Pregnant Women With IBD Are More Likely to be Adherent to Biologic Therapies Than Other Medications

Sangmin Lee; Cynthia H. Seow; Kamala Adhikari; Amy Metcalfe

Disclosures

Aliment Pharmacol Ther. 2020;51(5):544-552. 

In This Article

Discussion

In this retrospective population-based observational cohort study using the linked health administrative databases in Alberta, Canada, we examined whether medication adherence pattern for pregnant women with IBD differed by drug class during pregnancy and influenced neonatal outcomes or health care utilisation after delivery. Approximately, a quarter of pregnant women with IBD who were previously adherent to their maintenance IBD medications during the year prior to pregnancy were not adherent or discontinued their IBD medications during pregnancy. Although the reasons for medication non-adherence in women with IBD during pregnancy were not assessed in our study, based on existing literature, this large proportion of medication non-adherence is likely attributable to women's negative perspectives on the impact of IBD medications and concerns about adverse foetal outcomes associated with the use of medication.[14,15,23] Compared to a self-reported survey completed by women with IBD who were pregnant or were attempting to conceive in a study conducted in Ontario, Canada, the rate of non-adherence in our study based on administrative health databases was lower than the self-reported 46.5% rate of non-adherence.[24] The differences in the non-adherence rate may be attributable to biases in the self-reported answers from women with IBD compared to using administrative health databases, which records information for billing purposes on day-to-day basis. In a study that assessed medication adherence pattern using administrative health databases in pregnant women with one or more autoimmune diseases (where women with IBD represented 33.8% of the total sample, in British Columbia, Canada), the rate of non-adherence or discontinuation was similar (31%) to our results.[25]

Our study is the first to demonstrate that medication adherence pattern during pregnancy differs by the class of maintenance IBD medication prescribed; women were more likely to be adherent to biologic therapy than thiopurines or 5-aminosalicylates, although not statistically significant. Furthermore, our results showed that the rate of adherence to biologic therapy was higher in the first and third trimesters, but similar to thiopurines and 5-aminosalicylates in the second trimester, where women were more non-adherent to their IBD medications when compared to the first and third trimesters. This may reflect lack of pregnancy awareness in the first trimester and potentially an increase in disease flares necessitating increased adherence later in pregnancy. Furthermore, the increased adherence to biologic therapy in pregnant women with IBD may potentially be due to the route of administration as parenteral administration of biologic therapy (ie, subcutaneous or intravenous infusion of anti-TNF agents in out-patient clinics or hospital facilities) involves frequent monitoring and clinical visits with a health care providers.[26] Furthermore, inherent characteristics of these patients (ie, a history of moderate-to-severe disease necessitating the biologic therapy initially, and the associated risk of disease relapse on discontinuing biologics) may increase medication adherence in pregnant women with IBD who are on biologic therapies.[27] Future studies evaluating women's perspectives on the role of medical therapy during pregnancy (stratified by drug class) and the effect of preconception counselling in women with IBD are needed to further understand factors that may potentially influence the attitudes and beliefs of IBD medication adherence during pregnancy for women with IBD.

Another new finding from this study showed that infants born to mothers who were adherent to their medications during pregnancy were at a greater risk of being admitted into the neonatal intensive care unit when compared to women without IBD. We observed a similar trend for women with IBD who were not adherent to their maintenance IBD medications, but did not find a significant association potentially due to small sample size. A published study from a multidisciplinary high-risk clinic in a tertiary, university-affiliated medical centre compared the rate of admission into the neonatal intensive care unit in infants of women with IBD compared to infants of women without IBD.[28] In this study, similar to ours, the rate of admission into the neonatal intensive care unit was significantly increased in women with IBD compared to women without IBD (10.7% vs 4.0%).[28] However, this study did not mention the adherence pattern of medication for women with IBD during pregnancy. Lack of data on important confounders is a common limitation of administrative data and thus, our results should be interpreted with caution, as the E-value analysis demonstrates that a moderate unmeasured confounder (RR = 2.54) could change this result. Further studies are needed to understand if admission into the neonatal intensive care unit results from medication non-adherence secondly to sub-optimally controlled IBD or whether other confounding effects are influencing this association.

Medication adherence during pregnancy did not significantly influence neonatal length of stay at hospitals indicator of adverse outcomes or preterm birth for women with IBD. Correspondingly, the current literature showed no association between biologic therapy[29,30] or 5-aminosalicylates[31] on adverse pregnancy outcomes including preterm birth, low birth weight and congenital anomalies. For thiopurine exposure during pregnancy, conflicting evidence exists.[32–34] Broms et al observed increased risk of preterm birth with exposure to thiopurines during pregnancy in both women with stable or flaring disease;[10] other studies have shown no increased risks of spontaneous abortion, preterm birth or low birth weight with thiopurine exposure during pregnancy.[35,36] These studies, however, only showed exposure of medication during pregnancy and did not consider adherence, which could have resulted in conflicting results. Information on pregnancy and birth outcomes of medication adherence during pregnancy may potentially be helpful for women as they weigh the risks and benefits of either continuing their maintenance IBD medications throughout pregnancy to facilitate disease remission.

This study has many strengths; this population-based study utilised a number of provincial administrative health databases linking the mother and infant. This allowed for the assessment of the effects of medication adherence in a select cohort, ie, pregnant women with IBD. Therefore, the findings from this study are likely generalisable to pregnant women with IBD across Canada and other developed countries. Further, the use of a validated case definition for IBD in administrative databases reduces the risk of misclassification bias. Lastly, we have shown how an unmeasured confounder (eg, disease activity, smoking status, income)[37,38] might be associated to the exposure (ie, women with IBD who were adherent and not adherent to maintenance medication) and the neonatal outcomes to fully explain the observed risks using the E-value analysis.

There are, however, limitations to this study. Due to small sample sizes, women who discontinued their medications were grouped together with women who were not adherent to medication (ie intermittent dosing). This heterogeneity in the exposure to medication during pregnancy may have potentially overestimated the association between medication adherence and adverse pregnancy outcomes. In addition to grouping discontinued and not adherent group together, we were unable to generate meaningful results on other adverse pregnancy outcomes, such as stillbirth and small-for-gestational age infants (10th percentile) due to the small number of events. Lastly, our definition for adherence to medication while valid,[19,20] overestimates medication adherence as it assumes that the prescription dispensed matched the patient's consumption; it does not account for patients who may potentially consume less than what is dispensed from community pharmacies.[39]

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