Vitae Enters Phase II Clinical Trials

Vitae Pharmaceuticals, Inc.announced today that it has initiated Phase II clinical studies with VTP-201227 for the treatment of psoriasis and VTP-195183 to enhance immune celllevels in specific cancer treatments. "Within the last 18 months, Vitae has progressed multiple products intoPhase II trials, created a significant partnership with GlaxoSmithKline, andexpanded our robust pipeline of discovery projects," said Jeffrey Hatfield,CEO of Vitae Pharmaceuticals. "We now have significant development efforts inthree major disease areas, including oncology, dermatology and hypertension.The speed of our progress demonstrates the ability of our team, our uniqueapproach and the strength of our drug discovery capabilities and proprietarytechnologies." The first Phase II clinical compound, VTP-201227, has a novel mechanism ofaction and is being developed at Vitae Pharmaceuticals as a topical agent forthe treatment of psoriasis with potential extensions into other dermatologicalindications. The Phase II trial is designed to include 128 psoriasis patientsat 16 study sites in the U.S. The first psoriasis patient was enrolled anddosed in the study this month. VTP-201227 is a potent, selective inhibitor of two specific enzymes thatare active in the skin. Therapeutic targeting of these enzymes by VTP-201227promotes naturally-occurring healing processes within the skin. The compoundhas been designed to be rapidly inactivated in systemic circulation and thushas the potential to have a more favorable safety profile. In preclinicalanimal models, VTP-201227 was shown to exhibit a superior therapeutic indexcompared to other topical dermatology drugs. The second Phase II clinical compound, VTP-195183, is being studied incombination with other therapies for its potential to boost the levels ofinfection-fighting white blood cells in certain oncologic conditions. Vitaeadvanced the clinical program for this compound and initiated a Phase IIclinical trial in October. The Phase II trial is designed as a proof-of-biology study to determine the effectiveness of VTP-195183 in combination withGranulocyte Colony Stimulating Factor (G-CSF) to enhance mobilization ofperipheral blood progenitor cells in patients for whom high-dose chemotherapyis planned. VTP-195183 is a novel subtype-specific nuclear receptor agonistthat has been shown to be generally safe and well tolerated in cancer patientsin Phase I studies. The Phase II clinical trial of VTP-195183 is beingconducted outside of the U.S.

Understanding Scalp Psoriasis

Psoriasis is a common skin condition affecting 2-3% of the population of the United Kingdom and Ireland.
Psoriasis is in simple terms only a vast acceleration of the usual replacement processes of the skin. It appears as raised red patches of skin covered with silvery scales.

With scalp psoriasis there is thick scale and redness that is also evident around the scalp margins. Many patients experience severe itching and a feeling of tightness and some report soreness. One patient has described the build-up of scales as being like 'a mountain on my head'.

For those with scalp patches which flare up from time to time it is possible to manage at home. Shampoo treatments are improving all the time and can be bought over the counter. Your pharmacist should be able to advise. However if your scalp is covered with thick scale or it does not clear up do consult your GP who may arrange referral to a Dermatologist.

There is a range of treatments which can be prescribed including coal tar, dithranol, salicylic acid, cortico-steroids and Vitamin D derivatives to bring the flare-up to a manageable level.

The method of applying the treatment is most important. It involves parting the hair in sections and rubbing the treatment along the exposed area. It is best to do this in a sequential fashion working your way around the hair. You may need someone to help you in order to see the top of your head properly.

Providing care is taken to avoid scratching the scalp, combing and brushing to remove scaling is not only good but necessary.

Scalp psoriasis should not prevent any cosmetic procedures. Having a perm or colouring the hair can have a positive effect on your self esteem. Hair dyes are gentler than they used to be but it would be best to seek advice from a hairdresser who should have up to date information about possible options rather than colour or tint your hair at home. It is also a good idea to make sure that there are no scratches on the scalp when the hair is treated as the chemicals concerned can cause irritation on the broken skin.

A good hairdresser should be able to help you manage your hair and scalp. Telephone in advance and speak to a stylist to explain the situation or try to find a hairdresser who will visit you in your home.

