Psoriasis

SAN FRANCISCO — A novel over-the-counter topical leave-on coal tar solution achieved significantly greater and more persistent improvement compared to prescription calcipotriol cream in patients with moderate chronic plaque psoriasis in a randomized trial.

Equally noteworthy was the participants' rating of the topical coal tar solution as comparable to calcipotriol cream in terms of cosmetic acceptability, convenience, and aesthetics, Dr. Maria Beatrice Alora-Palli noted at the annual meeting of the American Academy of Dermatology.

For centuries topical coal tar has been recognized as safe and reliably effective for controlling the symptoms of plaque psoriasis. In recent decades, however, topical coal tar in its traditional form has come to be viewed as an unacceptably foul therapy: messy, inconvenient, smelly, and staining.

The novel coal tar solution, marketed as Psorent by NeoStrata Co., is a fast-drying product engineered to circumvent those shortcomings. It contains 15% liquor carbonis distillate, equivalent to 2.3% coal tar.

Dr. Alora-Palli of Massachusetts General Hospital, Boston, presented an 18-week investigator-blinded randomized trial involving 55 adults with chronic plaque psoriasis over 3%-15% of their body surface area. They applied either the topical coal tar solution or calcipotriol cream 0.005% (Dovonex) twice daily for 12 weeks, followed by a 6-week follow-up assessment of regression of improvement, during which the coal tar solution clearly outperformed the calcipotriol cream.

Twelve weeks of therapy resulted in a Psoriasis Area and Severity Index (PASI) 50 in 67% of the coal tar group, compared with 36% of those on calcipotriol cream. A PASI 75 was attained by 37% of the coal tar group and no one in the calcipotriol cream study arm. Moreover, PASI scores improved by a mean of 58% in the coal tar group, compared with 37% in the calcipotriol cream group.

Physician Global Assessment scores improved in the coal tar group from a mean of 3.1 at baseline to 1.3 at week 12 and 1.6 at week 18. This was significantly better than the scores in the calcipotriol group, which went from 2.9 at baseline to 2.0 at 12 weeks and then rebounded significantly to 2.6 at 18 weeks, Dr. Alora-Pilli continued.

During the first 6 weeks after completing 12 weeks of treatment, the coal tar solution group reported significantly better control of itch, redness, scaling and flaking, and skin texture changes than did the calcipotriol cream group.

A total of 70% of the coal tar group reported having good control of the overall discomfort and appearance of their psoriatic lesions, compared with about half as many patients in the calcipotriol group.

Psorent is supplied in 100-mL bottles topped with a dab-on applicator that enables patients to avoid touching the medication or their skin lesions.

Dr. Alora-Pilli received a research grant to conduct the NeoStrata-funded study.

SAN FRANCISCO — A novel over-the-counter topical leave-on coal tar solution achieved significantly greater and more persistent improvement compared to prescription calcipotriol cream in patients with moderate chronic plaque psoriasis in a randomized trial.

Equally noteworthy was the participants' rating of the topical coal tar solution as comparable to calcipotriol cream in terms of cosmetic acceptability, convenience, and aesthetics, Dr. Maria Beatrice Alora-Palli noted at the annual meeting of the American Academy of Dermatology.

For centuries topical coal tar has been recognized as safe and reliably effective for controlling the symptoms of plaque psoriasis. In recent decades, however, topical coal tar in its traditional form has come to be viewed as an unacceptably foul therapy: messy, inconvenient, smelly, and staining.

The novel coal tar solution, marketed as Psorent by NeoStrata Co., is a fast-drying product engineered to circumvent those shortcomings. It contains 15% liquor carbonis distillate, equivalent to 2.3% coal tar.

Dr. Alora-Palli of Massachusetts General Hospital, Boston, presented an 18-week investigator-blinded randomized trial involving 55 adults with chronic plaque psoriasis over 3%-15% of their body surface area. They applied either the topical coal tar solution or calcipotriol cream 0.005% (Dovonex) twice daily for 12 weeks, followed by a 6-week follow-up assessment of regression of improvement, during which the coal tar solution clearly outperformed the calcipotriol cream.

Twelve weeks of therapy resulted in a Psoriasis Area and Severity Index (PASI) 50 in 67% of the coal tar group, compared with 36% of those on calcipotriol cream. A PASI 75 was attained by 37% of the coal tar group and no one in the calcipotriol cream study arm. Moreover, PASI scores improved by a mean of 58% in the coal tar group, compared with 37% in the calcipotriol cream group.

