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The proper management of water resources plays a key role in the socioeconomic development of Armenia. On average, Armenia has sufficient water resources. Taking into account all available water resources in the country, Armenia has sufficient resources to supply approximately 3,100 cubic meters per capita per year well above the typically cited Falkenmark water stress indicator of 1,700 cubic meters per capita per year. These water resources are not evenly divided in space and time with significant seasonal and annual variability in river runoff. In order to address temporal variations in river runoff, the country has built 87 dams with a total capacity of 1.4 billion cubic meters. Most of these dams are single purpose, mainly for irrigation. Armenia also has considerable groundwater resources, which play an important role in the overall water balance. About 96 percent of the water used for drinking purposes and about 40 percent of water abstracted in the country comes from groundwater. Irrigation remains the largest consumptive user.

Abstract Disclosure: P. van Dommelen: Consulting Fee; Self; PvD has a consultancy agreement with Merck KGaA, Darmstadt, Germany. F. Michelis: Employee; Self; FL is an employee of Ares Trading SA, an affiliate of Merck KGaA. L. Arnaud: Employee; Self; LA is an employee of Ares Trading SA, an affiliate of Merck KGaA. S. Loche: Advisory Board Member; Self; SL has received advisory board fees from Merck KGaA, Darmstadt, Germany. Consulting Fee; Self; SL has received consultancy fees from Merck KGaA, Darmstadt, Germany. Speaker; Self; SL has received lecture fees from Merck KGaA, Darmstadt, Germany. E. Koledova: Employee; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Stock Owner; Self; EK holds shares in Merck KGaA, Darmstadt, Germany. Background: A data-driven clinical decision support system based on visual presentations for adherence risk management can support patients receiving recombinant human growth hormone (r-hGH) treatment. Our focus is on examining adherence patterns during the first 6 weeks of treatment, with a particular emphasis on the days of the week, the variability in injection timings and the summer holiday. Our aim is to assess whether these early patterns can serve as indicators for predicting adherence in the subsequent 7-12 weeks of treatment. Data and Methods: Adherence data between March-November 2023 were extracted from the newly launched third generation of easypod™ device (EP3) and GrowZen Connect Next ecosystem. EP3 is the only connected device that delivers r-hGH and monitors real-time adherence to therapy. EP3 was perceived by health care professionals as more intuitive, comfortable, user-friendly, simpler, and easier to use than previous EP2. Patients with age 2-18 years at treatment start, a 7-day regimen and complete adherence data available between 1-12 weeks of treatment were selected. Data about sex, age at start treatment, as well as adherence, classified as high (≥95%) versus low/medium <95%), standard deviation (SD) of adherence (%), log (to adjust for skewness) of the interquartile range (IQR) of the timing of injection throughout the day, median timing of the injection after midnight, and ≥50% versus <50% of the injections fall in the summer period (July-August) aggregated by day over the first 6 weeks of treatment were included in a generalized linear mixed model with adherence between 7-12 weeks as outcome. Results: In total, data for 232 patients (124 boys and 108 girls, median (Q25-Q75) age at treatment start was 10.5 (7.6-12.3)) were available. The model showed no difference in effect of adherence rates during Monday-Thursday. We, therefore, aggregated the data by weekday (Monday-Thursday) versus weekend day (Friday-Sunday, Friday was included due to the common practice of administering injections during the evening). Adherence, SD of adherence, IQR of timing of injections, and injections falling in summer were significant (p<0.05) predictors of adherence during a weekday and weekend between 7-12 weeks. Areas under the curves were both 0.96 during the weekday and weekend. Conclusions: Our research shows that adherence and timing of injections, as well as taking into account the summer holidays, can predict future adherence accurately. Visual presentations showing aggregated adherence rates and variation of timing of injections by days of the week, as well as highlighting the summer periods may improve adherence risk management and timely support. Presentation: 6/3/2024

Abstract Disclosure: S. Loche: Advisory Board Member; Self; SL has received advisory board fees from Merck KGaA, Darmstadt, Germany. Consulting Fee; Self; SL has received consultancy fees from Merck KGaA, Darmstadt, Germany. Speaker; Self; SL has received lecture fees from Merck KGaA, Darmstadt, Germany. P. van Dommelen: Consulting Fee; Self; PvD has a consultancy agreement with Merck KGaA, Darmstadt, Germany. V. Tornincasa: Employee; Self; VT is an employee of Ares Trading SA, an affiliate of Merck KGaA. L. Arnaud: Employee; Self; LA is an employee of Ares Trading SA, an affiliate of Merck KGaA. E. Koledova: Employee; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Stock Owner; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Background: The integration of data-driven strategies, such as clustering analysis with an alerting system, empowers healthcare professionals with actionable insights. In this study, we focused on clustering adherence patterns during the weekdays and weekends in the first 12 weeks of treatment. Our aim is to develop a data-driven clinical decision support system based on \"traffic light\" visualizations addressing adherence challenges during both weekdays and weekends in patients receiving Recombinant Human Growth Hormone Therapy. Data and Methods: Adherence data between March-November 2023 were extracted from the newly launched third generation