Comparative effectiveness of risk mitigation strategies to prevent fetal exposure to mycophenolate.
health policy
health services research
medication safety
pharmacoepidemiology
risk management
Journal
BMJ quality & safety
ISSN: 2044-5423
Titre abrégé: BMJ Qual Saf
Pays: England
ID NLM: 101546984
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
18
07
2019
revised:
03
10
2019
accepted:
13
10
2019
pubmed:
28
10
2019
medline:
16
9
2021
entrez:
26
10
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31649165
pii: bmjqs-2019-010098
doi: 10.1136/bmjqs-2019-010098
doi:
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Pagination
636-644Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.