Psoriasis Collection

Miami — Etanercept therapy in children and adolescents with moderate to severe plaque psoriasis remained safe, well tolerated, and efficacious in the first 96 weeks of a 5-year open-label extension study, Dr. Richard Langley reported at the annual meeting of the American Academy of Dermatology.

The multicenter study, designed to evaluate long-term safety and efficacy of the immunosuppressant drug in the pediatric population, followed an initial 48-week randomized controlled trial reported in 2008 (N. Engl. J. Med. 2008;358:241-51). Read our story here.

Of 211 patients aged 4-17 years included in the initial trial, 182 (86%) completed that trial or achieved Psoriasis Area Severity Index (PASI) of 50 or better on or after week 12 with no adverse events, and thus were eligible and agreed to participate in the extension study. Of these, most (80%) reported at least one adverse event by week 96 of the extension study, but only three reported a total of five serious adverse events, none of which were infectious or deemed attributable to etanercept, Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University, Halifax, N.S., said during a poster discussion session.

The most common adverse events were upper respiratory tract infections in 25% of patients, nasopharyngitis in 17%, streptococcal pharyngitis in 13%, headache in 12%, and sinusitis in 11%. Serious adverse events were anxiety in one patient, intestinal obstruction in one patient, and abdominal pain, dehydration, and elective abortion all in one patient, Dr. Langley said, stressing that no opportunistic infections or malignancies occurred, which is particularly important to consider when evaluating the safety of an immunosuppressive agent.

Only two patients in the extension phase withdrew due to adverse events, and neither of these (Crohn’s disease in one, and sinusitis in one) were considered to be due to etanercept. Other patients did withdraw, however, most often due to consent withdrawal (19 patients) and loss to follow-up (14 patients); 140 patients completed 96 weeks of the extension study, and most (89%) of these achieved PASI of 50 or better (relative to baseline in the initial 48-week trial), including 30% who achieved PASI of 90 or better.

The mean PASI improvement was about 70%, and static Physician Global Assessment scores of 0 or 1 (clear or almost clear) were achieved in 47% of patients.

Treatment in both the initial and extension phases of the trial involved once-weekly subcutaneous injection of 0.8 mg/kg of etanercept, with a maximum dose of 50 mg/kg. Patients were also allowed to use standard topical treatments.

The conclusion at this stage of the trial is that etanercept is acceptably safe in this population at 96 weeks, Dr. Langley said, adding that this is the longest extension in a randomized controlled trial of patients receiving etanercept. No new adverse events or serious adverse events were seen, compared with the initial research.

“We believe this supports the continued study [of etanercept] and we will continue to follow these patients up to 5 years for infections and major adverse events,” he said.

Dr. Langley disclosed that he was an adviser and investigator for Amgen, and he has received grants and honoraria from Amgen. This trial was funded by Immunex Corp., a wholly-owned subsidiary of Amgen. Amgen and Wyeth Pharmaceuticals Inc. (now a part of Pfizer) together market Enbrel (etanercept).

Miami — Etanercept therapy in children and adolescents with moderate to severe plaque psoriasis remained safe, well tolerated, and efficacious in the first 96 weeks of a 5-year open-label extension study, Dr. Richard Langley reported at the annual meeting of the American Academy of Dermatology.

The multicenter study, designed to evaluate long-term safety and efficacy of the immunosuppressant drug in the pediatric population, followed an initial 48-week randomized controlled trial reported in 2008 (N. Engl. J. Med. 2008;358:241-51). Read our story here.

Of 211 patients aged 4-17 years included in the initial trial, 182 (86%) completed that trial or achieved Psoriasis Area Severity Index (PASI) of 50 or better on or after week 12 with no adverse events, and thus were eligible and agreed to participate in the extension study. Of these, most (80%) reported at least one adverse event by week 96 of the extension study, but only three reported a total of five serious adverse events, none of which were infectious or deemed attributable to etanercept, Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University, Halifax, N.S., said during a poster discussion session.

The most common adverse events were upper respiratory tract infections in 25% of patients, nasopharyngitis in 17%, streptococcal pharyngitis in 13%, headache in 12%, and sinusitis in 11%. Serious adverse events were anxiety in one patient, intestinal obstruction in one patient, and abdominal pain, dehydration, and elective abortion all in one patient, Dr. Langley said, stressing that no opportunistic infections or malignancies occurred, which is particularly important to consider when evaluating the safety of an immunosuppressive agent.

