DAS28 values, and Health Assessment Questionnaire values at baseline, the relationship between sex and clinical outcomes, stratified by ACPA status, was investigated.ResultsIn total, 426 patients with early RA were included: 160 patients were ACPA negative and 266 patients were ACPA positive. At 12 months, 27.1% (38/140) of females and 24.1% (13/54) of males with ACPA-positive RA achieved DAS28 remission. In ACPA-negative RA, 16.0% (13/81) of females and 48.6% (18/37) of males achieved DAS28 remission at 12 months. Males had higher odds of reaching remission at 12 months in the ACPA-negative patient group (pooled adjusted odds ratio [OR] 4.79, 95% CI 1.97-11.6), but not in the ACPA-positive group (pooled adjusted OR 1.06, 95% CI 0.49-2.30).ConclusionMale sex was associated with better clinical outcomes in ACPA-negative early RA, but not in ACPA-positive early RA. The poor outcomes in females with early seronegative RA suggest that this represents a difficult-to-treat patient group.

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05046-4.

Objective To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. Design Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. Setting Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. Participants Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. Interventions Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. Main outcome measures The primary outcome was adjusted clinical disease activity index remission (CDAI≤2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. Results 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval −5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and −0.6% (−10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. Conclusions All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis. Trial registration EudraCT2011-004720-35, NCT01491815 .

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and harms of TNFi in patients with JIA.

OP0018 (2020) A MULTICENTER RANDOMIZED STUDY IN EARLY RHEUMATOID ARTHRITIS TO COMPARE ACTIVE CONVENTIONAL THERAPY VERSUS THREE BIOLOGICAL TREATMENTS: 24 WEEK EFFICACY RESULTS OF THE NORD-STAR TRIAL M. L. Hetland1, E. A. Haavardsholm1, A. Rudin1, D. Nordström1, M. Nurmohamed1, B. Gudbjornsson1, J. Lampa1, K. Hørslev-Petersen1, T. Uhlig1, G. Gröndal1, M. Ǿstergaard1, M. Heiberg1, J. Twisk1, S. Krabbe1, K. Lend1, I. Olsen1, J. Lindqvist1, A. K. H. Ekwall1, K. L. Grøn1, M. C. Kapetanovic1, F. Faustini1, R. Tuompo1, T. Lorenzen1, G. Cagnotto1, E. Baecklund1, O. Hendricks1, D. Vedder1, T. Sokka-Isler1, T. Husmark1, M. K. A. Ljosa1, E. Brodin1, T. Ellingsen1, A. Soderbergh1, M. Rizk1, Å. Reckner1, P. Larsson1, L. Uhrenholt1, S. A. Just1, D. Stevens1, T. B. Laurberg1, G. Bakland1, R. Van Vollenhoven1 1Denmark, Finland, Iceland, Netherlands, Norway, Sweden Background: The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (RA) is yet to be established. Objectives: The primary aim was to assess and compare the proportion of pts who achieved remission with active conventional therapy (ACT) and with three different biologic therapies after 24 wks. Secondary aims were to assess and compare other efficacy measures. Methods: The investigator-initiated NORD-STAR trial (NCT01491815) was conducted in the Nordic countries and Netherlands. In this multicenter, randomized, open-label, blinded-assessor study pts with treatment-naïve, early RA with DAS28>3.2, and positive RF or ACPA, or CRP >10mg/L were randomized 1:1:1:1. Methotrexate (25 mg/week after one month) was combined with: 1) (ACT): oral prednisolone (tapered quickly); or : sulphasalazine, hydroxychloroquine and mandatory intra-articular (IA) glucocorticoid (GC) injections in swollen joints

Background There are limited data regarding efficacy of abatacept treatment for rheumatoid arthritis (RA) outside clinical trials. Quality registers have been useful for observational studies on tumor necrosis factor inhibition in clinical practice. The aim of this study was to investigate clinical efficacy and tolerability of abatacept in RA, using a national register. Methods RA patients that started abatacept between 2006 and 2017 and were included in the Swedish Rheumatology Quality register (N = 2716) were investigated. Survival on drug was estimated using Kaplan-Meier analysis. The European League Against Rheumatism (EULAR) good response and Health Assessment Questionnaire (HAQ) response (improvement of ≥ 0.3) rates (LUNDEX corrected for drug survival) at 6 and at 12 months were assessed. Predictors of discontinuation were investigated by Cox regression analyses, and predictors of clinical response by logistic regression. Significance-based backward stepwise selection of variables was used for the final multivariate models. Results There was a significant difference in drug survival by previous biologic disease-modifying antirheumatic drug (bDMARD) exposure (p Conclusions In this population-based study of RA, bDMARD naïve patients and male patients were more likely to remain on abatacept with a major clinical response.