of easypod™ device (EP3) and GrowZen Connect Next ecosystem. EP3 is the only connected device that delivers r-hGH and monitors real-time adherence to therapy. EP3 was perceived by health care professionals as more intuitive, comfortable, user-friendly, simpler, and easier to use than previous EP2. Patients with age 2-18 years at treatment start, a 7-day regimen and complete adherence data available between 1-12 weeks of treatment were selected. Patients’ adherence to therapy was represented using mean and standard deviation (SD) of adherence (%) and the interquartile range (IQR) of the timing of injections throughout the day in minutes aggregated by weekday (Monday-Thursday) and weekend day (Friday-Sunday). Cluster analysis was used to categorize adherence patterns using a Gaussian mixture model. Following a traffic lights-inspired visualization approach, the algorithm was set to create three clusters: high (green), medium (yellow), and low adherence (red). The area under the receiver operating characteristic curve (AUC-ROC) was used to find optimum thresholds for independent traffic lights. Results: Data for 232 patients (124 boys and 108 girls, median (Q25-Q75) age at treatment start was 10.5 (7.6-12.3)) were available. The most appropriate traffic light used the SD of adherence during the weekend, with an AUC-ROC value of 0.87. For the weekday, adherence-based traffic lights using optimum thresholds were >98% (SD<10.2), 88-98% (SD:10.2-22.8) and <88% (SD>22.8) for high, medium, and low adherence, respectively. For IQR of the timing of injections throughout the weekday, optimum thresholds were <38, 38-70 and >70 (min). For the weekend, optimum thresholds were >96% (SD<7.7), 86-96% (SD:7.7-21.5) and <86% (SD>21.5). For IQR of the timing of injections throughout the weekend, optimum thresholds were <56, 56-84 and >84 (min). Conclusions: Our research indicates that implementing a practical data-driven alert system, utilizing our proposed traffic-light coding, would empower healthcare practitioners to monitor patients' adherence to growth hormone therapy comprehensively. By understanding patient behavior during the weekdays and weekend, healthcare practitioners can tailor interventions for improved treatment outcomes. Presentation: 6/3/2024

Background:There is an increasing need for integrated real-world data generation at the patient level across different siloes and healthcare settings (e.g., secondary and primary care) for clinical, scientific, and pharmaceutical research including AI methods. However, these data are scattered between different organizations, systems, and often remain unused for secondary purposes. Connecting and unlocking these data can advance clinical research to better understand disease and improve patient care. Thus, we established a clinical and scientific research platform that brings all these data into an integrated platform for researchers in a Rheumatology setting. The platform has been designed to bridge the gaps in the patient journey by integrating data throughout the patient journey within a centralized platform. This is not done in routine clinical practice in Germany.Objectives:Evaluate the informed broad consent (BC) for the platform predicated on the principles of the Medical Informatics Initiative in Germany that was implemented and administered to our patients scheduled for routine follow-ups and visits within the Rheumatology outpatient clinic at a tertiary centre.Methods:The analyses focused on the consent rates and options selected to the pre-given BC options. Positive ethics vote and DRKS registration were obtained.Results:From 07/2023 to 12/2023 n=254 outpatients (48% with university entrance diploma) signed the BC and agreed for their data to be processed for the purposes of the platform. The median years of age of the consented patients was 57, most of which were female (71%), and the median disease duration was 11 years. Disease groups included rheumatoid arthritis (36%), psoriatic arthritis (11%), spondyloarthritis (6%), systemic lupus erythematosus (28%), systemic sclerosis (4%), and others (6%).Apart from the signature, eight predefined BC options could be selected with either a ‘yes’ or ‘no’, with the average number of ‘yes’ answers (standard deviation (SD)) being 7.4±1.5, and the average number of ‘no’ answers being 0.2±0.5. The mean number of missings over 8 BC items was 0.4±1.5. No differences between disease groups were noted. Even where signed informed consent was given, n=6 (2%) did not select any of the BC options at all. In addition, n=198 (78%) signed with consenting to all BC options. The approval rates for the individual BC items are listed in Table 1.Conclusion:Our study focuses on the individual BC for a platform that collects and pools data from various sources within a centralized platform for scientific and clinical research Rheumatology embedded in routine care. The various aspects of our established BC are based on the template of the MII were well accepted by our predominantly female patients. Our patients extensive support for the integration of real-world data generation at the patient level across different siloes and healthcare settings gives us a high flexibility for performing clinical, scientific, and pharmaceutical research including AI methods, as well as a firm legal basis to do so that is rooted in informed consent pursuant to the GDPR. Detailed analyses on patients’ motivations and fears from an accompanying evaluation questionnaire are to be explored subsequently.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Jutta G. Richter: None declared, Hasan Acar: None declared, Antonia Becker: None declared, Waldemar Ockert., not grants, but professional fees for professional services performed, Dominykas Kriauciunas., not grants, but professional fees for professional services performed, Markus Schröder: None declared, Jörg Distler: None declared, Matthias Schneider: None declared.

