User login
Interleukin-23 inhibition for psoriasis shows ‘wow’ factor
GENEVA – The merits of addressing interleukin-23 as a novel therapeutic target in moderate to severe plaque psoriasis were abundantly displayed in 2-year outcomes data for two anti–IL-23 monoclonal antibodies – guselkumab and tildrakizumab – in studies presented back to back at the annual congress of the European Academy of Dermatology and Venereology.
These long-term, open-label extensions of previously reported phase 3, randomized, double-blind clinical trials provided evidence of multiple advantages for IL-23 inhibition. The story was similar for both agents: After 2 years of use in the extension studies, the two biologics demonstrated stellar treatment response rates that would have been unimaginable only a few years ago, maintenance of efficacy without drop-off over time, exceedingly low dropout rates, and a safety picture that remains reassuring as experience accumulates. Also, the subcutaneously administered IL-23 inhibitors are attractive from a patient convenience standpoint in that maintenance guselkumab is dosed at 100 mg once every 8 weeks, and tildrakizumab is given once every 12 weeks.
Still, there are differences between the two drugs, most notably in apparent effectiveness. While more than half of guselkumab-treated patients had a Psoriasis Area Severity Index (PASI) 100 response – that is, totally clear skin – at 2 years, that was the case for only one-quarter to one-third of patients on tildrakizumab.
Guselkumab (Tremfya) was approved by the Food and Drug Administration in July 2017 for treatment of adults with moderate to severe plaque psoriasis. Tildrakizumab remains investigational.
Guselkumab
The 2-year, open-label extension of the phase 3 VOYAGE 1 trial included 735 patients who were either on guselkumab continuously, crossed from adalimumab (Humira) to guselkumab after 48 weeks, or switched from placebo after 16 weeks.
PASI 100 rates at 2 years were 49%-55% in the three patient groups. Of the patients in these groups, 54%-59% achieved an Investigator’s Global Assessment (IGA) score of 0. IGA scores of 0 or 1, meaning clear or almost clear skin, were present in 82%-85% of patients at 2 years.
“Dropout rate is an important consideration in long-term studies,” observed Dr. Blauvelt, a dermatologist and president of Oregon Medical Research Center in Portland. “For patients on continuous guselkumab there was a 6% dropout rate in the first year and 6% in the second year, so 88% of patients that started guselkumab were still on guselkumab 2 years later. That’s impressive. In the other two groups, the dropout rate was 2% per year.”
A Dermatology Life Quality Index (DLQI) score of 0 or 1, meaning no disease effects on quality of life, was recorded in 62.5% of the continuous guselkumab group at 48 weeks and 71.1% at 2 years.
“The interesting thing here is that, even though the efficacy numbers are fairly constant between year 1 and year 2, the DLQI goes up and up. Surprising? Maybe not. I think it shows patients are getting happier and happier over time with their disease control,” Dr. Blauvelt continued.
Rates of serious adverse events remained low and stable, with no negative surprises during year 2. The serious infection rate was 1.02 cases/100 patient-years in year 1 and 0.84 cases/100 patient-years in year 2. No cases of tuberculosis, opportunistic infections, or serious hypersensitivity reactions occurred during 2 years of treatment.
Tildrakizumab
Two-year results from the ongoing 5-year extension of the phase 3 reSURFACE 1 and reSURFACE 2 trials were presented by Kim A. Papp, MD, PhD, president of Probity Medical Research, Waterloo, Ont. This presentation of 2-year outcomes for 1,237 study participants was a feat, considering that the 12-week results of the trials had been published less than 3 months earlier (Lancet. 2017 Jul 15;390[10091]:276-88).
“I think these data are very compelling that the loss of response over time is minimal,” according to the dermatologist. “We’ve also seen that safety over 2 years has no surprises; in fact, it’s remarkably quiet. The rate of severe infections, which is important to look at for any treatment suppressing the immune system, is low and occurs almost independent of dose, which is very hopeful. It’s a promising sign.”
Indeed, the serious infection rate was 0.8 cases/100 patient-years regardless of whether subjects were on tildrakizumab at 100 mg or 200 mg.
Controversy over how to report long-term outcomes
A hot topic among clinical trialists in dermatology concerns how to report study results. The traditional method in studies funded by pharmaceutical companies is known as the “last observation carried forward” analysis. It casts the study drug results in the most favorable possible light because, when a subject drops out of a trial for any reason, their last measured value for response to treatment is carried forward as though the patient completed the study. Thus, psoriasis patients who drop out because they couldn’t tolerate a therapy or developed a serious side effect dictating discontinuation will be scored on the basis of their last PASI response, creating a bias in favor of active treatment.
A more conservative analytic method is known as the “nonresponder imputation” analysis. By this method, a patient who drops out of a trial is automatically categorized as a treatment failure, even if the reason was that the patient moved and could no longer make visits to the study center.
The prespecified guselkumab analysis presented by Dr. Blauvelt involved nonresponder imputation through year 1 and imputation based on the reason for discontinuation in the second year. In contrast, the 2-year tildrakizumab analysis presented by Dr. Papp used the far more common last observation carried forward method.
To help the audience appreciate the importance of looking at the analytic methods used in a studies and help them understand the clinical significance of the results, Dr. Blauvelt provided a reanalysis of the 2-year guselkumab data using the last observation carried forward method. Across the board, the numbers became more favorable. For example, the PASI 75 rate of 95.7% using the prespecified nonresponder imputation analysis crept up to 96.8% under the last observation carried forward method; for comparison, the PASI 75 rates were 81%-84% in the tildrakizumab analysis.
“If you wanted to compare apples to apples with some other drugs, you would use these numbers – the as-observed analysis numbers used by most other companies with other drugs. If you wanted to determine what the true-life numbers are, they’d probably be something between the nonresponder imputation and as-observed numbers,” said to Dr. Blauvelt.
Dr. Papp was untroubled by the use of the last observation carried forward method in the particular case of the tildrakizumab long-term extension study.
“There is reason to believe the as-observed analysis doesn’t affect the integrity of the data because the dropout rate is extraordinarily low,” he said.
The guselkumab analysis was sponsored by Janssen Pharmaceutica; the tildrakizumab analysis was sponsored by Merck and by Sun Pharma. Dr. Blauvelt and Dr. Papp were paid investigators in both studies and serve as scientific advisers to virtually all companies invested in the psoriasis therapy developmental pipeline.
GENEVA – The merits of addressing interleukin-23 as a novel therapeutic target in moderate to severe plaque psoriasis were abundantly displayed in 2-year outcomes data for two anti–IL-23 monoclonal antibodies – guselkumab and tildrakizumab – in studies presented back to back at the annual congress of the European Academy of Dermatology and Venereology.
These long-term, open-label extensions of previously reported phase 3, randomized, double-blind clinical trials provided evidence of multiple advantages for IL-23 inhibition. The story was similar for both agents: After 2 years of use in the extension studies, the two biologics demonstrated stellar treatment response rates that would have been unimaginable only a few years ago, maintenance of efficacy without drop-off over time, exceedingly low dropout rates, and a safety picture that remains reassuring as experience accumulates. Also, the subcutaneously administered IL-23 inhibitors are attractive from a patient convenience standpoint in that maintenance guselkumab is dosed at 100 mg once every 8 weeks, and tildrakizumab is given once every 12 weeks.
Still, there are differences between the two drugs, most notably in apparent effectiveness. While more than half of guselkumab-treated patients had a Psoriasis Area Severity Index (PASI) 100 response – that is, totally clear skin – at 2 years, that was the case for only one-quarter to one-third of patients on tildrakizumab.
Guselkumab (Tremfya) was approved by the Food and Drug Administration in July 2017 for treatment of adults with moderate to severe plaque psoriasis. Tildrakizumab remains investigational.
Guselkumab
The 2-year, open-label extension of the phase 3 VOYAGE 1 trial included 735 patients who were either on guselkumab continuously, crossed from adalimumab (Humira) to guselkumab after 48 weeks, or switched from placebo after 16 weeks.
PASI 100 rates at 2 years were 49%-55% in the three patient groups. Of the patients in these groups, 54%-59% achieved an Investigator’s Global Assessment (IGA) score of 0. IGA scores of 0 or 1, meaning clear or almost clear skin, were present in 82%-85% of patients at 2 years.
“Dropout rate is an important consideration in long-term studies,” observed Dr. Blauvelt, a dermatologist and president of Oregon Medical Research Center in Portland. “For patients on continuous guselkumab there was a 6% dropout rate in the first year and 6% in the second year, so 88% of patients that started guselkumab were still on guselkumab 2 years later. That’s impressive. In the other two groups, the dropout rate was 2% per year.”
A Dermatology Life Quality Index (DLQI) score of 0 or 1, meaning no disease effects on quality of life, was recorded in 62.5% of the continuous guselkumab group at 48 weeks and 71.1% at 2 years.
“The interesting thing here is that, even though the efficacy numbers are fairly constant between year 1 and year 2, the DLQI goes up and up. Surprising? Maybe not. I think it shows patients are getting happier and happier over time with their disease control,” Dr. Blauvelt continued.
Rates of serious adverse events remained low and stable, with no negative surprises during year 2. The serious infection rate was 1.02 cases/100 patient-years in year 1 and 0.84 cases/100 patient-years in year 2. No cases of tuberculosis, opportunistic infections, or serious hypersensitivity reactions occurred during 2 years of treatment.
Tildrakizumab
Two-year results from the ongoing 5-year extension of the phase 3 reSURFACE 1 and reSURFACE 2 trials were presented by Kim A. Papp, MD, PhD, president of Probity Medical Research, Waterloo, Ont. This presentation of 2-year outcomes for 1,237 study participants was a feat, considering that the 12-week results of the trials had been published less than 3 months earlier (Lancet. 2017 Jul 15;390[10091]:276-88).
“I think these data are very compelling that the loss of response over time is minimal,” according to the dermatologist. “We’ve also seen that safety over 2 years has no surprises; in fact, it’s remarkably quiet. The rate of severe infections, which is important to look at for any treatment suppressing the immune system, is low and occurs almost independent of dose, which is very hopeful. It’s a promising sign.”
Indeed, the serious infection rate was 0.8 cases/100 patient-years regardless of whether subjects were on tildrakizumab at 100 mg or 200 mg.
Controversy over how to report long-term outcomes
A hot topic among clinical trialists in dermatology concerns how to report study results. The traditional method in studies funded by pharmaceutical companies is known as the “last observation carried forward” analysis. It casts the study drug results in the most favorable possible light because, when a subject drops out of a trial for any reason, their last measured value for response to treatment is carried forward as though the patient completed the study. Thus, psoriasis patients who drop out because they couldn’t tolerate a therapy or developed a serious side effect dictating discontinuation will be scored on the basis of their last PASI response, creating a bias in favor of active treatment.
A more conservative analytic method is known as the “nonresponder imputation” analysis. By this method, a patient who drops out of a trial is automatically categorized as a treatment failure, even if the reason was that the patient moved and could no longer make visits to the study center.
The prespecified guselkumab analysis presented by Dr. Blauvelt involved nonresponder imputation through year 1 and imputation based on the reason for discontinuation in the second year. In contrast, the 2-year tildrakizumab analysis presented by Dr. Papp used the far more common last observation carried forward method.
To help the audience appreciate the importance of looking at the analytic methods used in a studies and help them understand the clinical significance of the results, Dr. Blauvelt provided a reanalysis of the 2-year guselkumab data using the last observation carried forward method. Across the board, the numbers became more favorable. For example, the PASI 75 rate of 95.7% using the prespecified nonresponder imputation analysis crept up to 96.8% under the last observation carried forward method; for comparison, the PASI 75 rates were 81%-84% in the tildrakizumab analysis.
“If you wanted to compare apples to apples with some other drugs, you would use these numbers – the as-observed analysis numbers used by most other companies with other drugs. If you wanted to determine what the true-life numbers are, they’d probably be something between the nonresponder imputation and as-observed numbers,” said to Dr. Blauvelt.
Dr. Papp was untroubled by the use of the last observation carried forward method in the particular case of the tildrakizumab long-term extension study.
“There is reason to believe the as-observed analysis doesn’t affect the integrity of the data because the dropout rate is extraordinarily low,” he said.
The guselkumab analysis was sponsored by Janssen Pharmaceutica; the tildrakizumab analysis was sponsored by Merck and by Sun Pharma. Dr. Blauvelt and Dr. Papp were paid investigators in both studies and serve as scientific advisers to virtually all companies invested in the psoriasis therapy developmental pipeline.
GENEVA – The merits of addressing interleukin-23 as a novel therapeutic target in moderate to severe plaque psoriasis were abundantly displayed in 2-year outcomes data for two anti–IL-23 monoclonal antibodies – guselkumab and tildrakizumab – in studies presented back to back at the annual congress of the European Academy of Dermatology and Venereology.
These long-term, open-label extensions of previously reported phase 3, randomized, double-blind clinical trials provided evidence of multiple advantages for IL-23 inhibition. The story was similar for both agents: After 2 years of use in the extension studies, the two biologics demonstrated stellar treatment response rates that would have been unimaginable only a few years ago, maintenance of efficacy without drop-off over time, exceedingly low dropout rates, and a safety picture that remains reassuring as experience accumulates. Also, the subcutaneously administered IL-23 inhibitors are attractive from a patient convenience standpoint in that maintenance guselkumab is dosed at 100 mg once every 8 weeks, and tildrakizumab is given once every 12 weeks.
Still, there are differences between the two drugs, most notably in apparent effectiveness. While more than half of guselkumab-treated patients had a Psoriasis Area Severity Index (PASI) 100 response – that is, totally clear skin – at 2 years, that was the case for only one-quarter to one-third of patients on tildrakizumab.
Guselkumab (Tremfya) was approved by the Food and Drug Administration in July 2017 for treatment of adults with moderate to severe plaque psoriasis. Tildrakizumab remains investigational.
Guselkumab
The 2-year, open-label extension of the phase 3 VOYAGE 1 trial included 735 patients who were either on guselkumab continuously, crossed from adalimumab (Humira) to guselkumab after 48 weeks, or switched from placebo after 16 weeks.
PASI 100 rates at 2 years were 49%-55% in the three patient groups. Of the patients in these groups, 54%-59% achieved an Investigator’s Global Assessment (IGA) score of 0. IGA scores of 0 or 1, meaning clear or almost clear skin, were present in 82%-85% of patients at 2 years.
“Dropout rate is an important consideration in long-term studies,” observed Dr. Blauvelt, a dermatologist and president of Oregon Medical Research Center in Portland. “For patients on continuous guselkumab there was a 6% dropout rate in the first year and 6% in the second year, so 88% of patients that started guselkumab were still on guselkumab 2 years later. That’s impressive. In the other two groups, the dropout rate was 2% per year.”
A Dermatology Life Quality Index (DLQI) score of 0 or 1, meaning no disease effects on quality of life, was recorded in 62.5% of the continuous guselkumab group at 48 weeks and 71.1% at 2 years.
“The interesting thing here is that, even though the efficacy numbers are fairly constant between year 1 and year 2, the DLQI goes up and up. Surprising? Maybe not. I think it shows patients are getting happier and happier over time with their disease control,” Dr. Blauvelt continued.
Rates of serious adverse events remained low and stable, with no negative surprises during year 2. The serious infection rate was 1.02 cases/100 patient-years in year 1 and 0.84 cases/100 patient-years in year 2. No cases of tuberculosis, opportunistic infections, or serious hypersensitivity reactions occurred during 2 years of treatment.
Tildrakizumab
Two-year results from the ongoing 5-year extension of the phase 3 reSURFACE 1 and reSURFACE 2 trials were presented by Kim A. Papp, MD, PhD, president of Probity Medical Research, Waterloo, Ont. This presentation of 2-year outcomes for 1,237 study participants was a feat, considering that the 12-week results of the trials had been published less than 3 months earlier (Lancet. 2017 Jul 15;390[10091]:276-88).
“I think these data are very compelling that the loss of response over time is minimal,” according to the dermatologist. “We’ve also seen that safety over 2 years has no surprises; in fact, it’s remarkably quiet. The rate of severe infections, which is important to look at for any treatment suppressing the immune system, is low and occurs almost independent of dose, which is very hopeful. It’s a promising sign.”
Indeed, the serious infection rate was 0.8 cases/100 patient-years regardless of whether subjects were on tildrakizumab at 100 mg or 200 mg.
Controversy over how to report long-term outcomes
A hot topic among clinical trialists in dermatology concerns how to report study results. The traditional method in studies funded by pharmaceutical companies is known as the “last observation carried forward” analysis. It casts the study drug results in the most favorable possible light because, when a subject drops out of a trial for any reason, their last measured value for response to treatment is carried forward as though the patient completed the study. Thus, psoriasis patients who drop out because they couldn’t tolerate a therapy or developed a serious side effect dictating discontinuation will be scored on the basis of their last PASI response, creating a bias in favor of active treatment.
A more conservative analytic method is known as the “nonresponder imputation” analysis. By this method, a patient who drops out of a trial is automatically categorized as a treatment failure, even if the reason was that the patient moved and could no longer make visits to the study center.
The prespecified guselkumab analysis presented by Dr. Blauvelt involved nonresponder imputation through year 1 and imputation based on the reason for discontinuation in the second year. In contrast, the 2-year tildrakizumab analysis presented by Dr. Papp used the far more common last observation carried forward method.
To help the audience appreciate the importance of looking at the analytic methods used in a studies and help them understand the clinical significance of the results, Dr. Blauvelt provided a reanalysis of the 2-year guselkumab data using the last observation carried forward method. Across the board, the numbers became more favorable. For example, the PASI 75 rate of 95.7% using the prespecified nonresponder imputation analysis crept up to 96.8% under the last observation carried forward method; for comparison, the PASI 75 rates were 81%-84% in the tildrakizumab analysis.
“If you wanted to compare apples to apples with some other drugs, you would use these numbers – the as-observed analysis numbers used by most other companies with other drugs. If you wanted to determine what the true-life numbers are, they’d probably be something between the nonresponder imputation and as-observed numbers,” said to Dr. Blauvelt.
Dr. Papp was untroubled by the use of the last observation carried forward method in the particular case of the tildrakizumab long-term extension study.
“There is reason to believe the as-observed analysis doesn’t affect the integrity of the data because the dropout rate is extraordinarily low,” he said.
The guselkumab analysis was sponsored by Janssen Pharmaceutica; the tildrakizumab analysis was sponsored by Merck and by Sun Pharma. Dr. Blauvelt and Dr. Papp were paid investigators in both studies and serve as scientific advisers to virtually all companies invested in the psoriasis therapy developmental pipeline.
expert analysis from tHE EADV CONGRESS
Novel oral orphan drug tames pemphigus
GENEVA – An oral reversible Bruton tyrosine kinase inhibitor known as PRN1008 showed promising efficacy and safety for the treatment of pemphigus vulgaris in an interim analysis of an ongoing small-to-date, open-label phase 2 study, according to DeDee Murrell, MD.
PRN1008 is a designer drug intended as an alternative to the long-standing standard therapy for pemphigus, months to years of moderate- or high-dose systemic corticosteroids, with all the debilitating side effects that sledgehammer approach often brings, she said at the annual congress of the European Academy of Dermatology and Venereology.
Thus, PRN1008 inhibits a range of inflammatory cellular activities in mast cells, neutrophils, and other cells activated in autoimmune diseases, without killing those cells or directly affecting T cells. And – like corticosteroids – it works quickly, according to Dr. Murrell, professor of dermatology at the University of New South Wales in Sydney.
“The development of an oral, fast-acting treatment that could safely and effectively modulate B-cell function without depleting B cells would be a major advance in treating autoimmune diseases like pemphigus, vasculitis, immune thrombocytopenic purpura, multiple sclerosis, and rheumatoid arthritis,” she said.
Also, PRN1008 was designed to provide durable inhibition of BTK, coupled with rapid systemic clearance of the drug in order to minimize side effects.
The ongoing phase 2 multicenter international study, known as Believe-PV, to date includes 12 patients with biopsy-proven mild to moderate pemphigus vulgaris. Five patients were newly diagnosed and treatment naive, while seven had relapsing disease. All were placed on fixed-dose PRN1008 at 400 mg b.i.d. for 12 weeks with low-dose prednisone as needed, then followed for an additional 12 weeks off PRN1008 to evaluate the durability of responses.
The primary study endpoint was control of disease activity by week 4 on a background of little or no prednisone, which 5 of 12 patients achieved. The secondary endpoint of complete clinical remission at 12 weeks was achieved in half of patients. Total pemphigus disease activity index (PDAI) scores dropped throughout the study period, reaching a mean 70% reduction at 12 weeks from a baseline of 20 points. Scores on the autoimmune bullous quality of life metric improved by 43%.
Eight of the 11 individuals who completed the study had control of disease activity by week 4 and/or complete clinical remission at 12 weeks. Those results are comparable with those typically seen with high-dose steroids at 12 weeks, the dermatologist noted.
Levels of anti–desmoglein-1 and/or -3 autoantibodies, which were elevated at baseline in 10 of 12 subjects, decreased during treatment with PRN1008.
Seventy-five percent of Bruton tyrosine kinase receptors were occupied by PRN1008 by day 2 of the study, confirming earlier studies in canine models of pemphigus. It turns out that pemphigus foliaceus is as common in dogs as atopic dermatitis is in humans, according to Dr. Murrell.
Side effects were limited to mild headache in two patients. One patient developed serious grade 3 cellulitis. She was taken off the study medication, although it was deemed unlikely that the infection was treatment related because she had had a recent history of multiple episodes of cellulitis.
During the second 12-week phase of the trial, after discontinuation of PRN1008, most patients retained their on-treatment reduction in total PDAI scores.
Dr. Murrell noted that the gradient of improvement in PDAI scores seen with PRN1008 in the Believe-PV study was quite similar to that seen in a recent 90-patient French randomized trial of rituximab (Rituxan) for the treatment of pemphigus. That’s of considerable interest, she said, because rituximab is a much more powerful drug, which drastically depletes the B-cell population. Moreover, the gradient of improvement in the rituximab-treated patients in the French trial was achieved with the aid of moderate-dose prednisone at 1 or 1.5 mg/kg per day, while PRN1008-treated patients in Believe-PV were taking on average only 0.2 mg/kg per day.
Asked if she thinks PRN1008 has a future as a stand-alone treatment for pemphigus or is better suited as an adjunct to systemic corticosteroids, Dr. Murrell said she believes the drug can be used effectively without steroids. However, since it’s recommended that patients be screened for tuberculosis before going on rituximab, and PRN1008 also targets B cells, she and her coinvestigators followed the same practice in Believe-PV. And because it takes a couple of weeks for the results of the Quantiferon-TB Gold In-Tube test to come back, it would be unethical for patients newly diagnosed with pemphigus to go untreated and in pain during that period, they get corticosteroids, at least initially.
Dr. Murrell reported serving as a paid consultant to Principia Biopharma, which is developing PRN1008.
GENEVA – An oral reversible Bruton tyrosine kinase inhibitor known as PRN1008 showed promising efficacy and safety for the treatment of pemphigus vulgaris in an interim analysis of an ongoing small-to-date, open-label phase 2 study, according to DeDee Murrell, MD.
PRN1008 is a designer drug intended as an alternative to the long-standing standard therapy for pemphigus, months to years of moderate- or high-dose systemic corticosteroids, with all the debilitating side effects that sledgehammer approach often brings, she said at the annual congress of the European Academy of Dermatology and Venereology.
Thus, PRN1008 inhibits a range of inflammatory cellular activities in mast cells, neutrophils, and other cells activated in autoimmune diseases, without killing those cells or directly affecting T cells. And – like corticosteroids – it works quickly, according to Dr. Murrell, professor of dermatology at the University of New South Wales in Sydney.
“The development of an oral, fast-acting treatment that could safely and effectively modulate B-cell function without depleting B cells would be a major advance in treating autoimmune diseases like pemphigus, vasculitis, immune thrombocytopenic purpura, multiple sclerosis, and rheumatoid arthritis,” she said.
Also, PRN1008 was designed to provide durable inhibition of BTK, coupled with rapid systemic clearance of the drug in order to minimize side effects.
The ongoing phase 2 multicenter international study, known as Believe-PV, to date includes 12 patients with biopsy-proven mild to moderate pemphigus vulgaris. Five patients were newly diagnosed and treatment naive, while seven had relapsing disease. All were placed on fixed-dose PRN1008 at 400 mg b.i.d. for 12 weeks with low-dose prednisone as needed, then followed for an additional 12 weeks off PRN1008 to evaluate the durability of responses.
The primary study endpoint was control of disease activity by week 4 on a background of little or no prednisone, which 5 of 12 patients achieved. The secondary endpoint of complete clinical remission at 12 weeks was achieved in half of patients. Total pemphigus disease activity index (PDAI) scores dropped throughout the study period, reaching a mean 70% reduction at 12 weeks from a baseline of 20 points. Scores on the autoimmune bullous quality of life metric improved by 43%.
Eight of the 11 individuals who completed the study had control of disease activity by week 4 and/or complete clinical remission at 12 weeks. Those results are comparable with those typically seen with high-dose steroids at 12 weeks, the dermatologist noted.
Levels of anti–desmoglein-1 and/or -3 autoantibodies, which were elevated at baseline in 10 of 12 subjects, decreased during treatment with PRN1008.
Seventy-five percent of Bruton tyrosine kinase receptors were occupied by PRN1008 by day 2 of the study, confirming earlier studies in canine models of pemphigus. It turns out that pemphigus foliaceus is as common in dogs as atopic dermatitis is in humans, according to Dr. Murrell.
Side effects were limited to mild headache in two patients. One patient developed serious grade 3 cellulitis. She was taken off the study medication, although it was deemed unlikely that the infection was treatment related because she had had a recent history of multiple episodes of cellulitis.
During the second 12-week phase of the trial, after discontinuation of PRN1008, most patients retained their on-treatment reduction in total PDAI scores.
Dr. Murrell noted that the gradient of improvement in PDAI scores seen with PRN1008 in the Believe-PV study was quite similar to that seen in a recent 90-patient French randomized trial of rituximab (Rituxan) for the treatment of pemphigus. That’s of considerable interest, she said, because rituximab is a much more powerful drug, which drastically depletes the B-cell population. Moreover, the gradient of improvement in the rituximab-treated patients in the French trial was achieved with the aid of moderate-dose prednisone at 1 or 1.5 mg/kg per day, while PRN1008-treated patients in Believe-PV were taking on average only 0.2 mg/kg per day.
Asked if she thinks PRN1008 has a future as a stand-alone treatment for pemphigus or is better suited as an adjunct to systemic corticosteroids, Dr. Murrell said she believes the drug can be used effectively without steroids. However, since it’s recommended that patients be screened for tuberculosis before going on rituximab, and PRN1008 also targets B cells, she and her coinvestigators followed the same practice in Believe-PV. And because it takes a couple of weeks for the results of the Quantiferon-TB Gold In-Tube test to come back, it would be unethical for patients newly diagnosed with pemphigus to go untreated and in pain during that period, they get corticosteroids, at least initially.
Dr. Murrell reported serving as a paid consultant to Principia Biopharma, which is developing PRN1008.
GENEVA – An oral reversible Bruton tyrosine kinase inhibitor known as PRN1008 showed promising efficacy and safety for the treatment of pemphigus vulgaris in an interim analysis of an ongoing small-to-date, open-label phase 2 study, according to DeDee Murrell, MD.
PRN1008 is a designer drug intended as an alternative to the long-standing standard therapy for pemphigus, months to years of moderate- or high-dose systemic corticosteroids, with all the debilitating side effects that sledgehammer approach often brings, she said at the annual congress of the European Academy of Dermatology and Venereology.
Thus, PRN1008 inhibits a range of inflammatory cellular activities in mast cells, neutrophils, and other cells activated in autoimmune diseases, without killing those cells or directly affecting T cells. And – like corticosteroids – it works quickly, according to Dr. Murrell, professor of dermatology at the University of New South Wales in Sydney.
“The development of an oral, fast-acting treatment that could safely and effectively modulate B-cell function without depleting B cells would be a major advance in treating autoimmune diseases like pemphigus, vasculitis, immune thrombocytopenic purpura, multiple sclerosis, and rheumatoid arthritis,” she said.
Also, PRN1008 was designed to provide durable inhibition of BTK, coupled with rapid systemic clearance of the drug in order to minimize side effects.
The ongoing phase 2 multicenter international study, known as Believe-PV, to date includes 12 patients with biopsy-proven mild to moderate pemphigus vulgaris. Five patients were newly diagnosed and treatment naive, while seven had relapsing disease. All were placed on fixed-dose PRN1008 at 400 mg b.i.d. for 12 weeks with low-dose prednisone as needed, then followed for an additional 12 weeks off PRN1008 to evaluate the durability of responses.
The primary study endpoint was control of disease activity by week 4 on a background of little or no prednisone, which 5 of 12 patients achieved. The secondary endpoint of complete clinical remission at 12 weeks was achieved in half of patients. Total pemphigus disease activity index (PDAI) scores dropped throughout the study period, reaching a mean 70% reduction at 12 weeks from a baseline of 20 points. Scores on the autoimmune bullous quality of life metric improved by 43%.
Eight of the 11 individuals who completed the study had control of disease activity by week 4 and/or complete clinical remission at 12 weeks. Those results are comparable with those typically seen with high-dose steroids at 12 weeks, the dermatologist noted.
Levels of anti–desmoglein-1 and/or -3 autoantibodies, which were elevated at baseline in 10 of 12 subjects, decreased during treatment with PRN1008.
Seventy-five percent of Bruton tyrosine kinase receptors were occupied by PRN1008 by day 2 of the study, confirming earlier studies in canine models of pemphigus. It turns out that pemphigus foliaceus is as common in dogs as atopic dermatitis is in humans, according to Dr. Murrell.
Side effects were limited to mild headache in two patients. One patient developed serious grade 3 cellulitis. She was taken off the study medication, although it was deemed unlikely that the infection was treatment related because she had had a recent history of multiple episodes of cellulitis.
During the second 12-week phase of the trial, after discontinuation of PRN1008, most patients retained their on-treatment reduction in total PDAI scores.
Dr. Murrell noted that the gradient of improvement in PDAI scores seen with PRN1008 in the Believe-PV study was quite similar to that seen in a recent 90-patient French randomized trial of rituximab (Rituxan) for the treatment of pemphigus. That’s of considerable interest, she said, because rituximab is a much more powerful drug, which drastically depletes the B-cell population. Moreover, the gradient of improvement in the rituximab-treated patients in the French trial was achieved with the aid of moderate-dose prednisone at 1 or 1.5 mg/kg per day, while PRN1008-treated patients in Believe-PV were taking on average only 0.2 mg/kg per day.
Asked if she thinks PRN1008 has a future as a stand-alone treatment for pemphigus or is better suited as an adjunct to systemic corticosteroids, Dr. Murrell said she believes the drug can be used effectively without steroids. However, since it’s recommended that patients be screened for tuberculosis before going on rituximab, and PRN1008 also targets B cells, she and her coinvestigators followed the same practice in Believe-PV. And because it takes a couple of weeks for the results of the Quantiferon-TB Gold In-Tube test to come back, it would be unethical for patients newly diagnosed with pemphigus to go untreated and in pain during that period, they get corticosteroids, at least initially.
Dr. Murrell reported serving as a paid consultant to Principia Biopharma, which is developing PRN1008.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Five of 12 pemphigus vulgaris patients achieved control of disease activity within the first 4 weeks on the investigational oral Bruton tyrosine kinase inhibitor PRN1008.
Data source: An interim analysis of the first 12 patients with pemphigus vulgaris in an ongoing multicenter, international open-label, phase 2 clinical trial.
Disclosures: The study presenter reported serving as a paid consultant to Principia Biopharma, which is developing PRN1008 and sponsored the Believe-PV trial.
International survey sheds new light on adult atopic dermatitis
GENEVA – The prevalence of atopic dermatitis (AD) among adults ages 18-65 years varies across countries in North America, Europe, and Asia, and regionally within those countries as well, according to an unprecedented eight-country survey of roughly 90,000 subjects.
The industry-supported web-based survey included roughly 20,000 U.S. respondents along with 10,000 from each of seven other countries: Italy, Spain, France, Germany, United Kingdom, Canada, and Japan. Most prior studies have focused on pediatric AD, Laurent Eckert, PhD, observed at the annual congress of the European Academy of Dermatology and Venereology.
The prevalence of adult AD was highest in Italy (8.1%) and Spain (7.2%), followed by the United States (4.9%), France (3.6%), Canada (3.5%), United Kingdom (2.5%), Germany (2.2%), and Japan (2.1%). Other investigators had previously reported a lower figure for the United States: 3.2% versus the 4.9% found in the new international survey, noted Dr. Eckert, an epidemiologist at Sanofi in Chilly-Mazarin, France.
The United States was the only country in which the prevalence of AD was higher in men than women, albeit by the narrow margin of 5.1% versus 4.9%. The rate was similar in men and women in the United Kingdom, and significantly greater in women in the other six participating countries. For example, the male:female prevalence ratio in Canada was 3.0%:4:0%, while in Italy it was 6.0%:10.0%.
Some degree of regional variability in the prevalence of AD was seen within each country. The biggest regional differences were seen within Italy and France. “The regional variability within Italy was in accord with a previous study that showed higher rates in Mediterranean regions relative to those in a more northern, continental climate,” Dr. Eckert said.
Two-stage criteria had to be met to label a respondent as having AD in this web-based survey. The participant had to be positive on the basis of the U.K. Working Party’s diagnostic criteria for AD (Br J Dermatol. 1994 Sep;131[3]:406-16), the key element of which is an affirmative answer to the question, “In the past 12 months, did you ever have an itchy rash that was coming and going for at least 6 months?” And the subject also had to self-report having received a physician diagnosis of AD.
Dr. Eckert and his coinvestigators employed three different validated methods of assessing AD severity: Physician Global Assessment, the Patient-Oriented Eczema Measure, and the Patient-Oriented Scoring AD. These three methods yielded wide variability in the distribution of individuals labeled as having severe AD. The Physician Global Assessment categorized 3%-8% of adult AD patients as having severe disease, depending upon the country, while the Patient-Oriented Eczema Measure yielded a 9%-17% prevalence of severe disease, and Patient-Oriented Scoring AD rated 12%-21% of adults with AD as having severe disease.
“The variability is severity distribution based on the outcome measure used suggests a need for standardization of severity assessment,” Dr. Eckert said.
In most countries, the peak prevalence of adult AD occurred in the 35- to 44-year-old age group, then fell steadily. In the United States, however, the peak came a decade earlier: The prevalence was 4.5% among 18- to 24-year-olds, it was 7.2% in the 25-34 age bracket, and it declined to 6.0% at age 35-44, 3.8% at 45-54, and 2.7% among 55- to 65-year-olds.
Dr. Eckert was also first author of a new study of the burden of adult AD in the United States. The study, which analyzed health care resource utilization data from the 2013 National Health and Wellness Survey, showed that the cost burden of adult AD was comparable to that of psoriasis, although adults with AD had more emergency department visits and higher rates of asthma and other atopic comorbidities (J Am Acad Dermatol. 2017 Oct 7. pii: S0190-9622[17]32181-3. doi: 10.1016/j.jaad.2017.08.002. [Epub ahead of print]).
The international survey was supported by Sanofi, which markets dupilumab with Regeneron.
GENEVA – The prevalence of atopic dermatitis (AD) among adults ages 18-65 years varies across countries in North America, Europe, and Asia, and regionally within those countries as well, according to an unprecedented eight-country survey of roughly 90,000 subjects.
The industry-supported web-based survey included roughly 20,000 U.S. respondents along with 10,000 from each of seven other countries: Italy, Spain, France, Germany, United Kingdom, Canada, and Japan. Most prior studies have focused on pediatric AD, Laurent Eckert, PhD, observed at the annual congress of the European Academy of Dermatology and Venereology.
The prevalence of adult AD was highest in Italy (8.1%) and Spain (7.2%), followed by the United States (4.9%), France (3.6%), Canada (3.5%), United Kingdom (2.5%), Germany (2.2%), and Japan (2.1%). Other investigators had previously reported a lower figure for the United States: 3.2% versus the 4.9% found in the new international survey, noted Dr. Eckert, an epidemiologist at Sanofi in Chilly-Mazarin, France.
The United States was the only country in which the prevalence of AD was higher in men than women, albeit by the narrow margin of 5.1% versus 4.9%. The rate was similar in men and women in the United Kingdom, and significantly greater in women in the other six participating countries. For example, the male:female prevalence ratio in Canada was 3.0%:4:0%, while in Italy it was 6.0%:10.0%.
Some degree of regional variability in the prevalence of AD was seen within each country. The biggest regional differences were seen within Italy and France. “The regional variability within Italy was in accord with a previous study that showed higher rates in Mediterranean regions relative to those in a more northern, continental climate,” Dr. Eckert said.
Two-stage criteria had to be met to label a respondent as having AD in this web-based survey. The participant had to be positive on the basis of the U.K. Working Party’s diagnostic criteria for AD (Br J Dermatol. 1994 Sep;131[3]:406-16), the key element of which is an affirmative answer to the question, “In the past 12 months, did you ever have an itchy rash that was coming and going for at least 6 months?” And the subject also had to self-report having received a physician diagnosis of AD.
Dr. Eckert and his coinvestigators employed three different validated methods of assessing AD severity: Physician Global Assessment, the Patient-Oriented Eczema Measure, and the Patient-Oriented Scoring AD. These three methods yielded wide variability in the distribution of individuals labeled as having severe AD. The Physician Global Assessment categorized 3%-8% of adult AD patients as having severe disease, depending upon the country, while the Patient-Oriented Eczema Measure yielded a 9%-17% prevalence of severe disease, and Patient-Oriented Scoring AD rated 12%-21% of adults with AD as having severe disease.
“The variability is severity distribution based on the outcome measure used suggests a need for standardization of severity assessment,” Dr. Eckert said.
In most countries, the peak prevalence of adult AD occurred in the 35- to 44-year-old age group, then fell steadily. In the United States, however, the peak came a decade earlier: The prevalence was 4.5% among 18- to 24-year-olds, it was 7.2% in the 25-34 age bracket, and it declined to 6.0% at age 35-44, 3.8% at 45-54, and 2.7% among 55- to 65-year-olds.
Dr. Eckert was also first author of a new study of the burden of adult AD in the United States. The study, which analyzed health care resource utilization data from the 2013 National Health and Wellness Survey, showed that the cost burden of adult AD was comparable to that of psoriasis, although adults with AD had more emergency department visits and higher rates of asthma and other atopic comorbidities (J Am Acad Dermatol. 2017 Oct 7. pii: S0190-9622[17]32181-3. doi: 10.1016/j.jaad.2017.08.002. [Epub ahead of print]).
The international survey was supported by Sanofi, which markets dupilumab with Regeneron.
GENEVA – The prevalence of atopic dermatitis (AD) among adults ages 18-65 years varies across countries in North America, Europe, and Asia, and regionally within those countries as well, according to an unprecedented eight-country survey of roughly 90,000 subjects.
The industry-supported web-based survey included roughly 20,000 U.S. respondents along with 10,000 from each of seven other countries: Italy, Spain, France, Germany, United Kingdom, Canada, and Japan. Most prior studies have focused on pediatric AD, Laurent Eckert, PhD, observed at the annual congress of the European Academy of Dermatology and Venereology.
The prevalence of adult AD was highest in Italy (8.1%) and Spain (7.2%), followed by the United States (4.9%), France (3.6%), Canada (3.5%), United Kingdom (2.5%), Germany (2.2%), and Japan (2.1%). Other investigators had previously reported a lower figure for the United States: 3.2% versus the 4.9% found in the new international survey, noted Dr. Eckert, an epidemiologist at Sanofi in Chilly-Mazarin, France.
The United States was the only country in which the prevalence of AD was higher in men than women, albeit by the narrow margin of 5.1% versus 4.9%. The rate was similar in men and women in the United Kingdom, and significantly greater in women in the other six participating countries. For example, the male:female prevalence ratio in Canada was 3.0%:4:0%, while in Italy it was 6.0%:10.0%.
Some degree of regional variability in the prevalence of AD was seen within each country. The biggest regional differences were seen within Italy and France. “The regional variability within Italy was in accord with a previous study that showed higher rates in Mediterranean regions relative to those in a more northern, continental climate,” Dr. Eckert said.
Two-stage criteria had to be met to label a respondent as having AD in this web-based survey. The participant had to be positive on the basis of the U.K. Working Party’s diagnostic criteria for AD (Br J Dermatol. 1994 Sep;131[3]:406-16), the key element of which is an affirmative answer to the question, “In the past 12 months, did you ever have an itchy rash that was coming and going for at least 6 months?” And the subject also had to self-report having received a physician diagnosis of AD.
Dr. Eckert and his coinvestigators employed three different validated methods of assessing AD severity: Physician Global Assessment, the Patient-Oriented Eczema Measure, and the Patient-Oriented Scoring AD. These three methods yielded wide variability in the distribution of individuals labeled as having severe AD. The Physician Global Assessment categorized 3%-8% of adult AD patients as having severe disease, depending upon the country, while the Patient-Oriented Eczema Measure yielded a 9%-17% prevalence of severe disease, and Patient-Oriented Scoring AD rated 12%-21% of adults with AD as having severe disease.
“The variability is severity distribution based on the outcome measure used suggests a need for standardization of severity assessment,” Dr. Eckert said.
In most countries, the peak prevalence of adult AD occurred in the 35- to 44-year-old age group, then fell steadily. In the United States, however, the peak came a decade earlier: The prevalence was 4.5% among 18- to 24-year-olds, it was 7.2% in the 25-34 age bracket, and it declined to 6.0% at age 35-44, 3.8% at 45-54, and 2.7% among 55- to 65-year-olds.
Dr. Eckert was also first author of a new study of the burden of adult AD in the United States. The study, which analyzed health care resource utilization data from the 2013 National Health and Wellness Survey, showed that the cost burden of adult AD was comparable to that of psoriasis, although adults with AD had more emergency department visits and higher rates of asthma and other atopic comorbidities (J Am Acad Dermatol. 2017 Oct 7. pii: S0190-9622[17]32181-3. doi: 10.1016/j.jaad.2017.08.002. [Epub ahead of print]).
The international survey was supported by Sanofi, which markets dupilumab with Regeneron.
AT THE EADV CONGRESS
Key clinical point:
Major finding: The prevalence of atopic dermatitis among adults ages 18-65 ranged from a high of 8.1% in Italy to 2.1% in Japan.
Data source: A web-based survey of roughly 90,000 adults in the United States and seven other countries in North America, Europe, and Asia.
Disclosures: The survey was supported by Sanofi and presented by a company employee.
Serlopitant is itching to quell chronic pruritus
GENEVA – Serlopitant, a novel once-daily oral neurokinin-1 receptor antagonist, brought significant improvement for patients with treatment-resistant chronic pruritus as early as day 2, in a phase 2 randomized trial, Paul Kwon, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In a separate phase 2 study presented at the congress, serlopitant showed strong efficacy in patients with prurigo nodularis.
Serlopitant is an oral small molecule with high selectivity for the neurokinin-1 receptor (NK1R). At the 5-mg dose, the drug occupies more than 90% of CNS NK1Rs. The NK1R is the primary receptor for substance P, and thus plays an important role in pruritus signaling.
Chronic pruritus is an often-debilitating condition that can have a multitude of causes. It’s associated with increased rates of anxiety, depression, and sleep deprivation. Existing treatments often fail to provide adequate relief from the severe chronic itching, or they are associated with safety or tolerability issues.
“Chronic pruritus can disrupt quality of life to a level comparable to chronic pain,” the dermatologist observed. “I think we in the medical community are hearing more and more about treatment for chronic pruritus as being a major unmet medical need.”
Dr. Kwon noted that investigators at Emory University in Atlanta have found that the quality of life disruption imposed by chronic pruritus is comparable to that of chronic pain (Arch Dermatol. 2011 Oct;147[10]:1153-6).
The phase 2, randomized, double-blind, placebo-controlled, 6-week trial comprised 257 patients with chronic pruritus at 25 U.S. centers. All were non- or inadequate responders to topical corticosteroids or oral antihistamines. This was essentially an all-comers study that was not restricted to patients with any particular specific cause of their chronic itch. They had to have severe chronic pruritus, as defined by a baseline self-rated pruritus visual analogue score of at least 7 on a 0-10 scale. Patients were randomized to once-daily oral serlopitant at 0.25 mg, 1 mg, or 5 mg, or to placebo.
The primary endpoint was change in mean visual analogue score from baseline to week 6. The serlopitant 1-mg and 5-mg groups reported mean 41.4% and 42.5% reductions, respectively, which were significantly better than the 28.3% reduction in controls.
“It seems that the drug is working in a broad set of subjects,” Dr. Kwon said. “It is not entirely shutting off itch in significant numbers, but the majority of patients appear to be deriving benefit from serlopitant.”
He highlighted the rapidity with which chronic pruritus responded to serlopitant. The first dose was taken on the evening of day 1. The next day, the 1-mg serlopitant group already showed a significantly greater improvement than did placebo-treated controls. The day after that, so did the 5-mg group. Those between-group differences grew steadily larger throughout the 6-week study period.
That rapid response is clinically highly relevant, because numerous studies have demonstrated that fast onset of therapeutic effect improves patient satisfaction, quality of life, and compliance with treatment for a variety of medical conditions, he said.
Dr. Kwon characterized the safety profile of serlopitant in the trial as “fairly robust,” with only mild or moderate treatment-emergent adverse events being seen. Diarrhea and somnolence were the only adverse events more common with serlopitant than placebo, and their incidence was in the mid single digits.
“We have not uncovered any significant safety signal in this study,” Dr. Kwon declared.
Also at the EADV Congress, Sonja Ständer, MD, presented a phase 2 study of serlopitant in patients with prurigo nodularis. The randomized, double-blind, 8-week, 127-patient trial was conducted at 15 sites in Germany, where patients were randomized to once-daily serlopitant at 5 mg or placebo. All participants had a baseline pruritus VAS of 7 or more. Thirty percent of patients had more than a 10-year history of prurigo nodularis, and 24% had the condition for 5-10 years.
The primary endpoint was the difference from baseline to weeks 4 and 8 in the average pruritus VAS over the previous 24 hours. The baseline score was 7.9. The serlopitant group averaged a 1.0-point greater reduction, compared with controls, at week 4, and a 1.7-point greater decrease at week 8.
Multiple other measures of pruritus serving as secondary endpoints consistently showed significantly greater improvement in the serlopitant group. For example, at the week 8 assessment, 54% of serlopitant-treated patients reported no or only mild itch, compared with 29% of controls. And two-thirds of the serlopitant group reported some degree of improvement in the severity of their eruptive papulonodular lesions at week 8, versus 40% of controls, according to Dr. Ständer, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).
Of note, nasopharyngitis occurred in 17.2% of the serlopitant group and in 3.2% of controls. Diarrhea was also more common in the serlopitant group, by a margin of 10.9% versus 4.8%.
Dr. Kwon said additional phase 2 as well as phase 3 randomized trials of serlopitant are in the works for both chronic pruritus and prurigo nodularis. The drug is also under study for chronic itch due to other specific etiologies, as well as for refractory chronic cough.
Menlo Therapeutics sponsored the study. Dr. Kwon is a Menlo Therapeutics officer. Dr. Ständer, who was also principal investigator in the chronic pruritus trial, reported having no financial conflicts of interest.
GENEVA – Serlopitant, a novel once-daily oral neurokinin-1 receptor antagonist, brought significant improvement for patients with treatment-resistant chronic pruritus as early as day 2, in a phase 2 randomized trial, Paul Kwon, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In a separate phase 2 study presented at the congress, serlopitant showed strong efficacy in patients with prurigo nodularis.
Serlopitant is an oral small molecule with high selectivity for the neurokinin-1 receptor (NK1R). At the 5-mg dose, the drug occupies more than 90% of CNS NK1Rs. The NK1R is the primary receptor for substance P, and thus plays an important role in pruritus signaling.
Chronic pruritus is an often-debilitating condition that can have a multitude of causes. It’s associated with increased rates of anxiety, depression, and sleep deprivation. Existing treatments often fail to provide adequate relief from the severe chronic itching, or they are associated with safety or tolerability issues.
“Chronic pruritus can disrupt quality of life to a level comparable to chronic pain,” the dermatologist observed. “I think we in the medical community are hearing more and more about treatment for chronic pruritus as being a major unmet medical need.”
Dr. Kwon noted that investigators at Emory University in Atlanta have found that the quality of life disruption imposed by chronic pruritus is comparable to that of chronic pain (Arch Dermatol. 2011 Oct;147[10]:1153-6).
The phase 2, randomized, double-blind, placebo-controlled, 6-week trial comprised 257 patients with chronic pruritus at 25 U.S. centers. All were non- or inadequate responders to topical corticosteroids or oral antihistamines. This was essentially an all-comers study that was not restricted to patients with any particular specific cause of their chronic itch. They had to have severe chronic pruritus, as defined by a baseline self-rated pruritus visual analogue score of at least 7 on a 0-10 scale. Patients were randomized to once-daily oral serlopitant at 0.25 mg, 1 mg, or 5 mg, or to placebo.
The primary endpoint was change in mean visual analogue score from baseline to week 6. The serlopitant 1-mg and 5-mg groups reported mean 41.4% and 42.5% reductions, respectively, which were significantly better than the 28.3% reduction in controls.
“It seems that the drug is working in a broad set of subjects,” Dr. Kwon said. “It is not entirely shutting off itch in significant numbers, but the majority of patients appear to be deriving benefit from serlopitant.”
He highlighted the rapidity with which chronic pruritus responded to serlopitant. The first dose was taken on the evening of day 1. The next day, the 1-mg serlopitant group already showed a significantly greater improvement than did placebo-treated controls. The day after that, so did the 5-mg group. Those between-group differences grew steadily larger throughout the 6-week study period.
That rapid response is clinically highly relevant, because numerous studies have demonstrated that fast onset of therapeutic effect improves patient satisfaction, quality of life, and compliance with treatment for a variety of medical conditions, he said.
Dr. Kwon characterized the safety profile of serlopitant in the trial as “fairly robust,” with only mild or moderate treatment-emergent adverse events being seen. Diarrhea and somnolence were the only adverse events more common with serlopitant than placebo, and their incidence was in the mid single digits.
“We have not uncovered any significant safety signal in this study,” Dr. Kwon declared.
Also at the EADV Congress, Sonja Ständer, MD, presented a phase 2 study of serlopitant in patients with prurigo nodularis. The randomized, double-blind, 8-week, 127-patient trial was conducted at 15 sites in Germany, where patients were randomized to once-daily serlopitant at 5 mg or placebo. All participants had a baseline pruritus VAS of 7 or more. Thirty percent of patients had more than a 10-year history of prurigo nodularis, and 24% had the condition for 5-10 years.
The primary endpoint was the difference from baseline to weeks 4 and 8 in the average pruritus VAS over the previous 24 hours. The baseline score was 7.9. The serlopitant group averaged a 1.0-point greater reduction, compared with controls, at week 4, and a 1.7-point greater decrease at week 8.
Multiple other measures of pruritus serving as secondary endpoints consistently showed significantly greater improvement in the serlopitant group. For example, at the week 8 assessment, 54% of serlopitant-treated patients reported no or only mild itch, compared with 29% of controls. And two-thirds of the serlopitant group reported some degree of improvement in the severity of their eruptive papulonodular lesions at week 8, versus 40% of controls, according to Dr. Ständer, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).
Of note, nasopharyngitis occurred in 17.2% of the serlopitant group and in 3.2% of controls. Diarrhea was also more common in the serlopitant group, by a margin of 10.9% versus 4.8%.
Dr. Kwon said additional phase 2 as well as phase 3 randomized trials of serlopitant are in the works for both chronic pruritus and prurigo nodularis. The drug is also under study for chronic itch due to other specific etiologies, as well as for refractory chronic cough.
Menlo Therapeutics sponsored the study. Dr. Kwon is a Menlo Therapeutics officer. Dr. Ständer, who was also principal investigator in the chronic pruritus trial, reported having no financial conflicts of interest.
GENEVA – Serlopitant, a novel once-daily oral neurokinin-1 receptor antagonist, brought significant improvement for patients with treatment-resistant chronic pruritus as early as day 2, in a phase 2 randomized trial, Paul Kwon, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In a separate phase 2 study presented at the congress, serlopitant showed strong efficacy in patients with prurigo nodularis.
Serlopitant is an oral small molecule with high selectivity for the neurokinin-1 receptor (NK1R). At the 5-mg dose, the drug occupies more than 90% of CNS NK1Rs. The NK1R is the primary receptor for substance P, and thus plays an important role in pruritus signaling.
Chronic pruritus is an often-debilitating condition that can have a multitude of causes. It’s associated with increased rates of anxiety, depression, and sleep deprivation. Existing treatments often fail to provide adequate relief from the severe chronic itching, or they are associated with safety or tolerability issues.
“Chronic pruritus can disrupt quality of life to a level comparable to chronic pain,” the dermatologist observed. “I think we in the medical community are hearing more and more about treatment for chronic pruritus as being a major unmet medical need.”
Dr. Kwon noted that investigators at Emory University in Atlanta have found that the quality of life disruption imposed by chronic pruritus is comparable to that of chronic pain (Arch Dermatol. 2011 Oct;147[10]:1153-6).
The phase 2, randomized, double-blind, placebo-controlled, 6-week trial comprised 257 patients with chronic pruritus at 25 U.S. centers. All were non- or inadequate responders to topical corticosteroids or oral antihistamines. This was essentially an all-comers study that was not restricted to patients with any particular specific cause of their chronic itch. They had to have severe chronic pruritus, as defined by a baseline self-rated pruritus visual analogue score of at least 7 on a 0-10 scale. Patients were randomized to once-daily oral serlopitant at 0.25 mg, 1 mg, or 5 mg, or to placebo.
The primary endpoint was change in mean visual analogue score from baseline to week 6. The serlopitant 1-mg and 5-mg groups reported mean 41.4% and 42.5% reductions, respectively, which were significantly better than the 28.3% reduction in controls.
“It seems that the drug is working in a broad set of subjects,” Dr. Kwon said. “It is not entirely shutting off itch in significant numbers, but the majority of patients appear to be deriving benefit from serlopitant.”
He highlighted the rapidity with which chronic pruritus responded to serlopitant. The first dose was taken on the evening of day 1. The next day, the 1-mg serlopitant group already showed a significantly greater improvement than did placebo-treated controls. The day after that, so did the 5-mg group. Those between-group differences grew steadily larger throughout the 6-week study period.
That rapid response is clinically highly relevant, because numerous studies have demonstrated that fast onset of therapeutic effect improves patient satisfaction, quality of life, and compliance with treatment for a variety of medical conditions, he said.
Dr. Kwon characterized the safety profile of serlopitant in the trial as “fairly robust,” with only mild or moderate treatment-emergent adverse events being seen. Diarrhea and somnolence were the only adverse events more common with serlopitant than placebo, and their incidence was in the mid single digits.
“We have not uncovered any significant safety signal in this study,” Dr. Kwon declared.
Also at the EADV Congress, Sonja Ständer, MD, presented a phase 2 study of serlopitant in patients with prurigo nodularis. The randomized, double-blind, 8-week, 127-patient trial was conducted at 15 sites in Germany, where patients were randomized to once-daily serlopitant at 5 mg or placebo. All participants had a baseline pruritus VAS of 7 or more. Thirty percent of patients had more than a 10-year history of prurigo nodularis, and 24% had the condition for 5-10 years.
The primary endpoint was the difference from baseline to weeks 4 and 8 in the average pruritus VAS over the previous 24 hours. The baseline score was 7.9. The serlopitant group averaged a 1.0-point greater reduction, compared with controls, at week 4, and a 1.7-point greater decrease at week 8.
Multiple other measures of pruritus serving as secondary endpoints consistently showed significantly greater improvement in the serlopitant group. For example, at the week 8 assessment, 54% of serlopitant-treated patients reported no or only mild itch, compared with 29% of controls. And two-thirds of the serlopitant group reported some degree of improvement in the severity of their eruptive papulonodular lesions at week 8, versus 40% of controls, according to Dr. Ständer, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).
Of note, nasopharyngitis occurred in 17.2% of the serlopitant group and in 3.2% of controls. Diarrhea was also more common in the serlopitant group, by a margin of 10.9% versus 4.8%.
Dr. Kwon said additional phase 2 as well as phase 3 randomized trials of serlopitant are in the works for both chronic pruritus and prurigo nodularis. The drug is also under study for chronic itch due to other specific etiologies, as well as for refractory chronic cough.
Menlo Therapeutics sponsored the study. Dr. Kwon is a Menlo Therapeutics officer. Dr. Ständer, who was also principal investigator in the chronic pruritus trial, reported having no financial conflicts of interest.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Mean self-rated pruritus scores fell by 41% and 43% from baseline to week 6 in patients on serlopitant at 1 mg/day and 5 mg/day, compared with 28% in placebo-treated controls.
Data source: A randomized, double-blind, multicenter, placebo-controlled, 6-week, phase 2 clinical trial comprising 257 patients with treatment-resistant chronic pruritus.
Disclosures: Menlo Therapeutics sponsored the study. Dr. Kwon is a Menlo Therapeutics officer. Dr. Ständer reported having no financial conflicts of interest.
Topical tapinarof heads for phase 3 in atopic dermatitis and psoriasis
GENEVA – Tapinarof cream, a first-in-class topical nonsteroidal anti-inflammatory agent, successfully met its primary and secondary efficacy endpoints in a large international, phase 2, dose-ranging study and is moving on to a phase 3 trial for atopic dermatitis.
Tapinarof is a naturally derived compound whose therapeutic mechanism of action has recently been shown to involve activation of the aryl hydrocarbon receptor, Johnny Peppers, PhD, said at the annual congress of the European Academy of Dermatology and Venereology.
GlaxoSmithKline is also developing tapinarof cream for mild to moderate plaque psoriasis, a disease that hasn’t seen a novel nonsteroidal topical therapy approved in more than 25 years. After a strong showing in a phase 2 study, a phase 3 trial in psoriasis is now scheduled.
Dr. Peppers presented a phase 2, double-blind, vehicle-controlled randomized trial including 247 adolescent and adult patients with mild, moderate, or severe atopic dermatitis. The six study arms were tapinarof cream at 1% or 0.5% or vehicle, self-administered at a frequency of either once or twice daily. Participants had a mean baseline Investigator’s Global Assessment (IGA) score of 3.1 on a 5-point scale, an Eczema Area and Severity Index (EASI) score of 9.8-13.1 in the various study arms, and a 5.1-5.8 score on an 11-point self-rated itch severity score recorded weekly.
“The 1% tapinarof arm showed higher efficacy and had a quicker onset of action than the 0.5% arm or vehicle,” he reported.
Indeed, the 1% tapinarof cream groups separated from controls in terms of the efficacy endpoints as early as week 1, with the maximum treatment effect seen at weeks 8-12, Dr. Peppers added.
The primary endpoint was a composite requiring both an IGA of 0 or 1, meaning clear or almost clear, at 12 weeks, along with a minimum 2-point improvement on the IGA from baseline to week 12. This was achieved in 46% of patients on tapinarof cream 1% applied once daily, 53% of those on tapinarof cream 1% twice a day, and in about 25% of controls on vehicle.
Eighty percent of subjects who achieved the primary endpoint maintained that level of treatment effect 2 weeks post treatment, and 70% still held their treatment response 4 weeks after they stopped using the medication.
There were two secondary endpoints. One was achievement of a 75% improvement from baseline on EASI scores (EASI-75) response. This was seen in 51% of the tapinarof 1% once-daily group, 60% on twice a day therapy, and 26% and 25% of controls. Onset of action was fastest with tapinarof cream 1% once daily.
The other secondary endpoint was at least a 3-point improvement from baseline to week 4 on the 11-point self-rated itch scale. This was achieved by 37% and 33% of patients on tapinarof cream 1% once daily and twice daily, respectively, a success rate twice that seen in controls.
Four percent of patients on tapinarof cream and 7% on vehicle discontinued the trial because of treatment-emergent adverse events. There were no serious treatment-related adverse events. The most frequent adverse events associated with tapinarof were folliculitis and contact dermatitis. The phase 3 trial will incorporate patch testing for contact dermatitis.
“We are very excited about this program. This will be the first topical therapy – if we’re able to achieve treatment success and ultimately regulatory approval – that would be able to treat both psoriasis and atopic dermatitis since topical steroids,” Dr. Peppers said.
The study was funded by GlaxoSmithKline and presented by a company employee.
[email protected]
GENEVA – Tapinarof cream, a first-in-class topical nonsteroidal anti-inflammatory agent, successfully met its primary and secondary efficacy endpoints in a large international, phase 2, dose-ranging study and is moving on to a phase 3 trial for atopic dermatitis.
Tapinarof is a naturally derived compound whose therapeutic mechanism of action has recently been shown to involve activation of the aryl hydrocarbon receptor, Johnny Peppers, PhD, said at the annual congress of the European Academy of Dermatology and Venereology.
GlaxoSmithKline is also developing tapinarof cream for mild to moderate plaque psoriasis, a disease that hasn’t seen a novel nonsteroidal topical therapy approved in more than 25 years. After a strong showing in a phase 2 study, a phase 3 trial in psoriasis is now scheduled.
Dr. Peppers presented a phase 2, double-blind, vehicle-controlled randomized trial including 247 adolescent and adult patients with mild, moderate, or severe atopic dermatitis. The six study arms were tapinarof cream at 1% or 0.5% or vehicle, self-administered at a frequency of either once or twice daily. Participants had a mean baseline Investigator’s Global Assessment (IGA) score of 3.1 on a 5-point scale, an Eczema Area and Severity Index (EASI) score of 9.8-13.1 in the various study arms, and a 5.1-5.8 score on an 11-point self-rated itch severity score recorded weekly.
“The 1% tapinarof arm showed higher efficacy and had a quicker onset of action than the 0.5% arm or vehicle,” he reported.
Indeed, the 1% tapinarof cream groups separated from controls in terms of the efficacy endpoints as early as week 1, with the maximum treatment effect seen at weeks 8-12, Dr. Peppers added.
The primary endpoint was a composite requiring both an IGA of 0 or 1, meaning clear or almost clear, at 12 weeks, along with a minimum 2-point improvement on the IGA from baseline to week 12. This was achieved in 46% of patients on tapinarof cream 1% applied once daily, 53% of those on tapinarof cream 1% twice a day, and in about 25% of controls on vehicle.
Eighty percent of subjects who achieved the primary endpoint maintained that level of treatment effect 2 weeks post treatment, and 70% still held their treatment response 4 weeks after they stopped using the medication.
There were two secondary endpoints. One was achievement of a 75% improvement from baseline on EASI scores (EASI-75) response. This was seen in 51% of the tapinarof 1% once-daily group, 60% on twice a day therapy, and 26% and 25% of controls. Onset of action was fastest with tapinarof cream 1% once daily.
The other secondary endpoint was at least a 3-point improvement from baseline to week 4 on the 11-point self-rated itch scale. This was achieved by 37% and 33% of patients on tapinarof cream 1% once daily and twice daily, respectively, a success rate twice that seen in controls.
Four percent of patients on tapinarof cream and 7% on vehicle discontinued the trial because of treatment-emergent adverse events. There were no serious treatment-related adverse events. The most frequent adverse events associated with tapinarof were folliculitis and contact dermatitis. The phase 3 trial will incorporate patch testing for contact dermatitis.
“We are very excited about this program. This will be the first topical therapy – if we’re able to achieve treatment success and ultimately regulatory approval – that would be able to treat both psoriasis and atopic dermatitis since topical steroids,” Dr. Peppers said.
The study was funded by GlaxoSmithKline and presented by a company employee.
[email protected]
GENEVA – Tapinarof cream, a first-in-class topical nonsteroidal anti-inflammatory agent, successfully met its primary and secondary efficacy endpoints in a large international, phase 2, dose-ranging study and is moving on to a phase 3 trial for atopic dermatitis.
Tapinarof is a naturally derived compound whose therapeutic mechanism of action has recently been shown to involve activation of the aryl hydrocarbon receptor, Johnny Peppers, PhD, said at the annual congress of the European Academy of Dermatology and Venereology.
GlaxoSmithKline is also developing tapinarof cream for mild to moderate plaque psoriasis, a disease that hasn’t seen a novel nonsteroidal topical therapy approved in more than 25 years. After a strong showing in a phase 2 study, a phase 3 trial in psoriasis is now scheduled.
Dr. Peppers presented a phase 2, double-blind, vehicle-controlled randomized trial including 247 adolescent and adult patients with mild, moderate, or severe atopic dermatitis. The six study arms were tapinarof cream at 1% or 0.5% or vehicle, self-administered at a frequency of either once or twice daily. Participants had a mean baseline Investigator’s Global Assessment (IGA) score of 3.1 on a 5-point scale, an Eczema Area and Severity Index (EASI) score of 9.8-13.1 in the various study arms, and a 5.1-5.8 score on an 11-point self-rated itch severity score recorded weekly.
“The 1% tapinarof arm showed higher efficacy and had a quicker onset of action than the 0.5% arm or vehicle,” he reported.
Indeed, the 1% tapinarof cream groups separated from controls in terms of the efficacy endpoints as early as week 1, with the maximum treatment effect seen at weeks 8-12, Dr. Peppers added.
The primary endpoint was a composite requiring both an IGA of 0 or 1, meaning clear or almost clear, at 12 weeks, along with a minimum 2-point improvement on the IGA from baseline to week 12. This was achieved in 46% of patients on tapinarof cream 1% applied once daily, 53% of those on tapinarof cream 1% twice a day, and in about 25% of controls on vehicle.
Eighty percent of subjects who achieved the primary endpoint maintained that level of treatment effect 2 weeks post treatment, and 70% still held their treatment response 4 weeks after they stopped using the medication.
There were two secondary endpoints. One was achievement of a 75% improvement from baseline on EASI scores (EASI-75) response. This was seen in 51% of the tapinarof 1% once-daily group, 60% on twice a day therapy, and 26% and 25% of controls. Onset of action was fastest with tapinarof cream 1% once daily.
The other secondary endpoint was at least a 3-point improvement from baseline to week 4 on the 11-point self-rated itch scale. This was achieved by 37% and 33% of patients on tapinarof cream 1% once daily and twice daily, respectively, a success rate twice that seen in controls.
Four percent of patients on tapinarof cream and 7% on vehicle discontinued the trial because of treatment-emergent adverse events. There were no serious treatment-related adverse events. The most frequent adverse events associated with tapinarof were folliculitis and contact dermatitis. The phase 3 trial will incorporate patch testing for contact dermatitis.
“We are very excited about this program. This will be the first topical therapy – if we’re able to achieve treatment success and ultimately regulatory approval – that would be able to treat both psoriasis and atopic dermatitis since topical steroids,” Dr. Peppers said.
The study was funded by GlaxoSmithKline and presented by a company employee.
[email protected]
AT THE EADV CONGRESS
Key clinical point:
Major finding: Forty-six percent of atopic dermatitis patients on tapinarof cream 1% applied once daily, and 53% of atopic dermatitis patients on tapinarof cream applied twice daily, met the primary study endpoint, rates twice those in vehicle-treated controls.
Data source: A phase 2, double-blind, vehicle-controlled, international 12-week clinical trial in 247 adolescents and adults with moderate to severe atopic dermatitis.
Disclosures: The study was funded by GlaxoSmithKline and presented by a company employee.
Ustekinumab may reduce risk of nonmelanoma skin cancer
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology. 
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Psoriasis patients on ustekinumab had an adjusted 65% reduction in the risk of developing nonmelanoma skin cancer compared with patients on methotrexate.
Data source: An analysis of 6,782 psoriasis patients participating in an international prospective observational registry evaluating the long-term safety and clinical outcomes of systemic therapies.
Disclosures: The PSOLAR registry is funded by ustekinumab manufacturer Janssen; the study presenter is a company employee.
Nemolizumab continues to crush itch in 64-week atopic dermatitis study
GENEVA – Nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, maintained its early dramatic antipruritic effect in patients with moderate to severe atopic dermatitis (AD) throughout a year-long unblinded extension of a large, high-profile, 12-week, phase 2 randomized trial, Thomas Ruzicka, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In contrast, the 52-week extension study also showed the improvement in the dermatitis aspect of AD as measured by Eczema Area and Severity Index (EASI) scores was more gradual and less robust.
The study, 64 weeks in total, also demonstrated that what really matters to patients with moderate or severe AD is relief from the itch. Scores on the Dermatology Life Quality Index showed marked improvement even if their improvement in EASI scores was suboptimal.
“The dermatitis scores improved. But the most concerning symptom to patients is the pruritus; that’s what worsens their quality of life. And this improves dramatically very early in the course of the study,” Dr. Ruzicka explained. “If they drop their itch they are very happy. They don’t care about the redness of the skin so much as the pruritus. This is what really bothers them, as has been shown in epidemiologic studies.”
The original 12-week, phase 2, randomized, double-blind, dose-ranging trial drew extensive attention because it demonstrated convincingly for the first time that the inflammatory cytokine interleukin-31 plays a key role in the pathobiology of AD by promoting skin barrier dysfunction, pruritus, and the inflammatory response in AD – and that a biologic agent, nemolizumab, could inhibit those disease mechanisms (N Engl J Med. 2017 Mar 2;376[9]:826-35).
At a dose of 0.5 mg/kg administered by subcutaneous injection every 4 weeks, nemolizumab, a humanized monoclonal antibody directed against interleukin-31 receptor A, reduced scores on the pruritus visual-analogue scale by 60% as early as 4 weeks and maintained that effect through 12 weeks. At that point, the double-blind study ended and the 52-week extension began. Patients on nemolizumab in the double-blind phase stayed on the same dosage for the extension, while those who’d been on placebo were switched to nemolizumab at 0.1, 0.5, or 2.0 mg/kg every 4 weeks.
A total of 211 patients with moderate to severe AD inadequately controlled by topical therapies enrolled in the extension study. The combined 64-week experience convinced investigators and the sponsor, Chugai Pharmaceutical, that 0.5 mg/kg every 4 weeks is the optimal dose to take forward into planned advanced-stage clinical trials.
“At this dosage the IL-31 receptor is saturated, so higher dosages aren’t needed,” according to Dr. Ruzicka.
By week 64, patients in the 0.5-mg/kg arm of the study showed further gradual improvement in their pruritus visual-analogue score, from a 60% reduction from baseline at 12 weeks to close to an 80% reduction at week 64.
Roughly half of nemolizumab-treated patients achieved an EASI-50 response within the first 4 weeks of the double-blind phase of the study and stayed in that response zone throughout the extension study.
The EASI-75 and -90 responses followed a pattern different from EASI-50. Patients didn’t leap to those more robust levels of response early and then plateau. Instead, the EASI-75 and -90 responses were achieved via a gradual climb in efficacy throughout the study, such that by week 64 roughly 35%-40% of patients on the various nemolizumab dosages had reached EASI-75.
In the extension study, patients were permitted to use a mild topical steroid or topical calcineurin inhibitor as needed, and a potent or very potent topical steroid as rescue medication. Roughly half of participants resorted to any topical steroid at least once during the 64 months. An important new observation gleaned in the long-term study was that the patients who did use topical steroids were twice as likely to reach an EASI 75 response.
Roughly 20% of patients on the three highest dosages of nemolizumab achieved a static Investigator’s Global Assessment score of 0 or 1, meaning clear or almost clear, by week 64.
Scores on the Dermatology Life Quality Index fell steadily over the course of 64 weeks, from a baseline of about 16 to 5 at study’s close.
The side effect profile of nemolizumab was essentially the same as seen in the placebo arm during the double-blind phase. About one-quarter of patients experienced nasopharyngitis over the course of 64 weeks of treatment. A similar fraction reported exacerbations of their atopic dermatitis; however, these events were front-loaded in the first weeks of the initial double-blind study phase and appeared to have been triggered by the drug washout period prior to the patients’ receiving the first dose of nemolizumab, according to Dr. Ruzicka. No new safety signals emerged during the additional 52 weeks of treatment.
The study was funded by Chugai. Dr. Ruzicka reported serving as a paid company adviser.
GENEVA – Nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, maintained its early dramatic antipruritic effect in patients with moderate to severe atopic dermatitis (AD) throughout a year-long unblinded extension of a large, high-profile, 12-week, phase 2 randomized trial, Thomas Ruzicka, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In contrast, the 52-week extension study also showed the improvement in the dermatitis aspect of AD as measured by Eczema Area and Severity Index (EASI) scores was more gradual and less robust.
The study, 64 weeks in total, also demonstrated that what really matters to patients with moderate or severe AD is relief from the itch. Scores on the Dermatology Life Quality Index showed marked improvement even if their improvement in EASI scores was suboptimal.
“The dermatitis scores improved. But the most concerning symptom to patients is the pruritus; that’s what worsens their quality of life. And this improves dramatically very early in the course of the study,” Dr. Ruzicka explained. “If they drop their itch they are very happy. They don’t care about the redness of the skin so much as the pruritus. This is what really bothers them, as has been shown in epidemiologic studies.”
The original 12-week, phase 2, randomized, double-blind, dose-ranging trial drew extensive attention because it demonstrated convincingly for the first time that the inflammatory cytokine interleukin-31 plays a key role in the pathobiology of AD by promoting skin barrier dysfunction, pruritus, and the inflammatory response in AD – and that a biologic agent, nemolizumab, could inhibit those disease mechanisms (N Engl J Med. 2017 Mar 2;376[9]:826-35).
At a dose of 0.5 mg/kg administered by subcutaneous injection every 4 weeks, nemolizumab, a humanized monoclonal antibody directed against interleukin-31 receptor A, reduced scores on the pruritus visual-analogue scale by 60% as early as 4 weeks and maintained that effect through 12 weeks. At that point, the double-blind study ended and the 52-week extension began. Patients on nemolizumab in the double-blind phase stayed on the same dosage for the extension, while those who’d been on placebo were switched to nemolizumab at 0.1, 0.5, or 2.0 mg/kg every 4 weeks.
A total of 211 patients with moderate to severe AD inadequately controlled by topical therapies enrolled in the extension study. The combined 64-week experience convinced investigators and the sponsor, Chugai Pharmaceutical, that 0.5 mg/kg every 4 weeks is the optimal dose to take forward into planned advanced-stage clinical trials.
“At this dosage the IL-31 receptor is saturated, so higher dosages aren’t needed,” according to Dr. Ruzicka.
By week 64, patients in the 0.5-mg/kg arm of the study showed further gradual improvement in their pruritus visual-analogue score, from a 60% reduction from baseline at 12 weeks to close to an 80% reduction at week 64.
Roughly half of nemolizumab-treated patients achieved an EASI-50 response within the first 4 weeks of the double-blind phase of the study and stayed in that response zone throughout the extension study.
The EASI-75 and -90 responses followed a pattern different from EASI-50. Patients didn’t leap to those more robust levels of response early and then plateau. Instead, the EASI-75 and -90 responses were achieved via a gradual climb in efficacy throughout the study, such that by week 64 roughly 35%-40% of patients on the various nemolizumab dosages had reached EASI-75.
In the extension study, patients were permitted to use a mild topical steroid or topical calcineurin inhibitor as needed, and a potent or very potent topical steroid as rescue medication. Roughly half of participants resorted to any topical steroid at least once during the 64 months. An important new observation gleaned in the long-term study was that the patients who did use topical steroids were twice as likely to reach an EASI 75 response.
Roughly 20% of patients on the three highest dosages of nemolizumab achieved a static Investigator’s Global Assessment score of 0 or 1, meaning clear or almost clear, by week 64.
Scores on the Dermatology Life Quality Index fell steadily over the course of 64 weeks, from a baseline of about 16 to 5 at study’s close.
The side effect profile of nemolizumab was essentially the same as seen in the placebo arm during the double-blind phase. About one-quarter of patients experienced nasopharyngitis over the course of 64 weeks of treatment. A similar fraction reported exacerbations of their atopic dermatitis; however, these events were front-loaded in the first weeks of the initial double-blind study phase and appeared to have been triggered by the drug washout period prior to the patients’ receiving the first dose of nemolizumab, according to Dr. Ruzicka. No new safety signals emerged during the additional 52 weeks of treatment.
The study was funded by Chugai. Dr. Ruzicka reported serving as a paid company adviser.
GENEVA – Nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, maintained its early dramatic antipruritic effect in patients with moderate to severe atopic dermatitis (AD) throughout a year-long unblinded extension of a large, high-profile, 12-week, phase 2 randomized trial, Thomas Ruzicka, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
In contrast, the 52-week extension study also showed the improvement in the dermatitis aspect of AD as measured by Eczema Area and Severity Index (EASI) scores was more gradual and less robust.
The study, 64 weeks in total, also demonstrated that what really matters to patients with moderate or severe AD is relief from the itch. Scores on the Dermatology Life Quality Index showed marked improvement even if their improvement in EASI scores was suboptimal.
“The dermatitis scores improved. But the most concerning symptom to patients is the pruritus; that’s what worsens their quality of life. And this improves dramatically very early in the course of the study,” Dr. Ruzicka explained. “If they drop their itch they are very happy. They don’t care about the redness of the skin so much as the pruritus. This is what really bothers them, as has been shown in epidemiologic studies.”
The original 12-week, phase 2, randomized, double-blind, dose-ranging trial drew extensive attention because it demonstrated convincingly for the first time that the inflammatory cytokine interleukin-31 plays a key role in the pathobiology of AD by promoting skin barrier dysfunction, pruritus, and the inflammatory response in AD – and that a biologic agent, nemolizumab, could inhibit those disease mechanisms (N Engl J Med. 2017 Mar 2;376[9]:826-35).
At a dose of 0.5 mg/kg administered by subcutaneous injection every 4 weeks, nemolizumab, a humanized monoclonal antibody directed against interleukin-31 receptor A, reduced scores on the pruritus visual-analogue scale by 60% as early as 4 weeks and maintained that effect through 12 weeks. At that point, the double-blind study ended and the 52-week extension began. Patients on nemolizumab in the double-blind phase stayed on the same dosage for the extension, while those who’d been on placebo were switched to nemolizumab at 0.1, 0.5, or 2.0 mg/kg every 4 weeks.
A total of 211 patients with moderate to severe AD inadequately controlled by topical therapies enrolled in the extension study. The combined 64-week experience convinced investigators and the sponsor, Chugai Pharmaceutical, that 0.5 mg/kg every 4 weeks is the optimal dose to take forward into planned advanced-stage clinical trials.
“At this dosage the IL-31 receptor is saturated, so higher dosages aren’t needed,” according to Dr. Ruzicka.
By week 64, patients in the 0.5-mg/kg arm of the study showed further gradual improvement in their pruritus visual-analogue score, from a 60% reduction from baseline at 12 weeks to close to an 80% reduction at week 64.
Roughly half of nemolizumab-treated patients achieved an EASI-50 response within the first 4 weeks of the double-blind phase of the study and stayed in that response zone throughout the extension study.
The EASI-75 and -90 responses followed a pattern different from EASI-50. Patients didn’t leap to those more robust levels of response early and then plateau. Instead, the EASI-75 and -90 responses were achieved via a gradual climb in efficacy throughout the study, such that by week 64 roughly 35%-40% of patients on the various nemolizumab dosages had reached EASI-75.
In the extension study, patients were permitted to use a mild topical steroid or topical calcineurin inhibitor as needed, and a potent or very potent topical steroid as rescue medication. Roughly half of participants resorted to any topical steroid at least once during the 64 months. An important new observation gleaned in the long-term study was that the patients who did use topical steroids were twice as likely to reach an EASI 75 response.
Roughly 20% of patients on the three highest dosages of nemolizumab achieved a static Investigator’s Global Assessment score of 0 or 1, meaning clear or almost clear, by week 64.
Scores on the Dermatology Life Quality Index fell steadily over the course of 64 weeks, from a baseline of about 16 to 5 at study’s close.
The side effect profile of nemolizumab was essentially the same as seen in the placebo arm during the double-blind phase. About one-quarter of patients experienced nasopharyngitis over the course of 64 weeks of treatment. A similar fraction reported exacerbations of their atopic dermatitis; however, these events were front-loaded in the first weeks of the initial double-blind study phase and appeared to have been triggered by the drug washout period prior to the patients’ receiving the first dose of nemolizumab, according to Dr. Ruzicka. No new safety signals emerged during the additional 52 weeks of treatment.
The study was funded by Chugai. Dr. Ruzicka reported serving as a paid company adviser.
AT THE EADV CONGRESS
Key clinical point:
Major finding: The early dramatic antipruritic effect demonstrated by nemolizumab for atopic dermatitis in a 12-week randomized trial was maintained throughout an additional 52 weeks in an extension study.
Data source: This analysis focused on 211 patients with moderate to severe atopic dermatitis who participated in a 52-week open-label extension study after completing a previously reported 12-week, double-blind, placebo-controlled phase.
Disclosures: The presenter is a paid medical adviser to Chugai Pharmaceutical, which funded the study.
Moderate psoriasis: the new frontier for systemic therapies
GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.
“A large percentage of my patients who are on biologic therapy have less than 10% involved body surface area and would have a PASI [Psoriasis Area Severity Index] score, if I were to measure it, of under 12. Therefore they couldn’t get into a typical registration study for moderate to severe psoriasis,” he continued.
The UNVEIL trial included a 16-week, double-blind, placebo-controlled phase in which 221 systemic therapy–naive patients with plaque psoriasis on 5%-10% of their body surface area (BSA) were randomized 2:1 to apremilast at 30 mg twice a day or placebo. Thereafter, the placebo group was switched over to apremilast and the trial continued in open-label fashion out to 52 weeks. Apremilast (Otezla) is approved only for use in moderate to severe psoriasis.
At baseline, participants had a mean 15-year duration of psoriasis, an involved BSA of 7.1%, a PASI score of 8.1, a static Physician’s Global Assessment (PGA) score of 3 on a 0-5 scale, and a Dermatology Life Quality Index (DLQI) score of 11.
UNVEIL not only targeted a new population for a modern systemic therapy, it also debuted as its primary endpoint a novel metric for disease severity. Because PASI score is a relatively crude measure of change in a population with moderate psoriasis, Dr. Strober and his coinvestigators developed and employed as the primary outcome measure PGA+BSA, which can range from 15 to 30.
The mean baseline PGA+BSA was 21.8. At week 16, the placebo group averaged a 10% decrease in this metric, while the apremilast group showed a 48% reduction. At week 52, the group switched from placebo to apremilast at 16 weeks had a 42% improvement in PGA+BSA and patients on apremilast for the full study had a 49% improvement.
“So you can assume about half of patients with moderate psoriasis will experience a 50% reduction in the product of PGA+BSA on apremilast,” Dr. Strober observed.
At week 52, a PGA score of 0 or 1, meaning clear or almost clear, was present in 36% of the switchover group and 29% of patients on apremilast for 52 weeks.
A 75% improvement in PGA+BSA, or a PGA+BSA–75 response, occurred at week 52 in 45% of the switchover group and 37% of those on apremilast for the entire study.
The mean improvement in the DLQI at week 16 was 2.4 points in the placebo arm and twice that amount with apremilast. At 52 weeks, the switchover group averaged a 5.1-point reduction in DLQI from baseline and the full-time apremilast group had a 4.3-point reduction.
The incidence of apremilast-related adverse events didn’t increase over time. The main issues were diarrhea, nausea, and headache, as is the case when the oral drug is prescribed for its approved indication in patients with moderate to severe psoriasis.
In an interview, Dr. Strober said that despite the encouraging results of UNVEIL, the study is not by itself sufficient evidence to win an expanded indication for apremilast from regulatory agencies and the drug’s manufacturer, Celgene, is not interested in pursuing that course.
UNVEIL, a phase 4 study, was funded by Celgene. Dr. Strober reported serving as a consultant to and/or receiving research funding from that company and more than a dozen others.
GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.
“A large percentage of my patients who are on biologic therapy have less than 10% involved body surface area and would have a PASI [Psoriasis Area Severity Index] score, if I were to measure it, of under 12. Therefore they couldn’t get into a typical registration study for moderate to severe psoriasis,” he continued.
The UNVEIL trial included a 16-week, double-blind, placebo-controlled phase in which 221 systemic therapy–naive patients with plaque psoriasis on 5%-10% of their body surface area (BSA) were randomized 2:1 to apremilast at 30 mg twice a day or placebo. Thereafter, the placebo group was switched over to apremilast and the trial continued in open-label fashion out to 52 weeks. Apremilast (Otezla) is approved only for use in moderate to severe psoriasis.
At baseline, participants had a mean 15-year duration of psoriasis, an involved BSA of 7.1%, a PASI score of 8.1, a static Physician’s Global Assessment (PGA) score of 3 on a 0-5 scale, and a Dermatology Life Quality Index (DLQI) score of 11.
UNVEIL not only targeted a new population for a modern systemic therapy, it also debuted as its primary endpoint a novel metric for disease severity. Because PASI score is a relatively crude measure of change in a population with moderate psoriasis, Dr. Strober and his coinvestigators developed and employed as the primary outcome measure PGA+BSA, which can range from 15 to 30.
The mean baseline PGA+BSA was 21.8. At week 16, the placebo group averaged a 10% decrease in this metric, while the apremilast group showed a 48% reduction. At week 52, the group switched from placebo to apremilast at 16 weeks had a 42% improvement in PGA+BSA and patients on apremilast for the full study had a 49% improvement.
“So you can assume about half of patients with moderate psoriasis will experience a 50% reduction in the product of PGA+BSA on apremilast,” Dr. Strober observed.
At week 52, a PGA score of 0 or 1, meaning clear or almost clear, was present in 36% of the switchover group and 29% of patients on apremilast for 52 weeks.
A 75% improvement in PGA+BSA, or a PGA+BSA–75 response, occurred at week 52 in 45% of the switchover group and 37% of those on apremilast for the entire study.
The mean improvement in the DLQI at week 16 was 2.4 points in the placebo arm and twice that amount with apremilast. At 52 weeks, the switchover group averaged a 5.1-point reduction in DLQI from baseline and the full-time apremilast group had a 4.3-point reduction.
The incidence of apremilast-related adverse events didn’t increase over time. The main issues were diarrhea, nausea, and headache, as is the case when the oral drug is prescribed for its approved indication in patients with moderate to severe psoriasis.
In an interview, Dr. Strober said that despite the encouraging results of UNVEIL, the study is not by itself sufficient evidence to win an expanded indication for apremilast from regulatory agencies and the drug’s manufacturer, Celgene, is not interested in pursuing that course.
UNVEIL, a phase 4 study, was funded by Celgene. Dr. Strober reported serving as a consultant to and/or receiving research funding from that company and more than a dozen others.
GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.
“A large percentage of my patients who are on biologic therapy have less than 10% involved body surface area and would have a PASI [Psoriasis Area Severity Index] score, if I were to measure it, of under 12. Therefore they couldn’t get into a typical registration study for moderate to severe psoriasis,” he continued.
The UNVEIL trial included a 16-week, double-blind, placebo-controlled phase in which 221 systemic therapy–naive patients with plaque psoriasis on 5%-10% of their body surface area (BSA) were randomized 2:1 to apremilast at 30 mg twice a day or placebo. Thereafter, the placebo group was switched over to apremilast and the trial continued in open-label fashion out to 52 weeks. Apremilast (Otezla) is approved only for use in moderate to severe psoriasis.
At baseline, participants had a mean 15-year duration of psoriasis, an involved BSA of 7.1%, a PASI score of 8.1, a static Physician’s Global Assessment (PGA) score of 3 on a 0-5 scale, and a Dermatology Life Quality Index (DLQI) score of 11.
UNVEIL not only targeted a new population for a modern systemic therapy, it also debuted as its primary endpoint a novel metric for disease severity. Because PASI score is a relatively crude measure of change in a population with moderate psoriasis, Dr. Strober and his coinvestigators developed and employed as the primary outcome measure PGA+BSA, which can range from 15 to 30.
The mean baseline PGA+BSA was 21.8. At week 16, the placebo group averaged a 10% decrease in this metric, while the apremilast group showed a 48% reduction. At week 52, the group switched from placebo to apremilast at 16 weeks had a 42% improvement in PGA+BSA and patients on apremilast for the full study had a 49% improvement.
“So you can assume about half of patients with moderate psoriasis will experience a 50% reduction in the product of PGA+BSA on apremilast,” Dr. Strober observed.
At week 52, a PGA score of 0 or 1, meaning clear or almost clear, was present in 36% of the switchover group and 29% of patients on apremilast for 52 weeks.
A 75% improvement in PGA+BSA, or a PGA+BSA–75 response, occurred at week 52 in 45% of the switchover group and 37% of those on apremilast for the entire study.
The mean improvement in the DLQI at week 16 was 2.4 points in the placebo arm and twice that amount with apremilast. At 52 weeks, the switchover group averaged a 5.1-point reduction in DLQI from baseline and the full-time apremilast group had a 4.3-point reduction.
The incidence of apremilast-related adverse events didn’t increase over time. The main issues were diarrhea, nausea, and headache, as is the case when the oral drug is prescribed for its approved indication in patients with moderate to severe psoriasis.
In an interview, Dr. Strober said that despite the encouraging results of UNVEIL, the study is not by itself sufficient evidence to win an expanded indication for apremilast from regulatory agencies and the drug’s manufacturer, Celgene, is not interested in pursuing that course.
UNVEIL, a phase 4 study, was funded by Celgene. Dr. Strober reported serving as a consultant to and/or receiving research funding from that company and more than a dozen others.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Roughly half of apremilast-treated patients with moderate psoriasis as defined by an involved body surface area of 5%-10% experienced a 50% reduction in a novel outcome metric: the product of the Physician’s Global Assessment plus the involved body surface area.
Data source: This 52-week study of 221 patients with truly moderate psoriasis featured a 16-week, double-blind, placebo-controlled phase, after which everyone continued on open-label apremilast out to 51 weeks.
Disclosures: The UNVEIL study was sponsored by Celgene. The presenter reported receiving research funding from and serving as a consultant to that company and numerous others.
Guselkumab tops adalimumab for psychiatric comorbidities in psoriasis
GENEVA – Guselkumab for treatment of moderate to severe plaque psoriasis generated significantly greater improvement in comorbid anxiety and depression than adalimumab in the head-to-head VOYAGE 2 randomized trial, Kenneth B. Gordon, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The population enrolled in VOYAGE 2, which did not preselect to enrich the study population for anxiety and depression, reflected how common these mental health problems are among psoriasis patients. Fully 38.6% of the 992 randomized patients had a baseline Hospital Anxiety and Depression Score-Anxiety (HADS-A) of 8 or more (considered clinically important anxiety) on the 0-21 scale, and 27.7% had a HADS-D score of at least 8 (indicative of clinically meaningful depression), noted Dr. Gordon, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee.
The on-treatment reductions in psychiatric symptoms in VOYAGE 2 correlated closely with greater improvement in psoriasis, he added. For example, regardless of which drug they were on, patients with a baseline HADS-D of 8 or more averaged a 3.6-point reduction in HADS-D at week 24 if, at that point, they had a Psoriasis Area Severity Index (PASI) response of 75-89, a 4.0-point improvement if they had a PASI 90-99 response, and a 5.2-point reduction in HADS-D if they had a PASI 100 response.
VOYAGE 2 was a phase 3, double-blind, multicenter, placebo-controlled comparison of guselkumab (Tremfya), a human monoclonal antibody targeting the interleukin-23 p 19 subunit, and the tumor necrosis factor-alpha inhibitor adalimumab (Humira) in their standard dosing. Participants were randomized 2:1:1 to guselkumab, adalimumab, or placebo. The study’s primary outcomes have previously been reported (J Am Acad Dermatol. 2017 Mar;76[3]:418-31). For example, at week 24 the guselkumab group demonstrated PASI 75, 90, and 100 responses of 89.1%, 75.2%, and 44.2%, respectively, compared with adalimumab, with PASI 75, 90, and 100 responses of 71%, 54.8%, and 26.6%.
Serial measurement of anxiety and depression symptoms using the HADS-A and HADS-D were part of the study protocol. The mean baseline HADS-A and HADS-D scores were 6.8 and 5.3. At week 24, the mean reduction in the HADS-A score was 2.0 points in the guselkumab group, compared with 1.0 point in the adalimumab arm. HADS-D scores improved by 1.7 and 1.1 points, respectively, in the overall guselkumab and adalimumab groups.
More importantly, among patients with a baseline HADS-A of 8 or higher, by week 16 of the trial, the HADS-A score had dropped below 8 in 51.4% of those on guselkumab, compared with 44.9% of patients on adalimumab and 25.9% on placebo, Dr. Gordon reported. Similarly, 59.2% of guselkumab-treated patients with a high baseline HADS-D improved to a score below 8 at week 16, compared with 54.3% on adalimumab and 27% on placebo.
At week 24, 58.4% of guselkumab-treated patients with a high baseline HADS-A and 59.4% of those with a high HADS-D had scores below 8. Again, these responses were significantly better than the 42.9% and 46.4% rates, respectively, in the adalimumab arm.
VOYAGE 2 was sponsored by Janssen, which markets guselkumab, approved by the Food and Drug Administration in July 2017 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Dr. Gordon reported receiving research support from and serving as a consultant to Janssen and numerous other pharmaceutical companies.
GENEVA – Guselkumab for treatment of moderate to severe plaque psoriasis generated significantly greater improvement in comorbid anxiety and depression than adalimumab in the head-to-head VOYAGE 2 randomized trial, Kenneth B. Gordon, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The population enrolled in VOYAGE 2, which did not preselect to enrich the study population for anxiety and depression, reflected how common these mental health problems are among psoriasis patients. Fully 38.6% of the 992 randomized patients had a baseline Hospital Anxiety and Depression Score-Anxiety (HADS-A) of 8 or more (considered clinically important anxiety) on the 0-21 scale, and 27.7% had a HADS-D score of at least 8 (indicative of clinically meaningful depression), noted Dr. Gordon, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee.
The on-treatment reductions in psychiatric symptoms in VOYAGE 2 correlated closely with greater improvement in psoriasis, he added. For example, regardless of which drug they were on, patients with a baseline HADS-D of 8 or more averaged a 3.6-point reduction in HADS-D at week 24 if, at that point, they had a Psoriasis Area Severity Index (PASI) response of 75-89, a 4.0-point improvement if they had a PASI 90-99 response, and a 5.2-point reduction in HADS-D if they had a PASI 100 response.
VOYAGE 2 was a phase 3, double-blind, multicenter, placebo-controlled comparison of guselkumab (Tremfya), a human monoclonal antibody targeting the interleukin-23 p 19 subunit, and the tumor necrosis factor-alpha inhibitor adalimumab (Humira) in their standard dosing. Participants were randomized 2:1:1 to guselkumab, adalimumab, or placebo. The study’s primary outcomes have previously been reported (J Am Acad Dermatol. 2017 Mar;76[3]:418-31). For example, at week 24 the guselkumab group demonstrated PASI 75, 90, and 100 responses of 89.1%, 75.2%, and 44.2%, respectively, compared with adalimumab, with PASI 75, 90, and 100 responses of 71%, 54.8%, and 26.6%.
Serial measurement of anxiety and depression symptoms using the HADS-A and HADS-D were part of the study protocol. The mean baseline HADS-A and HADS-D scores were 6.8 and 5.3. At week 24, the mean reduction in the HADS-A score was 2.0 points in the guselkumab group, compared with 1.0 point in the adalimumab arm. HADS-D scores improved by 1.7 and 1.1 points, respectively, in the overall guselkumab and adalimumab groups.
More importantly, among patients with a baseline HADS-A of 8 or higher, by week 16 of the trial, the HADS-A score had dropped below 8 in 51.4% of those on guselkumab, compared with 44.9% of patients on adalimumab and 25.9% on placebo, Dr. Gordon reported. Similarly, 59.2% of guselkumab-treated patients with a high baseline HADS-D improved to a score below 8 at week 16, compared with 54.3% on adalimumab and 27% on placebo.
At week 24, 58.4% of guselkumab-treated patients with a high baseline HADS-A and 59.4% of those with a high HADS-D had scores below 8. Again, these responses were significantly better than the 42.9% and 46.4% rates, respectively, in the adalimumab arm.
VOYAGE 2 was sponsored by Janssen, which markets guselkumab, approved by the Food and Drug Administration in July 2017 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Dr. Gordon reported receiving research support from and serving as a consultant to Janssen and numerous other pharmaceutical companies.
GENEVA – Guselkumab for treatment of moderate to severe plaque psoriasis generated significantly greater improvement in comorbid anxiety and depression than adalimumab in the head-to-head VOYAGE 2 randomized trial, Kenneth B. Gordon, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The population enrolled in VOYAGE 2, which did not preselect to enrich the study population for anxiety and depression, reflected how common these mental health problems are among psoriasis patients. Fully 38.6% of the 992 randomized patients had a baseline Hospital Anxiety and Depression Score-Anxiety (HADS-A) of 8 or more (considered clinically important anxiety) on the 0-21 scale, and 27.7% had a HADS-D score of at least 8 (indicative of clinically meaningful depression), noted Dr. Gordon, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee.
The on-treatment reductions in psychiatric symptoms in VOYAGE 2 correlated closely with greater improvement in psoriasis, he added. For example, regardless of which drug they were on, patients with a baseline HADS-D of 8 or more averaged a 3.6-point reduction in HADS-D at week 24 if, at that point, they had a Psoriasis Area Severity Index (PASI) response of 75-89, a 4.0-point improvement if they had a PASI 90-99 response, and a 5.2-point reduction in HADS-D if they had a PASI 100 response.
VOYAGE 2 was a phase 3, double-blind, multicenter, placebo-controlled comparison of guselkumab (Tremfya), a human monoclonal antibody targeting the interleukin-23 p 19 subunit, and the tumor necrosis factor-alpha inhibitor adalimumab (Humira) in their standard dosing. Participants were randomized 2:1:1 to guselkumab, adalimumab, or placebo. The study’s primary outcomes have previously been reported (J Am Acad Dermatol. 2017 Mar;76[3]:418-31). For example, at week 24 the guselkumab group demonstrated PASI 75, 90, and 100 responses of 89.1%, 75.2%, and 44.2%, respectively, compared with adalimumab, with PASI 75, 90, and 100 responses of 71%, 54.8%, and 26.6%.
Serial measurement of anxiety and depression symptoms using the HADS-A and HADS-D were part of the study protocol. The mean baseline HADS-A and HADS-D scores were 6.8 and 5.3. At week 24, the mean reduction in the HADS-A score was 2.0 points in the guselkumab group, compared with 1.0 point in the adalimumab arm. HADS-D scores improved by 1.7 and 1.1 points, respectively, in the overall guselkumab and adalimumab groups.
More importantly, among patients with a baseline HADS-A of 8 or higher, by week 16 of the trial, the HADS-A score had dropped below 8 in 51.4% of those on guselkumab, compared with 44.9% of patients on adalimumab and 25.9% on placebo, Dr. Gordon reported. Similarly, 59.2% of guselkumab-treated patients with a high baseline HADS-D improved to a score below 8 at week 16, compared with 54.3% on adalimumab and 27% on placebo.
At week 24, 58.4% of guselkumab-treated patients with a high baseline HADS-A and 59.4% of those with a high HADS-D had scores below 8. Again, these responses were significantly better than the 42.9% and 46.4% rates, respectively, in the adalimumab arm.
VOYAGE 2 was sponsored by Janssen, which markets guselkumab, approved by the Food and Drug Administration in July 2017 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Dr. Gordon reported receiving research support from and serving as a consultant to Janssen and numerous other pharmaceutical companies.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Fifty-nine percent of gesulkumab-treated patients with moderate to severe psoriasis and clinically significant depression at baseline were below the depression threshold at week 24, compared with 46% of adalimumab-treated patients.
Data source: A phase 3, double-blind, multicenter, placebo-controlled comparison of guselkumab and adalimumab in 992 randomized patients with moderate to severe psoriasis.
Disclosures: VOYAGE 2 was sponsored by Janssen, which markets guselkumab. The presenter reported receiving research support from and serving as a consultant to Janssen and numerous other pharmaceutical companies.
Psoriasis patients face higher risk of alcohol-related death – but lower suicide risk
GENEVA – Psoriasis patients are roughly two-thirds more likely to die of alcohol-related causes than their peers in the general population, Rosa Parisi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Indeed, alcohol-related mortality appears to be an important contributor to the long-recognized elevated risk of premature mortality in patients who’ve been diagnosed with psoriasis, according to Dr. Parisi of the University of Manchester (England), who presented the results of a retrospective cohort study of alcohol-related deaths. The reasons for psoriasis patients’ increased risk of early mortality have been unclear, although it’s well established that psoriasis is associated with increased rates of unhealthy behaviors, including smoking and high alcohol consumption.
The study of alcohol-related deaths utilized a database of 398 primary care practices in England. The study population consisted of 55,537 patients diagnosed with psoriasis in 1998-2014 and 854,314 controls without psoriasis who were matched based on age, sex, and membership in the same primary care practice.
During a median 4.4 years of follow-up, the rate of deaths directly attributable to alcohol consumption was 4.8 per 10,000 person-years in the psoriasis group and 2.5 per 10,000 person-years in controls. Nearly two-thirds of the alcohol-related deaths were recorded as due to alcoholic liver disease and 24% to hepatic fibrosis and cirrhosis; 8% were attributed to mental and behavioral disorders due to alcohol.
In an analysis adjusted for socioeconomic status, the risk for alcohol-related death was increased 1.58-fold in the psoriasis group, compared with controls. Upon exclusion of all subjects who’d been on methotrexate on the grounds that the drug interacts with alcohol to accelerate liver damage, having psoriasis was associated with a 1.66-fold increased risk of alcohol-related death.
Such deaths occurred in women with psoriasis at a median age of 55 – a full 5 years younger than alcohol-related deaths in nonpsoriatic women. The age gap was smaller in men.
Medical records indicated that 82.2% of psoriasis patients who died of alcohol-related causes had previously been coded by their primary care practitioner as a heavy drinker, as were 75.5% of those without psoriasis who died of similar causes. Yet fewer than 11% of the psoriasis patients and controls who experienced alcohol-related mortality had ever received a prescription for a medication for alcohol dependence, such as disulfiram. Psychologic support for alcohol dependence had been offered within the primary care practices for only 19.7% of psoriasis patients with an alcohol-related death and 14.4% of controls.
These statistics contain an important message for clinicians, Dr. Parisi said.
“Alcohol misuse often remains unidentified and undertreated in primary care. Health care practitioners should be more aware of the psychologic difficulties of people with psoriasis. The Alcohol Use Disorders Identification Test screening tool, which has been developed by the World Health Organization, should be implemented in both primary and secondary care to detect alcohol misuse in psoriasis patients,” she asserted.
Elsewhere at the meeting, she presented a study on the risks of suicide and nonfatal deliberate self-harm among psoriasis patients. She utilized the same database of 398 English primary care medical practices. This analysis included 56,961 psoriasis patients and 876,919 matched controls.
The suicide rate was 1.1 per 10,000 person-years in the psoriasis group and 1.5 per 10,000 person-years in controls. In a proportional hazard analysis adjusted for socioeconomic status, psoriasis patients were at a significant 41% lower risk of suicide than their nonpsoriatic peers. Breaking down the data further based upon age at diagnosis of psoriasis, patients diagnosed before age 40 were at a nonsignificant 8% lower risk of suicide, while those diagnosed at age 40 years or older experienced a highly significant 62% reduction in risk of suicide, compared with controls.
This was the case even though the psoriasis group had a significantly greater prevalence of psychiatric comorbidities overall, by a margin of 29.2% versus 26.4%.
The analysis of risk of nonfatal deliberate self-harm was done after excluding all individuals in the suicide study who had a baseline history of self-harm. This resulted in a study population of 54,709 psoriasis patients and 813,699 controls matched by age, sex, and primary care practice. Bottom line: There was no evidence of an association between having a diagnosis of psoriasis and nonfatal deliberate self-harm. The rates – 18.9 events per 10,000 person-years in the psoriasis group and 16.3 per 10,000 person-years in controls – were closely similar after adjusting for socioeconomic status.
Simultaneous with her EADV presentation on alcohol-related deaths in psoriasis patients, Dr. Parisi’s study was published online (JAMA Dermatol. 2017 Sep 15. doi: 10.1001/jamadermatol.2017.3225).
She reported having no financial conflicts of interest regarding her presentations.
GENEVA – Psoriasis patients are roughly two-thirds more likely to die of alcohol-related causes than their peers in the general population, Rosa Parisi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Indeed, alcohol-related mortality appears to be an important contributor to the long-recognized elevated risk of premature mortality in patients who’ve been diagnosed with psoriasis, according to Dr. Parisi of the University of Manchester (England), who presented the results of a retrospective cohort study of alcohol-related deaths. The reasons for psoriasis patients’ increased risk of early mortality have been unclear, although it’s well established that psoriasis is associated with increased rates of unhealthy behaviors, including smoking and high alcohol consumption.
The study of alcohol-related deaths utilized a database of 398 primary care practices in England. The study population consisted of 55,537 patients diagnosed with psoriasis in 1998-2014 and 854,314 controls without psoriasis who were matched based on age, sex, and membership in the same primary care practice.
During a median 4.4 years of follow-up, the rate of deaths directly attributable to alcohol consumption was 4.8 per 10,000 person-years in the psoriasis group and 2.5 per 10,000 person-years in controls. Nearly two-thirds of the alcohol-related deaths were recorded as due to alcoholic liver disease and 24% to hepatic fibrosis and cirrhosis; 8% were attributed to mental and behavioral disorders due to alcohol.
In an analysis adjusted for socioeconomic status, the risk for alcohol-related death was increased 1.58-fold in the psoriasis group, compared with controls. Upon exclusion of all subjects who’d been on methotrexate on the grounds that the drug interacts with alcohol to accelerate liver damage, having psoriasis was associated with a 1.66-fold increased risk of alcohol-related death.
Such deaths occurred in women with psoriasis at a median age of 55 – a full 5 years younger than alcohol-related deaths in nonpsoriatic women. The age gap was smaller in men.
Medical records indicated that 82.2% of psoriasis patients who died of alcohol-related causes had previously been coded by their primary care practitioner as a heavy drinker, as were 75.5% of those without psoriasis who died of similar causes. Yet fewer than 11% of the psoriasis patients and controls who experienced alcohol-related mortality had ever received a prescription for a medication for alcohol dependence, such as disulfiram. Psychologic support for alcohol dependence had been offered within the primary care practices for only 19.7% of psoriasis patients with an alcohol-related death and 14.4% of controls.
These statistics contain an important message for clinicians, Dr. Parisi said.
“Alcohol misuse often remains unidentified and undertreated in primary care. Health care practitioners should be more aware of the psychologic difficulties of people with psoriasis. The Alcohol Use Disorders Identification Test screening tool, which has been developed by the World Health Organization, should be implemented in both primary and secondary care to detect alcohol misuse in psoriasis patients,” she asserted.
Elsewhere at the meeting, she presented a study on the risks of suicide and nonfatal deliberate self-harm among psoriasis patients. She utilized the same database of 398 English primary care medical practices. This analysis included 56,961 psoriasis patients and 876,919 matched controls.
The suicide rate was 1.1 per 10,000 person-years in the psoriasis group and 1.5 per 10,000 person-years in controls. In a proportional hazard analysis adjusted for socioeconomic status, psoriasis patients were at a significant 41% lower risk of suicide than their nonpsoriatic peers. Breaking down the data further based upon age at diagnosis of psoriasis, patients diagnosed before age 40 were at a nonsignificant 8% lower risk of suicide, while those diagnosed at age 40 years or older experienced a highly significant 62% reduction in risk of suicide, compared with controls.
This was the case even though the psoriasis group had a significantly greater prevalence of psychiatric comorbidities overall, by a margin of 29.2% versus 26.4%.
The analysis of risk of nonfatal deliberate self-harm was done after excluding all individuals in the suicide study who had a baseline history of self-harm. This resulted in a study population of 54,709 psoriasis patients and 813,699 controls matched by age, sex, and primary care practice. Bottom line: There was no evidence of an association between having a diagnosis of psoriasis and nonfatal deliberate self-harm. The rates – 18.9 events per 10,000 person-years in the psoriasis group and 16.3 per 10,000 person-years in controls – were closely similar after adjusting for socioeconomic status.
Simultaneous with her EADV presentation on alcohol-related deaths in psoriasis patients, Dr. Parisi’s study was published online (JAMA Dermatol. 2017 Sep 15. doi: 10.1001/jamadermatol.2017.3225).
She reported having no financial conflicts of interest regarding her presentations.
GENEVA – Psoriasis patients are roughly two-thirds more likely to die of alcohol-related causes than their peers in the general population, Rosa Parisi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Indeed, alcohol-related mortality appears to be an important contributor to the long-recognized elevated risk of premature mortality in patients who’ve been diagnosed with psoriasis, according to Dr. Parisi of the University of Manchester (England), who presented the results of a retrospective cohort study of alcohol-related deaths. The reasons for psoriasis patients’ increased risk of early mortality have been unclear, although it’s well established that psoriasis is associated with increased rates of unhealthy behaviors, including smoking and high alcohol consumption.
The study of alcohol-related deaths utilized a database of 398 primary care practices in England. The study population consisted of 55,537 patients diagnosed with psoriasis in 1998-2014 and 854,314 controls without psoriasis who were matched based on age, sex, and membership in the same primary care practice.
During a median 4.4 years of follow-up, the rate of deaths directly attributable to alcohol consumption was 4.8 per 10,000 person-years in the psoriasis group and 2.5 per 10,000 person-years in controls. Nearly two-thirds of the alcohol-related deaths were recorded as due to alcoholic liver disease and 24% to hepatic fibrosis and cirrhosis; 8% were attributed to mental and behavioral disorders due to alcohol.
In an analysis adjusted for socioeconomic status, the risk for alcohol-related death was increased 1.58-fold in the psoriasis group, compared with controls. Upon exclusion of all subjects who’d been on methotrexate on the grounds that the drug interacts with alcohol to accelerate liver damage, having psoriasis was associated with a 1.66-fold increased risk of alcohol-related death.
Such deaths occurred in women with psoriasis at a median age of 55 – a full 5 years younger than alcohol-related deaths in nonpsoriatic women. The age gap was smaller in men.
Medical records indicated that 82.2% of psoriasis patients who died of alcohol-related causes had previously been coded by their primary care practitioner as a heavy drinker, as were 75.5% of those without psoriasis who died of similar causes. Yet fewer than 11% of the psoriasis patients and controls who experienced alcohol-related mortality had ever received a prescription for a medication for alcohol dependence, such as disulfiram. Psychologic support for alcohol dependence had been offered within the primary care practices for only 19.7% of psoriasis patients with an alcohol-related death and 14.4% of controls.
These statistics contain an important message for clinicians, Dr. Parisi said.
“Alcohol misuse often remains unidentified and undertreated in primary care. Health care practitioners should be more aware of the psychologic difficulties of people with psoriasis. The Alcohol Use Disorders Identification Test screening tool, which has been developed by the World Health Organization, should be implemented in both primary and secondary care to detect alcohol misuse in psoriasis patients,” she asserted.
Elsewhere at the meeting, she presented a study on the risks of suicide and nonfatal deliberate self-harm among psoriasis patients. She utilized the same database of 398 English primary care medical practices. This analysis included 56,961 psoriasis patients and 876,919 matched controls.
The suicide rate was 1.1 per 10,000 person-years in the psoriasis group and 1.5 per 10,000 person-years in controls. In a proportional hazard analysis adjusted for socioeconomic status, psoriasis patients were at a significant 41% lower risk of suicide than their nonpsoriatic peers. Breaking down the data further based upon age at diagnosis of psoriasis, patients diagnosed before age 40 were at a nonsignificant 8% lower risk of suicide, while those diagnosed at age 40 years or older experienced a highly significant 62% reduction in risk of suicide, compared with controls.
This was the case even though the psoriasis group had a significantly greater prevalence of psychiatric comorbidities overall, by a margin of 29.2% versus 26.4%.
The analysis of risk of nonfatal deliberate self-harm was done after excluding all individuals in the suicide study who had a baseline history of self-harm. This resulted in a study population of 54,709 psoriasis patients and 813,699 controls matched by age, sex, and primary care practice. Bottom line: There was no evidence of an association between having a diagnosis of psoriasis and nonfatal deliberate self-harm. The rates – 18.9 events per 10,000 person-years in the psoriasis group and 16.3 per 10,000 person-years in controls – were closely similar after adjusting for socioeconomic status.
Simultaneous with her EADV presentation on alcohol-related deaths in psoriasis patients, Dr. Parisi’s study was published online (JAMA Dermatol. 2017 Sep 15. doi: 10.1001/jamadermatol.2017.3225).
She reported having no financial conflicts of interest regarding her presentations.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Psoriasis patients who had never been on methotrexate had a 66% higher rate of alcohol-related death than matched controls without psoriasis.
Data source: This retrospective cohort study of alcohol-related deaths included 55,537 psoriasis patients and 854,314 controls without psoriasis matched based on age, sex, and membership in the same primary care practice.
Disclosures: The study presenter reported having no financial conflicts of interest.