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 21.5,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,0.001). In fully adjusted time-dependent analyses, the all-cause mortality risk in noninflamed patients was higher only in the lowest BMI quintile (hazard ratio [HR, 1.80 . Thus, whereas a protective effect of high BMI was observed in inflamed patients, this effect was mitigated in noninflamed patients.

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IntroductionThere 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.MethodsEligible 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.ResultsOf 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).ConclusionIn 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.

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.

Background SB2 is approved in the EU as infliximab (IFX) biosimilar, having demonstrated bioequivalence and similar efficacy, safety and immunogenicity as the reference. Little evidence is published on real-world use of SB2 in patients who are either IFX-naïve, or transitioned from originator or another IFX biosimilar. PERFUSE is an ongoing non-interventional study of 1,374 patients receiving SB2 as routine therapy at 12 gastroenterology sites across France, with objectives to describe clinical characteristics, immunogenicity and SB2 persistence over 12 months. Methods Eligible adult patients are diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) and initiated SB2 in routine clinical practice after September 2017 as their first IFX or transitioning from treatment with reference IFX or another IFX biosimilar. Data are captured from routine patient records for up to 12 months (M12) following initiation. Outcome measures include persistence on SB2, clinical characteristics at baseline (time of initiation of SB2) and disease scores (Harvey–Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI)) and SB2 dose over time. Results This interim analysis (IA) includes 755 patients (580 with CD; 59 IFX-naïve, 521 transitioned from prior IFX: 175 with UC; 33 IFX-naïve, 142 transitioned from prior IFX). In the 663 patients with prior IFX, no clinically relevant difference in disease score from baseline to M12 was observed; mean individual change was −0.3 (95% CI −0.8, 0.1) and -0.2 (95% CI −0.6, 0.3) in the CD cohort transitioned from reference IFX (n = 157) and biosimilar IFX (n = 83), respectively; −0.3 (−1.1, 0.4) and 0.0 (-0.9, 0.9) in the UC cohort transitioned from reference IFX (n = 41) and biosimilar IFX (n = 26), respectively. Mean (95% CI) SB2 dose (mg/kg), was similarly unchanged from baseline to M12: 7.2 (5.0, 10.0) and 7.6 (5.0, 10.0) in patients with CD transitioned from reference IFX or from biosimilar IFX; 7.0 (5.0, 10.0) and 7.3 (5.0, 10.0), 7.5 (5.0, 10.0) and 7.7 (5.0, 10.0) in patients with UC transitioned from reference IFX or biosimilar IFX, respectively. By data extraction date (23 October 2019), 374 patients with CD and 105 with UC had reached M12; persistence on SB2 was 92.2% (95% CI 89.1, 94.7) and 90.5% (95% CI 83.2, 95.3) in CD and UC, respectively. Reasons for discontinuation (n) were: adverse event (9), primary loss of response (7), secondary loss of response (12) and unspecified (16). Conclusion This IA indicates that patients with IBD can be successfully and safely transitioned from reference or biosimilar IFX to SB2, with no loss of disease control and without need for dose escalation. Over 90% of transitioned patients continued SB2 treatment at M12 post-initiation.