Psoriasis Collection

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

SDEF and this news organization are owned by the same parent organization.

Side effects in conjunction with inadequate disease control lead patients with plaque psoriasis to discontinue methotrexate (MTX) treatment, Dr. Marisol Otero and her colleagues reported.

The investigators identified 85 adult patients with plaque psoriasis from the Continuous Assessment of Psoriasis Treatment Use Registry With Methotrexate (MTX-CAPTURE) who had been treated with MTX for up to of 5.2 years. All had been started on MTX in accordance with Dutch and European guidelines.

Dose adjustments during treatment were made at physicians’ discretion and most patients (84) received folic acid supplements to protect against gastrointestinal side effects. Patients were required to have at least one follow up session with their physician during the study, according to Dr. Otero of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and her colleagues.

At the end of 5 years, 55 patients (64.7%) had discontinued MTX, defined as cessation of MTX for more than 90 days or addition of another systemic psoriasis medication (Br J Dermatol. doi: 10.1111/bjd.15305).

Of the patients who discontinued treatment, 19 (34.5%) did so solely because of side effects, 14 (25.5%) discontinued because of lack of efficacy, and 7 (12.7%) cited the combination of side effects and ineffectiveness. Nine (16.4%) decided to end treatment for other reasons including personal decision, desire for pregnancy, and clinically inactive disease. Six (10.9%) were lost to for follow-up.

Side effects alone were the primary determinant in drug survival, with an overall drug survival rate for MTX of 1.8 years, Dr. Otero noted.

“It was remarkable that discontinuation due to side effects and ineffectiveness, were both common, while our hypothesis was that drug survival of MTX would be mainly limited by side effects,” the investigators said. “Side effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control solely.”
 

Side effects in conjunction with inadequate disease control lead patients with plaque psoriasis to discontinue methotrexate (MTX) treatment, Dr. Marisol Otero and her colleagues reported.

The investigators identified 85 adult patients with plaque psoriasis from the Continuous Assessment of Psoriasis Treatment Use Registry With Methotrexate (MTX-CAPTURE) who had been treated with MTX for up to of 5.2 years. All had been started on MTX in accordance with Dutch and European guidelines.

Dose adjustments during treatment were made at physicians’ discretion and most patients (84) received folic acid supplements to protect against gastrointestinal side effects. Patients were required to have at least one follow up session with their physician during the study, according to Dr. Otero of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and her colleagues.

At the end of 5 years, 55 patients (64.7%) had discontinued MTX, defined as cessation of MTX for more than 90 days or addition of another systemic psoriasis medication (Br J Dermatol. doi: 10.1111/bjd.15305).

Of the patients who discontinued treatment, 19 (34.5%) did so solely because of side effects, 14 (25.5%) discontinued because of lack of efficacy, and 7 (12.7%) cited the combination of side effects and ineffectiveness. Nine (16.4%) decided to end treatment for other reasons including personal decision, desire for pregnancy, and clinically inactive disease. Six (10.9%) were lost to for follow-up.

Side effects alone were the primary determinant in drug survival, with an overall drug survival rate for MTX of 1.8 years, Dr. Otero noted.

“It was remarkable that discontinuation due to side effects and ineffectiveness, were both common, while our hypothesis was that drug survival of MTX would be mainly limited by side effects,” the investigators said. “Side effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control solely.”
 

Side effects in conjunction with inadequate disease control lead patients with plaque psoriasis to discontinue methotrexate (MTX) treatment, Dr. Marisol Otero and her colleagues reported.

The investigators identified 85 adult patients with plaque psoriasis from the Continuous Assessment of Psoriasis Treatment Use Registry With Methotrexate (MTX-CAPTURE) who had been treated with MTX for up to of 5.2 years. All had been started on MTX in accordance with Dutch and European guidelines.

Dose adjustments during treatment were made at physicians’ discretion and most patients (84) received folic acid supplements to protect against gastrointestinal side effects. Patients were required to have at least one follow up session with their physician during the study, according to Dr. Otero of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and her colleagues.

At the end of 5 years, 55 patients (64.7%) had discontinued MTX, defined as cessation of MTX for more than 90 days or addition of another systemic psoriasis medication (Br J Dermatol. doi: 10.1111/bjd.15305).

Of the patients who discontinued treatment, 19 (34.5%) did so solely because of side effects, 14 (25.5%) discontinued because of lack of efficacy, and 7 (12.7%) cited the combination of side effects and ineffectiveness. Nine (16.4%) decided to end treatment for other reasons including personal decision, desire for pregnancy, and clinically inactive disease. Six (10.9%) were lost to for follow-up.

Side effects alone were the primary determinant in drug survival, with an overall drug survival rate for MTX of 1.8 years, Dr. Otero noted.

“It was remarkable that discontinuation due to side effects and ineffectiveness, were both common, while our hypothesis was that drug survival of MTX would be mainly limited by side effects,” the investigators said. “Side effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control solely.”
 

The Food and Drug Administration has proposed a regulatory path for biosimilar biologics that are interchangeable with the reference product, paving the way for a new generation of less-expensive versions of these unique drugs.

But bringing an interchangeable biosimilar to market won’t be easy. The bar for interchangeability will be high, requiring that manufacturers prove switching between the new and older products is safe. And clinicians, while cautiously optimistic, aren’t thrilled with the industry payoff that could come with the designation: freedom for insurance companies and pharmacies to switch products at the dispensing level without requiring a new prescription.

The draft FDA guidance for industry, “Considerations in Demonstrating Interchangeability With a Reference Product,” arises from the Biologics Price Competition and Innovation Act of 2009. That section of the Affordable Care Act provides for abbreviated approval pathways for biological products that are demonstrated to be “highly similar” (biosimilar) to or “interchangeable” with an FDA-approved biological product.

The difference between these appellations is subtle but critical to the regulatory process – and perhaps to patient safety. Regulators recognize that the structure of these large, highly complex molecules can never precisely replicate the reference product. But to be labeled a “biosimilar,” developers must prove that the new product functions essentially the same; there can be no clinically meaningful differences in terms of safety, purity, and potency. Unlike a generic medication, a biosimilar can’t be substituted for its reference product at the pharmacy level. If a physician wants the patient on that biosimilar, the script must specify it.

Interchangeables jump a higher regulatory bar

An “interchangeable biosimilar,” though, would have to jump a higher regulatory bar. Not only must it produce the same clinical result as the reference product, it also must be benignly interchangeable with it, conferring no additional risk if a patient switches from the reference to the biosimilar and back again. A pharmacist could, if permitted by state law, substitute an interchangeable product for the reference product without going through the prescriber.

Like biosimilars, interchangeable products need not be tested in every disease for which the reference drug is approved, according to the document. Once they are proved safe for one indication, those data can be extrapolated to allow approval for the other indications as well. Nor do biosimilars need to prove efficacy per se, as their molecular similarity to the reference product ensures that they bind to the same receptor and exert the same therapeutic effect.

The biosimilar/interchangeable market has been slow to take off in the United States. There are no approved interchangeable biosimilars, and only four biosimilars – three of which were approved in 2016:

• Sandoz’ filgrastim-sndz (Zarxio).

• Pfizer’s and Celltrion’s infliximab-dyyb (Inflectra).

• Sandoz’ etanercept-szzs (Erelzi).

• Amgen’s adalimumab-atto (Amjevita).

Switching studies is the key to achieving the interchangeable designation, according to the FDA document. They must include at least two full switches between the candidate product and the reference product, which must be licensed in the United States.

But because these products are so structurally diverse, the FDA isn’t imposing a one-size-fits-all process on them. Instead, the molecular complexity and immunogenicity of each product will dictate its approval requirements.

