High Stress Worsens Psoriasis

Posted on December 27, 2010 | 1 Comment

Chronic stress can lead to a  worsening of psoriasis. Peak levels of stress increase the risk of a psoriasis flare one month later.

The correlation of stress with psoriasis has been well known. Now, a study published in the October issue of the British Journal of Dermatology, “How Stress Gets Under the Skin“, shows how stress leads to changes in cortisol levels that influence psoriasis severity.

Cortisol is a hormone produced by the body that regulates a wide range of bodily functions, including inflammation. High levels of cortisol reduce inflammation. Acute stress acts via the HPA axis to increase cortisol levels in the body. However, chronic stress can lead to an overall reduction in cortisol levels

The researchers followed 62 patients with psoriasis for 6 months, measuring their self-reported measures of stress, psoriasis severity (as measured with the PASI score) and blood levels of serum cortisol.

The researchers found that peak levels of daily stress predicted an increase in psoriasis severity a month later. The peak levels of daily stress were also significantly associated with lower cortisol levels. Those who persistently experienced higher levels of daily stress had lower average cortisol levels than patients who experienced lower levels of daily stress.

The researchers concluded that the “results suggest that daily stressors influence disease outcome in patients with psoriasis by affecting cortisol levels at moments of high stress. Furthermore, patients with persistently high levels of stressors seem to have a specific psychophysiological profile of lowered cortisol levels and may be particularly vulnerable to the influence of stressors on their psoriasis.”

Here is concrete evidence of the mind-body connection and its role in psoriasis. Now, if only there were a cure for psoriasis.

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New Psoriasis Medications Reviewed by Psoriasis Experts

Posted on December 16, 2010 | Leave a comment
Craig Leonard, M.D. Dermatologist

Craig Leonard, M.D. - Psoriasis Expert

Psoriasis treatment options have expanded greatly over the last few years due to the development of new biologic medications.

In a story covered in Skin & Allergy News, dermatologists and psoriasis experts Dr. Craig Leonardi, M.D. and Dr. Alice Gottlieb, M.D. reviewed the latest research in new psoriasis medications and an evaluation of current therapies.

Briakinumab

The dermatologists noted that one of the most notable psoriasis medication in 2010 was of an investigational monoclonal antibody, briakinumab, made by Abbott. Like the recently approved psoriatic drug ustekinumab (Stelara), briakinumab is an injectable biologic agent that targets the interleukin-12 and -23 (IL-12/23) proteins, which are believed to promote the inflammation associated with psoriasis.

One briakinumab trial (M06-890) compared the efficacy and safety of briakinumab to placebo. The results showed that 80.7% of the 981 patients randomized to receive briakinumab every 4 weeks following an induction phase experienced a 75% improvement in psoriasis symptoms (PASI 75) at week 12, compared with 4.5% of the 484 patients randomized to placebo.

Three other trials compared briakinumab to etanercept (Enbrel) or methotrexate and found that significantly more patients randomized to receive briakinumab achieved improved clearance over those assigned etanercept, methotrexate or placebo.

Briakinumab has been submitted by the manufacturer to the FDA for approval.

Ustekinumab (Stelara)

Results of studies that investigated the use of Stelara for psoriasis found that there was a “favorable risk/benefit profile for up to 3 years of treatment.”

According to Dr. Leonardi, one of the study investigators, the maintenance of the favorable safety profile in patients who have been treated for several years is “encouraging”. He noted that ongoing 5-year follow-up studies will enable continued monitoring of the drug’s safety.

Psoriasis Medications in the Pipeline

The dermatologists reviewed additional psoriasis medications with a different mechanism of action. These include:

