By Jan Bowers, contributing writer, April 01, 2011
Dermatologists face a variety of challenges in the treatment of psoriasis and psoriatic arthritis; the complex disease can have devastating effects on a patient’s quality of life and is associated with a variety of comorbidities. The American Academy of Dermatology’s sixth guideline on the disease, published online Feb. 9 by the Journal of the American Academy of Dermatology and discussed by a panel of experts involved in their development for a standing-room-only crowd at the 69th Annual Meeting in New Orleans, included a discussion of seven real-life cases that illustrate how the earlier guidelines can be applied in specific clinical scenarios.
The first five guidelines, published in JAAD from 2008 to 2010, focused on each of the four major therapeutic areas for psoriasis — biologics, topical therapies, traditional systemic agents, and phototherapy and photochemotherapy —and on the treatment of psoriatic arthritis. A work group of recognized psoriasis experts convened to develop the scope of each guideline, evaluate the scientific evidence, and develop clinical recommendations based on the best available evidence. (See sidebar, p. 29, for more on the guideline development process.) During that process, the members of the guidelines committee decided to take the recommendations one step further.
“Clinical trials look at a very select group of patients. You exclude females of childbearing potential, for example, as well as patients whose hypertension or diabetes is not well controlled but you get those patients in clinical practice all the time,” said Alan Menter, MD, director of psoriasis research at Baylor University Medical Center and chair of the psoriasis guidelines committee. “What we tried to do in the sixth guideline is look at a spectrum of psoriasis patients that all of us are faced with on a day-to-day basis. These are patients with comorbidities such as obesity, which is a massive problem in the psoriasis population. Obesity can be accompanied by metabolic syndrome, hypertension, diabetes, and cardiac issues. The practicing clinician can read the case presentations, look at the clinical photographs, and recognize the kinds of patients they’re struggling with now.” [pagebreak]
The sixth guideline also features treatment algorithms for different types and levels of severity of psoriasis. For especially challenging clinical presentations, such as palmoplantar disease, an algorithm can include recommendations that extend as far as a fourth line of treatment. “For psoriasis, this is probably the first really comprehensive look at approaching the patient based on the clinical situation and using different modalities,” said Henry W. Lim, MD, chair of the department of dermatology at Henry Ford Hospital in Detroit. “There is no one-size-fits-all’ treatment. If one treatment fails, these guidelines give us good, logical next steps.”
The importance of tailoring treatment to the individual patient is addressed repeatedly in the guidelines and cannot be overemphasized, said Neil J. Korman, MD, PhD, professor of dermatology at University Hospitals Case Medical Center in Cleveland. “Too often I talk to people who don’t take all the issues surrounding a particular patient into consideration, but rather ask, What’s the best drug?’” he said. “We want the practitioner to become comfortable using all the therapies out there and become educated about how to do that. This means that if you have a patient with horrific palm and sole disease, you don’t just keep giving them topical ointments if that treatment isn’t working. Get more aggressive with them, and if that involves biologics, for example, and you’re not comfortable with that, refer them to a colleague who does have that experience and expertise.”
The introduction of new biologics, the experts said, coupled with a growing understanding of how comorbidities influence treatment and how different treatments can be combined and rotated, provide dermatologists with more tools and greater flexibility in treating their patients with psoriasis.
“Topical therapy is still the mainstay of dermatologic treatment of psoriasis patients,” said Steven R. Feldman, MD, PhD, professor of dermatology, pathology and public health sciences at Wake Forest University School of Medicine. “I think the guidelines are on the mark when we talk about topical steroids as first-line treatment, and the availability of multiple vehicles. We used to talk only about giving psoriasis patients ointments, and now that we recognize adherence as a critical component of the use of medicine, choosing a vehicle based on what patients will actually use is important.” The sixth guideline points out that scalp psoriasis, which is notoriously difficult to treat with ointments, might better be treated with solutions, foams, shampoos, or sprays. [pagebreak]
The newer vitamin D agents such as calcitriol, along with low-potency corticosteroids and calcineurin inhibitors, help dermatologists treat sensitive areas such as the genitalia, Dr. Feldman said. The sixth guideline singles out genital psoriasis as a source of “significant psychological impact” in affected patients. “In our first case in the guideline we addressed different aspects of genital psoriasis and inverse psoriasis, which nobody ever talks about,” Dr. Menter said. “Patients are often reluctant to mention it, but it’s remarkable how frequent it is. We don’t go looking for it, but we should be asking questions about it, even though it’s obviously a sensitive issue.”
