American Academy of Dermatology conference highlights
From May/June 2005 Psoriasis Advance
How the world can change in five days
Imagine a town that's created for only five days, populated with more than 14,000 people gathered to exchange ideas and learn from each other. Even if the town disappears after a few days, the ideas exchanged still change the lives of those who were there.
That's what the American Academy of Dermatology (AAD) meeting was like in late February. The New Orleans meeting drew a wide mix of people, from small-town doctors to thought leaders. Seminars on psoriasis—the equivalent of being in college for a week solid—provided insight, and the air buzzed with excitement.
This attention encourages more doctors to treat psoriasis and provide better care to an often-underserved community.
From the genetics of psoriasis, including new research on the role of the cellular messenger NFkB in the psoriasis pathways, to new topical steroids, the conference covered all the bases of psoriasis, illustrating that this is truly a systemic and genetic disease. One seminar on psoriasis was standing-room only, and featured such notable thought leaders as Mark Lebwohl, M.D., Steve Feldman, M.D., Ph.D., and Alan Menter, M.D., and new faces, including David Cohen, M.D., and Robert Kalb, M.D.
The National Psoriasis Foundation played a new role in this year's meeting, moving beyond simply educating doctors about psoriasis symptoms to providing facts about the burden of psoriasis with two presentations.
The Foundation had the opportunity to bring more awareness to this professional audience. Below, we discuss additional ways to evaluate psoriasis symptom improvement, review new topicals and systemics, and report on fresh approaches to combining tried-and-true treatments
for the individual patient. Like a New Orleans gumbo, the meeting was a mix of ingredients, providing a provocative blend of information and mirroring the Foundation's move into outreach with the medical community.
Defining psoriasis severity
The AAD conference illustrated that psoriasis and psoriatic arthritis are receiving intense interest, and that treatments are receiving greater scrutiny of efficacy and safety.
One of the resounding themes of the AAD meeting was how to maximize new and existing psoriasis treatments. Given the intense research and development of new treatments—and ways to improve the use of existing treatments—the sessions focused on the range of treatments available, which Craig Leonardi, M.D., referred to as the "treatment toolbox." This toolbox holds hope for the millions affected by psoriasis and/or psoriatic arthritis.
Before doctors can take advantage of the toolbox, researchers need to accurately judge the rate of psoriasis or psoriatic arthritis improvement.
Most recent psoriasis research done for the U.S. Food and Drug Administration (FDA) has used the Psoriasis Area and Severity Index (PASI) score of psoriasis symptoms to assess efficacy. This score has been noted for being time-consuming and complicated. The Physician's Global Assessment (PGA) is another scoring system that ranks the disease from clear to severe, but doesn't define these terms explicitly.
"Doctors want something easy to perform, that provides clear differences and that can be used in clinical trials and insurance," said Charles Ellis, M.D. Dr. Ellis created a scoring system that he says provides clear definitions in an easy-to-use, quick process called the Lattice System Psoriasis Global Assessment (LS-PGA) that also meets the needs of the FDA, which sets the standards for how treatments are evaluated.
Researchers in the United Kingdom compared these three scores—PASI, PGA and LS-PGA—to each other. The researchers found that the LS-PGA was comparable to PASI in terms of reliability, correlation and agreement.
Gail Zimmerman, president and CEO of the National Psoriasis Foundation, reported on another facet of the scoring system difficulties. The FDA looks at treatments that improve the psoriasis
severity score by 75 percent, but many patients—particularly those with mild psoriasis—would be happy with improvement of 50 percent or less. She emphasized the importance of providing assistance with mild psoriasis, which is often overlooked among the targeted treatments. Given the complexity of psoriasis, scoring systems will continue to be refined.
Older treatments re-evaluated, combined with new
While many researchers are investigating new treatments for psoriasis and psoriatic arthritis, others are re-evaluating existing treatments in an effort to show how effective they truly are, either used alone or with other treatments. Phototherapy, for one, has not had the breadth of research provided to biologics. In an effort to remedy this, John Koo, M.D., and other researchers from the University of California San Francisco, and Valeant Pharmaceuticals, presented preliminary results of a study of PUVA (psoralen plus ultraviolet light A).
By 12 weeks, more than 70 percent of those who used PUVA achieved 75 percent improvement in their psoriasis severity score and all achieved 50 percent improvement. The most common side effects were rash and nausea. "This [improvement] is comparable to the biologics," says Dr. Koo. The study will also follow patients for three years to assess the combination of PUVA and Enbrel (generic name etanercept).
Researchers from Baylor University Medical Center in Dallas, Texas, continued this theme in a poster that presented a table of the different uses of Soriatane (generic name acitretin). Jennifer Cather, M.D., and Alan Menter, M.D., explored how to combine Soriatane with UVA, PUVA, other retinoids, methotrexate, Enbrel or cyclosporine in order to maximize psoriasis treatment.
|
|
Fumaric acid esters crossing the Atlantic
Another oral systemic, BG00012, is a fumaric acid ester compound that Biogen Idec studied in 144 patients in a phase II trial. Fumaric acid esters are immunomodulators that have been used mainly in Europe for psoriasis treatment for more than 30 years, but haven't been clinically studied until recently.
Patients had plaque, guttate, erythrodermic, palmoplantar or pustular psoriasis for at least one year, and took one of three doses of the fumaric acid ester compound, BG00012. Of those who took the highest dose, by 12 weeks, 64 percent improved their psoriasis severity score by 50 percent, and 42 improved their score by 75 percent. Mild side effects included flushing and nasal passage inflammation. |
One benefit of using Soriatane in combination treatment for eligible patients, says Dr. Cather, is that the dose can be smaller, which decreases the risk of side effects. As researchers test this combination, they also may find it expands the benefits of treatments. For example, says Dr. Cather, "if you use a therapy like Amevive, (generic name alefacept) you may use it for a year, and then maintain the improvement by using Soriatane."
"With Soriatane, you have a nice chemopreventive [disease preventive] benefit," says Dr. Cather. This is helpful for people who have pre-cancers or skin cancers, who are not recommended for certain systemic treatments that inhibit the immune system.
This research provides promise that patients with psoriasis and psoriatic arthritis will continue to have new options—either as combination with older treatments or alone.
Topicals improved, evaluated
While much development is focused on injectable treatments, the conference also presented exciting research into topicals.
- Clobex shampoo for scalp psoriasis
Galderma researchers presented evidence about the efficacy of Clobex (generic name clobetasol proprionate) shampoo among 14 patients with scalp psoriasis. The researchers studied the effectiveness and safety of the shampoo in 14 people, compared to 12 using the gel formulation. The shampoo decreased the psoriasis severity score by about 70 percent, without signs of immune suppression or skin atrophy. Based on this, the researchers concluded that the shampoo may be suitable as first-line treatment for scalp psoriasis. For more information, contact your doctor.
- New salicylic acid cream
Researchers from the University of Nevada School of Medicine investigated a cream formulation containing salicylic acid for the treatment of chronic plaque psoriasis. The cream is different from other salicylic acid topicals because it releases its ingredients into the skin over time, which reduces the water loss from the skin. In the study, 15 patients with psoriasis were studied for eight weeks. Among those using topical steroids at the same time, the treatment with the
salicylic acid resulted in 66 percent as "significantly improved" by eight weeks.
- Shea butter derivative
Shea butter is often used in lotions and moisturizers. Researchers are studying a derivative of it, BSP-103, in a phase II trial to see if its anti-inflammatory properties can help reduce psoriasis symptoms. In 12 patients out of 20 with psoriasis, the plaques were smaller, and less inflamed and scaly after about three weeks of taking three capsules a day.
This research and development into new topicals offer hope to those frustrated with their current topical treatment.
Biologics added to the treatment mix
Like spices thrown into a mix of New Orleans Cajun cooking, researchers are exploring how best to use biologic medications for different types of psoriasis patients and in different combinations.
Two biologics that are approved for psoriasis and/or psoriatic arthritis are highlighted below.
