The first two sections of the AAD’s comprehensive undertaking focus on the biologics and psoriatic arthritis.

The American Academy of Dermatology’s recently released guidelines for psoriasis are noteworthy not only for their timeliness and comprehensiveness — the first two sections of what ultimately will be a five-section document present an in-depth overview of the evidence on and use of the five FDA-approved biologics and a succinct primer on psoriatic arthritis — but also for the rapidity with which they were developed. The guidelines work group first met in April 2007 and the first two sections of the document appeared in the May 2008 issue of the Journal of the American Academy of Dermatology.1,2 And that interval even included a period during which the draft was circulated to AAD members for comment.

“This is the quickest the Academy has ever delivered a guideline — a little over a year,” explains Alan Menter, MD, who chairs the work group that produced the “Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis” and is chair of the Psoriasis Research Institute at Baylor University Medical Center in Dallas, TX. “We were able to do it because we have a good group of people who did a great deal of legwork beforehand — and also because we’ve never had such a marvelous set of high-quality clinical trials to review.”

The latter’s availability, Dr. Menter, an acknowledged psoriasis expert, observes, made the group’s objective of delivering evidence-based — rather than consensus- or opinion-generated — guidelines, “much easier to accomplish.”

“We had a spectacular amount of high-quality, patient-oriented, A-grade evidence to review, which meant we didn’t have to go to posters and case demonstrations or use experts,” he added, to support the 12-member work group’s recommendations.

The Evidence-Based Approach to Creating Guidelines

That evidence-centered approach to guideline creation, which is now being used by many medical specialty organizations, marks a new chapter in psoriasis-management guidance, according to work group member Abby Van Voorhees, MD, Director of the Psoriasis and Phototherapy Treatment Center in the Department of Dermatology at the University of Pennsylvania in Philadelphia. “There is a big difference between this and the last psoriasis guideline, because this one truly is an evidence-based guideline — in which the evidence is gleaned and graded, and thought leaders are convened to write something based on the specific evidence, not on their opinions,” Dr. Van Voorhees says. Medical societies began switching to evidence-based guidelines about 8 years ago, she continues, “because everybody has started to become sensitive to the fact that opinion-based guidelines have significant limitations.”

Besides the obvious potential conflict-of-interest issues, Dr. Van Voorhees acknowledges that opinion-based development of guidelines is understandably prone to competitive posturing among experts and a possible “disconnect” between the evidence and the recommendations. “There are references in the [preceding] guidelines, of course. But there was not necessarily a connection between the references and the opinions that were expressed,” she explains.

The new AAD guidelines, which when complete will replace those developed a decade ago, are timely — perhaps even somewhat overdue, work group members claim. (See sidebar for highlights.) That’s because the five approved biologic therapies — alefacept (Amevive), efalizumab (Raptiva), adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade) — have been in use for 5 years, and the mounting collective evidence on their efficacy, safety and long-term use hasn’t been reported in a stand-alone publication. “This really gave us the opportunity to take the evidence by the scruff of the neck, shake it, and see what came out of it,” Dr. Menter quips.

AAD president C. William Hanke, MD, recently stated that the guidelines’ “impartial analysis of the most current research” gives dermatologists a resource that will enhance care quality for psoriasis patients, “and ultimately their [patients’] safety,” he said. “These guidelines should help further the understanding of the current psoriasis therapies.”

Other Changes from the Old Guidelines

In another departure from previous psoriasis guidelines, the new document also takes an in-depth look at psoriasis phenotyping, an area that has been poorly understood until recently. The document also offers a range of tools for evaluating psoriasis, something community-practicing dermatologists have pressed for in recent years, Dr. Menter notes.

In group studies, the phenotypes have been “all over the board,” he explains, making evaluation challenging. “And most clinical studies are based on plaque psoriasis,” Dr. Menter observes, “so we wanted to highlight that there are other forms of psoriasis and to provide evaluation tools, and then try to put that into some form of coherent message to the dermatologists.”

