Fertility in male patients with seronegative spondyloarthropathies treated with infliximab

Abstract

Objectives

The majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years. Tumor necrosis factor (TNF)α plays a pivotal role in the pathogenesis of both diseases. Today, anti-TNFα blockers are an essential treatment for these patients. To identify male patients who achieved pregnancy development during their management with anti-TNFα blockers (infliximab).

Methods

We reviewed the data of 65 patients with AS and 30 patients with PsA who were followed-up in our rheumatology outpatients clinic and they were on infliximab therapy between January 2001 and December 2010.

Results

We identified overall seven male patients with AS and three male patients with PsA who had fathered 14 healthy infants. Moreover, we recognized one man with PsA who was on infliximab and on concomitant therapy with MTX at the time of conception, whose wife had to proceed to therapeutic abortion due to congenital abnormalities of the fetus (hydrocephalia), while she was on the first trimester of pregnancy.

Conclusions

We described male patients with AS and PsA who demonstrated no fertility problems while they were on infliximab treatment. The data designated in this report provide some supportive evidence for the safe use of infliximab in male patients who are affected of those inflammatory diseases during their peak reproductive years.

Introduction

The majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years [1], [2], [3], [4], [5], [6], [7]. The fertility status and sexual function of patients with AS have been explored in several studies and controversial results have been obtained [8], [9], [10]. In testis, tumor necrosis factor (TNF)α is produced by germ cells and it has a role in the regulation of spermatogenesis [11]. TNFα levels are usually low in seminal plasma, but they tend to increase in inflammatory and infectious diseases. Spermatozoa exposed to pathological concentrations of TNFα can result in significant loss of their functional and genomic integrity [12]. TNFα blockers are indicated for the treatment of rheumatoid arthritis, Crohn's disease, AS, PsA, psoriasis and ulcerative colitis [13], [14], [15]. Infliximab, a chimeric IgG1 monoclonal antibody against TNFα is pregnancy category B according to the US Food and Drug Administration Classification. A growing body of evidence supports the notion that infliximab is low risk in pregnancy [16], [17]. However, more recently data on anti-TNFα use in pregnancy from 1999 to date have been published [18]. According to these data, congenital abnormalities were observed in 7 to 10% of children born to mothers taking anti-TNFα antagonists whilst pregnant.

Increasingly, men with spondyloarthropathies (SpAs) are concerned about fertility and other issues of reproductive health. Limited data have been published concerning the effects of infliximab on semen quality [19] and, thus, fertility and the reproductive ability. We have previously reported four cases of male patients with AS who were treated with infliximab and had fathered healthy infants while they were on therapy with infliximab [20]. In this report, we describe seven additional patients who achieved pregnancy development during their disease management with infliximab.