Those with relatively low structural complexity, high molecular similarity to the reference product, and a low incidence of immunogenic adverse events may only need a single switching study to achieve the “interchangeability” designation.

The bar will be higher for a product with high structural complexity that is not as similar to the reference product, or which has been associated with immunogenic adverse events. For this product, FDA might also require extensive safety postmarketing data for the product as a licensed biosimilar, as well as a switching study.

Pharmacokinetics, pharmacodynamics, immunogenicity, and safety will be the primary endpoints of a switching study. Efficacy data are not necessary but can be used as supportive endpoints. Any safety signals in a switching study would raise regulatory eyebrows whether they came from the candidate product or the reference product. Since the study replicates what could happen if the two were used sequentially, it makes little difference from which product the event might arise.

“If an apparent difference in immune response or adverse events is noticed between the switching and nonswitching arms of the study ... it would raise concerns as to whether the proposed interchangeable product is interchangeable, regardless of whether the proposed interchangeable product or the reference product or the switching of the two products actually caused the event,” the document notes.

The E.U. vs. U.S. experience

The United States is only now getting a taste of what has become common fare in the European Union, said Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee. The European Medicines Agency approved its first biosimilar in 2006. Since then, 23 such drugs have come on the market, at an average price of about 30% less than the reference drug. Prices for some drugs have dropped as much as 70% in countries in which national health care systems abandoned the reference product in favor of the competing biosimilar, Dr. Worthing said in an interview.

“But the U.S. doesn’t have a national health care system, so it won’t work like that here.” In fact, he noted, brand-new data show that Medicare actually paid 22% more for the infliximab biosimilar Inflectra than it did for Remicade in the last quarter of 2016.

It’s not immediately apparent why this is the case, but it’s probably related to company discounts and rebates on these very expensive drugs. According to the report in Inside Health Policy, Janssen Biotech may have increased its discount on the drug to compete with Inflectra’s launch price of 15% below Remicade’s wholesale cost. Prices won’t moderate as much in the United States as in the European Union until several biosimilars of the same class appear, Dr. Worthing said.

There have already been allegations that big pharma manipulates international and national pricing to reduce biosimilar competition.

In June, Russian biotech company Biocad filed a lawsuit in New York charging Roche/Genentech with price fixing. The suit alleges that the companies cut the cost of three cancer drugs (Avastin, Herceptin, and Rituxan/MabThera) in Russia, where Biocad markets biosimilars for each. At the same time, Biocad alleges, the companies raised U.S. prices on those drugs to make up for the money they were losing on the Russian market.

Nonmedical switching raises concerns

Academic medical societies and clinicians interviewed for this article view the proposed approval pathway with cautious optimism. While acknowledging the potential benefit of reducing the costs of prohibitively expensive drugs, they uniformly insist that patient safety – not economic pressure – should be the driving force here.

“I was initially skeptical, and I do believe that we need very close pharmacovigilance in monitoring these for safety,” said Gideon Smith, MD, PhD, a dermatologist at Massachusetts General Hospital, Boston. “But there has been huge uptake of these products in the E.U., and the data are so extensive that we can be reasonably confident these drugs are effective, and no good reason to believe the safety will be any different.”

He is not as comfortable with the prospect of pharmacy-level substitution of an interchangeable biosimilar with the reference product – a feeling that other clinicians echoed.

“I think this is a fundamental issue that should have been dealt with on a federal level. Physicians should always be involved in the decision,” said Dr. Smith, who spoke at an FDA advisory committee meeting last summer on behalf of the American Academy of Dermatology (AAD).

*This article was updated 1/31/2017.

[email protected]

On Twitter @alz_gal

The Food and Drug Administration has proposed a regulatory path for biosimilar biologics that are interchangeable with the reference product, paving the way for a new generation of less-expensive versions of these unique drugs.

But bringing an interchangeable biosimilar to market won’t be easy. The bar for interchangeability will be high, requiring that manufacturers prove switching between the new and older products is safe. And clinicians, while cautiously optimistic, aren’t thrilled with the industry payoff that could come with the designation: freedom for insurance companies and pharmacies to switch products at the dispensing level without requiring a new prescription.

The draft FDA guidance for industry, “Considerations in Demonstrating Interchangeability With a Reference Product,” arises from the Biologics Price Competition and Innovation Act of 2009. That section of the Affordable Care Act provides for abbreviated approval pathways for biological products that are demonstrated to be “highly similar” (biosimilar) to or “interchangeable” with an FDA-approved biological product.

The difference between these appellations is subtle but critical to the regulatory process – and perhaps to patient safety. Regulators recognize that the structure of these large, highly complex molecules can never precisely replicate the reference product. But to be labeled a “biosimilar,” developers must prove that the new product functions essentially the same; there can be no clinically meaningful differences in terms of safety, purity, and potency. Unlike a generic medication, a biosimilar can’t be substituted for its reference product at the pharmacy level. If a physician wants the patient on that biosimilar, the script must specify it.

Interchangeables jump a higher regulatory bar

An “interchangeable biosimilar,” though, would have to jump a higher regulatory bar. Not only must it produce the same clinical result as the reference product, it also must be benignly interchangeable with it, conferring no additional risk if a patient switches from the reference to the biosimilar and back again. A pharmacist could, if permitted by state law, substitute an interchangeable product for the reference product without going through the prescriber.

Like biosimilars, interchangeable products need not be tested in every disease for which the reference drug is approved, according to the document. Once they are proved safe for one indication, those data can be extrapolated to allow approval for the other indications as well. Nor do biosimilars need to prove efficacy per se, as their molecular similarity to the reference product ensures that they bind to the same receptor and exert the same therapeutic effect.

The biosimilar/interchangeable market has been slow to take off in the United States. There are no approved interchangeable biosimilars, and only four biosimilars – three of which were approved in 2016:

• Sandoz’ filgrastim-sndz (Zarxio).

• Pfizer’s and Celltrion’s infliximab-dyyb (Inflectra).

• Sandoz’ etanercept-szzs (Erelzi).

• Amgen’s adalimumab-atto (Amjevita).

Switching studies is the key to achieving the interchangeable designation, according to the FDA document. They must include at least two full switches between the candidate product and the reference product, which must be licensed in the United States.

But because these products are so structurally diverse, the FDA isn’t imposing a one-size-fits-all process on them. Instead, the molecular complexity and immunogenicity of each product will dictate its approval requirements.

Those with relatively low structural complexity, high molecular similarity to the reference product, and a low incidence of immunogenic adverse events may only need a single switching study to achieve the “interchangeability” designation.

The bar will be higher for a product with high structural complexity that is not as similar to the reference product, or which has been associated with immunogenic adverse events. For this product, FDA might also require extensive safety postmarketing data for the product as a licensed biosimilar, as well as a switching study.

Pharmacokinetics, pharmacodynamics, immunogenicity, and safety will be the primary endpoints of a switching study. Efficacy data are not necessary but can be used as supportive endpoints. Any safety signals in a switching study would raise regulatory eyebrows whether they came from the candidate product or the reference product. Since the study replicates what could happen if the two were used sequentially, it makes little difference from which product the event might arise.

“If an apparent difference in immune response or adverse events is noticed between the switching and nonswitching arms of the study ... it would raise concerns as to whether the proposed interchangeable product is interchangeable, regardless of whether the proposed interchangeable product or the reference product or the switching of the two products actually caused the event,” the document notes.

The E.U. vs. U.S. experience

The United States is only now getting a taste of what has become common fare in the European Union, said Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee. The European Medicines Agency approved its first biosimilar in 2006. Since then, 23 such drugs have come on the market, at an average price of about 30% less than the reference drug. Prices for some drugs have dropped as much as 70% in countries in which national health care systems abandoned the reference product in favor of the competing biosimilar, Dr. Worthing said in an interview.

