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Elderly patients with psoriasis can benefit from biologics with low rates of adverse events

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Elderly patients with psoriasis respond just as well to biologic treatments as do younger patients, with a low rate of serious adverse events, according to a new retrospective study.

Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.

Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.

As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”

To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.

The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.

The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.

Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.

The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.

The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.

The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.

There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.

Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).

None of the authors had financial disclosures, and the study had no funding source.

[email protected]

SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.

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Elderly patients with psoriasis respond just as well to biologic treatments as do younger patients, with a low rate of serious adverse events, according to a new retrospective study.

Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.

Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.

As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”

To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.

The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.

The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.

Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.

The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.

The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.

The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.

There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.

Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).

None of the authors had financial disclosures, and the study had no funding source.

[email protected]

SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.

 

Elderly patients with psoriasis respond just as well to biologic treatments as do younger patients, with a low rate of serious adverse events, according to a new retrospective study.

Among 266 older patients, 65% achieved a 75% improvement in Psoriasis Area Severity Index score (PASI 75) after 1 year of therapy; 50% reached a PASI 90, and 40% a PASI 100, Francesca Prignano MD, PhD, and her colleagues reported in the Journal of the European Academy of Dermatology and Venereology. The rate of serious adverse events was less than 10%.

Elderly patients – those aged 65 years and older – are commonly excluded from studies on biologic treatments because they have more medical comorbidities and are thought to be more at risk for serious adverse events, like infections and malignancy, wrote Dr. Prignano of the dermatology unit, University of Florence, Italy, and her colleagues.

As a result, they noted, there is a “lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biologic agents. Disease remission should be an objective for both younger patients and older patients, and biologic therapy should be considered a treatment option for all patients.”

To examine both the benefit and risk of biologics in this population, the team reviewed the records of 266 elderly psoriasis patients; everyone had been on a biologic treatment for at least 1 year.

The primary outcome was PASI score at weeks 8, 16, 28, and 52. The secondary outcomes were the rate and types of biologic-associated adverse events.

The study comprised 266 patients (mean age 72 years). Their mean psoriasis duration was 25.7 years. Comorbidities included psoriatic arthritis; hypertension and dyslipidemia; diabetes mellitus; cardiovascular, gastrointestinal and respiratory diseases; osteoporosis; thyroid dysfunction; depression; and cancer.

Adalimumab was the most commonly prescribed biologic (31%), followed by ustekinumab (28.9%), etanercept (20%), and secukinumab (15%). A smaller proportion of patients were taking infliximab, golimumab, or certolizumab pegol.

The mean baseline PASI was 16.5, although the range was wide (4-54). At the time of review, the average biologic treatment duration was 44 months. Almost half of the cohort (128) were on their second biologic, and 20 more had been on three biologics. A few patients were taking concomitant medications, including steroids, cyclosporine, and acitretin.

The mean PASI scores decreased to 3.7 at week 16, 1.6 at week 28, and 1.2 at week 52. The group exhibited a rapid response to biologic treatment. By 16 weeks, about 55% had achieved a PASI 75, about 28% a PASI 90, and about 20% a PASI 100. By 28 weeks, these numbers were about 64%, 45%, and 35%, respectively. At 1 year, they were about 65%, 50%, and 40%, respectively.

The rate of adverse events was 9.4%. There were 25 events in the cohort, the majority of which (48%) were infections; these included four respiratory infections, three urinary tract infections, two cases of mucocutaneous candidiasis, two cases of herpes zoster infection, and one case of erysipelas.

There were four malignancies: three nonmelanoma skin cancers and one vocal cord cancer.

Noting that, to date, their study represented “the broadest experience on the use of biological drugs” for elderly patients with psoriasis, they wrote that while “comorbidities should be taken into consideration when a long-term treatment is proposed, for the higher risk of side effects and drug interactions,” they wrote, noting that none of the 266 patients had a serious infection and the malignancy rate was low (1.5%).

None of the authors had financial disclosures, and the study had no funding source.

[email protected]

SOURCE: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018 Jun 15. doi: 10.1111/jdv.15139.

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Key clinical point: Patients aged 65 years and older responded well to biologics and had a low rate of serious adverse events.

Major finding: At 1 year, 65% achieved a PASI 75, 50% achieved a reached PASI 90, and 40% achieved a PASI 100, with a 9.4% rate of serious adverse events.

Study details: The retrospective study comprised 266 patients aged 65 years and older treated with biologics for psoriasis.

Disclosures: None of the authors had financial disclosures, and the study had no funding source.

Source: Ricceri F et al. J Eur Acad Dermatol Venereol. 2018. doi: 10.1111/jdv.15139.

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Adalimumab strikes out for aortic inflammation in psoriasis

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– Adalimumab (Humira) did not reduce aortic inflammation in a year-long, randomized trial that pitted the tumor necrosis factor (TNF) blocker against phototherapy and placebo in 97 psoriasis patients.

M. Alexander Otto/MDedge News
Dr. Joel M. Gelfand

“Now we have two trials that are definitively negative for TNF inhibitors” reducing aortic inflammation, a risk factor for cardiovascular events, said senior investigator Joel M. Gelfand, MD, a dermatology professor at the University of Pennsylvania, Philadelphia.

The other trial, from Canada, also found no effect in the ascending aorta after 52 weeks of treatment, but it did find a modest increase in carotid inflammation (J Invest Dermatol. 2017 Aug;137[8]:1638-45).

Both studies used positron emission tomography/computed tomography to assess vascular inflammation.

“We know patients with psoriasis are at increased risk for cardiovascular disease. We think the same kind of inflammation that occurs in atherosclerosis occurs in psoriasis, but we are still teasing out the impact of therapy and which one is most likely to lower the risk of heart attacks, strokes, and things of that nature,” Dr. Gelfand said at the International Investigative Dermatology meeting. The study was published when he gave his presentation (Circ Cardiovasc Imaging. 2018 Jun. doi: 10.1161/CIRCIMAGING.117.007394).

Although it didn’t reduce aortic inflammation, adalimumab had a positive effect on glycoprotein acetylation, a marker of inflammation and subclinical cardiovascular disease in psoriasis. Observational studies have also reported a drop in cardiovascular events with adalimumab. Taken together, the mixed findings “give us pause for thought,” Dr. Gelfand said.

In a previous trial, he and his colleagues had found that the interleukin blocker ustekinumab (Stelara) reduced aortic inflammation in psoriasis by about 19%, but Dr. Gelfand said at the meeting that it’s too early to opt for ustekinumab over adalimumab for cardiovascular protection: “I don’t think we are quite there yet; we are still not certain.”

Following washout of psoriasis treatments, the 97 subjects were randomized to either adalimumab for 12 months or ultraviolet B phototherapy or placebo for 12 weeks, followed by adalimumab for 12 months.

Aortic inflammation was used as a proxy for cardiovascular events because trials to assess actual event rates would require thousands of patients treated for several years. “They’re not likely to be done in psoriasis any time soon,” Dr. Gelfand said.

At both 12 and 52 weeks, adalimumab patients had no change in aortic inflammation, compared with placebo and baseline. Phototherapy patients had a 4% drop from baseline at 12 weeks, but it was not statistically significant when compared with placebo.

Both adalimumab and phototherapy decreased systemic inflammation as gauged by serum C-reactive protein and interleukin-6 levels, but only adalimumab reduced TNF levels and glycoprotein acetylation at 12 and 52 weeks. Neither treatment affected insulin, adiponectin, or leptin levels. Adalimumab dropped HDL cholesterol a bit, a known side effect, while phototherapy increased it.

About half of the patients in both treatment arms had a 75% reduction in the Psoriasis Area and Severity Index at 12 weeks, compared with 7% of those on placebo. Subjects were aged 43 years, on average, and more than two-thirds were men. They had a mean psoriasis duration of 17 years and a baseline PASI score of 19.

 

 

The work was funded by the National Institutes of Health and AbbVie, adalimumab’s maker. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.

SOURCE: Gelfand JM et al. IID 2018, Abstract 393.

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– Adalimumab (Humira) did not reduce aortic inflammation in a year-long, randomized trial that pitted the tumor necrosis factor (TNF) blocker against phototherapy and placebo in 97 psoriasis patients.

M. Alexander Otto/MDedge News
Dr. Joel M. Gelfand

“Now we have two trials that are definitively negative for TNF inhibitors” reducing aortic inflammation, a risk factor for cardiovascular events, said senior investigator Joel M. Gelfand, MD, a dermatology professor at the University of Pennsylvania, Philadelphia.

The other trial, from Canada, also found no effect in the ascending aorta after 52 weeks of treatment, but it did find a modest increase in carotid inflammation (J Invest Dermatol. 2017 Aug;137[8]:1638-45).

Both studies used positron emission tomography/computed tomography to assess vascular inflammation.

“We know patients with psoriasis are at increased risk for cardiovascular disease. We think the same kind of inflammation that occurs in atherosclerosis occurs in psoriasis, but we are still teasing out the impact of therapy and which one is most likely to lower the risk of heart attacks, strokes, and things of that nature,” Dr. Gelfand said at the International Investigative Dermatology meeting. The study was published when he gave his presentation (Circ Cardiovasc Imaging. 2018 Jun. doi: 10.1161/CIRCIMAGING.117.007394).

Although it didn’t reduce aortic inflammation, adalimumab had a positive effect on glycoprotein acetylation, a marker of inflammation and subclinical cardiovascular disease in psoriasis. Observational studies have also reported a drop in cardiovascular events with adalimumab. Taken together, the mixed findings “give us pause for thought,” Dr. Gelfand said.

In a previous trial, he and his colleagues had found that the interleukin blocker ustekinumab (Stelara) reduced aortic inflammation in psoriasis by about 19%, but Dr. Gelfand said at the meeting that it’s too early to opt for ustekinumab over adalimumab for cardiovascular protection: “I don’t think we are quite there yet; we are still not certain.”

Following washout of psoriasis treatments, the 97 subjects were randomized to either adalimumab for 12 months or ultraviolet B phototherapy or placebo for 12 weeks, followed by adalimumab for 12 months.

Aortic inflammation was used as a proxy for cardiovascular events because trials to assess actual event rates would require thousands of patients treated for several years. “They’re not likely to be done in psoriasis any time soon,” Dr. Gelfand said.

At both 12 and 52 weeks, adalimumab patients had no change in aortic inflammation, compared with placebo and baseline. Phototherapy patients had a 4% drop from baseline at 12 weeks, but it was not statistically significant when compared with placebo.

Both adalimumab and phototherapy decreased systemic inflammation as gauged by serum C-reactive protein and interleukin-6 levels, but only adalimumab reduced TNF levels and glycoprotein acetylation at 12 and 52 weeks. Neither treatment affected insulin, adiponectin, or leptin levels. Adalimumab dropped HDL cholesterol a bit, a known side effect, while phototherapy increased it.

About half of the patients in both treatment arms had a 75% reduction in the Psoriasis Area and Severity Index at 12 weeks, compared with 7% of those on placebo. Subjects were aged 43 years, on average, and more than two-thirds were men. They had a mean psoriasis duration of 17 years and a baseline PASI score of 19.

 

 

The work was funded by the National Institutes of Health and AbbVie, adalimumab’s maker. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.

SOURCE: Gelfand JM et al. IID 2018, Abstract 393.

 

– Adalimumab (Humira) did not reduce aortic inflammation in a year-long, randomized trial that pitted the tumor necrosis factor (TNF) blocker against phototherapy and placebo in 97 psoriasis patients.

M. Alexander Otto/MDedge News
Dr. Joel M. Gelfand

“Now we have two trials that are definitively negative for TNF inhibitors” reducing aortic inflammation, a risk factor for cardiovascular events, said senior investigator Joel M. Gelfand, MD, a dermatology professor at the University of Pennsylvania, Philadelphia.

The other trial, from Canada, also found no effect in the ascending aorta after 52 weeks of treatment, but it did find a modest increase in carotid inflammation (J Invest Dermatol. 2017 Aug;137[8]:1638-45).

Both studies used positron emission tomography/computed tomography to assess vascular inflammation.

“We know patients with psoriasis are at increased risk for cardiovascular disease. We think the same kind of inflammation that occurs in atherosclerosis occurs in psoriasis, but we are still teasing out the impact of therapy and which one is most likely to lower the risk of heart attacks, strokes, and things of that nature,” Dr. Gelfand said at the International Investigative Dermatology meeting. The study was published when he gave his presentation (Circ Cardiovasc Imaging. 2018 Jun. doi: 10.1161/CIRCIMAGING.117.007394).

Although it didn’t reduce aortic inflammation, adalimumab had a positive effect on glycoprotein acetylation, a marker of inflammation and subclinical cardiovascular disease in psoriasis. Observational studies have also reported a drop in cardiovascular events with adalimumab. Taken together, the mixed findings “give us pause for thought,” Dr. Gelfand said.

In a previous trial, he and his colleagues had found that the interleukin blocker ustekinumab (Stelara) reduced aortic inflammation in psoriasis by about 19%, but Dr. Gelfand said at the meeting that it’s too early to opt for ustekinumab over adalimumab for cardiovascular protection: “I don’t think we are quite there yet; we are still not certain.”

Following washout of psoriasis treatments, the 97 subjects were randomized to either adalimumab for 12 months or ultraviolet B phototherapy or placebo for 12 weeks, followed by adalimumab for 12 months.

