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Halifax,
N.S.-- While there have been anecdotal, conflicting reports
on the effects of mycophenolate mofetil on psoriasis, results from
a Vancouver-Hamilton study indicate it may be a plausible, alternative
systemic treatment for severe psoriasis.
"We have tested a large number of patients in this study and
found that a majority of patients do respond to mycophenolate mofetil
(MMF) in a safe and effective fashion," said Youwen Zhou, MD,
PhD, assistant professor of dermatology, University of British Columbia,
speaking at the annual meeting of the Canadian Dermatology Association.
MMF, a pro-drug, requires ester hydrolysis to form mycophenolic
acid, the active metabolite. It acts by inhibiting the de novo guanine
nucleotide synthesis, and preferentially targets T- and B-lymphocyte
activation due to lack of salvage pathway.
Today, the main indication for MMF is prevention of organ transplant
rejection. "In recent years it has found a dermatological fame
because it's reportedly effective for immune bullous diseases,"
Dr. Zhou said.
Unlike cyclosporin, methotrexate or acitretin, MMF does not have
a significant hepatotoxicity or renal toxicity and its main side
effects are related to gastrointestinal upsets and transit leukopenia,
he said.
"In theory, MMF should work for psoriasis because we now know
that it is primarily a T-cell-initiated disease, at least in the
early stages. We also have two anecdotal reports speaking about
a possible effect of MMF on psoriasis. Therefore, a systemic evaluation
was needed."
In a two-centre, prospective, open-label clinical trial, 23 patients
with an average PASI score of 21.7 were recruited to 2g to 3g of
MMF per day (1g to 1.5g PO b.i.d.) for 12 weeks. One patient withdrew
after two days due to angioedema. Eighteen patients continued therapy
for at least six weeks. Ten of 18 patients achieved more than 50
per cent reduction of PASI score at 12 weeks. An additional four
patients had between 37 and 50 per cent reduction, bringing the
total number of responders to 14 out of 18 patients, or 77 per cent.
Four patients had no or minimal response. No significant difference
was found between the MMF-responsive and nonresponsive patients
in baseline PASI scores.
Dr. Zhou noted that a long lag time is needed with the medication.
"Most responders required four to six weeks to achieve full
effect," he said. Upon discontinuation of therapy, most responders
relapsed in two to four weeks and responded to re-treatment. Two
patients had long-term improvement that lasted more than six months
after therapy.
"Five patients had significant reduction of disease or remission
and refused to stop taking the drug. Patients get very apprehensive
towards the end of the trial, as it has been the only thing that
has worked for them in a long time. One patient had complete remission
at the end treatment, and remained in remission six months after
treatment.
Side effects were minimal
Five patients
had mild GI symptoms, one patient had pruritus, and there were no
significant laboratory abnormalities. One patient experienced transient
leukopenia that resolved when the dosage was reduced.
Dr. Zhou said their results echo two previous clinical case reports.
While one study (Grundmann-Kollmann et al. IAAD, 2000:42:835-837)
has not supported their study conclusion, he postulated this was
because the authors in the previous study prescribed a lower dose.
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