Psoriasis

Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.

The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.

The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).

They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.

In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.

Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.

Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.

Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).

The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.

PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).

According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).

They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."

Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.

[email protected]

Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.

The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.

The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).

They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.

In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.

Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.

Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.

Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).

The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.

PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).

According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).

They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."

Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.

[email protected]

Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.

The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.

The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).

They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.

In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.

Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.

Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.

Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).

The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.

PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).

According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).

They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."

Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.

[email protected]

Smoking significantly raises the risk that patients with systemic lupus erythematosus will develop active cutaneous manifestations of the disease, based on data from a multicenter cohort study of 1,346 patients.

Overall, current smokers were 63% more likely than former or never smokers to have an active SLE rash after controlling for multiple variables. In addition, patients who had ever smoked were more than twice as likely to meet the American College of Rheumatology criteria for discoid rash (odds ratio, 2.36) and photosensitivity (odds ratio, 1.47).

©pmphoto/iStockphoto.com

The study is the largest to date examining the effect of smoking on cutaneous outcomes in systemic lupus erythematosus (SLE), said Dr. Josiane Bourré-Tessier of the University of Montreal and her associates.

The researchers examined a possible association between smoking status and skin activity using data from the 1000 Faces of Lupus Cohort, a cohort of SLE patients who presented for care at 14 participating specialty clinics across Canada. The study population included 1,346 participants aged 16 years and older who enrolled between 2005 and 2009 (Arthritis Care Res. 2013 Feb. 11 [doi:10.1002/acr.21966]).

The patients were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), which focuses on rash and alopecia; the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), which focuses on alopecia, extensive scarring, and skin ulceration; and the American College of Rheumatology (ACR) revised criteria for SLE, which focus on discoid rash, malar rash, and photosensitivity.

More than 90% of the study subjects were women, and 63% were white. The mean age was 47 years; mean disease duration was 13 years. Approximately 14% of the patients were current smokers and 27% were past smokers.

Most patients (70%) were taking antimalarials at the time of the study – 64% taking hydroxychloroquine and 6% taking chloroquine. Another 35% were taking immunosuppressants.

According to the SLEDAI-2K, 28% of patients had some mucocutaneous disease activity: 15% had rash, 13% had alopecia, 8% had mucosal ulcers, and 8% had at least two of these symptoms. According to the SDI, 12% had alopecia, including 4% with extensive scarring and 0.2% with skin ulceration. According to ACR criteria, 60% of patients had ever experienced malar rash; 17% had experienced discoid rash; 56%, photosensitivity; and 56%, ulcerations.

No association was found between past smoking and active skin manifestations, based on the SLEDAI-2K.

Based on the SDI, there was no association between smoking and cutaneous damage. This finding, however, may be due to the small number of patients with cutaneous damage, the researchers said. Alternatively, it may suggest that a longer observation period is needed to show a relationship between smoking and long-term cutaneous damage.

Both current and past smoking were associated with discoid rash and photosensitivity, based on the ACR criteria. Since ACR criteria are cumulative, this finding suggests that past smoking "may have triggered the prior emergence of cutaneous criteria," Dr. Bourré-Tessier and her associates said.

The association between smoking and skin manifestations of SLE "is not surprising, as cigarettes contain multiple chemical factors that may generate free radicals and alter inflammatory cell function and extracellular matrix turnover," the researchers wrote.

"These chemical factors may also interact with DNA and promote the production of autoantibodies directed against altered DNA," they suggested.

It was encouraging to find that current, but not past, smoking was associated with skin activity because that suggests the adverse effect may be reversible if patients stop smoking, the researchers noted.

The findings support the results of previous investigations showing that smoking promotes disease activity in a variety of autoimmune conditions. The data also give clinicians added incentive to encourage SLE patients to quit smoking, Dr. Bourré-Tessier and her associates said.

The study was limited by an inability to account for potential confounders such as medication adherence and sun exposure, they added.

The 1000 Faces of Lupus Cohort was funded by the Arthritis Society and the Lupus Society of Manitoba. No financial conflicts of interest were reported.

[email protected]

Smoking significantly raises the risk that patients with systemic lupus erythematosus will develop active cutaneous manifestations of the disease, based on data from a multicenter cohort study of 1,346 patients.

Overall, current smokers were 63% more likely than former or never smokers to have an active SLE rash after controlling for multiple variables. In addition, patients who had ever smoked were more than twice as likely to meet the American College of Rheumatology criteria for discoid rash (odds ratio, 2.36) and photosensitivity (odds ratio, 1.47).

©pmphoto/iStockphoto.com

The study is the largest to date examining the effect of smoking on cutaneous outcomes in systemic lupus erythematosus (SLE), said Dr. Josiane Bourré-Tessier of the University of Montreal and her associates.

The researchers examined a possible association between smoking status and skin activity using data from the 1000 Faces of Lupus Cohort, a cohort of SLE patients who presented for care at 14 participating specialty clinics across Canada. The study population included 1,346 participants aged 16 years and older who enrolled between 2005 and 2009 (Arthritis Care Res. 2013 Feb. 11 [doi:10.1002/acr.21966]).

The patients were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), which focuses on rash and alopecia; the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), which focuses on alopecia, extensive scarring, and skin ulceration; and the American College of Rheumatology (ACR) revised criteria for SLE, which focus on discoid rash, malar rash, and photosensitivity.

More than 90% of the study subjects were women, and 63% were white. The mean age was 47 years; mean disease duration was 13 years. Approximately 14% of the patients were current smokers and 27% were past smokers.

Most patients (70%) were taking antimalarials at the time of the study – 64% taking hydroxychloroquine and 6% taking chloroquine. Another 35% were taking immunosuppressants.

According to the SLEDAI-2K, 28% of patients had some mucocutaneous disease activity: 15% had rash, 13% had alopecia, 8% had mucosal ulcers, and 8% had at least two of these symptoms. According to the SDI, 12% had alopecia, including 4% with extensive scarring and 0.2% with skin ulceration. According to ACR criteria, 60% of patients had ever experienced malar rash; 17% had experienced discoid rash; 56%, photosensitivity; and 56%, ulcerations.

No association was found between past smoking and active skin manifestations, based on the SLEDAI-2K.

Based on the SDI, there was no association between smoking and cutaneous damage. This finding, however, may be due to the small number of patients with cutaneous damage, the researchers said. Alternatively, it may suggest that a longer observation period is needed to show a relationship between smoking and long-term cutaneous damage.

Both current and past smoking were associated with discoid rash and photosensitivity, based on the ACR criteria. Since ACR criteria are cumulative, this finding suggests that past smoking "may have triggered the prior emergence of cutaneous criteria," Dr. Bourré-Tessier and her associates said.

The association between smoking and skin manifestations of SLE "is not surprising, as cigarettes contain multiple chemical factors that may generate free radicals and alter inflammatory cell function and extracellular matrix turnover," the researchers wrote.

"These chemical factors may also interact with DNA and promote the production of autoantibodies directed against altered DNA," they suggested.

It was encouraging to find that current, but not past, smoking was associated with skin activity because that suggests the adverse effect may be reversible if patients stop smoking, the researchers noted.

The findings support the results of previous investigations showing that smoking promotes disease activity in a variety of autoimmune conditions. The data also give clinicians added incentive to encourage SLE patients to quit smoking, Dr. Bourré-Tessier and her associates said.

The study was limited by an inability to account for potential confounders such as medication adherence and sun exposure, they added.

The 1000 Faces of Lupus Cohort was funded by the Arthritis Society and the Lupus Society of Manitoba. No financial conflicts of interest were reported.

[email protected]

Smoking significantly raises the risk that patients with systemic lupus erythematosus will develop active cutaneous manifestations of the disease, based on data from a multicenter cohort study of 1,346 patients.

Overall, current smokers were 63% more likely than former or never smokers to have an active SLE rash after controlling for multiple variables. In addition, patients who had ever smoked were more than twice as likely to meet the American College of Rheumatology criteria for discoid rash (odds ratio, 2.36) and photosensitivity (odds ratio, 1.47).

©pmphoto/iStockphoto.com

The study is the largest to date examining the effect of smoking on cutaneous outcomes in systemic lupus erythematosus (SLE), said Dr. Josiane Bourré-Tessier of the University of Montreal and her associates.

The researchers examined a possible association between smoking status and skin activity using data from the 1000 Faces of Lupus Cohort, a cohort of SLE patients who presented for care at 14 participating specialty clinics across Canada. The study population included 1,346 participants aged 16 years and older who enrolled between 2005 and 2009 (Arthritis Care Res. 2013 Feb. 11 [doi:10.1002/acr.21966]).

The patients were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), which focuses on rash and alopecia; the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), which focuses on alopecia, extensive scarring, and skin ulceration; and the American College of Rheumatology (ACR) revised criteria for SLE, which focus on discoid rash, malar rash, and photosensitivity.

More than 90% of the study subjects were women, and 63% were white. The mean age was 47 years; mean disease duration was 13 years. Approximately 14% of the patients were current smokers and 27% were past smokers.