Objective: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. Methods: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. Results: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23–10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68–8.17]), and serum urate level (OR 1.31 [95% CI 1.06–1.62]). Conclusion: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. (Less)

Background:The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (RA) is yet to be established.Objectives:The primary aim was to assess and compare the proportion of pts who achieved remission with active conventional therapy (ACT) and with three different biologic therapies after 24 wks. Secondary aims were to assess and compare other efficacy measures.Methods:The investigator-initiated NORD-STAR trial (NCT01491815) was conducted in the Nordic countries and Netherlands. In this multicenter, randomized, open-label, blinded-assessor study pts with treatment-naïve, early RA with DAS28>3.2, and positive RF or ACPA, or CRP >10mg/L were randomized 1:1:1:1. Methotrexate (25 mg/week after one month) was combined with: 1) (ACT): oral prednisolone (tapered quickly);or: sulphasalazine, hydroxychloroquine and mandatory intra-articular (IA) glucocorticoid (GC) injections in swollen joints Results:812 pts were randomized. Age was 54.3±14.7 yrs (mean±SD), 31.2% were male, DAS28 5.0±1.1, 74.9% were RF and 81.9% ACPA positive. Fig 1 shows the adjusted CDAI remission rates over time with 95% CI. Table shows crude remission and response rates and absolute differences in adjusted remission and response rates (superiority analysis). Differences in remission and response rates with CZP and TCZ, but not with ABA, remained within the pre-defined non-inferiority margin versus ACT, Fig 2.Figure 1.CDAI remission over time (adj. estimates with 95% CI)Figure 2.Non-inferiority analysis of protocol population. Estimated differences in CDAI remission rates between Arm 1 (active conventional therapy) and Arms 2, 3, and 4 (biologic arms) as reference with 95% confidence intervals, adjusted for gender, ACPA status, country, age, body-mass index and baseline DAS28-CRP. ABA, abatacept; CZP, certolizumab-pegol; MTX, methotrexate; TCZ, tocilizumab.Conclusion:High remission rates were found across all four treatment arms at 24 wks. Higher CDAI remission rate was observed for ABA versus ACT (+9%) and for CZP (+4%), but not for TCZ (-1%). With the predefined 15% margin, ACT was non-inferior to CZP and TCZ, but not to ABA. This underscores the efficacy of active conventional therapy based on MTX combined with glucocorticoids and may guide future treatment strategies for early RA.Table.Primary and key secondary outcomes at 24 weeks (ITT)Active conventional therapy (ACT)Certolizumab+MTXAbatacept+MTXTocilizumab+MTXNo of pts (ITT)200203204188§Crude remission and response ratesCDAI remission42.0%47.8%52.5%41.0%ACR/EULAR Boolean remission34.0%38.4%37.3%31.4%DAS28 remission63.5%68.5%69.6%63.3%SDAI remission41.5%49.8%51.5%42.6%EULAR good response71.5%76.9%79.9%71.3%Difference (95% CI) in rates with Arm 1 as reference (adjusted)CDAI remissionRef4% (-5 to 13%)9% (0.1 to 19%)-1% (-10 to 9%)ACR/EULAR Boolean remissionRef4% (-6 to 13%)5% (-5 to 14%)-4% (-13 to 6%)DAS28 remissionRef3% (-6 to 11%)5% (-4 to 13%)-1% (-10 to 8%)SDAI remissionRef6% (-3 to 18%)9% (-0.3 to 18%)1% (-8 to 11%)EULAR good responseRef4% (-4 to 14%)8% (-2 to 18%)0.4% (-10 to 11%)§17 patients allocated to Tocilizumab did not receive it due to its unavailability and were excluded from ITT.Acknowledgments:Manufacturers provided CZP and ABA.Disclosure of Interests:Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD, Anna Rudin Consultant of: Astra/Zeneca, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Jon Lampa Speakers bureau: Pfizer, Janssen, Novartis, Kim Hørslev-Petersen: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Gerdur Gröndal: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Marte Heiberg: None declared, Jos Twisk: None declared, Simon Krabbe: None declared, Kristina Lend: None declared, Inge Olsen: None declared, Joakim Lindqvist: None declared, Anna-Karin H Ekwall Consultant of: AbbVie, Pfizer, Kathrine L. Grøn Grant/research support from: BMS, Meliha C Kapetanovic: None declared, Francesca Faustini: None declared, Riitta Tuompo: None declared, Tove Lorenzen: None declared, Giovanni Cagnotto: None declared, Eva Baecklund: None declared, Oliver Hendricks Grant/research support from: Pfizer, MSD, Daisy Vedder: None declared, Tuulikki Sokka-Isler: None declared, Tomas Husmark: None declared, Maud-Kristine A Ljosa: None declared, Eli Brodin: None declared, Torkell Ellingsen: None declared, Annika Soderbergh: None declared, Milad Rizk Speakers bureau: AbbVie, Åsa Reckner: None declared, Per Larsson: None declared, Line Uhrenholt Speakers bureau: Abbvie, Eli Lilly and Novartis (not related to the submitted work), Søren Andreas Just: None declared, David Stevens: None declared, Trine Bay Laurberg Consultant of: UCB Pharma (Advisory Board), Gunnstein Bakland Consultant of: Novartis, UCB, Ronald van Vollenhoven Grant/research support from: BMS, GSK, Lilly, UCB, Pfizer, Roche, Consultant of: AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Janssen, Pfizer, Servier, UCB, Speakers bureau: AbbVie, Pfizer, UCB