The other timing consideration was recognition that with the biologics — because of reported safety risks such as liver toxicity and infection, and contraindications in patients with certain viral or cardiovascular diseases — dermatologists may be avoiding or reducing even appropriate use. (See sidebar on safety issues.)

Dermatologists who aren’t familiar with the drugs, Dr. Menter and other sources indicated, may be avoiding biologics in patients who might benefit and could be safely screened to avoid treatment complications. The new guidelines attempt to address that understandable reluctance, Dr. Menter explains.

“By providing a broad-based, evidence-based review of the biologic therapies that are out there, we hoped to make life easier for the physicians in clinical practice to make [treatment] decisions,” he says. “If dermatologists are considering starting a patient on one of these five drugs, it’s not an industry-sponsored paper they’re looking at but rather a general review that we hope will give them some guidance for making rational decisions in how to choose a drug and monitor the patient for the long term.”

Reaction to the Guidelines

Dermatologists in clinical practice with whom Skin & Aging spoke applaud the effort undertaken by the guidelines authors, and they concur that a comprehensive single-source reference document that addresses the biologics — and psoriatic arthritis — was sorely needed. One is Jerry Bagel, MD, director of the Psoriasis Treatment Center of Central New Jersey in East Windsor. “It seems that 20% of the U.S. dermatologists are writing 80% of the biologics,” Dr. Bagel, a senior attending physician at the University Medical Center at Princeton, observes, adding that he thinks that many dermatologists are not writing for biologics at all out of safety fears.

“[These] guidelines may help dermatologists realize what testing should be done to more safely administer the drug — and therefore offer more patients the opportunity for a better qualify of life,” says Dr. Bagel, who is a member of the National Psoriasis Foundation’s medical advisory board. “Many dermatologists who use biologics sparingly are still uncomfortable with the safety issues, hence they are looking for guidelines to help them safely monitor their patients.”

Michael Zanolli, MD, a psoriasis expert in Nashville, TN, who worked on the psoriasis guidelines released in the early 1990s, concurs with Dr. Bagel about the guidelines’ utility and potential value to practicing dermatologists. Though Dr. Zanolli views the effort as “a good, valuable resource for dermatologists — and one that’s appropriately directed toward active clinicians,” he cites concerns about the ordering of the information and the serial release schedule.

In particular, Dr. Zanolli fears that leading the document with the biologics and adding sections on the standard therapies later gives the sense that “the authors sanction the biologics as the first step in the treatment of psoriasis.” He says, “I wish they had started with the topicals,” adding, “This will be a sort of one-source document when it’s complete. But I do think they need to hurry up and bring forth the basic treatment [sections] to overcome the perception that they’re just promoting the biologics.”

The authors were sensitive to the concerns Dr. Zanolli cites, but they decided to start with the biologics, Dr. Menter explains, “because there was more noise about biologics than anything else, and there wasn’t a concise document that looked at all of the evidence.” He and remaining members of the work group also decided to opt for extensive disclosures on their relationships with pharmaceutical manufacturers, and to ensure that the evidence drove content decisions.

“Most individuals and most organizations, like the Academy, are certainly under the microscope, and we wanted to be very sure that even though all of us have taken pharmaceutical money for research studies or consultation, that we disclosed every aspect of it,” Dr. Menter says. “We wanted to come up with guidelines that would be as fair and unbiased as we could make them.” He added that the final version of the first two sections includes or addresses many of the comments and concerns AAD members raised during the draft review period.

Both Dr. Menter and Dr. Van Voorhees acknowledge, however, that the remaining sections on topical, ultraviolet light and systemic non-biologic therapies, which will be released later this year or in early 2009, might prove more challenging than the first two. That’s because the quality and quantity of the evidence “just aren’t as good” for the standard therapies, Dr. Van Voorhees explains, some of which have been in use for several decades and were evaluated in trials whose protocol standards were not as well designed as they are today.

“Only recently have there been double-blinded controlled trials on some of the older medications,” Dr. Van Voorhees explains, citing methotrexate as a prime example. “And even those trials have limitations.”