Most patients (70%) were taking antimalarials at the time of the study – 64% taking hydroxychloroquine and 6% taking chloroquine. Another 35% were taking immunosuppressants.

According to the SLEDAI-2K, 28% of patients had some mucocutaneous disease activity: 15% had rash, 13% had alopecia, 8% had mucosal ulcers, and 8% had at least two of these symptoms. According to the SDI, 12% had alopecia, including 4% with extensive scarring and 0.2% with skin ulceration. According to ACR criteria, 60% of patients had ever experienced malar rash; 17% had experienced discoid rash; 56%, photosensitivity; and 56%, ulcerations.

No association was found between past smoking and active skin manifestations, based on the SLEDAI-2K.

Based on the SDI, there was no association between smoking and cutaneous damage. This finding, however, may be due to the small number of patients with cutaneous damage, the researchers said. Alternatively, it may suggest that a longer observation period is needed to show a relationship between smoking and long-term cutaneous damage.

Both current and past smoking were associated with discoid rash and photosensitivity, based on the ACR criteria. Since ACR criteria are cumulative, this finding suggests that past smoking "may have triggered the prior emergence of cutaneous criteria," Dr. Bourré-Tessier and her associates said.

The association between smoking and skin manifestations of SLE "is not surprising, as cigarettes contain multiple chemical factors that may generate free radicals and alter inflammatory cell function and extracellular matrix turnover," the researchers wrote.

"These chemical factors may also interact with DNA and promote the production of autoantibodies directed against altered DNA," they suggested.

It was encouraging to find that current, but not past, smoking was associated with skin activity because that suggests the adverse effect may be reversible if patients stop smoking, the researchers noted.

The findings support the results of previous investigations showing that smoking promotes disease activity in a variety of autoimmune conditions. The data also give clinicians added incentive to encourage SLE patients to quit smoking, Dr. Bourré-Tessier and her associates said.

The study was limited by an inability to account for potential confounders such as medication adherence and sun exposure, they added.

The 1000 Faces of Lupus Cohort was funded by the Arthritis Society and the Lupus Society of Manitoba. No financial conflicts of interest were reported.

[email protected]

The postpartum period is often a time when women with moderate to severe psoriasis experience a significant disease flare – and if they’re breastfeeding, treatment options are limited, according to Dr. Alan Menter.

This postpartum major flare of psoriasis is an underappreciated phenomenon that catches many dermatologists and most ob.gyns. off guard, he said.

"Fifty to 60% of psoriasis patients have genital involvement. A woman with genital psoriasis in the postpartum period or during delivery really needs help, and I think we in dermatology should be addressing these issues because most of the obstetricians are not sure how to treat these patients," said Dr. Menter, chief of the division of dermatology at Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

Psoriasis is equally common in men and women, and two-thirds of affected individuals present before age 40 – for women, the childbearing years. Thorny psoriasis management issues in pregnancy and postpartum are common.

Psoriasis slowly improves during pregnancy in roughly two-thirds of patients, as is true for other immune-mediated diseases. But for that other third, many of the mainstay therapies for tough psoriasis are off limits during pregnancy and/or post partum. UVB is a good, safe option, albeit inconvenient. Retinoids and cyclosporine are out because of teratogenicity.

Cyclosporine probably should be considered the go-to drug for significant disease during pregnancy. Its strengths are its fast onset of action and the safety reassurance provided by vast patient registries started back in the 1980s when the drug was first used in transplant recipients.

"We’re all comfortable using cyclosporine," Dr. Menter said. "Our AAD guidelines state it is appropriate for 1 year of continuous use. The European guidelines say, ‘2 years of continuous use.’ But I think most of us use it as an interventional therapy for 3-6 months. I actually think we should be using it a little more frequently as an interventional therapy."

Cyclosporine must be stopped in month 8 of pregnancy to allow the drug to clear from the patient’s system before delivery, since it is secreted in breast milk.

For the breastfeeding woman experiencing a major disease flare, the options are basically potent topical steroids, which physicians should feel comfortable in prescribing according to the standard dosing schedule used in nonpregnant patients, or – when topical therapy won’t get the job done – the biologic agents, listed by the Food and Drug Administration as category B.

The most forward-thinking approach to take with young women who require systemic therapy for psoriasis is to discuss pregnancy-related issues before pregnancy occurs. In particular, a prospective case-control study from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project concluded that women with psoriasis were significantly more likely to smoke, carry a diagnosis of depression, and be overweight or obese before pregnancy – factors that increase their risk for adverse pregnancy outcomes (Br. J. Dermatol. 2010;163:334-9).

Moreover, other studies have shown that psoriasis patients, men as well as women, have an increased prevalence of the metabolic syndrome, which increases their long-term risk of cardiovascular disease. Women with an adverse cardiovascular risk profile who are considering pregnancy and parenthood may be in a teachable moment where they are more amenable to lifestyle changes that reduce the risks both to their baby and themselves, Dr. Menter said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Of course, half of pregnancies in the United States are unplanned, so the potential for unintended first-trimester fetal exposure to a teratogenic drug is substantial. While methotrexate is rated by the FDA as category X in pregnancy, dermatologists can derive some comfort from a well-executed review of 101 methotrexate-exposed pregnancies in rheumatology patients (Clin. Exp. Rheumatol. 2009;27:678-84). The 23% miscarriage rate wasn’t significantly different from that seen in pregnant psoriasis patients not on systemic agents. The live birth rate was 66%, with a 5% rate of neonatal malformations, all minor.

"The outcomes were actually better than any of us would have anticipated," Dr. Menter commented.

Psoriasis appears to have an inherent adverse impact upon pregnancy, he continued, pointing to an Israeli study of 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls without psoriasis matched for age, parity, and gestational age.

"I think this is something we have to very gently discuss with our female patients who are considering pregnancy. We should tell them to be cautious in pregnancy because of this link between psoriasis and a slightly increased risk of spontaneous abortions. And I also discuss it with our ob.gyn. colleagues, who really are not aware of this link," the dermatologist said.

Dr. Menter reported receiving research support and/or consultant or lecture fees from roughly 20 pharmaceutical companies. SDEF and this news organization are owned by the same parent company.

[email protected]

*This story was updated March 1, 2013.

The postpartum period is often a time when women with moderate to severe psoriasis experience a significant disease flare – and if they’re breastfeeding, treatment options are limited, according to Dr. Alan Menter.

This postpartum major flare of psoriasis is an underappreciated phenomenon that catches many dermatologists and most ob.gyns. off guard, he said.

"Fifty to 60% of psoriasis patients have genital involvement. A woman with genital psoriasis in the postpartum period or during delivery really needs help, and I think we in dermatology should be addressing these issues because most of the obstetricians are not sure how to treat these patients," said Dr. Menter, chief of the division of dermatology at Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

Psoriasis is equally common in men and women, and two-thirds of affected individuals present before age 40 – for women, the childbearing years. Thorny psoriasis management issues in pregnancy and postpartum are common.

Psoriasis slowly improves during pregnancy in roughly two-thirds of patients, as is true for other immune-mediated diseases. But for that other third, many of the mainstay therapies for tough psoriasis are off limits during pregnancy and/or post partum. UVB is a good, safe option, albeit inconvenient. Retinoids and cyclosporine are out because of teratogenicity.

Cyclosporine probably should be considered the go-to drug for significant disease during pregnancy. Its strengths are its fast onset of action and the safety reassurance provided by vast patient registries started back in the 1980s when the drug was first used in transplant recipients.

"We’re all comfortable using cyclosporine," Dr. Menter said. "Our AAD guidelines state it is appropriate for 1 year of continuous use. The European guidelines say, ‘2 years of continuous use.’ But I think most of us use it as an interventional therapy for 3-6 months. I actually think we should be using it a little more frequently as an interventional therapy."

Cyclosporine must be stopped in month 8 of pregnancy to allow the drug to clear from the patient’s system before delivery, since it is secreted in breast milk.

For the breastfeeding woman experiencing a major disease flare, the options are basically potent topical steroids, which physicians should feel comfortable in prescribing according to the standard dosing schedule used in nonpregnant patients, or – when topical therapy won’t get the job done – the biologic agents, listed by the Food and Drug Administration as category B.

The most forward-thinking approach to take with young women who require systemic therapy for psoriasis is to discuss pregnancy-related issues before pregnancy occurs. In particular, a prospective case-control study from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project concluded that women with psoriasis were significantly more likely to smoke, carry a diagnosis of depression, and be overweight or obese before pregnancy – factors that increase their risk for adverse pregnancy outcomes (Br. J. Dermatol. 2010;163:334-9).

Moreover, other studies have shown that psoriasis patients, men as well as women, have an increased prevalence of the metabolic syndrome, which increases their long-term risk of cardiovascular disease. Women with an adverse cardiovascular risk profile who are considering pregnancy and parenthood may be in a teachable moment where they are more amenable to lifestyle changes that reduce the risks both to their baby and themselves, Dr. Menter said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Of course, half of pregnancies in the United States are unplanned, so the potential for unintended first-trimester fetal exposure to a teratogenic drug is substantial. While methotrexate is rated by the FDA as category X in pregnancy, dermatologists can derive some comfort from a well-executed review of 101 methotrexate-exposed pregnancies in rheumatology patients (Clin. Exp. Rheumatol. 2009;27:678-84). The 23% miscarriage rate wasn’t significantly different from that seen in pregnant psoriasis patients not on systemic agents. The live birth rate was 66%, with a 5% rate of neonatal malformations, all minor.

"The outcomes were actually better than any of us would have anticipated," Dr. Menter commented.

Psoriasis appears to have an inherent adverse impact upon pregnancy, he continued, pointing to an Israeli study of 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls without psoriasis matched for age, parity, and gestational age.

"I think this is something we have to very gently discuss with our female patients who are considering pregnancy. We should tell them to be cautious in pregnancy because of this link between psoriasis and a slightly increased risk of spontaneous abortions. And I also discuss it with our ob.gyn. colleagues, who really are not aware of this link," the dermatologist said.

Dr. Menter reported receiving research support and/or consultant or lecture fees from roughly 20 pharmaceutical companies. SDEF and this news organization are owned by the same parent company.

[email protected]

*This story was updated March 1, 2013.

The postpartum period is often a time when women with moderate to severe psoriasis experience a significant disease flare – and if they’re breastfeeding, treatment options are limited, according to Dr. Alan Menter.

This postpartum major flare of psoriasis is an underappreciated phenomenon that catches many dermatologists and most ob.gyns. off guard, he said.

"Fifty to 60% of psoriasis patients have genital involvement. A woman with genital psoriasis in the postpartum period or during delivery really needs help, and I think we in dermatology should be addressing these issues because most of the obstetricians are not sure how to treat these patients," said Dr. Menter, chief of the division of dermatology at Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

Psoriasis is equally common in men and women, and two-thirds of affected individuals present before age 40 – for women, the childbearing years. Thorny psoriasis management issues in pregnancy and postpartum are common.

Psoriasis slowly improves during pregnancy in roughly two-thirds of patients, as is true for other immune-mediated diseases. But for that other third, many of the mainstay therapies for tough psoriasis are off limits during pregnancy and/or post partum. UVB is a good, safe option, albeit inconvenient. Retinoids and cyclosporine are out because of teratogenicity.

Cyclosporine probably should be considered the go-to drug for significant disease during pregnancy. Its strengths are its fast onset of action and the safety reassurance provided by vast patient registries started back in the 1980s when the drug was first used in transplant recipients.

"We’re all comfortable using cyclosporine," Dr. Menter said. "Our AAD guidelines state it is appropriate for 1 year of continuous use. The European guidelines say, ‘2 years of continuous use.’ But I think most of us use it as an interventional therapy for 3-6 months. I actually think we should be using it a little more frequently as an interventional therapy."

Cyclosporine must be stopped in month 8 of pregnancy to allow the drug to clear from the patient’s system before delivery, since it is secreted in breast milk.

For the breastfeeding woman experiencing a major disease flare, the options are basically potent topical steroids, which physicians should feel comfortable in prescribing according to the standard dosing schedule used in nonpregnant patients, or – when topical therapy won’t get the job done – the biologic agents, listed by the Food and Drug Administration as category B.

The most forward-thinking approach to take with young women who require systemic therapy for psoriasis is to discuss pregnancy-related issues before pregnancy occurs. In particular, a prospective case-control study from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project concluded that women with psoriasis were significantly more likely to smoke, carry a diagnosis of depression, and be overweight or obese before pregnancy – factors that increase their risk for adverse pregnancy outcomes (Br. J. Dermatol. 2010;163:334-9).

Moreover, other studies have shown that psoriasis patients, men as well as women, have an increased prevalence of the metabolic syndrome, which increases their long-term risk of cardiovascular disease. Women with an adverse cardiovascular risk profile who are considering pregnancy and parenthood may be in a teachable moment where they are more amenable to lifestyle changes that reduce the risks both to their baby and themselves, Dr. Menter said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Of course, half of pregnancies in the United States are unplanned, so the potential for unintended first-trimester fetal exposure to a teratogenic drug is substantial. While methotrexate is rated by the FDA as category X in pregnancy, dermatologists can derive some comfort from a well-executed review of 101 methotrexate-exposed pregnancies in rheumatology patients (Clin. Exp. Rheumatol. 2009;27:678-84). The 23% miscarriage rate wasn’t significantly different from that seen in pregnant psoriasis patients not on systemic agents. The live birth rate was 66%, with a 5% rate of neonatal malformations, all minor.

"The outcomes were actually better than any of us would have anticipated," Dr. Menter commented.

Psoriasis appears to have an inherent adverse impact upon pregnancy, he continued, pointing to an Israeli study of 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls without psoriasis matched for age, parity, and gestational age.

"I think this is something we have to very gently discuss with our female patients who are considering pregnancy. We should tell them to be cautious in pregnancy because of this link between psoriasis and a slightly increased risk of spontaneous abortions. And I also discuss it with our ob.gyn. colleagues, who really are not aware of this link," the dermatologist said.

Dr. Menter reported receiving research support and/or consultant or lecture fees from roughly 20 pharmaceutical companies. SDEF and this news organization are owned by the same parent company.

[email protected]

*This story was updated March 1, 2013.

At the SDEF Hawaii Dermatology Seminar, Dr. Alan Menter of Baylor University discussed the particular challenges women with psoriasis face in the peripartum period. Many patients – and many ob.gyns.– are not well informed about postpartum psoriasis flare or what to do if genital psoriasis is present at delivery. The SDEF Hawaii Dermatology Seminar is presented by the Skin Disease Education Foundation/Global Academy for Medical Education and is owned by the same parent company as this news organization.

At the SDEF Hawaii Dermatology Seminar, Dr. Alan Menter of Baylor University discussed the particular challenges women with psoriasis face in the peripartum period. Many patients – and many ob.gyns.– are not well informed about postpartum psoriasis flare or what to do if genital psoriasis is present at delivery. The SDEF Hawaii Dermatology Seminar is presented by the Skin Disease Education Foundation/Global Academy for Medical Education and is owned by the same parent company as this news organization.

At the SDEF Hawaii Dermatology Seminar, Dr. Alan Menter of Baylor University discussed the particular challenges women with psoriasis face in the peripartum period. Many patients – and many ob.gyns.– are not well informed about postpartum psoriasis flare or what to do if genital psoriasis is present at delivery. The SDEF Hawaii Dermatology Seminar is presented by the Skin Disease Education Foundation/Global Academy for Medical Education and is owned by the same parent company as this news organization.

PRAGUE – The major role that the Janus kinases play in the pathogenesis of psoriasis is confirmed, based on the results of a phase II study of the investigational oral agent ASP015K, according to Dr. Bernhardt Zeiher.

ASP015K inhibits Janus kinase (JAK) 1 and 3, with relative sparing of JAK 2. In a 6-week dose-ranging study of 124 patients with moderate to severe psoriasis, all tested doses – 10, 25, 60, and 100 mg twice daily as well as 50 mg once daily – significantly outperformed placebo in terms of improvement in Psoriasis Area and Severity Index (PASI) scores.

Moreover, immunohistochemistry of skin biopsies gathered at baseline and at days 14 and 42 after initiation of ASP015K showed the drug reduced epidermal thickness, epidermal proliferation as measured by Ki67, and infiltration of CD3 T cells and CD11c dendritic cells. The greatest changes at the cellular level were seen at the highest dose, 100 mg twice daily.

"Although treatment was only for 6 weeks, the defining pathology of psoriasis was reversed in 62% of patients in the 100-mg b.i.d. cohort. In these patients, epidermal thickness was normalized and was comparable with nonlesional skin after treatment, parakeratosis was eliminated, and a granular layer was restored. Keratinocyte proliferation, judged by Ki67 staining, was reversed to levels of nonlesional skin. Major reductions in the number of T cells and inflammatory CD11c-positive dendritic cells were also measured in day 42 biopsies, along with elimination of organized lymphoid structures," according to Dr. Zeiher of Astellas Pharma, Deerfield, Ill., which is developing the JAK 1/3 inhibitor.

Improvements in cellular findings and PASI scores were largely dose-dependent.

Mean PASI scores fell by 12 points over a 6-week period in patients assigned to ASP015K at 100 mg b.i.d.; a 4-point drop in mean PASI scores was seen in placebo-treated controls.

Yet histologic improvements associated with the 50-mg once-daily dose were second in magnitude only to those seen with the 100-mg b.i.d. dose.

"When you look at the kinetics of the drug, you have more JAK inhibition holiday with once-a-day dosing," Dr. Zeiher explained. The notion that a daily JAK inhibition holiday provides added therapeutic benefit is both interesting and readily testable. A planned phase IIb study will evaluate once-daily oral dosing of ASP015K at a range of doses, with 150 mg as the maximum.

The JAK 1/3 inhibitor was well tolerated overall. Three subjects dropped out of the study because of drug-related side effects: two with decreased neutrophil counts but not frank neutropenia on doses of 60 and 100 mg b.i.d., and one as a result of GI upset while on 100 mg b.i.d.