Physician Global Assessment scores improved in the coal tar group from a mean of 3.1 at baseline to 1.3 at week 12 and 1.6 at week 18. This was significantly better than the scores in the calcipotriol group, which went from 2.9 at baseline to 2.0 at 12 weeks and then rebounded significantly to 2.6 at 18 weeks, Dr. Alora-Pilli continued.

During the first 6 weeks after completing 12 weeks of treatment, the coal tar solution group reported significantly better control of itch, redness, scaling and flaking, and skin texture changes than did the calcipotriol cream group.

A total of 70% of the coal tar group reported having good control of the overall discomfort and appearance of their psoriatic lesions, compared with about half as many patients in the calcipotriol group.

Psorent is supplied in 100-mL bottles topped with a dab-on applicator that enables patients to avoid touching the medication or their skin lesions.

Dr. Alora-Pilli received a research grant to conduct the NeoStrata-funded study.

SAN FRANCISCO — A novel over-the-counter topical leave-on coal tar solution achieved significantly greater and more persistent improvement compared to prescription calcipotriol cream in patients with moderate chronic plaque psoriasis in a randomized trial.

Equally noteworthy was the participants' rating of the topical coal tar solution as comparable to calcipotriol cream in terms of cosmetic acceptability, convenience, and aesthetics, Dr. Maria Beatrice Alora-Palli noted at the annual meeting of the American Academy of Dermatology.

For centuries topical coal tar has been recognized as safe and reliably effective for controlling the symptoms of plaque psoriasis. In recent decades, however, topical coal tar in its traditional form has come to be viewed as an unacceptably foul therapy: messy, inconvenient, smelly, and staining.

The novel coal tar solution, marketed as Psorent by NeoStrata Co., is a fast-drying product engineered to circumvent those shortcomings. It contains 15% liquor carbonis distillate, equivalent to 2.3% coal tar.

Dr. Alora-Palli of Massachusetts General Hospital, Boston, presented an 18-week investigator-blinded randomized trial involving 55 adults with chronic plaque psoriasis over 3%-15% of their body surface area. They applied either the topical coal tar solution or calcipotriol cream 0.005% (Dovonex) twice daily for 12 weeks, followed by a 6-week follow-up assessment of regression of improvement, during which the coal tar solution clearly outperformed the calcipotriol cream.

Twelve weeks of therapy resulted in a Psoriasis Area and Severity Index (PASI) 50 in 67% of the coal tar group, compared with 36% of those on calcipotriol cream. A PASI 75 was attained by 37% of the coal tar group and no one in the calcipotriol cream study arm. Moreover, PASI scores improved by a mean of 58% in the coal tar group, compared with 37% in the calcipotriol cream group.

Physician Global Assessment scores improved in the coal tar group from a mean of 3.1 at baseline to 1.3 at week 12 and 1.6 at week 18. This was significantly better than the scores in the calcipotriol group, which went from 2.9 at baseline to 2.0 at 12 weeks and then rebounded significantly to 2.6 at 18 weeks, Dr. Alora-Pilli continued.

During the first 6 weeks after completing 12 weeks of treatment, the coal tar solution group reported significantly better control of itch, redness, scaling and flaking, and skin texture changes than did the calcipotriol cream group.

A total of 70% of the coal tar group reported having good control of the overall discomfort and appearance of their psoriatic lesions, compared with about half as many patients in the calcipotriol group.

Psorent is supplied in 100-mL bottles topped with a dab-on applicator that enables patients to avoid touching the medication or their skin lesions.

Dr. Alora-Pilli received a research grant to conduct the NeoStrata-funded study.

David de Berker, BA, MBBS, MRCP

Nail involvement is common at some point in the life of the patient with psoriasis. Simple hand care, keeping nails cut short and avoiding nail trauma, will all help in management. Medical interventions include topical therapies used for psoriasis at other body sites, directed at the location of the disease within the nail unit. Individual digits may require focused intensive treatment, such as steroid injections. Systemic therapy for psoriatic nail disease can be justified when the disease presents in tandem with severe skin disease or where function and quality of life are sufficiently diminished by nail involvement. Biological therapy usually is indicated for widespread psoriasis, but studies show that therapy directed at nail symptoms can be effective in the treatment of coincident nail disease.

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

David de Berker, BA, MBBS, MRCP

Nail involvement is common at some point in the life of the patient with psoriasis. Simple hand care, keeping nails cut short and avoiding nail trauma, will all help in management. Medical interventions include topical therapies used for psoriasis at other body sites, directed at the location of the disease within the nail unit. Individual digits may require focused intensive treatment, such as steroid injections. Systemic therapy for psoriatic nail disease can be justified when the disease presents in tandem with severe skin disease or where function and quality of life are sufficiently diminished by nail involvement. Biological therapy usually is indicated for widespread psoriasis, but studies show that therapy directed at nail symptoms can be effective in the treatment of coincident nail disease.

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

David de Berker, BA, MBBS, MRCP

Nail involvement is common at some point in the life of the patient with psoriasis. Simple hand care, keeping nails cut short and avoiding nail trauma, will all help in management. Medical interventions include topical therapies used for psoriasis at other body sites, directed at the location of the disease within the nail unit. Individual digits may require focused intensive treatment, such as steroid injections. Systemic therapy for psoriatic nail disease can be justified when the disease presents in tandem with severe skin disease or where function and quality of life are sufficiently diminished by nail involvement. Biological therapy usually is indicated for widespread psoriasis, but studies show that therapy directed at nail symptoms can be effective in the treatment of coincident nail disease.

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

Most pediatric cases of psoriasis are mild and can be managed adequately with combinations of topical medicines, but some cannot, according to Dr. Kelly M. Cordoro.

“The true challenge exists in treating the subset of children who present with severe, rapidly evolving, and debilitating generalized plaque or pustular psoriasis and/or psoriatic arthropathy,” said Dr. Cordoro of the department of dermatology at the University of California, San Francisco.

The management of this subset of patients “requires immediate response with the utilization of systemic medications that are neither well studied nor [Food and Drug Administration] approved for this indication in children,” said Dr. Cordoro, who discussed such medications in a presentation at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

Targeted therapies that are aimed at specific components of the inflammatory cascade, such as anti-tumor necrosis factor agents, are widely used in adults with psoriasis and psoriatic arthritis.

Although none of the three TNF antagonists that have received FDA approval for adult psoriasis—etanercept, infliximab, and adalimumab—have been approved for pediatric psoriasis, off-label use of these agents has demonstrated some promise in children with severe disease, Dr. Cordoro said in an interview.

“Etanercept has the most significant published literature, and the fact that the drug has received FDA approval for use in children for other indications [ankylosing spondylitis and psoriatic arthropathy for children aged 2 years and older, and juvenile rheumatoid arthritis in children aged 4 years and older] substantiates recommendations for its use in the pediatric psoriasis population,” she said.

A recent, randomized controlled trial showed that etanercept can safely and effectively reduce disease severity in children and adolescents aged 4–17 years who have moderate to severe plaque psoriasis (N. Engl. J. Med. 2008;358:241–51).

Biologic agents have also been used in the treatment of children with generalized pustular psoriasis, a serious and rare form of the disease that can be fatal.

With respect to drug safety, “critical evaluation of the potential risk of the anti-TNF agents in children with psoriasis is difficult because of the small number of children treated and the short follow-up period,” Dr. Cordoro said.

Even so, “because the known side effect profiles of traditional systemic agents used for severe psoriasis in children [including methotrexate, cyclosporine, and acitretin] are unacceptable, the documented benefits of the TNF inhibitors in children affected by severe, debilitating psoriasis create a therapeutic niche for these agents,” she said.

Dr. Cordoro reported having no conflicts of interest with respect to her presentation.

SDEF and this newspaper are owned by Elsevier.

Off-label use of the three TNF antagonists has demonstrated some promise in children with severe disease. DR. CORDORO

Most pediatric cases of psoriasis are mild and can be managed adequately with combinations of topical medicines, but some cannot, according to Dr. Kelly M. Cordoro.

“The true challenge exists in treating the subset of children who present with severe, rapidly evolving, and debilitating generalized plaque or pustular psoriasis and/or psoriatic arthropathy,” said Dr. Cordoro of the department of dermatology at the University of California, San Francisco.

The management of this subset of patients “requires immediate response with the utilization of systemic medications that are neither well studied nor [Food and Drug Administration] approved for this indication in children,” said Dr. Cordoro, who discussed such medications in a presentation at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

Targeted therapies that are aimed at specific components of the inflammatory cascade, such as anti-tumor necrosis factor agents, are widely used in adults with psoriasis and psoriatic arthritis.

