Ashraf Mikhail

Epoetin Biosimilars in Europe: Five Years On

Biosimilars have been developed for several biologic therapeutic agents, including erythropoiesis-stimulating agents (ESAs). However, biosimilars cannot be assumed to be completely identical to the reference product, nor can two different biosimilars of the same reference product be considered equivalent. Accordingly, standards for approving biosimilars are distinct from those for generic versions of conventional pharmaceuticals.By late 2007, two biosimilar epoetins (HX575 and SB309) had been approved by the European Medicines Agency (EMA), following a series of pharmacokinetic and pharmacodynamic equivalence studies, as well as phase 3 clinical comparability evaluations. Additionally, the results of a limited number of postauthorization interventional or observational studies and quality comparisons were published subsequently on both products.The reported differences in glycosylation profiles between these epoetin biosimilars and their reference product, as well as the lack of long-term safety and efficacy evaluation, could indicate a need to develop a more comprehensive analysis of the available data, and to evaluate the post-authorization real-life data, in order to gain a better understanding of any potential implications of molecular structural or formulation differences on longterm safety and effectiveness.Switching between an original reference ESA and a biosimilar (and possibly also switching between biosimilar versions of the same product) should be regarded as a change in clinical management. Clinicians need to be fully involved in such decisions. Prescribing by brand name will prevent unintentional substitution by pharmacists and allow for effective pharmacovigilance, in accordance with recent EU directives. In this review, the authors have analyzed most of the published information on the two epoetin biosimilars, HX575 and SB309, to highlight the points that healthcare providers may need to consider when assessing an epoetin biosimilar.

An unusual cause of hypertension and renal failure: a case series of a family with Alagille syndrome

Alagille Syndrome (OMIM 118450) is a multisystem developmental disorder inherited in an autosomal dominant pattern with variable expression. It commonly manifests in children with early cholestatic jaundice due to paucity of interlobular biliary ducts. Renal involvement is less common but can take various forms including renovascular disease, renal agenesis or hypoplasia, cystic renal disease, mesangiolipidosis, tubulointerstitial nephritis and renal tubular acidosis. We describe a family of Alagille syndrome with JAG 1 mutation running through at least two generations, affecting four members with variable phenotypic expressions and disease severity. Alagille syndrome should be considered in the differential diagnosis of adults with renovascular disease and children with agenesis/dysgenesis of kidney and reflux nephropathy even in the absence of hepatic disease. Renal transplant can be successful in these patients although living related donation may not be appropriate given the high penetrance and variable expression of this condition. This syndrome may cause symptomatic bradyarrhythmias as described in our series.

Renal Association Clinical Practice Guideline on Anaemia of Chronic Kidney Disease

This clinical practice guideline provides recommendations on the management of anaemia of chronic kidney disease (CKD) and serves as an update of the 4th edition module published online in 2007. The recommendations in this update have been graded using the modified GRADE system to indicate both the strength of each recommendation (strong or weak) and level of evidence for the recommendation (A–D) [1, 2]. As in the previous module The Renal Association (RA) endorses the NICE Guidelines for Anaemia Management in Chronic Kidney Disease (CKD) 2006 [3]. These guidelines are an updated version of the previous ‘Complications of CKD Guidelines – Anaemia Section’. For this updated version, a systematic literature review was performed using MEDLINE & PUBMED, focusing on the topics of: