Accutane

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Accutane Use and Epidemiology

• John E. La Flore, MD, MSPH
• Vice President, Drug Safety Risk Management
• Hoffmann-La Roche Inc.

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Topics

• Accutane use and severe recalcitrant nodular acne
• Pregnancies

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Objectives

• The increased use of Accutane does not imply
  increased use outside the indication
• While use is increasing, pregnancy rates have
  been declining and numbers of pregnancy reports
  have remained stable
• The overall pregnancy rate from the Accutane
  Survey 2.8/1000 is supported by additional data

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Reporting of Accutane Use

• Three sources of data are summarized to
  generate the estimates of new patients and total
  prescriptions each month
• Total retails prescription in the U.S.
• 3rd Party payment tracking
• Roche factory shipments

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Estimated Number of Total Patients Using Accutane
Number ofPatients
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Accutane Use

• In order to be counted as an Accutane user in
  these data, the patient would have
• A. Been seen by a physician
• B. Been diagnosed with acne (98)
• C. Been prescribed Accutane

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Data Sources Used to Understand Accutane Use

• US National Health And Nutrition Examination
  Survey (NHANES) 1972-1974
• supported by similar more recent, international
  data
• Large surveys of physicians
• Medical utilization data

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Accutane Use

• The NHANES prevalence rate provides quantitative
  context for the use of Accutane in the treatment
  of severe recalcitrant nodular acne

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Accutane Use
Additional studies or surveys of prevalence since
Accutane has been available are consistent with
the NHANES point prevalence

• Daniel, et al, (2000)
• Kilkenny, et al, (1998)
• Lello, et al, (1995)

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Comparison of NHANES Prevalence of Severe Acne to
Accutane Utilization in 1998
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Females Have More Visits Than Males
Age (Years) Female Thousands Male
Thousands () ()
Value corrected from Briefing Document
NHAMCS
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Treatment Visits

• Less than 5 of female patients receive Accutane
  at their first visit to the dermatologist
• Female patients are 3.5 times more likely to
  receive antibiotics than Accutane at a visit
• Female Accutane patients are on average 5 years
  older than male patients

NHAMCS
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Prescription Patterns for Accutane

• Severe acne patients are seen on average 9 times
  per year
• 56 of patients with severe acne are treated with
  Accutane by the dermatologist
• Dermatologists use variety of medications before
  prescribing Accutane
• Physicians prescribe Accutane in small percentage
  of patients with less severe acne

Market Measures Inc.
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Accutane Use

• The increased use of Accutane does not imply
  increased use outside the indication

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Number of Reported Pregnancies 1982- Present by
Year of Therapy (US)
Reported Pregnancies
DateUnknown
Year
Note Cumulative data cut-off date of March 31,
2000 data were submitted to FDA in the 2nd
Accutane Quarterly Report for 2000.
Accutane Survey
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Reports of Pregnancy

• Solicited reports of pregnancies are collected
  from a defined denominator from the Accutane
  Survey by the Slone Epidemiology Unit
• This generates the pregnancy rate
• Spontaneous reports of pregnancies are received
  by
• Roche
• FDA
• CDC

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Analysis of Adverse Events and Pregnancies
Associated with Accutane Therapy
Per 1000 Patients
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Does the Age of Patients in the Accutane Survey
Represent the User Population?

• Age proportionality in Accutane Survey compared
  to Accutane users has remained consistent
• Proportional distribution of age in the Accutane
  Survey is similar to Accutane users except for
• Overrepresentation in age 20-29 years old
• Underrepresentation in age gt 40 years old

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Frequency and Incidence Rate of Pregnancy Among
Female Accutane Users
Rate adjusted for median of 140-day courses
Median duration of therapy was approximately
140-day courses.
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Frequency and Incidence Rate of Pregnancy Among
Female Accutane Users
Median duration of therapy was approximately
140-day courses.
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Summary

• The overall pregnancy rate from the Accutane
  Survey 2.8/1000
• Supported by additional supporting evidence
• Declining since the initiation of Pregnancy
  Prevention Plan

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Conclusion

• The evidence presented indicates that for
  every 1000 women treated with Accutane, pregnancy
  has not occurred in 997.