Although none of the three TNF antagonists that have received FDA approval for adult psoriasis—etanercept, infliximab, and adalimumab—have been approved for pediatric psoriasis, off-label use of these agents has demonstrated some promise in children with severe disease, Dr. Cordoro said in an interview.

“Etanercept has the most significant published literature, and the fact that the drug has received FDA approval for use in children for other indications [ankylosing spondylitis and psoriatic arthropathy for children aged 2 years and older, and juvenile rheumatoid arthritis in children aged 4 years and older] substantiates recommendations for its use in the pediatric psoriasis population,” she said.

A recent, randomized controlled trial showed that etanercept can safely and effectively reduce disease severity in children and adolescents aged 4–17 years who have moderate to severe plaque psoriasis (N. Engl. J. Med. 2008;358:241–51).

Biologic agents have also been used in the treatment of children with generalized pustular psoriasis, a serious and rare form of the disease that can be fatal.

With respect to drug safety, “critical evaluation of the potential risk of the anti-TNF agents in children with psoriasis is difficult because of the small number of children treated and the short follow-up period,” Dr. Cordoro said.

Even so, “because the known side effect profiles of traditional systemic agents used for severe psoriasis in children [including methotrexate, cyclosporine, and acitretin] are unacceptable, the documented benefits of the TNF inhibitors in children affected by severe, debilitating psoriasis create a therapeutic niche for these agents,” she said.

Dr. Cordoro reported having no conflicts of interest with respect to her presentation.

SDEF and this newspaper are owned by Elsevier.

Off-label use of the three TNF antagonists has demonstrated some promise in children with severe disease. DR. CORDORO

Most pediatric cases of psoriasis are mild and can be managed adequately with combinations of topical medicines, but some cannot, according to Dr. Kelly M. Cordoro.

“The true challenge exists in treating the subset of children who present with severe, rapidly evolving, and debilitating generalized plaque or pustular psoriasis and/or psoriatic arthropathy,” said Dr. Cordoro of the department of dermatology at the University of California, San Francisco.

The management of this subset of patients “requires immediate response with the utilization of systemic medications that are neither well studied nor [Food and Drug Administration] approved for this indication in children,” said Dr. Cordoro, who discussed such medications in a presentation at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

Targeted therapies that are aimed at specific components of the inflammatory cascade, such as anti-tumor necrosis factor agents, are widely used in adults with psoriasis and psoriatic arthritis.

Although none of the three TNF antagonists that have received FDA approval for adult psoriasis—etanercept, infliximab, and adalimumab—have been approved for pediatric psoriasis, off-label use of these agents has demonstrated some promise in children with severe disease, Dr. Cordoro said in an interview.

“Etanercept has the most significant published literature, and the fact that the drug has received FDA approval for use in children for other indications [ankylosing spondylitis and psoriatic arthropathy for children aged 2 years and older, and juvenile rheumatoid arthritis in children aged 4 years and older] substantiates recommendations for its use in the pediatric psoriasis population,” she said.

A recent, randomized controlled trial showed that etanercept can safely and effectively reduce disease severity in children and adolescents aged 4–17 years who have moderate to severe plaque psoriasis (N. Engl. J. Med. 2008;358:241–51).

Biologic agents have also been used in the treatment of children with generalized pustular psoriasis, a serious and rare form of the disease that can be fatal.

With respect to drug safety, “critical evaluation of the potential risk of the anti-TNF agents in children with psoriasis is difficult because of the small number of children treated and the short follow-up period,” Dr. Cordoro said.

Even so, “because the known side effect profiles of traditional systemic agents used for severe psoriasis in children [including methotrexate, cyclosporine, and acitretin] are unacceptable, the documented benefits of the TNF inhibitors in children affected by severe, debilitating psoriasis create a therapeutic niche for these agents,” she said.

Dr. Cordoro reported having no conflicts of interest with respect to her presentation.

SDEF and this newspaper are owned by Elsevier.

Off-label use of the three TNF antagonists has demonstrated some promise in children with severe disease. DR. CORDORO

Follow-on biologics legislation without a long period of data exclusivity for the original drug would significantly hinder future innovation, according to one economist.

Meanwhile, legislators' insistence that incentives for innovation be balanced with generics' promise of affordability means that a regulatory pathway for the drugs could remain uncharted in 2009.

Data exclusivity for follow-on biologics is the “period of time after [a biologic drug's] approval before a follow-on biologic can enter the market with an abbreviated filing” that relies on the original drug's safety and efficacy data, said Henry G. Grabowski, Ph.D., at a recent audioconference sponsored by Avalere Health LLC, a health care consultancy.

