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Objective PERFUSE is a non-interventional study of 1233 adult patients (rheumatology, n = 496; IBD, n = 737) receiving routine infliximab (IFX) biosimilar SB2 therapy. The aim of this report was to investigate the 12-month persistence, effectiveness and safety outcomes of routine SB2 treatment in patients with chronic inflammatory rheumatic disease. Methods Patients with a diagnosis of RA, PsA or axial spondyloarthritis (axSpA) were assigned to one of three study cohorts according to whether SB2 treatment initiated after September 2017 had been the first IFX treatment (IFX naïve) or followed transition from reference IFX (IFX ref) or another IFX biosimilar (IFX bs). Outcomes to month 12 (±2) included persistence (primary outcome), SB2 dose, disease status, immunogenicity and safety. Results At month 12, persistence on SB2 in IFX-naïve, IFX ref and IFX bs cohorts, respectively, [mean percentage (95% CI)] by indication was as follows: 59% (36.1, 76.2), 75% (57.5, 86.1) and 85% (69.6, 93.0) for RA (n = 98); 64% (34.3, 83.3), 87% (65.6, 95.7) and 83% (60.0, 93.1) for PsA (n = 62); and 56% (44.4, 66.5), 80% (70.8, 86.1) and 80% (72.5, 85.6) for axSpA (n = 336). Disease activity was comparable at baseline and month 12 within the IFX ref and bs subgroups of all cohorts by indication. No immunogenicity concerns or new safety signals were detected. Conclusion SB2 was safe and effective in IFX-naïve patients and in patients transitioned from prior IFX ref or bs. Trial registration clinicaltrials.gov, NCT03662919

Introduction In 2016, SB4 (Benepali®) became the first etanercept (ETN) biosimilar to obtain marketing authorisation in Europe. Despite robust analytical and clinical comparisons, outstanding questions remain on SB4 use in routine practice. Methods A systematic search for publications on real-world evidence of SB4 effectiveness, safety and drug survival was undertaken using search terms (SB4 OR Benepali OR biosimilar etanercept OR innovator etanercept) in the BIOSIS® Toxicology, BIOSIS Previews®, Embase® and MEDLINE® databases up to 17 January 2019. Results Of 959 articles identified, eight journal articles, two journal letters and 23 congress abstracts were selected on criteria of original real-world evidence with a clinical focus. As expected with real-world evidence, quality scoring showed that the evidence had high external validity but lower internal validity. A total of 13,552 patients were described across nine European countries and all approved SB4 indications: 2499 were ETN-naïve and 11,053 switched from reference ETN to SB4 (switchers). Switch acceptance rates (a combination of clinicians offering and patients accepting initiation on SB4) ranged between 51.6% and 99.0%; patient support programmes positively contributed to acceptance. Disease activity was generally similar pre- and post-switch (typically 3-month timeframe). Retention rates across studies were at least 75% (up to 12 months follow-up). No new safety signals were identified. Differences in discontinuation rates versus historic controls reported in some studies may have been influenced by differences in treatment practices, lack of clinician confidence and nocebo effects. Conclusion Nearly 2500 ETN-naïve patients have been initiated on SB4 and outcomes are similar to those patients receiving reference ETN. Overall this systematic review of real-world evidence provides additional reassurance that SB4 is as effective and safe as reference ETN in both switched and naïve patients. Funding Biogen International GmbH. Electronic Supplementary Material The online version of this article (10.1007/s40744-019-00169-4) contains supplementary material, which is available to authorized users.

The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA).Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA.In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort.Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.

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

The European Medical Information Framework (EMIF) project, funded through the IMI programme (Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115372), has designed and implemented a federated platform to connect health data from a variety of sources across Europe, to facilitate large scale clinical and life sciences research. It enables approved users to analyse securely multiple, diverse, data via a single portal, thereby mediating research opportunities across a large quantity of research data. EMIF developed a code of practice (ECoP) to ensure the privacy protection of data subjects, protect the interests of data sharing parties, comply with legislation and various organisational policies on data protection, uphold best practices in the protection of personal privacy and information governance, and eventually promote these best practices more widely. EMIF convened an Ethics Advisory Board (EAB), to provide feedback on its approach, platform, and the EcoP. The most important challenges the ECoP team faced were: how to define, control and monitor the purposes (kinds of research) for which federated health data are used; the kinds of organisation that should be permitted to conduct permitted research; and how to monitor this. This manuscript explores those issues, offering the combined insights of the EAB and EMIF core ECoP team. For some issues, a consensus on how to approach them is proposed. For other issues, a singular approach may be premature but the challenges are summarised to help the community to debate the topic further. Arguably, the issues and their analyses have application beyond EMIF, to many research infrastructures connected to health data sources., Minds and Machines, 29 (3)

Background:SB5, a biosimilar to reference adalimumab (ADL), received EU marketing authorisation in August 2017, based on the totality of evidence from pre-clinical and clinical Phase I and III studies that demonstrated bioequivalence, similar efficacy, and comparable safety and immunogenicity to the reference. This real-world study provides data on outcomes of the transition from reference to biosimilar ADL outside the controlled, randomised, clinical trial setting.Objectives:To evaluate candidate predictors of persistence on SB5 in EU patients (pts) across multiple indications.Methods:This ongoing observational study enrolled 1000 pts with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), ulcerative colitis, or Crohn’s disease who initiated SB5 as part of routine clinical practice following a minimum of 16 weeks’ treatment with reference ADL, at clinics in Belgium, Germany, Ireland, Italy, Spain, and the UK. Data are captured from clinic records retrospectively for the 24 weeks prior to transition, and prospectively and/or retrospectively for 48 weeks following transition. Primary outcome measures include baseline clinical characteristics, disease activity scores and clinical management over time; data on COVID-19 infection has recently been captured. This interim analysis (IA) provides an overview of baseline characteristics, disease scores and dose regimen up to 48 weeks post-initiation of SB5, and COVID-19 infection reported to date, in subjects with RA, axSpA, or PsA enrolled at 35 specialist sites and followed up to the data extract date of 18th December 2020.Results:Of the 504 pts included in this IA, 201 have RA, 169 have PsA, and 134 axSpA. At time of data extract, 216 pts had completed 48 weeks on SB5, 73 pts had discontinued SB5, and 8 had discontinued the study.RA (N=201)axSpA (N=134)PsA (N=169)Mean (SD)Q1, Q3Mean (SD)Q1, Q3Mean (SD)Q1, Q3Age at SB5 initiation (years)60.2 (11.7)53, 6850.5 (13.6)38, 6153.0 (12.2)43, 62Duration of disease (years)13.5 (11.7)4.5, 2018.7 (13.2)9, 2512.7 (9.9)4, 20n%n%n%Women14471.64130.67745.6SB5 Dosing regimen:Baseline 40 mg Q2W14974.112089.615692.3Week 48 40mg Q2W6977.56785.99892.5Baseline Other*5225.91410.4137.7Week 48 Other*2022.41114.187.5Disease Score(paired patients)DAS28FFbHBASDAITender Joint CountSwollen Joint CountBaseline, n, mean (95% CI)692.5 (2.3–2.7)2273.9 (65.6–82.1)422.8 (2.3–3.4)491.8 (0.1–3.0)490.6 (0.2–0.9)Week 48, n, mean (95% CI)692.6 (2.3–2.8)2272.1 (64.0–80.2)423.0 (2.4–3.7)491.9 (0.5–3.3)490.6 (0.1–1.1)Patient diagnosed with COVID-19 at any time on-study, n (%)No14295.39688.114098.6Yes32.010.910.7Unknown42.71211.010.7Imraldi regimen stopped or changed due to COVID-19, regardless of diagnosis, n (%)No13098.510697.2134100Yes21.532.800SD standard deviation; Q1 1st quartile, Q3 3rd quartile; CI Confidence Interval*Other includes all other reported doses and/or dosing intervals: 40mg QW, 80mg Q2W, and unspecified frequencyDAS28 Disease Activity Score 28; FFbH Hanover Functional Ability Questionnaire; BASDAI Bath Ankylosing Spondylitis Disease Activity IndexConclusion:This IA provides a first insight into clinical management of pts over 48 weeks, in a contemporary cohort of EU pts with established RA, axSpA and PsA, switched from reference to biosimilar ADL SB5 in clinical practice. The majority of pts showed no meaningful difference in disease score or dose regimen of SB5 by Week 48 post-transition. As of data extract date, the proportion of pts with a known positive COVID-19 test was low (1.3%) and a small minority (1.3%) had SB5 treatment changed or interrupted as a result of the COVID-19 pandemic. With follow-up of pts ongoing to Q4 2021, the study will continue to provide pertinent information about clinical outcomes of transition from reference to biosimilar ADL in real-world practice and in indications not investigated in controlled studies.Acknowledgements:Statistical services gave been provided by FGK Clinical Research GmbH, Munich, Germany. Data management services were provided by Worldwide Clinical trial, Research Triangle Park, NC, USA; funding was provided by Biogen International GmbH.Disclosure of Interests:Ulf Müller-Ladner Consultant of: Biogen, Grant/research support from: Biogen, Karl Gaffney Consultant of: AbbVie, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, and UCB, Deepak Jadon Consultant of: AbbVie, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Oxford University Press, Pfizer, Roche, Sandoz, UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Oxford University Press, Pfizer, Roche, Sandoz, UCB, Ulrich Freudensprung Shareholder of: Biogen, Employee of: Biogen, Janet Addison Shareholder of: Biogen, Employee of: Biogen

