Is Topical Therapy for Psoriasis Resurging?

Recent surveys detailing the negative impact of psoriasis on patients weren't exactly news to the dermatologists who treat the disease every day. Sure, these studies are valuable because they quantify the extent of the disease's effects on patients. But dermatologists could tell that psoriasis is a frustrating and burdensome disease by simply listening to patients and taking note of the way they fall into and out of treatment.

While the so-called "Era of Biologics" is still nascent, the introduction of new systemic therapies has changed not only the way dermatologists treat psoriasis, but also how they understand the disease overall. The developmental investigations and clinical trials for the biologics have provided insights into the pathogenesis of psoriasis. According to Alan Menter, MD, President of the International Psoriasis Council and Chairman of the Division of Dermatology at Baylor University Medical Center in Dallas, the advent of biologics for psoriasis has sparked research into the immunopathogenesis and genetics of the disease. "The manufacturers have provided tremendous support for research, not just for marketing, but for high quality research into immunopathogenesis and genetics," he says.

This research coupled with the practical insights gained from up to six years of clinical experience using biologics for psoriasis allows clinicians to effectively employ biologic therapies to provide meaningful improvement to many patients with moderate to severe psoriasis. "Now we have to go back and try to take this data and experience and put it into perspective," Dr. Menter says. "Biologics are great for those patients with moderate to severe disease. What are the numbers of those? Probably 20 percent, 25 percent of the population of psoriasis patients would be candidates for biologics. So now we go back to the remaining 75 percent and have to consider what therapies are best for them." The answer in most cases involves topical therapy. "We know that up to 75 percent of psoriasis patients will at least be maintained with topical therapy," he notes.

TOPICAL TRENDS
Given the reality that most psoriasis patients will use topical therapies, there has been increased attention paid to them in recent years. Abby Van Voorhees, MD, Assistant Professor of Dermatology and Director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania notes three trends in the topical therapy arena. First, she says, the emergence of new vehicles in recent years has been a welcome development for physicians and patients. Newly formulated products, often improvements of older therapies, continue to emerge. Next, she says she considers calcipotriene/betamethasone topical scalp solution to still be a relatively new development and one that continues to be well received by patients. Finally, she says, the availability of calcipotriol ointment is a welcome new development, particularly among patients who had previously used the similar calcipotriene ointment that is no longer on the market.

Further prompting interest in topical therapies may be emerging concerns about the risks of progressive multifocal leukoencephalopathy or PML associated with efalizumab (Raptiva, Genentech), Dr. Van Voorhees observes. So far, three patients taking the T-cell modulator have developed the rare brain infection, prompting the FDA to issue new warnings in February and the European Medicines Agency to recommend suspension of the treatment. While she notes that there is still much to learn about the risks associated with efalizumab therapy, Dr. Van Voorhees suspects that the reports may prompt some patients to reconsider systemic therapy, at least in the short term.

In terms of vehicles, mousses and foams are outpacing creams and ointments, Dr. Van Voorhees observes, and there are now generic products featuring these vehicles available to cost-conscious patients. "The elegance of mousses and foams appeals to patients, and they are generally more user-friendly," she says.

Vehicle improvements aren't limited to prescription agents. Two relatively new non-prescription coal-tar formulations are now available. NeoStrata's Psorent features 15% liquor carbonis distillate (LCD) in a quick-drying formulation containing liquid wax. The product comes in a bottle with a dab-on applicator and is formulated to be lightly occlusive, according to the company. It is distributed in-office.

Scytera Foam 2% from Promius features coal tar in a foam vehicle that permits mess-free application with minimal odor. Speaking at the AAD Annual Meting last month, Mark Lebwohl, MD described the formulation as "cosmetically nicer" than older coal tar products, noting favorable patient response to it. Scytera is an over-the-counter or as Promius terms it, behind-the-counter product. Patients must simply ask the pharmacist for the product, no prescription is needed.

Dr. Lebwohl also highlighted recent findings regarding indigo naturalis. According to a November 2008 study in Archives of Dermatology, an investigational ointment made with the botanical extract showed promise for the management of psoriasis. After 12 weeks, treatment produced significant improvement in scaling, erythema, and induration compared to vehicle. The authors reported an 81 percent improvement in symptoms among treated patients versus 26 percent for controls.