Because a “typical” new biologic drug might cost up to $1.2 billion in research and development, the “data exclusivity [period] acts as an insurance policy to ensure that there is adequate incentive” to produce the drugs in the first place, said Dr. Grabowski, a professor of economics and director of the program in pharmaceuticals and health economics at Duke University in Durham, N.C.

Ann Witt, a health care adviser to Rep. Henry Waxman (D-Calif.), who cosponsored the 1984 generic drugs legislation, disagreed with Dr. Grabowski's assessment. “Many of the arguments we heard here today were also made in 1984 by the then-manufacturers of small molecule drugs, who insisted that innovation would come to an end” with the advent of generics, she pointed out. Since then, “I have never heard anyone claim that that bill reduced innovation in the pharmaceutical industry,” she said.

The Food and Drug Administration's stance seems to side with Dr. Grabowski and the drugmakers. A Sept. 18, 2008, letter from the FDA's then-chief scientist, Dr. Frank M. Torti, states: “The Agency believes that sponsors that develop innovative biotechnology products should be eligible for a significant period of market and/or data exclusivity, independent from any patent protections that might be applicable to the product, to ensure continued innovation.”

Dr. Torti has since taken over as the FDA's acting commissioner.

The letter was addressed to the chairman of the House Subcommittee on Health, Rep. Frank Pallone Jr. (D-N.J.). The subcommittee is a division of the House Committee on Energy and Commerce, of which Rep. Waxman was recently appointed chairman. Ms. Witt said that legislation supporting a follow-on biologics pathway would be a high priority for the committee in 2009.

Follow-on biologics legislation without a long period of data exclusivity for the original drug would significantly hinder future innovation, according to one economist.

Meanwhile, legislators' insistence that incentives for innovation be balanced with generics' promise of affordability means that a regulatory pathway for the drugs could remain uncharted in 2009.

Data exclusivity for follow-on biologics is the “period of time after [a biologic drug's] approval before a follow-on biologic can enter the market with an abbreviated filing” that relies on the original drug's safety and efficacy data, said Henry G. Grabowski, Ph.D., at a recent audioconference sponsored by Avalere Health LLC, a health care consultancy.

Because a “typical” new biologic drug might cost up to $1.2 billion in research and development, the “data exclusivity [period] acts as an insurance policy to ensure that there is adequate incentive” to produce the drugs in the first place, said Dr. Grabowski, a professor of economics and director of the program in pharmaceuticals and health economics at Duke University in Durham, N.C.

Ann Witt, a health care adviser to Rep. Henry Waxman (D-Calif.), who cosponsored the 1984 generic drugs legislation, disagreed with Dr. Grabowski's assessment. “Many of the arguments we heard here today were also made in 1984 by the then-manufacturers of small molecule drugs, who insisted that innovation would come to an end” with the advent of generics, she pointed out. Since then, “I have never heard anyone claim that that bill reduced innovation in the pharmaceutical industry,” she said.

The Food and Drug Administration's stance seems to side with Dr. Grabowski and the drugmakers. A Sept. 18, 2008, letter from the FDA's then-chief scientist, Dr. Frank M. Torti, states: “The Agency believes that sponsors that develop innovative biotechnology products should be eligible for a significant period of market and/or data exclusivity, independent from any patent protections that might be applicable to the product, to ensure continued innovation.”

Dr. Torti has since taken over as the FDA's acting commissioner.

The letter was addressed to the chairman of the House Subcommittee on Health, Rep. Frank Pallone Jr. (D-N.J.). The subcommittee is a division of the House Committee on Energy and Commerce, of which Rep. Waxman was recently appointed chairman. Ms. Witt said that legislation supporting a follow-on biologics pathway would be a high priority for the committee in 2009.

Follow-on biologics legislation without a long period of data exclusivity for the original drug would significantly hinder future innovation, according to one economist.

Meanwhile, legislators' insistence that incentives for innovation be balanced with generics' promise of affordability means that a regulatory pathway for the drugs could remain uncharted in 2009.

Data exclusivity for follow-on biologics is the “period of time after [a biologic drug's] approval before a follow-on biologic can enter the market with an abbreviated filing” that relies on the original drug's safety and efficacy data, said Henry G. Grabowski, Ph.D., at a recent audioconference sponsored by Avalere Health LLC, a health care consultancy.

Because a “typical” new biologic drug might cost up to $1.2 billion in research and development, the “data exclusivity [period] acts as an insurance policy to ensure that there is adequate incentive” to produce the drugs in the first place, said Dr. Grabowski, a professor of economics and director of the program in pharmaceuticals and health economics at Duke University in Durham, N.C.

Ann Witt, a health care adviser to Rep. Henry Waxman (D-Calif.), who cosponsored the 1984 generic drugs legislation, disagreed with Dr. Grabowski's assessment. “Many of the arguments we heard here today were also made in 1984 by the then-manufacturers of small molecule drugs, who insisted that innovation would come to an end” with the advent of generics, she pointed out. Since then, “I have never heard anyone claim that that bill reduced innovation in the pharmaceutical industry,” she said.

The Food and Drug Administration's stance seems to side with Dr. Grabowski and the drugmakers. A Sept. 18, 2008, letter from the FDA's then-chief scientist, Dr. Frank M. Torti, states: “The Agency believes that sponsors that develop innovative biotechnology products should be eligible for a significant period of market and/or data exclusivity, independent from any patent protections that might be applicable to the product, to ensure continued innovation.”

Dr. Torti has since taken over as the FDA's acting commissioner.

The letter was addressed to the chairman of the House Subcommittee on Health, Rep. Frank Pallone Jr. (D-N.J.). The subcommittee is a division of the House Committee on Energy and Commerce, of which Rep. Waxman was recently appointed chairman. Ms. Witt said that legislation supporting a follow-on biologics pathway would be a high priority for the committee in 2009.

Data from a Food and Drug Administration registry suggesting an increase in birth defects among women treated with etanercept and infliximab have rekindled controversy over the use of tumor necrosis factor blockers in pregnancy.

Authors of a new review of FDA data advise clinicians against prescribing anti-TNF agents to pregnant women based on their findings that etanercept and infliximab may be responsible for a “seemingly high number” of congenital anomalies. “Clinicians should not prescribe TNF antagonists to women during pregnancy,” wrote the authors of the review.

However, conflicting preliminary data from an ongoing study by the Organization of Teratology Information Specialists (OTIS) argue that anti-tumor necrosis factor agents are safe for this population. Dr. Christina Chambers, a coinvestigator on the OTIS study, said it was alarmist to recommend avoiding anti-TNF agents in pregnancy, and said that reviews of the FDA adverse events database are “inherently biased.” Based on her group's results, she said, “We're not able to draw any conclusions that suggest that we are seeing any specific pattern of defects, whether major or minor, based on the children that have been evaluated so far.”

Dr. John J. Cush, who is not involved with either of these studies but who has conducted his own surveys on the issue, said in an interview that “the FDA database serves an important role in providing insight into what may be a potential hazard to those receiving these drugs.”

However, he added, “There are biases regarding underreporting, sources of reports, the lack of a denominator, and a grossly underestimated numerator.” Of course, all databases—including the OTIS database—have inherent biases, he cautioned.

“Nonetheless, there is no reason or convincing data to emphatically deny effective anti-TNF therapy to patients who need it to control their disease, either before or during pregnancy,” said Dr. Cush, director of the clinical rheumatology program at Baylor Research Institute in Dallas.

The review of the FDA adverse events database, led by Dr. John D. Carter, involved more than 120,000 adverse events for all entries between 1999 and 2005 found with the keywords “congenital anomaly,” “congenital anomalies,” “birth defect,” and “birth defects.” A total of 41 children with 61 congenital anomalies born to 40 different mothers who were taking a TNF antagonist during pregnancy were recorded (J. Rheumatol. 2008 Dec. 15 [doi:10.3899/jrheum.080545

Overall, 22 of these mothers had been taking etanercept at some point during their pregnancy; 19 had been taking infliximab. “In all 41 cases, the TNF-α antagonist was considered the 'primary suspect' as the cause of the birth defect,” wrote Dr. Carter of the division of rheumatology at the University of South Florida, Tampa.

A total of 34 different types of birth defects were seen, 19 of which were part of the VACTERL spectrum.

In an interview, Dr. Chambers took issue with the VACTERL findings, noting that to include children's defects as part of the VACTERL spectrum means that they must exhibit at least three of the seven defects in the spectrum—not just one. And though the authors emphasize that 24 of 41 children (59%) “had one or more congenital anomalies that are part of VACTERL,” only one was diagnosed with the pattern of associated birth defects within the original study period, according to Dr. Chambers.