Background Abatacept (ABA) is a biologic DMARD (bDMARD) used to treat rheumatoid arthritis (RA) since 2006. There are limited data on real life efficacy of ABA, and on predictors for ABA treatment response. Objectives Objectives: To compare the effectiveness of ABA in the treatment of RA between bionaive patients and patients with previous bDMARDs and to investigate predictors of clinical response to ABA. Methods In an observational cohort study, based on data from a large national quality register database, patients with RA diagnosis who initiated treatment with ABA between April 2006 and November 2017 were included. LUNDEX corrected response was defined as the fractions remaining on the drug and achieving the outcome among all who initiated treatment (1). Clinical response at 6 and 12 months was evaluated by means of LUNDEX corrected EULAR (L-EULAR) Good Response and LUNDEX corrected HAQ response (change of ≥0.3 from baseline) (L-HAQ). Predictors for clinical response were investigated using logistic regression, with significance based backwards selection of variables for the final multivariate model. The study was supported by an unrestricted grant from Bristol Myers-Squibb. Results 2716 RA patients were included in the study. More patients in the bionaive population achieved L-EULAR Good Response and L-HAQ response at 6 and 12 months than bDMARDs experienced patients (Fig. 1a and 1b). Male sex, no previous bDMARD exposure and a low HAQ score were independent predictors of L-EULAR Good Response at 6 and 12 months (Table 1). Lack of previous bDMARD exposure also predicted L-HAQ response at 6 and 12 months. There was a positive associations between baseline HAQ and L-HAQ response at 6 months (multivariate adjusted odds ratio 1.73; 95% CI 1.46-2.05). Conclusion In patients with RA, response rates for treatment with abatacept were substantially higher in bionaive patients than in those with previous bDMARD experience. Male sex also predicted LUNDEX corrected EULAR good response to abatacept. Patients with extensive disability, measured by HAQ, were less likely to remain on treatment and achieve a EULAR Good Response, but more likely to have significant HAQ improvement. Reference [1] Kristensen, et al. Arthritis Rheum. 2006;54(2):600-6. Disclosure of Interests Giovanni Cagnotto Consultant for: Novartis, less than 3000 Euro, Minna Willim: None declared, Lennart Jacobsson Consultant for: Eli-Lily, Janssen, Novartis, Pfizer, Speakers bureau: Abbvie., Michele Compagno: None declared, Saedis Saevarsdottir Employee of: Part-time employee at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project., Carl Turesson: None declared

