AB1209 A SYSTEMATIC REVIEW ON THE EFFECT OF DMARDS ON FERTILITY IN RHEUMATOID ARTHRITIS
Authors: L. Brants, I. Soenen, S. Pazmino, R. Westhovens, P. Verschueren, D. De Cock
Journal: Annals of the Rheumatic Diseases (2020)

Background: Patients with rheumatoid arthritis (RA) seem to experience a diminished fertility. Reasons for this lowered fertility are insufficiently defined and probably multifactorial. Although the effect of DMARDs on pregnancy outcomes have been studied, there is a lack of data on the effect of DMARDs on the fertility of patients with RA. Objectives: To evaluate all studies that concern an effect of DMARDs on the fertility of men and women with RA in a systematic review. Methods: A search was conducted at 18/10/2019 in three databases including Embase, Pubmed (Medline) and Web Of Science with specific search strings for each database, constructed with the help from a health sciences librarian. We included studies involving women or men diagnosed with RA, of fertile age (18-45years) and on a DMARD therapy, with as outcome a fertility parameter. Systematic reviews, meta-analyses, case reports, case series and animal studies were excluded. Studies not in English or Dutch or written more than 15 years ago were excluded. Article selection was firstly based on title/abstract (double blind, two researchers, LB and IS) and then full text (two researchers, LB and IS). In case consensus could not be reached, a third researcher (DDC) was consulted. The references of included articles were reviewed (“snowballing”) to include and minimize the missing articles. A quality check of the included full text papers was performed using the CASP Appraisal Checklists. A chart was made based on outcomes of interest. Results: After duplicate removal, 9030 articles were found. After title/abstract screening, 82 articles remained. After full text screening, 4 articles could be retained. No additional studies were found through snowballing. Only studies about women could be included, as the evidence found for men was all in papers with exclusion criteria for our systematic review (e.g. case reports). Table 1 summarizes these papers. The included studies investigated the following DMARDs: methotrexate (MTX), certolizumab pegol (CZP), etanercept (ETN) and sulfasalazine (SSZ). No detrimental effects of these DMARDs on fertility, defined as time-to-pregnancy (TTP), anti-Müllerian hormone serum level or presence of a history of infertility, were reported. Table 1. Characteristics of studies included in the systematic review Authors Location Sample DMARD Outcome Method Design Result Akintayo et al. 2018 Nigeria 50 women with RA and 50 women without RA MTX Infertility or history of infertility Interviewer-administered questionnaire Retrospective study MTX was associated with a negative history of infertility Shimada et al. 2019 Japan 25 pregnancies in 19 patients with RA CZP and ETN TTP (time to pregnancy) medical records Retrospective study bDMARD treatment shortened the TTP Brouwer et al. 2013 The Netherlands 72 women with recent-onset RA compared to 509 healthy women MTX Level of serum AMH medical records, serum samples (2 time points) Retrospective study AMH levels were not lower with MTX. Brouwer et al. 2014 The Netherlands 245 women with RA MTX and SSZ TTP Questionnaires and interviews Prospective cohort study MTX and SSZ did not prolong TTP RA = Rheumatoid Arthritis; MTX = Methotrexate; TNFi = Tumor Necrosis Factor inhibitor; CZP = Certolizumab pegol; ETN = Etanercept; SSZ = Sulfasalazine; TTP = Time to Pregnancy; DMARD = Disease Modifying Antirheumatic Drug; AMH = Anti-Müllerian hormone Conclusion: This systematic review underlines the knowledge gap on the effect of DMARDs on fertility in human studies. Only 4 studies on women, and no studies on men were found. In the 4 included studies, DMARD treatment, even with MTX in contrast to general belief, had no harmful effect on fertility, probably because disease activity was better controlled with DMARD therapy. However, effects of other RA medication such as NSAIDs were excluded. More research is needed to improve guidance for patients with RA with a child wish. Disclosure of Interests: Liesbeth Brants: None declared, Isaline Soenen: None declared, Sofia Pazmino: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Diederik De Cock: None declared