Some people with severe psoriasis suffer temporary thinning of the hair. This can be very distressing but the hair will grow again once the flare up has subsided.

Psoriasis is known as the waxing and waning condition, and it can and does go away. Some people may be lucky enough not to suffer a further flare up, others may experience long remissions. It is unusual for anyone to suffer extensive scalp psoriasis for a long time, provided they seek medical help and use treatments as directed.

Children Suffer From Psoriatic Arthritis Also

Juvenile psoriatic arthritis can be tricky to diagnose. While psoriasis is a common skin condition, associated primarily with a chronic rash all over the, only about 12 to 14 percent of people with psoriasis will develop related arthritis.CausesGenetic and environmental factors play a strong role in the development of psoriatic arthritis. A family history of psoriasis is linked to many children with juvenile psoriatic arthritis, as well as a family history of other forms of spondyloarthropathy. There is little relationship between the severity of a rash and the risk of getting juvenile psoriatic arthritis, however.NOTE: In some people with juvenile psoriatic arthritis, the arthritis shows up before the rash. In these cases, diagnosis can be so difficult that it may take up to 10 years to be certain of a definite diagnosis.Signs and Symptoms
Pitting or thickening and yellowing of the fingernails and toenails
A small round scaly patch on the scalp, belly button or buttocks
Joint problems in large joints, such as the hip and sacroiliac joints
Joint problems can occur on just one side or in the same joints on both sides of the body
Swelling of entire fingers or toes, making them resemble sausages (dactylitis)
Eye inflammation occurs in 10 to 20 percent of children
NOTE: Children with juvenile psoriatic arthritis should be examined by an eye specialist (ophthalmologist) annually to check for eye problems.Long-term Concerns
Damage to the eyes or other eye problems
Decreased range of motion of a joint
Shortening or lengthening of a limb or digit
Damaged cartilage and/or enlargement of a joint
NOTE: Many children have no long-term consequences of having juvenile psoriatic arthritis. Your child may have none, one or several of the concerns listed above, but you should be on the lookout for any or all of them.

Psoriasis Cover ups

People are curious when they see something different, especially on your skin. You have many choices about how to react to their curiosity. You may choose to ignore their attention, or you can explain that psoriasis is a skin disease that is not contagious. Educating people about psoriasis is very valuable because it helps them to accept people who live with skin that is different.
But when you wish to go out in public without addressing your skin condition, certain techniques can help you cope. Wearing long sleeves, pants, turtlenecks, hats or scarves, for example, can make coping in public a lot easier on days when you don't have the emotional energy to accept the stares and questions.
Cosmetic cover-up products can help for those times when clothing won't do. Masking psoriasis lesions and camouflaging redness can make it easier to feel confident in social situations. Dermablend is one brand name of a body makeup that some people use. It can be found in major department stores.
Caution: Never apply cosmetic cover-up to open skin lesions, unhealed cuts or raw or irritated skin. Avoid using cosmetics if skin allergies are present. If you're ever in doubt about applying a cover-up, seek the advice of your physician.
Note: Not all types of psoriasis can be camouflaged. Masking pustular or erythrodermic psoriasis is not a good idea, because minor irritants in cosmetics can produce stinging and redness, and this skin is already inflamed.
What can I do to make my psoriasis less noticeable?Using moisturizers regularly can help improve the redness and scaling of psoriasis lesions. Also, remove as much scale as possible if you are going to use a cosmetic cover-up. There are two ways you can get rid of psoriasis scale on your own:
Occlusion: You can coat each plaque with a thick layer of heavy, over-the-counter emollient cream and then cover it overnight with a plastic wrap. In the morning, wash away the scales in the shower. Note: never occlude a prescription drug without first consulting your doctor.
Hydration: After soaking for 10 to 15 minutes in warm water and bath oil, gently rub your skin with a towel to remove the scales