Background:Abatacept is a biologic disease-modifying anti-rheumatic drug (bDMARD) used to treat rheumatoid arthritis (RA) since 2006, acting by inhibition of T-cell co-stimulation. There are limited data on factors predicting clinical outcomes in RA after start of treatment with abatacept.Objectives:The primary aim was to identify predictors of change in disease activity in RA-patients after start of treatment with abatacept.Methods:This cohort study was based on data from the Swedish Rheumatology Quality register (SRQ). All patients with RA who started treatment with abatacept between 2006 and 2017 were included. Clinical data from the SRQ included demographics, disease characteristics and antirheumatic treatment. Disease activity was measured according to DAS28-ESR (Disease Activity Score of 28 joints based on erythrocyte sedimentation rate) at inclusion and at follow-up visits at 6 and 12 months from start of treatment with abatacept. Baseline predictors of change in disease activity were investigated using linear regression models bivariately and adjusted for baseline values of DAS28. Covariates with a p-value of Results:In a total of 2716 patients, 872 had data on change in DAS28 at 12 months. Among these, most patients were women (79.6%) and the mean age at start of abatacept was 58.4 years (SD 13.6). The majority of patients had established RA, with a mean disease duration of 13.5 years (SD 11.1). Most patients had severe, active disease, with substantial pain and disability, despite extensive treatment. The mean number of bDMARDs that a patient had been exposed to was 1.90 (SD 1.32). DAS28 decreased significantly over the first year (mean 1.22: 95 % CI 1.12, 1.32). The greatest decrease in DAS28 (mean 1.09) occurred during the first 6 months from start of abatacept. The multivariate regression model identified male sex and limited previous bDMARD exposure as independent predictors of change in DAS28 at 12 months from start of abatacept – adjusted for baseline DAS28, RA duration and current treatment with methotrexate or prednisolone (Table 1).Table 1.Determinants for retransitioningBivariateAdjusted for baseline DAS28MultivariateVariablesB95% CIP-valueB95% CIP-valueB95% CIP-valueMale sex0.39[0.13, 0.64]0.0030.43[0.20, 0.66]0.42[0.19, 0.64]Age (per SD)0.10[-0.004, 0.21]0.0580.044[-0.051, 0.14]0.37N/ARA duration (per SD)-0.14[-0.25, -0.037]0.008-0.11[-0.21, -0.016]0.022-0.030[-0.13, 0.065]0.54HAQ (per SD)0.12[0.007, 0.23]0.037-0.24[-0.35, -0.13]N/AVAS pain (per SD)0.26[0.15, 0.37]-0.058[-0.17, 0.054]0.31MTX10.20[-0.013, 0.41]0.0660.17[-0.018, 0.36]0.0760.11[-0.076, 0.29]0.25Prednisolone1-0.19[-0.41, 0.017]0.072-0.17[-0.36, 0.024]0.087-0.14[-0.33, 0.043]0.13bDMARDs2 (per SD)-0.30[-0.40, -0.20]-0.32[-0.41, -0.23]-0.31[-0.40, -0.21]B=beta coefficient; N/A=not applicable; SD=standard deviation; CI=confidence interval. Bold text indicates significant associations.DAS28, Disease activity Score of 28 joints; RA, rheumatoid arthritis; HAQ, Health Assessment Questionnaire; VAS, visual analogue scale; MTX, methotrexate; bDMARD, biologic disease-modifying antirheumatic drug.1Current treatment2Number of previous bDMARDsConclusion:In this national register study, male sex and limited previous exposure to bDMARDs were independent predictors of reduction of disease activity one year after start of treatment with abatacept for RA, possibly reflecting a better prognosis overall in such patients.Disclosure of Interests:Julia Liukkonen: None declared, Giovanni Cagnotto: None declared, Jan-Åke Nilsson: None declared, Saedis Saevarsdottir: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol Myers-Squibb, Medac, Pfizer, Roche., Consultant of: Roche, Grant/research support from: This study was supported by an unrestricted grant from Bristol-Myers Squibb

Background Rheumatoid factor (RF) and anti-citrullinated peptides antibodies (anti-CCP) are universally recognised negative prognostic factors in rheumatoid arthritis (RA). The majority of studies of early RA have focused on RF and anti-CCP positive patients. Much less is known about prognostic markers in seronegative RA. Several studies report worse drug survival and worse patient reported outcomes in women with RA. This affects outcomes such as the 28-joint disease activity score (DAS28) and the health assessment questionnaire (HAQ). How these differences relate to autoantibody status is unknown. Objectives To investigate if the relation between sex and clinical outcomes varies by autoantibody status in patients with early RA. Methods An inception cohort of patients with early RA (n=233; symptoms duration ≤12 months), recruited in 1995–2005, was studied. All the patients fulfilled the 1987 American College of Rheumatology criteria for RA. The patients were managed according to usual care, with no pre-specified protocol for pharmacotherapy or rehabilitation. In a structured follow-up program, all patients were examined by the same rheumatologist. In the present study we divided the patient population in three groups according to autoantibodies status: RF and anti-CCP seropositive (double positive), RF or anti-CCP seropositive, RF and anti-CCP seronegative (double negative). We examined the relation between sex and different outcomes at 12 months (EULAR good response, clinical remission (DAS28 Results Complete data on autoantibody status at baseline was available for 201 patients (mean age at inclusion 61 years, 72% female, 60% RF positive and 58% anti-CCP positive). Twenty-eight% of the patients were double negative, 27% were single positive and 45% were double positive. Mean baseline DAS28 was 4.53. All patients were treated with a conventional synthetic DMARD (48% with methotrexate). Oral glucocorticoids were prescribed in 38% of patients. At the 1 year follow up, 19% had a EULAR good response, 21% were in remission, 40% had low pain and 53% low HAQ. Male patients in the double negative group were more likely to reach remission (odds ratio (OR) 6.40; 95% confidence interval (CI) 1.6–26.2) and EULAR good response (OR 4.67; 95% CI 1.2–18.3) compared to females. There were no such associations among the double positive patients (Table). Results were similar in analyses adjusted for DAS28 at baseline (Table). There was a similar pattern among double negative patients for low pain at 1 year (OR for male vs female patients 2.25; 95% CI 0.58–8.67 – adjusted for baseline pain), but no association between male sex and low HAQ at 1 year in double negative patients (OR 0.99; 95% CI 0.23–4.22 – adjusted for baseline HAQ) or the other subgroups. Conclusions In the subgroup of patients with seronegative early RA, male patients are more likely than female patients to reach DAS28 remission and EULAR Good Response after treatment with conventional synthetic DMARDs. Disclosure of Interest G. Cagnotto Paid instructor for: Novartis, E. Rydell: None declared, L. Jacobsson Consultant for: Pfizer, Abbvie, Novartis, Eli-Lilly, C. Turesson Grant/research support from: Abbvie, Bristol Myers-Squibb, Roche, Consultant for: MSD, Bristol Myers-Squibb, Roche, Paid instructor for: Abbvie, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche and UCB

