News from the Psoriasis Research Pipeline
Visitors to this
Web site often ask, “What is happening in psoriasis research?” Given
recent scientific advances, this is not surprising. Genes
that can trigger psoriasis have been identified, and we now know
that the immune system plays a key role. This discovery led to the
much-publicized biologics research. What people may not know is that
researchers continue to study other therapies. This article
highlights other therapies in the research pipeline.
Corticosteriods (also known as steroids, cortisones, glucocorticoids,
and glucocorticosteriods) remain the most frequently prescribed
treatment for mild to moderate psoriasis. Potent corticosteroids
have the potential to clear or nearly clear psoriatic plaques more
effectively than other topical therapies. Long-term use, however,
can lead to irreversible thinning of the skin and decreasing
effectiveness. Additionally, corticosteroids cannot be used around
the eyes due to the risk of developing glaucoma.
Research continues to look for steroid-free alternatives. Recent
studies show that two topical medications, calcitriol and tacrolimus,
may hold promise.
Calcitriol. This topical form of vitamin D is used in some
countries to treat psoriasis. One European study1
concluded that calcitriol is almost as effective as the topical
corticosteroid, betamethasone dipropionate, in clearing chronic
plaque psoriasis. This study also found that patients treated with
calcitriol experienced longer periods of remission than the patients
treated with betamethasone dipropionate.
Several other studies have shown that calcitriol can effectively
treat mild to moderate plaque psoriasis on sensitive areas, such as
the face, hairline, and body folds. In one European study, patients
said the redness, swelling, and stinging/burning were significantly
less with topical calcitriol than with topical calcipotriene,2
a synthetic form of vitamin D that is approved for treatment of
psoriasis in the United States. Calcitriol has not been approved for
use in the United States due to its potential to raise calcium
levels in the blood. Raised calcium levels can cause kidney disease
and other serious medical conditions.
Since calcitriol appears to be effective for treating sensitive
areas and a topical medication that can effectively treat sensitive
areas without causing irritation would greatly benefit patients,
synthetic forms of calcitriol are being developed and tested.
Synthetic forms have the potential to lessen serious side effects.
Some patients with mild to moderate plaque psoriasis are finding
Tacrolimus. In pill form, this medication is a potent
immunosuppressant that is used to prevent organ-transplant
rejection. Oral tacrolimus also can effectively treat severe
plaque-type psoriasis that does not respond to other treatment. Due
to its ability to suppress the immune system, oral tacrolimus is
reserved for treating severe psoriasis that is not helped by other
Tacrolimus ointment, while not yet approved for this use, is
effective in treating inverse
psoriasis and psoriasis on the face. Recently, an exploratory
study4 was conducted to find out if tacrolimus ointment
could effectively treat plaque psoriasis found on other areas of the
body when combined with 6% salicylic acid gel. Salicylic acid can
help topical medication penetrate the skin. The study found that
combining 0.1% tacrolimus ointment and 6% salicyclic acid gel, which
helps remove scale, proves effective and is well-tolerated. A total
of 24 adults with plaque-type psoriasis completed the 12-week study.
There was greater clearance of plaques treated with salicylic acid
plus tacrolimus than those treated with salicylic acid alone.
This was a very small, short-term study. More research is needed to
determine if tacrolimus ointment can be used safely and effectively
to treat mild to moderate plaque psoriasis.
Topical medications and phototherapy target psoriasis lesions from
the outside. Systemic medications, which are swallowed or injected,
provide more powerful psoriasis treatment. However, side effects
from systemic medications used to treat psoriasis often require that
a medication not be used long term. The search continues for an
effective and safer systemic medication that can be used long term.
Most of this research now focuses on the biologics. However,
clinical trials continue to study other systemic medications. A
medication known as fumaric acid esters is being studied.
esters. This medication has been used in Germany since 1959 to
treat psoriasis.5 Today, a few other European countries
use this medication. Reports indicate that fumaric acid esters
improve psoriasis for the majority of patients prescribed this
patients quit taking this medication due to common side effects that
include flushing, diarrhea, nausea, and stomach pain. A less common,
but more severe, side effect is the potential for kidney damage. For
this reason, patients must be closely monitored, and usage is
usually restricted to people with severe psoriasis who have not been
helped by other treatments. Despite these side effects, some
patients have successfully taken this medication for as long as 14
trials conducted in Europe studied a new formulation, currently
called BG00012, which is much less likely to cause diarrhea, nausea,
and stomach pain. A phase II study7 — the phase in which
the safety and effectiveness are studied in volunteers who have the
condition — concluded at the end of the 24-week trial that BG00012
consistently improves psoriasis and is tolerable.
