Published Online, 9 September 2008, www.theannals.com, DOI 10.1345/aph.1K522b.
The Annals of Pharmacotherapy: Vol. 42, No. 10, pp. 1519-1520. DOI 10.1345/aph.1K522b
© 2008 Harvey Whitney Books Company.
Comment: Abacavir Hypersensitivity Reaction: An Update
Cindy H Brothers, MSPH
Director Infectious Disease Medicine Development Center
GlaxoSmithKline 5 Moore Drive Research Triangle Park, North Carolina 27709 fax
919/315-6029
cindy.h.brothers{at}gsk.com
Arlene R Hughes, PhD
Director Pharmacogenetics GlaxoSmithKline Research Triangle
Park
Jaime E Hernandez, MD
Director Infectious Disease Medicine Development Center
GlaxoSmithKline Research Triangle Park
Helen M Steel, MD FRCPath
Director Global Safety and Pharmacovigilance GlaxoSmithKline
Middlesex, United Kingdom
Lloyd Curtis, MA MRCP
Director Global Safety and Pharmacovigilance GlaxoSmithKline
Middlesex
Published Online, September 9, 2008. www.theannals.com, DOI 10.1345/aph.1K522b
TO THE EDITOR: We read with interest the review by Hughes et
al.1 on
abacavir hypersensitivity reaction (HSR) with emphasis on the roles of
pretherapy screening for HLA-B*5701 and skin patch
testing. The summary of the clinical presentation, description of
identification, and study of pharmacogenetic risk factors are accurate and
supported by the literature. While we agree with the focus of the paper, we
strongly disagree with the authors' recommended clinical algorithm, outlined
in Figure 1 of their paper, which includes cautious rechallenge with abacavir,
in a hospital setting, based on negative skin patch test results. We base our
disagreement on the following reasons. First, rechallenge with abacavir once
the drug has been stopped for suspected hypersensitivity is contraindicated in
world-wide product labeling due to potentially life-threatening complications.
Second, with few exceptions in extremely limited numbers, skin patch testing
has been used only as a research tool to more accurately characterize cases of
hypersensitivity for analysis
purposes.2
Neither its clinical usefulness nor its safety as a clinical diagnostic tool
has been studied or proven in controlled clinical trials. While it is an
excellent adjunctive test for refining case definitions in the research
setting, it is not appropriate to use these test results to justify a
rechallenge, as evidenced by 6 patients in the PREDICT-1 trial with clinically
diagnosed abacavir HSR who were HLA-B*5701–positive
but who had negative skin patch test
results.3
Here, the estimated diagnostic sensitivity of patch testing was only 87%,
showing that a negative test does not preclude the diagnosis of abacavir HSR.
Importantly, in recently reported randomized controlled clinical trials that
used skin patch testing as a research
tool,3,4
the use of skin patch test results to guide clinical management of patients
(eg, rechallenge following a negative skin patch test) was explicitly
prohibited in the protocol. Third, all of these clinical trials followed very
standardized conditions, with centrally prepared patch tests, rigorous
clinical procedures, and collection of photographic results for independent
dermatological review and adjudication. Standardized patch tests and
procedures are not available; the implications of deviating from the
methodology that has been used and reported are unknown.
The approach to diagnosis and management recommended by GlaxoSmithKline and
described in approved product labeling is conservative and aims to limit
serious adverse outcomes. In the presence of a clinical syndrome compatible
with abacavir HSR, prompt discontinuation of abacavir and avoidance of
rechallenge has resulted in a low occurrence of serious complications. Because
the safety and utility of specifically using patch testing to guide clinical
management of patients is unproven, we do not support any recommendation to
rechallenge with abacavir following its cessation for suspected
hypersensitivity in routine clinical practice regardless of any diagnostic
test results.
Footnotes
Comments on articles previously published are submitted to the authors of
those articles. When no reply is published, either the author chose not to
respond or did not do so in a timely fashion. Comments and replies are not
peer reviewed.–ED.
References
- Hughes CA, Foisy MM, Dewhurst N, et al. Abacavir hypersensitivity
reaction: an update. Ann Pharmacother 2008;42:387-96.
Epub 26 Feb 2008. DOI 10.1345/aph.1K522[Abstract/Free Full Text]
- Shear NH, Milpied B, Bruynzeel DP, Phillips EJ. A review of drug
patch testing and implications for HIV clinicians. AIDS 2008;22:999-1007.[CrossRef][Medline]
- Mallal S, Phillips E, Carosi G, et al.
HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358:568-79.[Abstract/Free Full Text]
- Saag M, Balu R, Phillips E, et al. High sensitivity of human
leukocyte antigen-b*5701 in immunologically confirmed cases of
abacavir hypersensitivity in white and black patients. Clin Infect
Dis 2008;46:1111-8.[CrossRef][Medline]