Background Anti-MDA5 antibodies are a known set of antibodies observed mainly in dermatomyositis, typically associated with cutaneous involvement, presence and often rapid progression (RP) of interstitial lung disease (ILD) and amyopathic muscle involvement. Despite the increased attention, described cohorts involves only a limited number of cases Objectives to define clinical characteristics of a large cohort of anti-MDA5 antibodies positive patients Methods Retrospective assessment of anti-MDA5 positive patients from centres referring to our group Results 82 anti-MDA5 positive cases (56 females) were collected. In median: onset age was 44 Y (IQR 22.57), diagnostic delay 4 Mo (IQR 1–10), follow-up 13 Mo (IQR 3–43). Fifty-three patients had ILD, that was RP in 24 cases (15 at ILD onset, 9 after ILD onset). Fifthteen ILD patients were admitted in Intensive Care Unit (ICU): 4 were treated with Extracorporeal-Membrane-Oxygenation, 7 with mechanical-invasive and 2 with mechanical-non-invasive ventilation. Forthy-nine patients had muscle involvement (39 symptomatic), 42 arthritis, 54 cutaneous involvement, 9 history of malignancy. Twelve patients died (ILD=7, ILD and sepsis=3, neoplasia=1, not specified=1), 7 of those in ICU Conclusions In our cohort, ILD was the most frequent finding. A RP of ILD was common, occurring also in ILD with symptomatic/chronic onset. The low rate of survival in ICU raised the problem of follow up and early treatment of ILD. In our cohort arthritis was common and muscle involvement mainly symptomatic. Finally, the high percentage of observed malignancies suggests a careful neoplastic screening and follow up Reference [1] Labrador-Horrillo M, et al. J Immunol Res2014;2014:290797. Disclosure of Interest None declared