Background:Targeting interleukin (IL)-6 has become a major therapeutic strategy and sarilumab (SAR) and tocilizumab (TCZ) are available in the treatment of rheumatoid arthritis (RA) [1]. Although SAR and TCZ have different forms of antibodies, dosages, routes, affinities to IL-6 receptors (IL-6R), and inhibition of IL-6/STAT3 signaling [2, 3], direct comparisons of IL-6R inhibitors have not been conducted in patients with RA.Objectives:We aimed to examine the real-world comparative effectiveness of subcutaneous SAR (SAR-SC), TCZ-SC, and intravenous TCZ (TCZ-IV) in patients with RA in a multicentre cohort study.Methods:Patients with RA who initiated with SAR-SC (200mg once every 2 weeks [q2w]), TCZ-SC (162mg q2w; may increase to qw based on clinical response; approved dose in Japan and USA), and TCZ-IV (8mg/kg q4w) were included. The primary outcome of interest was changes in the clinical disease activity index (CDAI) at 24 weeks. Multiple propensity score-based inverse probability weighting (IPW) was used to reduce confounding by indication. IPW mixed-effect models for repeated measures with an unstructured covariance structure were applied to examine changes in the CDAI from baseline at four post-intervention time points (4, 12, 24, and 48 weeks) after multiple imputation by chained equations for missing values. Drug retention was compared among IL-6R inhibitors using IPW Cox proportional hazards models.Results:A total of 1224 treatment courses from 1095 patients was included (SAR-SC, 274; TCZ-SC, 657; TCZ-IV, 293). The improvement in CDAI at 24 weeks as the primary outcome was significantly greater in the SAR-SC group than in the TCZ-SC group (-1.98, 95% confidence interval: -3.61 to -0.35, p = 0.017), with differences observed as early as week 12 (-2.13 [-3.65 to -0.60], p = 0.006) (Figure 1). The improvement in CDAI was similar between the TCZ-IV and the TCZ-SC group (0.90 [-0.73 to 2.53], p = 0.28) (Figure 1). The effect of SAR-SC compared with TCZ-SC on change in CDAI was greater irrespective of baseline disease activity, disease duration, body weight, positivity of rheumatoid factor, positivity of anti-citrullinated peptide antibodies, the status of inadequate responses to tumor necrosis factor inhibitors (TNFi-IR), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig)-IR, or Janus kinase inhibitor (JAKi)-IR. Similar retention rates at 48 weeks were identified among SAR-SC and TCZ-IV compared to TCZ-SC (Figure 2).Conclusion:Among IL-6R inhibitors, SAR-SC showed greater effectiveness compared with TCZ-SC in disease activity from early administration while no significant difference was identified between TCZ-IV and TCZ-SC. SAR-SC may represent an effective treatment option for patients with multiple poor prognostic factors.REFERENCES:[1] Aletaha, D., et al., Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Ann Rheum Dis, 2023. 82(6): p. 773-787.[2] Xu, C., et al., Differential Binding of Sarilumab and Tocilizumab to IL-6Rα and Effects of Receptor Occupancy on Clinical Parameters. J Clin Pharmacol, 2021. 61(5): p. 714-724.[3] Saito, S., et al., Differences in the strength of inhibition of interleukin-6 signalling by subcutaneous sarilumab and tocilizumab in rheumatoid arthritis patients. Clin Exp Rheumatol, 2023. 41(7): p. 1451-1455.Figure 1.Change in CDAI after introducing subcutaneous sarilumab, subcutaneous tocilizumab, and intravenous tocilizumab.The figure was derived from inverse probability weighting mixed-effect models for repeated measures. The mean ± standard error is shown.CDAI, clinical disease activity index; IV, intravenous; SAR, sarilumab; SC, subcutaneous; TCZ, tocilizumab.Figure 2.Adjusted drug retention rates of subcutaneous sarilumab, subcutaneous tocilizumab, and intravenous tocilizumab.IV, intravenous; SAR, sarilumab; SC, subcutaneous; TCZ, tocilizumab.Acknowledgements:NIL.Disclosure of Interests:Akira Onishi received speaker fees from Pfizer Inc., Bristol Myers Squibb, Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., Ono Pharmaceutical Co., UCB Japan Co., Mitsubishi Tanabe Pharma Co., Eisai Co. Ltd., AbbVie Inc., Takeda Pharmaceutical Co. Ltd., and Daiichi Sankyo Co. Ltd., received research grants s from Pfizer Inc., and Bristol Myers Squibb., Masao Tanaka received speaker fees from AbbVie GK, Asahi Kasei Pharma Corp., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kyowa Kirin Co., Ltd., Pfizer Inc., Taisho Pharmaceutical Co., Ltd., Tanabe Mitsubishi Pharma Corp., Teijin Pharma, Ltd., UCB Japan Co., Ltd., Hideo Onizawa received speaker fees from AbbVie, Asahi Kasei, Astellas Pharma Inc., Eisai Co., Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, and Daiichi Sankyo Co., Ltd., Takayuki Fujii received speaker fees from AbbVie GK, Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., and Janssen Pharmaceutical K.K., Koichi Murata received a speaking fee from Eisai Co. Ltd., Chugai Pharmaceutical Co. Ltd.; Asahi Kasei Pharma Corp., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Co., Janssen Pharmaceutical K.K. and Daiichi Sankyo Co. Ltd., Kosaku Murakami received speaker fees from Eisai