  • IL-17 inhibitors. Recent studies have suggested that immune system cells (T cells) produce IL-17A that may have acrucial role in the development of psoriasis. This has made IL-17  a potential treatment target. Two antibodies against IL-17 are being researched by Novartis and Amgen.
  • Oral and topical janus kinase (JAK) inhibitors are in phase II and III trials and have had promising results so far
  • Oral phosphodiesterase inhibitors, such as apremilast. Results from a Phase III studies regarding apremilast for the treatment of plaque psoriais is expected by summer 2011. Apremilast is manufactured by Celgene.
  • Topical niacin/calcipotriene. Calcipotriene is a vitamin D derivative that is a well established treatment for psoriasis. New studies are looking at combining this medication with other psoriasis medications for improved results. A recent double-blind, randomized trial reported that 50% of patients randomized to combination therapy with 0.005% calcipotriene and 1.4% nicotinamide achieved symptom clearance or near clearance, compared to 18.8% of those receiving placebo, 25% of those using nicotinamide alone, and 31.5% of those using calcipotriene alone. The findings suggest that the combination therapy “may prove effective as an alternative therapeutic option to calcipotriene monotherapy” according to the study authors.( Pilot, multicenter, double-blind, randomized placebo-controlled bilateral comparative study of a combination of calcipotriene and nicotinamide for the treatment of psoriasis.)

During the presentation, Dr. Leonardi stressed that the existing category of biologic medications, including tumor necrosis factor (TNF) antagonists (Enbrel, Humira, Remicade) continue to perform well.

Dr. Leonardi pointed out that “Given that the class is now 12 years old and includes 2 million patients, we are unlikely to learn of major safety risks at this point”.

What this means in clinical practice is that ustekinumab or briakinumab may be reasonable options for patients with a history of failure of TNF antagonists or a history of central or peripheral demyelination, but until longer-term safety data are available, it should not be the first choice in the majority of treatment-naive patients, said Dr. Leonardi.

Read the full story “Briakinumab, Ustekinumab trials point to future of psoriasis treatment“.

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Guttate Psoriasis Outcome Relatively Good

Posted on June 24, 2010 | 3 Comments

Guttate psoriasis appears to have a better prognosis than other forms of psoriasis. That is the conclusion of a recent study published in the June issue of the Journal of Dermatology.

“Clinical course of guttate psoriasis: Long-term follow-up study“studied 26 patients with guttate psoriasis and found that 61.1% experienced complete involution of their psoriasis with long remission of at least one year.

Family history of psoriasis tended to be associated with a poor prognosis, although only four (11.1%) of the patients had a family history of psoriasis. Psoriasis in three of these patients developed into chronic psoriasis.

Similar to previous reports, the trunk and extremities were the sites most commonly involved and pruritus and itching were more common in patients with a good prognosis, although not significantly so.

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Stelara (ustekinumab) improves depression and anxiety.

Posted on June 3, 2010 | 3 Comments
Steve Feldman, M.D.

Study Author, Dermatologist, Steve Feldman, M.D.

Stelara (ustekinumab), one of the newer biologic medications prescribed for the treatment of psoriasis was found to reduce mild-to-severe anxiety in psoriasis patients after 12 weeks of use.
The research study by, Richard G. Langley, M.D., Steve Feldman, M.D., Alexa Kimball, M.D. and others published in the May 2010 issue the Journal of the American Academy of Dermatology (JAAD), “Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis” showed that treatment with Stelara provided relief of anxiety and depressive symptoms in patients with moderate-to-severe psoriasis.

The researchers analyzed the effect of Stelara on anxiety, depression, and impaired quality of life in 1230 patients with moderate-to-severe psoriasis who were randomly assigned to receive Stelara (ustekinumab) 45 or 90 mg/day or placebo. This was part of the PHOENIX 2 trial.

At baseline, the patients had an average Psoriasis Area and Severity Index score of 20, and 40.3% of patients reported symptoms of anxiety and 26.7% symptoms of depression.

After 12 weeks of treatment, patients receiving either 45 or 90 mg/day of Stelara had significantly greater improvements in depression and anxiety symptoms than patients taking placebo.

By 12 weeks, the proportion of patients with mild-to-severe anxiety and mild-to-severe depression had decreased by 34% and 55%, respectively, in patients receiving ustekinumab, compared with corresponding increases of 1.4% and 10.2% in placebo-treated patients.

One of the study authors, Dr. Kimball concluded that “these benefits in mood are important to quantify and should remind clinicians to ensure the patients at risk are appropriately identified and treated.”

