Original article
The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system

Results from southern California were presented in an abstract as a poster at the 15th Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research in Atlanta, Georgia, May 18, 2010.
https://doi.org/10.1016/j.jaad.2010.09.017Get rights and content

Background

Preventing fetal exposure to isotretinoin is widely acknowledged as an important safety issue. The iPLEDGE program is the latest in a series of Food and Drug Administration–mandated risk management programs designed to prevent pregnancies in female patients of childbearing potential (FCBP) taking isotretinoin.

Objective

We sought to evaluate the effect of iPLEDGE relative to the prior risk management program (system to manage Accutane-related teratogenicity [SMART]) on the risk of isotretinoin fetal exposure in FCBP in a managed care setting.

Methods

All FCBP at Kaiser Permanente Southern and Northern California who filled at least one prescription for isotretinoin during a 4-year period (March 1, 2004, to February 29, 2008) were included in this retrospective cohort study (n = 8344). Chart review was performed to confirm fetal exposures and outcomes. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals.

Results

There were a total of 29 fetal exposures and 9912 isotretinoin treatment courses. After iPLEDGE was implemented, the unadjusted rate of fetal exposure decreased from 3.11 to 2.67 per 1000 treatment courses (P = .69). The hazard ratio = 0.76 (95% confidence interval 0.36-1.61) for fetal exposures to isotretinoin during treatment courses filled after iPLEDGE implementation compared with SMART.

Limitations

Limitations include limited generalizability of results, small sample size (n = 29 total documented fetal exposures), and potential uncontrolled confounders.

Conclusion

Evaluating the impact of iPLEDGE on isotretinoin fetal exposures is important in understanding the full risks and benefits of isotretinoin treatment. We found no evidence that iPLEDGE significantly decreased the risk of fetal exposure in FCBP compared to the SMART program.

Section snippets

Methods

This study was conducted at KPSC and KPNC. Kaiser Permanente is a nonprofit, managed care organization that provides integrated health care services to more than 6 million members in California. The linked patient databases available at KPSC and KPNC were used as the primary data source. The database contains patient-level information on pharmacy prescription records, laboratory results, and outpatient and inpatient procedure and diagnosis codes. All patient information is linked by a distinct

Results

Between March 1, 2004, and February 29, 2008, a total of 8344 FCBP received 9912 treatment courses of isotretinoin. There were 5788 treatment courses during the SMART program, and 4124 treatment courses during the iPLEDGE program. Overall there was a 29% reduction in number of treatment courses and patients treated after the implementation of iPLEDGE. Slightly less than half (46.5%) of patients were from KPSC. The mean patient age was 24.2 years and 67.2% of patients were in the 18- to 39-year

Discussion

In this study we analyzed 9912 courses of treatment and found no evidence that the iPLEDGE program lowered the risk of fetal exposures to isotretinoin. Results from both the unadjusted analysis of fetal exposure rates (3.11 before vs 2.67 fetal exposures per 1000 treatment courses after, P = .69) and the adjusted Cox proportional hazard model (HR = 0.76, 95% CI 0.36-1.61) failed to show a benefit after implementation of the iPLEDGE program.

In 5 of the potential cases, fetal exposure could not

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Supported by Kaiser Permanente Southern California Regional Research Committee and Kaiser Permanente Northern California Community Benefit.

Disclosure: Dr Cheetham has a first-degree relative employed by Allergan (compensated by salary and stock options). Dr McCombs is an investigator for Eli Lilly (compensated by grants), Bristol-Myers Squibb (compensated by grants and honoraria), and Wyeth (compensated by grants). Dr Shin is a consultant for Bristol-Myers Squibb (compensated by grants). Drs Wong, Kass, Yoshinaga, and Sidney; Ms Niu; and Mr Sorel have no conflicts of interest to declare.

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