Aortic inflammation was used as a proxy for cardiovascular events because trials to assess actual event rates would require thousands of patients treated for several years. “They’re not likely to be done in psoriasis any time soon,” Dr. Gelfand said.

At both 12 and 52 weeks, adalimumab patients had no change in aortic inflammation, compared with placebo and baseline. Phototherapy patients had a 4% drop from baseline at 12 weeks, but it was not statistically significant when compared with placebo.

Both adalimumab and phototherapy decreased systemic inflammation as gauged by serum C-reactive protein and interleukin-6 levels, but only adalimumab reduced TNF levels and glycoprotein acetylation at 12 and 52 weeks. Neither treatment affected insulin, adiponectin, or leptin levels. Adalimumab dropped HDL cholesterol a bit, a known side effect, while phototherapy increased it.

About half of the patients in both treatment arms had a 75% reduction in the Psoriasis Area and Severity Index at 12 weeks, compared with 7% of those on placebo. Subjects were aged 43 years, on average, and more than two-thirds were men. They had a mean psoriasis duration of 17 years and a baseline PASI score of 19.

 

 

The work was funded by the National Institutes of Health and AbbVie, adalimumab’s maker. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.

SOURCE: Gelfand JM et al. IID 2018, Abstract 393.

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REPORTING FROM IID 2018

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Key clinical point: Adalimumab does not appear to reduce aortic inflammation in psoriasis, a risk factor for cardiovascular events.

Major finding: After a year of treatment, patients had no change in aortic inflammation, compared with placebo and baseline.

Study details: Randomized, controlled trial of 97 patients

Disclosures: The National Institutes of Health and AbbVie, adalimumab’s maker, funded the work. Among many industry ties, Dr. Gelfand is a consultant for Janssen, maker of ustekinumab, and receives research grants from Janssen and AbbVie.

Source: Gelfand JM et al. IID 2018, abstract 393

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Psoriasis therapy with biologics not linked to increased cancer risk

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Biologic treatments were not associated with an increased risk of cancer among patients with psoriasis in the medium term, in a study that analyzed data from patient registries.

“Cumulative length of exposure to biologics was not associated with the risk of developing cancers, even after controlling for the effect of age, gender, location,” as well as for previous exposure to methotrexate, cyclosporine, and phototherapy; duration of psoriasis; and comorbidities, reported Ignacio García-Doval, MD, of the Fundación Academia Española de Dermatología y Venereología, Madrid, and his associates.

Christine Langer-p?schel/Thinkstock
Data from four studies in Psonet from Israel, Italy, Spain, and the United Kingdom were analyzed, with each cancer case matched with up to four cancer-free controls in each cohort. Exposure to biologic therapies, methotrexate, and cyclosporine were calculated as cumulative years of exposure, as were other expected confounders such as duration of psoriasis, length of exposure to phototherapy, and the modified Charlson Comorbidity Index. There were data on 579 cancer cases and 2,671 matched controls; this included 41 cases of squamous cell carcinoma and 108 cases of basal cell carcinoma. Psonet is a surveillance network in Europe that is monitoring the longterm effectiveness and safety of systemic agents in patients with psoriasis.



The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02 (95% confidence interval, 0.92-1.13), demonstrating no significantly increased risk of cancer per cumulative year of biologic exposure for psoriasis therapy, Dr. García-Doval and his associates reported in the study, published in the British Journal of Dermatology. This was true even when broken down within the registries for comparison, and when analyzed by type of cancers, such as squamous cell carcinoma and basal cell carcinoma.

A limitation of the study was inadequate power to detect and compare risk between individual biologics, they said. Also, “as our data describe limited follow-up and latencies, it is still possible that a risk after longer periods of exposure and latencies exists.”

Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

SOURCE: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

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Biologic treatments were not associated with an increased risk of cancer among patients with psoriasis in the medium term, in a study that analyzed data from patient registries.

“Cumulative length of exposure to biologics was not associated with the risk of developing cancers, even after controlling for the effect of age, gender, location,” as well as for previous exposure to methotrexate, cyclosporine, and phototherapy; duration of psoriasis; and comorbidities, reported Ignacio García-Doval, MD, of the Fundación Academia Española de Dermatología y Venereología, Madrid, and his associates.

Christine Langer-p?schel/Thinkstock
Data from four studies in Psonet from Israel, Italy, Spain, and the United Kingdom were analyzed, with each cancer case matched with up to four cancer-free controls in each cohort. Exposure to biologic therapies, methotrexate, and cyclosporine were calculated as cumulative years of exposure, as were other expected confounders such as duration of psoriasis, length of exposure to phototherapy, and the modified Charlson Comorbidity Index. There were data on 579 cancer cases and 2,671 matched controls; this included 41 cases of squamous cell carcinoma and 108 cases of basal cell carcinoma. Psonet is a surveillance network in Europe that is monitoring the longterm effectiveness and safety of systemic agents in patients with psoriasis.



The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02 (95% confidence interval, 0.92-1.13), demonstrating no significantly increased risk of cancer per cumulative year of biologic exposure for psoriasis therapy, Dr. García-Doval and his associates reported in the study, published in the British Journal of Dermatology. This was true even when broken down within the registries for comparison, and when analyzed by type of cancers, such as squamous cell carcinoma and basal cell carcinoma.

A limitation of the study was inadequate power to detect and compare risk between individual biologics, they said. Also, “as our data describe limited follow-up and latencies, it is still possible that a risk after longer periods of exposure and latencies exists.”

Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

SOURCE: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

 

Biologic treatments were not associated with an increased risk of cancer among patients with psoriasis in the medium term, in a study that analyzed data from patient registries.

“Cumulative length of exposure to biologics was not associated with the risk of developing cancers, even after controlling for the effect of age, gender, location,” as well as for previous exposure to methotrexate, cyclosporine, and phototherapy; duration of psoriasis; and comorbidities, reported Ignacio García-Doval, MD, of the Fundación Academia Española de Dermatología y Venereología, Madrid, and his associates.

Christine Langer-p?schel/Thinkstock
Data from four studies in Psonet from Israel, Italy, Spain, and the United Kingdom were analyzed, with each cancer case matched with up to four cancer-free controls in each cohort. Exposure to biologic therapies, methotrexate, and cyclosporine were calculated as cumulative years of exposure, as were other expected confounders such as duration of psoriasis, length of exposure to phototherapy, and the modified Charlson Comorbidity Index. There were data on 579 cancer cases and 2,671 matched controls; this included 41 cases of squamous cell carcinoma and 108 cases of basal cell carcinoma. Psonet is a surveillance network in Europe that is monitoring the longterm effectiveness and safety of systemic agents in patients with psoriasis.



The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02 (95% confidence interval, 0.92-1.13), demonstrating no significantly increased risk of cancer per cumulative year of biologic exposure for psoriasis therapy, Dr. García-Doval and his associates reported in the study, published in the British Journal of Dermatology. This was true even when broken down within the registries for comparison, and when analyzed by type of cancers, such as squamous cell carcinoma and basal cell carcinoma.

A limitation of the study was inadequate power to detect and compare risk between individual biologics, they said. Also, “as our data describe limited follow-up and latencies, it is still possible that a risk after longer periods of exposure and latencies exists.”

Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

SOURCE: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

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FROM THE BRITISH JOURNAL OF DERMATOLOGY

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Key clinical point: There was no significantly increased risk of cancer per cumulative year of exposure to biologics for psoriasis treatment.

Major finding: The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02.

Study details: Patient data were drawn from four national databases within Psonet, which included 579 cancer cases and 2,671 matched controls.

Disclosures: Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

Source: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

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CBC values linked to CVD risk in psoriasis

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Elevated red blood cell distribution width and mean platelet volume were correlated with cardiovascular disease in a review of 39,510 psoriasis patients conducted by researchers at Case Western Reserve University, Cleveland.*

It’s generally accepted that psoriasis increases the risk of cardiovascular disease (CVD), but it’s not clear who’s most at risk. “We really wanted to find something that is cheap and easy to risk stratify these patients” said lead investigator Rosalynn Conic, MD, of Case Western’s department of dermatology.

Dr. Rosalynn Conic
Red blood cell distribution width (RDW) – a measure of the range of red blood cell volumes in a given sample – and mean platelet volume (MPV) fit the bill. In many places, they are already routinely reported on CBCs, so there’s no need for any special equipment or tests. Meanwhile, RDW and MPV elevations have been previously linked to CVD risk in the HIV and cardiology literature. The investigators wondered if they’d find a similar association in psoriasis, so they queried nearly 40,000 patients in the Explorys electronic health record database.

What they found was “very impressive, for sure,” Dr. Conic said at the International Investigative Dermatology meeting.

The incidence of MI was highest among the 1,920 patients (5%) with elevated RDW and MPV (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001), followed by the 7,060 (18%) patients with high RDW and normal MPV (OR, 2.4; 95% CI, 2.1-2.8; P less than .001), as compared with normal/low MPV and RDW patients.

Elevated RDW or elevated RDW plus MPV increased the odds of atrial fibrillation, coronary artery disease, heart failure, and peripheral vascular disease anywhere from 2 to 8.3 times (P less than .001). Among psoriatic arthritis patients, elevated RDW almost doubled the risk of MI (OR, 1.8; P less than .001). Results were adjusted for age, gender, and hypertension.

In a subanalysis of treatment effects, 4 of 23 psoriasis patients at Case Western had elevated RDWs at baseline. Values normalized in the three patients who achieved a 75% reduction in the Psoriasis Area and Severity Index score after about a year of systemic treatment.

 

 


“We aim to validate [the study results] with a Veterans Administration data set,” Dr. Conic said. If it pans out, “one use would be to send [patients with elevated values] to a cardiologist earlier” so other CVD risk factors can be monitored and treated. The findings also add to the case for good control, she noted.

Systemic inflammation is the common denominator between the blood value elevations and CVD. The same inflammatory cytokines that cause skin problems in psoriasis also stimulate bone marrow to release immature red blood cells, which are larger than mature cells, leading to an increased RDW. Similarly, elevated MPV indicates a higher number of larger, younger platelets in the blood.

“It’s probably something along those lines, but I think we need to go back to basic science and really figure it out,” Dr. Conic said.

Patients were 18-65 years old. The study excluded patients with diabetes, Crohn’s disease, RA, and generalized atherosclerosis.

The National Institutes of Health funded the work. Dr. Conic reported no relevant financial disclosures.

*This article was updated on May 30, 2018.

SOURCE: Conic R et al. IID 2018, Abstract 550.

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Elevated red blood cell distribution width and mean platelet volume were correlated with cardiovascular disease in a review of 39,510 psoriasis patients conducted by researchers at Case Western Reserve University, Cleveland.*

It’s generally accepted that psoriasis increases the risk of cardiovascular disease (CVD), but it’s not clear who’s most at risk. “We really wanted to find something that is cheap and easy to risk stratify these patients” said lead investigator Rosalynn Conic, MD, of Case Western’s department of dermatology.

Dr. Rosalynn Conic
Red blood cell distribution width (RDW) – a measure of the range of red blood cell volumes in a given sample – and mean platelet volume (MPV) fit the bill. In many places, they are already routinely reported on CBCs, so there’s no need for any special equipment or tests. Meanwhile, RDW and MPV elevations have been previously linked to CVD risk in the HIV and cardiology literature. The investigators wondered if they’d find a similar association in psoriasis, so they queried nearly 40,000 patients in the Explorys electronic health record database.

What they found was “very impressive, for sure,” Dr. Conic said at the International Investigative Dermatology meeting.

The incidence of MI was highest among the 1,920 patients (5%) with elevated RDW and MPV (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001), followed by the 7,060 (18%) patients with high RDW and normal MPV (OR, 2.4; 95% CI, 2.1-2.8; P less than .001), as compared with normal/low MPV and RDW patients.

Elevated RDW or elevated RDW plus MPV increased the odds of atrial fibrillation, coronary artery disease, heart failure, and peripheral vascular disease anywhere from 2 to 8.3 times (P less than .001). Among psoriatic arthritis patients, elevated RDW almost doubled the risk of MI (OR, 1.8; P less than .001). Results were adjusted for age, gender, and hypertension.

In a subanalysis of treatment effects, 4 of 23 psoriasis patients at Case Western had elevated RDWs at baseline. Values normalized in the three patients who achieved a 75% reduction in the Psoriasis Area and Severity Index score after about a year of systemic treatment.

 

 


“We aim to validate [the study results] with a Veterans Administration data set,” Dr. Conic said. If it pans out, “one use would be to send [patients with elevated values] to a cardiologist earlier” so other CVD risk factors can be monitored and treated. The findings also add to the case for good control, she noted.

Systemic inflammation is the common denominator between the blood value elevations and CVD. The same inflammatory cytokines that cause skin problems in psoriasis also stimulate bone marrow to release immature red blood cells, which are larger than mature cells, leading to an increased RDW. Similarly, elevated MPV indicates a higher number of larger, younger platelets in the blood.

“It’s probably something along those lines, but I think we need to go back to basic science and really figure it out,” Dr. Conic said.

Patients were 18-65 years old. The study excluded patients with diabetes, Crohn’s disease, RA, and generalized atherosclerosis.

The National Institutes of Health funded the work. Dr. Conic reported no relevant financial disclosures.

*This article was updated on May 30, 2018.

SOURCE: Conic R et al. IID 2018, Abstract 550.

 

Elevated red blood cell distribution width and mean platelet volume were correlated with cardiovascular disease in a review of 39,510 psoriasis patients conducted by researchers at Case Western Reserve University, Cleveland.*

It’s generally accepted that psoriasis increases the risk of cardiovascular disease (CVD), but it’s not clear who’s most at risk. “We really wanted to find something that is cheap and easy to risk stratify these patients” said lead investigator Rosalynn Conic, MD, of Case Western’s department of dermatology.

Dr. Rosalynn Conic
Red blood cell distribution width (RDW) – a measure of the range of red blood cell volumes in a given sample – and mean platelet volume (MPV) fit the bill. In many places, they are already routinely reported on CBCs, so there’s no need for any special equipment or tests. Meanwhile, RDW and MPV elevations have been previously linked to CVD risk in the HIV and cardiology literature. The investigators wondered if they’d find a similar association in psoriasis, so they queried nearly 40,000 patients in the Explorys electronic health record database.

What they found was “very impressive, for sure,” Dr. Conic said at the International Investigative Dermatology meeting.

The incidence of MI was highest among the 1,920 patients (5%) with elevated RDW and MPV (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001), followed by the 7,060 (18%) patients with high RDW and normal MPV (OR, 2.4; 95% CI, 2.1-2.8; P less than .001), as compared with normal/low MPV and RDW patients.

Elevated RDW or elevated RDW plus MPV increased the odds of atrial fibrillation, coronary artery disease, heart failure, and peripheral vascular disease anywhere from 2 to 8.3 times (P less than .001). Among psoriatic arthritis patients, elevated RDW almost doubled the risk of MI (OR, 1.8; P less than .001). Results were adjusted for age, gender, and hypertension.

In a subanalysis of treatment effects, 4 of 23 psoriasis patients at Case Western had elevated RDWs at baseline. Values normalized in the three patients who achieved a 75% reduction in the Psoriasis Area and Severity Index score after about a year of systemic treatment.

 

 


“We aim to validate [the study results] with a Veterans Administration data set,” Dr. Conic said. If it pans out, “one use would be to send [patients with elevated values] to a cardiologist earlier” so other CVD risk factors can be monitored and treated. The findings also add to the case for good control, she noted.

Systemic inflammation is the common denominator between the blood value elevations and CVD. The same inflammatory cytokines that cause skin problems in psoriasis also stimulate bone marrow to release immature red blood cells, which are larger than mature cells, leading to an increased RDW. Similarly, elevated MPV indicates a higher number of larger, younger platelets in the blood.

“It’s probably something along those lines, but I think we need to go back to basic science and really figure it out,” Dr. Conic said.

Patients were 18-65 years old. The study excluded patients with diabetes, Crohn’s disease, RA, and generalized atherosclerosis.

The National Institutes of Health funded the work. Dr. Conic reported no relevant financial disclosures.

*This article was updated on May 30, 2018.

SOURCE: Conic R et al. IID 2018, Abstract 550.

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Key clinical point: Elevated red blood cell distribution width and mean platelet volume might identify psoriasis patients at risk for cardiovascular disease.

Major finding: The incidence of MI was highest among the 1,920 patients with elevated red cell distribution width and mean platelet volume (odds ratio, 3.4; 95% confidence interval, 2.7-4.2; P less than .001).

Study details: A database review of 39,510 patients with psoriasis.

Disclosures: The National Institutes of Health funded the work. The lead investigator had no disclosures to report.

Source: Conic R et al. IID 2018, Abstract 550.

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Topical corticosteroid-retinoid combination effective in moderate to severe psoriasis

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The combination of a topical corticosteroid and a topical retinoid for the treatment of plaque psoriasis resulted in significant improvements in clinical signs, in two multicenter, double-blind, vehicle-controlled phase 3 studies.

In the two studies, investigators randomized a total of 418 adults with moderate to severe plaque psoriasis to a lotion containing halobetasol propionate (0.01%) and tazarotene (0.045%) or vehicle lotion, applied once a day to affected areas. After 8 weeks of treatment, 35.8% of adults in the first study and 45.3% of those in the second study had achieved the primary outcome of at least a two-grade improvement in the Investigator’s Global Assessment score and reaching “clear” or “almost clear,” compared with 7.0% and 12.5%, respectively, of patients treated with the vehicle (P less than .001). The report was published online in the Journal of the American Academy of Dermatology.

At 8 weeks, reduction in erythema was achieved by 44.2% and 49.6% of patients in the treatment arms, compared with 10% and 18.7% of patients in the control arms. Plaque elevation was reduced in 59.3% and 59.7% of patients in the treatment arms, compared with 17.9% and 21.3% of patients in the control arms; and scaling was reduced in 59.4% and 62.9% of those on treatment, compared with 20.6% and 21.0%, respectively. All differences between the treatment and control groups were statistically significant (P less than .001).

Participants who received the treatment also reported significantly lower scores for itching, dryness, and burning or stinging compared with those who received the vehicle lotion.

Dr. Linda Stein Gold of Henry Ford Hospital in Detroit, and her coauthors, wrote that while clinical studies have established the benefit of using a topical corticosteroid as an adjunct to tazarotene for plaque psoriasis, data on their combined use was limited. This combination “was consistently more effective than vehicle in achieving treatment success; effectively reducing affected area and psoriasis signs at the target lesion, and improving QoL [quality of life],” they wrote.

Most patients maintained these improvements over the 4-week posttreatment period.

Patients who received the halobetasol propionate/tazarotene lotion reported more adverse events than did those who received the control lotion, but most were mild to moderate and included contact dermatitis (6.3%), pruritus (2.2%) and application site pain (2.6%). Three serious adverse events were not related to treatment.

The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including with Valeant Pharmaceuticals. Five authors are employees of the company.

SOURCE: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.

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The combination of a topical corticosteroid and a topical retinoid for the treatment of plaque psoriasis resulted in significant improvements in clinical signs, in two multicenter, double-blind, vehicle-controlled phase 3 studies.

In the two studies, investigators randomized a total of 418 adults with moderate to severe plaque psoriasis to a lotion containing halobetasol propionate (0.01%) and tazarotene (0.045%) or vehicle lotion, applied once a day to affected areas. After 8 weeks of treatment, 35.8% of adults in the first study and 45.3% of those in the second study had achieved the primary outcome of at least a two-grade improvement in the Investigator’s Global Assessment score and reaching “clear” or “almost clear,” compared with 7.0% and 12.5%, respectively, of patients treated with the vehicle (P less than .001). The report was published online in the Journal of the American Academy of Dermatology.

At 8 weeks, reduction in erythema was achieved by 44.2% and 49.6% of patients in the treatment arms, compared with 10% and 18.7% of patients in the control arms. Plaque elevation was reduced in 59.3% and 59.7% of patients in the treatment arms, compared with 17.9% and 21.3% of patients in the control arms; and scaling was reduced in 59.4% and 62.9% of those on treatment, compared with 20.6% and 21.0%, respectively. All differences between the treatment and control groups were statistically significant (P less than .001).

Participants who received the treatment also reported significantly lower scores for itching, dryness, and burning or stinging compared with those who received the vehicle lotion.

Dr. Linda Stein Gold of Henry Ford Hospital in Detroit, and her coauthors, wrote that while clinical studies have established the benefit of using a topical corticosteroid as an adjunct to tazarotene for plaque psoriasis, data on their combined use was limited. This combination “was consistently more effective than vehicle in achieving treatment success; effectively reducing affected area and psoriasis signs at the target lesion, and improving QoL [quality of life],” they wrote.

Most patients maintained these improvements over the 4-week posttreatment period.

Patients who received the halobetasol propionate/tazarotene lotion reported more adverse events than did those who received the control lotion, but most were mild to moderate and included contact dermatitis (6.3%), pruritus (2.2%) and application site pain (2.6%). Three serious adverse events were not related to treatment.

The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including with Valeant Pharmaceuticals. Five authors are employees of the company.

SOURCE: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.

 

The combination of a topical corticosteroid and a topical retinoid for the treatment of plaque psoriasis resulted in significant improvements in clinical signs, in two multicenter, double-blind, vehicle-controlled phase 3 studies.

In the two studies, investigators randomized a total of 418 adults with moderate to severe plaque psoriasis to a lotion containing halobetasol propionate (0.01%) and tazarotene (0.045%) or vehicle lotion, applied once a day to affected areas. After 8 weeks of treatment, 35.8% of adults in the first study and 45.3% of those in the second study had achieved the primary outcome of at least a two-grade improvement in the Investigator’s Global Assessment score and reaching “clear” or “almost clear,” compared with 7.0% and 12.5%, respectively, of patients treated with the vehicle (P less than .001). The report was published online in the Journal of the American Academy of Dermatology.

At 8 weeks, reduction in erythema was achieved by 44.2% and 49.6% of patients in the treatment arms, compared with 10% and 18.7% of patients in the control arms. Plaque elevation was reduced in 59.3% and 59.7% of patients in the treatment arms, compared with 17.9% and 21.3% of patients in the control arms; and scaling was reduced in 59.4% and 62.9% of those on treatment, compared with 20.6% and 21.0%, respectively. All differences between the treatment and control groups were statistically significant (P less than .001).

Participants who received the treatment also reported significantly lower scores for itching, dryness, and burning or stinging compared with those who received the vehicle lotion.

Dr. Linda Stein Gold of Henry Ford Hospital in Detroit, and her coauthors, wrote that while clinical studies have established the benefit of using a topical corticosteroid as an adjunct to tazarotene for plaque psoriasis, data on their combined use was limited. This combination “was consistently more effective than vehicle in achieving treatment success; effectively reducing affected area and psoriasis signs at the target lesion, and improving QoL [quality of life],” they wrote.

Most patients maintained these improvements over the 4-week posttreatment period.

Patients who received the halobetasol propionate/tazarotene lotion reported more adverse events than did those who received the control lotion, but most were mild to moderate and included contact dermatitis (6.3%), pruritus (2.2%) and application site pain (2.6%). Three serious adverse events were not related to treatment.

The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including with Valeant Pharmaceuticals. Five authors are employees of the company.

SOURCE: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.

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Key clinical point: Topical halobetasol propionate and tazarotene can significantly improve plaque psoriasis symptoms.

Major finding: Nearly half of adults treated with topical halobetasol propionate and tazarotene were “clear” or “almost clear” after 8 weeks.

Study details: Two multicenter, double-blind, vehicle-controlled phase 3 studies of 418 adults with psoriasis.

Disclosures: The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America. Four authors disclosed advisory, consultancy and speaking positions and other funding from the pharmaceutical industry, including Valeant Pharmaceuticals. Five authors are employees of the company.

Source: Gold L et al. J Am Acad Dermatol. 2018 Mar 31. pii: S0190-9622(18)30494-8. doi: 10.1016/j.jaad.2018.03.040.

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Secukinumab Emerges as a Rapidly Effective Therapy for Pityriasis Rubra Pilaris

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Secukinumab Emerges as a Rapidly Effective Therapy for Pityriasis Rubra Pilaris

Although there currently are no formal guidelines for the treatment of refractory pityriasis rubra pilaris (PRP), successful off-label treatment of the condition with multiple biologics approved for psoriasis has been reported.1,2 Secukinumab, an IL-17A antagonist, has shown particularly striking results in the treatment of PRP in 2 recent case reports.3,4 We report 2 additional cases of severe refractory PRP that responded rapidly to treatment with secukinumab. In both cases, the patients’ erythematous plaques resolved or had nearly resolved by week 4 of treatment. Our findings suggest that IL-17 plays an important role in PRP pathogenesis and support future clinical trials of anti–IL-17 agents for treatment of this entity.

Case Reports

Patient 1
A 60-year-old man with a history of biopsy-proven PRP presented with persistent generalized erythema, scattered patches of normal skin, and hyperkeratotic plaques on the bilateral palms of 1 year’s duration. Previous therapies included topical steroids, topical calcipotriene, adalimumab 40 mg once every other week, infliximab 5 mg/kg once every 8 weeks, ustekinumab 90 mg once every 12 weeks, acitretin 25 mg once daily, and most recently cyclosporine 200 mg twice daily. Of these treatments, infliximab was the only treatment that provided minimal relief; however, the patient continued to have itching and painful plaques covering approximately 20% of body surface area (Figure 1A). Infliximab was therefore discontinued and treatment with cyclosporine was started. After failure on cyclosporine, the patient was started on secukinumab, with loading doses of 300 mg injected subcutaneously once weekly for 5 weeks.

At 4 weeks’ follow-up, there was a marked decrease in erythema and scaling. The body surface area affected had decreased to 5%, and improvement of palmar keratoderma was noted. The patient continued with maintenance dosing of secukinumab 300 mg once every 4 weeks. By week 8, the erythema had fully resolved (Figure 1B), and he remained clear at week 24. No adverse events were noted since initiation of therapy.

Figure 1. Painful plaques on the chest in Patient 1 at initial presentation (A) and at week 8 of treatment with secukinumab for refractory pityriasis rubra pilaris (B).


Patient 2
A 74-year-old woman with a history of PRP that had previously been misdiagnosed as psoriasis by an outside physician presented for evaluation of palmoplantar keratoderma (Figure 2A), follicular hyperkeratosis, and erythematous plaques on the trunk and arms of 5 years’ duration. Previous therapies included topical steroids, topical urea, methotrexate 20 mg once weekly, adalimumab 40 mg once every other week, infliximab 10 mg/kg once every 4 weeks, ustekinumab 90 mg once every 12 weeks, and most recently acitretin 50 mg once daily.

The patient had been maintained on ustekinumab and acitretin for 2 years with only mild improvement. Ustekinumab was then discontinued, and after 3 months treatment with secukinumab was added to the once-daily acitretin. Similar to Patient 1, loading doses of secukinumab 300 mg were administered once weekly for 5 weeks. The plaques on the trunk and arms had resolved by week 4, but the palmoplantar keratoderma persisted. The patient continued with the maintenance dose of secukinumab 300 mg once every 4 weeks and reported an increase in peeling of the palms and soles at week 8.

Figure 2. Plantar keratoderma in Patient 2 at initial presentation (A) and at week 12 of treatment with secukinumab for refractory pityriasis rubra pilaris (B). Note the considerable improvement of plantar keratoderma.

By week 12 of treatment, the palmar keratoderma had resolved, and debridement of the soles revealed patches of normal skin (Figure 2B). By week 52, no adverse events had been noted. The patient continued to experience mild keratoderma of the soles, making us reluctant to discontinue acitretin; however, she has maintained her maximal response, and her quality of life has significantly improved. The patient was continued on acitretin and secukinumab, and her condition remained stable.

 

 

Comment

Because there are no formal treatment guidelines for refractory PRP, case reports play an important role in clinical decision-making. When a patient is unresponsive to topical medications and first-line traditional systemic therapies (eg, methotrexate, cyclosporine, acitretin), biologic drugs effective in the treatment of psoriasis are widely accepted as the next therapeutic step.1 The biologic medications that are most often reported in the treatment of PRP are the TNF-α antagonists, as they have been available the longest.1-2 In a systematic review of 15 patients with PRP who were treated with TNF-α antagonists,2 80% of patients achieved complete response (mean time to maximal response, 5 months). There also are a number of reports of successful treatment of PRP with the IL-12/23 antagonist ustekinumab, which has been commercially available since 2009.5-9 Although improvement was noted in most of these patients at the time of the second injection (week 4 of therapy), maximal response with ustekinumab typically occurs between weeks 12 and 28.10

In our cases of PRP treated with secukinumab as well as 2 others that were recently reported in the literature, resolution of erythema and plaques was rapid. This superiority of the response rate parallels the performance of secukinumab relative to ustekinumab in patients with psoriasis11 In one case of a 67-year-old man with PRP treated with secukinumab, scaling and pruritus were reduced by week 3 of treatment and erythema had cleared by week 8.3 In another case of a 33-year-old woman with PRP, pruritus resolved after 1 week of treatment and erythematous plaques and palmoplantar keratoderma improved by week 2.4 In both of our cases, plaques had resolved or nearly resolved by week 4 of follow-up. Patient 1 achieved complete response at week 8 of therapy. Patient 2 never attained complete response, but by week 12 she achieved maximal response, which still resulted in markedly increased quality of life. We do not intend to make additions to her treatment plan because she is currently the clearest she has been since onset of symptoms and is happy with her present condition.

Although it is difficult to predict the long-term prognosis in our 2 patients, we will continue their current regimens indefinitely—as long as the response persists and no adverse events are experienced. This approach is consistent with guidelines for management of plaque psoriasis with secukinumab.12

This accumulation of evidence suggests the importance of the role of IL-17 in the pathogenesis of PRP. The serum level of IL-17 was not evaluated in our patients, but elevation of IL-17 has been reported in a case of PRP.13 Further studies are needed to clarify the role of IL-17 in this disease entity.

Conclusion

Given the refractory nature of PRP and the relative safety of targeted immunotherapy, trials of new biologics and potent small molecules approved for psoriasis treatment are worth exploring for PRP. In light of our reports and those in the literature and given the relative safety of anti–IL-17 agents, it may be reasonable to consider such agents as a first-line therapy for this predictably refractory disease.

References
  1. Klein A, Landthaler M, Karrer S. Pityriasis rubra pilaris. Am J Clin Dermatol. 2010;11:157-170.
  2. Petrof G, Almaani N, Archer CB, et al. A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists. J Eur Acad Dermatol Venereol. 2013;27:E131-E135.
  3. Schuster D, Pfister-Wartha A, Bruckner-Tuderman L, et al. Successful treatment of refractory pityriasis rubra pilaris with secukinumab. JAMA Dermatol. 2016;152:1278-1280.
  4. Gauci ML, Jachiet M, Gottlieb J, et al. Successful treatment of type II pityriasis rubra pilaris with secukinumab. JAAD Case Rep. 2016;2:462-264.
  5. Chowdhary M, Davila U, Cohen DJ. Ustekinumab as an alternative treatment option for chronic pityriasis rubra pilaris. Case Rep Dermatol. 2015;7:46-50.
  6. Wohlrab J, Kreft B. Treatment of pityriasis rubra pilaris with ustekinumab. Br J Dermatol. 2010;163:655-656.
  7. Villaverde RR, Cano DS. Successful treatment of type 1 pityriasis rubra pilaris with ustekinumab therapy. Eur J Dermatol. 2010;20:630-631.
  8. Di Stefani A, Galluzzo M, Talamonti M, et al. Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris. J Dermatol Case Rep. 2013;7:5-9.
  9. Eytan O, Sarig O, Sprecher E, et al. Clinical response to ustekinumab in familial pityriasis rubra pilaris caused by a novel mutation in CARD14. Br J Dermatol. 2014;171:420-422.
  10. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675-1684.
  11. Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73:400-409.
  12. van de Kerkhof PC, Griffiths CE, Reich K, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75:83-98.
  13. Adnot-Desanlis L, Antonicelli F, Tabary T, et al. Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro-inflammatory cytokine inhibition. Dermatology. 2013;226:41-46.
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From the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.

Ms. Bonomo reports no conflict of interest. Dr. Levitt has served on advisory boards for AbbVie Inc; Amgen Inc; Castle Biosciences, Inc; Eli Lilly and Company; Genentech, Inc; Janssen Biotech, Inc; Novartis Pharmaceuticals Corporation; Pfizer Inc; Promius Pharma, LLC; Ranbaxy Laboratories Limited; and UCB, Inc.

Correspondence: Jacob O. Levitt, 5 E 98th St, 5th Floor, New York, NY 10029 ([email protected]).

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Ms. Bonomo reports no conflict of interest. Dr. Levitt has served on advisory boards for AbbVie Inc; Amgen Inc; Castle Biosciences, Inc; Eli Lilly and Company; Genentech, Inc; Janssen Biotech, Inc; Novartis Pharmaceuticals Corporation; Pfizer Inc; Promius Pharma, LLC; Ranbaxy Laboratories Limited; and UCB, Inc.

Correspondence: Jacob O. Levitt, 5 E 98th St, 5th Floor, New York, NY 10029 ([email protected]).

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From the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.

Ms. Bonomo reports no conflict of interest. Dr. Levitt has served on advisory boards for AbbVie Inc; Amgen Inc; Castle Biosciences, Inc; Eli Lilly and Company; Genentech, Inc; Janssen Biotech, Inc; Novartis Pharmaceuticals Corporation; Pfizer Inc; Promius Pharma, LLC; Ranbaxy Laboratories Limited; and UCB, Inc.

Correspondence: Jacob O. Levitt, 5 E 98th St, 5th Floor, New York, NY 10029 ([email protected]).

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Although there currently are no formal guidelines for the treatment of refractory pityriasis rubra pilaris (PRP), successful off-label treatment of the condition with multiple biologics approved for psoriasis has been reported.1,2 Secukinumab, an IL-17A antagonist, has shown particularly striking results in the treatment of PRP in 2 recent case reports.3,4 We report 2 additional cases of severe refractory PRP that responded rapidly to treatment with secukinumab. In both cases, the patients’ erythematous plaques resolved or had nearly resolved by week 4 of treatment. Our findings suggest that IL-17 plays an important role in PRP pathogenesis and support future clinical trials of anti–IL-17 agents for treatment of this entity.

Case Reports

Patient 1
A 60-year-old man with a history of biopsy-proven PRP presented with persistent generalized erythema, scattered patches of normal skin, and hyperkeratotic plaques on the bilateral palms of 1 year’s duration. Previous therapies included topical steroids, topical calcipotriene, adalimumab 40 mg once every other week, infliximab 5 mg/kg once every 8 weeks, ustekinumab 90 mg once every 12 weeks, acitretin 25 mg once daily, and most recently cyclosporine 200 mg twice daily. Of these treatments, infliximab was the only treatment that provided minimal relief; however, the patient continued to have itching and painful plaques covering approximately 20% of body surface area (Figure 1A). Infliximab was therefore discontinued and treatment with cyclosporine was started. After failure on cyclosporine, the patient was started on secukinumab, with loading doses of 300 mg injected subcutaneously once weekly for 5 weeks.

At 4 weeks’ follow-up, there was a marked decrease in erythema and scaling. The body surface area affected had decreased to 5%, and improvement of palmar keratoderma was noted. The patient continued with maintenance dosing of secukinumab 300 mg once every 4 weeks. By week 8, the erythema had fully resolved (Figure 1B), and he remained clear at week 24. No adverse events were noted since initiation of therapy.

Figure 1. Painful plaques on the chest in Patient 1 at initial presentation (A) and at week 8 of treatment with secukinumab for refractory pityriasis rubra pilaris (B).


Patient 2
A 74-year-old woman with a history of PRP that had previously been misdiagnosed as psoriasis by an outside physician presented for evaluation of palmoplantar keratoderma (Figure 2A), follicular hyperkeratosis, and erythematous plaques on the trunk and arms of 5 years’ duration. Previous therapies included topical steroids, topical urea, methotrexate 20 mg once weekly, adalimumab 40 mg once every other week, infliximab 10 mg/kg once every 4 weeks, ustekinumab 90 mg once every 12 weeks, and most recently acitretin 50 mg once daily.

The patient had been maintained on ustekinumab and acitretin for 2 years with only mild improvement. Ustekinumab was then discontinued, and after 3 months treatment with secukinumab was added to the once-daily acitretin. Similar to Patient 1, loading doses of secukinumab 300 mg were administered once weekly for 5 weeks. The plaques on the trunk and arms had resolved by week 4, but the palmoplantar keratoderma persisted. The patient continued with the maintenance dose of secukinumab 300 mg once every 4 weeks and reported an increase in peeling of the palms and soles at week 8.

Figure 2. Plantar keratoderma in Patient 2 at initial presentation (A) and at week 12 of treatment with secukinumab for refractory pityriasis rubra pilaris (B). Note the considerable improvement of plantar keratoderma.

By week 12 of treatment, the palmar keratoderma had resolved, and debridement of the soles revealed patches of normal skin (Figure 2B). By week 52, no adverse events had been noted. The patient continued to experience mild keratoderma of the soles, making us reluctant to discontinue acitretin; however, she has maintained her maximal response, and her quality of life has significantly improved. The patient was continued on acitretin and secukinumab, and her condition remained stable.

 

 

Comment

Because there are no formal treatment guidelines for refractory PRP, case reports play an important role in clinical decision-making. When a patient is unresponsive to topical medications and first-line traditional systemic therapies (eg, methotrexate, cyclosporine, acitretin), biologic drugs effective in the treatment of psoriasis are widely accepted as the next therapeutic step.1 The biologic medications that are most often reported in the treatment of PRP are the TNF-α antagonists, as they have been available the longest.1-2 In a systematic review of 15 patients with PRP who were treated with TNF-α antagonists,2 80% of patients achieved complete response (mean time to maximal response, 5 months). There also are a number of reports of successful treatment of PRP with the IL-12/23 antagonist ustekinumab, which has been commercially available since 2009.5-9 Although improvement was noted in most of these patients at the time of the second injection (week 4 of therapy), maximal response with ustekinumab typically occurs between weeks 12 and 28.10

In our cases of PRP treated with secukinumab as well as 2 others that were recently reported in the literature, resolution of erythema and plaques was rapid. This superiority of the response rate parallels the performance of secukinumab relative to ustekinumab in patients with psoriasis11 In one case of a 67-year-old man with PRP treated with secukinumab, scaling and pruritus were reduced by week 3 of treatment and erythema had cleared by week 8.3 In another case of a 33-year-old woman with PRP, pruritus resolved after 1 week of treatment and erythematous plaques and palmoplantar keratoderma improved by week 2.4 In both of our cases, plaques had resolved or nearly resolved by week 4 of follow-up. Patient 1 achieved complete response at week 8 of therapy. Patient 2 never attained complete response, but by week 12 she achieved maximal response, which still resulted in markedly increased quality of life. We do not intend to make additions to her treatment plan because she is currently the clearest she has been since onset of symptoms and is happy with her present condition.

Although it is difficult to predict the long-term prognosis in our 2 patients, we will continue their current regimens indefinitely—as long as the response persists and no adverse events are experienced. This approach is consistent with guidelines for management of plaque psoriasis with secukinumab.12

This accumulation of evidence suggests the importance of the role of IL-17 in the pathogenesis of PRP. The serum level of IL-17 was not evaluated in our patients, but elevation of IL-17 has been reported in a case of PRP.13 Further studies are needed to clarify the role of IL-17 in this disease entity.

Conclusion

Given the refractory nature of PRP and the relative safety of targeted immunotherapy, trials of new biologics and potent small molecules approved for psoriasis treatment are worth exploring for PRP. In light of our reports and those in the literature and given the relative safety of anti–IL-17 agents, it may be reasonable to consider such agents as a first-line therapy for this predictably refractory disease.

Although there currently are no formal guidelines for the treatment of refractory pityriasis rubra pilaris (PRP), successful off-label treatment of the condition with multiple biologics approved for psoriasis has been reported.1,2 Secukinumab, an IL-17A antagonist, has shown particularly striking results in the treatment of PRP in 2 recent case reports.3,4 We report 2 additional cases of severe refractory PRP that responded rapidly to treatment with secukinumab. In both cases, the patients’ erythematous plaques resolved or had nearly resolved by week 4 of treatment. Our findings suggest that IL-17 plays an important role in PRP pathogenesis and support future clinical trials of anti–IL-17 agents for treatment of this entity.

Case Reports

Patient 1
A 60-year-old man with a history of biopsy-proven PRP presented with persistent generalized erythema, scattered patches of normal skin, and hyperkeratotic plaques on the bilateral palms of 1 year’s duration. Previous therapies included topical steroids, topical calcipotriene, adalimumab 40 mg once every other week, infliximab 5 mg/kg once every 8 weeks, ustekinumab 90 mg once every 12 weeks, acitretin 25 mg once daily, and most recently cyclosporine 200 mg twice daily. Of these treatments, infliximab was the only treatment that provided minimal relief; however, the patient continued to have itching and painful plaques covering approximately 20% of body surface area (Figure 1A). Infliximab was therefore discontinued and treatment with cyclosporine was started. After failure on cyclosporine, the patient was started on secukinumab, with loading doses of 300 mg injected subcutaneously once weekly for 5 weeks.

At 4 weeks’ follow-up, there was a marked decrease in erythema and scaling. The body surface area affected had decreased to 5%, and improvement of palmar keratoderma was noted. The patient continued with maintenance dosing of secukinumab 300 mg once every 4 weeks. By week 8, the erythema had fully resolved (Figure 1B), and he remained clear at week 24. No adverse events were noted since initiation of therapy.

Figure 1. Painful plaques on the chest in Patient 1 at initial presentation (A) and at week 8 of treatment with secukinumab for refractory pityriasis rubra pilaris (B).


Patient 2
A 74-year-old woman with a history of PRP that had previously been misdiagnosed as psoriasis by an outside physician presented for evaluation of palmoplantar keratoderma (Figure 2A), follicular hyperkeratosis, and erythematous plaques on the trunk and arms of 5 years’ duration. Previous therapies included topical steroids, topical urea, methotrexate 20 mg once weekly, adalimumab 40 mg once every other week, infliximab 10 mg/kg once every 4 weeks, ustekinumab 90 mg once every 12 weeks, and most recently acitretin 50 mg once daily.

The patient had been maintained on ustekinumab and acitretin for 2 years with only mild improvement. Ustekinumab was then discontinued, and after 3 months treatment with secukinumab was added to the once-daily acitretin. Similar to Patient 1, loading doses of secukinumab 300 mg were administered once weekly for 5 weeks. The plaques on the trunk and arms had resolved by week 4, but the palmoplantar keratoderma persisted. The patient continued with the maintenance dose of secukinumab 300 mg once every 4 weeks and reported an increase in peeling of the palms and soles at week 8.

Figure 2. Plantar keratoderma in Patient 2 at initial presentation (A) and at week 12 of treatment with secukinumab for refractory pityriasis rubra pilaris (B). Note the considerable improvement of plantar keratoderma.

By week 12 of treatment, the palmar keratoderma had resolved, and debridement of the soles revealed patches of normal skin (Figure 2B). By week 52, no adverse events had been noted. The patient continued to experience mild keratoderma of the soles, making us reluctant to discontinue acitretin; however, she has maintained her maximal response, and her quality of life has significantly improved. The patient was continued on acitretin and secukinumab, and her condition remained stable.

 

 

Comment

Because there are no formal treatment guidelines for refractory PRP, case reports play an important role in clinical decision-making. When a patient is unresponsive to topical medications and first-line traditional systemic therapies (eg, methotrexate, cyclosporine, acitretin), biologic drugs effective in the treatment of psoriasis are widely accepted as the next therapeutic step.1 The biologic medications that are most often reported in the treatment of PRP are the TNF-α antagonists, as they have been available the longest.1-2 In a systematic review of 15 patients with PRP who were treated with TNF-α antagonists,2 80% of patients achieved complete response (mean time to maximal response, 5 months). There also are a number of reports of successful treatment of PRP with the IL-12/23 antagonist ustekinumab, which has been commercially available since 2009.5-9 Although improvement was noted in most of these patients at the time of the second injection (week 4 of therapy), maximal response with ustekinumab typically occurs between weeks 12 and 28.10

In our cases of PRP treated with secukinumab as well as 2 others that were recently reported in the literature, resolution of erythema and plaques was rapid. This superiority of the response rate parallels the performance of secukinumab relative to ustekinumab in patients with psoriasis11 In one case of a 67-year-old man with PRP treated with secukinumab, scaling and pruritus were reduced by week 3 of treatment and erythema had cleared by week 8.3 In another case of a 33-year-old woman with PRP, pruritus resolved after 1 week of treatment and erythematous plaques and palmoplantar keratoderma improved by week 2.4 In both of our cases, plaques had resolved or nearly resolved by week 4 of follow-up. Patient 1 achieved complete response at week 8 of therapy. Patient 2 never attained complete response, but by week 12 she achieved maximal response, which still resulted in markedly increased quality of life. We do not intend to make additions to her treatment plan because she is currently the clearest she has been since onset of symptoms and is happy with her present condition.

Although it is difficult to predict the long-term prognosis in our 2 patients, we will continue their current regimens indefinitely—as long as the response persists and no adverse events are experienced. This approach is consistent with guidelines for management of plaque psoriasis with secukinumab.12

This accumulation of evidence suggests the importance of the role of IL-17 in the pathogenesis of PRP. The serum level of IL-17 was not evaluated in our patients, but elevation of IL-17 has been reported in a case of PRP.13 Further studies are needed to clarify the role of IL-17 in this disease entity.

Conclusion

Given the refractory nature of PRP and the relative safety of targeted immunotherapy, trials of new biologics and potent small molecules approved for psoriasis treatment are worth exploring for PRP. In light of our reports and those in the literature and given the relative safety of anti–IL-17 agents, it may be reasonable to consider such agents as a first-line therapy for this predictably refractory disease.

References
  1. Klein A, Landthaler M, Karrer S. Pityriasis rubra pilaris. Am J Clin Dermatol. 2010;11:157-170.
  2. Petrof G, Almaani N, Archer CB, et al. A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists. J Eur Acad Dermatol Venereol. 2013;27:E131-E135.
  3. Schuster D, Pfister-Wartha A, Bruckner-Tuderman L, et al. Successful treatment of refractory pityriasis rubra pilaris with secukinumab. JAMA Dermatol. 2016;152:1278-1280.
  4. Gauci ML, Jachiet M, Gottlieb J, et al. Successful treatment of type II pityriasis rubra pilaris with secukinumab. JAAD Case Rep. 2016;2:462-264.
  5. Chowdhary M, Davila U, Cohen DJ. Ustekinumab as an alternative treatment option for chronic pityriasis rubra pilaris. Case Rep Dermatol. 2015;7:46-50.
  6. Wohlrab J, Kreft B. Treatment of pityriasis rubra pilaris with ustekinumab. Br J Dermatol. 2010;163:655-656.
  7. Villaverde RR, Cano DS. Successful treatment of type 1 pityriasis rubra pilaris with ustekinumab therapy. Eur J Dermatol. 2010;20:630-631.
  8. Di Stefani A, Galluzzo M, Talamonti M, et al. Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris. J Dermatol Case Rep. 2013;7:5-9.
  9. Eytan O, Sarig O, Sprecher E, et al. Clinical response to ustekinumab in familial pityriasis rubra pilaris caused by a novel mutation in CARD14. Br J Dermatol. 2014;171:420-422.
  10. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675-1684.
  11. Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73:400-409.
  12. van de Kerkhof PC, Griffiths CE, Reich K, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75:83-98.
  13. Adnot-Desanlis L, Antonicelli F, Tabary T, et al. Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro-inflammatory cytokine inhibition. Dermatology. 2013;226:41-46.
References
  1. Klein A, Landthaler M, Karrer S. Pityriasis rubra pilaris. Am J Clin Dermatol. 2010;11:157-170.
  2. Petrof G, Almaani N, Archer CB, et al. A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists. J Eur Acad Dermatol Venereol. 2013;27:E131-E135.
  3. Schuster D, Pfister-Wartha A, Bruckner-Tuderman L, et al. Successful treatment of refractory pityriasis rubra pilaris with secukinumab. JAMA Dermatol. 2016;152:1278-1280.
  4. Gauci ML, Jachiet M, Gottlieb J, et al. Successful treatment of type II pityriasis rubra pilaris with secukinumab. JAAD Case Rep. 2016;2:462-264.
  5. Chowdhary M, Davila U, Cohen DJ. Ustekinumab as an alternative treatment option for chronic pityriasis rubra pilaris. Case Rep Dermatol. 2015;7:46-50.
  6. Wohlrab J, Kreft B. Treatment of pityriasis rubra pilaris with ustekinumab. Br J Dermatol. 2010;163:655-656.
  7. Villaverde RR, Cano DS. Successful treatment of type 1 pityriasis rubra pilaris with ustekinumab therapy. Eur J Dermatol. 2010;20:630-631.
  8. Di Stefani A, Galluzzo M, Talamonti M, et al. Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris. J Dermatol Case Rep. 2013;7:5-9.
  9. Eytan O, Sarig O, Sprecher E, et al. Clinical response to ustekinumab in familial pityriasis rubra pilaris caused by a novel mutation in CARD14. Br J Dermatol. 2014;171:420-422.
  10. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675-1684.
  11. Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73:400-409.
  12. van de Kerkhof PC, Griffiths CE, Reich K, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75:83-98.
  13. Adnot-Desanlis L, Antonicelli F, Tabary T, et al. Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro-inflammatory cytokine inhibition. Dermatology. 2013;226:41-46.
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Practice Points

  • In patients with pityriasis rubra pilaris (PRP) who have not responded to topical treatments, off-label treatment with systemic therapies approved for plaque psoriasis can be considered.
  • Secukinumab, an IL-17A antagonist, has shown particularly striking results in the treatment of PRP.
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Hidradenitis suppurativa packs mighty QOL impact

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– Anyone who has treated patients with hidradenitis suppurativa (HS) recognizes that this can be a debilitating disease. Helping put that into fuller perspective, recent evidence has shown that the quality of life effects of moderate to severe HS are objectively worse than those of moderate to severe psoriasis, according to Iltefat H. Hamzavi, MD, president of the Hidradenitis Suppurativa Foundation and a dermatologist at Henry Ford Hospital in Detroit.

He was lead author of a study in which he and his coinvestigators compared weighted averages of a variety of quality of life measures in patients with moderate to severe HS or psoriasis who participated in five AbbVie-sponsored randomized clinical trials of biologic agents (J Am Acad Dermatol. 2017 Dec;77[6]:1038-46).

The results were consistent: “In every measure, unfortunately, HS wins,” Dr. Hamzavi observed at the Hawaii Dermatology Seminar provided by the Skin Disease Education Foundation/Global Academy for Medical Education.

“The number of HS patients who experience downward drift – losing their job and their health insurance and ultimately being unable to move out of a lower socioeconomic group – is staggering,” the dermatologist said.

Hidradenitis suppurativa has been associated with increased rates of depression, anxiety, social isolation, and low self-esteem, which underscores the importance of a psychiatric evaluation as part of routine care for patients with this dermatologic disease. “Suicide is much more common in the HS population than in almost any other dermatologic disease,” Dr. Hamzavi added.

He reported serving as a consultant for AbbVie, Incyte, and UCB.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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– Anyone who has treated patients with hidradenitis suppurativa (HS) recognizes that this can be a debilitating disease. Helping put that into fuller perspective, recent evidence has shown that the quality of life effects of moderate to severe HS are objectively worse than those of moderate to severe psoriasis, according to Iltefat H. Hamzavi, MD, president of the Hidradenitis Suppurativa Foundation and a dermatologist at Henry Ford Hospital in Detroit.

He was lead author of a study in which he and his coinvestigators compared weighted averages of a variety of quality of life measures in patients with moderate to severe HS or psoriasis who participated in five AbbVie-sponsored randomized clinical trials of biologic agents (J Am Acad Dermatol. 2017 Dec;77[6]:1038-46).

The results were consistent: “In every measure, unfortunately, HS wins,” Dr. Hamzavi observed at the Hawaii Dermatology Seminar provided by the Skin Disease Education Foundation/Global Academy for Medical Education.

“The number of HS patients who experience downward drift – losing their job and their health insurance and ultimately being unable to move out of a lower socioeconomic group – is staggering,” the dermatologist said.

Hidradenitis suppurativa has been associated with increased rates of depression, anxiety, social isolation, and low self-esteem, which underscores the importance of a psychiatric evaluation as part of routine care for patients with this dermatologic disease. “Suicide is much more common in the HS population than in almost any other dermatologic disease,” Dr. Hamzavi added.

He reported serving as a consultant for AbbVie, Incyte, and UCB.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

 

– Anyone who has treated patients with hidradenitis suppurativa (HS) recognizes that this can be a debilitating disease. Helping put that into fuller perspective, recent evidence has shown that the quality of life effects of moderate to severe HS are objectively worse than those of moderate to severe psoriasis, according to Iltefat H. Hamzavi, MD, president of the Hidradenitis Suppurativa Foundation and a dermatologist at Henry Ford Hospital in Detroit.

He was lead author of a study in which he and his coinvestigators compared weighted averages of a variety of quality of life measures in patients with moderate to severe HS or psoriasis who participated in five AbbVie-sponsored randomized clinical trials of biologic agents (J Am Acad Dermatol. 2017 Dec;77[6]:1038-46).

The results were consistent: “In every measure, unfortunately, HS wins,” Dr. Hamzavi observed at the Hawaii Dermatology Seminar provided by the Skin Disease Education Foundation/Global Academy for Medical Education.

“The number of HS patients who experience downward drift – losing their job and their health insurance and ultimately being unable to move out of a lower socioeconomic group – is staggering,” the dermatologist said.

Hidradenitis suppurativa has been associated with increased rates of depression, anxiety, social isolation, and low self-esteem, which underscores the importance of a psychiatric evaluation as part of routine care for patients with this dermatologic disease. “Suicide is much more common in the HS population than in almost any other dermatologic disease,” Dr. Hamzavi added.

He reported serving as a consultant for AbbVie, Incyte, and UCB.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR

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Psoriasis duration reflects cardiovascular event risk

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– The recent report that the risk of a major adverse cardiovascular event increases by 1% more than in the general population for each additional year of psoriasis duration is sobering news for physicians who treat pediatric psoriasis.

“If I have a 16-year-old who has a 5-year history of psoriasis, what does that mean for when she’s 30 or 40? And should we be intervening more aggressively?” Lawrence F. Eichenfield, MD, asked at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News
Dr. Lawrence F. Eichenfield
The question was rhetorical. As lead author of the first-ever pediatric psoriasis comorbidity screening guidelines, he is an advocate for a proactive approach. The published screening guidelines (JAMA Dermatol. 2017 Jul 1;153[7]:698-704), largely based upon expert consensus, were a joint project of the Pediatric Dermatology Research Alliance and the National Psoriasis Foundation.

“Even though there’s not a great deal of evidence, there’s some evidence to rationalize early screening in psoriasis,” according to Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego.



Psoriasis develops during childhood in almost one-third of patients.

The pediatric psoriasis screening guidelines describe a simple routine screening program and timeline for early identification of overweight or obesity, type 2 diabetes, hypertension, nonalcoholic fatty liver disease, anxiety, depression, substance abuse, inflammatory bowel disease, and quality of life issues, all of which are encountered with increased frequency in pediatric psoriasis patients. A fasting lipid panel is recommended in children aged 9-11 years with psoriasis and again at age 17-21 years.

“Don’t forget arthritis. For a kid with psoriasis, at every office visit, I ask about morning stiffness or limp. Those are probably the two most sensitive questions in screening for psoriatic arthritis,” according to Dr. Eichenfield.

 

 


It has been clear for some time that the skin is not the only organ affected by psoriatic inflammation. The study that quantified the relationship between psoriasis duration and cardiovascular risk – a 1% increase for each year of psoriasis – was a collaboration between investigators at the University of Copenhagen and the University of Pennsylvania, Philadelphia.

The two-part project included aortal imaging of 190 psoriasis patients using fludeoxyglucose F 18 PET/CT scan, which showed a strong relationship between duration of psoriasis and the degree of vascular inflammation. This was bolstered by a population-based study using Danish national registry data on 87,161 psoriasis patients and 4.2 million controls from the general Danish population (J Am Acad Dermatol. 2017 Oct;77[4]:650-56.e3).

Dr. Eichenfield reported serving as a consultant to and/or recipient of research grants from more than a dozen pharmaceutical companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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– The recent report that the risk of a major adverse cardiovascular event increases by 1% more than in the general population for each additional year of psoriasis duration is sobering news for physicians who treat pediatric psoriasis.

“If I have a 16-year-old who has a 5-year history of psoriasis, what does that mean for when she’s 30 or 40? And should we be intervening more aggressively?” Lawrence F. Eichenfield, MD, asked at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News
Dr. Lawrence F. Eichenfield
The question was rhetorical. As lead author of the first-ever pediatric psoriasis comorbidity screening guidelines, he is an advocate for a proactive approach. The published screening guidelines (JAMA Dermatol. 2017 Jul 1;153[7]:698-704), largely based upon expert consensus, were a joint project of the Pediatric Dermatology Research Alliance and the National Psoriasis Foundation.

“Even though there’s not a great deal of evidence, there’s some evidence to rationalize early screening in psoriasis,” according to Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego.



Psoriasis develops during childhood in almost one-third of patients.

The pediatric psoriasis screening guidelines describe a simple routine screening program and timeline for early identification of overweight or obesity, type 2 diabetes, hypertension, nonalcoholic fatty liver disease, anxiety, depression, substance abuse, inflammatory bowel disease, and quality of life issues, all of which are encountered with increased frequency in pediatric psoriasis patients. A fasting lipid panel is recommended in children aged 9-11 years with psoriasis and again at age 17-21 years.

“Don’t forget arthritis. For a kid with psoriasis, at every office visit, I ask about morning stiffness or limp. Those are probably the two most sensitive questions in screening for psoriatic arthritis,” according to Dr. Eichenfield.

 

 


It has been clear for some time that the skin is not the only organ affected by psoriatic inflammation. The study that quantified the relationship between psoriasis duration and cardiovascular risk – a 1% increase for each year of psoriasis – was a collaboration between investigators at the University of Copenhagen and the University of Pennsylvania, Philadelphia.

The two-part project included aortal imaging of 190 psoriasis patients using fludeoxyglucose F 18 PET/CT scan, which showed a strong relationship between duration of psoriasis and the degree of vascular inflammation. This was bolstered by a population-based study using Danish national registry data on 87,161 psoriasis patients and 4.2 million controls from the general Danish population (J Am Acad Dermatol. 2017 Oct;77[4]:650-56.e3).

Dr. Eichenfield reported serving as a consultant to and/or recipient of research grants from more than a dozen pharmaceutical companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

 

– The recent report that the risk of a major adverse cardiovascular event increases by 1% more than in the general population for each additional year of psoriasis duration is sobering news for physicians who treat pediatric psoriasis.

“If I have a 16-year-old who has a 5-year history of psoriasis, what does that mean for when she’s 30 or 40? And should we be intervening more aggressively?” Lawrence F. Eichenfield, MD, asked at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News
Dr. Lawrence F. Eichenfield
The question was rhetorical. As lead author of the first-ever pediatric psoriasis comorbidity screening guidelines, he is an advocate for a proactive approach. The published screening guidelines (JAMA Dermatol. 2017 Jul 1;153[7]:698-704), largely based upon expert consensus, were a joint project of the Pediatric Dermatology Research Alliance and the National Psoriasis Foundation.

“Even though there’s not a great deal of evidence, there’s some evidence to rationalize early screening in psoriasis,” according to Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego.



Psoriasis develops during childhood in almost one-third of patients.

The pediatric psoriasis screening guidelines describe a simple routine screening program and timeline for early identification of overweight or obesity, type 2 diabetes, hypertension, nonalcoholic fatty liver disease, anxiety, depression, substance abuse, inflammatory bowel disease, and quality of life issues, all of which are encountered with increased frequency in pediatric psoriasis patients. A fasting lipid panel is recommended in children aged 9-11 years with psoriasis and again at age 17-21 years.

“Don’t forget arthritis. For a kid with psoriasis, at every office visit, I ask about morning stiffness or limp. Those are probably the two most sensitive questions in screening for psoriatic arthritis,” according to Dr. Eichenfield.

 

 


It has been clear for some time that the skin is not the only organ affected by psoriatic inflammation. The study that quantified the relationship between psoriasis duration and cardiovascular risk – a 1% increase for each year of psoriasis – was a collaboration between investigators at the University of Copenhagen and the University of Pennsylvania, Philadelphia.

The two-part project included aortal imaging of 190 psoriasis patients using fludeoxyglucose F 18 PET/CT scan, which showed a strong relationship between duration of psoriasis and the degree of vascular inflammation. This was bolstered by a population-based study using Danish national registry data on 87,161 psoriasis patients and 4.2 million controls from the general Danish population (J Am Acad Dermatol. 2017 Oct;77[4]:650-56.e3).

Dr. Eichenfield reported serving as a consultant to and/or recipient of research grants from more than a dozen pharmaceutical companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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Is PASI 100 the new benchmark in psoriasis?

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Tue, 02/07/2023 - 16:54

 

The current high-performance biologic agents for psoriasis are so unprecedentedly effective that it’s finally come to this: “Is PASI 90 good enough? I think we should just do away with PASI 90 [90% improvement in Psoriasis Area and Severity Index score] and look at how well our drugs do against the metric of PASI 100. The whole ball of wax. Let’s just go for complete clearance,” Craig L. Leonardi, MD, declared in a provocative presentation at the Hawaii Dermatology Seminar provided by Skin Disease Education Foundation/Global Academy for Medical Education.

He advocates using number needed to treat (NNT) as a performance yardstick. He finds it helpful in translating sometimes-arcane clinical trial results into useful information to guide everyday practice. The NNT is the average number of patients who need to be treated with a drug or procedure in order to achieve one additional good outcome, compared with a control intervention or placebo. It’s the inverse of the absolute risk reduction. The lower the NNT, the better an intervention is performing.

Bruce Jancin/Frontline Medical News
Dr. Craig Leonardi
“I think this gives you a different view on how these drugs perform. It kind of gives a feel for what you might have reasonable expectations of seeing when you pick one of these drugs. Another reason to be aware of this type of analysis is that I can assure you every pharmacy benefits manager and insurance industry insider uses NNT all the time,” said to Dr. Leonardi, a dermatologist and clinical trialist at Saint Louis University.

He presented a chart that summarized the NNTs to achieve a PASI 100 response for various systemic agents commonly used in treating moderate to severe psoriasis. He obtained the data from Food and Drug Administration–regulated product labeling and phase 3 clinical trials.



Dr. Leonardi drew attention to the worst performers on the list: methotrexate, with an NNT of 25 to achieve a PASI 100 response, and etanercept, with an NNT of 23.3.

“Methotrexate is a drug that the insurance industry says we have to flow through on our way to biologic drugs. But if complete clearance is your goal, this is an exercise in futility. These patients will never, ever get to complete clearance – or it’s at least very unlikely. We shouldn’t be asked to go through methotrexate on our way to anything. We shouldn’t be asked to use methotrexate at all. We should be bypassing it. And some of us are working on this,” he said.

Ustekinumab and adalimumab are the current market leaders in biologic therapy for psoriasis, but they don’t stack up so well when viewed through the filter of PASI 100 response, with NNTs of 9.2 and 5.3, respectively.

 

 


“These market leaders may not be the most relevant drugs in the current era,” according to the dermatologist.

In contrast, the high-performance biologics – the interleukin-17 inhibitors secukinumab, ixekizumab, and brodalumab and the interleukin-23 antagonist guselkumab – have impressively low NNTs of 2.4-3.6 in order to achieve complete clearance.

Turning his attention to the more modest goal of achieving a PASI 75 response, he noted that the performance of apremilast and methotrexate is “not that bad, actually, not that bad at all,” with NNTs of 3.6 and 3.2. The market leaders, adalimumab and ustekinumab, are tied with NNTs of 1.6.

“But our IL-17 and IL-23 antagonists are markedly different from all other therapies, with NNTs of 1.3-1.1. With an NNT of 1.1, if you treated 11 patients with ixekizumab, 10 of them would achieve a PASI 75,” he explained.

 

 


“This is really quite remarkable,” Dr. Leonardi commented. “Our first drug back in 2002 was alefacept, and that drug was a ‘twenty-one percenter’: 21% of patients achieved a PASI 75. And quite frankly, we thought that was rocking voodoo science back in the day. Well, we’re really out there now. This is utterly amazing data: a PASI 75 of 81.6% for secukinumab, 86% for brodalumab, 90% for ixekizumab, and 91.2% for guselkumab. This is why we’re publishing this stuff in the best medical journals, because these results are absolutely amazing. So many different medical specialties are interested in what we’re doing with these drugs.”

He reported serving as a consultant to AbbVie, Amgen, Boehringer Ingelheim, Dermira, Eli Lilly, Janssen, Leo, Pfizer, Sandoz, and UCB and receiving research funding from 21 pharmaceutical companies.

The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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The current high-performance biologic agents for psoriasis are so unprecedentedly effective that it’s finally come to this: “Is PASI 90 good enough? I think we should just do away with PASI 90 [90% improvement in Psoriasis Area and Severity Index score] and look at how well our drugs do against the metric of PASI 100. The whole ball of wax. Let’s just go for complete clearance,” Craig L. Leonardi, MD, declared in a provocative presentation at the Hawaii Dermatology Seminar provided by Skin Disease Education Foundation/Global Academy for Medical Education.

He advocates using number needed to treat (NNT) as a performance yardstick. He finds it helpful in translating sometimes-arcane clinical trial results into useful information to guide everyday practice. The NNT is the average number of patients who need to be treated with a drug or procedure in order to achieve one additional good outcome, compared with a control intervention or placebo. It’s the inverse of the absolute risk reduction. The lower the NNT, the better an intervention is performing.

Bruce Jancin/Frontline Medical News
Dr. Craig Leonardi
“I think this gives you a different view on how these drugs perform. It kind of gives a feel for what you might have reasonable expectations of seeing when you pick one of these drugs. Another reason to be aware of this type of analysis is that I can assure you every pharmacy benefits manager and insurance industry insider uses NNT all the time,” said to Dr. Leonardi, a dermatologist and clinical trialist at Saint Louis University.

He presented a chart that summarized the NNTs to achieve a PASI 100 response for various systemic agents commonly used in treating moderate to severe psoriasis. He obtained the data from Food and Drug Administration–regulated product labeling and phase 3 clinical trials.



Dr. Leonardi drew attention to the worst performers on the list: methotrexate, with an NNT of 25 to achieve a PASI 100 response, and etanercept, with an NNT of 23.3.

“Methotrexate is a drug that the insurance industry says we have to flow through on our way to biologic drugs. But if complete clearance is your goal, this is an exercise in futility. These patients will never, ever get to complete clearance – or it’s at least very unlikely. We shouldn’t be asked to go through methotrexate on our way to anything. We shouldn’t be asked to use methotrexate at all. We should be bypassing it. And some of us are working on this,” he said.

Ustekinumab and adalimumab are the current market leaders in biologic therapy for psoriasis, but they don’t stack up so well when viewed through the filter of PASI 100 response, with NNTs of 9.2 and 5.3, respectively.

 

 


“These market leaders may not be the most relevant drugs in the current era,” according to the dermatologist.

In contrast, the high-performance biologics – the interleukin-17 inhibitors secukinumab, ixekizumab, and brodalumab and the interleukin-23 antagonist guselkumab – have impressively low NNTs of 2.4-3.6 in order to achieve complete clearance.

Turning his attention to the more modest goal of achieving a PASI 75 response, he noted that the performance of apremilast and methotrexate is “not that bad, actually, not that bad at all,” with NNTs of 3.6 and 3.2. The market leaders, adalimumab and ustekinumab, are tied with NNTs of 1.6.

“But our IL-17 and IL-23 antagonists are markedly different from all other therapies, with NNTs of 1.3-1.1. With an NNT of 1.1, if you treated 11 patients with ixekizumab, 10 of them would achieve a PASI 75,” he explained.

 

 


“This is really quite remarkable,” Dr. Leonardi commented. “Our first drug back in 2002 was alefacept, and that drug was a ‘twenty-one percenter’: 21% of patients achieved a PASI 75. And quite frankly, we thought that was rocking voodoo science back in the day. Well, we’re really out there now. This is utterly amazing data: a PASI 75 of 81.6% for secukinumab, 86% for brodalumab, 90% for ixekizumab, and 91.2% for guselkumab. This is why we’re publishing this stuff in the best medical journals, because these results are absolutely amazing. So many different medical specialties are interested in what we’re doing with these drugs.”

He reported serving as a consultant to AbbVie, Amgen, Boehringer Ingelheim, Dermira, Eli Lilly, Janssen, Leo, Pfizer, Sandoz, and UCB and receiving research funding from 21 pharmaceutical companies.

The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

 

The current high-performance biologic agents for psoriasis are so unprecedentedly effective that it’s finally come to this: “Is PASI 90 good enough? I think we should just do away with PASI 90 [90% improvement in Psoriasis Area and Severity Index score] and look at how well our drugs do against the metric of PASI 100. The whole ball of wax. Let’s just go for complete clearance,” Craig L. Leonardi, MD, declared in a provocative presentation at the Hawaii Dermatology Seminar provided by Skin Disease Education Foundation/Global Academy for Medical Education.

He advocates using number needed to treat (NNT) as a performance yardstick. He finds it helpful in translating sometimes-arcane clinical trial results into useful information to guide everyday practice. The NNT is the average number of patients who need to be treated with a drug or procedure in order to achieve one additional good outcome, compared with a control intervention or placebo. It’s the inverse of the absolute risk reduction. The lower the NNT, the better an intervention is performing.

Bruce Jancin/Frontline Medical News
Dr. Craig Leonardi
“I think this gives you a different view on how these drugs perform. It kind of gives a feel for what you might have reasonable expectations of seeing when you pick one of these drugs. Another reason to be aware of this type of analysis is that I can assure you every pharmacy benefits manager and insurance industry insider uses NNT all the time,” said to Dr. Leonardi, a dermatologist and clinical trialist at Saint Louis University.

He presented a chart that summarized the NNTs to achieve a PASI 100 response for various systemic agents commonly used in treating moderate to severe psoriasis. He obtained the data from Food and Drug Administration–regulated product labeling and phase 3 clinical trials.



Dr. Leonardi drew attention to the worst performers on the list: methotrexate, with an NNT of 25 to achieve a PASI 100 response, and etanercept, with an NNT of 23.3.

“Methotrexate is a drug that the insurance industry says we have to flow through on our way to biologic drugs. But if complete clearance is your goal, this is an exercise in futility. These patients will never, ever get to complete clearance – or it’s at least very unlikely. We shouldn’t be asked to go through methotrexate on our way to anything. We shouldn’t be asked to use methotrexate at all. We should be bypassing it. And some of us are working on this,” he said.

Ustekinumab and adalimumab are the current market leaders in biologic therapy for psoriasis, but they don’t stack up so well when viewed through the filter of PASI 100 response, with NNTs of 9.2 and 5.3, respectively.

 

 


“These market leaders may not be the most relevant drugs in the current era,” according to the dermatologist.

In contrast, the high-performance biologics – the interleukin-17 inhibitors secukinumab, ixekizumab, and brodalumab and the interleukin-23 antagonist guselkumab – have impressively low NNTs of 2.4-3.6 in order to achieve complete clearance.

Turning his attention to the more modest goal of achieving a PASI 75 response, he noted that the performance of apremilast and methotrexate is “not that bad, actually, not that bad at all,” with NNTs of 3.6 and 3.2. The market leaders, adalimumab and ustekinumab, are tied with NNTs of 1.6.

“But our IL-17 and IL-23 antagonists are markedly different from all other therapies, with NNTs of 1.3-1.1. With an NNT of 1.1, if you treated 11 patients with ixekizumab, 10 of them would achieve a PASI 75,” he explained.

 

 


“This is really quite remarkable,” Dr. Leonardi commented. “Our first drug back in 2002 was alefacept, and that drug was a ‘twenty-one percenter’: 21% of patients achieved a PASI 75. And quite frankly, we thought that was rocking voodoo science back in the day. Well, we’re really out there now. This is utterly amazing data: a PASI 75 of 81.6% for secukinumab, 86% for brodalumab, 90% for ixekizumab, and 91.2% for guselkumab. This is why we’re publishing this stuff in the best medical journals, because these results are absolutely amazing. So many different medical specialties are interested in what we’re doing with these drugs.”

He reported serving as a consultant to AbbVie, Amgen, Boehringer Ingelheim, Dermira, Eli Lilly, Janssen, Leo, Pfizer, Sandoz, and UCB and receiving research funding from 21 pharmaceutical companies.

The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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Surgical excision essential in severe hidradenitis suppurativa

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– Medical therapy alone is never sufficient in Hurley stage III hidradenitis suppurativa (HS), Iltefat H. Hamzavi, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

“Even with the advances in biologics and antibiotic therapy, you still have to excise once you’re in full-blown Hurley stage III disease. Surgery has to be part of your protocol,” according to Dr. Hamzavi, a dermatologist at Henry Ford Hospital in Detroit, which runs one of the nation’s largest hidradenitis suppurativa clinics, with roughly 1,600 patients.

Elsevier
He outlined the Henry Ford Hospital’s HS treatment algorithm. Where good evidence exists, the algorithm is evidence-based, and where evidence is lacking, it’s based upon expert opinion and considerable anecdotal experience.

“Of course we’re biased. But until the data can set us free, you’re stuck with me,” the dermatologist quipped.

A core principle of the Henry Ford algorithm is this: “Medical therapy [for patients with advanced HS] stabilizes them and reduces their draining and pain, then you try to bring them back to a lower stage with surgical options,” he explained.

Although other HS staging systems exist, Dr. Hamzavi and his colleagues rely on the Hurley staging system to guide their treatment. Basically, Hurley stage I consists of follicular nodules and abscesses. When the nodules connect to form sinus tracts with scarring, that’s stage II. And if the sinus tracts interconnect throughout an entire area, that’s stage III.

 

 

Hurley stage I

First-line treatment of localized Hurley stage I disease at Henry Ford is a 10% topical benzoyl peroxide wash left on for 5 minutes before bathing, followed by postbathing topical clindamycin 1% lotion or solution applied to the nodules. If this maintenance regimen isn’t sufficient to prevent formation of new and worsening nodules, Dr. Hamzavi supplements it with up to three once-monthly 1064-nm Nd:YAG laser sessions aimed at follicular ablation. It’s a laser application he and his colleagues pioneered (Dermatol Surg. 2009 Aug;35[8]:1188-98). They subsequently documented the histopathologic basis of the procedure’s efficacy, which entails selective thermolysis of follicles, destruction of inflammatory lesions in the superficial to mid-dermis, followed by fibrosis and scarring (Arch Dermatol. 2011 Jan;147[1]:21-8).

Bruce Jancin/MDedge News
Dr. Iltefat H. Hamzavi
“Our experience, and that of most people in the HS community, has been that, if you limit the hair follicles you limit the disease state,” said Dr. Hamzavi, who is the current president of the Hidradenitis Suppurativa Foundation.

In generalized Hurley stage I HS, the Henry Ford approach is to supplement the topical regimen and laser sessions with oral doxycycline at 100-150 mg daily for 1-6 months.

“The theory here is this is a dysbiotic event. The antibiotics reduce commensal bacteria, which ultimately reduces the reactive inflammatory response. But when you stop the antibiotics, the inflammatory response returns. So antibiotics can help stabilize the disease state but really can’t reverse the disease state. For that we have to turn to ablative treatment options: laser, surgery,” the dermatologist continued.

 

 

Hurley stage II

“At this point you’re looking at procedures,” according to Dr. Hamzavi. “Once you have sinus tracts it’s critical to remove them.”

The treatment backbone in stage II disease is 8-10 weeks of oral clindamycin and rifampin, both at 300 mg twice daily.

“This is one of the fundamental building blocks of HS clinics throughout the world,” he noted.

Clostridium difficile infection is exceedingly rare in HS patients on this regimen, for reasons still unclear.

If this dual-antibiotic regimen doesn’t dramatically reduce drainage and pain, he adds levofloxacin at 500 mg twice daily for up to 2 weeks in an effort to calm down unstable, decompensating disease.

 

 

Dapsone at 50-150 mg/day for up to 12 weeks is an additional option. It’s most useful in patients with nodules that are disproportionately painful, in Dr. Hamzavi’s experience.

Deroofing is a simple procedure that should be considered for all sinus tracts. It entails numbing the area with a ring block then introducing a curette or surgical probe into the sinus tract to open it up and get rid of the gelatinous material within. Dutch investigators have detailed the technique (J Am Acad Dermatol. 2010 Sep;63[3]:475-80).

Tumor necrosis factor–inhibitor therapy has been a major advance in Hurley stage II and III disease. “It doesn’t work in everybody, but a lot of patients can be stabilized,” Dr. Hamzavi observed.

Efficacy has been amply demonstrated for adalimumab (Humira) and infliximab (Remicade). In Dr. Hamzavi’s experience infliximab works better, probably because it offers more dosing options.

Assuming medical therapy has resulted in disease stabilization, CO2 laser excision of sinus tracts under local anesthesia can then be employed as an office procedure to turn back the clock and return to an earlier stage of disease. Dermatologists at the Cleveland Clinic have described the technique in detail (Dermatol Surg. 2010 Feb;36[2]:208-13).
 

 

Hurley stage III

If biologic therapy doesn’t bring disease stabilization, the patient is likely headed for surgical excision using the CO2 laser. The Henry Ford team favors a specific regimen of surgical preparation using wide-spectrum antibiotics. The program begins with 6 weeks of IV ertapenem at 1 g/day delivered by a peripherally inserted central catheter managed by infectious disease colleagues.

“IV ertapenem is a drug you may not know much about. We find it works really well as a great way to bridge patients towards surgery,” the dermatologist explained.

The IV ertapenem is followed by 6 weeks of oral triple therapy with rifampin, moxifloxacin, and metronidazole then another 6 weeks of rifampin plus moxifloxacin. Next it’s surgical excision time.

 

 

Lifestyle modification

Lifestyle modification deserves to be a major priority in all HS patients, regardless of Hurley stage. Smoking cessation results in significantly greater likelihood of favorable response to first-line therapy. In obese patients, greater than 15% weight loss has been associated with significant reduction in disease severity. A sartorial shift to loose-fitting clothing can quiet down skin lesions through decreased friction and pressure. And proper utilization of warm compression will rapidly decrease acute lesional pain.

Dr. Hamzavi and his coinvestigators have described the Henry Ford Hospital treatment algorithm in a review of HS published in an open-access journal meant to serve as a resource for patients and physicians alike (F1000Res. 2017 Jul 28;6:1272. doi: 10.12688/f1000research.11337.1. eCollection 2017).

He reported serving as a consultant to AbbVie, Incyte, and UCB.

The Global Academy for Medical Education/SDEF and this news organization are owned by the same parent company.

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– Medical therapy alone is never sufficient in Hurley stage III hidradenitis suppurativa (HS), Iltefat H. Hamzavi, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

“Even with the advances in biologics and antibiotic therapy, you still have to excise once you’re in full-blown Hurley stage III disease. Surgery has to be part of your protocol,” according to Dr. Hamzavi, a dermatologist at Henry Ford Hospital in Detroit, which runs one of the nation’s largest hidradenitis suppurativa clinics, with roughly 1,600 patients.

Elsevier
He outlined the Henry Ford Hospital’s HS treatment algorithm. Where good evidence exists, the algorithm is evidence-based, and where evidence is lacking, it’s based upon expert opinion and considerable anecdotal experience.

“Of course we’re biased. But until the data can set us free, you’re stuck with me,” the dermatologist quipped.

A core principle of the Henry Ford algorithm is this: “Medical therapy [for patients with advanced HS] stabilizes them and reduces their draining and pain, then you try to bring them back to a lower stage with surgical options,” he explained.

Although other HS staging systems exist, Dr. Hamzavi and his colleagues rely on the Hurley staging system to guide their treatment. Basically, Hurley stage I consists of follicular nodules and abscesses. When the nodules connect to form sinus tracts with scarring, that’s stage II. And if the sinus tracts interconnect throughout an entire area, that’s stage III.

 

 

Hurley stage I

First-line treatment of localized Hurley stage I disease at Henry Ford is a 10% topical benzoyl peroxide wash left on for 5 minutes before bathing, followed by postbathing topical clindamycin 1% lotion or solution applied to the nodules. If this maintenance regimen isn’t sufficient to prevent formation of new and worsening nodules, Dr. Hamzavi supplements it with up to three once-monthly 1064-nm Nd:YAG laser sessions aimed at follicular ablation. It’s a laser application he and his colleagues pioneered (Dermatol Surg. 2009 Aug;35[8]:1188-98). They subsequently documented the histopathologic basis of the procedure’s efficacy, which entails selective thermolysis of follicles, destruction of inflammatory lesions in the superficial to mid-dermis, followed by fibrosis and scarring (Arch Dermatol. 2011 Jan;147[1]:21-8).

Bruce Jancin/MDedge News
Dr. Iltefat H. Hamzavi
“Our experience, and that of most people in the HS community, has been that, if you limit the hair follicles you limit the disease state,” said Dr. Hamzavi, who is the current president of the Hidradenitis Suppurativa Foundation.

In generalized Hurley stage I HS, the Henry Ford approach is to supplement the topical regimen and laser sessions with oral doxycycline at 100-150 mg daily for 1-6 months.

“The theory here is this is a dysbiotic event. The antibiotics reduce commensal bacteria, which ultimately reduces the reactive inflammatory response. But when you stop the antibiotics, the inflammatory response returns. So antibiotics can help stabilize the disease state but really can’t reverse the disease state. For that we have to turn to ablative treatment options: laser, surgery,” the dermatologist continued.

 

 

Hurley stage II

“At this point you’re looking at procedures,” according to Dr. Hamzavi. “Once you have sinus tracts it’s critical to remove them.”

The treatment backbone in stage II disease is 8-10 weeks of oral clindamycin and rifampin, both at 300 mg twice daily.

“This is one of the fundamental building blocks of HS clinics throughout the world,” he noted.

Clostridium difficile infection is exceedingly rare in HS patients on this regimen, for reasons still unclear.

If this dual-antibiotic regimen doesn’t dramatically reduce drainage and pain, he adds levofloxacin at 500 mg twice daily for up to 2 weeks in an effort to calm down unstable, decompensating disease.

 

 

Dapsone at 50-150 mg/day for up to 12 weeks is an additional option. It’s most useful in patients with nodules that are disproportionately painful, in Dr. Hamzavi’s experience.

Deroofing is a simple procedure that should be considered for all sinus tracts. It entails numbing the area with a ring block then introducing a curette or surgical probe into the sinus tract to open it up and get rid of the gelatinous material within. Dutch investigators have detailed the technique (J Am Acad Dermatol. 2010 Sep;63[3]:475-80).

Tumor necrosis factor–inhibitor therapy has been a major advance in Hurley stage II and III disease. “It doesn’t work in everybody, but a lot of patients can be stabilized,” Dr. Hamzavi observed.

Efficacy has been amply demonstrated for adalimumab (Humira) and infliximab (Remicade). In Dr. Hamzavi’s experience infliximab works better, probably because it offers more dosing options.

Assuming medical therapy has resulted in disease stabilization, CO2 laser excision of sinus tracts under local anesthesia can then be employed as an office procedure to turn back the clock and return to an earlier stage of disease. Dermatologists at the Cleveland Clinic have described the technique in detail (Dermatol Surg. 2010 Feb;36[2]:208-13).
 

 

Hurley stage III

If biologic therapy doesn’t bring disease stabilization, the patient is likely headed for surgical excision using the CO2 laser. The Henry Ford team favors a specific regimen of surgical preparation using wide-spectrum antibiotics. The program begins with 6 weeks of IV ertapenem at 1 g/day delivered by a peripherally inserted central catheter managed by infectious disease colleagues.

“IV ertapenem is a drug you may not know much about. We find it works really well as a great way to bridge patients towards surgery,” the dermatologist explained.

The IV ertapenem is followed by 6 weeks of oral triple therapy with rifampin, moxifloxacin, and metronidazole then another 6 weeks of rifampin plus moxifloxacin. Next it’s surgical excision time.

 

 

Lifestyle modification

Lifestyle modification deserves to be a major priority in all HS patients, regardless of Hurley stage. Smoking cessation results in significantly greater likelihood of favorable response to first-line therapy. In obese patients, greater than 15% weight loss has been associated with significant reduction in disease severity. A sartorial shift to loose-fitting clothing can quiet down skin lesions through decreased friction and pressure. And proper utilization of warm compression will rapidly decrease acute lesional pain.

Dr. Hamzavi and his coinvestigators have described the Henry Ford Hospital treatment algorithm in a review of HS published in an open-access journal meant to serve as a resource for patients and physicians alike (F1000Res. 2017 Jul 28;6:1272. doi: 10.12688/f1000research.11337.1. eCollection 2017).

He reported serving as a consultant to AbbVie, Incyte, and UCB.

The Global Academy for Medical Education/SDEF and this news organization are owned by the same parent company.

– Medical therapy alone is never sufficient in Hurley stage III hidradenitis suppurativa (HS), Iltefat H. Hamzavi, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

“Even with the advances in biologics and antibiotic therapy, you still have to excise once you’re in full-blown Hurley stage III disease. Surgery has to be part of your protocol,” according to Dr. Hamzavi, a dermatologist at Henry Ford Hospital in Detroit, which runs one of the nation’s largest hidradenitis suppurativa clinics, with roughly 1,600 patients.

Elsevier
He outlined the Henry Ford Hospital’s HS treatment algorithm. Where good evidence exists, the algorithm is evidence-based, and where evidence is lacking, it’s based upon expert opinion and considerable anecdotal experience.

“Of course we’re biased. But until the data can set us free, you’re stuck with me,” the dermatologist quipped.

A core principle of the Henry Ford algorithm is this: “Medical therapy [for patients with advanced HS] stabilizes them and reduces their draining and pain, then you try to bring them back to a lower stage with surgical options,” he explained.

Although other HS staging systems exist, Dr. Hamzavi and his colleagues rely on the Hurley staging system to guide their treatment. Basically, Hurley stage I consists of follicular nodules and abscesses. When the nodules connect to form sinus tracts with scarring, that’s stage II. And if the sinus tracts interconnect throughout an entire area, that’s stage III.

 

 

Hurley stage I

First-line treatment of localized Hurley stage I disease at Henry Ford is a 10% topical benzoyl peroxide wash left on for 5 minutes before bathing, followed by postbathing topical clindamycin 1% lotion or solution applied to the nodules. If this maintenance regimen isn’t sufficient to prevent formation of new and worsening nodules, Dr. Hamzavi supplements it with up to three once-monthly 1064-nm Nd:YAG laser sessions aimed at follicular ablation. It’s a laser application he and his colleagues pioneered (Dermatol Surg. 2009 Aug;35[8]:1188-98). They subsequently documented the histopathologic basis of the procedure’s efficacy, which entails selective thermolysis of follicles, destruction of inflammatory lesions in the superficial to mid-dermis, followed by fibrosis and scarring (Arch Dermatol. 2011 Jan;147[1]:21-8).

Bruce Jancin/MDedge News
Dr. Iltefat H. Hamzavi
“Our experience, and that of most people in the HS community, has been that, if you limit the hair follicles you limit the disease state,” said Dr. Hamzavi, who is the current president of the Hidradenitis Suppurativa Foundation.

In generalized Hurley stage I HS, the Henry Ford approach is to supplement the topical regimen and laser sessions with oral doxycycline at 100-150 mg daily for 1-6 months.

“The theory here is this is a dysbiotic event. The antibiotics reduce commensal bacteria, which ultimately reduces the reactive inflammatory response. But when you stop the antibiotics, the inflammatory response returns. So antibiotics can help stabilize the disease state but really can’t reverse the disease state. For that we have to turn to ablative treatment options: laser, surgery,” the dermatologist continued.

 

 

Hurley stage II

“At this point you’re looking at procedures,” according to Dr. Hamzavi. “Once you have sinus tracts it’s critical to remove them.”

The treatment backbone in stage II disease is 8-10 weeks of oral clindamycin and rifampin, both at 300 mg twice daily.

“This is one of the fundamental building blocks of HS clinics throughout the world,” he noted.

Clostridium difficile infection is exceedingly rare in HS patients on this regimen, for reasons still unclear.

If this dual-antibiotic regimen doesn’t dramatically reduce drainage and pain, he adds levofloxacin at 500 mg twice daily for up to 2 weeks in an effort to calm down unstable, decompensating disease.

 

 

Dapsone at 50-150 mg/day for up to 12 weeks is an additional option. It’s most useful in patients with nodules that are disproportionately painful, in Dr. Hamzavi’s experience.

Deroofing is a simple procedure that should be considered for all sinus tracts. It entails numbing the area with a ring block then introducing a curette or surgical probe into the sinus tract to open it up and get rid of the gelatinous material within. Dutch investigators have detailed the technique (J Am Acad Dermatol. 2010 Sep;63[3]:475-80).

Tumor necrosis factor–inhibitor therapy has been a major advance in Hurley stage II and III disease. “It doesn’t work in everybody, but a lot of patients can be stabilized,” Dr. Hamzavi observed.

Efficacy has been amply demonstrated for adalimumab (Humira) and infliximab (Remicade). In Dr. Hamzavi’s experience infliximab works better, probably because it offers more dosing options.

Assuming medical therapy has resulted in disease stabilization, CO2 laser excision of sinus tracts under local anesthesia can then be employed as an office procedure to turn back the clock and return to an earlier stage of disease. Dermatologists at the Cleveland Clinic have described the technique in detail (Dermatol Surg. 2010 Feb;36[2]:208-13).
 

 

Hurley stage III

If biologic therapy doesn’t bring disease stabilization, the patient is likely headed for surgical excision using the CO2 laser. The Henry Ford team favors a specific regimen of surgical preparation using wide-spectrum antibiotics. The program begins with 6 weeks of IV ertapenem at 1 g/day delivered by a peripherally inserted central catheter managed by infectious disease colleagues.

“IV ertapenem is a drug you may not know much about. We find it works really well as a great way to bridge patients towards surgery,” the dermatologist explained.

The IV ertapenem is followed by 6 weeks of oral triple therapy with rifampin, moxifloxacin, and metronidazole then another 6 weeks of rifampin plus moxifloxacin. Next it’s surgical excision time.

 

 

Lifestyle modification

Lifestyle modification deserves to be a major priority in all HS patients, regardless of Hurley stage. Smoking cessation results in significantly greater likelihood of favorable response to first-line therapy. In obese patients, greater than 15% weight loss has been associated with significant reduction in disease severity. A sartorial shift to loose-fitting clothing can quiet down skin lesions through decreased friction and pressure. And proper utilization of warm compression will rapidly decrease acute lesional pain.

Dr. Hamzavi and his coinvestigators have described the Henry Ford Hospital treatment algorithm in a review of HS published in an open-access journal meant to serve as a resource for patients and physicians alike (F1000Res. 2017 Jul 28;6:1272. doi: 10.12688/f1000research.11337.1. eCollection 2017).

He reported serving as a consultant to AbbVie, Incyte, and UCB.

The Global Academy for Medical Education/SDEF and this news organization are owned by the same parent company.

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