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ISTANBUL – With the majority of psoriasis patients now achieving PASI 90 responses in randomized trials of the latest-generation biologic agents, a push is on to replace PASI 75 with PASI 90 as the new goal defining treatment success. But some dermatologists have misgivings about raising the bar.
"More and more, editorialists are promoting the idea of silencing psoriasis in all patients. This is a tricky and challenging goal," Dr. Hervé Bachelez said at the annual congress of the European Academy of Dermatology and Venereology.
"You’ve probably noticed that PASI 90 and even PASI 100 are becoming important as secondary endpoints in virtually all clinical trials. It’s good, it’s legitimate, and the PASI 90 probably better reflects the wishes of the patient and the physician than the PASI 75. But we have to wait and see what the caveats of this are. You can say, ‘Let’s push the response rate up to PASI 100 in all patients,’ but the danger is that if you cross a line, you may be unable to precisely regulate the level of immunosuppression in some patients. Basically you can expect some safety issues in real life that you would not see in clinical trials," cautioned Dr. Bachelez, professor of dermatology and head of the inflammatory skin diseases unit at Saint Louis University Hospital, Paris.
Not so many years ago the notion of PASI 90 responses in high double figures seemed a pipedream, he observed. For example, the week-12 PASI 90 rate in published randomized trials of methotrexate was only 9%, while for the first-generation tumor necrosis factor inhibitor etanercept, the rates were 19%-23%. In contrast, among the highlights of this year’s EADV congress were the presentation of results from clinical trials of two investigational interleukin-17 inhibitors: In the pivotal Phase III FIXTURE trial, secukinumab-treated patients had a PASI 90 response rate of 72% at week 16, while the week-16 PASI 90 rate in the Phase II OLE trial was 87% in patients on brodalimab, and even out to week 96, it was 78%.
Underscoring Dr. Bachelez’ concern that the randomized trial experience likely underestimates the true extent of safety hazards posed by potent therapies in daily clinical practice was a report by a consortium of 13 Spanish dermatology departments responsible for the BIOBADADERM registry. The Spanish registry is focused on safety and includes only psoriasis patients on systemic therapy, whether biologics or classic drugs. Among the first 1,042 enrollees receiving systemic therapy, fully 30% would not have been eligible for participation in randomized controlled trials for various reasons, including age greater than 70 years, having chronic kidney or liver disease, a history of hepatitis B or C, HIV infection, or cancer, or having psoriasis of a type other than chronic plaque disease.
The disturbing finding was that during 2,179 person-years of prospective follow-up, the large group of patients ineligible for randomized trials had a 2.7-fold increased risk of serious adverse events compared with patients on systemic therapy who were eligible for study participation.
The number needed to harm was calculated as follows: For every 40 patients treated with systemic therapy for 2.1 years despite not being eligible for randomized trials, one additional serious adverse event can be expected compared with similar treatment in randomized trial-eligible patients, according to the investigators (Arch. Dermatol. 2012;148:463-70). And that’s without pushing the envelope by trying to aim for a PASI 90 response, Dr. Bachelez noted.
A contrary view regarding PASI 90 as an emerging standard of treatment excellence was put forth elsewhere at the meeting by Dr. Peter van de Kerkhof, professor and head of the department of dermatology at Radboud University in Nijmegen, the Netherlands.
He cited multiple studies demonstrating that substantial PASI reductions may not translate into tangible improvements in patients’ quality of life. For example, among psoriasis patients who achieved a PASI 75 response in one European study, 65% still had a Dermatology Life Quality Index (DLQI) score of 2 or more (Eur. J. Dermatol. 2010;20:62-7).
"This implies that there is something more to be wished for by patients, even when PASI 75 is reached," according to Dr. van de Kerkhof.
Moreover, in another trial, even among patients with a PASI score of 0 at week 24, only 70% had an optimal DLQI of 0, not 100% as most dermatologists might expect (Br. J. Dermatol. 2006;154:1161-8).