“But the U.S. doesn’t have a national health care system, so it won’t work like that here.” In fact, he noted, brand-new data show that Medicare actually paid 22% more for the infliximab biosimilar Inflectra than it did for Remicade in the last quarter of 2016.

It’s not immediately apparent why this is the case, but it’s probably related to company discounts and rebates on these very expensive drugs. According to the report in Inside Health Policy, Janssen Biotech may have increased its discount on the drug to compete with Inflectra’s launch price of 15% below Remicade’s wholesale cost. Prices won’t moderate as much in the United States as in the European Union until several biosimilars of the same class appear, Dr. Worthing said.

There have already been allegations that big pharma manipulates international and national pricing to reduce biosimilar competition.

In June, Russian biotech company Biocad filed a lawsuit in New York charging Roche/Genentech with price fixing. The suit alleges that the companies cut the cost of three cancer drugs (Avastin, Herceptin, and Rituxan/MabThera) in Russia, where Biocad markets biosimilars for each. At the same time, Biocad alleges, the companies raised U.S. prices on those drugs to make up for the money they were losing on the Russian market.

Nonmedical switching raises concerns

Academic medical societies and clinicians interviewed for this article view the proposed approval pathway with cautious optimism. While acknowledging the potential benefit of reducing the costs of prohibitively expensive drugs, they uniformly insist that patient safety – not economic pressure – should be the driving force here.

“I was initially skeptical, and I do believe that we need very close pharmacovigilance in monitoring these for safety,” said Gideon Smith, MD, PhD, a dermatologist at Massachusetts General Hospital, Boston. “But there has been huge uptake of these products in the E.U., and the data are so extensive that we can be reasonably confident these drugs are effective, and no good reason to believe the safety will be any different.”

He is not as comfortable with the prospect of pharmacy-level substitution of an interchangeable biosimilar with the reference product – a feeling that other clinicians echoed.

“I think this is a fundamental issue that should have been dealt with on a federal level. Physicians should always be involved in the decision,” said Dr. Smith, who spoke at an FDA advisory committee meeting last summer on behalf of the American Academy of Dermatology (AAD).

*This article was updated 1/31/2017.

[email protected]

On Twitter @alz_gal

The Food and Drug Administration has proposed a regulatory path for biosimilar biologics that are interchangeable with the reference product, paving the way for a new generation of less-expensive versions of these unique drugs.

But bringing an interchangeable biosimilar to market won’t be easy. The bar for interchangeability will be high, requiring that manufacturers prove switching between the new and older products is safe. And clinicians, while cautiously optimistic, aren’t thrilled with the industry payoff that could come with the designation: freedom for insurance companies and pharmacies to switch products at the dispensing level without requiring a new prescription.

The draft FDA guidance for industry, “Considerations in Demonstrating Interchangeability With a Reference Product,” arises from the Biologics Price Competition and Innovation Act of 2009. That section of the Affordable Care Act provides for abbreviated approval pathways for biological products that are demonstrated to be “highly similar” (biosimilar) to or “interchangeable” with an FDA-approved biological product.

The difference between these appellations is subtle but critical to the regulatory process – and perhaps to patient safety. Regulators recognize that the structure of these large, highly complex molecules can never precisely replicate the reference product. But to be labeled a “biosimilar,” developers must prove that the new product functions essentially the same; there can be no clinically meaningful differences in terms of safety, purity, and potency. Unlike a generic medication, a biosimilar can’t be substituted for its reference product at the pharmacy level. If a physician wants the patient on that biosimilar, the script must specify it.

Interchangeables jump a higher regulatory bar

An “interchangeable biosimilar,” though, would have to jump a higher regulatory bar. Not only must it produce the same clinical result as the reference product, it also must be benignly interchangeable with it, conferring no additional risk if a patient switches from the reference to the biosimilar and back again. A pharmacist could, if permitted by state law, substitute an interchangeable product for the reference product without going through the prescriber.

Like biosimilars, interchangeable products need not be tested in every disease for which the reference drug is approved, according to the document. Once they are proved safe for one indication, those data can be extrapolated to allow approval for the other indications as well. Nor do biosimilars need to prove efficacy per se, as their molecular similarity to the reference product ensures that they bind to the same receptor and exert the same therapeutic effect.

The biosimilar/interchangeable market has been slow to take off in the United States. There are no approved interchangeable biosimilars, and only four biosimilars – three of which were approved in 2016:

• Sandoz’ filgrastim-sndz (Zarxio).

• Pfizer’s and Celltrion’s infliximab-dyyb (Inflectra).

• Sandoz’ etanercept-szzs (Erelzi).

• Amgen’s adalimumab-atto (Amjevita).

Switching studies is the key to achieving the interchangeable designation, according to the FDA document. They must include at least two full switches between the candidate product and the reference product, which must be licensed in the United States.

But because these products are so structurally diverse, the FDA isn’t imposing a one-size-fits-all process on them. Instead, the molecular complexity and immunogenicity of each product will dictate its approval requirements.

Those with relatively low structural complexity, high molecular similarity to the reference product, and a low incidence of immunogenic adverse events may only need a single switching study to achieve the “interchangeability” designation.

The bar will be higher for a product with high structural complexity that is not as similar to the reference product, or which has been associated with immunogenic adverse events. For this product, FDA might also require extensive safety postmarketing data for the product as a licensed biosimilar, as well as a switching study.

Pharmacokinetics, pharmacodynamics, immunogenicity, and safety will be the primary endpoints of a switching study. Efficacy data are not necessary but can be used as supportive endpoints. Any safety signals in a switching study would raise regulatory eyebrows whether they came from the candidate product or the reference product. Since the study replicates what could happen if the two were used sequentially, it makes little difference from which product the event might arise.

“If an apparent difference in immune response or adverse events is noticed between the switching and nonswitching arms of the study ... it would raise concerns as to whether the proposed interchangeable product is interchangeable, regardless of whether the proposed interchangeable product or the reference product or the switching of the two products actually caused the event,” the document notes.

The E.U. vs. U.S. experience

The United States is only now getting a taste of what has become common fare in the European Union, said Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee. The European Medicines Agency approved its first biosimilar in 2006. Since then, 23 such drugs have come on the market, at an average price of about 30% less than the reference drug. Prices for some drugs have dropped as much as 70% in countries in which national health care systems abandoned the reference product in favor of the competing biosimilar, Dr. Worthing said in an interview.

“But the U.S. doesn’t have a national health care system, so it won’t work like that here.” In fact, he noted, brand-new data show that Medicare actually paid 22% more for the infliximab biosimilar Inflectra than it did for Remicade in the last quarter of 2016.

It’s not immediately apparent why this is the case, but it’s probably related to company discounts and rebates on these very expensive drugs. According to the report in Inside Health Policy, Janssen Biotech may have increased its discount on the drug to compete with Inflectra’s launch price of 15% below Remicade’s wholesale cost. Prices won’t moderate as much in the United States as in the European Union until several biosimilars of the same class appear, Dr. Worthing said.

There have already been allegations that big pharma manipulates international and national pricing to reduce biosimilar competition.

In June, Russian biotech company Biocad filed a lawsuit in New York charging Roche/Genentech with price fixing. The suit alleges that the companies cut the cost of three cancer drugs (Avastin, Herceptin, and Rituxan/MabThera) in Russia, where Biocad markets biosimilars for each. At the same time, Biocad alleges, the companies raised U.S. prices on those drugs to make up for the money they were losing on the Russian market.