Co. Ltd., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, UCB Japan Co. Ltd., Daiichi Sankyo Co. Ltd., and Astellas Pharma Inc., Motomu Hashimoto received research grants and/or speaker fee from Abbvie, Asahi Kasei, Astellas, Brystol Meyers, Chugai, EA Pharma, Eisai, Daiichi Sankyo, Eli Lilly, Novartis Pharma, Taisho Toyama, Tanabe Mitsubishi., Ryu Watanabe received a speaker’s fee from Asahi Kasei, Chugai, Eli Lilly, GSK, and Sanofi.,, received a research grant from AbbVie.,, Yuji Nozaki: None declared, Chisato Ashida: None declared, Wataru Yamamoto: None declared, Hirotaka Yamada received speaker fees from AbbVie, Asahi Kasei Pharma, Astellas Chugai, Eisai Gilead Sciences, and Taiho Pharmaceuticals., Sho Sendo: None declared, Kosuke Ebina received a speaker fee from AbbVie, Amgen, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho, and UCB Japan, received research grants from AbbVie, Asahi-Kasei, Eisai, Mitsubishi-Tanabe, and Teijin Pharma., Makino Hidehiko: None declared, Yonsu Son received speaker fees from Bristol-Myers Squibb, Chugai, Janssen, Eisai, and AbbVie., Yumiko Wada: None declared, Kenichiro Hata received speaker fees from Abbvie, Asahi-Kasei, Astellas, Chugai, Eisai, Eli Lilly, Gilead Sciences, Janssen, and Mitsubishi-Tanabe., Shuichi Matsuda received speaker fees from Pfizer Inc., Akio Morinobu has received honorarium from AbbVie G.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Eisai Co. Ltd., Pfizer Inc., Bristol-Myers Squibb., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., and Gilead Sciences Japan., received research grants from AbbVie G.K., Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co. and Eisai Co. Ltd.

Background:The randomized controlled NORD-STAR trial demonstrated remission rates of 40-60% in patients with early rheumatoid arthritis (RA) at 24 and 48 weeks according to the Clinical Disease Activity Index (CDAI) when treated early with methotrexate in combination with prednisolone (active conventional therapy (ACT)), certolizumab pegol (CZP), abatacept (ABA) or tocilizumab (TCZ) (1, 2). However, clinical remission criteria reflect in part subjective measures of pain and well-being and not necessarily inflammatory activity. Ultrasound is an imaging tool that aims to measure joint and tendon inflammation objectively. In the NORD-STAR trial, a subset of patients in Norway and Sweden was assessed by ultrasound of joints and tendons.Objectives:To compare ultrasound remission rates at week 48 in patients receiving active conventional treatment versus each of the three biological treatments in early RA and explore the effect of conventional and biological DMARDs on ultrasound-measured inflammation.Methods:NORD-STAR is an investigator-initiated, randomized, blinded-assessor study. Treatment-naïve early RA patients with moderate-severe disease activity were randomized 1:1:1:1 to methotrexate combined with: 1) oral prednisolone (tapered quickly; discontinued at week 36); 2) CZP; 3) ABA or 4) TCZ. Patients in Norway (all 5 sites) and at Karolinska University Hospital in Sweden were assessed with ultrasound of joints/tendons and ultrasound scores were calculated according to the USRA9 score, including assessment of 8 joints (MCP 1-3, PIP 2-3, radiocarpal, MTP2-3) and 1 tendon (extensor carpi ulnaris) bilaterally with a 0-3 score for grey scale and power Doppler, respectively. Ultrasound remission was defined as Doppler sum score=0. Remission rates (w48) were assessed without imputation of missing values and compared between treatment arms using logistic regression adjusted for multiple testing by the Dunnett’s procedure and adjusted for age, gender, center, anti-CCP status at baseline and baseline value for the dependent variable.Results:Of the total of 812 patients in the NORD-STAR trial, 239 patients were included in the ultrasound analyses (Norway n=114, Sweden n=125). Patient characteristics were well balanced across the treatment arms. The patients were representative for the whole NORD-STAR population (1,2). Ultrasound remission rates at week 48 were 74 % for ACT, 94 % for CZP, 90 % for ABA and 87 % for TCZ (Table 1, Figure 1).In the primary analysis (adjusted logistic regression), ultrasound remission rates were higher with borderline statistical significance for CZP vs ACT, OR (95%CI) 5.46 (1.33, 22.52) p=0.05and ABA vs ACT OR 4.51 (1.27, 16.00) p=0.06 and not significant for TCZ vs ACT, OR 2,26 (0.71, 7.19) p=0.40.More patients achieved ultrasound remission compared to clinical remission in all treatment arms at 48 weeks. Patients in ultrasound remission, but not in clinical remission (n=56) had higher tender joint counts (8.5 vs 0.6), patient’s global (28.1 vs 4.8) and physician’s global (10.8 vs 1.3) scores than patients who were in both ultrasound and clinical remission. Swollen joint count (1.0 vs 0.1), ESR (9.3 vs 10.7) and CRP (2.6 vs 2.5) were similar in both groups.Conclusion:A large proportion of patients with early RA achieved ultrasound remission in the NORD-STAR trial. Higher remission rates were achieved in the biologic treatment arms compared to active conventional treatment which is in line with the clinical results. Substantially more patients achieved ultrasound remission than CDAI remission.REFERENCES:[1] Hetland et al. BMJ 2020;371:m4328.