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RA: update for women of child bearing potential (and men!)

Fertility in the context of RMDs is a daily concern for a lot of rheumatologists and patients.

EULAR this year proposed new fertility data, especially in Rheumatoid Arthritis, along with an update of the EULAR points to consider for use of antirheumatic drugs in reproduction, pregnancy and lactation.

Treat to target and time to pregnancy

POS0436, presented by Quack and colleagues, looked into Time to Pregnancy (TTP) or the duration of time required for conception. Infertility corresponds to a TTP exceeding one year. The authors utilized data from the Pregnancy-induced Amelioration of RA (PARA) cohort (215 pts), which looked into risk factors for infertility in RA. High disease activity, daily nonsteroidal anti-inflammatory drug use and daily prednisone intake exceeding 7.5 mg were identified as being associated with a higher risk. This cohort was compared with data from the Preconception Counselling in Active RA (PreCARA) study (245 pts), which studied the effect of treat-to-target (T2T) on pregnancy outcomes. Women included were followed up more regularly and started on csDMARDs (sulfasalazine or hydroxychloroquine) and/or TNFi when needed. First, disease activity data: DAS28CRP was significantly lower in the PreCARA study 2.33 compared to 3.84 in PARA. In PARA over one in 3 patients did not take any medication during the preconception period; one out of 2 used GC with dose >7.5mg and only 3% used TNFi. On the opposite, in PreCARA, only 3% were unmedicated, 1 out of 5 patients treated w/ GCs and 1 out of 2 treated w/ TNFi. Interestingly, the median TTP in the T2T cohort was half (84 days) the TTP in the historical cohort (196 days). TTP exceeded 12 months in 23% of PreCARA patients compared to 42% in the PARA patients.

Does MTX affect the ovarian reserve?

A study presented by Rostom et al. (POS0041) suggested that women treated with MTX in RA had a more pronounced decrease in their ovarian reserve, measured with the levels of hormone antimuller as a surrogate for ovarian function. Interestingly, the age of the onset of MTX did negatively correlates with the hormone levels. Unfortunately, there did not seem to be any adjustment on the disease activity and other factors.

This highlights the importance of disease control in RA, during the conception period, and the need to achieve remission or LDA through frequent reviews and prescription of cs/bioDMARDs. The innocuity of some RA drugs for the fetus are now well demonstrated and have been summarized in the EULAR points to consider (PtC) for the use of antirheumatic drugs before pregnancy, and during pregnancy and lactation published in 2016.

The EULAR points to consider 2024 update

These guidelines have very recently been updated, with new data on biologic safety and paternal use and were presented at the ELAR recommendations session this year in Vienna. A total of 12 PtC for the use of antirheumatic drugs before and during pregnancy, 4 PtC for the use of antirheumatic drugs in lactation and 3 for the use of antirheumatic drugs in male patients were formulated.

The use of the following drugs was deemed compatible with pregnancy in women: synthetic DMARDs (azathioprine or mercaptopurine, chloroquine, colchicine, cyclosporine, hydroxychloroquine, sulfasalazine, and tacrolimus) and the use of all 5 TNFi (and also other MoA) is more permissive, due to a more favourable risk–benefit profile; while the use of NSAIDs glucocorticoids is presented with a more restrictive approach.

What about lactation?

During lactation, compatible drugs include azathioprine or mercaptopurine, celecoxib, chloroquine, colchicine, cyclosporine, hydroxychloroquine, IVIG, methylprednisolone pulses, non-selective NSAIDs (e.g., ibuprofen), prednisone and prednisolone, sulfasalazine, and tacrolimus and this was suggested along with a more permissive use of bDMARDs.

What about paternal treatment?

In males with RA looking to procreate; compatible options include azathioprine or mercaptopurine, colchicine, cyclosporine, hydroxychloroquine and chloroquine, IVIG, leflunomide, methotrexate (≤25 mg/week), mycophenolate, NSAIDs, prednisone and prednisolone, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. 


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