Background: Abatacept is a biologic disease modifying anti-rheumatic drug (bDMARD) used to treat rheumatoid arthritis (RA). There is growing experience with abatacept in many countries. National registers are useful resources for investigation of long term real world outcomes. Objectives: To compare the effectiveness of abatacept in the treatment of RA between bionaive patients and patients with previous bDMARD treatment, and to investigate predictors of remaining on treatment with abatacept. Methods: This was an observational cohort study, based on a national quality register database. Patients with a diagnosis of RA who initiated treatment with abatacept between April 1, 2006 and November 20, 2017, were included. Patients were censored at abatacept discontinuation, death, migration, or the end of the study period. Analyses were stratified by previous exposure to bDMARDs. Survival on drug was estimated using the Kaplan-Meier method. Predictors of discontinuation of abatacept were investigated in Cox Proportional Hazards analyses, with significance-based backwards stepwise selection of variables for the final multivariate model. Results: A total of 2716 patients with RA (80 % females, mean age 59 years, mean duration of RA 14 years) started abatacept during the study period. Of these, 17 % had no previous bDMARD treatment (bionaive patients), 27 % had received 1bDMARD previously, and 56 % had been treated with ≥2 bDMARDs. Fifty percent each of the patients received intravenous and subcutaneous therapy. At the time of abatacept initiation, 57 % were on methotrexate (MTX), and 48 % were treated with glucocorticosteroids. There were significant differences in drug survival across categories of previous bDMARD exposure (p=0.002). The median survival time on treatment was 2.23 years for bionaive patients (95 % confidence interval (CI) 1.69–2.79)), 1.68 years for those with 1 previous bDMARD (95 % CI 1.34–2.01) and 1.56 years for those with ≥2 previous bDMARDs (95 % CI 1.35–1.76). At 6 months, 88 % of bionaive patients remained on abatacept, compared to 74 % at 12 months. The corresponding figures for those with 1 or ≥2 previous bDMARDs were 78 % and 61 %, and 76 % and 59 %, respectively. In bivariate analyses, bionaive patients were less likely to discontinue treatment compared to those treated with ≥2 previous bDMARDs previously (Table). Bionaive patients were more often male (28 % vs 18 %) and had lower pain scores (mean Visual analogue scale score 58 vs 62) compared to those previously exposed to ≥2 bDMARDs. Measures of disease severity were associated with reduced drug survival (Table), but age, RA duration and method of administration had no significant impact on discontinuation. In the final multivariate model, pain increased the risk of abatacept discontinuation, whereas male patients and those on concurrent MTX had a reduced risk of stopping abatacept (Table). Conclusions: Survival on abatacept was significantly longer in bionaive RA patients compared to those previously exposed to bDMARDs. In the bionaive subset, 50 % of the patients remained on treatment after 2.2 years. Concomitant MTX therapy, male sex and low pain scores were associated with longer drug survival for abatacept. Disclosure of Interest: G. Cagnotto Paid instructor for: Novartis, M. Willim: None declared, J.-A. Nilsson: None declared, S. Saevarsdottir: None declared, C. Turesson Grant/research support from: Abbvie, Bristol Myers-Squibb, Roche. The present study was supported by an unrestricted grant from Bristol Myers-Squibb, Consultant for: MSD, Bristol Myers-Squibb, Roche, Paid instructor for: Abbvie, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche and UCB

ObjectiveTo define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation.MethodsA multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models.Results361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months.ConclusionsPD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.

Background Arthritis, myositis and Interstital lung disease (ILD) represent the classic clinical triad of antisynthetase syndrome (ASSD). In anti Jo-1 positive patients, these findings may appear also during the follow-up. Even if a similar cumulative trend has been showed also in non anti Jo-1 positive ASSD, a head to head comparison of clinical spectrum time course in these patients is still lacking Objectives To assess the clinical spectrum time course in non anti Jo-1 positive ASSD, according to different underlying non anti Jo-1 specificities Methods Clinical, laboratory and instrumental data collection of anti PL-7, PL-12, and EJ positive patients from an international database of ASSD Results We identified 63 (42%) anti PL-7, 66 (44%) anti PL-12 and 20 (14%) anti EJ positive patients, reporting their characteristics in table 1 (disease onset) and 2 (last follow-up). At disease onset, no substantial differences were observed. At the end of follow-up, we observed some differences between anti PL-12 and both anti PL-7 and anti-EJ positive patients. In particular, anti PL-12 positive patients presented less frequently ex-novo triad findings and had a reduced prevalence of myositis. From the clinical point of view, the main pattern of disease presentation was an isolated ILD in all groups at the onset and only in anti-PL12 positive ASSD at last follow-up. Conclusions Our study seems to indicate that clinical spectrum time course of anti PL-12 positive ASSD is different from that of anti PL7 and of anti EJ positive ASSD. The clinical pattern associated with these two latter antibodies was very similar. Furthermore, anti PL-12 positive patients seems to have a more stable disease, with a less common occurrence of ex-novo triad findings during the follow-up References Cavagna L. Medicine 2015. Cavagna L. CRAI 2016. Cavagna L. ARD 2016 (Abstract). Trallero Araguas E. Scand J Rheumatol 2016. Acknowledgements To all members of the AENEAS collaborative group. Disclosure of Interest None declared

