, Volume 71, Issue 17, pp 2327-2345
Date: 24 Sep 2012


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Eculizumab is a humanized monoclonal antibody indicated for the treatment of paroxysmal nocturnal haemoglobinuria (PNH). It binds specifically and with high affinity to the complement protein C5, thereby preventing the formation of the terminal complement complex C5b-9, which mediates cell lysis. In patients with PNH, eculizumab inhibits terminal complement mediated intravascular haemolysis.

In clinical trials of PNH patients, eculizumab reduced intravascular haemolysis compared with baseline and placebo, as determined by significantly decreased lactate dehydrogenase (LDH) levels. Significant reductions in LDH levels were achieved within the first week of treatment, with near normal levels achieved at week 2 and maintained throughout longer term treatment, including periods of up to 36 months. Eculizumab achieved rapid and sustained efficacy, regardless of baseline LDH levels or platelet counts.

In adults with PNH, eculizumab treatment for 26 weeks achieved stabilization of haemoglobin levels in significantly more patients than placebo treatment, and reduced the requirement for packed red cell transfusions to a significantly greater extent than placebo. Half of all patients in the eculizumab group became transfusion independent compared with no patients in the placebo group. Eculizumab was also associated with significant improvements in fatigue and health-related quality-of-life scores in several trials. Over the long term, the survival of PNH patients treated with eculizumab was normalized.

Eculizumab was generally well tolerated in clinical trials of PNH patients, including treatment periods of up to 5.5 years. The risk of Neisseria meningitidis is increased with eculizumab and patients must be vaccinated prior to treatment and monitored throughout.

Thus, eculizumab, the first targeted terminal complement inhibitor, provides an effective and generally well tolerated treatment for PNH patients, who have previously been without adequate treatment options.

Various sections of the manuscript reviewed by: R.A. Brodsky, Division of Hematology, John Hopkins School of Medicine, Baltimore, MD, USA; J.-C. Davin, Emma Children’s Hospital-Academic Medical Centre, Amsterdam, the Netherlands; Queen Fabiola Academic Children’s Hospital, Free University of Brussels, Brussels, Belgium; R. Kelly, Department of Haematology, Leeds Teaching Hospitals, Leeds, UK; G.D. Simonetti, Division of Pediatric Nephrology, Children’s Hospital, University of Bern, Bern, Switzerland.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘eculizumab’ was identified by searching databases (including MEDLINE, EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘eculizumab’ and (‘hemoglobinuria, paroxysmal’ or ‘paroxysmal nocturnal hemoglobinuria’ or ‘paroxysmal nocturnal haemoglobinuria’). Searches were last updated 3 November 2011.
Selection: Studies in patients with paroxysmal nocturnal haemoglobinuria who received eculizumab. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Eculizumab, paroxysmal nocturnal haemoglobinuria, pharmacodynamics, pharmacokinetics, therapeutic use.