A recent survey of 2,151 European psoriasis patients and their dermatologists highlighted a substantial degree of dissatisfaction with current therapies. Patients on biologics had higher rates of improvement from severe to moderate or mild disease than did those on any other forms of psoriasis therapy, yet 41% of patients on biologics were dissatisfied with their treatment (J. Dermatolog. Treat. 2013;24:193-8).
"I think it’s extremely important that we continue to innovate treatment possibilities for psoriasis in order to improve outcomes for our patients," Dr. van de Kerkhof said.
What patients really want, surveys suggest, are treatments that render them clear or nearly clear, and do so quickly. In one survey, patients rated as the most important characteristic about a therapy the rapidity with which it could achieve a moderate 50% improvement in symptoms. They rated that as higher in importance to them than the therapy’s long-term risks (Arch. Dermatol. 2007;143:1175-9), Dr. van de Kerkhof noted.
Patients also place a high priority on improvement of a broad array of symptoms that aren’t captured by either the PASI or the DLQI, Dr. Bruce E. Strober noted in a separate presentation. These include itching, plaque-related pain, altered skin appearance, flaking, and bleeding.
For this reason, he and a group of his coworkers have created and are now validating a new tool for the assessment of patient-related outcomes in psoriasis called the Psoriasis Symptom Diary (Value Health 2013;16:1014-22). The 16-item tool takes less than 5 minutes for a patient to fill out and is designed to replace the DLQI both in clinical trials and everyday practice. The goal is to be able to walk into the examination room, take a quick look at the Psoriasis Symptom Diary, and know from that how a patient is currently doing even before asking for the patient to disrobe.
"Let’s face it: Outside of skin cancer, when we’re doing dermatology, we’re in the quality of life business. That means we’re asking patients how they’re doing at every visit for psoriasis, atopic dermatitis, or severe acne. The DLQI does that, but it’s not psoriasis specific," said Dr. Strober, vice chair and director of the clinical trials unit in the department of dermatology at the University of Connecticut, Farmington.
As for the PASI, he doesn’t use it except in structured clinical trials. It’s too time consuming and has a high rate of inter- and intrarater variability.
"In the United States, dermatologists never do PASI scores in their clinics. The PASI score has numerous drawbacks that make it impractical in a regular practice setting," Dr. Strober said. "In my own practice, I routinely do a 5-point Physician’s Global Assessment along with an estimate of involved body surface area. I think that gives you a good picture of the objective level of psoriasis severity."
Dr. Bachelez, Dr. van de Kerkhof, and Dr. Strober each reported receiving research grants from and serving on advisory boards for 9-14 pharmaceutical companies engaged in developing new treatments for psoriasis.
ISTANBUL – With the majority of psoriasis patients now achieving PASI 90 responses in randomized trials of the latest-generation biologic agents, a push is on to replace PASI 75 with PASI 90 as the new goal defining treatment success. But some dermatologists have misgivings about raising the bar.
"More and more, editorialists are promoting the idea of silencing psoriasis in all patients. This is a tricky and challenging goal," Dr. Hervé Bachelez said at the annual congress of the European Academy of Dermatology and Venereology.
"You’ve probably noticed that PASI 90 and even PASI 100 are becoming important as secondary endpoints in virtually all clinical trials. It’s good, it’s legitimate, and the PASI 90 probably better reflects the wishes of the patient and the physician than the PASI 75. But we have to wait and see what the caveats of this are. You can say, ‘Let’s push the response rate up to PASI 100 in all patients,’ but the danger is that if you cross a line, you may be unable to precisely regulate the level of immunosuppression in some patients. Basically you can expect some safety issues in real life that you would not see in clinical trials," cautioned Dr. Bachelez, professor of dermatology and head of the inflammatory skin diseases unit at Saint Louis University Hospital, Paris.
Not so many years ago the notion of PASI 90 responses in high double figures seemed a pipedream, he observed. For example, the week-12 PASI 90 rate in published randomized trials of methotrexate was only 9%, while for the first-generation tumor necrosis factor inhibitor etanercept, the rates were 19%-23%. In contrast, among the highlights of this year’s EADV congress were the presentation of results from clinical trials of two investigational interleukin-17 inhibitors: In the pivotal Phase III FIXTURE trial, secukinumab-treated patients had a PASI 90 response rate of 72% at week 16, while the week-16 PASI 90 rate in the Phase II OLE trial was 87% in patients on brodalimab, and even out to week 96, it was 78%.
Underscoring Dr. Bachelez’ concern that the randomized trial experience likely underestimates the true extent of safety hazards posed by potent therapies in daily clinical practice was a report by a consortium of 13 Spanish dermatology departments responsible for the BIOBADADERM registry. The Spanish registry is focused on safety and includes only psoriasis patients on systemic therapy, whether biologics or classic drugs. Among the first 1,042 enrollees receiving systemic therapy, fully 30% would not have been eligible for participation in randomized controlled trials for various reasons, including age greater than 70 years, having chronic kidney or liver disease, a history of hepatitis B or C, HIV infection, or cancer, or having psoriasis of a type other than chronic plaque disease.
The disturbing finding was that during 2,179 person-years of prospective follow-up, the large group of patients ineligible for randomized trials had a 2.7-fold increased risk of serious adverse events compared with patients on systemic therapy who were eligible for study participation.
The number needed to harm was calculated as follows: For every 40 patients treated with systemic therapy for 2.1 years despite not being eligible for randomized trials, one additional serious adverse event can be expected compared with similar treatment in randomized trial-eligible patients, according to the investigators (Arch. Dermatol. 2012;148:463-70). And that’s without pushing the envelope by trying to aim for a PASI 90 response, Dr. Bachelez noted.
A contrary view regarding PASI 90 as an emerging standard of treatment excellence was put forth elsewhere at the meeting by Dr. Peter van de Kerkhof, professor and head of the department of dermatology at Radboud University in Nijmegen, the Netherlands.
He cited multiple studies demonstrating that substantial PASI reductions may not translate into tangible improvements in patients’ quality of life. For example, among psoriasis patients who achieved a PASI 75 response in one European study, 65% still had a Dermatology Life Quality Index (DLQI) score of 2 or more (Eur. J. Dermatol. 2010;20:62-7).
"This implies that there is something more to be wished for by patients, even when PASI 75 is reached," according to Dr. van de Kerkhof.
Moreover, in another trial, even among patients with a PASI score of 0 at week 24, only 70% had an optimal DLQI of 0, not 100% as most dermatologists might expect (Br. J. Dermatol. 2006;154:1161-8).
A recent survey of 2,151 European psoriasis patients and their dermatologists highlighted a substantial degree of dissatisfaction with current therapies. Patients on biologics had higher rates of improvement from severe to moderate or mild disease than did those on any other forms of psoriasis therapy, yet 41% of patients on biologics were dissatisfied with their treatment (J. Dermatolog. Treat. 2013;24:193-8).
"I think it’s extremely important that we continue to innovate treatment possibilities for psoriasis in order to improve outcomes for our patients," Dr. van de Kerkhof said.
What patients really want, surveys suggest, are treatments that render them clear or nearly clear, and do so quickly. In one survey, patients rated as the most important characteristic about a therapy the rapidity with which it could achieve a moderate 50% improvement in symptoms. They rated that as higher in importance to them than the therapy’s long-term risks (Arch. Dermatol. 2007;143:1175-9), Dr. van de Kerkhof noted.
Patients also place a high priority on improvement of a broad array of symptoms that aren’t captured by either the PASI or the DLQI, Dr. Bruce E. Strober noted in a separate presentation. These include itching, plaque-related pain, altered skin appearance, flaking, and bleeding.
For this reason, he and a group of his coworkers have created and are now validating a new tool for the assessment of patient-related outcomes in psoriasis called the Psoriasis Symptom Diary (Value Health 2013;16:1014-22). The 16-item tool takes less than 5 minutes for a patient to fill out and is designed to replace the DLQI both in clinical trials and everyday practice. The goal is to be able to walk into the examination room, take a quick look at the Psoriasis Symptom Diary, and know from that how a patient is currently doing even before asking for the patient to disrobe.
"Let’s face it: Outside of skin cancer, when we’re doing dermatology, we’re in the quality of life business. That means we’re asking patients how they’re doing at every visit for psoriasis, atopic dermatitis, or severe acne. The DLQI does that, but it’s not psoriasis specific," said Dr. Strober, vice chair and director of the clinical trials unit in the department of dermatology at the University of Connecticut, Farmington.
As for the PASI, he doesn’t use it except in structured clinical trials. It’s too time consuming and has a high rate of inter- and intrarater variability.
"In the United States, dermatologists never do PASI scores in their clinics. The PASI score has numerous drawbacks that make it impractical in a regular practice setting," Dr. Strober said. "In my own practice, I routinely do a 5-point Physician’s Global Assessment along with an estimate of involved body surface area. I think that gives you a good picture of the objective level of psoriasis severity."
Dr. Bachelez, Dr. van de Kerkhof, and Dr. Strober each reported receiving research grants from and serving on advisory boards for 9-14 pharmaceutical companies engaged in developing new treatments for psoriasis.
ISTANBUL – With the majority of psoriasis patients now achieving PASI 90 responses in randomized trials of the latest-generation biologic agents, a push is on to replace PASI 75 with PASI 90 as the new goal defining treatment success. But some dermatologists have misgivings about raising the bar.
"More and more, editorialists are promoting the idea of silencing psoriasis in all patients. This is a tricky and challenging goal," Dr. Hervé Bachelez said at the annual congress of the European Academy of Dermatology and Venereology.
"You’ve probably noticed that PASI 90 and even PASI 100 are becoming important as secondary endpoints in virtually all clinical trials. It’s good, it’s legitimate, and the PASI 90 probably better reflects the wishes of the patient and the physician than the PASI 75. But we have to wait and see what the caveats of this are. You can say, ‘Let’s push the response rate up to PASI 100 in all patients,’ but the danger is that if you cross a line, you may be unable to precisely regulate the level of immunosuppression in some patients. Basically you can expect some safety issues in real life that you would not see in clinical trials," cautioned Dr. Bachelez, professor of dermatology and head of the inflammatory skin diseases unit at Saint Louis University Hospital, Paris.
Not so many years ago the notion of PASI 90 responses in high double figures seemed a pipedream, he observed. For example, the week-12 PASI 90 rate in published randomized trials of methotrexate was only 9%, while for the first-generation tumor necrosis factor inhibitor etanercept, the rates were 19%-23%. In contrast, among the highlights of this year’s EADV congress were the presentation of results from clinical trials of two investigational interleukin-17 inhibitors: In the pivotal Phase III FIXTURE trial, secukinumab-treated patients had a PASI 90 response rate of 72% at week 16, while the week-16 PASI 90 rate in the Phase II OLE trial was 87% in patients on brodalimab, and even out to week 96, it was 78%.
Underscoring Dr. Bachelez’ concern that the randomized trial experience likely underestimates the true extent of safety hazards posed by potent therapies in daily clinical practice was a report by a consortium of 13 Spanish dermatology departments responsible for the BIOBADADERM registry. The Spanish registry is focused on safety and includes only psoriasis patients on systemic therapy, whether biologics or classic drugs. Among the first 1,042 enrollees receiving systemic therapy, fully 30% would not have been eligible for participation in randomized controlled trials for various reasons, including age greater than 70 years, having chronic kidney or liver disease, a history of hepatitis B or C, HIV infection, or cancer, or having psoriasis of a type other than chronic plaque disease.
The disturbing finding was that during 2,179 person-years of prospective follow-up, the large group of patients ineligible for randomized trials had a 2.7-fold increased risk of serious adverse events compared with patients on systemic therapy who were eligible for study participation.
The number needed to harm was calculated as follows: For every 40 patients treated with systemic therapy for 2.1 years despite not being eligible for randomized trials, one additional serious adverse event can be expected compared with similar treatment in randomized trial-eligible patients, according to the investigators (Arch. Dermatol. 2012;148:463-70). And that’s without pushing the envelope by trying to aim for a PASI 90 response, Dr. Bachelez noted.
A contrary view regarding PASI 90 as an emerging standard of treatment excellence was put forth elsewhere at the meeting by Dr. Peter van de Kerkhof, professor and head of the department of dermatology at Radboud University in Nijmegen, the Netherlands.
He cited multiple studies demonstrating that substantial PASI reductions may not translate into tangible improvements in patients’ quality of life. For example, among psoriasis patients who achieved a PASI 75 response in one European study, 65% still had a Dermatology Life Quality Index (DLQI) score of 2 or more (Eur. J. Dermatol. 2010;20:62-7).
"This implies that there is something more to be wished for by patients, even when PASI 75 is reached," according to Dr. van de Kerkhof.
Moreover, in another trial, even among patients with a PASI score of 0 at week 24, only 70% had an optimal DLQI of 0, not 100% as most dermatologists might expect (Br. J. Dermatol. 2006;154:1161-8).
A recent survey of 2,151 European psoriasis patients and their dermatologists highlighted a substantial degree of dissatisfaction with current therapies. Patients on biologics had higher rates of improvement from severe to moderate or mild disease than did those on any other forms of psoriasis therapy, yet 41% of patients on biologics were dissatisfied with their treatment (J. Dermatolog. Treat. 2013;24:193-8).
"I think it’s extremely important that we continue to innovate treatment possibilities for psoriasis in order to improve outcomes for our patients," Dr. van de Kerkhof said.
What patients really want, surveys suggest, are treatments that render them clear or nearly clear, and do so quickly. In one survey, patients rated as the most important characteristic about a therapy the rapidity with which it could achieve a moderate 50% improvement in symptoms. They rated that as higher in importance to them than the therapy’s long-term risks (Arch. Dermatol. 2007;143:1175-9), Dr. van de Kerkhof noted.
Patients also place a high priority on improvement of a broad array of symptoms that aren’t captured by either the PASI or the DLQI, Dr. Bruce E. Strober noted in a separate presentation. These include itching, plaque-related pain, altered skin appearance, flaking, and bleeding.
For this reason, he and a group of his coworkers have created and are now validating a new tool for the assessment of patient-related outcomes in psoriasis called the Psoriasis Symptom Diary (Value Health 2013;16:1014-22). The 16-item tool takes less than 5 minutes for a patient to fill out and is designed to replace the DLQI both in clinical trials and everyday practice. The goal is to be able to walk into the examination room, take a quick look at the Psoriasis Symptom Diary, and know from that how a patient is currently doing even before asking for the patient to disrobe.
"Let’s face it: Outside of skin cancer, when we’re doing dermatology, we’re in the quality of life business. That means we’re asking patients how they’re doing at every visit for psoriasis, atopic dermatitis, or severe acne. The DLQI does that, but it’s not psoriasis specific," said Dr. Strober, vice chair and director of the clinical trials unit in the department of dermatology at the University of Connecticut, Farmington.
As for the PASI, he doesn’t use it except in structured clinical trials. It’s too time consuming and has a high rate of inter- and intrarater variability.
"In the United States, dermatologists never do PASI scores in their clinics. The PASI score has numerous drawbacks that make it impractical in a regular practice setting," Dr. Strober said. "In my own practice, I routinely do a 5-point Physician’s Global Assessment along with an estimate of involved body surface area. I think that gives you a good picture of the objective level of psoriasis severity."
Dr. Bachelez, Dr. van de Kerkhof, and Dr. Strober each reported receiving research grants from and serving on advisory boards for 9-14 pharmaceutical companies engaged in developing new treatments for psoriasis.
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