Biology Reference
In-Depth Information
of patients compared to 6% in the placebo group after 4 months treatment. Still,
significant improvement was achieved with apremilast at the lower dose of 20 mg
BID (29% of patients).
In a trial exploring the effects of the PDE4 inhibitor on patients with psoriatic
arthritis, 43.5% of patients on apremilast at 20 mg BID, 35.8% of patients on
apremilast at 40 mg OD, and 11.8% of patients on placebo achieved the primary
end point of ACR20 (a composite end point indicating
20% improvement of
tender and swollen joint counts, pain, physical function, an inflammation laboratory
marker, and overall disease activity, defined by the American College of Rheuma-
tology, ACR) after only a 3-month treatment period.
Most common adverse events were nausea (18% [apremilast 30 mg BID] vs. 8%
[placebo]), diarrhea (14% vs. 5%), headache, nasopharyngitis, and fatigue.
According to the clinical trials register, studies to explore efficacy of apremilast
in an array of dermal indications such as contact dermatitis, gouty arthritis, rosacea,
severe acne, uveitis, severe lichen planus, dermatomyositis, cutaneous sarcoidosis
but also for other indications such as ankylosing spondylitis, and chronic prostatitis
are currently ongoing or initiated.
2.7.3 Topical PDE4 Inhibitors
As an option to further improve their therapeutic index, PDE4 inhibitors, designed
for topical administration either by the inhaled route for asthma and COPD, or as
creams or ointments for atopic dermatitis and psoriasis, are under scrutiny by
several companies (Fig.
2
).
N
H
3
C
O
CI
CI
O
NN
CH
3
O
O
NH
O
N
N
HO
H
3
C
S
N
NH
3
N
S
O
O
N
N
H
3
C
CH
3
F
8
9
10
CH
3
H
N
O
OH
N
F
O
CH
B
N
H
O
O
O
F
F
11
12
Fig. 2 Chemical structures of PDE4 inhibitors delivered by the topical route. (8) AWD 12-281;
(9) GSK256066; (10) Tofimilast; (11) UK-500,001, (12) AN2728