[email protected]

PRAGUE – The major role that the Janus kinases play in the pathogenesis of psoriasis is confirmed, based on the results of a phase II study of the investigational oral agent ASP015K, according to Dr. Bernhardt Zeiher.

ASP015K inhibits Janus kinase (JAK) 1 and 3, with relative sparing of JAK 2. In a 6-week dose-ranging study of 124 patients with moderate to severe psoriasis, all tested doses – 10, 25, 60, and 100 mg twice daily as well as 50 mg once daily – significantly outperformed placebo in terms of improvement in Psoriasis Area and Severity Index (PASI) scores.

Moreover, immunohistochemistry of skin biopsies gathered at baseline and at days 14 and 42 after initiation of ASP015K showed the drug reduced epidermal thickness, epidermal proliferation as measured by Ki67, and infiltration of CD3 T cells and CD11c dendritic cells. The greatest changes at the cellular level were seen at the highest dose, 100 mg twice daily.

"Although treatment was only for 6 weeks, the defining pathology of psoriasis was reversed in 62% of patients in the 100-mg b.i.d. cohort. In these patients, epidermal thickness was normalized and was comparable with nonlesional skin after treatment, parakeratosis was eliminated, and a granular layer was restored. Keratinocyte proliferation, judged by Ki67 staining, was reversed to levels of nonlesional skin. Major reductions in the number of T cells and inflammatory CD11c-positive dendritic cells were also measured in day 42 biopsies, along with elimination of organized lymphoid structures," according to Dr. Zeiher of Astellas Pharma, Deerfield, Ill., which is developing the JAK 1/3 inhibitor.

Improvements in cellular findings and PASI scores were largely dose-dependent.

Mean PASI scores fell by 12 points over a 6-week period in patients assigned to ASP015K at 100 mg b.i.d.; a 4-point drop in mean PASI scores was seen in placebo-treated controls.

Yet histologic improvements associated with the 50-mg once-daily dose were second in magnitude only to those seen with the 100-mg b.i.d. dose.

"When you look at the kinetics of the drug, you have more JAK inhibition holiday with once-a-day dosing," Dr. Zeiher explained. The notion that a daily JAK inhibition holiday provides added therapeutic benefit is both interesting and readily testable. A planned phase IIb study will evaluate once-daily oral dosing of ASP015K at a range of doses, with 150 mg as the maximum.

The JAK 1/3 inhibitor was well tolerated overall. Three subjects dropped out of the study because of drug-related side effects: two with decreased neutrophil counts but not frank neutropenia on doses of 60 and 100 mg b.i.d., and one as a result of GI upset while on 100 mg b.i.d.

[email protected]

PRAGUE – The major role that the Janus kinases play in the pathogenesis of psoriasis is confirmed, based on the results of a phase II study of the investigational oral agent ASP015K, according to Dr. Bernhardt Zeiher.

ASP015K inhibits Janus kinase (JAK) 1 and 3, with relative sparing of JAK 2. In a 6-week dose-ranging study of 124 patients with moderate to severe psoriasis, all tested doses – 10, 25, 60, and 100 mg twice daily as well as 50 mg once daily – significantly outperformed placebo in terms of improvement in Psoriasis Area and Severity Index (PASI) scores.

Moreover, immunohistochemistry of skin biopsies gathered at baseline and at days 14 and 42 after initiation of ASP015K showed the drug reduced epidermal thickness, epidermal proliferation as measured by Ki67, and infiltration of CD3 T cells and CD11c dendritic cells. The greatest changes at the cellular level were seen at the highest dose, 100 mg twice daily.

"Although treatment was only for 6 weeks, the defining pathology of psoriasis was reversed in 62% of patients in the 100-mg b.i.d. cohort. In these patients, epidermal thickness was normalized and was comparable with nonlesional skin after treatment, parakeratosis was eliminated, and a granular layer was restored. Keratinocyte proliferation, judged by Ki67 staining, was reversed to levels of nonlesional skin. Major reductions in the number of T cells and inflammatory CD11c-positive dendritic cells were also measured in day 42 biopsies, along with elimination of organized lymphoid structures," according to Dr. Zeiher of Astellas Pharma, Deerfield, Ill., which is developing the JAK 1/3 inhibitor.

Improvements in cellular findings and PASI scores were largely dose-dependent.

Mean PASI scores fell by 12 points over a 6-week period in patients assigned to ASP015K at 100 mg b.i.d.; a 4-point drop in mean PASI scores was seen in placebo-treated controls.

Yet histologic improvements associated with the 50-mg once-daily dose were second in magnitude only to those seen with the 100-mg b.i.d. dose.

"When you look at the kinetics of the drug, you have more JAK inhibition holiday with once-a-day dosing," Dr. Zeiher explained. The notion that a daily JAK inhibition holiday provides added therapeutic benefit is both interesting and readily testable. A planned phase IIb study will evaluate once-daily oral dosing of ASP015K at a range of doses, with 150 mg as the maximum.

The JAK 1/3 inhibitor was well tolerated overall. Three subjects dropped out of the study because of drug-related side effects: two with decreased neutrophil counts but not frank neutropenia on doses of 60 and 100 mg b.i.d., and one as a result of GI upset while on 100 mg b.i.d.

[email protected]

As revenue sources for research dwindle, academic medical centers are under great stress today. There is a drop in patient care fees, Medicare and Medicaid reimbursement, money through philanthropy, state support, and grant support. At every center, institutional support for research is under pressure. And for those just starting their careers – particularly those with an interest in lupus research – these problems could not come at a worse time.

Lupus offers many challenges to researchers: It is hard to diagnose, it ravages different parts of the body, its symptoms come and go and often imitate other illnesses, and it manifests differently in each individual. Despite these challenges, we have come a long way, and the lupus community of clinician-scientists has worked persistently to unravel the mystery of lupus. In recent years, lupus research has produced important clues about the origin and effects of the disease. For instance, we know more than ever before about how the immune system malfunctions to cause lupus. We are beginning to recognize which individuals are at higher risk for life-threatening complications. We have learned which therapies used in other diseases are effective for treating symptoms of lupus.

But just as we reached this pivotal time, we were hit by a downturn in the economy. Funding for key research was harder to come by as the federal government, who along with the pharmaceutical industry represents the largest funders of research, was making cutbacks to all of its programs. For lupus alone, federal funding was reported to be $134 million in 2009 but dropped to just $105 million in 2012. Included in the cuts are programs supporting the growth and development of the scientific community.

As a result of the lack of funding, several promising young lupus investigators have decided not to pursue academic careers but have moved to private practice or industry. Even a number of senior lupus investigators have left academics primarily to enter the biopharmaceutical industry. Other investigators at academic institutions are focusing more on clinical trials rather than independent research.

Nonprofit organizations like the Lupus Foundation of America are making an effort to compensate for some of the loss in funding by creating comprehensive award programs of their own through private funding. Recently, the foundation announced a new Career Development Award that will offer professional development support to early-career clinician-scientists – a step meant to help stem the hemorrhage of young lupus researchers. The foundation already offers awards meant to support lupus researchers at all other stages in their career. Such support has been crucial in retaining some researchers in the field.

But without public funding, retaining scientists in the numbers that lupus really needs will remain close to impossible because the truth is that one cannot make an academic research career on foundation money alone, especially given the stress that academic centers are undergoing. Support from the National Institutes of Health and the Department of Defense, among other federal agencies that have supported lupus research, is key.

The most disturbing impact of failing to keep up the momentum of lupus research could be on treatment development and patient care for the estimated 1.5 million Americans with the disease. While there has not been a significant impact on those so far, it is easy to see the problems we may face down the road. Research and discovery conducted at the academic level is vital to target development. If there are no academics to develop ideas, there will be no new lupus drugs in the pipeline.

Another way that the drop in lupus researchers could impact patients is that most academic centers now have lupologists, individuals who specialize in lupus. The number of lupologists continues to dwindle because of financial stress on academic centers, and not as many new lupologists are entering the field. This makes the Lupus Foundation of America’s Career Development Award important because it offers a start to retaining early-career lupus specialists.

Studies indicate that patients do better when they are cared for by lupologists, who see a large number of lupus patients, compared with rheumatologists who see a more limited number. That’s because as with anything else, you get better at doing something you do all the time. If you see a lot of people with lupus, you get better at treating it. With the loss of lupologists at academic research centers, this specialized expertise will no longer be available and patient care could suffer.

Dr. Gilkeson is chair of the Lupus Foundation of America’s Medical-Scientific Advisory Council and professor of medicine and associate dean of faculty affairs and faculty development at the Medical University of South Carolina, Charleston. He reported having no relevant financial disclosures.

As revenue sources for research dwindle, academic medical centers are under great stress today. There is a drop in patient care fees, Medicare and Medicaid reimbursement, money through philanthropy, state support, and grant support. At every center, institutional support for research is under pressure. And for those just starting their careers – particularly those with an interest in lupus research – these problems could not come at a worse time.

