Humira® and Enbrel®—weighing the risks
Two biological response modifiers
that are approved for treatment for psoriasis and psoriatic arthritis are the fusion
protein, etanercept, and the monoclonal antibody, adalimumab.
These are their "generic names"—etanercept is manufactured and marketed
under the trade name Enbrel by the pharmaceutical company Wyeth.
Adalimumab is produced by Abbott Labs and marketed as Humira, an
abbreviation of "human monoclonal antibody in rheumatoid arthritis" derived
from the treatment for which adalimumab was first developed.
Both of these biological response modifiers work by inhibiting the pro-inflammatory
role of the cytokine, tumor necrosis factor-alpha, or TNF-a, within the
body's immune system. Both drugs are the product of recombinant DNA technology,
and are engineered to consist of the constant F portion of human IgG antibodies
and a TNF-a binding component. Both are priced at roughly the same cost for patients:
$1200 to $1700 per month. And both companies offer the drugs through patient assistance
programs for those who have difficulty with the cost of treatment, although the
terms and length of time each program is available to patients may vary.
Creating Humira and Enbrel—recombinant DNA technology
Recombinant DNA technologies are the methods that have been developed to splice
two or more individual gene segments together with the intent to design a protein
that possesses particular qualities or activities. In a very simplified version
of normal gene expression, a gene, made up of a double helix of DNA, is "transcribed"
by certain cell components to form a single strand of RNA. The RNA strand can then
be "processed" through other cell "machinery" to create specific
proteins that the cell then uses to send signals, or messages, to yet other cell
components, or that carry out specific functions critical to cell metabolism, such
as peptides, cellular membrane portals, or activation factors. Many things can happen
along this pathway to modify the protein and its specific functions or activities.
Recombinant DNA technology takes advantage of these processes to customize and synthesize
a final protein product for use as a drug, as is the case with these biologics.
(And again, this description is a highly simplified explanation of a very complex
set of reactions that take place continually in a living organism.)
In the case of Enbrel, the gene segment for the human p75 TNF receptor is coupled
with the gene segment that produces the Fc portion of human IgG (immunoglobulin
G, the body's most common antibody). When this recombinant DNA structure
is expressed by a Chinese hamster ovary (mammalian) cell expression system, the
"fusion protein" that emerges has the ability to bind to TNF-a when injected
into a patient, rendering TNF-a biologically inactive. With Humira, recombinant
technology is used to create fully human monoclonal antibodies with an affinity
for TNF-a, which similarly when injected into a patient renders TNF-a inactive.
In psoriasis and psoriatic arthritis there is an abundance of TNF-a generated at
the sites of inflammation by the autoimmune reaction at the heart of the disease.
Rendering excess TNF-a inactive reduces inflammation by limiting the generation
of additional pro-inflammatory factors to what the immune system considers a challenge.
Tampering with TNF-alpha: a key cytokine
A cytokine is a signaling protein that facilitates cellular communication,
often in response to injury, infection, or an autoimmune reaction. TNF-a is a key
cytokine that plays many amazing roles in the body, from regulating inflammation
to assisting in the normal and necessary apoptosis, or programmed cell
death. Apoptosis is the process responsible for fingers and toes differentiating
into hands and feet in the developing fetus, or for breaking down unneeded cell
components that the body recycles and reuses. A chief role, though, for TNF-a is
as a signal protein regulating inflammation in the body, and as such, it is found
in high concentrations in skin involved in psoriatic lesions.
TNF-a is secreted by many different cells in the body, but primarily from the white
blood cells called macrophages. When TNF-a is released in response to a
challenge to the immune system, it binds with either of two receptors, TNF-R1 or
TNF-R2, which in turn act to initiate additional reactions. TNF-R1 is by far the
more active TNF-a binding site, where binding leads to a set of complex reactions
that increase inflammation in the area where the immune system senses a challenge
is taking place. In psoriasis, an unknown trigger challenges the body's immune system
which responds by producing excessive TNF-a, along with a number of other pro-inflammatory
factors, such as T-cells, interferons, and interleukins which have been shown to
play roles in the rapid skin turnover that is behind plaque formation.
By designing drugs that place the TNF-R1 receptor onto human IgG antibodies, TNF-a
can be selectively removed from the sequence of events that cause inflammation.