THE FACTS ON PSORIATIC ARTHRITIS

Psoriatic arthritis is a genetically determined autoimmune disease that occurs in less than 10 percent of persons with psoriasis. Its treatment often requires consultation with a rheumatologist in addition to treatment of the skin lesions by a dermatologist. Psoriatic arthritis is classified with the disease grouping called seronegative spondyloarthropathies which also includes ankylosing spondylitis, enteropathic arthritis, and Reiter’s Syndrome. It occurs most frequently in psoriasis patients whose disease is active, especially in persons with the pustular type of psoriasis. Occasionally it appears in a person who has no dermatologic signs or symptoms of psoriasis, in which case it must be diagnosed by its unique laboratory test results. Psoriasis of the fingernails and toenails is associated with a higher incidence of psoriatic arthritis.
Symptoms of psoriatic arthritis resemble those of rheumatoid arthritis, although the diseases are otherwise quite different. Arthritis changes cause deterioration and pain in small joints of the hands and feet, large joints of the legs and spine, and tendons. Nonspecific foot pain or "tennis elbow" may be an early symptom to appear and may be overlooked if not associated with psoriatic skin or nail lesions.
Confirmation of a diagnosis of psoriatic arthritis requires specific blood and serum tests to differentiate it from conditions such as rheumatoid arthritis and other autoimmune diseases.
Please see the National Psoriasis Foundation for information on the treatment of psoriatic arthritis.
A pediatric form of psoriatic arthritis may appear as early as age 2 to 4 years in girls. A peak period of pediatric onset is age 11 to 12 in both girls and boys. In children the arthritis may appear several years prior to the onset of psoriatic skin lesions; this may pose a problem in recognizing the nature of the underlying disease, especially if there is no known family history of psoriasis.
Although psoriatic arthritis and psoriasis occasionally occur in the absence of a history of psoriasis in the family, a genetic predisposition for psoriasis is considered to be a necessary condition for development of psoriatic arthritis. The evidence for inheritability is well established.
As in the case of psoriasis, an environmental "trigger" may initiate the development of psoriatic arthritis in a genetically predisposed person.

Nail Psoriasis

About 50 percent of persons with active psoriasis have psoriatic changes in fingernails and/or toenails. In some instances psoriasis may occur only in the nails and nowhere else on the body. Psoriatic changes in nails range from mild to severe, generally reflecting the extent of psoriatic involvement of the nail plate, nail matrix (tissue from which the nail grows), nail bed (tissue under the nail), and skin at the base of the nail. Damage to the nail bed by the pustular psoriasis can result in loss of the nail.

Nail changes in psoriasis fall into general categories that may occur singly or all together:
The nail plate is deeply pitted, probably due to defects in nail growth caused by psoriasis.
The nail has a yellow to yellow-pink discoloration, probably due to psoriatic involvement of the nail bed.

White areas appear under the nail plate. These are air bubbles marking spots where the nail plate is becoming detached from the nail bed (onycholysis). There may be reddened skin around the nail.

The nail plate crumbles in yellowish patches (onychodystrophy), probably due to psoriatic involvement in the nail matrix.

Psoriasis of the nails can resemble other conditions such as chronic infection or inflammation of the nail bed or nail fold. Psoriasis of the toenails can resemble chronic fungal infection of the nails.

A person with psoriatic nails should avoid any injury - bumps, scrapes, etc. - that may trigger a worsening of psoriasis (Koebner’s phenomenon). Nail psoriasis is treated by the dermatologist as part of the overall treatment of the disease.

Nail psoriasis is frequently associated with psoriatic arthritis

Psoriasis Sufferers Face Increased Risks From Heart Disease

People severely afflicted by psoriasis have a significantly increased risk of dying from heart disease, new research shows.
A Swedish study found that patients hospitalised with the skin disorder were 50% more likely to die from a heart condition than expected.
The extra risk increased sharply as patients got younger, rising to 162% for those admitted under the age of 40.
For severe psoriasis sufferers aged 40-59 when they were hospitalised, the risk was 91% higher than in the average population.
However the same trend was not seen in less seriously affected individuals who were not admitted to hospital.
The findings emerge from a Swedish study of almost 9,000 psoriasis patients admitted to dermatology wards and more than 19,000 outpatients.
They suggest a genetic defect linking the skin condition and heart problems.
Serious psoriasis sufferers are known to have raised levels of blood cholesterol, which is a chief indicator of heart and artery disease.
Previously this was blamed on the age of older patients or the long term effect of drugs used to treat the disorder.
But the Swedish researchers found high cholesterol levels in a group of 600 newly diagnosed patients who had been suffering from psoriasis for less than a year.

