Food and Drug Administration
Center for Drug Evaluation
and Research
Arthritis Advisory Committee
Silver Spring Holiday Inn,
Questions
1.
Please comment on the characteristics of the cases of lymphomas (e.g., age at
time of diagnosis, distribution of NHL
vs. HD, histology, etc.) observed in patients treated with TNF inhibitors
relative to the experience in the general population and relative to the
experience in people with underlying RA or Crohn’s
Disease.
2.
Please discuss the strength of the available evidence (including the
pre-marketing controlled trial experience, open label extension studies,
post-marketing registry data, and post-marketing spontaneous reports, incidence
rates over time, etc.) and any conclusions you are able to draw regarding an
association between TNF-blocking treatments and lymphoma.
3.
As part of post marketing studies, all 3 manufacturers have committed to follow
between 1000 and 2000 patients with RA and to provide the agency with updated
information on malignancies annually for a minimum of
5 years. At 5 years, the agency will
determine whether additional follow up will be necessary. The yearly update includes numbers and types
of tumors, based on histology and other standard assessments.
4. Should the companies be asked to obtain
additional specific types of information not normally assessed in patient
management that could help elucidate the relationship between anti-TNF therapy
and lymphoma? What findings would
suggest that there be continued active follow up of this nature?
5.
Please discuss how best to communicate information about lymphomas to health
care providers and patients. For each of
the respective product labels, please discuss how the agency should present the
data on the observed incidence of lymphoma, the degree to which the data
suggest an association, and the degree of uncertainty about the association. Should the standardized incidence ratio (SIR)
with respect to the general population be presented? Should the SIR with respect to the RA
population be presented? Should the
labels be similar for each product?
6.
Please comment on the incidence and types of other malignancies observed in the
clinical trial and post-marketing experience with the TNF blocking agents. Do these data raise any concerns at the
present time?
1.
Please comment on the data observed in the randomized controlled trials in
patients with New York Heart Association class III and IV heart failure as well
as the spontaneous reports of adverse cardiac events in patients with RA. Is it reasonable to discuss CHF related
safety concerns in labels for all TNF blocking agents? Other than product label changes that will
caution use in patients with pre-existing CHF or who develop CHF while on
treatment, should the companies be asked to develop additional procedures for
CHF risk management?
.
2.
Please comment on any other concerns based on the safety updates provided and
any specific actions the agency and the various companies should undertake to
address them.