Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence

Abstract

There is limited evidence relating to the impact of disease modifying anti-rheumatic drugs (DMARDs) upon male fertility and peri-conception paternal exposure in men with rheumatic disease. Therefore, we conducted a systematic review of available evidence to update information on this subject and guide paternal counselling. A systematic search of PubMed and Embase was carried out up to September 2017, to find relevant peer-reviewed papers, using keywords for fertility/spermatogenesis/conception, men, and disease modifying or biologic drugs commonly prescribed in patients with rheumatic disease. The search yielded 724 papers, and the titles/abstracts were screened independently by 2 authors, duplicates removed and 233 potentially relevant papers selected for full text review. A total of 84 papers were included in the final analysis which covered the impact on fertility of over 611 male exposures to relevant drugs, and over 5986 pregnancies conceived during paternal exposure to (or within 3 months of stopping) these drugs. Aside from the known adverse impact of cyclophosphamide and sulfasalazine on spermatogenesis, overall there was no firm evidence of harm to fertility or pregnancy outcomes with paternal exposure to anti-TNF therapies, abatacept, rituximab, azathioprine, cyclosporine A, hydroxychloroquine, leflunomide, methotrexate or mycophenolate mofetil. There was no evidence found pertaining to the effects of male exposure to IVIG, tacrolimus, golimumab, anakinra or belimumab on fertility or pregnancy outcomes. These results provide further reassurance as to the safety of many DMARDs for men trying to conceive and will be useful when counselling men about risks of anti-rheumatic drugs to fertility and pregnancies, and following accidental conception.

The exposure to biologic and targeted synthetic disease-modifying antirheumatic drugs in pregnancy and lactation

“…Moreover, based on the analysed literature, the authors prove that there are no solid data confirming the negative effect of TNF-αi, rituximab and abatacept on fertility and an increased number of complications due to paternal exposure [ 54 ].…”

Practical recommendations for systemic treatment in psoriasis according to age, pregnancy, metabolic syndrome, mental health, psoriasis subtype and treatment history (BETA‐PSO: Belgian Evidence‐based Treatment Advice in Psoriasis; part 1)

“…On the use of biologics (TNF inhibitors, IL17 blockers, IL17 receptor blocker and IL23 blockers) in males wishing to conceive, there is currently no clear evidence pointing to an increased risk 22 …”

“…21 On the use of biologics (TNF inhibitors, IL17 blockers, IL17 receptor blocker and IL23 blockers) in males wishing to conceive, there is currently no clear evidence pointing to an increased risk. 22 Mental health Psychiatric disorders. Patients with psoriasis are more affected by depression, anxiety, suicidal ideation behaviour (SIB), lack of confidence, insomnia and poor quality of life (QOL), and we also know that these symptoms are reduced with effective treatment in these patients.…”

Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases

“…(424) However, there are no clear human data of a negative effect of mycophenolate on gonadal function or fertility. Favorable outcomes are seen in pregnancies fathered by men who underwent transplantation and are taking MPA-inclusive immunosuppressants, (425,426) although more data are needed.…”