Background Subclinical synovial inflammation detected by ultrasonography (US) in patients with rheumatoid arthritis (RA) in clinical remission relates to disease flare. The impact of tenosynovitis in this context is not known. Objectives To evaluate the association between US-detected tenosynovitis and synovitis in RA patients in clinical remission and flare over 12-months. Methods STARTER is a multicentre cohort study of the US Study Group of the Italian Society for Rheumatology. Participants were selected on the basis of a reliability exercise and the availability of high-end equipment. Patients with RA in clinical remission underwent clinical evaluation and US synovitis (-S) and tenosynovitis (-T) were assessed categorically for Grey Scale (GS) and power Doppler (PD) at 11 joints, extensor and flexor tendons in both hands and wrists. Patients were seen at 6 and 12 months. Flare within 12 months was defined as increase of >1.2 or >0.6 if final DAS28>3.2. The relationship between the presence of GS-T/-S, PD-T/-S was evaluated by logistic models, presented as odds ratios (OR) and 95% confidence interval (CI), adjusted for pre-specified confounders. Results 361 patients (72.3% f, mean age (sd) 56.1 (13.3), median disease duration (IQR) 7.1 years (3.6–13.5)) were included. 98/326 (30.6%) patients had a flare within 12 months. Considering US variables separately, only PD-S significantly predicted flare (OR 1.87 (1.12,3.14)). When the model included both –T and –S, only the concurrent presence of –T and –S predicted flare (PD-T+-S: OR 2.06 (1.04, 4.07); GS-T+-S: OR 2.27, (1.01,5.10)), while isolated –S and –T did not. Conclusions In patients with RA in clinical remission, US-detected synovial and tenosynovial inflammation identifies patients at risk of flare. US might help decisions on management in this population. Disclosure of Interest None declared

Systemic lupus erythematosus (SLE) is an autoimmune condition with a wide range of manifestations. Among the various targets of the disease, the kidney holds a very important place. In fact, renal involvement is one of the most important and frequent features of the disease, deeply affecting a patient's prognosis and influencing the therapeutic approach. In the last few years, some progress has been achieved in terms of both disease classification and treatment. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) published the new classification criteria for SLE and the American College of Rheumatology established recommendations for the screening, treatment, and management of SLE nephritis. These new points of view derived from the recent evolution of medical knowledge, technology, and practice in the field of SLE in general, and lupus nephritis in particular. Moreover, it is important to remember that SLE still remains a systemic disorder and that a multi-disciplinary approach is the optimal way to manage these patients.

In the last decades a large amount of evidence linked rheumatoid arthritis (RA) to atherosclerosis. In fact, RA patients have an increased risk of cardiovascular events that is not fully explained by other classic cardiovascular risk factors. RA and atherosclerosis may share several common pathomechanisms and inflammation undoubtedly plays a primary role. The proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD). In RA, inflammation alters HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, induces atherosclerosis. Interestingly, some genetic polymorphisms associated with RA occurrence enhance atherosclerosis, however, other polymorphisms associated with RA susceptibility do not increase CVD risk. Several other mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular are really wide and different. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of CVD occurrence.

Objectives To develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region. Design Case–control and cohort diagnostic accuracy study. Methods In a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region. Results The algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%). Conclusions AHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.

Background Anti-citrullinated protein antibodies (ACPA) are a major risk factor for bone destruction in rheumatoid arthritis (RA). ACPA may directly induce bone loss by stimulating osteoclast differentiation [1]. Accordingly, the trabecular bone microarchitecture at peripheral sites is significantly compromised in ACPA(+) subjects irrespective of joint inflammation [2,3]. Whether ACPA positivity also influences systemic bone changes is however unknown. Objectives To investigate the relationship between generalised bone loss and the ACPA status in patients with early RA. Methods We evaluated 102 consecutive untreated patients with early RA (symptoms duration Results The study population included 73 women (63% in post-menopause) and 29 men, with a mean age of 57 (±14) years and a median disease duration of 3 (IQR 1.9-6) months. All patients had active disease, with a mean DAS28 of 4.41 (±1.11). Thirty-nine patients (38.2%) were ACPA(+), with ACPA values >3 times the upper limit of normal (ULN) in 89.7% of the cases. In the overall group, BMD measurements at baseline were almost comparable to the normal range when corrected for age and sex. Z scores were 0.03 (±1.31) at the lumbar spine, and -0.11 (±0.97) at the femoral neck. Z scores were not significantly influenced by disease variables such as symptoms duration, overall disease activity, the clinical and the US joint count, and acute phase reactants. In contrast, ACPA(+) patients had lower Z scores at the lumbar spine compared to ACPA(-) patients (-0.33 [±1.11] vs 0.26 [±1.38], p=0.03), whilst no differences were found at the femoral neck. Furthermore, in ACPA(+) patients, the lumbar Z score was inversely related to ACPA titers (r -0.33, p=0.04 for log-transformed ACPA). Accordingly, 40% of the patients with ACPA values >3 times the ULN had a Z score Conclusions Vertebral BMD in patients with early RA is significantly reduced in relation with ACPA positivity. This finding supports the hypothesis that autoimmunity associated with RA may have a significant role in bone remodeling, either directly by stimulating osteoclasts or indirectly by eliciting subclinical inflammation. References Harre U, et al. J Clin Invest 2012;122:1791-802. Kocijan R, et al. Ann Rheum Dis 2013;doi: 10.1136/annrheumdis-2013-203791. Kleyer A, et al. Ann Rheum Dis 2013;doi:10.1136/annrheumdis-2012-202958. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4941