[2] Østergaard M et al. Ann Rheum Dis. 2023;82(10):1286-1295.Table 1. Demographics/baseline (BL) characteristics and 48 weeks results. Values are mean (SD), if not otherwise indicated.Figure 1.Proportion of patients in ultrasound remission. Completer analysis.Acknowledgements:NIL.Disclosure of Interests:Marte S Heiberg: None declared, Yogan Kisten: None declared, Amirhossein Kazemi: None declared, Hamed Rezaei: None declared, Erik af Klint: None declared, Maud-Kristine A Ljosa: None declared, Eli Brodin: None declared, David Stevens: None declared, Gunnstein Bakland UCB, Lars Fridtjof Karoliussen: None declared, Pernille Bolton-King: None declared, Joakim Lindqvist: None declared, Kristina Lend: None declared, Jon Lampa: None declared, Till Uhlig: None declared, Merete Lund Hetland MLH received research grants from AbbVie, Biogen, BMS, Celtrion, Eli Lily, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis; and institution pay from Pfizer, Medac, AbbVie and Sandoz; chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies; cochairs EuroSpA, which generates real-world evidence of treatmentof psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis., Anna Rudin: None declared, Dan Nordström DCN received consulting fees from AbbVie, BMS, Lilly,MSD, Novartis, Pfizer, Roche and UCB’ meeting support from Pfizer; advisory board participation fee from Novartis; and other service fee by BMS., Bjorn Gudbjornsson: None declared, Michael T Nurmohamed MTN received research grants from AbbVie, BMS, Pfizer, Galapagos, Amgen and Eli Lily. BG received consulting fee from Novartis and honorary lecture payment from Novartis and Nordic-Pharma., Mikkel Østergaard MØ received the study drug from BMS and UCB; research grants from Abbvie, BMS, Merck, Novartis and UCB; speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB; and consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz and UCB., Gerdur Grondal: None declared, Tuulikki Sokka-Isler: None declared, Hilde Berner Hammer: None declared, Ronald F. van Vollenhoven RFvV received the study drug from BMS and UCB; research grants from BMS, GSK, UCB and AstraZeneca; consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB; expert fees from AbbVie, Galapagos,GSK, Janssen, Pfizer, R-Pharma and UCB; and advisory board fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB., Espen Haavardsholm: None declared.

Background:It has been reported that female rheumatoid arthritis (RA) patients have a longer time to pregnancy than healthy women (1), and that high Disease Activity Score with 28 joint count (DAS28) -CRP in preconception increases the frequency of infertility (2). Before the era of biologics, RA treatment tended to be inadequate from pregnancy planning to the end of lactation. And it was not uncommon for female RA patients to be unable to get pregnant or develop physical dysfunction as a result of insufficient control of the disease. There are some reports of disease activity during pregnancy and postpartum in RA patients, and the effects of RA disease activity on pregnancy and childbirth outcomes (3-5), but there are few reports focusing on the physical function during pregnancy planning of RA patients.Objectives:To investigate disease activity and physical function in female patients with RA who planned and didn’t plan pregnancy.Methods:The IORRA cohort is a large, single institute-based, observational cohort of RA patients established at the Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. We identified female RA patients aged 20-49 years who answered ‘pregnant’ or ‘delivered’ in the IORRA survey in 2010-2015 and whose pregnancy and the pregnancy planning time was confirmed in the medical records, and defined them as the pregnancy planning (PP) group. Matched control was extracted at 1:3 ratio from patients without pregnancy plan based on entry time, age, RA disease duration, DAS28-CRP, Japanese version of Health Assessment Questionnaire (J-HAQ) score, and comorbidities. The primary endpoint was J-HAQ at 3years from the baseline, which was defined as the most recent IORRA survey before planning pregnancy. The mixed-effect model for repeated measures was used to analyze group difference.Results:There were 40 patients in the PP group (average 32.2 years, disease duration 5.7 years, DAS28-CRP 1.7, J-HAQ 0.26), and 120 patients in the control group (average 32.4 years, disease duration 5.9 years, DAS28-CRP 1.7, J-HAQ 0.21). The proportion of user and dosage of MTX and glucocorticoid (GC) and bDMARDs user at baseline were comparable between the groups (MTX: PP 87.5% [9.8 mg/week], control 85.0% [8.8 mg/week]; GC: PP 32.5% [3.6 mg/day], control 27.5% [4.4 mg/day]; bDMARDs: PP 40.0%, control 27.5%). DAS28-CRP at year 3 of the PP group elevated and was higher than the control group (PP 2.3, control 1.7, p<0.01), while J-HAQ was stable over the observation period and did not differ significantly at year 3 (PP 0.21, control 0.22, p=0.92). At year 3, the proportion of patients taking MTX was lower and taking GC was higher in the PP group than those in the control group (MTX: PP 36.7%, control 76.7%, p<0.01; GC: PP 70.0%, control 25.6%, p<0.01). The proportion of patients taking bDMARDs was not different in both groups (PP 36.7%, control 32.6%, p=0.68).Conclusion:Physical function in pregnancy planning patients with RA did not deteriorate as well as the control patients in clinical settings.References:[1]Arthritis Rheum. 