Successful Pregnancy of a Patient with Cystic Fibrosis Genotype F508del/ F508del and Progressed Pulmonary Destruction on lumacaftor/ivacaftor

Outcomes of pregnancy in women with cystic fibrosis (CF) taking CFTR modulators – an international survey

“…We present the first and largest case series of the outcomes of pregnancy in women with CF taking CFTR modulators throughout part or the entirety of their pregnancy. We are aware of 5 previously published case reports of pregnancies in women with CF taking CFTR modulators [17][18][19][20][21] . In the first case, a 25-year old woman with G551D/3272-26A > G CF and normal lung function conceived while taking IVA and therapy was continued throughout pregnancy [18] .…”

“…This data showed that both LUM and IVA traversed the placenta and that LUM concentrations in the cord plasma sample were higher than in maternal plasma. In the fourth case, a 29-year old with F508del homozygous CF became pregnant having taken LUM/IVA for 10 months and the combination treatment was discontinued at 10 weeks gestation due to potential concerns regarding safety of CFTR modulators in pregnancy [21] . However, LUM/IVA was restarted at 15 weeks gestation due to deterioration of the mother's clinical status and was continued during the remaining pregnancy, with no evidence of adverse effects.…”

“…The small number of individual case reports currently published for women who chose to continue or discontinue CFTR modulators during pregnancy [17][18][19][20][21] makes it difficult for health care providers and for women with CF to make evidence-based decisions when making the important choice to continue or interrupt therapy with CFTR modulators for pregnancy. In order to provide further evidence on the safety of CFTR modulators, we conducted a survey of CF clinicians in the USA, UK, Europe, Israel and Australia in order to identify and describe pregnancy outcomes for women with CF who became pregnant while taking CFTR modulators.…”

CFTR Modulators: Impact on Fertility, Pregnancy, and Lactation in Women with Cystic Fibrosis

“…While ivacaftor, tezacaftor, and elexacaftor, given at maternally toxic doses, caused minor abnormalities (decreased body weight in rats given ivacaftor at 7 times the MRHD, decreased body weight, delayed pinna attachment and eye opening in rabbits given tezacaftor at 1 times the MRHD, and decreased body weight in rats given ≥4 times the MRHD), none of the approved modulators impacted organogenesis at normal human doses [ 35 , 36 , 37 , 38 ] ( Table 1 ). Although this animal data is reassuring, because of the lack of data in pregnant women, caution is advised for use in pregnancy, and some clinicians have advised women to discontinue use of modulators during pregnancy [ 40 , 41 , 43 , 44 , 45 ].…”

“…There are no studies of the use of CFTR modulators in pregnant women with CF; however, several case reports have appeared in the literature that include women who unintentionally and intentionally became pregnant while being treated with ivacaftor and lumacaftor/ivacaftor [ 39 , 40 , 41 , 43 , 44 , 45 , 46 ] ( Table 2 ). Of the six pregnancies reported in five women using ivacaftor, four of the infants were exposed to ivacaftor in all trimesters (the number of trimesters of exposure was not reported in one case, and in one case, a woman discontinued ivacaftor when it was determined that she was pregnant) [ 39 , 40 , 43 , 46 ].…”