HEAD CASE
Management of scalp psoriasis has been a particular challenge for patients and physicians. It's inconvenient to apply many topical products to the hair-bearing scalp. While the development of foams has improved the delivery of medications to the top of the head, liquid formulations are also popular because they can effectively reach the targeted skin.

Taclonex Scalp Topical Suspension (calcipotriene 0.005% and betamethasone dipropionate 0.064%, Warner Chilcott) has been on the market for less than a year, but it has been well-received. "It's nice to have the convenience of being able to put something on once a day," Dr. Van Voorhees says of the combination solution, which is indicated for moderate to severe psoriasis. Like its predecessor Taclonex Ointment (calcipotriene 0.005% and betamethasone dipropionate 0.064%, Warner Chilcott), the scalp solution features a vitamin D analog in combination with a potent corticosteroid in a special formulation that maintains the viability of each component (the two actives would otherwise degrade when combined).

One drawback of the product is that patients can only use it for a finite period of time. Due to risks associated with long-term application of topical corticosteroids, patients must discontinue use of Taclonex in order to provide a steroid "holiday."

A NEW D
Similar to calipotriene is a compound new to the US market—calcitriol (Vectical Ointment, Galderma). Available in Europe for many years, topical calcitriol is a naturally occurring, active form of vitamin D3. One benefit of calcitriol over calcipotriol/calcipotriene is that the former appears to be better tolerated. A 2003 study in the British Journal of Dermatology showed that perilesional erythema, perilesional edema, and stinging/burning were less severe with calcitriol compared to calcipotriol when the agents were applied to sensitive areas, such as the face, hairline, retroauricaular, and flexural areas.

"We couldn't use calcipotriol in sensitive areas, like the face or flexural areas because of its irritancy potential," observes Dr. Menter. "But this more naturally occurring form, calcitriol, is far less irritating. The irritancy potential for this is very low, indeed."

Dr. Van Voorhees also notes the utility of topical calcitriol for treatment of sensitive areas, especially the face and around the ears. Furthermore, she says many patients who have been dissatisfied with calcipotriol cream—the ointment is no longer available—may embrace calcitriol ointment.

Calcitriol ointment is ideally suited for application to localized plaques. Dr. Menter suspects dermatologists will adopt it into practice in two primary ways. Calcitriol ointment may become a first-line monotherapy option for traditionally sensitive areas. "The face and body folds—breast and groin folds—are certainly an area of concern for physicians, because you can't use anything more than just a mild corticosteroid due to risk of atrophy," Dr. Menter notes. "I would imagine calcitriol ointment in the long-term is going to be a very valuable addition for those areas. We also use calcineurin inhibitors like Protopic and Elidel for the face and groin, but no one has done a head-to-head with Vectical and Protopic and Elidel."

Like calcipotriol, topical calcitriol ointment will likely be used in combination with topical corticosteroids as an adjunct or a maintenance therapy. "Derms are very good at mixing and matching," Dr. Menter observes. "There is the potential to combine calcitriol with potent steroids." Dermatologists may choose to treat localized plaques with a preferred clobetasol ointment, foam, or spray in conjunction with topical calcitriol, withdrawing the steroid once psoriasis is controlled but continuing calcitriol for maintentance.

There is some evidence that the benefits of topical corticosteroid therapy diminish with time. "Patients either stop using it or you get tachyphylaxis," Dr. Menter says. "It's nice to have calcitriol as a maintenance therapy." As a monotherapy, calcitriol "does not have the immediate impact that a topical steroid would have. But for long-term safe maintenance of control it's a welcome addition," he adds.

One question associated with topical vitamin D3 is whether topical application will interfere with systemic calcium metabolism. Speaking at the AAD Annual Meeting, Bruce Strober, MD, PhD, Assistant Professor of Dermatology at New York University said the evidence suggests that topical application probably poses little if any risk for normal patients. "The safety issue of this drug is extremely good," Dr. Menter says.

FUTURE DIRECTIONS
Across dermatologic diseases, the approval of new agents for topical therapy has been limited. But the need for safe and effective therapies remains. "We certainly do need more topicals for psoriasis," Dr. Lebwohl observed in his presentation.

A potential topical therapy for psoriasis is under investigation, according to Dr. Strober. CP-690, 550 inhibits Janus Tyrosine Kinase 3 or JAK3, which is linked to immune system activation and expressed by T-cells among others. It is currently being investigated as both an oral and a topical therapy for psoriasis.