Dr. Carter said that he thinks women of child-bearing age taking anti-TNFs should be strongly encouraged to use contraception, as they are with known teratogenic drugs such as Accutane.

Dr. Carter did not declare any conflicts of interest with regard to his study. Dr. Chambers said she did not have any personal conflicts, but that OTIS receives grant funding from nine different pharmaceutical companies, two of which are manufacturers of anti-TNFs. Dr. Cush has served as a consultant or advisor to, or received grant money from, multiple pharmaceutical companies, including the makers of the three anti-TNFs looked at in these studies.

Data from a Food and Drug Administration registry suggesting an increase in birth defects among women treated with etanercept and infliximab have rekindled controversy over the use of tumor necrosis factor blockers in pregnancy.

Authors of a new review of FDA data advise clinicians against prescribing anti-TNF agents to pregnant women based on their findings that etanercept and infliximab may be responsible for a “seemingly high number” of congenital anomalies. “Clinicians should not prescribe TNF antagonists to women during pregnancy,” wrote the authors of the review.

However, conflicting preliminary data from an ongoing study by the Organization of Teratology Information Specialists (OTIS) argue that anti-tumor necrosis factor agents are safe for this population. Dr. Christina Chambers, a coinvestigator on the OTIS study, said it was alarmist to recommend avoiding anti-TNF agents in pregnancy, and said that reviews of the FDA adverse events database are “inherently biased.” Based on her group's results, she said, “We're not able to draw any conclusions that suggest that we are seeing any specific pattern of defects, whether major or minor, based on the children that have been evaluated so far.”

Dr. John J. Cush, who is not involved with either of these studies but who has conducted his own surveys on the issue, said in an interview that “the FDA database serves an important role in providing insight into what may be a potential hazard to those receiving these drugs.”

However, he added, “There are biases regarding underreporting, sources of reports, the lack of a denominator, and a grossly underestimated numerator.” Of course, all databases—including the OTIS database—have inherent biases, he cautioned.

“Nonetheless, there is no reason or convincing data to emphatically deny effective anti-TNF therapy to patients who need it to control their disease, either before or during pregnancy,” said Dr. Cush, director of the clinical rheumatology program at Baylor Research Institute in Dallas.

The review of the FDA adverse events database, led by Dr. John D. Carter, involved more than 120,000 adverse events for all entries between 1999 and 2005 found with the keywords “congenital anomaly,” “congenital anomalies,” “birth defect,” and “birth defects.” A total of 41 children with 61 congenital anomalies born to 40 different mothers who were taking a TNF antagonist during pregnancy were recorded (J. Rheumatol. 2008 Dec. 15 [doi:10.3899/jrheum.080545

Overall, 22 of these mothers had been taking etanercept at some point during their pregnancy; 19 had been taking infliximab. “In all 41 cases, the TNF-α antagonist was considered the 'primary suspect' as the cause of the birth defect,” wrote Dr. Carter of the division of rheumatology at the University of South Florida, Tampa.

A total of 34 different types of birth defects were seen, 19 of which were part of the VACTERL spectrum.

In an interview, Dr. Chambers took issue with the VACTERL findings, noting that to include children's defects as part of the VACTERL spectrum means that they must exhibit at least three of the seven defects in the spectrum—not just one. And though the authors emphasize that 24 of 41 children (59%) “had one or more congenital anomalies that are part of VACTERL,” only one was diagnosed with the pattern of associated birth defects within the original study period, according to Dr. Chambers.

Dr. Carter said that he thinks women of child-bearing age taking anti-TNFs should be strongly encouraged to use contraception, as they are with known teratogenic drugs such as Accutane.

Dr. Carter did not declare any conflicts of interest with regard to his study. Dr. Chambers said she did not have any personal conflicts, but that OTIS receives grant funding from nine different pharmaceutical companies, two of which are manufacturers of anti-TNFs. Dr. Cush has served as a consultant or advisor to, or received grant money from, multiple pharmaceutical companies, including the makers of the three anti-TNFs looked at in these studies.

Data from a Food and Drug Administration registry suggesting an increase in birth defects among women treated with etanercept and infliximab have rekindled controversy over the use of tumor necrosis factor blockers in pregnancy.

Authors of a new review of FDA data advise clinicians against prescribing anti-TNF agents to pregnant women based on their findings that etanercept and infliximab may be responsible for a “seemingly high number” of congenital anomalies. “Clinicians should not prescribe TNF antagonists to women during pregnancy,” wrote the authors of the review.

However, conflicting preliminary data from an ongoing study by the Organization of Teratology Information Specialists (OTIS) argue that anti-tumor necrosis factor agents are safe for this population. Dr. Christina Chambers, a coinvestigator on the OTIS study, said it was alarmist to recommend avoiding anti-TNF agents in pregnancy, and said that reviews of the FDA adverse events database are “inherently biased.” Based on her group's results, she said, “We're not able to draw any conclusions that suggest that we are seeing any specific pattern of defects, whether major or minor, based on the children that have been evaluated so far.”

Dr. John J. Cush, who is not involved with either of these studies but who has conducted his own surveys on the issue, said in an interview that “the FDA database serves an important role in providing insight into what may be a potential hazard to those receiving these drugs.”

However, he added, “There are biases regarding underreporting, sources of reports, the lack of a denominator, and a grossly underestimated numerator.” Of course, all databases—including the OTIS database—have inherent biases, he cautioned.

“Nonetheless, there is no reason or convincing data to emphatically deny effective anti-TNF therapy to patients who need it to control their disease, either before or during pregnancy,” said Dr. Cush, director of the clinical rheumatology program at Baylor Research Institute in Dallas.

The review of the FDA adverse events database, led by Dr. John D. Carter, involved more than 120,000 adverse events for all entries between 1999 and 2005 found with the keywords “congenital anomaly,” “congenital anomalies,” “birth defect,” and “birth defects.” A total of 41 children with 61 congenital anomalies born to 40 different mothers who were taking a TNF antagonist during pregnancy were recorded (J. Rheumatol. 2008 Dec. 15 [doi:10.3899/jrheum.080545

Overall, 22 of these mothers had been taking etanercept at some point during their pregnancy; 19 had been taking infliximab. “In all 41 cases, the TNF-α antagonist was considered the 'primary suspect' as the cause of the birth defect,” wrote Dr. Carter of the division of rheumatology at the University of South Florida, Tampa.

A total of 34 different types of birth defects were seen, 19 of which were part of the VACTERL spectrum.

In an interview, Dr. Chambers took issue with the VACTERL findings, noting that to include children's defects as part of the VACTERL spectrum means that they must exhibit at least three of the seven defects in the spectrum—not just one. And though the authors emphasize that 24 of 41 children (59%) “had one or more congenital anomalies that are part of VACTERL,” only one was diagnosed with the pattern of associated birth defects within the original study period, according to Dr. Chambers.

Dr. Carter said that he thinks women of child-bearing age taking anti-TNFs should be strongly encouraged to use contraception, as they are with known teratogenic drugs such as Accutane.

Dr. Carter did not declare any conflicts of interest with regard to his study. Dr. Chambers said she did not have any personal conflicts, but that OTIS receives grant funding from nine different pharmaceutical companies, two of which are manufacturers of anti-TNFs. Dr. Cush has served as a consultant or advisor to, or received grant money from, multiple pharmaceutical companies, including the makers of the three anti-TNFs looked at in these studies.

Divya Railan, MD, and Tina S. Alster, MD

Lasers frequently are used by dermatologists for their multiple aesthetic applications, but they also can be used to treat a variety of medical dermatology conditions. Conditions such as acne vulgaris, psoriasis, and vitiligo can all be successfully treated with laser, thereby providing the patient with additional therapeutic options. Lasers have also been used for years to improve the appearance of scars. The newer fractionated lasers have been especially effective in enhancing the clinical outcomes of scar revision.

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

Divya Railan, MD, and Tina S. Alster, MD

Lasers frequently are used by dermatologists for their multiple aesthetic applications, but they also can be used to treat a variety of medical dermatology conditions. Conditions such as acne vulgaris, psoriasis, and vitiligo can all be successfully treated with laser, thereby providing the patient with additional therapeutic options. Lasers have also been used for years to improve the appearance of scars. The newer fractionated lasers have been especially effective in enhancing the clinical outcomes of scar revision.

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

Divya Railan, MD, and Tina S. Alster, MD

Lasers frequently are used by dermatologists for their multiple aesthetic applications, but they also can be used to treat a variety of medical dermatology conditions. Conditions such as acne vulgaris, psoriasis, and vitiligo can all be successfully treated with laser, thereby providing the patient with additional therapeutic options. Lasers have also been used for years to improve the appearance of scars. The newer fractionated lasers have been especially effective in enhancing the clinical outcomes of scar revision.

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

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.