Background Osteoporosis (OP) is a frequent complication of a number of chronic inflammatory diseases. Only Rheumatoid Arthritis (RA) is included in the FRAX algorythm to calculate fracture risk but also Systemic Sclerosis (SSc) displays many disease-specific OP risk factors (chronic inflammation, malnutrition, steroid use, etc.) Objectives To determine OP frequency and fracture risk by FRAX in outpatients with SSc Methods After consent, in outpatients with SSc (le Roy criteria) of a University Hospital, bone mineral density (BMD) was calculated by Dual Energy X-Ray Absorptiometry (DEXA) at the femoral neck and lumbar spine and FRAX was obtained by the calculation tool (http://www.shef.ac.uk/FRAX). A routine SSc evaluation (according to EUSTAR) was performed as well. Age- and BMI-matched early AR (ACR/EULAR 2010 criteria) patients and healthy controls (HC) were enrolled as well. Results Seventy-one SSc patients (3:68 M:F, age 66±9yrs, 57:14 limited:diffuse cutaneous, median disease duration 8.5, 2.4-14.7yrs, median disease activity 1, 0.25-2), 44 AR (11:33 M:F, age 62±12yrs, median DAS28 4.42, 3.94-5) and 29 healthy controls (all F, 60.1±10.7yrs) were enrolled. OP was detected in 42/71 (59%) SSc patients. Disease duration was significantly higher in SSc-OP patients (10.5, 4.3-16.6 vs 5.5, 1.6-9.8, p Conclusions We have detected a very high OP frequency in our SSc patients, significantly higher than a control early AR cohort and significantly associated to disease duration. Routine DEXA evaluation and risk factors for OP should always be considered and treated when possible in every SSc patient, especially after 5 years of disease duration. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5172

Background The use of administrative health databases (AHD) is a promising strategy to study the impact of rheumatoid arthritis (RA) at population level. Previous studies, using different methodologies, have shown moderate to excellent accuracy in case identification with sensitivity (Se) and specificity (Sp) ranging from 65 to 100% and from 55 to 97%, respectively. Objectives To derive and validate a diagnostic algorithm that accurately identifies RA cases in general population using AHD of the Italian health system. Methods A cross-sectional diagnostic study design was applied. To derive the algorithm, a first random sample of 900 visits between 2007-2010 was drawn from electronic medical records of a tertiary rheumatology centre, applying a case:control ratio of 1:2 [1]. A second sample of 138 patients from a secondary care rheumatology clinic with the same case control ratio and a third sample of 4457 subjects from general population (primary care registry) were used for external validation. Diagnoses were clinically validated, according to standardized criteria [2]. Clinical and administrative data were linked using deterministic record linkage through tax code. Useful items for the identification of RA cases were defined through a process informed by literature involving clinicians, analysts and statisticians. Using a priori beliefs and empirical data, an algorithm that applied the more specific criteria in the first step and progressively more sensitive criteria in the subsequent was developed. Accuracy was assessed calculating Se and Sp, and 95% confidence intervals (CI). The consistency of these estimates was tested both by internal validation (bootstrap), and by two fully independent external validations. Positive and negative predictive values (PPV and NPV) were also estimated in the general population sample. Results The following variables were included in the algorithm: ICD9 code 714.0 by rheumatologist, ICD9 codes for other rheumatologic diseases, code 714 in Hospital Discharge Form, prescription of DMARDs including biologics, and steroids. In the derivation sample, a four-steps algorithm identified clinically diagnosed RA cases with a Se of 96.4 (95%CI:93.6-98.2) and a Sp of 90.3 (87.5-92.7), confirmed by bootstrap estimates [Se 96.3 (95%CI:96.2-96.4); Sp 90.3 (90.2-90.4)]. The external validation on the sample from secondary care showed highly consistent results: Se 93.8 (95%CI:79.2-99.2) and Sp 90.7 (81.7-96.2). Final validation at population showed: Se of 93.3 (95%CI:77.9-99.2); Sp of 99.7 (99.5-99.9); PPV of 70 (53.5-84.4) and NPV of 100 (99.8-100). Conclusions AHD is a valuable tool for the identification of RA cases at the population level: impact studies of population are feasible. Data on misclassification will be useful to improve estimates of occurrence and in selecting subjects for cohort studies. References Steinberg DM, Biostatistics 2009; 10: 94-105 - Mac Gregor A. J Rheumatol 1994; 21:1420-6. Disclosure of Interest None Declared