Rheumatoid arthritis (RA) sufferers have been served up
a pretty raw deal this year, and it seems there's just
no end to the bad news. Hot on the heels of the COX-2
controversy and the removal of Vioxx from the market,
comes news that tumour necrosis factor (TNF)-alpha-blocking
agents cause skin disease in a quarter of RA patients
treated with them.
"Dermatological conditions are
a significant and clinically important problem in RA
patients receiving TNF-alpha-blocking therapy," explain
Dr Marcel Flendrie and colleagues from Radboud University
Nijmegen Medical Centre in the Netherlands in their
paper published April 4 in Arthritis Research &
Therapy. Although skin conditions have been reported
in clinical trials on these drugs, this is the first
prospective cohort study that confirms the connection.
The study included 289 RA patients
who were started on TNF-alpha-blocking treatment between
June 1994 and December 2003. Each of these patients
had a matched control with RA but no history of this
type of treatment. Median followup time was 2.3 years.
TNF-alpha-blocking agents investigated
in the study were the anti-TNF antibodies infliximab
and adalimumab. The TNF-alpha receptors etanercept and
lenercept were included as well. All "dermatological
events" defined as any new onset of disease or exacerbation
of a pre-existing skin condition were noted by the researchers.
GUILTY
AS CHARGED
The study found that one-quarter of patients on TNF-alpha-blocking
treatment needed to see a dermatologist. Of these, 26%
had events severe enough to require treatment discontinuation.
Visits to the dermatologist were significantly more
frequent in this group than in the control group, only
13% of whom required a trip to the dermatologist. A
significantly higher number of events occurred during
active TNF-alpha-blocking therapy than afterwards, suggesting
these agents were at least partially responsible. The
most commonly recorded events were infections, eczema
and drug-related eruptions.
Although frequent skin infections
are normally seen in RA patients, the results of this
study suggest that TNF-alpha-blocking agents increase
the risk of these infections, particularly the risk
of fungal infections and folliculitis. Given the important
role TNF-alpha plays in the immune response, this isn't
surprising. The specific shift in the immune response
caused by TNF-alpha-blocking medications may also make
RA patients more susceptible to eczema and other atopic
disorders. This finding is especially interesting as
the immuno-logical characteristics of RA normally protect
against these disorders.
"The occurrence of dermatological
events during TNF-alpha- blocking therapy is not restricted
to RA patients," note the study authors. This conclusion
is based on a separate analysis of 28 patients with
non-RA rheumatic diseases conducted by the authors.
In this group, dermatological reactions were also seen
in patients with juvenile idiopathic arthritis and ankylosing
spondylitis.
The study findings could significantly
influence the treatment of various rheumatological disorders.
And the impact is likely to be even greater as more
COX-2 inhibitors get pulled off the market. Given the
frequency and severity of skin disease with the use
of TNF-alpha-blocking agents, a further narrowing of
treatment options may be a painful reality for many
patients with rheumatic disease.
Arthritis Res Ther Apr 4,
2005;7(3):R666-76
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