FRI0160 Certolizumab PEGOL did not result in a decrease in semen quality in healthy volunteers: Results from a phase 1 study:
Authors: S. Perrier d’Hauterive, S. Kesseler, P. Ruggeri, M. Timmermans, O. Gaspard, T. Kumke, G. Parker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Effective anti-TNF treatment in large doses may affect sperm count and reduce fertility.<sup>1,2,3</sup> More controlled clinical studies to investigate effects of anti-TNF agents on semen quality are required. <h3>Objectives</h3> To examine the effect of a single dose of certolizumab pegol (CZP) on the semen quality of healthy subjects, to identify the intra- and inter-subject variability in semen quality variables at baseline, and to investigate the safety and tolerability of CZP treatment. <h3>Methods</h3> 20 healthy males were included in this phase 1, single-centre, double-blind, placebo (PBO)-controlled study (NCT01091220). Subjects were randomized in a 3:1 ratio to receive CZP 400mg (2x200mg subcutaneous injections) or PBO. A screening period (up to 3 weeks) was followed by a 14 week follow up period after the day of dosing. Primary variables for assessment of semen included total motility and morphology (% of normal ovoid forms by Tygerberg criteria<sup>4</sup>). Treatment effects were assessed using a linear repeated measures model. A mixed effect model (visit - fixed effect; subject - random effect) was applied to the screening data to assess intra- and inter-subject variability. Safety of CZP was evaluated by the number of adverse events (AEs) and routine biochemistry and haemotology laboratory analyses. <h3>Results</h3> Highest intra-subject variability was found in non progressive motility, spermatozoa count and concentration (66.2%, 43.9% and 36.2%, respectively). Highest inter-subject variability was detected in spermatozoa count, concentration, semen volume and morphology (61.7%, 52.2%, 45.4% and 36.3%, respectively). CZP treatment was found to have no effect on the semen quality variables assessed vs PBO (Table). The changes in semen quality variables during the treatment period were generally within the range of intra- and inter-subject variability seen during screening. The reporting of AEs was broadly similar between the two arms. No AEs were regarded as serious or led to discontinuation from the study. <h3>Conclusions</h3> Considerable intra- and inter-subject semen quality variability exists in healthy male subjects. A single 400mg CZP dose was well tolerated and did not produce any treatment effects on semen quality in healthy males compared to PBO. <h3>References</h3> Pentikainen et al. J Clin Endocrinol Metab. 2001;86(9):4480-82. Suominen et al.Eur J Endocrinol. 2004;151(5):629-40 2004. Mahadevan et al. Inflamm Bowel Dis. 2005;11(4):395-9. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. Geneva: World Health Organization Press; 2010. <h3>Disclosure of Interest</h3> S. Perrier d'Hauterive Grant/Research support from: UCB Pharma, S. Kesseler Grant/Research support from: UCB Pharma, P. Ruggeri Grant/Research support from: UCB Pharma, M. Timmermans Grant/Research support from: UCB Pharma, O. Gaspard Grant/Research support from: UCB Pharma, T. Kumke Employee of: UCB Pharma, G. Parker Employee of: UCB Pharma