Lupus offers many challenges to researchers: It is hard to diagnose, it ravages different parts of the body, its symptoms come and go and often imitate other illnesses, and it manifests differently in each individual. Despite these challenges, we have come a long way, and the lupus community of clinician-scientists has worked persistently to unravel the mystery of lupus. In recent years, lupus research has produced important clues about the origin and effects of the disease. For instance, we know more than ever before about how the immune system malfunctions to cause lupus. We are beginning to recognize which individuals are at higher risk for life-threatening complications. We have learned which therapies used in other diseases are effective for treating symptoms of lupus.

But just as we reached this pivotal time, we were hit by a downturn in the economy. Funding for key research was harder to come by as the federal government, who along with the pharmaceutical industry represents the largest funders of research, was making cutbacks to all of its programs. For lupus alone, federal funding was reported to be $134 million in 2009 but dropped to just $105 million in 2012. Included in the cuts are programs supporting the growth and development of the scientific community.

As a result of the lack of funding, several promising young lupus investigators have decided not to pursue academic careers but have moved to private practice or industry. Even a number of senior lupus investigators have left academics primarily to enter the biopharmaceutical industry. Other investigators at academic institutions are focusing more on clinical trials rather than independent research.

Nonprofit organizations like the Lupus Foundation of America are making an effort to compensate for some of the loss in funding by creating comprehensive award programs of their own through private funding. Recently, the foundation announced a new Career Development Award that will offer professional development support to early-career clinician-scientists – a step meant to help stem the hemorrhage of young lupus researchers. The foundation already offers awards meant to support lupus researchers at all other stages in their career. Such support has been crucial in retaining some researchers in the field.

But without public funding, retaining scientists in the numbers that lupus really needs will remain close to impossible because the truth is that one cannot make an academic research career on foundation money alone, especially given the stress that academic centers are undergoing. Support from the National Institutes of Health and the Department of Defense, among other federal agencies that have supported lupus research, is key.

The most disturbing impact of failing to keep up the momentum of lupus research could be on treatment development and patient care for the estimated 1.5 million Americans with the disease. While there has not been a significant impact on those so far, it is easy to see the problems we may face down the road. Research and discovery conducted at the academic level is vital to target development. If there are no academics to develop ideas, there will be no new lupus drugs in the pipeline.

Another way that the drop in lupus researchers could impact patients is that most academic centers now have lupologists, individuals who specialize in lupus. The number of lupologists continues to dwindle because of financial stress on academic centers, and not as many new lupologists are entering the field. This makes the Lupus Foundation of America’s Career Development Award important because it offers a start to retaining early-career lupus specialists.

Studies indicate that patients do better when they are cared for by lupologists, who see a large number of lupus patients, compared with rheumatologists who see a more limited number. That’s because as with anything else, you get better at doing something you do all the time. If you see a lot of people with lupus, you get better at treating it. With the loss of lupologists at academic research centers, this specialized expertise will no longer be available and patient care could suffer.

Dr. Gilkeson is chair of the Lupus Foundation of America’s Medical-Scientific Advisory Council and professor of medicine and associate dean of faculty affairs and faculty development at the Medical University of South Carolina, Charleston. He reported having no relevant financial disclosures.

As revenue sources for research dwindle, academic medical centers are under great stress today. There is a drop in patient care fees, Medicare and Medicaid reimbursement, money through philanthropy, state support, and grant support. At every center, institutional support for research is under pressure. And for those just starting their careers – particularly those with an interest in lupus research – these problems could not come at a worse time.

Lupus offers many challenges to researchers: It is hard to diagnose, it ravages different parts of the body, its symptoms come and go and often imitate other illnesses, and it manifests differently in each individual. Despite these challenges, we have come a long way, and the lupus community of clinician-scientists has worked persistently to unravel the mystery of lupus. In recent years, lupus research has produced important clues about the origin and effects of the disease. For instance, we know more than ever before about how the immune system malfunctions to cause lupus. We are beginning to recognize which individuals are at higher risk for life-threatening complications. We have learned which therapies used in other diseases are effective for treating symptoms of lupus.

But just as we reached this pivotal time, we were hit by a downturn in the economy. Funding for key research was harder to come by as the federal government, who along with the pharmaceutical industry represents the largest funders of research, was making cutbacks to all of its programs. For lupus alone, federal funding was reported to be $134 million in 2009 but dropped to just $105 million in 2012. Included in the cuts are programs supporting the growth and development of the scientific community.

As a result of the lack of funding, several promising young lupus investigators have decided not to pursue academic careers but have moved to private practice or industry. Even a number of senior lupus investigators have left academics primarily to enter the biopharmaceutical industry. Other investigators at academic institutions are focusing more on clinical trials rather than independent research.

Nonprofit organizations like the Lupus Foundation of America are making an effort to compensate for some of the loss in funding by creating comprehensive award programs of their own through private funding. Recently, the foundation announced a new Career Development Award that will offer professional development support to early-career clinician-scientists – a step meant to help stem the hemorrhage of young lupus researchers. The foundation already offers awards meant to support lupus researchers at all other stages in their career. Such support has been crucial in retaining some researchers in the field.

But without public funding, retaining scientists in the numbers that lupus really needs will remain close to impossible because the truth is that one cannot make an academic research career on foundation money alone, especially given the stress that academic centers are undergoing. Support from the National Institutes of Health and the Department of Defense, among other federal agencies that have supported lupus research, is key.

The most disturbing impact of failing to keep up the momentum of lupus research could be on treatment development and patient care for the estimated 1.5 million Americans with the disease. While there has not been a significant impact on those so far, it is easy to see the problems we may face down the road. Research and discovery conducted at the academic level is vital to target development. If there are no academics to develop ideas, there will be no new lupus drugs in the pipeline.

Another way that the drop in lupus researchers could impact patients is that most academic centers now have lupologists, individuals who specialize in lupus. The number of lupologists continues to dwindle because of financial stress on academic centers, and not as many new lupologists are entering the field. This makes the Lupus Foundation of America’s Career Development Award important because it offers a start to retaining early-career lupus specialists.

Studies indicate that patients do better when they are cared for by lupologists, who see a large number of lupus patients, compared with rheumatologists who see a more limited number. That’s because as with anything else, you get better at doing something you do all the time. If you see a lot of people with lupus, you get better at treating it. With the loss of lupologists at academic research centers, this specialized expertise will no longer be available and patient care could suffer.

Dr. Gilkeson is chair of the Lupus Foundation of America’s Medical-Scientific Advisory Council and professor of medicine and associate dean of faculty affairs and faculty development at the Medical University of South Carolina, Charleston. He reported having no relevant financial disclosures.

LAS VEGAS – If psoriasis patients don’t improve after 2 months of methotrexate therapy, the drug’s probably not going to work, according to Dr. Bruce Strober, of the University of Connecticut in Farmington.

But "don’t give up" if there’s even a slight improvement at that point. Up to 45% of patients achieve psoriasis area and severity index (PASI) scores of 75 on methotrexate, but "you really have to allow the drug 24 weeks to see that. If you see any hint of efficacy, keep going," he said at the SDEF Las Vegas Dermatology Seminar.

Dr. Strober shared insights about using methotrexate culled from more than a decade of experience. He starts most patients on 15 mg/week, but smaller people at perhaps 10-12.5 mg. He’ll dose down the elderly, as well, if he suspects renal insufficiency.

"I give it all in one dose, except if it’s at 17.5 mg or more per week, then I will divide the dose, either half in the morning, half at night," or a few days apart. "I never do the q [every] 12 hours x 3-day dosing. It’s based on no science, and you don’t have to make your patient’s life so hard," he said.

Not infrequently, Dr. Strober has patients self-inject a subcutaneous formulation in lieu of oral therapy. "It likely has better bioavailability and efficacy, [and] studies suggest avoiding first pass metabolism" is safer for the liver. Liver toxicity will be a problem in up to a quarter of patients, with the obese perhaps facing a higher risk. As with CBC and renal function, monthly liver testing is a must with methotrexate, at least for the first year.

"I don’t do liver biopsies anymore. I think it’s an extremely poor test laden with sampling error, and it has its own risks," he said. Instead, "I use liver function tests pretty exclusively" to look for marked, persistent LFT [liver function test] elevations above baseline, even if patients stay in the normal range. "Not uncommonly, a patient’s LFT could be 15 over 16 AST [aspartate aminotransferase] over ALT [alanine aminotransferase], and then 3 months into methotrexate, 45 over 42. It might be in the normal range, but I think that should give you pause. You caused a threefold increase in the liver tests," he said.

"Liver-induced changes are reversible if you react early enough by reducing the dose or just stopping the drug," Dr. Strober said.

Folate supplementation helps to protect the liver and reduce GI side effects. Dr. Strober often adds folinic acid, three 5 mg-doses per week, if GI side effects persist with folic acid alone. It’s as effective as folic acid, but "folic acid is cheaper. That’s why I start with it," he said.

The risk of pancytopenia is increased with poor renal function or use of sulfonamide-based antibiotics. "Monitor the CBC closely in the first few visits. You need folinic acid for rescue if it becomes a problem," he said.

Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – If psoriasis patients don’t improve after 2 months of methotrexate therapy, the drug’s probably not going to work, according to Dr. Bruce Strober, of the University of Connecticut in Farmington.

But "don’t give up" if there’s even a slight improvement at that point. Up to 45% of patients achieve psoriasis area and severity index (PASI) scores of 75 on methotrexate, but "you really have to allow the drug 24 weeks to see that. If you see any hint of efficacy, keep going," he said at the SDEF Las Vegas Dermatology Seminar.

Dr. Strober shared insights about using methotrexate culled from more than a decade of experience. He starts most patients on 15 mg/week, but smaller people at perhaps 10-12.5 mg. He’ll dose down the elderly, as well, if he suspects renal insufficiency.

"I give it all in one dose, except if it’s at 17.5 mg or more per week, then I will divide the dose, either half in the morning, half at night," or a few days apart. "I never do the q [every] 12 hours x 3-day dosing. It’s based on no science, and you don’t have to make your patient’s life so hard," he said.

Not infrequently, Dr. Strober has patients self-inject a subcutaneous formulation in lieu of oral therapy. "It likely has better bioavailability and efficacy, [and] studies suggest avoiding first pass metabolism" is safer for the liver. Liver toxicity will be a problem in up to a quarter of patients, with the obese perhaps facing a higher risk. As with CBC and renal function, monthly liver testing is a must with methotrexate, at least for the first year.

"I don’t do liver biopsies anymore. I think it’s an extremely poor test laden with sampling error, and it has its own risks," he said. Instead, "I use liver function tests pretty exclusively" to look for marked, persistent LFT [liver function test] elevations above baseline, even if patients stay in the normal range. "Not uncommonly, a patient’s LFT could be 15 over 16 AST [aspartate aminotransferase] over ALT [alanine aminotransferase], and then 3 months into methotrexate, 45 over 42. It might be in the normal range, but I think that should give you pause. You caused a threefold increase in the liver tests," he said.

"Liver-induced changes are reversible if you react early enough by reducing the dose or just stopping the drug," Dr. Strober said.

Folate supplementation helps to protect the liver and reduce GI side effects. Dr. Strober often adds folinic acid, three 5 mg-doses per week, if GI side effects persist with folic acid alone. It’s as effective as folic acid, but "folic acid is cheaper. That’s why I start with it," he said.

The risk of pancytopenia is increased with poor renal function or use of sulfonamide-based antibiotics. "Monitor the CBC closely in the first few visits. You need folinic acid for rescue if it becomes a problem," he said.

Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – If psoriasis patients don’t improve after 2 months of methotrexate therapy, the drug’s probably not going to work, according to Dr. Bruce Strober, of the University of Connecticut in Farmington.

But "don’t give up" if there’s even a slight improvement at that point. Up to 45% of patients achieve psoriasis area and severity index (PASI) scores of 75 on methotrexate, but "you really have to allow the drug 24 weeks to see that. If you see any hint of efficacy, keep going," he said at the SDEF Las Vegas Dermatology Seminar.

Dr. Strober shared insights about using methotrexate culled from more than a decade of experience. He starts most patients on 15 mg/week, but smaller people at perhaps 10-12.5 mg. He’ll dose down the elderly, as well, if he suspects renal insufficiency.

"I give it all in one dose, except if it’s at 17.5 mg or more per week, then I will divide the dose, either half in the morning, half at night," or a few days apart. "I never do the q [every] 12 hours x 3-day dosing. It’s based on no science, and you don’t have to make your patient’s life so hard," he said.

Not infrequently, Dr. Strober has patients self-inject a subcutaneous formulation in lieu of oral therapy. "It likely has better bioavailability and efficacy, [and] studies suggest avoiding first pass metabolism" is safer for the liver. Liver toxicity will be a problem in up to a quarter of patients, with the obese perhaps facing a higher risk. As with CBC and renal function, monthly liver testing is a must with methotrexate, at least for the first year.

"I don’t do liver biopsies anymore. I think it’s an extremely poor test laden with sampling error, and it has its own risks," he said. Instead, "I use liver function tests pretty exclusively" to look for marked, persistent LFT [liver function test] elevations above baseline, even if patients stay in the normal range. "Not uncommonly, a patient’s LFT could be 15 over 16 AST [aspartate aminotransferase] over ALT [alanine aminotransferase], and then 3 months into methotrexate, 45 over 42. It might be in the normal range, but I think that should give you pause. You caused a threefold increase in the liver tests," he said.

"Liver-induced changes are reversible if you react early enough by reducing the dose or just stopping the drug," Dr. Strober said.

Folate supplementation helps to protect the liver and reduce GI side effects. Dr. Strober often adds folinic acid, three 5 mg-doses per week, if GI side effects persist with folic acid alone. It’s as effective as folic acid, but "folic acid is cheaper. That’s why I start with it," he said.

The risk of pancytopenia is increased with poor renal function or use of sulfonamide-based antibiotics. "Monitor the CBC closely in the first few visits. You need folinic acid for rescue if it becomes a problem," he said.

Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

LOS ANGELES – The largest-ever U.S. study of the long-term risk of cardiovascular events in survivors of childhood acute Kawasaki disease paints a highly reassuring picture overall.

Indeed, the cardiovascular event rate in 546 patients during an average 15-year follow-up since their acute illness was extremely low – no different, in fact, than in 2,218 matched controls, Dr. Taylor J. Holve reported at the annual scientific sessions of the American Heart Association.

The composite endpoint of acute coronary syndrome, coronary revascularization heart failure, ventricular arrhythmia, valvular heart disease, aortic aneurysm, or all-cause mortality occurred in two patients with a history of Kawasaki disease and in seven controls. That translated to an adjusted incidence rate of 0.246 events per 1,000 person-years in the Kawasaki disease group and a similar figure of 0.217 per 1,000 person-years in controls, according to Dr. Holve of Kaiser San Francisco Medical Center.

Twenty-five patients in the Kawasaki disease group had a persistent coronary artery aneurysm. Both of the cardiovascular events that occurred during long-term follow-up – one case of acute coronary syndrome (ACS), and another of ACS followed by coronary artery bypass surgery – were in the small subgroup with persistent coronary aneurysm.

Other investigators have previously described the increased long-term risk posed by formation of a persistent aneurysm in survivors of acute Kawasaki disease. It’s clear from this large study that survivors with persistent coronary aneurysm are a higher-risk subgroup meriting long-term cardiovascular surveillance. In contrast, Kawasaki disease survivors without persistent aneurysm had a cardiovascular event rate of zero. A caveat: The average age of these patients at 15 years of follow-up was slightly over 21 years; continued follow-up will be required to exclude the possibility of an elevated risk of cardiovascular events once patients without a persistent coronary aneurysm hit their mid-20s and beyond, Dr. Holve noted.

The various treatment strategies employed in treating acute Kawasaki disease showed no association with short- or long-term complication rates.

Dr. Holve reported having no financial conflicts.

[email protected]

LOS ANGELES – The largest-ever U.S. study of the long-term risk of cardiovascular events in survivors of childhood acute Kawasaki disease paints a highly reassuring picture overall.

Indeed, the cardiovascular event rate in 546 patients during an average 15-year follow-up since their acute illness was extremely low – no different, in fact, than in 2,218 matched controls, Dr. Taylor J. Holve reported at the annual scientific sessions of the American Heart Association.

The composite endpoint of acute coronary syndrome, coronary revascularization heart failure, ventricular arrhythmia, valvular heart disease, aortic aneurysm, or all-cause mortality occurred in two patients with a history of Kawasaki disease and in seven controls. That translated to an adjusted incidence rate of 0.246 events per 1,000 person-years in the Kawasaki disease group and a similar figure of 0.217 per 1,000 person-years in controls, according to Dr. Holve of Kaiser San Francisco Medical Center.

Twenty-five patients in the Kawasaki disease group had a persistent coronary artery aneurysm. Both of the cardiovascular events that occurred during long-term follow-up – one case of acute coronary syndrome (ACS), and another of ACS followed by coronary artery bypass surgery – were in the small subgroup with persistent coronary aneurysm.

Other investigators have previously described the increased long-term risk posed by formation of a persistent aneurysm in survivors of acute Kawasaki disease. It’s clear from this large study that survivors with persistent coronary aneurysm are a higher-risk subgroup meriting long-term cardiovascular surveillance. In contrast, Kawasaki disease survivors without persistent aneurysm had a cardiovascular event rate of zero. A caveat: The average age of these patients at 15 years of follow-up was slightly over 21 years; continued follow-up will be required to exclude the possibility of an elevated risk of cardiovascular events once patients without a persistent coronary aneurysm hit their mid-20s and beyond, Dr. Holve noted.

The various treatment strategies employed in treating acute Kawasaki disease showed no association with short- or long-term complication rates.

Dr. Holve reported having no financial conflicts.

[email protected]

LOS ANGELES – The largest-ever U.S. study of the long-term risk of cardiovascular events in survivors of childhood acute Kawasaki disease paints a highly reassuring picture overall.