Thymodepressin Now in Clinical Development In US

Few diseases cause more misery than psoriasis, a condition that occurs when a person's immune system overreacts and begins to attack the skin. Psoriasis is a non-contagious skin disorder which most commonly appears as inflamed, fluid-filled skin lesions covered with a silvery white scale. In its more severe phase, the scaly, red blotches can become itchy or painful and cover large areas of skin.
Approximately 2% of the population suffers from this often painful inflammatory condition. In the United States alone, this translates to about 5.5 million patients, many of whom are suffering from a reduced quality of life, and its effect can be as bad as or worse than many other well known diseases or conditions.
GenaDerm, a specialty dermatological company, is in the race to provide better therapies for more effective treatment of psoriasis. GenaDerm is a subsidiary of Bioaccelerate Holdings Inc. (OTCBB:BACL). The privately held company is co-developing with Immunotech Developments Inc., for Thymodepressin(r) the first synthetic peptide developed for the treatment of autoimmune diseases including psoriasis. Immunotech is a biotechnology-focused firm that works to develop novel therapeutic peptides for the treatment of large market diseases.
Now in clinical development and testing in North America, Thymodepressin(r) has already proved to be an effective treatment for psoriasis in Russia, where the drug was invented and is currently sold.
Professor Vladislav Deigin, Chief Executive Officer and President of Immunotech and inventor of Thymodepressin(r) said, "Immunotech was established to pursue the development and commercialization opportunities presented by a scientific platform for the identification and production of peptides. We are delighted that this has been the basis of developing an effective treatment for such a chronic and debilitating condition. Key therapeutic goals in the treatment of psoriasis are alleviation of the condition, and sustainability of the relief provided by treatment. After successfully treating many psoriasis patients in Russia we are optimistic that clinical trials will confirm this efficacy in other countries."
Christopher O'Toole, Head of Specialty Pharmaceuticals for Bioaccelerate said, "In the United States alone, 30% of psoriasis sufferers or 1.5 million patients are seeking treatment. Of these, roughly one third have moderate to severe psoriasis. We are confident that Thymodepressin(r) will demonstrate similar clinical efficacy for this group of patients as it progresses through its planned clinical trial program, and thus provide more treatment options in the future."

Psoriasis And The Social Connection

People with psoriasis perceive they have less social support, have difficulty expressing their feelings and have more trouble with social relationships than others, a new study shows.
Newswise — The study says these life stresses may make them more prone to outbreaks of their psoriasis.
Researchers led by Angelo Picardi, M.D., suggest in the November-December issue of Psychomatics that “psychological interventions aimed at increasing emotional awareness, fostering the security felt in close interpersonal relationships and increasing social support might help reduce” outbreaks or at least lessen their severity.
The scientists from La Sapienza University in Rome studied 33 patients with psoriasis who had a recent worsening of their symptoms and 73 patients who had other minor skin conditions. Both groups were asked about stressful events over the past year, specifically about their social and emotional lives.
Psoriasis is an inflammatory skin condition that affects about 7 million Americans. The study participants had plaque psoriasis, the most common form, which appears as patches of raised, reddish skin covered by silvery-white scales and forms most commonly on the elbows, knees and lower back.
The researchers found that, in comparison with the group that had minor conditions, the patients with a recent psoriasis outbreak had lower perceived social support, more characteristics of bottled-up emotions and higher “attachment-related anxiety.” There were no differences in their scores, however, on measures that tested experiences in close relationships.
People who are high in attachment-related anxiety tend to worry about whether their partners really love them and often fear rejection. In addition, some people are more avoidant that others. People who are high in attachment-related avoidance are less comfortable depending on and opening up to others and are reluctant to ask their partners for comfort or support.
Age, gender, education, marital status and alcohol consumption were taken into consideration when assessing patient outcomes.
“Theoretical models emphasize that these persons tend to rely more on cognition and cognitive information than on feelings and emotional information,” Picardi said. “Clearly, self-regulation is compromised both internally and externally, which may increase susceptibility to disease.
“Perceived social support is a subjective measure, but when the level is higher, it is associated with better health,” Picardi added. “Immunological processes play a major role in the pathophysiology of psoriasis.” He said that prior research has shown that stress has particular effects on the skin, including slower wound healing, greater susceptibility of skin cells and a higher propensity for inflammation.
Picardi A, et al. Stress, social support, emotional regulation, and exacerbation of diffuse plaque psoriasis. Psychomatics 46(6), 2005.