Nonmedical switching raises concerns

Academic medical societies and clinicians interviewed for this article view the proposed approval pathway with cautious optimism. While acknowledging the potential benefit of reducing the costs of prohibitively expensive drugs, they uniformly insist that patient safety – not economic pressure – should be the driving force here.

“I was initially skeptical, and I do believe that we need very close pharmacovigilance in monitoring these for safety,” said Gideon Smith, MD, PhD, a dermatologist at Massachusetts General Hospital, Boston. “But there has been huge uptake of these products in the E.U., and the data are so extensive that we can be reasonably confident these drugs are effective, and no good reason to believe the safety will be any different.”

He is not as comfortable with the prospect of pharmacy-level substitution of an interchangeable biosimilar with the reference product – a feeling that other clinicians echoed.

“I think this is a fundamental issue that should have been dealt with on a federal level. Physicians should always be involved in the decision,” said Dr. Smith, who spoke at an FDA advisory committee meeting last summer on behalf of the American Academy of Dermatology (AAD).

*This article was updated 1/31/2017.

[email protected]

On Twitter @alz_gal

To the Editor:

Anti–tumor necrosis factor (TNF) α treatments have radically improved the management of chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, and bowel diseases (eg, Crohn disease, ulcerative colitis [UC]). Because the number of patients treated with these agents has increased, uncommon adverse reactions have increasingly occurred. Cutaneous adverse reactions that have been reported with anti-TNF agents include immediate injection-site reaction, systemic infusion reactions, and delayed reactions.¹ Among the delayed adverse reactions, psoriatic and eczematous eruptions as well as cutaneous infections are the most common, while cutaneous adverse effects related to an immune imbalance syndrome including vasculitis; lupuslike, lichenlike, and granulomatous eruptions; and skin cancer rarely are observed.¹ Although most of the cutaneous adverse effects do not require anti-TNF treatment discontinuation and are resolved with symptomatic treatment, anti-TNF therapy must be stopped in more severe cases. We report the case of severe Henoch-Schönlein purpura (HSP) following treatment with infliximab.

A 46-year-old man who was a nonsmoker with quiescent UC on infliximab for 30 months presented with palpable necrotic purpura on both legs (Figure) and arms as well as the abdomen of 10 days’ duration, along with diffuse joint pain and swelling. He had no history of infectious or gastrointestinal symptoms. The last infliximab infusion was performed 6 weeks prior to developing the purpura. His UC was diagnosed 10 years prior to the current presentation and was not associated with any extragastrointestinal manifestations. Since diagnosis, UC had failed to respond to therapies such as azathioprine, cyclosporine, and purinethol. The complete blood cell count was normal. The C-reactive protein level was 18.7 mg/L (reference range, <5 mg/L) and the erythrocyte sedimentation rate was 30 mm/h (reference range, 0–20 mm/h). Electrolytes, urea, creatinine clearance, and liver function were normal, and a chest radiograph and radiographs of the swollen joints were unremarkable. The total IgA level was elevated at 4 g/L (reference range, 0.7–4 g/L), with IgG and IgM levels within reference range. There was no hematuria or proteinuria on urinalysis. Tests for antinuclear antibodies, rheumatoid factor, circulating immune complexes, and antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels also were normal. A skin biopsy confirmed a leukocytoclastic vasculitis of small vessels with C3 deposition. Serologic tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. Based on these findings, the diagnosis of HSP was made. Systemic corticosteroids—120 mg daily of intravenous methylprednisolone for 3 days, followed by 1 mg/kg daily of oral prednisone for 2 weeks—were then introduced with rapid clinical improvement. Henoch-Schönlein purpura and joint symptoms completely resolved, but UC relapsed with bloody diarrhea and severe abdominal pain. Oral prednisone was maintained (1 mg/kg daily). Because of the severity of cutaneous vasculitis (HSP), a multidisciplinary decision was taken to definitively stop the anti-TNF agents and to first add azathioprine (2 mg/kg daily for 2 months), then subcutaneous methotrexate (25 mg weekly). Colonoscopy did not show any dysplasia or adenocarcinoma and confirmed the diagnosis of UC. After 6 months of combined therapy, UC was still active and we decided to perform a total colectomy with ileostomy formation. Complete remission of UC was obtained and maintained after 28 months of follow-up.

Henoch-Schönlein purpura is a multisystem small vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. Clinical manifestations may include palpable purpura, arthritis, enteritis, and nephritis. Henoch-Schönlein purpura usually affects children. Adult onset is rare but associated with more severe symptoms and a poor prognosis.² The criteria for HSP, as defined by the American College of Rheumatology,³ include palpable purpura, 20 years or younger at disease onset, bowel angina, and presence of vascular wall granulocytes on biopsy. At least 2 of these criteria are required for HSP diagnosis. Various viral or bacterial infections and drugs can trigger HSP, which also can be associated with autoinflammatory or autoimmune diseases. The association of HSP and UC is a rare event, as demonstrated by de Oliveira et al.⁴ Although only 2 cases of cutaneous vasculitis mimicking HSP have been described in UC,⁴ we cannot exclude a possible association between HSP and UC. However, our patient had UC for 10 years and never had clinical manifestations of vasculitis.

There are 5 reports of HSP following etanercept^5,6 or adalimumab^7-9 therapy and 1 following infliximab therapy.¹⁰ In all cases, HSP occurred after several months of anti-TNF therapy. However, there also are reports of cutaneous vasculitis associated with arthralgia and glomerulonephritis that resolved after withdrawal of anti-TNF agents.^11,12 It is possible that some of these reactions may have been manifestations of undiagnosed HSP. In a series of 113 patients who developed cutaneous vasculitis after anti-TNF agents, visceral vasculitis was observed in 24% of patients. Treatment of vasculitis involved withdrawal of the anti-TNF therapy in 101 cases (89%).¹³ In these UC patients with few therapeutic alternatives, the continuation of anti-TNF agents should be discussed. In the previous series,¹³ of 16 patients who were rechallenged with the same or a different TNF antagonist, 12 (75%) experienced vasculitis relapse, suggesting a class effect of TNF inhibition. Because of the severity of cutaneous vasculitis and as previously suggested in a recent analytical and comprehensive overview on paradoxical reactions under TNF blockers,¹ we decided not to re-expose our patient to infliximab or to other anti-TNF agents.

In conclusion, HSP may occur during anti-TNF therapy and physicians need to be aware of this potentially serious complication.

To the Editor:

Anti–tumor necrosis factor (TNF) α treatments have radically improved the management of chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, and bowel diseases (eg, Crohn disease, ulcerative colitis [UC]). Because the number of patients treated with these agents has increased, uncommon adverse reactions have increasingly occurred. Cutaneous adverse reactions that have been reported with anti-TNF agents include immediate injection-site reaction, systemic infusion reactions, and delayed reactions.¹ Among the delayed adverse reactions, psoriatic and eczematous eruptions as well as cutaneous infections are the most common, while cutaneous adverse effects related to an immune imbalance syndrome including vasculitis; lupuslike, lichenlike, and granulomatous eruptions; and skin cancer rarely are observed.¹ Although most of the cutaneous adverse effects do not require anti-TNF treatment discontinuation and are resolved with symptomatic treatment, anti-TNF therapy must be stopped in more severe cases. We report the case of severe Henoch-Schönlein purpura (HSP) following treatment with infliximab.