Only two patients in the extension phase withdrew due to adverse events, and neither of these (Crohn’s disease in one, and sinusitis in one) were considered to be due to etanercept. Other patients did withdraw, however, most often due to consent withdrawal (19 patients) and loss to follow-up (14 patients); 140 patients completed 96 weeks of the extension study, and most (89%) of these achieved PASI of 50 or better (relative to baseline in the initial 48-week trial), including 30% who achieved PASI of 90 or better.

The mean PASI improvement was about 70%, and static Physician Global Assessment scores of 0 or 1 (clear or almost clear) were achieved in 47% of patients.

Treatment in both the initial and extension phases of the trial involved once-weekly subcutaneous injection of 0.8 mg/kg of etanercept, with a maximum dose of 50 mg/kg. Patients were also allowed to use standard topical treatments.

The conclusion at this stage of the trial is that etanercept is acceptably safe in this population at 96 weeks, Dr. Langley said, adding that this is the longest extension in a randomized controlled trial of patients receiving etanercept. No new adverse events or serious adverse events were seen, compared with the initial research.

“We believe this supports the continued study [of etanercept] and we will continue to follow these patients up to 5 years for infections and major adverse events,” he said.

Dr. Langley disclosed that he was an adviser and investigator for Amgen, and he has received grants and honoraria from Amgen. This trial was funded by Immunex Corp., a wholly-owned subsidiary of Amgen. Amgen and Wyeth Pharmaceuticals Inc. (now a part of Pfizer) together market Enbrel (etanercept).

Miami — Etanercept therapy in children and adolescents with moderate to severe plaque psoriasis remained safe, well tolerated, and efficacious in the first 96 weeks of a 5-year open-label extension study, Dr. Richard Langley reported at the annual meeting of the American Academy of Dermatology.

The multicenter study, designed to evaluate long-term safety and efficacy of the immunosuppressant drug in the pediatric population, followed an initial 48-week randomized controlled trial reported in 2008 (N. Engl. J. Med. 2008;358:241-51). Read our story here.

Of 211 patients aged 4-17 years included in the initial trial, 182 (86%) completed that trial or achieved Psoriasis Area Severity Index (PASI) of 50 or better on or after week 12 with no adverse events, and thus were eligible and agreed to participate in the extension study. Of these, most (80%) reported at least one adverse event by week 96 of the extension study, but only three reported a total of five serious adverse events, none of which were infectious or deemed attributable to etanercept, Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University, Halifax, N.S., said during a poster discussion session.

The most common adverse events were upper respiratory tract infections in 25% of patients, nasopharyngitis in 17%, streptococcal pharyngitis in 13%, headache in 12%, and sinusitis in 11%. Serious adverse events were anxiety in one patient, intestinal obstruction in one patient, and abdominal pain, dehydration, and elective abortion all in one patient, Dr. Langley said, stressing that no opportunistic infections or malignancies occurred, which is particularly important to consider when evaluating the safety of an immunosuppressive agent.

Only two patients in the extension phase withdrew due to adverse events, and neither of these (Crohn’s disease in one, and sinusitis in one) were considered to be due to etanercept. Other patients did withdraw, however, most often due to consent withdrawal (19 patients) and loss to follow-up (14 patients); 140 patients completed 96 weeks of the extension study, and most (89%) of these achieved PASI of 50 or better (relative to baseline in the initial 48-week trial), including 30% who achieved PASI of 90 or better.

The mean PASI improvement was about 70%, and static Physician Global Assessment scores of 0 or 1 (clear or almost clear) were achieved in 47% of patients.

Treatment in both the initial and extension phases of the trial involved once-weekly subcutaneous injection of 0.8 mg/kg of etanercept, with a maximum dose of 50 mg/kg. Patients were also allowed to use standard topical treatments.

The conclusion at this stage of the trial is that etanercept is acceptably safe in this population at 96 weeks, Dr. Langley said, adding that this is the longest extension in a randomized controlled trial of patients receiving etanercept. No new adverse events or serious adverse events were seen, compared with the initial research.

“We believe this supports the continued study [of etanercept] and we will continue to follow these patients up to 5 years for infections and major adverse events,” he said.

Dr. Langley disclosed that he was an adviser and investigator for Amgen, and he has received grants and honoraria from Amgen. This trial was funded by Immunex Corp., a wholly-owned subsidiary of Amgen. Amgen and Wyeth Pharmaceuticals Inc. (now a part of Pfizer) together market Enbrel (etanercept).