Indeed, the cardiovascular event rate in 546 patients during an average 15-year follow-up since their acute illness was extremely low – no different, in fact, than in 2,218 matched controls, Dr. Taylor J. Holve reported at the annual scientific sessions of the American Heart Association.

The composite endpoint of acute coronary syndrome, coronary revascularization heart failure, ventricular arrhythmia, valvular heart disease, aortic aneurysm, or all-cause mortality occurred in two patients with a history of Kawasaki disease and in seven controls. That translated to an adjusted incidence rate of 0.246 events per 1,000 person-years in the Kawasaki disease group and a similar figure of 0.217 per 1,000 person-years in controls, according to Dr. Holve of Kaiser San Francisco Medical Center.

Twenty-five patients in the Kawasaki disease group had a persistent coronary artery aneurysm. Both of the cardiovascular events that occurred during long-term follow-up – one case of acute coronary syndrome (ACS), and another of ACS followed by coronary artery bypass surgery – were in the small subgroup with persistent coronary aneurysm.

Other investigators have previously described the increased long-term risk posed by formation of a persistent aneurysm in survivors of acute Kawasaki disease. It’s clear from this large study that survivors with persistent coronary aneurysm are a higher-risk subgroup meriting long-term cardiovascular surveillance. In contrast, Kawasaki disease survivors without persistent aneurysm had a cardiovascular event rate of zero. A caveat: The average age of these patients at 15 years of follow-up was slightly over 21 years; continued follow-up will be required to exclude the possibility of an elevated risk of cardiovascular events once patients without a persistent coronary aneurysm hit their mid-20s and beyond, Dr. Holve noted.

The various treatment strategies employed in treating acute Kawasaki disease showed no association with short- or long-term complication rates.

Dr. Holve reported having no financial conflicts.

[email protected]

PRAGUE – Two biologic agents addressing novel therapeutic targets in psoriasis continue to advance in the developmental pipeline, as highlighted in studies presented at the annual congress of the European Academy of Dermatology and Venereology.

Merck’s MK-3222 is a monoclonal antibody directed against the interleukin-23 p19 subunit. MK-3222 specifically binds and neutralizes IL23, and thereby inhibits IL23-dependent Th17 cells, which mediate inflammatory injury in psoriasis.

Dr. Tamara Kopp of the Medical University of Vienna presented a proof-of-concept study which suggested that targeting IL23p19 via MK-3222 could be an important new form of therapy for moderate to severe psoriasis. But there was a potential red flag: Eighteen percent of patients treated with just three doses of the antibody over the course of up to 12 weeks developed antidrug antibodies. The clinical significance of these antibodies will require additional study.

Separately, Dr. Richard Langley presented a secondary analysis of data from a phase II, 125-patient, double-blind, placebo-controlled, dose-ranging study of secukinumab, a fully human monoclonal antibody directed against the proinflammatory cytokine IL17A (Br. J. Dermatol. 2012 Oct. 27 [doi: 10.1111/bjd.12110]). The objective was to determine how long it takes for psoriasis symptoms to return after 8 weeks of therapy.

The answer is that relapse takes a very long time.

At the most effective dose tested in the trial, which was 150 mg of secukinumab given subcutaneously at weeks 0, 4, and 8, a Psoriasis Area and Severity Index (PASI) 75 response was seen at week 12 in 82% of patients assigned to the monoclonal antibody, compared with 9% of placebo-treated controls. A PASI 90 response – that is, at least a 90% reduction in the PASI score compared with baseline – was documented at week 12 in 52% of patients on secukinumab and 5% of controls.

At week 32, fully 24 weeks since the final 150-mg dose, only half of PASI 75 responders to secukinumab had relapsed as defined by loss of at least 50% of the maximum PASI improvement seen at week 12. Median time to relapse was 174 days, reported Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University in Halifax, N.S.

Secukinumab was quite well tolerated. Indeed, the overall adverse events and serious adverse events were generally similar in nature to placebo, but less frequent.

Based upon the phase II time-to-relapse analysis, it’s likely that two maintenance therapy schedules will be tested in larger studies: one involving retreatment at 4-week intervals, and another in which retreatment is held in abeyance until relapse commences, according to Dr. Langley.

Dr. Kopp reported that the MK-3222 study involved 77 enrollees, 66 of whom completed the 16-week dose-ranging study. Only 2 of the 11 dropouts did so because of adverse events.

All 11 patients who received intravenous MK-3222 at either 3 or 10 mg/kg on days 1, 56, and 84 had a PASI 75 response at week 16. So did 10 of 15 who received 3 mg/kg and 13 of 14 who received 10 mg/kg on days 1, 28, and 56.

The anti-IL23p19 antibody was generally well tolerated, with no dose-related increase in adverse events and no ECG or laboratory abnormalities.

Of the nine patients who developed antidrug antibodies during the study, five had serum drug concentrations that were significantly lower than those of subjects without antidrug antibodies; two of these five patients – those with the most pronounced reduction in drug concentrations – also had neutralizing antidrug antibodies to MK-3222. However, patients with antidrug antibodies did not differ from the others in terms of their clinical response to treatment as reflected in PASI improvement, and their adverse event profile was not outstanding.

Dr. Kopp serves as a consultant to Merck, which is developing MK-3222. The secukinumab study was funded by Novartis. Dr. Langley is a consultant to the company.

[email protected]

PRAGUE – Two biologic agents addressing novel therapeutic targets in psoriasis continue to advance in the developmental pipeline, as highlighted in studies presented at the annual congress of the European Academy of Dermatology and Venereology.

Merck’s MK-3222 is a monoclonal antibody directed against the interleukin-23 p19 subunit. MK-3222 specifically binds and neutralizes IL23, and thereby inhibits IL23-dependent Th17 cells, which mediate inflammatory injury in psoriasis.

Dr. Tamara Kopp of the Medical University of Vienna presented a proof-of-concept study which suggested that targeting IL23p19 via MK-3222 could be an important new form of therapy for moderate to severe psoriasis. But there was a potential red flag: Eighteen percent of patients treated with just three doses of the antibody over the course of up to 12 weeks developed antidrug antibodies. The clinical significance of these antibodies will require additional study.

Separately, Dr. Richard Langley presented a secondary analysis of data from a phase II, 125-patient, double-blind, placebo-controlled, dose-ranging study of secukinumab, a fully human monoclonal antibody directed against the proinflammatory cytokine IL17A (Br. J. Dermatol. 2012 Oct. 27 [doi: 10.1111/bjd.12110]). The objective was to determine how long it takes for psoriasis symptoms to return after 8 weeks of therapy.

The answer is that relapse takes a very long time.

At the most effective dose tested in the trial, which was 150 mg of secukinumab given subcutaneously at weeks 0, 4, and 8, a Psoriasis Area and Severity Index (PASI) 75 response was seen at week 12 in 82% of patients assigned to the monoclonal antibody, compared with 9% of placebo-treated controls. A PASI 90 response – that is, at least a 90% reduction in the PASI score compared with baseline – was documented at week 12 in 52% of patients on secukinumab and 5% of controls.

At week 32, fully 24 weeks since the final 150-mg dose, only half of PASI 75 responders to secukinumab had relapsed as defined by loss of at least 50% of the maximum PASI improvement seen at week 12. Median time to relapse was 174 days, reported Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University in Halifax, N.S.

Secukinumab was quite well tolerated. Indeed, the overall adverse events and serious adverse events were generally similar in nature to placebo, but less frequent.

Based upon the phase II time-to-relapse analysis, it’s likely that two maintenance therapy schedules will be tested in larger studies: one involving retreatment at 4-week intervals, and another in which retreatment is held in abeyance until relapse commences, according to Dr. Langley.

Dr. Kopp reported that the MK-3222 study involved 77 enrollees, 66 of whom completed the 16-week dose-ranging study. Only 2 of the 11 dropouts did so because of adverse events.

All 11 patients who received intravenous MK-3222 at either 3 or 10 mg/kg on days 1, 56, and 84 had a PASI 75 response at week 16. So did 10 of 15 who received 3 mg/kg and 13 of 14 who received 10 mg/kg on days 1, 28, and 56.

The anti-IL23p19 antibody was generally well tolerated, with no dose-related increase in adverse events and no ECG or laboratory abnormalities.

Of the nine patients who developed antidrug antibodies during the study, five had serum drug concentrations that were significantly lower than those of subjects without antidrug antibodies; two of these five patients – those with the most pronounced reduction in drug concentrations – also had neutralizing antidrug antibodies to MK-3222. However, patients with antidrug antibodies did not differ from the others in terms of their clinical response to treatment as reflected in PASI improvement, and their adverse event profile was not outstanding.

Dr. Kopp serves as a consultant to Merck, which is developing MK-3222. The secukinumab study was funded by Novartis. Dr. Langley is a consultant to the company.

[email protected]

PRAGUE – Two biologic agents addressing novel therapeutic targets in psoriasis continue to advance in the developmental pipeline, as highlighted in studies presented at the annual congress of the European Academy of Dermatology and Venereology.

Merck’s MK-3222 is a monoclonal antibody directed against the interleukin-23 p19 subunit. MK-3222 specifically binds and neutralizes IL23, and thereby inhibits IL23-dependent Th17 cells, which mediate inflammatory injury in psoriasis.