Amevive for psoriatic arthritis: About 185 patients used either Amevive (generic name alefacept) with methotrexate or methotrexate alone. Of those using the combination, more than half achieved at least a 20 percent improvement in their psoriatic arthritis severity score at 24 weeks; in comparison, about one quarter of those solely on methotrexate achieved this score. The study was important because it showed that the combination treatment is effective in psoriatic arthritis.
Amevive for elderly patients: Amevive was found to be effective and well-tolerated in elderly patients. About 30 percent achieved 75 percent improvement in their psoriasis severity score during the first course of treatment. The most common side effects were minor and appeared to decrease over time with each course of Amevive. Serious side effects, including pneumonia and malignancy, were rare and did not increase with each course. This study was important because elderly patients are often at higher risk of serious side effects. Amevive is manufactured by Biogen Idec.
Enbrel in the "real world": A study of Enbrel (generic name etanercept) in "real-life" situations mirrored that of the clinical trials. More than 1,000 patients using Enbrel for their psoriatic arthritis were followed in clinics. More than 70 percent of them achieved a psoriasis status of "mild" or "better" at week 12.
Enbrel quality of life correlation with psoriasis improvement: A study found that when patients were retreated after a period of no Enbrel treatment, their quality of life improved in proportion to their psoriasis severity score improvement. The measurements for both were very similar to that experienced with initial Enbrel treatment, suggesting that the patient's perception of the effect on quality of life can be improved again if Enbrel is stopped for any reason and then started again. Enbrel is manufactured by Amgen, Inc.
Future developments: Treatment stops psoriasis earlier in the pathway
What would it be like if one dose of a treatment could greatly improve your psoriasis? Scientists are asking this same question, and are coming closer to realizing new treatments that may offer longer improvement times with fewer side effects. Researchers, led by Alice Gottlieb, M.D., Ph.D., presented evidence at the AAD meeting about the effects of one such treatment, called anti-IL-12p40.
This research stems from discoveries about the psoriasis development pathways; specifically, how the genes involved in psoriasis lead to inflammation and skin cell development. Anti-IL-12p40 blocks psoriasis at an earlier stage of the psoriasis development pathway.
Treatments are known to take a decade or longer from initial experiments to approval by the U.S. Food and Drug Administration. However, this research points to continued development of treatments based on increased knowledge of the many factors involved in psoriasis. |
Raptiva studied over three years
One of the big unknowns with biologics as a treatment for moderate to severe psoriasis is long-term safety. In the first study of its kind, Genentech, manufacturer of the biologic Raptiva (generic name efalizumab), enrolled 300 patients in a three-year study to assess efficacy and safety. Participants were allowed to use topical treatments and phototherapy over the course of the study.
Nearly half of the patients followed from the beginning of the study achieved 75 percent improvement in their psoriasis severity score throughout the study, and did not experience a significant increase in side effects over the course of the study.
"This trial shows us how to use the drug over the long haul," said Craig Leonardi, M.D., who led the St. Louis, Mo., arm of the study.
Keith Farmer, 46, of Scott City, Mo., provided testimony to the improvement offered during the 36 months. Farmer has had plaque psoriasis for more than 20 years, and psoriatic arthritis for about 15 years. He had tried phototherapy and methotrexate, and when these treatments failed,
Farmer enrolled in the Raptiva study.
Farmer now experiences a few flares he believes are related to stress and has some psoriasis on his ears. His psoriatic arthritis flared during Raptiva treatment and is now being controlled by cyclosporine. Genentech plans to follow patients who are using Raptiva to determine the incidence of psoriatic arthritis.
Dr. Leonardi reported that in his study there was no upward trend in serious infections or nonserious infections, like a cold. Malignancies, such as squamous cell carcinoma, were what you would expect in a population that had tried immunosuppressive treatments, said Dr. Leonardi.
As researchers learn more about how to manage the treatment effectively and safely, patients such as Farmer are more optimistic about treatments for themselves and their families. "Two of my nephews have psoriasis, so I'm hopeful that they'll know even more about how to safely treat psoriasis in the future," commented Farmer.
|