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Calcitriol Helps Heal Corticosteroid-Damaged Skin

Posted on May 25, 2010 | 1 Comment

Researchers have found that calcitriol, the active ingredient of Vectical, can help to heal skin damaged by the use of topical corticosteroids. Both Vectical and corticosteroids are commonly prescribed medications for the treatment of psoriasis, but corticosteroids are known to harm the skin, even after short term use.

In a study published in the June 2010 issue of the British Journal of Dermatology, “Topical calcitriol restores the impairment of epidermal permeability and antimicrobial barriers induced by corticosteroids,” researchers investigated the changes to the skin of mice that had been exposed to corticosteroids, and the response to treatment with calcitriol (Vectical).

The skin treated with corticosteroids and calcitriol showed an improvement in the integrity of the outer layer (stratum corneum) and a recovery of the epidermal barrier that is important for controlling water loss and preventing infections.

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Biologics Cost-Effective for Select Cases of Psoriasis

Posted on May 25, 2010 | 1 Comment

The use of biologic medications for the treatment of psoriasis may offer cost-saving benefits when prescribed for patients who might otherwise require long hospitalizations for their psoriasis.

This was the conclusion of a June 2010 issue of the British Journal of Dermatology, “The economic impact of high-need psoriasis in daily clinical practice before and after the introduction of biologics.”

A treatment course with biologics can be very expensive, and there has been concern about whether the high price is sufficiently offset by the clinical benefits and potential cost-savings from reducing the number of flares and use of other medications, as well as reduced risk of hospitalization.

The study investigated the medical costs associated with the treatment of 67 patients with “high need” psoriasis. Direct costs were calculated for the period of time prior to the availability of biologics and compared to the cost after their introduction. Direct costs for a subset of hospitalized psoriasis patients were analyzed separately.

Average total direct costs were 10,146 pounds per patient per year ($14,575) in the pre-biologic treatment period, compared with 17, 772 pounds ($25,445) in the biologic treatment period. For six patients in the cohort, introduction of biologics led to a reduction of direct costs, as these patients did not need long hospitalizations.

Treatment with biologics led to a decrease in the PASI (psoriasis severity score) from 19.0 at the start of biologic therapy to 6.4 at analysis (a 66·4% reduction).

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Psoriasis Research Grants Awarded to Advance Psoriasis Treatments

Posted on May 18, 2010 | 1 Comment

The National Psoriasis Foundation (NPF) awarded $800,000 in research grants to 10 of the nation’s top dermatology researchers whose projects have great potential to advance psoriasis treatments and ultimately lead to a cure for psoriasis.

Psoriasis affects as many as 7.5 million Americans and is one of the most prevalent autoimmune diseases in the U.S.

The grant recipients include:

  • Maria Eugenia Ariza, Ph.D. will study a protein called HERV-K dUTPase to determine whether it triggers the immune system to promote psoriasis. This knowledge could help identify new therapeutic treatments to prevent the initiation of psoriasis.
  • Ruby Ghadially, M.D. will study whether skin stem cells, which are always present, or transit amplifying cells, an immediate offspring of the stem cell, are increased in psoriasis. This study will resolve a fundamental question in psoriasis and may lead to the development of new agents effective in treating psoriasis.
  • Nima Gharavi, M.D. will look at mechanisms contributing to cardiovascular disease in psoriasis patients by studying oxidized lipids, biological compounds including cholesterol and fat, and whether they are present in psoriasis lesions. The results could lead to a better understanding of the underlying causes of psoriasis and how they contribute to cardiovascular disease.
  • Andrew Johnston, Ph.D. will examine interleukin-1 proteins, which are abundant in psoriasis skin and absent in healthy skin, to determine their effects on the immune cells. This knowledge could help unlock new therapeutic approaches to psoriasis management.
  • Smitri Kundu-Raychaudhuri, M.D. will study a potential new treatment called PAP-1 by examining white blood cells called effector memory T cells, which are overactive in psoriasis and trigger inflammation of skin and joints, to see if psoriasis improves with the novel treatment.
  • Wilson Liao, M.D. will study next-generation DNA sequencing to look at the genetic variants that influence psoriasis. This research might help make it easier to predict how a person’s psoriasis will behave and which medications will work best.
  • Nehal Mehta, M.D., M.S.C.E. will examine whether psoriasis is a risk factor in a disease of the arteries called atherosclerosis by studying shared cells in both chronic diseases. The goal of Dr. Mehta’s research is to understand the effect of psoriasis and its severity on atherosclerosis and plaque activity in humans.
  • Nicole Ward, Ph.D. will determine the connection between psoriasis and cardiovascular comorbidities like atherosclerosis and heart disease. Ward’s goal is to identify the cellular and molecular links to psoriasis and these associated diseases in order to provide new insight into therapeutic treatments.
  • Elaine Husni, M.D., M.P.H. will examine evidence that psoriatic arthritis patients are at increased risk for heart disease by studying the connections between joint inflammation and cardiovascular inflammation. Husni hopes to identify key biomarkers that may allow for early detection of these risks in psoriatic arthritis patients. Dr. Husni’s grant is co-funded by the Arthritis National Research Foundation.
  • Christopher Ritchlin, M.D., M.P.H. will study whether elevated levels of a protein called DC-STAMP correlate with more severe skin and joint disease to reveal why some psoriatic arthritis patients have mild disease and others suffer severe joint damage. This knowledge will help identify patients with more aggressive disease earlier in order to tailor their therapy.