A 46-year-old man who was a nonsmoker with quiescent UC on infliximab for 30 months presented with palpable necrotic purpura on both legs (Figure) and arms as well as the abdomen of 10 days’ duration, along with diffuse joint pain and swelling. He had no history of infectious or gastrointestinal symptoms. The last infliximab infusion was performed 6 weeks prior to developing the purpura. His UC was diagnosed 10 years prior to the current presentation and was not associated with any extragastrointestinal manifestations. Since diagnosis, UC had failed to respond to therapies such as azathioprine, cyclosporine, and purinethol. The complete blood cell count was normal. The C-reactive protein level was 18.7 mg/L (reference range, <5 mg/L) and the erythrocyte sedimentation rate was 30 mm/h (reference range, 0–20 mm/h). Electrolytes, urea, creatinine clearance, and liver function were normal, and a chest radiograph and radiographs of the swollen joints were unremarkable. The total IgA level was elevated at 4 g/L (reference range, 0.7–4 g/L), with IgG and IgM levels within reference range. There was no hematuria or proteinuria on urinalysis. Tests for antinuclear antibodies, rheumatoid factor, circulating immune complexes, and antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels also were normal. A skin biopsy confirmed a leukocytoclastic vasculitis of small vessels with C3 deposition. Serologic tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. Based on these findings, the diagnosis of HSP was made. Systemic corticosteroids—120 mg daily of intravenous methylprednisolone for 3 days, followed by 1 mg/kg daily of oral prednisone for 2 weeks—were then introduced with rapid clinical improvement. Henoch-Schönlein purpura and joint symptoms completely resolved, but UC relapsed with bloody diarrhea and severe abdominal pain. Oral prednisone was maintained (1 mg/kg daily). Because of the severity of cutaneous vasculitis (HSP), a multidisciplinary decision was taken to definitively stop the anti-TNF agents and to first add azathioprine (2 mg/kg daily for 2 months), then subcutaneous methotrexate (25 mg weekly). Colonoscopy did not show any dysplasia or adenocarcinoma and confirmed the diagnosis of UC. After 6 months of combined therapy, UC was still active and we decided to perform a total colectomy with ileostomy formation. Complete remission of UC was obtained and maintained after 28 months of follow-up.

Henoch-Schönlein purpura is a multisystem small vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. Clinical manifestations may include palpable purpura, arthritis, enteritis, and nephritis. Henoch-Schönlein purpura usually affects children. Adult onset is rare but associated with more severe symptoms and a poor prognosis.² The criteria for HSP, as defined by the American College of Rheumatology,³ include palpable purpura, 20 years or younger at disease onset, bowel angina, and presence of vascular wall granulocytes on biopsy. At least 2 of these criteria are required for HSP diagnosis. Various viral or bacterial infections and drugs can trigger HSP, which also can be associated with autoinflammatory or autoimmune diseases. The association of HSP and UC is a rare event, as demonstrated by de Oliveira et al.⁴ Although only 2 cases of cutaneous vasculitis mimicking HSP have been described in UC,⁴ we cannot exclude a possible association between HSP and UC. However, our patient had UC for 10 years and never had clinical manifestations of vasculitis.

There are 5 reports of HSP following etanercept^5,6 or adalimumab^7-9 therapy and 1 following infliximab therapy.¹⁰ In all cases, HSP occurred after several months of anti-TNF therapy. However, there also are reports of cutaneous vasculitis associated with arthralgia and glomerulonephritis that resolved after withdrawal of anti-TNF agents.^11,12 It is possible that some of these reactions may have been manifestations of undiagnosed HSP. In a series of 113 patients who developed cutaneous vasculitis after anti-TNF agents, visceral vasculitis was observed in 24% of patients. Treatment of vasculitis involved withdrawal of the anti-TNF therapy in 101 cases (89%).¹³ In these UC patients with few therapeutic alternatives, the continuation of anti-TNF agents should be discussed. In the previous series,¹³ of 16 patients who were rechallenged with the same or a different TNF antagonist, 12 (75%) experienced vasculitis relapse, suggesting a class effect of TNF inhibition. Because of the severity of cutaneous vasculitis and as previously suggested in a recent analytical and comprehensive overview on paradoxical reactions under TNF blockers,¹ we decided not to re-expose our patient to infliximab or to other anti-TNF agents.

In conclusion, HSP may occur during anti-TNF therapy and physicians need to be aware of this potentially serious complication.

To the Editor:

Anti–tumor necrosis factor (TNF) α treatments have radically improved the management of chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, and bowel diseases (eg, Crohn disease, ulcerative colitis [UC]). Because the number of patients treated with these agents has increased, uncommon adverse reactions have increasingly occurred. Cutaneous adverse reactions that have been reported with anti-TNF agents include immediate injection-site reaction, systemic infusion reactions, and delayed reactions.¹ Among the delayed adverse reactions, psoriatic and eczematous eruptions as well as cutaneous infections are the most common, while cutaneous adverse effects related to an immune imbalance syndrome including vasculitis; lupuslike, lichenlike, and granulomatous eruptions; and skin cancer rarely are observed.¹ Although most of the cutaneous adverse effects do not require anti-TNF treatment discontinuation and are resolved with symptomatic treatment, anti-TNF therapy must be stopped in more severe cases. We report the case of severe Henoch-Schönlein purpura (HSP) following treatment with infliximab.

A 46-year-old man who was a nonsmoker with quiescent UC on infliximab for 30 months presented with palpable necrotic purpura on both legs (Figure) and arms as well as the abdomen of 10 days’ duration, along with diffuse joint pain and swelling. He had no history of infectious or gastrointestinal symptoms. The last infliximab infusion was performed 6 weeks prior to developing the purpura. His UC was diagnosed 10 years prior to the current presentation and was not associated with any extragastrointestinal manifestations. Since diagnosis, UC had failed to respond to therapies such as azathioprine, cyclosporine, and purinethol. The complete blood cell count was normal. The C-reactive protein level was 18.7 mg/L (reference range, <5 mg/L) and the erythrocyte sedimentation rate was 30 mm/h (reference range, 0–20 mm/h). Electrolytes, urea, creatinine clearance, and liver function were normal, and a chest radiograph and radiographs of the swollen joints were unremarkable. The total IgA level was elevated at 4 g/L (reference range, 0.7–4 g/L), with IgG and IgM levels within reference range. There was no hematuria or proteinuria on urinalysis. Tests for antinuclear antibodies, rheumatoid factor, circulating immune complexes, and antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels also were normal. A skin biopsy confirmed a leukocytoclastic vasculitis of small vessels with C3 deposition. Serologic tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. Based on these findings, the diagnosis of HSP was made. Systemic corticosteroids—120 mg daily of intravenous methylprednisolone for 3 days, followed by 1 mg/kg daily of oral prednisone for 2 weeks—were then introduced with rapid clinical improvement. Henoch-Schönlein purpura and joint symptoms completely resolved, but UC relapsed with bloody diarrhea and severe abdominal pain. Oral prednisone was maintained (1 mg/kg daily). Because of the severity of cutaneous vasculitis (HSP), a multidisciplinary decision was taken to definitively stop the anti-TNF agents and to first add azathioprine (2 mg/kg daily for 2 months), then subcutaneous methotrexate (25 mg weekly). Colonoscopy did not show any dysplasia or adenocarcinoma and confirmed the diagnosis of UC. After 6 months of combined therapy, UC was still active and we decided to perform a total colectomy with ileostomy formation. Complete remission of UC was obtained and maintained after 28 months of follow-up.

Henoch-Schönlein purpura is a multisystem small vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. Clinical manifestations may include palpable purpura, arthritis, enteritis, and nephritis. Henoch-Schönlein purpura usually affects children. Adult onset is rare but associated with more severe symptoms and a poor prognosis.² The criteria for HSP, as defined by the American College of Rheumatology,³ include palpable purpura, 20 years or younger at disease onset, bowel angina, and presence of vascular wall granulocytes on biopsy. At least 2 of these criteria are required for HSP diagnosis. Various viral or bacterial infections and drugs can trigger HSP, which also can be associated with autoinflammatory or autoimmune diseases. The association of HSP and UC is a rare event, as demonstrated by de Oliveira et al.⁴ Although only 2 cases of cutaneous vasculitis mimicking HSP have been described in UC,⁴ we cannot exclude a possible association between HSP and UC. However, our patient had UC for 10 years and never had clinical manifestations of vasculitis.