Living With Psoriasis

"People judge us on the basis of our skin — our whole culture is based on cosmetics, lotions, creams and all that," said Finkelstein, of Oakland, Calif. "With (psoriasis), there's a whole layer of psychosocial problems, feelings of embarrassment, of shame, of ultimately feeling isolated."
But these days, Finkelstein, a filmmaker, has cast off the shy persona and is sharing his story with a new documentary, "My Skin's on Fire: Living With Psoriasis." DVDs of the film can be ordered for free at www.beyondpsoriasis.com.
He said now is an ideal time to shed light on the skin disease that affects more than 5 million people because, thanks to new medications, it's no longer a disease that needs to remain hopelessly hidden.
Rather than treating the disease topically, a new class of drugs known as "biologics" and "immuno-supressants" target the internal cause — an immune system on overdrive, which leads to the visible pile-up of inflamed skin cells. Inflammation normally protects the body, but too much of it is harmful.
"Here, really in the last 2 to 3 years, they've changed the disease of psoriasis. For many years it was considered an inflammatory skin disease. Now it's known as an 'immune-mediated disease,'" he says. "They've been able to pinpoint some of the mechanisms that misfire in the immune system."
But as Finkelstein's film shows, living with psoriasis is often far more than just a bothersome condition. Its obvious symptoms — flaky, red skin — can be a tremendous mental burden as well.
In the film, Finkelstein follows the typical trajectory of dealing with psoriasis. First, small patches of flaky skin crop up, usually when a person is a young adult. Then comes the diagnosis of psoriasis. The person may feel confused, wondering where they got such a disease, but a bit of questioning often reveals that it runs in the family — a trait kept hidden from most family members. Then, the person goes through a long trial of different treatments, many of which don't work.
Thankfully, that last step has been shortened by the advent of biologic drugs, said Dr. Alan Menter, a clinical professor of dermatology at the University of Texas Southwestern Medical School in Dallas and founder of the International Psoriasis Council.
Menter, who was interviewed for Finkelstein's film, said it accurately portrays the emotional burden of the disease.
For example, when patients first come to him for medical help, they often are overweight and depressed, Menter said. Most newly-diagnosed patients are young adults.
"For example, you take a 25-year-old, standing in the mirror seeing these crusted patches all over his or her body. They're trying to go out and get a date and it's crushing. They can hide it with clothing but that can't hide it from themselves or when they relationship starts becoming intimate," he said.
But Menter and Finkelstein are both optimistic that this will be less of a problem in the coming years, as more people are treated with medicines that truly help quell the disease.
"Right now I think there are something like 40 new drugs," Finkelstein said. "The future looks very bright for all of us who have suffered for so many years. I think it's a very good time to be talking about psoriasis."

What is Psoriasis?

Psoriasis is a common immune-mediated chronic skin disease that comes in different forms and varying levels of severity. Most researchers now conclude that it is related to the immune system (psoriasis is often called an "immune-mediated" disorder).It is not contagious. In general, it is a condition that is frequently found on the knees, elbows, scalp, hands, feet or lower back. Many treatments are available to help manage its symptoms. More than 4.5 million adults in the United States have it. Between 10 percent and 30 percent of people with psoriasis also develop a related form of arthritis, called psoriatic arthritis.