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s genetic and immunologic profile.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s genetic and immunologic profile.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s genetic and immunologic profile.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general population. Numerous studies have evaluated the increased prevalence of comorbid diseases and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease, smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis, with its comorbidities, must be approached in a multidisciplinary manner to effectively and comprehensively understand, manage, and treat those with this complex disorder.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general population. Numerous studies have evaluated the increased prevalence of comorbid diseases and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease, smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis, with its comorbidities, must be approached in a multidisciplinary manner to effectively and comprehensively understand, manage, and treat those with this complex disorder.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general population. Numerous studies have evaluated the increased prevalence of comorbid diseases and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease, smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis, with its comorbidities, must be approached in a multidisciplinary manner to effectively and comprehensively understand, manage, and treat those with this complex disorder.

*For a PDF of the full article, click on the link to the left of this introduction.

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disease that is not uncommon in children and adolescents. While exact prevalence rates of pediatric psoriasis have not been determined, 30% to 40% of adults with psoriasis report onset of their signs and symptoms before age 16.1-4 Although the diagnosis of pediatric psoriasis remains predominantly clinical, its presentation varies in clinical course, distribution, and morphology. The management of psoriasis in children ranges from topical medications for mild and moderate disease to the use of systemic immunomodulatory agents for more severe disease. None of the systemic medications, including methotrexate, cyclosporine, and biological agents, such as etanercept, infliximab, adalimumab, and ustekinumab have specific indication by the United States Food and Drug Administration (FDA) for pediatric psoriasis. The pediatric dermatologic literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding adult literature. Subsequently, experts rely on unpublished clinical experience and studies of these systemic medications for other pediatric conditions, such as those published in the rheumatologic, transplant, oncological, and gastroenterologic literature. In this article, we discuss the systemic treatment options for pediatric  psoriasis, including drug mechanism of action and associated risks and benefits of treatment, to aid dermatologists in treating psoriasis in this special population.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disease that is not uncommon in children and adolescents. While exact prevalence rates of pediatric psoriasis have not been determined, 30% to 40% of adults with psoriasis report onset of their signs and symptoms before age 16.1-4 Although the diagnosis of pediatric psoriasis remains predominantly clinical, its presentation varies in clinical course, distribution, and morphology. The management of psoriasis in children ranges from topical medications for mild and moderate disease to the use of systemic immunomodulatory agents for more severe disease. None of the systemic medications, including methotrexate, cyclosporine, and biological agents, such as etanercept, infliximab, adalimumab, and ustekinumab have specific indication by the United States Food and Drug Administration (FDA) for pediatric psoriasis. The pediatric dermatologic literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding adult literature. Subsequently, experts rely on unpublished clinical experience and studies of these systemic medications for other pediatric conditions, such as those published in the rheumatologic, transplant, oncological, and gastroenterologic literature. In this article, we discuss the systemic treatment options for pediatric  psoriasis, including drug mechanism of action and associated risks and benefits of treatment, to aid dermatologists in treating psoriasis in this special population.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disease that is not uncommon in children and adolescents. While exact prevalence rates of pediatric psoriasis have not been determined, 30% to 40% of adults with psoriasis report onset of their signs and symptoms before age 16.1-4 Although the diagnosis of pediatric psoriasis remains predominantly clinical, its presentation varies in clinical course, distribution, and morphology. The management of psoriasis in children ranges from topical medications for mild and moderate disease to the use of systemic immunomodulatory agents for more severe disease. None of the systemic medications, including methotrexate, cyclosporine, and biological agents, such as etanercept, infliximab, adalimumab, and ustekinumab have specific indication by the United States Food and Drug Administration (FDA) for pediatric psoriasis. The pediatric dermatologic literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding adult literature. Subsequently, experts rely on unpublished clinical experience and studies of these systemic medications for other pediatric conditions, such as those published in the rheumatologic, transplant, oncological, and gastroenterologic literature. In this article, we discuss the systemic treatment options for pediatric  psoriasis, including drug mechanism of action and associated risks and benefits of treatment, to aid dermatologists in treating psoriasis in this special population.

*For a PDF of the full article, click on the link to the left of this introduction.

The development of biologics has dramatically altered the treatment of moderate-to-severe psoriasis while also introducing new standards of care for therapeutic monitoring. Currently, the biologics approved by the US Food and Drug Administration are divided into 3 classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors. Although the US Food and Drug Administration has established recommendations for pre- and peri-treatment screening evaluations, much of the evidence comes from clinical trials evaluating the short-term safety and efficacy of each medication, rather than longterm data, or studies that summarize either the appropriateness or feasibility of screening. Instead of following a blanket algorithm, providers must understand the evidence as it relates to each medication to determine which tests are appropriate for any specific patient. This chapter summarizes the current body of evidence and recommends a practical approach for monitoring psoriasis patients who are receiving biologic therapies.

*For a PDF of the full article, click on the link to the left of this introduction.

