A model derived from a trial treating psoriatic arthritis has proven predictive
of success in a broader psoriasis trial that did not measure arthritis. The
results were presented in a poster here at American Academy of Dermatology 67th
Annual Meeting.

About a quarter of psoriasis patients concurrently exhibit evidence of psoriatic
arthritis. The 2006 ADEPT trial established the utility of the tumor necrosis
factor-alpha monoclonal antibody adalimumab (Humira) in treating psoriatic
arthritis, but large trials are not equipped at every site to measure arthritis
response.

This study used data generated in ADEPT and plugged it into a model of the large
(814 patients) REVEAL trial for label indication of adalimumab for psoriasis. At
baseline, 28% of the REVEAL patient population had psoriatic arthritis, and the
model correctly predicted 86% of the concurrent responses to both comorbidities.

Lead author Philip Mease, MD, from Seattle Rheumatology Associates, in
Washington, explained that in the ADEPT trial, the key measure was "the
concurrent time that patients were having both a 75% or more reduction from
baseline in the Psoriasis Area and Severity Index score and a 20% or more
response for arthritis in American College of Rheumatology criteria.

Dr. Mease said that "39% of the time during the 16 weeks of the trial the
patients were experiencing a significant response in both their joints and
skin." Looking at week 16 alone, the drug provided benefit to both joints and
skin in 57% of the patients, compared with virtually none of the patients
receiving placebo.

"This serves as a reminder to dermatologists to be aware that at least a quarter
of their patients are experiencing arthritis," and that this drug has been shown
to be significantly effective at treating psoriasis and arthritis alone and as
comorbidities, Dr. Mease said.

When asked if measures to reduce obesity had an effect on the arthritic
response, Dr. Mease told Medscape Dermatology that there are no definitive data,
but the field is trying to get the answer through retrospective analysis of
existing data from arthritis trials.

"There are more data if you look at just the skin aspect ¡X obesity, metabolic
syndrome, hyperlipidemia, risk for cardiovascular disease" ¡X that reducing
other risk factors has a positive effect on both disease and response to
therapy.

He noted that the average weight of a psoriasis patient is 94 kg, the average
weight of a rheumatoid arthritis patient is about 74 kg, and a typical comorbid
patient weighs 86 kg. Increased weight is associated with fatty liver disease,
and there is concern that psoriasis drugs metabolized through the liver might
put additional strain on that organ. Adalimumab does not carry this risk.

"Rheumatoid arthritis patients die 7 to 10 years earlier than age- and
gender-matched individuals, predominately because of inflammation-induced
atherogenesis and premature heart attack and stroke. It is inflammation driven,
independent of weight." Psoriasis patients suffer from increased weight and
metabolic syndrome, so the comorbidities feed upon each other in a vicious
cycle, according to Dr. Mease.

The pendulum of clinical care is swinging back from a disease-specific focus to
greater acknowledgement and treatment of associated comorbidities, "which is a
key point that a lot of people don't think about," he said.

Dr. Mease's rheumatoid arthritis practice has a close working relationship with
a dermatologist, although patients are not seen by both physicians at the same
time. Dr. Mease said he has more time to spend with a patient than a
dermatologist typically does, he can inject medications into the joints, and he
has extensive occupational-therapy referrals to meet other patient needs.

However, "if the dermatologist feels comfortable and sophisticated enough to
manage the arthritis, by all means, he should do so," he said. It may make sense
for the dermatologist to become the "medical home" in managing the comorbid
conditions, if there is interest and reimbursement issues make it possible, Dr.
Mease added.

Mark Lebwohl, MD, from Mount Sinai Medical Center, in New York City, said models
can be helpful in gaining insight into the interrelationships of treating
psoriasis and arthritis, but he cautioned that randomized clinical trials should
be conducted to reach definitive conclusions.

He told Medscape Dermatology that it is appropriate for dermatologists to pass
on general-health guidelines to their patients and to suggest that those with
specific risk factors for comorbidities, such as arthritis and cardiovascular
disease, see a specialist. Dermatologists seldom order cholesterol and other
tests to monitor for comorbidities, although that may change as the interaction
of comorbidities becomes clearer, he said.

Abbott Laboratories supported the current study, the ADEPT study, and the REVEAL
study. Dr. Mease is a private practitioner who has participated in those trials.
Dr. Lebwohl has speaking and consulting contacts with several companies,
although none are relevant to this discussion.

American Academy of Dermatology (AAD) 67th Annual Meeting: Poster 3367.
Presented March 8, 2009.