Psoriasis and the T-Cell Connection

Scientists believe that certain white blood cells called T lymphocytes (T cells) play an important role in psoriasis. "And the disease has a genetic component," says Lindstrom. In about one-third of psoriasis cases, there is a family history of the disease.
T cells circulate throughout the body, orchestrating the immune system's response to foreign invaders like bacteria or viruses. In people with psoriasis, the defective T cells are overactive and migrate to the skin as if to heal a wound or ward off an infection. This process leads to the rapid growth of skin cells, triggering inflammation and the development of lesions.
Both the environment and genetics may play a role in the development of psoriasis. "In genetically predisposed children, psoriasis can be triggered by a strep or other infection," says Lindstrom. That's what happened to author John Updike. After an attack of measles at the age of 6, Updike developed psoriasis "in all its flaming scabbiness from head to toe," as he later described it in his memoir, Self-Consciousness.

PSORIASIS: CURE OR REMISSION

While the disease never goes away, the symptoms of psoriasis subside for a while (remission) and then return (flare-up, or reactivation). Remission can last for years in some people; in others, flare-ups occur every few weeks. Certain triggers, such as stress and seasonal changes, can reactivate psoriasis. "Certain drugs may also exacerbate it," says Lindstrom, including lithium, prescribed for bipolar disorder (also called manic-depressive illness), beta-blockers used to treat high blood pressure, and antimalarial drugs.

Arthritis Drug Treats Psoriasis

A drug for rheumatoid arthritis can relieve the suffering of patients with moderate to severe psoriasis for a year, researchers said on Friday.
They found that infliximab, which is marketed under the name Remicade by Johnson & Johnson in the United States and by Schering-Plough Corp in other markets, improved symptoms of the chronic skin condition that affects 2 percent of the population in western countries.
"This is the first study to show that the very rapid and dramatic improvement that you see with psoriasis can, in the majority of patients, be maintained over at least the medium term -- over the course of a year," said Professor Christopher Griffiths, of the University of Manchester in England.
Previous trials have only looked into the impact of the drug on psoriasis over a short period of about 12 weeks.
The study published in The Lancet medical journal also showed patients saw a significant improvement in one of the most disturbing features of psoriasis: nail disease.
"Up until now it has been extremely difficult to treat," Griffiths told Reuters.
He and his colleagues compared the effects of the intravenous treatment to a placebo, or dummy drug, on 378 patients with the illness.
Each patient was given three intravenous infusions of the drug or a placebo over six weeks and then every 8 weeks for nearly a year. After less than 3 months on the treatment, 80 percent of the patients showed at least a 75 percent improvement, compared to 3 percent in the placebo group.
By the end of the trial, the drug completely cleared the skin condition in a quarter of patients but no one in the placebo group had the same result.
"Some of the patients were improved to the extent that they had no psoriasis and there was no impairment of their quality of life. So this is the best result you could possibly aim for with a treatment for psoriasis," said Griffiths.
"Compared with the other available treatments, it does work extremely effectively and extremely quickly."
The scientists said none of the patients given the drug had any serious side effects. But they stressed that the treatment is not a cure. It is likely patients would have to be on a long-term maintenance programme.
Psoriasis, an immune mediated disease, can develop at any age but it occurs most commonly before the age of 40. Psoriasis patches can also show up on the fingernails and toenails. About 15 percent of patients also suffer from arthritis linked to the condition.
European regulators recently approved infliximab for the treatment of psoriasis but the drug has not yet been approved for the skin condition in the United States.
The drug is also used as a treatment for Crohn's disease, an inflammatory bowel condition.

TREATING PSORIASIS WITH LIGHT THERAPY

Exposing the skin to ultraviolet (UV) light--either from the sun or an artificial source--sets off a biological process that kills T cells, which slows the buildup of skin cells and reduces inflammation.
Light boxes that emit UV light to treat moderate-to-severe psoriasis and other skin diseases are medical devices that require licensing by the FDA. A person steps into the light box, which is about the size of a telephone booth, while lamps direct the light onto the body.
"Treatment with these devices is complex," says Richard Felten, an FDA chemist and senior medical device reviewer. The physician must determine an individual's sensitivity to UV and adjust the light emissions for the most effective treatment with the least risk of side effects, he says. Side effects may include burning, darkened skin, premature aging, and skin cancer. Three to five treatments per week for several weeks or months may be needed to get the psoriasis under control, followed by weekly maintenance treatments.
Light therapy, or phototherapy, is usually done in the physician's office or a medical facility that has the devices, says Felten. "The FDA has cleared some devices for home use under certain conditions and with a doctor's prescription," he says. Home devices include handheld devices for scalp psoriasis and stand-alone light boxes for other areas of the body.
Light therapy usually involves a short wavelength of ultraviolet light, called UVB. For people with resistant moderate-to-severe psoriasis, a combination of an oral or topical drug called psoralen and a longer wavelength ultraviolet A (UVA) light is used. This treatment is called "psoralen plus UVA" (PUVA).
"Psoralen makes the patient more sensitive to the UVA," says Lindstrom, "so once they've taken a dose of psoralen, a smaller dose of UVA is needed to treat them." Patients must be very careful to protect both skin and eyes for 24 hours after psoralen use to prevent damage, she says.
The FDA has also approved a special type of laser, an excimer laser, as a phototherapy device to treat mild-to-moderate psoriasis. "These lasers can deliver a much more controlled beam of light to small areas of the affected skin," says Felten.

