Postmarketing surveillance for drug safety
System database and exposure was estimated from IMSAmerica, Ltd, data. The reporting rates of PN (per 100,000
person-years of exposure) are as follows: 25.74 for lefluno-
The recent commentary by Griffin et concerning a
mide, 42.02 for etanercept, 23.67 for infliximab, and 1.01 for
report on peripheral neuropathy and leflunomide patients
methotrexate. The reporting rate for methotrexate is consid-
claims that, as of October 2003, none of the 6 postmarketing
erably lower than that for the newer disease-modifying anti-
studies committed to by Aventis (Bridgewater, NJ) at the time
rheumatic drugs, consistent with the underreporting of events
of approval had been started, at least according to a Food and
that is known to occur with well-established therapies over time.
Drug Administration (FDA) database. In fact, all 6 of these
Since 1998, worldwide patient experience with lefluno-
studies were initiated between 1998 and 2003, and results
mide has exceeded 770,000 patients and has confirmed a
from completed and ongoing studies have been
favorable benefit/risk profile for the treatment of adult pa-
Aventis has performed many postmarketing studies in close
tients with RA. Potential safety signals generated from active
cooperation with regulatory authorities around the world sup-
and intensive postmarketing surveillance have been further
porting the positive benefit-risk profile of leflunomide.
tested and analyzed in large observational cohort studies.
The report by Bonnel and in the same issue raises
Physician and patient information has been continually up-
several methodologic concerns that make the interpretation of
dated to reflect current knowledge about the safety of this
the selective data presented difficult, especially in a rheuma-
The event of interest in the report, peripheral neuropathy,
has been reported during leflunomide treatment in postmar-
keting experience as stated in the prescribing information.
The authors selected events in the FDA database identified as
Global Pharmacovigilance and Epidemiology
peripheral neuropathy occurring in patients treated with le-
flunomide. Peripheral neuropathy was not defined by stan-
E-mail: [email protected]
dardized criteria other than subjective physician assessmentand electrodiagnostic testing, if the latter was available. Spon-
Both authors are full-time employees of Aventis.
taneous report information, the data source for this article, isoften lacking the kind of detail necessary for a complex
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