乌鸦传媒視頻

WASHINGTON -- Dermatologists agreed that complete clearance should represent the treatment goal for all patients with psoriasis, but they remained divided over the best standard for good, but incomplete, responses, following arguments here.

The emergence of biologic and targeted therapies has made complete clearance of psoriasis a reality for more patients than ever, and results with new agents still in clinical evaluation suggest a potential for complete clearance in most patients.

When a response falls short of complete clearance, 75% improvement in the (PASI 75) represents a familiar and useful standard, , of Innovaderm Research in Montreal, argued during a debate at the American Academy of Dermatology meeting.

PASI 90 represents incremental improvement over PASI 75 but remains statistically inferior to PASI 100 (complete clearance).

Stating a case for PASI 90 as the new standard, , of Eastern Virginia Medical School in Norfolk, said the availability of more potent therapies that attain higher rates of complete clearance also argues for a higher standard for a good response.

Case for PASI 75

Though used most often in education and clinical trial settings, the issue of the most appropriate PASI score for good response goes beyond academic arguments.

"The selection of efficacy endpoints should be driven by patient expectations," Bissonnette said. "What do our psoriatic patients expect? In my practice, patients first want good improvement. They come to see me with significant disease. It's itchy. The plaques are thick and are on areas that are problematic, like the face, genitals, and hands. They want to get better.

"They want clearance. They didn't have psoriasis before, but they do now, and what they want is to be clear of psoriasis. Ideally, they would like remission or even cure. Just like a patient with pneumonia, a patient with psoriasis wants to get treated and wants the psoriasis to go away and never come back. This is what psoriasis patients are looking for."

The PASI 75 is consistent with the continuum of patient expectations, Bissonnette continued. In support of that assertion, he cited recent studies showing an association between extent of psoriasis clearance and health-related quality of life (hr-QOL).

In , patients exhibited little or no improvement in hr-QOL in association with PASI <75 but substantial improvement with PASI 75 and the greatest improvement in association with PASI 100. A evaluated QOL scores in patients who achieved clear versus almost-clear skin with different types of psoriasis therapy. The results showed significantly better QOL scores in the subgroup that had clear skin. Taken together, the data support PASI 75 as a reliable index of good improvement, Bissonnette said.

showed a large improvement in QOL in patients who achieved a PASI 75 versus those who did not. Patients who achieved PASI 90 had further improvement in QOL as compared with those in the PASI 75 subgroup, but QOL still lagged significantly behind that of patients in the PASI 100 category.

"PASI 90 is not what patients are looking for," Bissonnette said. "PASI 75 is already a good measure of clinical improvement. Beyond clinical improvement, patients are looking for clearance, which means PASI 100. PASI 100 is a good measure of clearance and should be used in conjunction with PASI 75."

Case for PASI 90

Borrowing from an automobile manufacturer advertisement from years gone by, Pariser said PASI 75 "is your father's Oldsmobile and should be relegated to history books."

Pariser agreed with Bissonnette that PASI scores track closely with QOL scores, specifically the Dermatology Quality of Life Index (DLQI). However, he maintained that "the data show that DLQI scores are clearly better in people who have PASI 90 than PASI 75 and even 'more better' in people who have PASI 100."

A of the association between PASI scores and QOL documented the superiority of PASI 90 over PASI 75. The difference should increase with the introduction of anti-IL-17 drugs that offer the potential of "achieving PASI 90 response or better in the majority of patients, and initial data suggest that the PASI 90 benchmark provides better discriminatory value as regards achievement of DLQI = 0-1 response." The author concluded that PASI 90 response should be considered "the new standard for therapeutic efficacy in psoriasis."

The emergence of new therapeutic classes for psoriasis has brought into focus the need to "set the bar higher" and adopt PASI 90 as the new standard for a good response, Pariser said. Rates of PASI 75 responses have not differed much between newer and older drugs, but new agents, such as the anti-IL-17 and anti-IL-23 drugs have led to dramatically higher rates of PASI 90 response, he said.

"Isn't it our obligation to set the expectations correctly for patients?" Pariser asked. "PASI 75 is good enough for regulatory purposes, but as a clinician, I want my patients to have PASI 90. It's a realistic goal in more than half the patients. PASI 100 is an attainable goal in over a third of patients with the new drugs that are out there."

"How can I not offer that to my patients?" Pariser added. "That's what they want. They want to be clear."

More Opinions

The audience response suggested the debate ended in a draw. The electronic tally showed that 51% of voters sided with Pariser and 49% with Bissonnette.

During a discussion that followed the presentations, differing viewpoints continued to play out.

"Perhaps the only advantage of keeping PASI 75 is that it does allow us a comparator to the standard that has been used by the FDA and the EMA (European Medicines Agency) for years, so we can see how new drugs do in comparison to drugs hat existed in the past," said , of the Oregon Medical Research Center in Portland.

"I will also say that the majority of improvement in quality of life that occurs does so with achieving PASI 75, but then the incremental improvement in quality of life unquestionably is [important]. Once a patient achieves PASI 100, they start to get nervous when that little bit of psoriasis comes back. There are clear advantages to getting those incremental improvements."

Arguments over the most appropriate PASI score overlook a key issue, said , of Probity Medical in Waterloo, Ontario. "We should remember that clinical trial results do not tell us how to manage patients. We somehow get led astray by the fact that we see results and [think] therefore this is how we should manage patients. That's not the case.

"A clinical trial informs us of how a specific population will respond when you treat them in a specific way," Papp added. "It is up to us to decide, with help from the patient...what is best for the patient. Outcome is one measure, whether you're looking at PASI 75 or PASI 90, but it's a negotiation. It is a trust that we have with patients and they with us to provide the best care possible for them."

Comment