Systemic Psoriasis Treatments

The FDA has approved oral and injected drugs that circulate throughout the body to treat psoriasis that is moderate, severe, or disabling. These systemic drugs are very powerful, and while some may be used continuously, others can only be used for a limited time because of their severe side effects. Once a drug is discontinued, the psoriasis may reactivate. The risk of birth defects prevents many systemics from being taken by pregnant women or women planning to become pregnant.
Systemic drugs that may be prescribed for psoriasis include acitretin, methotrexate, cyclosporine, and biologics, which are drugs made from proteins of living cells. Methotrexate, cyclosporine, and the biologic drugs are immunosuppressants, meaning they lower the body's normal immune response. "These drugs suppress the immune cells that cause psoriasis, but they don't distinguish these cells from the immune cells that protect our body from infections," says Elektra Papadopoulos, M.D., an FDA dermatologist.
Acitretin, a retinoid that is given orally for severe psoriasis, helps normalize the growth of skin cells. One of the side effects is raised fat (lipid) levels in the blood, and people taking this drug must get regular blood tests to monitor their cholesterol and triglyceride levels.
Methotrexate and cyclosporine slow the growth of skin cells. Methotrexate, taken orally or by injection, is also a chemotherapy drug for cancer patients. Cyclosporine, taken orally, was first approved to prevent organ rejection in transplant recipients. People using either of these drugs must be closely monitored and should use them only for short periods of time because of serious, potentially fatal, side effects.
Biologics are the newest systemic psoriasis treatments. Since 2003, the FDA has licensed three biologics to treat moderate-to-severe plaque psoriasis: Amevive (alefacept), manufactured by Biogen Inc.; Raptiva (efalizumab), made by Genentech Inc.; and Enbrel (etanercept), marketed by Amgen Inc. and Wyeth Pharmaceuticals. Enbrel was first licensed in 2002 to treat the arthritis associated with psoriasis, and in 2004 to treat psoriasis itself.
"All are immunosuppressive and have different proposed mechanisms," says Papadopoulos. Amevive simultaneously reduces the number of immune cells, including T cells, and inhibits T-cell activation. Raptiva inhibits the activation of T cells and the migration of those cells across blood vessels and into tissues, including the skin.
Enbrel inhibits the action of an inflammatory chemical messenger in the immune system called tumor necrosis factor-alpha (TNF-alpha), which is believed to play a role in both the skin and the joint symptoms of psoriasis.
All three biologics are injected. The FDA has licensed Amevive to be given in a physician's office, either injected into the muscle or into a vein (intravenously). It's a once-a-week treatment for 12 weeks; further treatments may be given after a waiting period.
The FDA has licensed Raptiva and Enbrel for home treatment. People can inject themselves with Raptiva under the skin once a week or with Enbrel once or twice a week. Both drugs are recommended for continuous use to maintain results.
Since biologic drugs are immunosuppressants, they may carry an increased risk of infection and cancer. Rare but serious effects have also included blood abnormalities and autoimmune diseases such as lupus. Other side effects are flu-like symptoms and pain and inflammation at the injection site.
Some dermatologists prescribe biologics alone for psoriasis or in combination with topical treatments. Leonardi says when he prescribes biologics, "I don't have to resort to adding other systemic therapies such as methotrexate, cyclosporine, acitretin, or phototherapy."
"Biologics are an alternative treatment to some of the traditional therapies," says Papadopoulos.
"Now we need to get the expense down," says Leonardi, who has patients who pay $30,000 per year on drugs to treat psoriasis.
Bird feels fortunate that her insurance company covers most of the expense of Enbrel, which is prescribed for both her psoriasis and psoriatic arthritis. Because of the arthritis pain, she has used a cane to help her walk and has had surgery on her wrist to correct some of the arthritis damage. Although Enbrel has been less effective over time for the psoriasis, she says, it's reduced her arthritic pain by about 95 percent. "I can jog down to the corner to chase after the dog," she says. "And last summer, I went hiking with my children in Colorado."

