Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria.

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.