2011;63:1517-1521.[2]Ann Rheum Dis. 2015;10:1836-1841.[3]J Rheumatol. 2015;42:1376-1382.[4]J Rheumatol. 2019;46:245-250.[5]Arthritis Care Res. 2017;69:1297-1303.Disclosure of Interests:Moeko Ochiai: None declared, Eiichi Tanaka Consultant of: ET has received lecture fees or consulting fees from Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Speakers bureau: ET has received lecture fees or consulting fees from Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Mai Abe: None declared, Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, higuchi yoko: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Ikari Katsunori Speakers bureau: KI has received speaker’s fee from Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Background:The treat-to target (T2T) concept is the standard for treating rheumatoid arthritis (RA) patients worldwide1. However, difficulties that patients encounter in achieving disease control may differ between regions, which may impact the type of support needed for successful T2T implementation.Objectives:To compare differences in patient-reported challenges to controlling RA-related issues between Romanian and US patients.Methods:A cross-sectional study that recruited 403 RA patients was conducted in six centers in Romania. Patients were invited to complete an RA-related questionnaire. We compared their responses to those from a previous published study that included patients with RA from the US2. The survey included items on subjective beliefs about RA treatment (e.g. adherence, cost, adverse events) and knowledge about T2T strategy. Approval for US data use was given by the study coordinator2.Results:All patients in the Romanian cohort were Caucasian, with a mean age of 58.7 years (SD 11.6). 78% were females and the mean disease duration was 11.2 years (SD 8.3). Data was concordant with results from the previously published study. More patients from US had college education (60% vs 43.9%).Among the respondents, 93.3% Romanians were on a synthetic DMARD versus 97.7% Americans and 64.01% were currently on a biologic of choice compared to 74% patients in the US. More than half of the patients in both regions had a history of biologic DMARD use.Asked to grade (0 very good, 10 very bad) their disease activity on the survey day, a large category of patients (37.4%, SD 14.1) marked an average state (4-6), while 19.08% (SD 11.2) were feeling poorly related to their disease.Patients were asked to define their adherence to RA treatment in the last 30 days. While the US study reported that 93% of patients were adherent2, in our study only 62.5% of the Romanian patients reported adherence (p<0.01). A significantly lower proportion of Romanian patients were aware of T2T strategy (35 %, p 0.04).Regarding patient beliefs on their disease, statements were grouped into categories such as difficulty managing pain, medication safety, adherence, lifestyle. Most European patients would agree to change treatment to lower pain. Almost 82% stated they would accept rare adverse events in order to avoid invalidity, to confirm a better future outcome. US patients were more prone to stick to current therapy than escalade to increase clinical response. However, asked about novel therapies, Romanians were reluctant to changing treatment despite insufficient benefit, if the risk of cancer was noted. There was a high agreement that a delay in treatment would be unsatisfactory for both familial and professional chores.Conclusion:There are regional differences in knowledge and perceptions about RA treatment. Romanian patients know less on T2T algorithm. Improving awareness of the T2T strategy among RA patients may need different types of support depending on the patient’s place of residence.References:[1]Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann. Rheum. Dis. 76, 960–977 (2017).[2]Owensby, J. K. et al. Patient- and Rheumatologist- Perspectives Regarding Challenges to Achieving Optimal Disease Control in Rheumatoid Arthritis. Arthritis Care Res. (Hoboken). 0–2 (2019).Disclosure of Interests:CLAUDIA COBILINSCHI Speakers bureau: novartis, Maria Danila Speakers bureau: as personally stated, Daniela Opris-Belinski Speakers bureau: as declared, Ioana Saulescu Speakers bureau: Eli-Lilly, Pfizer, Laura Groseanu Speakers bureau: novartis, eli-lilly, ucb, pfizer,sandoz, Sanziana Daia-Iliescu Speakers bureau: sandoz, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Razvan Ionescu Speakers bureau: as personally stated, Magda Parvu Consultant of: Speaker fee and consultant: Pfizer, Novartis, Roche, Abbvie, UCB, Eli-Lilly, Speakers bureau: Speaker fee and consultant: Pfizer, Novartis, Roche, Abbvie, UCB, Eli-Lilly, Horatiu Popoviciu Speakers bureau: as personally stated, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Elena Rezus: None declared, Claudia Mihailov Speakers bureau: as personally stated, Ruxandra Ionescu Consultant of: Consulting fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Speakers bureau: Consulting and speaker fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz

Background:Lupus nephritis (LN) is one of the most critical organ involvement in systemic lupus erythematosus (SLE). While there are effective treatment options such as MMF and cyclophosphamide, there are still unmet medical needs: refractory cases to existing therapies and difficult cases to reduce GC. Therefore, the emergence of new treatment options is expected. Recently, rituximab (RTX), an anti-CD20 antibody, is expected to be a new treatment option for LN based on the results of clinical trials. Indeed, the EULAR recommends the use of RTX for refractory LN. In Japan, RTX for LN was approved in August 2023, ahead of the world. However, the effectiveness and safety of RTX in real-world clinical practice have not been fully verified.Objectives:This study aimed to assess the effectiveness and safety of RTX for LN in real-world clinical practice.Methods:This study included 117 patients with LN. The effectiveness and safety were compared between High-dose GC + RTX group (RTX group, n = 58) and high-dose GC + CY and MMF group (standard of care: SoC group, n = 59) in remission induction therapy for patients with LN. Both groups were treated in addition to standard of care including HCQ. Selection bias was minimized by the propensity score-based inverse probability of treatment weighting (PS-IPTW) method and compared between the groups. The primary endpoint was the Complete Renal Response (CRR) achieving rate and uPCR less than 1.0 (g/g・cre) at week 52. Secondary endpoints were treatment retention rate, safety, SLEDAI, and GC reduction rate at 52 weeks. Peripheral blood immunophenotypes (CD4 T cell, CD8 T cell, B cell, NK, monocyte, DC) of LN(n=76) just before the remission induction therapy were compared to those of age- and sex-matched HC (n=109). Additionally, the impact of RTX on immunophenotypes was evaluated by comparing before and after RTX in 21 patients.Results:The 52-week treatment retention rate was 94.8% (55/58) in the RTX group and 83.1% (49/59) in the SoC group, with no difference between the two groups. Infusion reactions were the most frequent adverse event in the RTX group at 20.7% (12/58), and infections were the most frequent in the SoC group at 47.5% (28/59). SLEDAI scores significantly decreased in both groups. Patient baseline characteristics were adjusted by PS-IPTW method. The primary endpoint achievement rate was 1) CRR achieving rate: RTX group; 58.1%, SoC group; 52.2% (p=0.38), uPCR<1.0 achieving rate: RTX group; 83.2%, SoC; 81.3% (p=0.54). There was no significant difference between the groups. There was also no difference in GC sparing effect, the secondary endpoint, between the two groups (RTX group; -81.1%, SoC group; -89.3%, p=0.65). Immune phenotyping revealed increased class-switched memory B cells (CM B cells: CD19+ CD27+ IgM-) and plasmocytes (CD19+ CD27+ CD38+) in SLE compared to HCs. Naïve B cells (CD19+ CD27- IgM+), CM B cells, and plasmocytes disappeared after 26 weeks of RTX introduction. plasmocytes remained low for 52 weeks in cases that achieved the primary endpoint(n=16). On the contrary, CM B cells and plasmocytes increased in cases that did not achieve the primary endpoint (n=5). Patients who relapsed within 3 years after achieving the primary endpoint by RTX were 5/16 cases, in which CM B cells and plasmocytes increased again. Naïve B cells re-elevated while CM B cells and plasmocytes remained absent in the non-relapse cases.Conclusion:Rituximab can be an effective treatment option in real-world clinical practice achieving remission and suppressing relapse by depleting CM B cells and plasmocytes.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Masanobu Ueno Masanobu Ueno has received a speaking fee from GlaxoSmithKline., Shingo Nakayamada S. Nakayamada has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, Astellas, Asahi-kasei, Sanofi, Abbvie, Eisai, Chugai, Gilead, and Boehringer Ingelheim, and has received research grants from Mitsubishi-Tanabe., S. Nakayamada has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, Astellas, Asahi-kasei, Sanofi, Abbvie, Eisai, Chugai, Gilead, and Boehringer Ingelheim, and has received research grants from Mitsubishi-Tanabe., Ippei Miyagawa: None declared, Satoshi Kubo Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, Abbvie, Eisai, Pfizer, Astra-Zeneca and also research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Yusuke Miyazaki Y. Miyazaki has received speaking fees from Eli Lilly, and has received research grants from GlaxoSmithKline., Kentaro Hanami: None declared, Koshiro Sonomoto: None declared, Hiroaki Tanaka: None declared, Yoshiya Tanaka Yoshiya Tanaka has received speaking fee from Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, and Taiho., Yoshiya Tanaka has received grant from Mitsubishi-Tanabe, Eisai, Chugai, and Taisho.

BackgroundWomen with axial spondyloarthritis (axSpA) tend to have higher scores on patient-reported outcome measures (PROMs), such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI), compared to men with the same condition. However, it is not well known whether these sex differences are maintained over time during treatment with tumor necrosis factor inhibitors (TNFi), or which factors can potentially explain these sex-based differences.ObjectivesTo examine sex differences in BASDAI and BASFI over time in axSpA patients treated with their first TNFi, and to identify potential factors contributing to observed sex differences.MethodsPooled data were collected from biologic-naive axSpA patients initiating their first TNFi in the EuroSpA registries. A three-level linear mixed model structure was employed to analyze sex differences in PROMs (BASDAI and BASFI, scale 0-100) over time (sex*time), accounting for correlations between repeated measurements within subjects and between subjects within countries. Baseline characteristics were explored as potential explanatory variables for observed sex differences over time, and interactions between sex, time, and explanatory variables were analyzed. Univariable analysis was performed by incorporating one explanatory variable at a time, while multivariable analysis was used to investigate the effect of multiple explanatory variables on the regression coefficient of sex*time. Only explanatory variables that affected this regression coefficient by more than 10% in univariable analysis were considered for multivariable analysis. A complete case analysis was performed when data were missing for explanatory variables.ResultsThis study analyzed data from 11,753 axSpA patients (37% female) with at least two BASDAI measurements over two years, and from 9,780 patients (38% female) with at least two BASFI measurements over the same period. At baseline, women were older and had higher BASDAI/BASFI scores, while men had higher CRP levels, longer disease duration, and higher HLA-B27 positivity. During the follow-up period, women had significantly higher mean BASDAI scores than men (mean difference 6.05; 95% CI 5.27 to 6.83). Additionally, the differences in BASDAI scores between women and men increased by an average of 0.67 (95% CI 0.04 to 1.29) per year. These findings indicate that the sex differences in BASDAI scores persisted and increased over time. In the univariable analysis of explanatory variables, increased age (-8.9%) and longer disease duration (-4.7%) notably explained the sex differences in the BASDAI scores (Figure 1). However, no explanatory variables were eligible for inclusion in the multivariable analysis. We also observed that the sex differences in BASDAI scores were reduced over time in HLA-B27-positive patients, but increased in those with psoriasis (Figure 1). Although women had slightly higher overall BASFI scores than men (mean difference 3.25; 95% CI 2.32 to 4.19), this difference did not vary by time (β = 0.25; 95% CI -0.36 to 0.86).ConclusionWomen with axSpA treated with their first TNFi had significantly higher mean BASDAI and BASFI scores compared to men over a two-year follow-up period. The mean difference in BASDAI scores increased slightly over time, and the magnitude of this difference was affected by HLA-B27 positivity (reduced) and psoriasis (increased). Further research is needed to understand the mechanisms behind these sex differences and their clinical implications.AcknowledgementsThe EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG. Novartis had no influence on the data collection, statistical analyses, abstract preparation, or decision to submit the abstract.Disclosure of InterestsPasoon Hellamand Grant/research support from: Research grant from Novartis., Marleen G.H. van de Sande Consultant of: Research grant and/or consulting fee, and/or speaker fee from Eli Lilly, Novartis, UCB, Janssen, Abbvie, Michael T Nurmohamed: None declared, Ronald van Vollenhoven Speakers bureau: AbbVie, AstraZeneca, BMS, Galapagos, GSK, Janssen, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Pfizer, and UCB, Grant/research support from: Research support: BMS and UCB, Support for Educational programs (institutional grants): MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Rosemary Hollick Speakers bureau: Gilead, Eli, and Lilly, Ovidiu Rotariu: None declared, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, and Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, and Janssen, Katja Pirkmajer Speakers bureau: Abbvie, Novartis, MSD, Medis, Eli Lilly, Pfizer, Lek, and Janssen, Consultant of: Abbvie, Novartis, Medis, Eli Lilly, Pfize, and Boehringer Ingelheim, Dan Nordström Speakers bureau: Novartis, Pfizer, and UCB, Consultant of: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: MSD, Anna-Mari Hokkanen Grant/research support from: MSD, Brigitte Michelsen Grant/research support from: Research grant from Novartis (paid to employer), Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, and UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, and UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, and UCB, Bente Glintborg Grant/research support from: Research grants from Pfizer, Abbvie, BMS, and Sandoz, Anne Gitte Loft Speakers bureau: Speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: Research grant from Novartis, Karel Pavelka Speakers bureau: AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, and Novartis, Consultant of: AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, and Novartis, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, and Sobi, Isabel Castrejon Speakers bureau: Speaker and/or consultancy fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, and GSK, Lucía Otero-Varela: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Nordic Pharma, Consultant of: Novartis, Olafur Palsson: None declared, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Novartis and UCB, Merete Lund Hetland Speakers bureau: Pfizer, Medac, and Sandoz, Grant/research support from: Research grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, and Novartis, Johan K Wallman Speakers bureau: AbbVie and Amgen, Grant/research support from: Research support from AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer, Daniela Di Giuseppe: None declared, Adrian Ciurea Speakers bureau: AbbVie and Novartis, Consultant of: AbbVie and Novartis, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis, and Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis, and Pfizer, Tuba Demirci Yildirim: None declared, Fatos Onen Speakers bureau: AbbVie, Amgen, Celltrion, Lilly, Pfizer, Roche, Novartis, Abdi İbrahim, and UCB, Grant/research support from: Research grant from Pfizer, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, and Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, and Pfizer, Corina Mogosan Speakers bureau: Speaker fees from AbbVie, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, and Pfizer, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis, and Pfizer, Elsa Vieira-Sousa Speakers bureau: Novartis, Abbvie, MSD, Celgene, and UCB, Grant/research support from: Research grants from MSD, Pfizer, and UCB., Florenzo Iannone Speakers bureau: consulting and/or speaking from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Giovanni Lapadula: None declared, Lykke Midtbøll Ørnbjerg Grant/research support from: Research grant from Novartis, Jos Twisk: None declared, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer and MSD, Consultant of: Abbvie, UCB, MSD, Novartis and Lilly, Grant/research support from: MSD, Pfizer, AbbVie and UCB.