Background:SB2 is approved in the EU as an infliximab (IFX) biosimilar, having demonstrated bioequivalence and similar efficacy, safety and immunogenicity as the reference. PERFUSE is an ongoing non-interventional study of 1233 patients (496 with rheumatology diagnoses, 737 with gastroenterology diagnoses) receiving SB2 as routine therapy.Objectives:The aim of the study is to provide data on long-term outcomes in patients initiating SB2 in the real-world setting.Methods:Adult patients eligible for inclusion in the rheumatology study cohorts have a diagnosis of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Axial Spondyloarthritis (axSpA) and had initiated SB2 in routine clinical practice after September 2017, either as their first IFX or transitioning from treatment with IFX reference or another IFX biosimilar. Outcome measures include SB2 dose, disease activity scores and persistence on SB2, over time and up to 24 months after initiation. This interim analysis is the first complete analysis of 12 month data on all rheumatology patients enrolled into the study at 9 specialist sites and followed up to the data extract date of 29th October 2020. The analysis provides an overview of baseline characteristics, disease scores, SB2 dose and persistence at 12 months post-initiation of SB2.Results:Table 1.Mean Disease Activity Score-28 erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) over the course of ICHIBAN. BL, baseline; SD, standard deviation.axSpA cohort(N=336;IFX naïve 81, IFX-prior 255)RA cohort(N=98;IFX naïve 22, IFX-prior 76)PsA cohort(N=62;IFX naïve 14, IFX-prior 48)Baseline characteristicsAge in years, mean (SD):IFX-naïve43.1 (11.1)53.1 (15.9)48.5 (12.2)Transitioned from IFX48.9 (12.4)57.3 (13.1)53.1 (13.0)Disease duration in years, mean (SD):IFX-naïve7.2 (9.3)11.3 (9.8)4.2 (3.9)Transitioned from IFX16.6 (11.6)17.3 (8.8)12.9 (11.3)Women, n (%):IFX-naïve26 (32.1)16 (72.7)6 (42.9)Transitioned from IFX79 (31.0)60 (78.9)15 (31.3)SB2 Dose: n, mean mg/kg (SD)IFX-naïve:Baseline81383.8 (85.5)22266.2 (145.9)14395.4 (108.9)Month 1247436.8 (153.3)13285.5 (90.7)6508.0 (147.6)Transitioned from IFX:Baseline255396.7 (109.6)76291.8 (103.4)48408.5 (91.3)Month 12195392.1 (105.5)60287.8 (106.6)41421.4 (101.6)Disease score, mean (SD)IFX-naïve:nBASDAInDAS28nDAS28Baseline545.8 (2.1)144.3 (1.6)-*-*Month 12303.5 (2.7)93.2 (1.2)Transitioned from IFX:Baseline2063.0 (2.0)622.6 (1.2)202.2 (1.2)Month 121513.0 (2.1)472.7 (1.2)192.1 (0.9)KM estimate of persistence on SB2 by Month 12; proportion, (95% CI)IFX-naïve56.26 (44.43; 66.51)59.09 (36.10; 76.21)64.29 (34.33; 83.31)Transitioned from IFX79.86 (74.37; 84.30)80.26 (69.42; 87.60)85.04 (71.11; 92.58)*Blank as disease score data for both baseline and Month 12 were provided by a single patient who was IFX-naïve and had PsA; IFX = infliximab; axSpA = Axial Spondyloarthritis; RA = Rheumatoid Arthritis; PsA = Psoriatic Arthritis; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; DAS28 = Disease Activity Score 28; CI = confidence interval; SD = standard deviation; KM = Kaplan Meier.Conclusion:This 12-month analysis indicates that patients with axSpA or RA can be successfully initiated on SB2 as the first infliximab therapy, and patients with axSpA, RA or PsA can be transitioned from originator or biosimilar IFX to SB2 without loss of disease control and with no dose penalty over 12 months post-transition. Over 56% of IFX- naïve patients and over 79% of patients transitioned from prior IFX remained on SB2 at 12 months post-initiation. With follow-up of patients ongoing to 24 months post-initiation of SB2, the study will continue to provide pertinent information about clinical outcomes of initiation on SB2 as first IFX or after transition from reference or IFX biosimilar to SB2.Acknowledgements:Data management for the study was provided by Sanoïa E-health services, Digital CRO, Gémenos, France; funding was provided by Biogen International GmbH.Disclosure of Interests:Bruno Fautrel Speakers bureau: AbbVie, Biogen, Boehringer-Ingelheim, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, SOBI, UCB., Consultant of: AbbVie, Biogen, Boehringer-Ingelheim, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, SOBI, UCB., Grant/research support from: AbbVie, MSD, Pfizer., Yoram Bouhnik Speakers bureau: AbbVie, Biogaran, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoly Spindler, Merck, Merck Sharp & Dohme, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB, Vifor Pharma., Consultant of: AbbVie, Biogaran, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoly Spindler, Merck, Merck Sharp & Dohme, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB, Vifor Pharma., Maxime Dougados Grant/research support from: Biogen, Ulrich Freudensprung Shareholder of: Biogen, Employee of: Biogen, Janet Addison Shareholder of: Biogen, Employee of: Biogen