A role for narrowband-UVB, alone or in combination with acitretin, was suggested in the case of a postmenopausal woman with multiple sclerosis, 15 percent of her body surface area affected by psoriasis, a history of worsening psoriasis, and a habit of drinking 12 to 15 beers each weekend. The guideline notes that TNF-alpha-inhibiting biologics are contraindicated in patients with demyelinating disease, and that methotrexate is also contraindicated due to the patient’s alcohol use. “Phototherapy is an attractive option in this case because it can be done despite the patient’s comorbidities that would preclude systemic treatment,” Dr. Feldman said. He added, however, that many patients resist treatments that require two or three office visits a week, and that home phototherapy for induction and/or maintenance is becoming an attractive alternative for appropriate patients but should be conducted as the guideline indicates, with patients under a dermatologist’s supervision. “Use of a home phototherapy device that provides a limited number of treatments helps assure that supervision,” Dr. Feldman said.
Updated recommendations for hepatotoxicity monitoring in patients taking methotrexate were described in detail in the AAD’s fourth psoriasis guideline, but “I still get that question every time I speak to a group of dermatologists about methotrexate and psoriasis,” said Mark Lebwohl, MD, professor and chairman of the department of dermatology at Mount Sinai. “We used to get liver biopsies on everyone who went on methotrexate for psoriasis,” Dr. Lebwohl said. “Dermatologists should know that patients who have no risk factors for liver disease, have normal blood tests, and are neither obese nor diabetic don’t necessarily have to have liver biopsies.” [pagebreak]
Though the percentage of patients with psoriasis who will develop psoriatic arthritis is a matter of controversy with frequencies ranging from 5 to 30 percent of patients with psoriasis, the guidelines emphasize the importance of detecting joint disease early. “The degree of psoriasis doesn’t mean anything vis a vis joint disease,” Dr. Menter said. “At every visit, dermatologists should look for joint disease in their patients with psoriasis and ask whether the patient is having morning stiffness or trouble getting out of a car after a long ride.” It’s worth a look back at the second guideline, which is devoted to the management of psoriatic arthritis, to understand how the disease is diagnosed and scored, Dr. Lebwohl said. “The American College of Rheumatology scores for psoriatic arthritis are explained very well in the guideline, as are the new CASPAR [Classification of Psoriatic Arthritis] criteria and the Sharp score, which is a radiologic assessment of joint damage,” he said. “I think most of our colleagues coming across those scores might read them without knowing what they mean.”
A new biologic, golimumab, was approved for treatment of psoriatic arthritis since the second guideline was published. In the sixth guideline, the authors include golimumab with three other TNF-alpha inhibitors, any of which is appropriate for treatment of psoriatic arthritis, alone or in combination with methotrexate. Golimumab is approved only for the treatment of psoriatic arthritis, not for psoriasis.
The withdrawal of efalizumab from the market after four cases of progressive multifocal leukoencephalopathy (PML) were reported in patients taking the drug was a “wakeup call to dermatology,” said Craig Leonardi, MD, clinical professor of dermatology at St. Louis University School of Medicine. “We had a lot of confidence about biologic drugs, and yet we had efalizumab, which was dermatology-specific, and it was five years into our experience with the drug before we saw these cases of PML,” he noted. [pagebreak]
The sixth guideline notes the withdrawal of efalizumab, but the guideline was completed before the manufacturer of briakinumab, another biologic agent, withdrew its application for the drug (its use in clinical trials continues). “Briakinumab had quite a safety signal in their Phase 3 trial for the treatment of plaque psoriasis when more patients in the group receiving the drug experienced major cardiovascular events than in the placebo group,” Dr. Leonardi said. (Dr. Menter stressed that while Major Adverse Cardiac Events had occurred in the briakinumab study, the immunopathogenesis of coronary artery disease is so complex that at this stage the exact mechanism whereby briakinumab had been responsible for the small number of those events is still unsure.)
“It would be fair to say that most investigators feel that briakinumab was the most efficacious drug they’ve ever used,” Dr. Leonardi said. “However, its safety issues draw attention to ustekinumab because the drugs share the same mechanism of action; clearly there was a problem with briakinumab, and we’re left wondering if there’s going to be any advice from the FDA regarding the use of ustekinumab in our psoriasis patients.” In the meantime, Dr. Leonardi advises dermatologists to consider all options when prescribing a biologic therapy. “If we learned anything from efalizumab, it’s that we should take it easy and gain some experience with new drugs,” he said. “I keep telling dermatologists that new drugs are new and we’ll know a lot more about them as we gain experience using them.”
