Reduction of adverse effects by systemic antihistamines in drug therapy with fumarates in severe chronic plaque psoriasis: a doubleblind, randomized, placebo controlled clinical trial

Psoriasis is a T-cell mediated skin disease affecting 2-3 % of the world*s
population.
The anti-psoriatic drug, Fumaderm® or Fumarate '120', further referred to as
*fumarate therapy* or *fumarates* has proven to be effective in psoriasis
vulgaris. Systemic therapy with fumarates may be given to patients for
prolonged periods because of its lack of serious side effects. Commonly
reported side-effects of fumarates are flushing, gastrointestinal complaints,
nausea, and tiredness. These side effects usually occur during the induction of
fumarate therapy. H1- histamine receptors are thought to be responsible for
these side- effects.Anti-histamines, more precisely H1-receptor blockers may be
of clinical value in overcoming the common side effects of fumarate therapy.
H1-receptor blockers may also have anti-psoriatic effects, supporting those of
fumarates, by shifting the balance of proinflammatory cytokines produced by
Th-1 T cells (IFN-γ,TNF-α, IL-12) to Th2-type cytokines, including
IL-4,IL-5,IL-10 and IL-13. H1-receptor blockers would then be as effective as
fumarates, which also shift the balance from type-1 to type-2 cytokine
production.

The aim of this study is to determine the effects of fumarate therapy in
combination with the H1-receptor blocker Cetirizine in psoriasis patients.
Further to evaluate whether there is a decrease in the side effects of fumarate
therapy during the first three months. This study is also to investigate the
possible synergestic/additional anti-psoriatic effects of H1-receptor blocker
Cetirizine during fumarate therapy and to study the immunological effects of
this combination therapy.

Patients will be randomized into 2 groups consisting of 25 patients each. One
group (25 patients) will receive fumarate therapy combined with Levocetirizine.
The other group (25 Patients) will receive fumarate therapy* combined with a
placebo instead of Levocetirizine. All patients will be treated for 12 weeks
with a follow-up period of 8 weeks. Laboratory tests and skin biopsies will be
taken at weeks 0, 4, 8, 12 and 20.
*Treatment scheme:

Week 1 1 dd 1 Fumaderm initial® + 1 dd 1 Xyzal®
Week 2 2 dd 1 Fumaderm initial® + 1 dd 1 Xyzal®
Week 3 3 dd 1 Fumaderm initial® + 1 dd 1
Xyzal®
Week 4 1 dd 1 Fumaderm® + 1 dd 1 Xyzal®
Week 5 2 dd 1 Fumaderm® + 1 dd 1
Xyzal®
Week 6 3 dd 1 Fumaderm® + 1 dd 1
Xyzal®
Week 7 2 dd 2 Fumaderm® + 1 dd 1
Xyzal®
Week 8 2 dd 2 Fumaderm® + 1 dd 1
Fumaderm® + 1 dd 1
Xyzal®
Week 9 - Week 12 3 dd 2 Fumaderm® + 1 dd 1 Xyzal®

psoriasis vulgaris

There will be a significant chance for the patient of a secondary
woundinfection of the injection- and biopsie place and collaps during taking
the bloodsamples. Furthermore patients might experience the side-effects of the
fumaratetherapy.