Background: UK NICE guidance recommends initiation of tumour necrosis factor-alpha inhibitor (TNFi) for patients with severe RA unresponsive to intensive therapy with conventional disease-modifying anti-rheumatic drugs (cDMARD). Data comparing cDMARD and TNFi in clinical trial settings are common, but there is limited published real-world evidence on their comparative effectiveness. Objectives: Compare disease status and outcomes in UK patients with RA receiving cDMARD vs TNFi. Methods: Data derive from Adelphi’s RA Disease Specific Programme 2017, a cross-sectional survey of 49 UK rheumatologists providing information on demographics, disease history, disease status and treatment of patients with RA. All patients (n=640) were included in the RA treatment analysis; patients were included in the comparative analysis if at the time of survey they had been receiving current treatment for at least 3 months, with either cDMARD (and had never received biologic(b)DMARD), or a TNFi (and had never received prior bDMARD). A propensity score based on BMI, duration on current therapy, RA severity and disease duration at initiation of current therapy was used to match treatment groups. Using Abadie-Imbens standard errors, clinical characteristics and measures of disease activity were compared between the matched groups. Results: Current therapy of 640 patients: 379 (59.2%) bDMARD, of which 253 (66.8%) were receiving TNFi; 212 (33%) cDMARD; 18 (2.8%) had never received any DMARD, 15 (2.3%) had discontinued bDMARD. Mean DAS28 at initiation of therapy was 4.94 in overall cDMARD and 5.77 in TNFi groups. Table 1 shows the comparative analysis of cDMARD vs TNFi matched treatment groups. The cDMARD group had a higher proportion of moderate/severe and active/very active disease at time of survey, a higher proportion of patients in this group had no improvement in disease severity or activity since initiation of current therapy, and they were less likely to have achieved a EULAR response. A higher proportion of cDMARD patients and physicians were not satisfied with their disease control. Mean DAS28 scores at time of survey had declined from time of initiation of therapy to time of survey in matched cDMARD vs TNFi groups, from 5.27 to 3.1 vs 5.77 to 2.7 respectively. Conclusions: UK patients with RA receiving cDMARD have poorer outcomes, in terms of measured disease status and control, than their matched counterparts receiving TNFi. Despite having a higher mean DAS score at initiation, patients in the TNFi group had a lower mean score at time of survey than patients receiving cDMARD. This real-world evidence highlights the continued utility of TNFi as effective treatments for patients with RA. Potential benefit of early TNFi initiation merits further research. Disclosure of Interest: J. Addison Shareholder of: Biogen, Employee of: Biogen, S. Lobosco Employee of: Adelphi Real World, B. Hoskin Employee of: Adelphi Real World, E. Sullivan Employee of: Adelphi Real World, J. Pike Employee of: Adelphi Real World, S. Fenwick Shareholder of: Biogen, Employee of: Biogen