Dr. Tamara Kopp of the Medical University of Vienna presented a proof-of-concept study which suggested that targeting IL23p19 via MK-3222 could be an important new form of therapy for moderate to severe psoriasis. But there was a potential red flag: Eighteen percent of patients treated with just three doses of the antibody over the course of up to 12 weeks developed antidrug antibodies. The clinical significance of these antibodies will require additional study.

Separately, Dr. Richard Langley presented a secondary analysis of data from a phase II, 125-patient, double-blind, placebo-controlled, dose-ranging study of secukinumab, a fully human monoclonal antibody directed against the proinflammatory cytokine IL17A (Br. J. Dermatol. 2012 Oct. 27 [doi: 10.1111/bjd.12110]). The objective was to determine how long it takes for psoriasis symptoms to return after 8 weeks of therapy.

The answer is that relapse takes a very long time.

At the most effective dose tested in the trial, which was 150 mg of secukinumab given subcutaneously at weeks 0, 4, and 8, a Psoriasis Area and Severity Index (PASI) 75 response was seen at week 12 in 82% of patients assigned to the monoclonal antibody, compared with 9% of placebo-treated controls. A PASI 90 response – that is, at least a 90% reduction in the PASI score compared with baseline – was documented at week 12 in 52% of patients on secukinumab and 5% of controls.

At week 32, fully 24 weeks since the final 150-mg dose, only half of PASI 75 responders to secukinumab had relapsed as defined by loss of at least 50% of the maximum PASI improvement seen at week 12. Median time to relapse was 174 days, reported Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University in Halifax, N.S.

Secukinumab was quite well tolerated. Indeed, the overall adverse events and serious adverse events were generally similar in nature to placebo, but less frequent.

Based upon the phase II time-to-relapse analysis, it’s likely that two maintenance therapy schedules will be tested in larger studies: one involving retreatment at 4-week intervals, and another in which retreatment is held in abeyance until relapse commences, according to Dr. Langley.

Dr. Kopp reported that the MK-3222 study involved 77 enrollees, 66 of whom completed the 16-week dose-ranging study. Only 2 of the 11 dropouts did so because of adverse events.

All 11 patients who received intravenous MK-3222 at either 3 or 10 mg/kg on days 1, 56, and 84 had a PASI 75 response at week 16. So did 10 of 15 who received 3 mg/kg and 13 of 14 who received 10 mg/kg on days 1, 28, and 56.

The anti-IL23p19 antibody was generally well tolerated, with no dose-related increase in adverse events and no ECG or laboratory abnormalities.

Of the nine patients who developed antidrug antibodies during the study, five had serum drug concentrations that were significantly lower than those of subjects without antidrug antibodies; two of these five patients – those with the most pronounced reduction in drug concentrations – also had neutralizing antidrug antibodies to MK-3222. However, patients with antidrug antibodies did not differ from the others in terms of their clinical response to treatment as reflected in PASI improvement, and their adverse event profile was not outstanding.

Dr. Kopp serves as a consultant to Merck, which is developing MK-3222. The secukinumab study was funded by Novartis. Dr. Langley is a consultant to the company.

[email protected]

LAS VEGAS – To prevent immunogenicity to biologics, it’s best to have psoriasis patients on methotrexate at baseline, according to Dr. Bruce Strober of the University of Connecticut, Farmington.

Once patients develop antibodies to a biologic, “the horse is already out of the barn. It may be too late to recover efficacy by adding methotrexate,” Dr. Strober said. “Add the biologic to the methotrexate, not visa versa” (Br. J. Dermatol. 2012;167:649-57).

Anti–tumor necrosis factors and other biologics often lose their effects as patients build antibodies to the foreign proteins they contain. “Drug levels fall off a cliff when you have a lot of immunogenicity. The major challenge [is] making sure patients 1-3 years out see the response they got in the first 6 months,” Dr. Strober said at the SDEF Las Vegas Dermatology Seminar.

Methotrexate is thought to diminish the antibody response, blocking immunogenicity. “Biologics invariably show greater and more durable efficacy” with methotrexate “even when methotrexate is ineffective on its own,” he said. When oral therapy is indicated, Dr. Strober said he starts most of his psoriasis patients on about 15 mg/wk and waits 8-12 weeks to see whether this works. If there is no response, he will add a biologic and continue the methotrexate.

The dose of methotrexate needed to tame the antibody response remains unclear. “The consensus in the rheumatology world is somewhere around 15 mg weekly, but I don’t always use that dose. I will go down to 7.5 mg to 12.5 mg in many patients,” said Dr. Strober. “It appears anecdotally that there’s good protection of the [biologic] response with those doses. It’s something you might vary based on the size of the patient,” he said. “Episodic dosing gives you the greatest percent of patients getting antibodies, [so] dose biologics without interruption if you can,” he added (J. Am. Acad. Dermatol. 2007;56:31.e1-15).

Immunogenicity to one biologic does not necessarily translate to immunogenicity to another. Also, increasing infusion frequency can help recapture a biologic’s effect, he noted.

SDEF and this news organization are owned by Frontline Medical Communications. Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen.

LAS VEGAS – To prevent immunogenicity to biologics, it’s best to have psoriasis patients on methotrexate at baseline, according to Dr. Bruce Strober of the University of Connecticut, Farmington.

Once patients develop antibodies to a biologic, “the horse is already out of the barn. It may be too late to recover efficacy by adding methotrexate,” Dr. Strober said. “Add the biologic to the methotrexate, not visa versa” (Br. J. Dermatol. 2012;167:649-57).

Anti–tumor necrosis factors and other biologics often lose their effects as patients build antibodies to the foreign proteins they contain. “Drug levels fall off a cliff when you have a lot of immunogenicity. The major challenge [is] making sure patients 1-3 years out see the response they got in the first 6 months,” Dr. Strober said at the SDEF Las Vegas Dermatology Seminar.

Methotrexate is thought to diminish the antibody response, blocking immunogenicity. “Biologics invariably show greater and more durable efficacy” with methotrexate “even when methotrexate is ineffective on its own,” he said. When oral therapy is indicated, Dr. Strober said he starts most of his psoriasis patients on about 15 mg/wk and waits 8-12 weeks to see whether this works. If there is no response, he will add a biologic and continue the methotrexate.

The dose of methotrexate needed to tame the antibody response remains unclear. “The consensus in the rheumatology world is somewhere around 15 mg weekly, but I don’t always use that dose. I will go down to 7.5 mg to 12.5 mg in many patients,” said Dr. Strober. “It appears anecdotally that there’s good protection of the [biologic] response with those doses. It’s something you might vary based on the size of the patient,” he said. “Episodic dosing gives you the greatest percent of patients getting antibodies, [so] dose biologics without interruption if you can,” he added (J. Am. Acad. Dermatol. 2007;56:31.e1-15).

Immunogenicity to one biologic does not necessarily translate to immunogenicity to another. Also, increasing infusion frequency can help recapture a biologic’s effect, he noted.

SDEF and this news organization are owned by Frontline Medical Communications. Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen.

LAS VEGAS – To prevent immunogenicity to biologics, it’s best to have psoriasis patients on methotrexate at baseline, according to Dr. Bruce Strober of the University of Connecticut, Farmington.

Once patients develop antibodies to a biologic, “the horse is already out of the barn. It may be too late to recover efficacy by adding methotrexate,” Dr. Strober said. “Add the biologic to the methotrexate, not visa versa” (Br. J. Dermatol. 2012;167:649-57).

Anti–tumor necrosis factors and other biologics often lose their effects as patients build antibodies to the foreign proteins they contain. “Drug levels fall off a cliff when you have a lot of immunogenicity. The major challenge [is] making sure patients 1-3 years out see the response they got in the first 6 months,” Dr. Strober said at the SDEF Las Vegas Dermatology Seminar.

Methotrexate is thought to diminish the antibody response, blocking immunogenicity. “Biologics invariably show greater and more durable efficacy” with methotrexate “even when methotrexate is ineffective on its own,” he said. When oral therapy is indicated, Dr. Strober said he starts most of his psoriasis patients on about 15 mg/wk and waits 8-12 weeks to see whether this works. If there is no response, he will add a biologic and continue the methotrexate.

The dose of methotrexate needed to tame the antibody response remains unclear. “The consensus in the rheumatology world is somewhere around 15 mg weekly, but I don’t always use that dose. I will go down to 7.5 mg to 12.5 mg in many patients,” said Dr. Strober. “It appears anecdotally that there’s good protection of the [biologic] response with those doses. It’s something you might vary based on the size of the patient,” he said. “Episodic dosing gives you the greatest percent of patients getting antibodies, [so] dose biologics without interruption if you can,” he added (J. Am. Acad. Dermatol. 2007;56:31.e1-15).

Immunogenicity to one biologic does not necessarily translate to immunogenicity to another. Also, increasing infusion frequency can help recapture a biologic’s effect, he noted.

SDEF and this news organization are owned by Frontline Medical Communications. Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen.