Psoriasis

SEOUL, SOUTH KOREA – Nearly two-thirds of patients treated with etanercept for scalp psoriasis had a 90% improvement in Psoriasis Scalp Severity Index score at week 12, compared with just 7% of controls, in a phase IV, double-blind, placebo-controlled randomized trial.

Topical scalp psoriasis treatments are often messy and inconvenient, and earn low marks for patient satisfaction and compliance. That is why Dr. Stephen K. Tyring said he and his coinvestigators conducted the phase IV trial of the tumor necrosis factor inhibitor etanercept (Enbrel) for moderate-to-severe scalp psoriasis.

The 124 participants had a baseline mean 64% scalp surface area involvement with a Psoriasis Scalp Severity Index (PSSI) score of 34.5, a 22.3% body surface area involvement, and a Psoriasis Area and Severity Index of 17.5.

Half of the subjects were randomized to etanercept at 50 mg twice weekly for 12 weeks, followed by once-weekly etanercept at 50 mg plus a subcutaneous placebo injection for another 12 weeks. The controls got 12 weeks of twice-weekly placebo injections, followed by 12 weeks of twice-weekly etanercept at 50 mg per dose.

The prespecified primary study end point was the mean percentage improvement in PSSI from baseline through week 12, which was 87% in the etanercept arm and 20% among controls. At week 12, 63% of the etanercept group had a PSSI 90 response – that is, at least a 90% improvement in PSSI – compared with just 7% of controls. A significant difference between the two study arms was evident as early as week 4, Dr. Tyring reported at the World Congress of Dermatology.

A week 12 PSSI 75 response was noted in 86% of the etanercept group, compared with 11% of controls. The etanercept group had a mean 74% reduction in PASI score at week 12, versus an 11% improvement among controls.

The improvement in scalp itch seen with etanercept was particularly impressive, he said. At baseline, less than 2% of patients had a Scalp Pruritus Score of 0, but by week 12 this was the case for 42% of the etanercept group and 8% of controls, noted Dr. Tyring, a dermatologist at the University of Texas in Houston.

The improvements in scalp and skin psoriasis seen with 12 weeks of twice-weekly etanercept were maintained through week 24, despite the switch to a lower dose. Moreover, patients initially assigned to 12 weeks of placebo showed improvements at week 24 – after 12 weeks on etanercept – similar to those seen at 12 weeks among patients assigned to the tumor necrosis factor inhibitor from the start.

For example, at week 24 a PASI 90 was achieved in 68% of the all-etanercept group and 67% in patients on 12 weeks of placebo followed by etanercept. At week 24, PASI 75 response was noted in 69% of the all-etanercept group and 59% of those on etanercept after placebo. And at week 24, a Scalp Pruritus Score of 0 was documented in 47% of patients on etanercept throughout the study and 49% of those on the biologic alone for the last 12 weeks.

The most common adverse events among study participants were upper respiratory infections in 12%, nasopharyngitis in 8%, and injection site reactions in 6%.

The clinical trial was sponsored by Amgen. Dr. Tyring has received research funding from, and has been a speaker for, the company.

SEOUL, SOUTH KOREA – Nearly two-thirds of patients treated with etanercept for scalp psoriasis had a 90% improvement in Psoriasis Scalp Severity Index score at week 12, compared with just 7% of controls, in a phase IV, double-blind, placebo-controlled randomized trial.

Topical scalp psoriasis treatments are often messy and inconvenient, and earn low marks for patient satisfaction and compliance. That is why Dr. Stephen K. Tyring said he and his coinvestigators conducted the phase IV trial of the tumor necrosis factor inhibitor etanercept (Enbrel) for moderate-to-severe scalp psoriasis.

The 124 participants had a baseline mean 64% scalp surface area involvement with a Psoriasis Scalp Severity Index (PSSI) score of 34.5, a 22.3% body surface area involvement, and a Psoriasis Area and Severity Index of 17.5.

Half of the subjects were randomized to etanercept at 50 mg twice weekly for 12 weeks, followed by once-weekly etanercept at 50 mg plus a subcutaneous placebo injection for another 12 weeks. The controls got 12 weeks of twice-weekly placebo injections, followed by 12 weeks of twice-weekly etanercept at 50 mg per dose.

The prespecified primary study end point was the mean percentage improvement in PSSI from baseline through week 12, which was 87% in the etanercept arm and 20% among controls. At week 12, 63% of the etanercept group had a PSSI 90 response – that is, at least a 90% improvement in PSSI – compared with just 7% of controls. A significant difference between the two study arms was evident as early as week 4, Dr. Tyring reported at the World Congress of Dermatology.

A week 12 PSSI 75 response was noted in 86% of the etanercept group, compared with 11% of controls. The etanercept group had a mean 74% reduction in PASI score at week 12, versus an 11% improvement among controls.

The improvement in scalp itch seen with etanercept was particularly impressive, he said. At baseline, less than 2% of patients had a Scalp Pruritus Score of 0, but by week 12 this was the case for 42% of the etanercept group and 8% of controls, noted Dr. Tyring, a dermatologist at the University of Texas in Houston.

The improvements in scalp and skin psoriasis seen with 12 weeks of twice-weekly etanercept were maintained through week 24, despite the switch to a lower dose. Moreover, patients initially assigned to 12 weeks of placebo showed improvements at week 24 – after 12 weeks on etanercept – similar to those seen at 12 weeks among patients assigned to the tumor necrosis factor inhibitor from the start.

For example, at week 24 a PASI 90 was achieved in 68% of the all-etanercept group and 67% in patients on 12 weeks of placebo followed by etanercept. At week 24, PASI 75 response was noted in 69% of the all-etanercept group and 59% of those on etanercept after placebo. And at week 24, a Scalp Pruritus Score of 0 was documented in 47% of patients on etanercept throughout the study and 49% of those on the biologic alone for the last 12 weeks.

The most common adverse events among study participants were upper respiratory infections in 12%, nasopharyngitis in 8%, and injection site reactions in 6%.

The clinical trial was sponsored by Amgen. Dr. Tyring has received research funding from, and has been a speaker for, the company.

SEOUL, SOUTH KOREA – Nearly two-thirds of patients treated with etanercept for scalp psoriasis had a 90% improvement in Psoriasis Scalp Severity Index score at week 12, compared with just 7% of controls, in a phase IV, double-blind, placebo-controlled randomized trial.

Topical scalp psoriasis treatments are often messy and inconvenient, and earn low marks for patient satisfaction and compliance. That is why Dr. Stephen K. Tyring said he and his coinvestigators conducted the phase IV trial of the tumor necrosis factor inhibitor etanercept (Enbrel) for moderate-to-severe scalp psoriasis.

The 124 participants had a baseline mean 64% scalp surface area involvement with a Psoriasis Scalp Severity Index (PSSI) score of 34.5, a 22.3% body surface area involvement, and a Psoriasis Area and Severity Index of 17.5.

Half of the subjects were randomized to etanercept at 50 mg twice weekly for 12 weeks, followed by once-weekly etanercept at 50 mg plus a subcutaneous placebo injection for another 12 weeks. The controls got 12 weeks of twice-weekly placebo injections, followed by 12 weeks of twice-weekly etanercept at 50 mg per dose.

The prespecified primary study end point was the mean percentage improvement in PSSI from baseline through week 12, which was 87% in the etanercept arm and 20% among controls. At week 12, 63% of the etanercept group had a PSSI 90 response – that is, at least a 90% improvement in PSSI – compared with just 7% of controls. A significant difference between the two study arms was evident as early as week 4, Dr. Tyring reported at the World Congress of Dermatology.

A week 12 PSSI 75 response was noted in 86% of the etanercept group, compared with 11% of controls. The etanercept group had a mean 74% reduction in PASI score at week 12, versus an 11% improvement among controls.

The improvement in scalp itch seen with etanercept was particularly impressive, he said. At baseline, less than 2% of patients had a Scalp Pruritus Score of 0, but by week 12 this was the case for 42% of the etanercept group and 8% of controls, noted Dr. Tyring, a dermatologist at the University of Texas in Houston.

The improvements in scalp and skin psoriasis seen with 12 weeks of twice-weekly etanercept were maintained through week 24, despite the switch to a lower dose. Moreover, patients initially assigned to 12 weeks of placebo showed improvements at week 24 – after 12 weeks on etanercept – similar to those seen at 12 weeks among patients assigned to the tumor necrosis factor inhibitor from the start.

For example, at week 24 a PASI 90 was achieved in 68% of the all-etanercept group and 67% in patients on 12 weeks of placebo followed by etanercept. At week 24, PASI 75 response was noted in 69% of the all-etanercept group and 59% of those on etanercept after placebo. And at week 24, a Scalp Pruritus Score of 0 was documented in 47% of patients on etanercept throughout the study and 49% of those on the biologic alone for the last 12 weeks.

The most common adverse events among study participants were upper respiratory infections in 12%, nasopharyngitis in 8%, and injection site reactions in 6%.

The clinical trial was sponsored by Amgen. Dr. Tyring has received research funding from, and has been a speaker for, the company.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

SEOUL, SOUTH KOREA – Early- and late-onset psoriasis are genetically and immunologically distinct diseases that happen to look similar clinically, according to Dr. Christopher E. Griffiths.

"All the research funding in psoriasis that has been spent in trying to understand the genetics of the disease comes down to one key finding: early-onset psoriasis, occurring before age 40, is strikingly associated with the HLA-Cw6 allele or something close to it," Dr. Griffiths said at the World Congress of Dermatology.

The class I human leukocyte antigen, HLA-Cw6, is found in 55%-80% of patients with psoriasis beginning before the age of 40. Early-onset disease accounts for 75% of all cases of psoriasis.

Late-onset psoriasis peaks in occurrence at the ages of 55-60. The frequency of the HLA-Cw6 allele in patients with late-onset disease is 15%-20%, comparable to that in the general population, said Dr. Griffiths, professor of dermatology at the University of Manchester (England).

Multiple genetic studies have shown that guttate psoriasis is predominantly found in patients who are HLA-Cw6 positive. An Icelandic study found that Cw6-positive patients also tended to have more severe psoriasis, a greater incidence of Koebner’s phenomenon, and more extensive plaques on their trunk, arms, and legs, while Cw6-negative status was associated with an increased likelihood of nail dystrophy, psoriatic arthritis, and later age of psoriasis onset (J. Invest. Dermatol. 2002;118:362-5).

Dr. Griffiths and his coworkers demonstrated that patients with early- and late-onset psoriasis also differ in terms of epidermal Langerhans cell function. These cells comprise the outermost surveillance post of the immune system. They are tasked with identifying invading pathogens and foreign antigens and transporting them from the epidermis to draining lymph nodes. Normally, this migration to lymph nodes is highly dependent upon two cytokines: interleukin-1 (IL-1) beta and tumor necrosis factor (TNF).

Dr. Griffiths and his co-investigators demonstrated that epidermal Langerhans cell mobilization and migration are greatly impaired in nonlesional skin of early-onset psoriasis patients, as compared to individuals without psoriasis.

Intradermal injection of TNF-alpha or IL-1 beta stimulated Langerhans cell migration in patients without psoriasis, but it had little or no effect on Langerhans cell function in uninvolved skin of patients with early-onset psoriasis.

In contrast, Langerhans cell migration was normal in response to intradermal injection of IL-1 beta in uninvolved skin of late-onset psoriasis patients. However, Langerhans cell migration in nonlesional skin was impaired in response to administration of TNF-alpha in the patients with late-onset psoriasis (J. Invest. Dermatol. 2010;130:1940-2).

University of Utah investigators have identified two different forms of chronic plaque psoriasis based not upon genetic or immunologic distinctions, but upon plaque morphology. In a prospective study involving 500 patients in the Utah Psoriasis Initiative, 29% of subjects characterized their plaques as thick when their psoriasis was at its most severe, while 25% rated the plaques as thin.

Thick-plaque patients were more likely to be male and have a higher body mass index, larger plaques affecting a greater body surface area, and an increased likelihood of nail dystrophy and psoriatic arthritis. Patients with thin plaques were more likely to have an eczematous component, were more prone to develop skin cancer, and were more likely to have had guttate psoriasis at some stage (J. Invest. Dermatol. 2006;126:2397-413).

"Until we understand much more about the pathogenesis and the immunology and the genetics of psoriasis, this simple clinical characterization would actually be very helpful in the clinic," said Dr. Griffiths. "I had a medical student working with me a couple of summers ago whose main task was to classify the patterns of disease in all the patients we saw in our psoriasis clinic; he could reliably differentiate 10 different forms of chronic plaque psoriasis."

Soon, it may be possible to classify plaque psoriasis by molecular phenotyping, which will help in matching the best possible treatment for a given individual, he said.

Dr. Griffiths disclosed that he has been a consultant to or has received research funds from numerous companies that manufacture drugs used in treating psoriasis.

SEOUL, SOUTH KOREA – Early- and late-onset psoriasis are genetically and immunologically distinct diseases that happen to look similar clinically, according to Dr. Christopher E. Griffiths.

"All the research funding in psoriasis that has been spent in trying to understand the genetics of the disease comes down to one key finding: early-onset psoriasis, occurring before age 40, is strikingly associated with the HLA-Cw6 allele or something close to it," Dr. Griffiths said at the World Congress of Dermatology.

The class I human leukocyte antigen, HLA-Cw6, is found in 55%-80% of patients with psoriasis beginning before the age of 40. Early-onset disease accounts for 75% of all cases of psoriasis.

Late-onset psoriasis peaks in occurrence at the ages of 55-60. The frequency of the HLA-Cw6 allele in patients with late-onset disease is 15%-20%, comparable to that in the general population, said Dr. Griffiths, professor of dermatology at the University of Manchester (England).

Multiple genetic studies have shown that guttate psoriasis is predominantly found in patients who are HLA-Cw6 positive. An Icelandic study found that Cw6-positive patients also tended to have more severe psoriasis, a greater incidence of Koebner’s phenomenon, and more extensive plaques on their trunk, arms, and legs, while Cw6-negative status was associated with an increased likelihood of nail dystrophy, psoriatic arthritis, and later age of psoriasis onset (J. Invest. Dermatol. 2002;118:362-5).

Dr. Griffiths and his coworkers demonstrated that patients with early- and late-onset psoriasis also differ in terms of epidermal Langerhans cell function. These cells comprise the outermost surveillance post of the immune system. They are tasked with identifying invading pathogens and foreign antigens and transporting them from the epidermis to draining lymph nodes. Normally, this migration to lymph nodes is highly dependent upon two cytokines: interleukin-1 (IL-1) beta and tumor necrosis factor (TNF).

Dr. Griffiths and his co-investigators demonstrated that epidermal Langerhans cell mobilization and migration are greatly impaired in nonlesional skin of early-onset psoriasis patients, as compared to individuals without psoriasis.

Intradermal injection of TNF-alpha or IL-1 beta stimulated Langerhans cell migration in patients without psoriasis, but it had little or no effect on Langerhans cell function in uninvolved skin of patients with early-onset psoriasis.

In contrast, Langerhans cell migration was normal in response to intradermal injection of IL-1 beta in uninvolved skin of late-onset psoriasis patients. However, Langerhans cell migration in nonlesional skin was impaired in response to administration of TNF-alpha in the patients with late-onset psoriasis (J. Invest. Dermatol. 2010;130:1940-2).

University of Utah investigators have identified two different forms of chronic plaque psoriasis based not upon genetic or immunologic distinctions, but upon plaque morphology. In a prospective study involving 500 patients in the Utah Psoriasis Initiative, 29% of subjects characterized their plaques as thick when their psoriasis was at its most severe, while 25% rated the plaques as thin.

Thick-plaque patients were more likely to be male and have a higher body mass index, larger plaques affecting a greater body surface area, and an increased likelihood of nail dystrophy and psoriatic arthritis. Patients with thin plaques were more likely to have an eczematous component, were more prone to develop skin cancer, and were more likely to have had guttate psoriasis at some stage (J. Invest. Dermatol. 2006;126:2397-413).

"Until we understand much more about the pathogenesis and the immunology and the genetics of psoriasis, this simple clinical characterization would actually be very helpful in the clinic," said Dr. Griffiths. "I had a medical student working with me a couple of summers ago whose main task was to classify the patterns of disease in all the patients we saw in our psoriasis clinic; he could reliably differentiate 10 different forms of chronic plaque psoriasis."

Soon, it may be possible to classify plaque psoriasis by molecular phenotyping, which will help in matching the best possible treatment for a given individual, he said.

Dr. Griffiths disclosed that he has been a consultant to or has received research funds from numerous companies that manufacture drugs used in treating psoriasis.

SEOUL, SOUTH KOREA – Early- and late-onset psoriasis are genetically and immunologically distinct diseases that happen to look similar clinically, according to Dr. Christopher E. Griffiths.

"All the research funding in psoriasis that has been spent in trying to understand the genetics of the disease comes down to one key finding: early-onset psoriasis, occurring before age 40, is strikingly associated with the HLA-Cw6 allele or something close to it," Dr. Griffiths said at the World Congress of Dermatology.

The class I human leukocyte antigen, HLA-Cw6, is found in 55%-80% of patients with psoriasis beginning before the age of 40. Early-onset disease accounts for 75% of all cases of psoriasis.

Late-onset psoriasis peaks in occurrence at the ages of 55-60. The frequency of the HLA-Cw6 allele in patients with late-onset disease is 15%-20%, comparable to that in the general population, said Dr. Griffiths, professor of dermatology at the University of Manchester (England).

Multiple genetic studies have shown that guttate psoriasis is predominantly found in patients who are HLA-Cw6 positive. An Icelandic study found that Cw6-positive patients also tended to have more severe psoriasis, a greater incidence of Koebner’s phenomenon, and more extensive plaques on their trunk, arms, and legs, while Cw6-negative status was associated with an increased likelihood of nail dystrophy, psoriatic arthritis, and later age of psoriasis onset (J. Invest. Dermatol. 2002;118:362-5).

Dr. Griffiths and his coworkers demonstrated that patients with early- and late-onset psoriasis also differ in terms of epidermal Langerhans cell function. These cells comprise the outermost surveillance post of the immune system. They are tasked with identifying invading pathogens and foreign antigens and transporting them from the epidermis to draining lymph nodes. Normally, this migration to lymph nodes is highly dependent upon two cytokines: interleukin-1 (IL-1) beta and tumor necrosis factor (TNF).

Dr. Griffiths and his co-investigators demonstrated that epidermal Langerhans cell mobilization and migration are greatly impaired in nonlesional skin of early-onset psoriasis patients, as compared to individuals without psoriasis.

Intradermal injection of TNF-alpha or IL-1 beta stimulated Langerhans cell migration in patients without psoriasis, but it had little or no effect on Langerhans cell function in uninvolved skin of patients with early-onset psoriasis.

In contrast, Langerhans cell migration was normal in response to intradermal injection of IL-1 beta in uninvolved skin of late-onset psoriasis patients. However, Langerhans cell migration in nonlesional skin was impaired in response to administration of TNF-alpha in the patients with late-onset psoriasis (J. Invest. Dermatol. 2010;130:1940-2).

University of Utah investigators have identified two different forms of chronic plaque psoriasis based not upon genetic or immunologic distinctions, but upon plaque morphology. In a prospective study involving 500 patients in the Utah Psoriasis Initiative, 29% of subjects characterized their plaques as thick when their psoriasis was at its most severe, while 25% rated the plaques as thin.

Thick-plaque patients were more likely to be male and have a higher body mass index, larger plaques affecting a greater body surface area, and an increased likelihood of nail dystrophy and psoriatic arthritis. Patients with thin plaques were more likely to have an eczematous component, were more prone to develop skin cancer, and were more likely to have had guttate psoriasis at some stage (J. Invest. Dermatol. 2006;126:2397-413).

"Until we understand much more about the pathogenesis and the immunology and the genetics of psoriasis, this simple clinical characterization would actually be very helpful in the clinic," said Dr. Griffiths. "I had a medical student working with me a couple of summers ago whose main task was to classify the patterns of disease in all the patients we saw in our psoriasis clinic; he could reliably differentiate 10 different forms of chronic plaque psoriasis."

Soon, it may be possible to classify plaque psoriasis by molecular phenotyping, which will help in matching the best possible treatment for a given individual, he said.

Dr. Griffiths disclosed that he has been a consultant to or has received research funds from numerous companies that manufacture drugs used in treating psoriasis.

SEOUL, SOUTH KOREA – Alefacept in combination with narrow-band UVB was found to be more effective than alefacept monotherapy, as demonstrated in the Canadian Alefacept Phototherapy Psoriasis Study.

The combination therapy group had a PASI 75 response rate twice that seen with alefacept (Amevive) monotherapy, along with impressively long improvement after completing a 12-week course of treatment, Dr. Wayne Gulliver said at the World Congress of Dermatology.

"I think the value of this combination is you get sustained improvement for many weeks and months off therapy," he observed. "I have some patients who take a course every 2 years, and they're happy with that."

The multicenter, open-label, blinded-assessment Canadian clinical trial involved 98 patients with moderate to severe chronic plaque psoriasis who were randomized to alefacept 15 mg IM once weekly alone or in combination with narrow-band UVB phototherapy thrice weekly for 12 weeks, followed by a 24-week observation period.

The primary outcome measure was a PASI 75 response at week 16. This occurred in 45% of patients receiving combination therapy, compared with 22% receiving alefacept monotherapy, according to Dr. Gulliver, professor of dermatology and chairman of medicine at Memorial University of Newfoundland, St. John's.

Ten patients in the dual-therapy group achieved a PASI 90 response at week 16, compared with 4 on alefacept alone. Twenty-nine patients in the combination treatment arm were rated as clear or almost clear by Physician's Global Assessment at any time during the study, compared with 17 patients on monotherapy.

PASI 50 and PASI 75 improvements often occurred several months earlier with alefacept plus narrow-band UVB. The combination was "extremely well tolerated," with a side-effect profile quite similar to that of alefacept alone, he said.

He added that he considers this combination especially useful in patients who have failed numerous other potent therapies. "This gives us one more option for patients who really are running out of options," Dr. Gulliver said.

The other situation in which he finds alefacept in combination with narrow-band UVB particularly advantageous is for patients who would like to be off of systemic therapy for a long while, such as women who are interested in having a baby.

Dr. Gulliver disclosed that has been a consultant to and/or has been paid for clinical trials for 20 pharmaceutical companies, including Astellas Pharma Canada, which markets alefacept.

SEOUL, SOUTH KOREA – Alefacept in combination with narrow-band UVB was found to be more effective than alefacept monotherapy, as demonstrated in the Canadian Alefacept Phototherapy Psoriasis Study.

The combination therapy group had a PASI 75 response rate twice that seen with alefacept (Amevive) monotherapy, along with impressively long improvement after completing a 12-week course of treatment, Dr. Wayne Gulliver said at the World Congress of Dermatology.

"I think the value of this combination is you get sustained improvement for many weeks and months off therapy," he observed. "I have some patients who take a course every 2 years, and they're happy with that."

The multicenter, open-label, blinded-assessment Canadian clinical trial involved 98 patients with moderate to severe chronic plaque psoriasis who were randomized to alefacept 15 mg IM once weekly alone or in combination with narrow-band UVB phototherapy thrice weekly for 12 weeks, followed by a 24-week observation period.

The primary outcome measure was a PASI 75 response at week 16. This occurred in 45% of patients receiving combination therapy, compared with 22% receiving alefacept monotherapy, according to Dr. Gulliver, professor of dermatology and chairman of medicine at Memorial University of Newfoundland, St. John's.

Ten patients in the dual-therapy group achieved a PASI 90 response at week 16, compared with 4 on alefacept alone. Twenty-nine patients in the combination treatment arm were rated as clear or almost clear by Physician's Global Assessment at any time during the study, compared with 17 patients on monotherapy.

PASI 50 and PASI 75 improvements often occurred several months earlier with alefacept plus narrow-band UVB. The combination was "extremely well tolerated," with a side-effect profile quite similar to that of alefacept alone, he said.

He added that he considers this combination especially useful in patients who have failed numerous other potent therapies. "This gives us one more option for patients who really are running out of options," Dr. Gulliver said.

The other situation in which he finds alefacept in combination with narrow-band UVB particularly advantageous is for patients who would like to be off of systemic therapy for a long while, such as women who are interested in having a baby.

Dr. Gulliver disclosed that has been a consultant to and/or has been paid for clinical trials for 20 pharmaceutical companies, including Astellas Pharma Canada, which markets alefacept.

SEOUL, SOUTH KOREA – Alefacept in combination with narrow-band UVB was found to be more effective than alefacept monotherapy, as demonstrated in the Canadian Alefacept Phototherapy Psoriasis Study.

The combination therapy group had a PASI 75 response rate twice that seen with alefacept (Amevive) monotherapy, along with impressively long improvement after completing a 12-week course of treatment, Dr. Wayne Gulliver said at the World Congress of Dermatology.

"I think the value of this combination is you get sustained improvement for many weeks and months off therapy," he observed. "I have some patients who take a course every 2 years, and they're happy with that."

The multicenter, open-label, blinded-assessment Canadian clinical trial involved 98 patients with moderate to severe chronic plaque psoriasis who were randomized to alefacept 15 mg IM once weekly alone or in combination with narrow-band UVB phototherapy thrice weekly for 12 weeks, followed by a 24-week observation period.

The primary outcome measure was a PASI 75 response at week 16. This occurred in 45% of patients receiving combination therapy, compared with 22% receiving alefacept monotherapy, according to Dr. Gulliver, professor of dermatology and chairman of medicine at Memorial University of Newfoundland, St. John's.

Ten patients in the dual-therapy group achieved a PASI 90 response at week 16, compared with 4 on alefacept alone. Twenty-nine patients in the combination treatment arm were rated as clear or almost clear by Physician's Global Assessment at any time during the study, compared with 17 patients on monotherapy.

PASI 50 and PASI 75 improvements often occurred several months earlier with alefacept plus narrow-band UVB. The combination was "extremely well tolerated," with a side-effect profile quite similar to that of alefacept alone, he said.

He added that he considers this combination especially useful in patients who have failed numerous other potent therapies. "This gives us one more option for patients who really are running out of options," Dr. Gulliver said.

The other situation in which he finds alefacept in combination with narrow-band UVB particularly advantageous is for patients who would like to be off of systemic therapy for a long while, such as women who are interested in having a baby.

Dr. Gulliver disclosed that has been a consultant to and/or has been paid for clinical trials for 20 pharmaceutical companies, including Astellas Pharma Canada, which markets alefacept.

It has been 25 years since the establishment of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and great strides have been made in diagnosis, treatment, and management of numerous conditions, "but you ain't seen nothing yet," said Dr. Francis Collins, director of the National Institutes of Health.

Opportunities for medical research have never been as great as they are today, said Dr. Collins, who gave the welcome address for NIAMS' 25th anniversary at the NIH campus in Bethesda, Md.

Although prominent researchers in the field agreed that research has come a long way in the past 25 years, they stressed that there is still a long way to go. Currently, the molecular basis for 4,000 diseases is known, said Dr. Collins. "But we have effective treatment for only 200."

In broad strokes, the day-long event touched on the past, present, and future of major diseases of bones, joints, muscles, and skin through panels and discussion involving prominent researchers, physicians, and patient advocates.

"These diseases are chronic, crippling, and common," said Dr. Stephen Katz, director of NIAMS, in his opening address. "They affect every family in the United States."

Among the attendees were many researchers and clinicians who said they felt loyalty and appreciation for receiving funding from NIAMS at some point in their career. For some, the progress in the past 2 decades was quite tangible.

"Public investment in osteoporosis research has really changed how we take care of the patients," said Dr. Sundeep Khosla, president of the American Society for Bone and Mineral Research. Dr. Khosla, professor at the Mayo Medical School, Rochester, Minn., recalled a time more than 2 decades ago when calcium, vitamin D, and estrogen were the only options he could offer to patients with osteoporosis.

A few years later, bisphosphonates became available, then came anabolic drugs, and now more drugs are in the pipeline. Patient diagnosis also has advanced, he said. Although he agreed that the field still has a long way to go, he was optimistic about more progress. "Who knows what will happen in the next 25 years," he said.

There was talk of individualized therapy, balancing research and treatment, and a closer collaboration among scientists, all in the spirit of bringing better diagnosis and treatment to patients.

"We're in a different world from when all we had was aspirin," said Dr. Daniel Kastner, a scientific director at the National Human Genome Research Institute. "But what we really want is a cure. And we're not there yet."

--Naseem S. Miller (@NaseemSMiller)

It has been 25 years since the establishment of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and great strides have been made in diagnosis, treatment, and management of numerous conditions, "but you ain't seen nothing yet," said Dr. Francis Collins, director of the National Institutes of Health.

Opportunities for medical research have never been as great as they are today, said Dr. Collins, who gave the welcome address for NIAMS' 25th anniversary at the NIH campus in Bethesda, Md.

Although prominent researchers in the field agreed that research has come a long way in the past 25 years, they stressed that there is still a long way to go. Currently, the molecular basis for 4,000 diseases is known, said Dr. Collins. "But we have effective treatment for only 200."

In broad strokes, the day-long event touched on the past, present, and future of major diseases of bones, joints, muscles, and skin through panels and discussion involving prominent researchers, physicians, and patient advocates.

"These diseases are chronic, crippling, and common," said Dr. Stephen Katz, director of NIAMS, in his opening address. "They affect every family in the United States."

Among the attendees were many researchers and clinicians who said they felt loyalty and appreciation for receiving funding from NIAMS at some point in their career. For some, the progress in the past 2 decades was quite tangible.

"Public investment in osteoporosis research has really changed how we take care of the patients," said Dr. Sundeep Khosla, president of the American Society for Bone and Mineral Research. Dr. Khosla, professor at the Mayo Medical School, Rochester, Minn., recalled a time more than 2 decades ago when calcium, vitamin D, and estrogen were the only options he could offer to patients with osteoporosis.

A few years later, bisphosphonates became available, then came anabolic drugs, and now more drugs are in the pipeline. Patient diagnosis also has advanced, he said. Although he agreed that the field still has a long way to go, he was optimistic about more progress. "Who knows what will happen in the next 25 years," he said.

There was talk of individualized therapy, balancing research and treatment, and a closer collaboration among scientists, all in the spirit of bringing better diagnosis and treatment to patients.

"We're in a different world from when all we had was aspirin," said Dr. Daniel Kastner, a scientific director at the National Human Genome Research Institute. "But what we really want is a cure. And we're not there yet."

--Naseem S. Miller (@NaseemSMiller)

It has been 25 years since the establishment of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and great strides have been made in diagnosis, treatment, and management of numerous conditions, "but you ain't seen nothing yet," said Dr. Francis Collins, director of the National Institutes of Health.

Opportunities for medical research have never been as great as they are today, said Dr. Collins, who gave the welcome address for NIAMS' 25th anniversary at the NIH campus in Bethesda, Md.

Although prominent researchers in the field agreed that research has come a long way in the past 25 years, they stressed that there is still a long way to go. Currently, the molecular basis for 4,000 diseases is known, said Dr. Collins. "But we have effective treatment for only 200."

In broad strokes, the day-long event touched on the past, present, and future of major diseases of bones, joints, muscles, and skin through panels and discussion involving prominent researchers, physicians, and patient advocates.

"These diseases are chronic, crippling, and common," said Dr. Stephen Katz, director of NIAMS, in his opening address. "They affect every family in the United States."

Among the attendees were many researchers and clinicians who said they felt loyalty and appreciation for receiving funding from NIAMS at some point in their career. For some, the progress in the past 2 decades was quite tangible.

"Public investment in osteoporosis research has really changed how we take care of the patients," said Dr. Sundeep Khosla, president of the American Society for Bone and Mineral Research. Dr. Khosla, professor at the Mayo Medical School, Rochester, Minn., recalled a time more than 2 decades ago when calcium, vitamin D, and estrogen were the only options he could offer to patients with osteoporosis.

A few years later, bisphosphonates became available, then came anabolic drugs, and now more drugs are in the pipeline. Patient diagnosis also has advanced, he said. Although he agreed that the field still has a long way to go, he was optimistic about more progress. "Who knows what will happen in the next 25 years," he said.

There was talk of individualized therapy, balancing research and treatment, and a closer collaboration among scientists, all in the spirit of bringing better diagnosis and treatment to patients.

"We're in a different world from when all we had was aspirin," said Dr. Daniel Kastner, a scientific director at the National Human Genome Research Institute. "But what we really want is a cure. And we're not there yet."

--Naseem S. Miller (@NaseemSMiller)

SEOUL, SOUTH KOREA – The combination of calcipotriene and nicotinamide may be an attractive corticosteroid-sparing option for topical psoriasis therapy, according to results from a pilot trial.

"Both agents are somewhat effective for psoriasis; the combination of the two is markedly superior," Dr. Mark Lebwohl said in summarizing the findings of a pilot bilateral comparative study presented at the World Congress of Dermatology.

The investigational topical combination therapy is being developed by Dermipsor, an Israeli pharmaceutical company.

Dr. Lebwohl was a coinvestigator in the multicenter, double-blind, 12-week pilot study involving 168 patients with symmetric moderate psoriasis (defined as not more than 15% body surface area involvement).

The patients were randomized to two of seven treatments: calcipotriene 0.005% monotherapy, nicotinamide 1.4% alone, placebo, or calcipotriene 0.005% plus nicotinamide in a concentration of either 0.05%, 0.1%, 0.7%, or 1.4%. Patients treated the lesions on one side of the body with one of their two assigned treatments, and lesions on the opposite side with the other.

The primary end point was efficacy (defined as a clear to almost-clear outcome at week 12), which was achieved in 19% of patients who were treated with placebo, 25% of those on nicotinamide 1.4% alone, 31.5% of those treated with calcipotriene alone, and 50% of patients in the calcipotriene plus nicotinamide 1.4% group, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.

The 50% clear or almost-clear rate with calcipotriene plus nicotinamide 1.4% is similar to the 48% rate of absent to very mild disease that was previously reported with a calcipotriol/betamethasone combination in a 52-week study (Dermatology 2006;213:319-26).

Thus, the calcipotriene/nicotinamide combination is an agent that will be investigated further in larger, lengthier studies as a possible steroid-sparing agent in comparative trials vs. calcipotriene-steroid combination therapy, Dr. Lebwohl said.

Topical combination therapy continues to be an active area in psoriasis research, he observed.

"It's really a no-brainer: The combination of two ingredients is going to be superior to either one alone. It's a very simple concept: Two is better than one," he said.

Dr. Lebwohl disclosed that he is a consultant to Dermipsor and has advisory board relationships with other pharmaceutical companies that are developing dermatologic drugs.

SEOUL, SOUTH KOREA – The combination of calcipotriene and nicotinamide may be an attractive corticosteroid-sparing option for topical psoriasis therapy, according to results from a pilot trial.

"Both agents are somewhat effective for psoriasis; the combination of the two is markedly superior," Dr. Mark Lebwohl said in summarizing the findings of a pilot bilateral comparative study presented at the World Congress of Dermatology.

The investigational topical combination therapy is being developed by Dermipsor, an Israeli pharmaceutical company.

Dr. Lebwohl was a coinvestigator in the multicenter, double-blind, 12-week pilot study involving 168 patients with symmetric moderate psoriasis (defined as not more than 15% body surface area involvement).

The patients were randomized to two of seven treatments: calcipotriene 0.005% monotherapy, nicotinamide 1.4% alone, placebo, or calcipotriene 0.005% plus nicotinamide in a concentration of either 0.05%, 0.1%, 0.7%, or 1.4%. Patients treated the lesions on one side of the body with one of their two assigned treatments, and lesions on the opposite side with the other.

The primary end point was efficacy (defined as a clear to almost-clear outcome at week 12), which was achieved in 19% of patients who were treated with placebo, 25% of those on nicotinamide 1.4% alone, 31.5% of those treated with calcipotriene alone, and 50% of patients in the calcipotriene plus nicotinamide 1.4% group, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.

The 50% clear or almost-clear rate with calcipotriene plus nicotinamide 1.4% is similar to the 48% rate of absent to very mild disease that was previously reported with a calcipotriol/betamethasone combination in a 52-week study (Dermatology 2006;213:319-26).

Thus, the calcipotriene/nicotinamide combination is an agent that will be investigated further in larger, lengthier studies as a possible steroid-sparing agent in comparative trials vs. calcipotriene-steroid combination therapy, Dr. Lebwohl said.

Topical combination therapy continues to be an active area in psoriasis research, he observed.

"It's really a no-brainer: The combination of two ingredients is going to be superior to either one alone. It's a very simple concept: Two is better than one," he said.

Dr. Lebwohl disclosed that he is a consultant to Dermipsor and has advisory board relationships with other pharmaceutical companies that are developing dermatologic drugs.

SEOUL, SOUTH KOREA – The combination of calcipotriene and nicotinamide may be an attractive corticosteroid-sparing option for topical psoriasis therapy, according to results from a pilot trial.

"Both agents are somewhat effective for psoriasis; the combination of the two is markedly superior," Dr. Mark Lebwohl said in summarizing the findings of a pilot bilateral comparative study presented at the World Congress of Dermatology.

The investigational topical combination therapy is being developed by Dermipsor, an Israeli pharmaceutical company.

Dr. Lebwohl was a coinvestigator in the multicenter, double-blind, 12-week pilot study involving 168 patients with symmetric moderate psoriasis (defined as not more than 15% body surface area involvement).

The patients were randomized to two of seven treatments: calcipotriene 0.005% monotherapy, nicotinamide 1.4% alone, placebo, or calcipotriene 0.005% plus nicotinamide in a concentration of either 0.05%, 0.1%, 0.7%, or 1.4%. Patients treated the lesions on one side of the body with one of their two assigned treatments, and lesions on the opposite side with the other.

The primary end point was efficacy (defined as a clear to almost-clear outcome at week 12), which was achieved in 19% of patients who were treated with placebo, 25% of those on nicotinamide 1.4% alone, 31.5% of those treated with calcipotriene alone, and 50% of patients in the calcipotriene plus nicotinamide 1.4% group, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.

The 50% clear or almost-clear rate with calcipotriene plus nicotinamide 1.4% is similar to the 48% rate of absent to very mild disease that was previously reported with a calcipotriol/betamethasone combination in a 52-week study (Dermatology 2006;213:319-26).

Thus, the calcipotriene/nicotinamide combination is an agent that will be investigated further in larger, lengthier studies as a possible steroid-sparing agent in comparative trials vs. calcipotriene-steroid combination therapy, Dr. Lebwohl said.

Topical combination therapy continues to be an active area in psoriasis research, he observed.

"It's really a no-brainer: The combination of two ingredients is going to be superior to either one alone. It's a very simple concept: Two is better than one," he said.

Dr. Lebwohl disclosed that he is a consultant to Dermipsor and has advisory board relationships with other pharmaceutical companies that are developing dermatologic drugs.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a new report in JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes.

They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a new report in JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes.

They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a new report in JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes.

They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

SEOUL, SOUTH KOREA – Treatment of psoriasis patients with biologic agents isn't associated with increased risk of herpes zoster, according to a large population-based Israeli study.

In contrast, the use of methotrexate, cyclosporine, acitretin, and systemic corticosteroids is associated with an increased risk of herpes zoster in psoriasis patients, Dr. Arnon D. Cohen said at the World Congress of Dermatology.

He reported on 22,330 psoriasis patients followed over 10 years at Clalit Health Services, Israel’s largest HMO. This was a real-world patient population, 53% of whom were female, in contrast to the highly selected populations in randomized clinical trials, which are typically 65%-69% male.

During nearly 220,000 person-years of follow-up there were 1,321 cases of herpes zoster. The baseline rate during periods when patients weren’t on any form of systemic therapy was 4.6 cases/1,000 patient-years. In contrast, the rate during cyclosporine therapy was more than 10-fold higher at 48.4 cases/1,000 patient-years.

Eighteen percent of psoriasis patients were on systemic corticosteroids at some point during the study period; that medication was associated with a herpes zoster rate of 25.7/1,000 patient-years of exposure.

Other therapies that conferred significantly increased risk were methotrexate at 17 cases/1,000 patient-years and acitretin (Soriatane) at 5.4 cases/1,000 patient-years, reported Dr. Cohen, director of the department of quality measures at Clalit and a dermatologist at Ben-Gurion University of the Negev, Beer-Sheva, Israel.

In contrast, no cases of herpes zoster occurred in psoriasis patients on Amevive, Raptiva, or, Humira. Nor was the incidence increased beyond baseline in patients on PUVA, UVB, or Enbrel.

In a , systemic corticosteroid therapy was associated with a 2.4-fold increased risk of developing herpes zoster. Being female was associated with a significant 16% increase in risk. Remicade therapy was associated with a 1.8-fold increase in risk, a trend that did not achieve statistical significance (P =.09).

Dr. Cohen and his coinvestigators conducted this study because, even though the biologic agents are recognized as conferring increased risk of tuberculosis and serious bacterial infections, very little is known about their association, if any, with viral infections.

Dr. Cohen declared having no relevant financial interests.

SEOUL, SOUTH KOREA – Treatment of psoriasis patients with biologic agents isn't associated with increased risk of herpes zoster, according to a large population-based Israeli study.

In contrast, the use of methotrexate, cyclosporine, acitretin, and systemic corticosteroids is associated with an increased risk of herpes zoster in psoriasis patients, Dr. Arnon D. Cohen said at the World Congress of Dermatology.

He reported on 22,330 psoriasis patients followed over 10 years at Clalit Health Services, Israel’s largest HMO. This was a real-world patient population, 53% of whom were female, in contrast to the highly selected populations in randomized clinical trials, which are typically 65%-69% male.

During nearly 220,000 person-years of follow-up there were 1,321 cases of herpes zoster. The baseline rate during periods when patients weren’t on any form of systemic therapy was 4.6 cases/1,000 patient-years. In contrast, the rate during cyclosporine therapy was more than 10-fold higher at 48.4 cases/1,000 patient-years.

Eighteen percent of psoriasis patients were on systemic corticosteroids at some point during the study period; that medication was associated with a herpes zoster rate of 25.7/1,000 patient-years of exposure.

Other therapies that conferred significantly increased risk were methotrexate at 17 cases/1,000 patient-years and acitretin (Soriatane) at 5.4 cases/1,000 patient-years, reported Dr. Cohen, director of the department of quality measures at Clalit and a dermatologist at Ben-Gurion University of the Negev, Beer-Sheva, Israel.

In contrast, no cases of herpes zoster occurred in psoriasis patients on Amevive, Raptiva, or, Humira. Nor was the incidence increased beyond baseline in patients on PUVA, UVB, or Enbrel.

In a , systemic corticosteroid therapy was associated with a 2.4-fold increased risk of developing herpes zoster. Being female was associated with a significant 16% increase in risk. Remicade therapy was associated with a 1.8-fold increase in risk, a trend that did not achieve statistical significance (P =.09).

Dr. Cohen and his coinvestigators conducted this study because, even though the biologic agents are recognized as conferring increased risk of tuberculosis and serious bacterial infections, very little is known about their association, if any, with viral infections.

Dr. Cohen declared having no relevant financial interests.

SEOUL, SOUTH KOREA – Treatment of psoriasis patients with biologic agents isn't associated with increased risk of herpes zoster, according to a large population-based Israeli study.

In contrast, the use of methotrexate, cyclosporine, acitretin, and systemic corticosteroids is associated with an increased risk of herpes zoster in psoriasis patients, Dr. Arnon D. Cohen said at the World Congress of Dermatology.

He reported on 22,330 psoriasis patients followed over 10 years at Clalit Health Services, Israel’s largest HMO. This was a real-world patient population, 53% of whom were female, in contrast to the highly selected populations in randomized clinical trials, which are typically 65%-69% male.

During nearly 220,000 person-years of follow-up there were 1,321 cases of herpes zoster. The baseline rate during periods when patients weren’t on any form of systemic therapy was 4.6 cases/1,000 patient-years. In contrast, the rate during cyclosporine therapy was more than 10-fold higher at 48.4 cases/1,000 patient-years.

Eighteen percent of psoriasis patients were on systemic corticosteroids at some point during the study period; that medication was associated with a herpes zoster rate of 25.7/1,000 patient-years of exposure.

Other therapies that conferred significantly increased risk were methotrexate at 17 cases/1,000 patient-years and acitretin (Soriatane) at 5.4 cases/1,000 patient-years, reported Dr. Cohen, director of the department of quality measures at Clalit and a dermatologist at Ben-Gurion University of the Negev, Beer-Sheva, Israel.

In contrast, no cases of herpes zoster occurred in psoriasis patients on Amevive, Raptiva, or, Humira. Nor was the incidence increased beyond baseline in patients on PUVA, UVB, or Enbrel.

In a , systemic corticosteroid therapy was associated with a 2.4-fold increased risk of developing herpes zoster. Being female was associated with a significant 16% increase in risk. Remicade therapy was associated with a 1.8-fold increase in risk, a trend that did not achieve statistical significance (P =.09).

Dr. Cohen and his coinvestigators conducted this study because, even though the biologic agents are recognized as conferring increased risk of tuberculosis and serious bacterial infections, very little is known about their association, if any, with viral infections.

Dr. Cohen declared having no relevant financial interests.

GRAPEVINE, TEX. – The 308-nm excimer laser significantly reduced palmoplantar psoriasis severity in a study of 30 patients.

Multiple studies have demonstrated the efficacy of the excimer laser in the treatment of plaque psoriasis, but few have investigated its use for palmoplantar psoriasis. "Palmoplantar psoriasis is difficult to treat and often recalcitrant to traditional therapies such as corticosteroids. Since the excimer laser can selectively treat psoriatic plaque with higher fluences than is tolerated with traditional phototherapy, it could be a therapeutic modality for the thicker skin on the palms and soles," said Dr. David Goldberg, director of dermatologic laser research at Mount Sinai School of Medicine, New York.

Photo credit:  Courtesy Dr. David J. Goldberg

The 30 patients were aged 18-75 years, with mild to severe psoriasis on their hands and/or feet. All discontinued other treatments 4 weeks prior to starting the study. By study design, patients could receive up to 16 biweekly laser treatments over the course of 3 months with an excimer laser (PHAROS EX-308, RA Medical Systems). Fluences ranged from 400-600 mJ/cm² depending on disease severity. Short pulses were delivered with a flexible handpiece, with a maximal output of 15 mJ/pulse (J. Cosmet. Laser Ther. 2011;13:47-9).

Each treatment was tailored to the individual patient’s response from the previous session. If there was no response or minimal erythema, the dose was increased by 30%. If there was moderate erythema, the dose was increased by 20%, and if significant erythema, the dose was increased by 10% until the patient could not tolerate further increases. For severe reactions or blistering, the dose was decreased by 20%. The number of sessions ranged from 7 to 14, with a mean of 11.

All of the subjects had some improvement by week 5, as measured by the Psoriasis Area and Severity Index (PASI). At the end of the treatments, all showed 50%-100% reductions in scaling, erythema, and flattened plaques. No patient had a relapse detected at the 3-month follow-up, but two-thirds of the patients had relapses by 6 months. There was no evidence of persistent pigmentary changes or scarring. Periodic retreatments will be required, Dr. Goldberg said.

"Although no treatment can be expected to ‘cure’ palmoplantar psoriasis, our data do support the use of the excimer laser to treat patients with hand and foot psoriasis. The excimer laser should be strongly considered for patients with palmoplantar psoriasis unresponsive to other treatments," he concluded.

The excimer laser study was provided on loan by the manufacturer during the course of the study. Dr. Goldberg stated that he had no other disclosures.

GRAPEVINE, TEX. – The 308-nm excimer laser significantly reduced palmoplantar psoriasis severity in a study of 30 patients.

Multiple studies have demonstrated the efficacy of the excimer laser in the treatment of plaque psoriasis, but few have investigated its use for palmoplantar psoriasis. "Palmoplantar psoriasis is difficult to treat and often recalcitrant to traditional therapies such as corticosteroids. Since the excimer laser can selectively treat psoriatic plaque with higher fluences than is tolerated with traditional phototherapy, it could be a therapeutic modality for the thicker skin on the palms and soles," said Dr. David Goldberg, director of dermatologic laser research at Mount Sinai School of Medicine, New York.

Photo credit:  Courtesy Dr. David J. Goldberg

The 30 patients were aged 18-75 years, with mild to severe psoriasis on their hands and/or feet. All discontinued other treatments 4 weeks prior to starting the study. By study design, patients could receive up to 16 biweekly laser treatments over the course of 3 months with an excimer laser (PHAROS EX-308, RA Medical Systems). Fluences ranged from 400-600 mJ/cm² depending on disease severity. Short pulses were delivered with a flexible handpiece, with a maximal output of 15 mJ/pulse (J. Cosmet. Laser Ther. 2011;13:47-9).

Each treatment was tailored to the individual patient’s response from the previous session. If there was no response or minimal erythema, the dose was increased by 30%. If there was moderate erythema, the dose was increased by 20%, and if significant erythema, the dose was increased by 10% until the patient could not tolerate further increases. For severe reactions or blistering, the dose was decreased by 20%. The number of sessions ranged from 7 to 14, with a mean of 11.

All of the subjects had some improvement by week 5, as measured by the Psoriasis Area and Severity Index (PASI). At the end of the treatments, all showed 50%-100% reductions in scaling, erythema, and flattened plaques. No patient had a relapse detected at the 3-month follow-up, but two-thirds of the patients had relapses by 6 months. There was no evidence of persistent pigmentary changes or scarring. Periodic retreatments will be required, Dr. Goldberg said.

"Although no treatment can be expected to ‘cure’ palmoplantar psoriasis, our data do support the use of the excimer laser to treat patients with hand and foot psoriasis. The excimer laser should be strongly considered for patients with palmoplantar psoriasis unresponsive to other treatments," he concluded.

The excimer laser study was provided on loan by the manufacturer during the course of the study. Dr. Goldberg stated that he had no other disclosures.

GRAPEVINE, TEX. – The 308-nm excimer laser significantly reduced palmoplantar psoriasis severity in a study of 30 patients.

Multiple studies have demonstrated the efficacy of the excimer laser in the treatment of plaque psoriasis, but few have investigated its use for palmoplantar psoriasis. "Palmoplantar psoriasis is difficult to treat and often recalcitrant to traditional therapies such as corticosteroids. Since the excimer laser can selectively treat psoriatic plaque with higher fluences than is tolerated with traditional phototherapy, it could be a therapeutic modality for the thicker skin on the palms and soles," said Dr. David Goldberg, director of dermatologic laser research at Mount Sinai School of Medicine, New York.

Photo credit:  Courtesy Dr. David J. Goldberg

The 30 patients were aged 18-75 years, with mild to severe psoriasis on their hands and/or feet. All discontinued other treatments 4 weeks prior to starting the study. By study design, patients could receive up to 16 biweekly laser treatments over the course of 3 months with an excimer laser (PHAROS EX-308, RA Medical Systems). Fluences ranged from 400-600 mJ/cm² depending on disease severity. Short pulses were delivered with a flexible handpiece, with a maximal output of 15 mJ/pulse (J. Cosmet. Laser Ther. 2011;13:47-9).

Each treatment was tailored to the individual patient’s response from the previous session. If there was no response or minimal erythema, the dose was increased by 30%. If there was moderate erythema, the dose was increased by 20%, and if significant erythema, the dose was increased by 10% until the patient could not tolerate further increases. For severe reactions or blistering, the dose was decreased by 20%. The number of sessions ranged from 7 to 14, with a mean of 11.

All of the subjects had some improvement by week 5, as measured by the Psoriasis Area and Severity Index (PASI). At the end of the treatments, all showed 50%-100% reductions in scaling, erythema, and flattened plaques. No patient had a relapse detected at the 3-month follow-up, but two-thirds of the patients had relapses by 6 months. There was no evidence of persistent pigmentary changes or scarring. Periodic retreatments will be required, Dr. Goldberg said.

"Although no treatment can be expected to ‘cure’ palmoplantar psoriasis, our data do support the use of the excimer laser to treat patients with hand and foot psoriasis. The excimer laser should be strongly considered for patients with palmoplantar psoriasis unresponsive to other treatments," he concluded.

The excimer laser study was provided on loan by the manufacturer during the course of the study. Dr. Goldberg stated that he had no other disclosures.