A total of 144
patients with plaque, guttate, erythrodermic, palmoplantar, or
pustular psoriasis were enrolled in this study. Each patient had
psoriasis for at least one year. Improvement was seen as early as
two weeks. At week 12, 64% of patients taking 240 milligrams
achieved a 50% improvement and 42% experienced a 75% improvement as
measured by the Psoriasis Area and Severity Index (PASI), which
measures improvements in severity. By comparison, 50% of the
patients taking 120 milligrams spaced evenly throughout the day
scored a PASI 50.
Common side effects
were flushing and inflammation of the nasal passage and pharynx.
These were mild and disappeared without treatment. The
gastrointestinal side effects — diarrhea, nausea, and stomach pain —
that are common in other formulations were reported in only one
These finings indicate that BG00012 may be effective and less toxic
than other currently approved systemic medications. Phase 3 studies
are underway. One phase III trial8 is looking at the
safety and effectiveness of BG00012 in patients with chronic plaque
Research also is beginning to investigate the effects of combining
biologics with other psoriasis treatments. Recently, a study looked
at treating lesions with topical calcipotriol, a synthetic form of
vitamin D approved to treat psoriasis, when a patient is receiving
the biologic, alefacept.
Alefacept plus topical calcipotriol. A total of seven
patients with moderate to severe plaque psoriasis participated in
this study designed to find out if there was improved clearance when
patients applied the topical medication, calcipotriol, to their
lesions while receiving the biologic, alefacept.9 Each
patient received alefacept once a week for 12 weeks. During these 12
weeks, each patient was instructed to apply calcipotriol cream every
other day to all but one lesion.
During the first 12
weeks, adding calcipotriol resulted in faster improvement. When the
psoriasis required additional treatment with alefacept, the patients
again treated all but one lesion with topical calcipotriol. During
the second 12-week period, calcipotriol did not cause faster
1 Camarasa JM et
al. “Calcitriol shows greater persistence in treatment effect than
betamethasone dipropionate in topical psoriasis therapy.” Journal
of Dermatologic Treatment, 2003 January;14(1):8-13.
2 Ortonne JP et al.
“Intra-individual comparison of the cutaneous safety and efficacy
of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg
g(-1) ointment on chronic plaque psoriasis localized in facial,
hairline, retroauricular or flexural areas.” British Journal of
Dermatology. 2003 February;148(2):326-33.
Lebwohl, M. “Psoriasis: New Developments.” Presented at the 63nd
Annual Meeting of the American Academy of Dermatology: Symposium
302. February 2005: New Orleans.
4 Carroll, CL et al.
“Topical tacrolimus ointment combined with 6% salicylic acid gel for
plaque psoriasis treatment.” Archives of Dermatology. 2005
5 Mrowietz U et al. “Dimethylfumarate for
psoriasis: more than a dietary curiosity.” Trends in Molecular
Medicine. 2005 January;11(1):43-8.
6 Lebwohl M et al.
“Treatment of psoriasis. Part 2. Systemic therapies. Journal of
the American Academy of Dermatology. 2001 November;45(5):649-61.
7 Langner A et al. “Results of a phase 2
dose-ranging and safety extension study of a novel oral fumarate,
BG00012, in patients with severe psoriasis.” Presented at the 63rd
Annual Meeting of the American Academy of Dermatology: Poster P2787.
February 2005: New Orleans.
8 Mrowietz U et al. “A novel formulation of an
oral fumarate, BG00012, in patients with moderate to severe plaque
psoriasis: a phase 3 study.” Presented at the 63rd
Annual Meeting of the American Academy of Dermatology: Poster P2743.
February 2005: New Orleans.
9 van Duijinhoven MWFM et
al. “Effects of alefacept and alefacept in combination with
calcipotriol on epidermal cell populations in psoriatic lesions.”
Poster presented at the 63rd Annual Meeting of the
American Academy of Dermatology: Poster P2742. February 2005: New
All content solely
developed by the American Academy of Dermatology