High body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007-2009 (312 facilities; 15 European countries) with ≥3 months of follow-up. Patients were classified by presence (n=3231) or absence (n=2673) of inflammation (C-reactive protein ≥10 mg/l and/or albumin ≤35 g/l). Patients were divided into quintiles by BMI (Q1-Q5: 24.0-26.4, >26.4-29.8, and >29.8 kg/m(2), respectively). Noninflamed patients in BMI Q5 formed the reference group. During a median follow-up period of 36.7 months, 1929 deaths occurred (822 cardiovascular), with 655 patients censored for renal transplantation and 1183 for loss to follow-up. Greater mortality was observed in inflamed patients (P

Background Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD). Methods In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded. Results A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5 %) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0 %), gastroenteritis (6.0 %), and hypertension (4.1 %). Six patients (1.9 %) died (unrelated to DA). Four patients (1.3 %) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4–2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2–11.7 g/dl, respectively. Overall, 48 patients (15.0 %) received ≥1 transfusion. Conclusions No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.

Background: Familial hypercholesterolaemia (FH) is a genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease (CVD). This retrospective observational study examined the clinical characteristics and management of FH subjects in Bulgaria over a 12-month period. Materials and methods: Twelve cardiology sites participated in this study from May 2015 to May 2016. Eligible subjects had at least two routine low-density lipo-protein cholesterol (LDL C) measurements and a prescription for lipid-lowering therapy (LLT) at the start of the observation period. Mean values for gender, age and cardiovascular (CV) event history at baseline and LDL-C over time were estimated. Results: Of the 220 eligible subjects, 196 fulfilled the criteria for FH diagnosis: 27 definite, 94 probable and 75 possible. Mean age at enrolment was 54.4 years and 64.1% of subjects were male. Mean CV risk classification at baseline was 26.8% high-risk (HR) and 73.2% very high-risk (VHR). Mean LDL-C was 5.6 mmol/L at enrolment and 4.1 mmol/L at last observation visit (12 months). The ESC/EAS Guideline LDL-C targets (applicable at the time of the study) were achieved by 14.5% of HR and 5.0% of VHR subjects. Most subjects (n=219) received statins. One subject was statin intolerant (ezetimibe therapy). Intensive statin treatment (atorvastatin 40–80 mg/daily and rosuvastatin 20–40 mg/daily) was used in 38.6% of individuals during the observation period and 10% of subjects received combination therapy (statin plus ezetimibe or other LLT). Conclusions: Most subjects with FH do not reach the ESC/EAS defined LDL-C targets. Early identification and physician education may improve FH management.

Introduction There is scant real-world information on switching treatment for anemia associated with chronic kidney disease (CKD) from methoxy polyethylene glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi-center, observational study designed to describe the time course of hemoglobin (Hb) concentration (primary outcome measure) and other parameters of clinical management of anemia in European hemodialysis patients in clinical practice before and after a switch from PEG-Epo to DA. Methods Eligible subjects were adult patients with CKD dialyzed at European dialysis centers for ≥26 weeks and treated with PEG-Epo for ≥14 weeks immediately prior to being switched to DA and no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb values were recorded for the 14-week pre-switch and 26-week post-switch periods. Results Of the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7 European countries, 785 were included in analyses. Mean (95% confidence interval [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and 11.29 (11.20, 11.37) g/dL at month −1 pre-switch and months 3 and 6 post-switch, respectively. The geometric mean (95% CI) PEG-Epo dose at month −1 was 27.4 (26.0, 28.8) µg/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6 (24.1, 27.1) µg/week at months 1, 4, and 6, respectively. The geometric mean (95% CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio categories 1.2 at switching, mean DA dose and Hb converged within narrow ranges by month 6 post-switch: 23.9–27.0 µg/week and 11.1–11.5 g/dL, respectively. Hb excursions

Background Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naive subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naive patients.

Introduction There is limited information published on switching erythropoiesis-stimulating agent (ESA) treatment for anemia associated with chronic kidney disease (CKD) from darbepoetin alfa (DA) to methoxy polyethylene glycol-epoetin beta (PEG-Epo) outside the protocol of interventional clinical studies. AFFIRM (Aranesp Efficiency Relative to Mircera) was a retrospective, multi-site, observational study designed to estimate the population mean maintenance dose conversion ratio [DCR; dose ratio achieving comparable hemoglobin level (Hb) between two evaluation periods] in European hemodialysis patients whose treatment was switched from DA to PEG-Epo. Methods Eligible patients had received hemodialysis for ≥12 months and DA for ≥7 months. Data were collected from 7 months before until 7 months after switching treatment. DCR was calculated for patients with Hb and ESA data available in both evaluation periods (EP; Months 1 and 2 were defined as the pre-switch EP, and Months 6 and 7 as the post-switch EP). Red blood cell transfusions pre- and post-switch were quantified. Results Of 302 patients enrolled, 206 had data available for DCR analysis. The geometric mean DCR was 1.17 (95% CI 1.05, 1.29). Regression analysis indicated a non-linear relationship between pre- and post-switch ESA doses; DCR decreased with increasing pre-switch DA dose. The geometric mean weekly ESA doses were 24.1 μg DA in the pre-switch EP and 28.6 μg PEG-Epo in the post-switch EP. Mean Hb was 11.5 g/dL in the pre-switch EP and 11.4 g/dL in the post-switch EP. There were 16 transfusions and 34 units transfused in the pre-switch period, versus 48 transfusions and 95 units transfused post-switch. Excluding patients receiving a transfusion within 90 days of or during either EP, the DCR was 1.21 (95% CI 1.09, 1.35). Conclusion In these hemodialysis patients switched from DA to PEG-Epo the DCR was 1.17 and 1.21 after accounting for the effect of transfusions. The number of transfusions and units transfused increased approximately threefold from the pre-switch to the post-switch period.

Background. Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population. Methods. Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible. Retrospective and/or prospective data including haemoglobin levels and erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before and 12 months after DA initiation. Mean Hb levels were calculated every 3 months, and ESA dose was converted to a geometric mean weekly DA equivalent dose and summarized monthly. Results. Data from 4278 patients showed that patients receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence interval) Hb level of 11.9 g/dL (11.8–12.0 g/ dL) at initiation and 11.6 g/dL (11.6–11.7 g/dL) at Months 10–12, with mean ESA dose of 22 lg/week (21–23 lg/week) prior to initiation, 16 lg/week (15–16 lg/week) at initiation and 16 lg/week (15–16 lg/week) at Month 12. In ESA-naive patients, Hb levels increased from 10.3 g/dL (10.2–10.3 g/dL) at initiation to 11.7 g/dL at Months 4–6 and were maintained at a mean level of 11.7 g/dL (11.7–11.8 g/dL) at Months 10– 12, with mean ESA dose of 16 lg/week (16–17 lg/week) at initiation and 16 lg/week (16–17 lg/week) at Month 12. In the 85% of patients receiving DA at extended intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA-related adverse reactions. Conclusion. DA Q2W/QM was an effective treatment of anaemia in the general CKD-NoD patient population and a dose increase was not required in patients switching from a previous ESA regimen.