The sixth guideline includes biologics as a treatment option in several cases, notably one in which a patient with recalcitrant psoriasis and multiple comorbidities (including obesity) had few therapeutic options. “I would say that the guidelines establish quite clearly a major role for biologic therapy in the universe of psoriasis treatments,” Dr. Leonardi said. “Since 2002, we’ve had six major biologic agents introduced, and the pipeline is amazingly rich right now. Time will tell how it all pans out, but the future is very bright for patients with moderate to severe disease, for whom 10 years ago it was the Stone Age.”
Dr. Korman noted that the medical community is coming to realize the impact that psoriasis can have on a patient’s longevity and quality of life. “The data showing all the comorbidities, the serious psychosocial impact, and the higher mortality rate prove that this disease is more than a trivial skin disease, which is what most of us were taught when we were in training,” he said. “We want people to take this seriously, be aware of all the different therapies, including biologics, and make them available to patients. We have the opportunity to help them turn their lives around.” [pagebreak]
Forging a stronger patient-physician relationship
The success of psoriasis treatment, particularly topical therapy, can depend to a large extent on how well the patient understands and follows the dermatologist’s instructions. Psoriasis experts tackled the issue head-on in the sixth guideline, suggesting that dermatologists not only take steps to ensure patients are fully informed about their treatment, but also counsel patients regarding lifestyle modifications and encourage them to establish an ongoing relationship with a primary care provider.
“We all struggle with patient education, and it’s amazing to me that we get patients who come in with fairly significant disease and know nothing about their disease,” said Alan Menter, MD, director of psoriasis research at Baylor University Medical Center and chair of the psoriasis guidelines committee. “We need to create a milieu in which doctors, nurse practitioners, physician assistants, medical assistants, and everyone acts as a team to bring patients into the modern era and help them maintain their treatment. Scalp psoriasis, for instance, is a terribly difficult condition to treat, so we need to provide them with detailed instruction that will help them. We should also send patients to the National Psoriasis Foundation site, which has excellent patient education material.”
A recognized expert on patient adherence, Steven R. Feldman, MD, PhD, emphasizes the importance of the physician-patient relationship. “It’s not just making the diagnosis and knowing what medicine to prescribe, but the relationship has to be strong enough so that patients trust and use the medicine,” said Dr. Feldman, professor of dermatology, pathology and public health sciences at Wake Forest University School of Medicine. “We can be so efficient at making diagnoses and prescribing accurate treatments that patients’ may feel we didn’t take the time to do a thorough examination or adequately consider the treatment options. In addition to making the right diagnosis and the right treatment, we need to do those things that make patients realize that we are thorough, caring doctors.”
The Academy offers resources to help patients live with their psoriasis. For example, educational information is available on the PsoriasisNet on the AAD’s SkinCarePhysicians.com website and on Dermatology A to Z on the Academy’s main website, AAD.org. The Academy also worked with the National Psoriasis Foundation, Psoriasis Cure Now, the Dermatology Nurses’ Association, and the Society of Dermatology Physician Assistants on the Addressing Psoriasis website, available at www.addresspsoriasis.com, which is funded with support from Amgen and Pfizer. Television star and fashion expert Tim Gunn, host of Project Runway, encourages psoriasis patients to take an active role in their condition and their style. The site includes the “Psophisticated Style: A Guide to Everyday Style and Psoriasis,” which features Gunn and dermatologist Susan C. Taylor, MD, offering practical insights for individuals with psoriasis to help them live with their condition.
Process ensures that guidelines are developed in unbiased fashion
The American Academy of Dermatology’s evidence-based guideline development process has been refined in recent years to make it more efficient, transparent, and reflective of concerns about conflict of interest.
The biggest change to the process is evident when development of a new guideline begins and the work group charged with crafting it is chosen. New steps are taken to ensure that potential conflicts of interest are eliminated or mitigated. Other changes include a review process for guidelines developed by other organizations and a more robust, cross-organization needs assessment process to determine which clinical areas need guidelines. A guideline for melanoma was recently approved; upcoming guidelines will cover office-based surgery and the use of anesthesia, atopic dermatitis, and the reporting of adverse drug reactions.
The Journal of the American Academy of Dermatology published an article about the organization’s guideline development process online on Jan. 29; it is available at www.eblue.org/article/S0190-9622(10)02013-X/fulltext.