Background In 2012, the US Food and Drug Administration approved a Risk Evaluation and Mitigation Strategy (REMS) programme including mandatory prescriber training and a patient/provider acknowledgement form to prevent fetal exposure to mycophenolate. Prior to the REMS, the teratogenic risk was solely mitigated via written information (black box warning, medication guide (MG period)). To date, there is no evidence on the effectiveness of the REMS.
Methods We used a national private health insurance claims database to identify women aged 15–44 who filled ≥1 mycophenolate prescription. To compare fetal exposure during REMS with the MG period, we estimated the prevalence of pregnancy at treatment initiation in a pre/post comparison (analysis 1) and the rate of conception during treatment in a retrospective cohort study (analysis 2). Pregnancy episodes were measured based on diagnosis and procedure codes for pregnancy outcomes or prenatal screening. We used generalised estimating equation models with inverse probability of treatment weighting to calculate risk estimates.
Results The adjusted proportion of existing pregnancy per 1000 treatment initiations was 1.7 (95% CI 1.0 to 2.9) vs 4.1 (95% CI 3.2 to 5.4) during the REMS and MG period. The adjusted prevalence ratio and prevalence difference were 0.42 (95% CI 0.24 to 0.74) and −2.4 (95% CI −3.8 to −1.0), respectively. In analysis 2, the adjusted rate of conception was 12.5 (95% CI 8.9 to 17.6) vs 12.9 (95% CI 9.9 to 16.9) per 1000 years of mycophenolate exposure time in the REMS versus MG periods. The adjusted risk ratio and risk difference were 0.97 (95% CI 0.63 to 1.49) and −0.4 (95% CI −5.9 to 5.0), respectively. Sensitivity analyses on the estimated conception date demonstrated robustness of our findings.
Conclusion While the REMS programme achieved less pregnancies at treatment initiation, it failed to prevent the onset of pregnancy during treatment. Enhanced approaches to ensure effective contraception during treatment should be considered.
- risk management
- medication safety
- health policy
- health services research
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Contributors AS, YA and AGW conceptualised the study. AS, YA and ME performed data analyses. JMHC and BAB contributed to study design and analytical approach. AS prepared the draft of the manuscript and all the coauthors revised the draft critically.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was exempted from approval by the Institutional Review Board at the University of Florida due to use of deidentified data.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available.