For some, these drugs reduce inflammation and provide relief from their psoriasis
symptoms, while for others the effect seems to be less effective, or not effective
Weighing the risks—are Enbrel and Humira safe?
Because these drugs act directly upon a key component of our body's natural immunity
mechanism, they both carry significant risks with their use. The strikingly cautionary
tone of the labeling required by the FDA on all marketing materials in print and
online clearly indicates this risk. TNF-a is a critical component of our body's
natural defense system. Deliberately interfering with this system, in particular,
can and has resulted in severe unintended consequences. Serious bacterial and fungal
infections, tuberculosis, cancer, blood and nervous system problems, and even deaths
have occurred in patients using these treatments. They have offered many psoriasis
patients significant benefits with few to no apparent side effects, while others
have found the treatments to be only marginally effective, or not effective at all.
Some patients have used one treatment over a period of time, before switching to
another in the effort to find relief. Some have experienced upon stopping a treatment
"rebound" effects, with their psoriatic flares returning to the same or
worse status than before treatment was started. Psoriasis is a highly individualized
disease and patient experience has shown that what works for one person may not
work at all, or only marginally for another. Any psoriasis sufferer must weigh the
risks and benefits of these treatments very carefully before beginning their use.
Taking care of yourself—the choice is yours
Strictly approved for those with moderate to severe psoriasis, these and the other
biological response modifiers that are on the market have shown some promise in
relieving the symptoms and discomfort experienced in psoriasis and psoriatic arthritis.
But to date, all come with serious risks of severe infection, disease, and even
death. Great care should be taken when considering their use. A good starting point
for undertaking such considerations is arguably one that includes making deliberate
diet and lifestyle changes that promote systemic good health: Eliminate any dietary,
environmental, and emotional factors that trigger or exacerbate psoriasis flares.
Ensure any nutritional gaps are covered by taking a high-grade multivitamin–mineral
complex daily. Avoid unhealthy lifestyle choices that compromise one's general good
health. If one can make deliberate improvements to one's general state of health,
this launching point is optimum for finding lasting, effective relief through any
number of psoriasis treatments available.
DermaHarmony is a great place to start
In 2005 DermaHarmony began to "rethink" psoriasis — its nature,
causes and treatment — starting a revolution natural in skin health that continues
to this day. Our programs and products promote healthy skin with nutritional supplements,
cleansing and detoxification, pH balancing, mild topical treatments and dietary
- To learn more about the approach, visit How it Works.
- To assess your symptoms, take our on-line Skin
- If you have questions, don't hesitate to call us toll-free at 1-800-827-3730.
We're here to listen and help.
How We Help
Visit DermaHarmony to learn more about our alternative, science-based approach to psoriasis and other common skin conditions. At DermaHarmony our goals are to educate chronic skin care sufferers about the latest alternative research in dermatology, encourage a holistic approach to healthy skin and wellness, and to support our readers in every way we can. Our programs promote healthy skin from the inside out—with pharmaceutical-grade nutritional supplements, topical treatments, expert dietary guidance, and a whole-person approach to health and wellness. Learn more about our programs or call us toll-free at 1-800-827-3730. Our support desk is open 9:00 a.m.–6:00 p.m. ET, Monday–Friday.
Our Skin Health Assessment is designed to help you gain better understanding of your symptoms, and to facilitate our ability to make effective, individualized dietary and lifestyle recommendations for you. It is simple, free, and takes just five minutes to complete. Start on your way to healthier skin and better health today.
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Inverse psoriasis is found in skin folds such as the armpits, groin, under the breasts, around genitals and the buttocks. Inverse psoriasis is more common in people who are overweight and people with deep skin folds where friction and sweating occur.
Plaque psoriasis is the most typical form of this skin condition—4 out of 5 people with psoriasis have plaque psoriasis. The technical or scientific name for plaque psoriasis is psoriasis vulgaris (vulgaris means "common").
In pustular (PUHS-choo-ler) psoriasis, blisters of noninfectious pus appear on the skin. Attacks of pustular psoriasis may be triggered by medications, infections, stress, or exposure to certain chemicals.
Scalp psoriasis is one of the most common types of psoriasis—occurring in just over half of all people who suffer from psoriasis. Scalp psoriasis can range from mild, with slight fine scaling, to severe, with thick red plaques affecting the entire scalp.
Principal Authors: M. Ofiyeva
Date of Publication: 06/17/2009