The development of biologics has dramatically altered the treatment of moderate-to-severe psoriasis while also introducing new standards of care for therapeutic monitoring. Currently, the biologics approved by the US Food and Drug Administration are divided into 3 classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors. Although the US Food and Drug Administration has established recommendations for pre- and peri-treatment screening evaluations, much of the evidence comes from clinical trials evaluating the short-term safety and efficacy of each medication, rather than longterm data, or studies that summarize either the appropriateness or feasibility of screening. Instead of following a blanket algorithm, providers must understand the evidence as it relates to each medication to determine which tests are appropriate for any specific patient. This chapter summarizes the current body of evidence and recommends a practical approach for monitoring psoriasis patients who are receiving biologic therapies.

*For a PDF of the full article, click on the link to the left of this introduction.

The development of biologics has dramatically altered the treatment of moderate-to-severe psoriasis while also introducing new standards of care for therapeutic monitoring. Currently, the biologics approved by the US Food and Drug Administration are divided into 3 classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors. Although the US Food and Drug Administration has established recommendations for pre- and peri-treatment screening evaluations, much of the evidence comes from clinical trials evaluating the short-term safety and efficacy of each medication, rather than longterm data, or studies that summarize either the appropriateness or feasibility of screening. Instead of following a blanket algorithm, providers must understand the evidence as it relates to each medication to determine which tests are appropriate for any specific patient. This chapter summarizes the current body of evidence and recommends a practical approach for monitoring psoriasis patients who are receiving biologic therapies.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is one of the most common systemic inflammatory diseases and affects the quality of life of the affected persons profoundly. Further knowledge of the pathogenesis and new biotechnological techniques have made it possible to develop new targeted therapies, such as antibodies against tumor necrosis factor (TNF)-alpha. Today, 3 TNF inhibitors, infliximab, adalimumab, and Etanercept, have been approved for the treatment of psoriasis arthritis, psoriasis, and other indications like Crohn’s disease, depending on the distinct substance by the European Medicines Agency. Golimumab was approved in September 2009 for the use in psoriasis arthritis, respectively. These substances have added new effective treatment options to the therapeutic armamentarium of psoriasis. To use these new treatments for the best of our patients, it is important to know the correct application, the advantages, as well as contraindications or possible adverse effects of the substances. This article provides an update on the TNF-alpha inhibitors with emphasis on practical daily use. Most data are on the basis of high-quality studies and official guidelines, but if necessary, data from recent publications or clinical expertise have been added. In summary, with TNF inhibitors we have gained effective new treatment options showing a favorable safety profile when paying attention to safety aspects before and during therapy (screening, monitoring).

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is one of the most common systemic inflammatory diseases and affects the quality of life of the affected persons profoundly. Further knowledge of the pathogenesis and new biotechnological techniques have made it possible to develop new targeted therapies, such as antibodies against tumor necrosis factor (TNF)-alpha. Today, 3 TNF inhibitors, infliximab, adalimumab, and Etanercept, have been approved for the treatment of psoriasis arthritis, psoriasis, and other indications like Crohn’s disease, depending on the distinct substance by the European Medicines Agency. Golimumab was approved in September 2009 for the use in psoriasis arthritis, respectively. These substances have added new effective treatment options to the therapeutic armamentarium of psoriasis. To use these new treatments for the best of our patients, it is important to know the correct application, the advantages, as well as contraindications or possible adverse effects of the substances. This article provides an update on the TNF-alpha inhibitors with emphasis on practical daily use. Most data are on the basis of high-quality studies and official guidelines, but if necessary, data from recent publications or clinical expertise have been added. In summary, with TNF inhibitors we have gained effective new treatment options showing a favorable safety profile when paying attention to safety aspects before and during therapy (screening, monitoring).

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is one of the most common systemic inflammatory diseases and affects the quality of life of the affected persons profoundly. Further knowledge of the pathogenesis and new biotechnological techniques have made it possible to develop new targeted therapies, such as antibodies against tumor necrosis factor (TNF)-alpha. Today, 3 TNF inhibitors, infliximab, adalimumab, and Etanercept, have been approved for the treatment of psoriasis arthritis, psoriasis, and other indications like Crohn’s disease, depending on the distinct substance by the European Medicines Agency. Golimumab was approved in September 2009 for the use in psoriasis arthritis, respectively. These substances have added new effective treatment options to the therapeutic armamentarium of psoriasis. To use these new treatments for the best of our patients, it is important to know the correct application, the advantages, as well as contraindications or possible adverse effects of the substances. This article provides an update on the TNF-alpha inhibitors with emphasis on practical daily use. Most data are on the basis of high-quality studies and official guidelines, but if necessary, data from recent publications or clinical expertise have been added. In summary, with TNF inhibitors we have gained effective new treatment options showing a favorable safety profile when paying attention to safety aspects before and during therapy (screening, monitoring).

