Psoriasis is a common skin condition characterized by itchy
or sore patches of thick, dry, red skin with silvery scales. Psoriasis
affects 2-3% of
the global population. It can have a significant negative impact on the
health-related quality of life.
changes the life cycle of skin cells. Normally, skin cells that grow
deep in the skin rise to the surface in a month's time. However, in psoriasis
patients, this process happens in a few days time because the cells rise too fast.
Instead of being shed, these skin cells begin to pile up, leading to painful
and scaly patches on the scalp, knees, elbows and lower back. These psoriatic
patches can crack and bleed.
The severity of
psoriasis is typically graded as mild or moderate to severe depending on the
extent of skin involvement and the impact the disease has on the individual's
health-related quality of life. There
may be times when the symptoms of psoriasis get better while on other occasions
they might worsen. There is no permanent cure for psoriasis. But, treatments
may offer significant relief.
The exact cause of psoriasis is not known. It is believed to be associated with environmental and genetic factors that lead to disturbances in the immune responses tothe skin. The immune system signaling protein interleukin 17 (IL-17) that controls cells and activates inflammation, is thought to be a potent driver of psoriasis.
In a normal person, when
there is a cut or a scrape, IL-17 signals the body's immune system to send
cells to the surface to fight infection and heal the wound. In people with
psoriasis, these immune signals can be faulty, and the immune system gets
mobilized for an unknown reason. People with psoriasis lesions have 30 times
more IL-17 than people without lesions.
In a bid to offer better treatment options for psoriasis, clinical trials with drugs that block the
function of IL-17 are being conducted. Results of a multicenter clinical trial led by Mount Sinai researchers has revealed that an experimental and biologic treatment, called brodalumab
, has achieved 100% decrease in psoriasis symptoms in twice as many patients as a second, commonly used treatment.
Brodalumab is a monoclonal antibody
that was designed to block the function of IL-17
. Early clinical studies have suggested brodalumab to be efficacious in the treatment of psoriasis.
For the phase III study of brodalumab, researchers randomly assigned patients with moderate to severe psoriasis to receive brodalumab, ustekinumab (Stelara) or placebo
Ustekinumab is already
approved by the United States Food and Drug Administration (FDA) and is widely
used for the treatment of psoriasis. It blocks the related inflammatory
signalling chemicals or cytokines (IL-12 and IL-23).
Brodalumab in the dose of 210 mg or 140 mg every 2 weeks, while 45mg of
ustekinumab was given to patients with a body weight ≤100 kg and 90 mg for
patients >100 kg.
At week 12, the study
subjects who received brodalumab were randomly put on a brodalumab maintenance
dose of 210 mg every 2 weeks or brodalumab 140 mg every 2 weeks, every 4 weeks,
or every 8 weeks. Patients who were given ustekinumab continued with the same
every 12 weeks. Study participants who received placebo, were then assigned to
receive 210 mg of brodalumab every 2 weeks.
The treatment efficacy
was measured as the degree of reduction in the Psoriasis Area Severity Index or PASI
, which assesses redness,
scaling and thickening of the psoriatic skin lesions and the extent of the
disease. A PASI 100 refers to a 100% reduction in symptoms.
After 12 weeks, 44% of patients who were randomized to
receive 210 mg dosage of brodalumab every two weeks, had achieved PASI 100,
compared with 22% of patients treated with ustekinumab.
In the second study, 37%
of patients who were randomized to receive 210 mg brodalumab every two weeks
achieved PASI 100, as compared with 19% of patients treated with ustekinumab.
With 140 mg of brodalumab, the PASI 100 response rates were 26%.
86% of patients
reportedly achieved PASI 75 with 210 mg brodalumab, and 67% patients achieved
PSAI 75 with 140 mg brodalumab.
The research team
observed that episodes of low white blood cell count were higher with
brodalumab and with ustekinumab as compared to that of placebo. Mild or
moderate fungal infections were more commonly reported with brodalumab than
with ustekinumab or placebo. The overall frequencies of the most common adverse
events such as upper respiratory tract infection, headache and joint pain were
similar between the treatment and placebo group.
The researchers concluded that treatment with brodalumab resulted in significant clinical improvements in patients presenting with moderate to severe psoriasis.
The results of the current studies will be relevant when the FDA considers the application of brodalumab for psoriasis treatment
The research has been
published online in the New England
Journal of Medicine