Unmasking Lupus Pregnancy: Adherence and Drug Monitoring Dilemmas Save

Risk of poor pregnancy outcomes in lupus patients continues to remain high, especially in the setting of high disease activity. Significant racial and ethnic disparities are also described in this population. About 2 or 3 decades ago, patients with lupus were advised against pregnancy to avoid adverse pregnancy outcomes, including maternal and fetal mortality. However, over time, with advances in therapeutics and better understanding of the disease, pregnancy is not discouraged (of course in the right setting only!). Now, patients are counseled to plan pregnancies when disease activity is low/ remission and lupus medications are switched to ones that are relatively safe in pregnancy. For example, patients on mycophenolate are switched to azathioprine or tacrolimus. While azathioprine and tacrolimus are recommended in specific SLE pregnancy scenarios, there is a lack of evidence to guide drug monitoring in this context.

Optimizing disease activity in pregnancy to prevent adverse fetal and maternal morbidity remain the key. 

Preliminary data from a lupus pregnancy LEGACY cohort presented at EULAR 2023 are alarming. This is a prospective lupus pregnancy cohort enrolling patients from seven international lupus clinics. They record disease activity, demographics as well as whole blood monitoring of azathioprine metabolites and tacrolimus trough levels. They report levels of both drugs 3 months prior to the first pregnancy visit using cutoff from non-pregnancy cohorts as - non-adherent, sub-therapeutic, therapeutic, and supra therapeutic. 

Even though only a small number of patients (n= 64) were reported in the abstract (POS1151), only 9% patients were therapeutic and 33% were non adherent to azathioprine, and 50% were therapeutic on tacrolimus. Considering that most patients are switched to azathioprine during pregnancy – these numbers raise concerns. 57% of those who were non adherent to azathioprine didn’t have low disease activity – showing that the risk of adverse pregnancy outcomes in those patients is really high. While no patients on tacrolimus were identified as non-adherent, it is important to note that those who are usually switched to tacrolimus may have organ involvement and somewhat active disease to begin with; in addition monitoring may be required from time to time for trough levels. Thus compliance may be higher somewhat in patients on tacrolimus.  

Personalizing SLE therapies to optimize pregnancy outcomes remains a challenge. This study highlights some of the gaps in managing patients with lupus pregnancy. Several myths about medications in pregnancy are perpetuated in society and us as physicians taking care of high-risk patients need to be able to discuss these. A multidisciplinary approach with adequate counselling for patients to understand the importance of these medications in pregnancy outcomes is needed.

With the advent of precision medicine, drug monitoring and adherence will remain key challenges to improve maternal and fetal outcomes.