*For a PDF of the full article, click on the link to the left of this introduction.

The choice of therapeutic agents for patients with moderate-to-severe psoriasis has expanded significantly in the past decade. With new understanding of the immunologic basis of psoriasis, multiple new potential targets for therapy have been identified. It is likely that a series of new medications to focus on the newly identified pathways is on the horizon. The first pathway targeted by new medications focuses on the p40 subunit that is shared by interleukin (IL)-12 and IL-23. Two human anti-p40 antibodies have been used therapeutically in psoriasis to date, ustekinumab (CNTO-1275, Stelara, Centocor, Horsham, PA) and briakinumab (ABT-874, Abbott, Abbott Park, IL). Ustekinumab was recently approved by the United States Food and Drug Administration, making it the first medication approved in the United States to work by this pathway while briakinumab is currently in phase III clinical trials. 

*For a PDF of the full article, click on the link to the left of this introduction.

The choice of therapeutic agents for patients with moderate-to-severe psoriasis has expanded significantly in the past decade. With new understanding of the immunologic basis of psoriasis, multiple new potential targets for therapy have been identified. It is likely that a series of new medications to focus on the newly identified pathways is on the horizon. The first pathway targeted by new medications focuses on the p40 subunit that is shared by interleukin (IL)-12 and IL-23. Two human anti-p40 antibodies have been used therapeutically in psoriasis to date, ustekinumab (CNTO-1275, Stelara, Centocor, Horsham, PA) and briakinumab (ABT-874, Abbott, Abbott Park, IL). Ustekinumab was recently approved by the United States Food and Drug Administration, making it the first medication approved in the United States to work by this pathway while briakinumab is currently in phase III clinical trials. 

*For a PDF of the full article, click on the link to the left of this introduction.

The choice of therapeutic agents for patients with moderate-to-severe psoriasis has expanded significantly in the past decade. With new understanding of the immunologic basis of psoriasis, multiple new potential targets for therapy have been identified. It is likely that a series of new medications to focus on the newly identified pathways is on the horizon. The first pathway targeted by new medications focuses on the p40 subunit that is shared by interleukin (IL)-12 and IL-23. Two human anti-p40 antibodies have been used therapeutically in psoriasis to date, ustekinumab (CNTO-1275, Stelara, Centocor, Horsham, PA) and briakinumab (ABT-874, Abbott, Abbott Park, IL). Ustekinumab was recently approved by the United States Food and Drug Administration, making it the first medication approved in the United States to work by this pathway while briakinumab is currently in phase III clinical trials. 

*For a PDF of the full article, click on the link to the left of this introduction.

Alefacept was the first biological agent approved by the Food and Drug Administration for the treatment of psoriasis. Alefacept was initially approved as an intravenous and intramuscular medication. It is available only as an intramuscular medication. Alefacept is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 linked to the Fc (hinge, CH2, CH3 domains) portion of human immunoglobulin G. Alefacept selectively blocks the leukocyte function antigen-3:CD2 costimulatory pathway, which is important in the reactivation of memory effector T cells. Alefacept also reduces the number of memory effector T cells in the blood and in the skin.

*For a PDF of the full article, click on the link to the left of this introduction.

Alefacept was the first biological agent approved by the Food and Drug Administration for the treatment of psoriasis. Alefacept was initially approved as an intravenous and intramuscular medication. It is available only as an intramuscular medication. Alefacept is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 linked to the Fc (hinge, CH2, CH3 domains) portion of human immunoglobulin G. Alefacept selectively blocks the leukocyte function antigen-3:CD2 costimulatory pathway, which is important in the reactivation of memory effector T cells. Alefacept also reduces the number of memory effector T cells in the blood and in the skin.

*For a PDF of the full article, click on the link to the left of this introduction.

Alefacept was the first biological agent approved by the Food and Drug Administration for the treatment of psoriasis. Alefacept was initially approved as an intravenous and intramuscular medication. It is available only as an intramuscular medication. Alefacept is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 linked to the Fc (hinge, CH2, CH3 domains) portion of human immunoglobulin G. Alefacept selectively blocks the leukocyte function antigen-3:CD2 costimulatory pathway, which is important in the reactivation of memory effector T cells. Alefacept also reduces the number of memory effector T cells in the blood and in the skin.

*For a PDF of the full article, click on the link to the left of this introduction.