Reducing Psoriasis Treatment Risks

Biologics, other systemic drugs, and phototherapy are powerful treatments with increased risks, says Lindstrom.
Biologics may raise the risk for developing cancer and serious bacterial or fungal infections that spread throughout the body (sepsis).
Cyclosporine can damage the kidneys, methotrexate puts the liver and lungs at risk, and phototherapy can cause skin cancer. To reduce these risks, doctors often put patients on "rotational therapy." "The thought is by moving from one therapy to another therapy over time, the risk to any individual organ is reduced," says Lindstrom.
"We also try to choose a drug with an appropriate benefit-risk ratio," she says. For mild psoriasis, a topical steroid may be appropriate. For more severe disease, where it becomes impractical to apply topicals over a large surface area several times a day, a patient may need a systemic treatment.
Most of the highly effective treatments for psoriasis affect the immune system in some way. For steroid drugs, which have been around for more than 50 years, the risks are well known. But less is known about the long-term side effects of newer drugs, such as the biologics. The safety and side effects of biologics and other immune-suppressing drugs to treat psoriasis continue to be monitored by drug manufacturers and the FDA

The Future of Psoriasis Treatments

Researchers continue to look for reasons why immune cells overreact and what genes may be responsible for psoriasis, hoping to find better treatments, and eventually a cure. Psoriasis research is aided by the visibility of the symptoms on the skin.
"You can see the disease," says Leonardi. "You don't have to do invasive testing to see the effects of therapy." Psoriasis research has a "tremendous spillover into other fields besides dermatology," he adds. "There is a huge need for drugs to suppress the immune system without the side effects."
Multiple sclerosis, Crohn's disease, rheumatoid arthritis, and type 1 diabetes are just a few of the diseases that may also benefit from psoriasis research.

Finding the Right Treatment for Psoriasis

You may need to try different treatments before you find one that works well for you. It is important to discuss your treatment and progress with your doctor.
A recent study found that education, stress reduction, and muscle relaxation training can be beneficial to many people with psoriasis. Adding these elements to a treatment plan can reduce disability, anxiety, and stress related to dealing with psoriasis.
Treatments for psoriasis have potential side effects. People with moderate or severe psoriasis may need treatment for the rest of their lives. Many doctors will recommend that treatments be changed or rotated after a certain period of time to improve treatment effectiveness and reduce side effects.

Treating Psoriasis: Amevive

AMEVIVE is the first biologic approved by the FDA for the treatment of moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. AMEVIVE is a prescription medication that is injected by your doctor (15 mg IM, into the muscle) once a week, for a total of 12 doses.

Amevivie is not without side effects.
The most serious adverse reactions were:
Lymphopenia (see WARNINGS)
Malignancies (see WARNINGS)
Serious Infections requiring hospitalization (see WARNINGS)
Hypersensitivity Reactions (see PRECAUTIONS, Allergic Reactions)
Commonly observed adverse events seen in the first course of placebo-controlled clinical trials with at least a 2% higher incidence in the AMEVIVE®-treated patients compared to placebo-treated patients were: pharyngitis, dizziness, increased cough, nausea, pruritus, myalgia, chills, injection site pain, injection site inflammation, and accidental injury. The only adverse event that occurred at a 5% or higher incidence among AMEVIVE®-treated patients compared to placebo-treated patients was chills (1% placebo vs. 6% AMEVIVE®), which occurred predominantly with intravenous administration.