Since 1975, the NPF has awarded more than $6 million in grants to support promising psoriasis research and is the largest charitable funder of psoriatic disease research worldwide.

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Psoriasis in Children – Risk Increases with Increasing Age.

Posted on May 13, 2010 | 2 Comments

“Incidence of psoriasis in children” is a new study published in the June 2010 issue of the Journal of the American Academy of Dermatology (JAAD) that investigated the incidence of psoriasis in children.

The study of mostly white patients in the upper Midwest investigated medical records over 20 years, starting in January 1970. Each record was reviewed by a dermatologist.

A diagnosis of psoriasis was made by a dermatologist in 33.2 cases per 100,000. Plaque psoriasis was the most common type of psoriasis, occurring in 73.7% of patients studied. The extremities and scalp were the most common areas for psoriasis lesions to appear,  59.9% and 46.8% of cases respectively. The incidence of psoriasis in children was found to increase with increasing age in both boys and girls.

Interestingly, the study also showed that the incidence of psoriasis in children increased over time from 29.6 per 100,000 in 1970 to 62.7 per 100,000 from 1995 to 1999.

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Methoxsalen Shortage Creates Challenges for Psoriasis Patients

Posted on May 7, 2010 | 2 Comments

Dermatologists have reported a shortage of methoxsalen to the FDA.

Methoxsalen, is a psoralen, a key component of PUVA therapy used for the treatment of psoriasis, eczema, vitiligo and other skin conditions. PUVA involves the application of a psoralen to the skin prior to exposing the skin to UV light. The psoralen sensitizes the skin for improved clinical outcomes.  Without the psoralen medication, psoriasis patients cannot be treated with PUVA.

The manufacturer of the medication, Valeant Pharmaceuticals, reports that the shortage is “due to an unanticipated change in supplier of the active ingredient.” In response the Food and Drug Administration (FDA) has agreed to allow the mportation of the drug under its personal importation policy (PIP).

Refer to the American Academy of Dermatology for more information about the methoxsalen shortage.

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Psoriatic Arthritis Development May be Predicted by Psoriasis Severity and Family History

Posted on April 26, 2010 | 1 Comment

Psoriatric arthritis is more likely to develop among people with a family history of psoriatic arthritis and a greater greater maximum body surface (BSA) affected by psoriasis. This was the conclusion of a study published in the April issue of the The Journal of Dermatology “Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis“.

The study recruited 400 people with psoriasis attending a psoriasis clinic in Singapore. 134 (33.5%) of the participants also had psoriatic arthritis.

The researcher found that 25% of participants with a family history of psoriatic arthritis were 20.5 times more likely to also have psoriatic arthritis than those without a family history. Previous episodes of severe psoriasis, as defined by the body surface area (BSA) affected by psoriasis and documented in previous medical records, was also a risk factor for developing psoriatic arthritis.

Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption

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