There are 5 reports of HSP following etanercept^5,6 or adalimumab^7-9 therapy and 1 following infliximab therapy.¹⁰ In all cases, HSP occurred after several months of anti-TNF therapy. However, there also are reports of cutaneous vasculitis associated with arthralgia and glomerulonephritis that resolved after withdrawal of anti-TNF agents.^11,12 It is possible that some of these reactions may have been manifestations of undiagnosed HSP. In a series of 113 patients who developed cutaneous vasculitis after anti-TNF agents, visceral vasculitis was observed in 24% of patients. Treatment of vasculitis involved withdrawal of the anti-TNF therapy in 101 cases (89%).¹³ In these UC patients with few therapeutic alternatives, the continuation of anti-TNF agents should be discussed. In the previous series,¹³ of 16 patients who were rechallenged with the same or a different TNF antagonist, 12 (75%) experienced vasculitis relapse, suggesting a class effect of TNF inhibition. Because of the severity of cutaneous vasculitis and as previously suggested in a recent analytical and comprehensive overview on paradoxical reactions under TNF blockers,¹ we decided not to re-expose our patient to infliximab or to other anti-TNF agents.

In conclusion, HSP may occur during anti-TNF therapy and physicians need to be aware of this potentially serious complication.

Individuals who have psoriasis or psoriatic arthritis are at a significantly higher risk of also suffering bone fractures, particularly in their hip and vertebrae, according to a new study published in the Annals of the Rheumatic Diseases.

“To our knowledge, these are the first population-based estimates of the risk for incident fracture and osteoporosis in patients with psoriasis and/or PsA [psoriatic arthritis] and the first longitudinal cohort study to address this issue,” wrote the authors of the study, led by Alexis Ogdie-Beatty, MD, of the University of Pennsylvania in Philadelphia (Ann Rheum Dis. 2017 Jan 16. doi: 10.1136/annrheumdis-2016-210441).

[email protected]

Individuals who have psoriasis or psoriatic arthritis are at a significantly higher risk of also suffering bone fractures, particularly in their hip and vertebrae, according to a new study published in the Annals of the Rheumatic Diseases.

“To our knowledge, these are the first population-based estimates of the risk for incident fracture and osteoporosis in patients with psoriasis and/or PsA [psoriatic arthritis] and the first longitudinal cohort study to address this issue,” wrote the authors of the study, led by Alexis Ogdie-Beatty, MD, of the University of Pennsylvania in Philadelphia (Ann Rheum Dis. 2017 Jan 16. doi: 10.1136/annrheumdis-2016-210441).

[email protected]

Individuals who have psoriasis or psoriatic arthritis are at a significantly higher risk of also suffering bone fractures, particularly in their hip and vertebrae, according to a new study published in the Annals of the Rheumatic Diseases.

“To our knowledge, these are the first population-based estimates of the risk for incident fracture and osteoporosis in patients with psoriasis and/or PsA [psoriatic arthritis] and the first longitudinal cohort study to address this issue,” wrote the authors of the study, led by Alexis Ogdie-Beatty, MD, of the University of Pennsylvania in Philadelphia (Ann Rheum Dis. 2017 Jan 16. doi: 10.1136/annrheumdis-2016-210441).

[email protected]

MIAMI – In an ongoing drive to identify an alternative to the mainstay treatment of psoriasis with topical corticosteroids, researchers evaluated a fixed-dose combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion compared to its monads and vehicle in 212 people with moderate to severe psoriasis.

After 8 weeks of once-daily applications, combination therapy yielded significantly greater reductions in erythema, plaque elevation, and scaling at the target lesion, compared with the other groups in the phase II trial. The investigators also reported at safety profile consistent with halobetasol propionate or tazarotene monotherapy, meaning no new safety concerns emerged with the combination.

Efficacy evaluation

At 8 weeks, 53% of the combination group achieved treatment success, defined as at least a 2-point gain in Investigator’s Global Assessment of Disease Severity and a score of “clear” or “almost clear.” In contrast, 33% of the halobetasol propionate group, 19% in the tazarotene, and 10% of the vehicle only group achieved those endpoints in the intent-to-treat-analysis. The difference in efficacy between the combination group and vehicle was statistically significant (P less than .001).

On individual clinical efficacy measures, more than half of the patients in the combination treatment group achieved at least a 2-point improvement from baseline: 54% for erythema, 68% for plaque elevation, 65% for scaling. Each of these outcomes was significantly superior compared to the tazarotene or vehicle group (P less than or equal to .001).

“I was not surprised by the findings as the drugs work by complimentary mechanisms of action – so combination therapy should be effective,” Dr. Stein Gold said.

At baseline, IGA severity score of 3 was most common in each group and for each psoriasis sign at the target lesions. In each group, the mean age of participants ranged from 48 to 56 years; the proportion of men ranged from 59% to 68%; and 87% to 95% were white. The median target lesion sizes ranged from 25 to 32 cm².

Safety outcomes

One patient in the vehicle-only group died. Three other participants experienced serious adverse events – one in each of the noncombination groups. None of these events were related to the study medications, the investigators noted. Application site reactions were the most common treatment-associated adverse events. Some skin atrophy was reported.

“These results show that the fixed combination of halobetasol propionate and tazarotene was effective and well tolerated,” said Dr. Stein Gold, who serves as division head of dermatology at Henry Ford Health System, West Bloomfield, Mich. “This would be a nice addition to our treatment armamentarium for patients with plaque psoriasis.”

Dr. Stein Gold is a speaker, consultant, and study investigator for Valeant Pharmaceuticals, which supported the study.

MIAMI – In an ongoing drive to identify an alternative to the mainstay treatment of psoriasis with topical corticosteroids, researchers evaluated a fixed-dose combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion compared to its monads and vehicle in 212 people with moderate to severe psoriasis.

After 8 weeks of once-daily applications, combination therapy yielded significantly greater reductions in erythema, plaque elevation, and scaling at the target lesion, compared with the other groups in the phase II trial. The investigators also reported at safety profile consistent with halobetasol propionate or tazarotene monotherapy, meaning no new safety concerns emerged with the combination.

Efficacy evaluation

At 8 weeks, 53% of the combination group achieved treatment success, defined as at least a 2-point gain in Investigator’s Global Assessment of Disease Severity and a score of “clear” or “almost clear.” In contrast, 33% of the halobetasol propionate group, 19% in the tazarotene, and 10% of the vehicle only group achieved those endpoints in the intent-to-treat-analysis. The difference in efficacy between the combination group and vehicle was statistically significant (P less than .001).

On individual clinical efficacy measures, more than half of the patients in the combination treatment group achieved at least a 2-point improvement from baseline: 54% for erythema, 68% for plaque elevation, 65% for scaling. Each of these outcomes was significantly superior compared to the tazarotene or vehicle group (P less than or equal to .001).

“I was not surprised by the findings as the drugs work by complimentary mechanisms of action – so combination therapy should be effective,” Dr. Stein Gold said.

At baseline, IGA severity score of 3 was most common in each group and for each psoriasis sign at the target lesions. In each group, the mean age of participants ranged from 48 to 56 years; the proportion of men ranged from 59% to 68%; and 87% to 95% were white. The median target lesion sizes ranged from 25 to 32 cm².

Safety outcomes

One patient in the vehicle-only group died. Three other participants experienced serious adverse events – one in each of the noncombination groups. None of these events were related to the study medications, the investigators noted. Application site reactions were the most common treatment-associated adverse events. Some skin atrophy was reported.

“These results show that the fixed combination of halobetasol propionate and tazarotene was effective and well tolerated,” said Dr. Stein Gold, who serves as division head of dermatology at Henry Ford Health System, West Bloomfield, Mich. “This would be a nice addition to our treatment armamentarium for patients with plaque psoriasis.”

Dr. Stein Gold is a speaker, consultant, and study investigator for Valeant Pharmaceuticals, which supported the study.

MIAMI – In an ongoing drive to identify an alternative to the mainstay treatment of psoriasis with topical corticosteroids, researchers evaluated a fixed-dose combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion compared to its monads and vehicle in 212 people with moderate to severe psoriasis.

After 8 weeks of once-daily applications, combination therapy yielded significantly greater reductions in erythema, plaque elevation, and scaling at the target lesion, compared with the other groups in the phase II trial. The investigators also reported at safety profile consistent with halobetasol propionate or tazarotene monotherapy, meaning no new safety concerns emerged with the combination.

Efficacy evaluation

At 8 weeks, 53% of the combination group achieved treatment success, defined as at least a 2-point gain in Investigator’s Global Assessment of Disease Severity and a score of “clear” or “almost clear.” In contrast, 33% of the halobetasol propionate group, 19% in the tazarotene, and 10% of the vehicle only group achieved those endpoints in the intent-to-treat-analysis. The difference in efficacy between the combination group and vehicle was statistically significant (P less than .001).

On individual clinical efficacy measures, more than half of the patients in the combination treatment group achieved at least a 2-point improvement from baseline: 54% for erythema, 68% for plaque elevation, 65% for scaling. Each of these outcomes was significantly superior compared to the tazarotene or vehicle group (P less than or equal to .001).

“I was not surprised by the findings as the drugs work by complimentary mechanisms of action – so combination therapy should be effective,” Dr. Stein Gold said.

At baseline, IGA severity score of 3 was most common in each group and for each psoriasis sign at the target lesions. In each group, the mean age of participants ranged from 48 to 56 years; the proportion of men ranged from 59% to 68%; and 87% to 95% were white. The median target lesion sizes ranged from 25 to 32 cm².

Safety outcomes

One patient in the vehicle-only group died. Three other participants experienced serious adverse events – one in each of the noncombination groups. None of these events were related to the study medications, the investigators noted. Application site reactions were the most common treatment-associated adverse events. Some skin atrophy was reported.

“These results show that the fixed combination of halobetasol propionate and tazarotene was effective and well tolerated,” said Dr. Stein Gold, who serves as division head of dermatology at Henry Ford Health System, West Bloomfield, Mich. “This would be a nice addition to our treatment armamentarium for patients with plaque psoriasis.”

Dr. Stein Gold is a speaker, consultant, and study investigator for Valeant Pharmaceuticals, which supported the study.

Parents of children with psoriasis experience significant negative quality-of-life issues, according to Dr. Megha Tollefson and her associates.

In interviews with 31 parents of children with psoriasis, four themes impacting quality of life emerged. Parental health and self-care were negatively affected, with 52% reporting affected sleep patterns and 35% reporting difficulty in maintaining self-care. Mental health issues were common as well, with 65% of parents reporting concern over their child’s condition and nearly half of parents reporting excess stress and sadness, anxiety, or depression.

Lori Farmer/Frontline Medical News

[email protected]

Parents of children with psoriasis experience significant negative quality-of-life issues, according to Dr. Megha Tollefson and her associates.

In interviews with 31 parents of children with psoriasis, four themes impacting quality of life emerged. Parental health and self-care were negatively affected, with 52% reporting affected sleep patterns and 35% reporting difficulty in maintaining self-care. Mental health issues were common as well, with 65% of parents reporting concern over their child’s condition and nearly half of parents reporting excess stress and sadness, anxiety, or depression.

Lori Farmer/Frontline Medical News

[email protected]

Parents of children with psoriasis experience significant negative quality-of-life issues, according to Dr. Megha Tollefson and her associates.

In interviews with 31 parents of children with psoriasis, four themes impacting quality of life emerged. Parental health and self-care were negatively affected, with 52% reporting affected sleep patterns and 35% reporting difficulty in maintaining self-care. Mental health issues were common as well, with 65% of parents reporting concern over their child’s condition and nearly half of parents reporting excess stress and sadness, anxiety, or depression.

Lori Farmer/Frontline Medical News

[email protected]

Myth: Systemic steroids cause pustular psoriasis

The advent of biologic therapy for psoriasis has changed the landscape of treatments offered to patients. Nevertheless, systemic therapies still play an important role, according to the American Academy of Dermatology psoriasis treatment guidelines, due to their oral route of administration and low cost compared to biologics. They are options for patients with moderate to severe psoriasis that is unresponsive to topical therapies or phototherapy. However, many dermatologists feel that it is inappropriate to prescribe oral steroids to psoriasis patients due to the risk for steroid-induced conversion to pustular psoriasis, the long-term side effects of steroids, and deterioration of psoriasis after withdrawal of steroids.

Pustular psoriasis appears clinically as white pustules (blisters of noninfectious pus) surrounded by red skin. The pus consists of white blood cells. There are a number of triggers in addition to systemic steroids, such as internal medications, irritating topical agents, overexposure to UV light, and pregnancy. Stopping an oral steroid abruptly can cause serious disease flares, fatigue, and joint pain.

Westphal et al described the case of a 70-year-old woman with palmoplantar psoriasis who was diagnosed with acute generalized exanthematous pustulosis that was treated with corticotherapy by injection and then oral prednisone. She experienced improvement, but her symptoms worsened when she was in the process of reducing the prednisone dose. The dose was increased again, and the same worsening of symptoms was experienced when the dose was reduced. After completely abandoning oral steroid therapy, she developed a severe case of generalized pustular psoriasis that was treated with acitretin. This case illustrates the dangerous consequences of abruptly discontinuing oral steroids.

However, dermatologists may be using oral steroids for psoriasis more often than treatment guidelines suggest. In 2014, Al-Dabagh et al evaluated how frequently systemic corticosteroids are prescribed for psoriasis in the United States. The researchers reported, "Despite the absence or discouragement of systemic corticosteroids in psoriasis management guidelines, systemic corticosteroids are among the most common systemic treatments used for psoriasis." They found that systemic corticosteroids were prescribed at 650,000 of 21,020,000 psoriasis visits, of which 93% were visits to dermatologists. Prednisone was the most commonly prescribed systemic corticosteroid, followed by methylprednisolone and dexamethasone. To prevent rebound flares, systemic corticosteroids were prescribed with a topical corticosteroid in 45% of the visits in patients with psoriasis as the sole diagnosis. They concluded, "The striking contrast between the guidelines for psoriasis management and actual practice suggests that there is an acute need to better understand the use of systemic corticosteroids for psoriasis."

The benefits of systemic corticosteroids versus the frequency of adverse reactions should be weighed by dermatologists and patients to make evidence-based decisions about treatment. Patients should take oral steroids exactly as prescribed by physicians.

References

Al-Dabagh A, Al-Dabagh R, Davis SA, et al. Systemic corticosteroids are frequently prescribed for psoriasis. J Cutan Med Surg. 2014;18:195-199.

Delzell E. What you need to know about steroids. National Psoriasis Foundation website. https://www.psoriasis.org/advance/what-you-need-to-know-about-steroids. Published September 2, 2015. Accessed January 13, 2017.

Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.

Pustular psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/about-psoriasis/types/pustular. Accessed January 13, 2017.

Westphal DC, Schettini APM, de Souza PP, et al. Generalized pustular psoriasis induced by systemic steroid dose reduction. An Bras Dermatol. 2016;91:664-666.

Expert Commentaries on next page

Expert Commentaries

When I was a resident, I was trained not to use systemic steroids in psoriasis patients for the reasons noted above, and I have faithfully followed these instructions 9 years into practice. However, I see many patients with severe psoriasis who are given systemic steroids by other physicians (ie, rheumatologists for psoriatic arthritis, pulmonologists for asthma). I often tell patients afterwards of the dangers of systemic steroids and to have them tell their other doctors to be cautious when giving another course of systemic steroids. However, I have yet to see a generalized pustular psoriasis outbreak or flare in psoriasis vulgaris after a course of systemic steroids. While I do not recommend systemic steroids for psoriasis patients since we have so many other systemic agents, I wonder if the risks that we were all trained about are really that high.

—Jashin J. Wu, MD (Los Angeles, California)

How bad is it to give patients with psoriasis systemic steroids? Are psoriasis patients treated with systemic steroids likely to get a pustular flare? Are patients with psoriasis who suddenly stop their corticosteroids more likely to get a pustular flare than psoriasis patients who suddenly stop other systemic psoriasis treatments? I don't have the answers to these questions. My sense is that we have a lot of dogma and strong opinions but very little hard evidence to answer these questions.

I don't typically prescribe systemic steroids to psoriasis patients, but systemic steroids are widely used. Sometimes there are problems. I have seen patients who received systemic steroids for psoriasis and who went on to have a pustular flare, but it's possible the systemic steroid was given because those patients were headed toward the pustular flare already.

I once had a psoriasis patient who came to see me with a suddenly inflamed tender joint. Not knowing what to do, I called a rheumatologist to see the patient. The rheumatologist, too busy to work the patient in, told me to give the patient a 2-week prednisone taper. I did, and nothing untoward happened with the psoriasis. This one anecdote doesn't give me much confidence that systemic steroids are safe for psoriasis patients.

Clearly, long-term steroids cause a host of problems (eg, osteoporosis, diabetes). But I'm not sure that the dogma that systemic steroids should be avoided in patients with psoriasis is well supported. Systemic steroids are being widely used, and I don't see an epidemic of pustular flares.

Is it a mistake to give systemic steroids to psoriasis patients? I just don't know.
—Steven R. Feldman, MD, PhD (Winston-Salem, North Carolina)

Myth: Systemic steroids cause pustular psoriasis

The advent of biologic therapy for psoriasis has changed the landscape of treatments offered to patients. Nevertheless, systemic therapies still play an important role, according to the American Academy of Dermatology psoriasis treatment guidelines, due to their oral route of administration and low cost compared to biologics. They are options for patients with moderate to severe psoriasis that is unresponsive to topical therapies or phototherapy. However, many dermatologists feel that it is inappropriate to prescribe oral steroids to psoriasis patients due to the risk for steroid-induced conversion to pustular psoriasis, the long-term side effects of steroids, and deterioration of psoriasis after withdrawal of steroids.

Pustular psoriasis appears clinically as white pustules (blisters of noninfectious pus) surrounded by red skin. The pus consists of white blood cells. There are a number of triggers in addition to systemic steroids, such as internal medications, irritating topical agents, overexposure to UV light, and pregnancy. Stopping an oral steroid abruptly can cause serious disease flares, fatigue, and joint pain.

Westphal et al described the case of a 70-year-old woman with palmoplantar psoriasis who was diagnosed with acute generalized exanthematous pustulosis that was treated with corticotherapy by injection and then oral prednisone. She experienced improvement, but her symptoms worsened when she was in the process of reducing the prednisone dose. The dose was increased again, and the same worsening of symptoms was experienced when the dose was reduced. After completely abandoning oral steroid therapy, she developed a severe case of generalized pustular psoriasis that was treated with acitretin. This case illustrates the dangerous consequences of abruptly discontinuing oral steroids.

However, dermatologists may be using oral steroids for psoriasis more often than treatment guidelines suggest. In 2014, Al-Dabagh et al evaluated how frequently systemic corticosteroids are prescribed for psoriasis in the United States. The researchers reported, "Despite the absence or discouragement of systemic corticosteroids in psoriasis management guidelines, systemic corticosteroids are among the most common systemic treatments used for psoriasis." They found that systemic corticosteroids were prescribed at 650,000 of 21,020,000 psoriasis visits, of which 93% were visits to dermatologists. Prednisone was the most commonly prescribed systemic corticosteroid, followed by methylprednisolone and dexamethasone. To prevent rebound flares, systemic corticosteroids were prescribed with a topical corticosteroid in 45% of the visits in patients with psoriasis as the sole diagnosis. They concluded, "The striking contrast between the guidelines for psoriasis management and actual practice suggests that there is an acute need to better understand the use of systemic corticosteroids for psoriasis."

The benefits of systemic corticosteroids versus the frequency of adverse reactions should be weighed by dermatologists and patients to make evidence-based decisions about treatment. Patients should take oral steroids exactly as prescribed by physicians.

References

Al-Dabagh A, Al-Dabagh R, Davis SA, et al. Systemic corticosteroids are frequently prescribed for psoriasis. J Cutan Med Surg. 2014;18:195-199.

Delzell E. What you need to know about steroids. National Psoriasis Foundation website. https://www.psoriasis.org/advance/what-you-need-to-know-about-steroids. Published September 2, 2015. Accessed January 13, 2017.

Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.

Pustular psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/about-psoriasis/types/pustular. Accessed January 13, 2017.

Westphal DC, Schettini APM, de Souza PP, et al. Generalized pustular psoriasis induced by systemic steroid dose reduction. An Bras Dermatol. 2016;91:664-666.

Expert Commentaries on next page

Expert Commentaries

When I was a resident, I was trained not to use systemic steroids in psoriasis patients for the reasons noted above, and I have faithfully followed these instructions 9 years into practice. However, I see many patients with severe psoriasis who are given systemic steroids by other physicians (ie, rheumatologists for psoriatic arthritis, pulmonologists for asthma). I often tell patients afterwards of the dangers of systemic steroids and to have them tell their other doctors to be cautious when giving another course of systemic steroids. However, I have yet to see a generalized pustular psoriasis outbreak or flare in psoriasis vulgaris after a course of systemic steroids. While I do not recommend systemic steroids for psoriasis patients since we have so many other systemic agents, I wonder if the risks that we were all trained about are really that high.

—Jashin J. Wu, MD (Los Angeles, California)

How bad is it to give patients with psoriasis systemic steroids? Are psoriasis patients treated with systemic steroids likely to get a pustular flare? Are patients with psoriasis who suddenly stop their corticosteroids more likely to get a pustular flare than psoriasis patients who suddenly stop other systemic psoriasis treatments? I don't have the answers to these questions. My sense is that we have a lot of dogma and strong opinions but very little hard evidence to answer these questions.

I don't typically prescribe systemic steroids to psoriasis patients, but systemic steroids are widely used. Sometimes there are problems. I have seen patients who received systemic steroids for psoriasis and who went on to have a pustular flare, but it's possible the systemic steroid was given because those patients were headed toward the pustular flare already.

I once had a psoriasis patient who came to see me with a suddenly inflamed tender joint. Not knowing what to do, I called a rheumatologist to see the patient. The rheumatologist, too busy to work the patient in, told me to give the patient a 2-week prednisone taper. I did, and nothing untoward happened with the psoriasis. This one anecdote doesn't give me much confidence that systemic steroids are safe for psoriasis patients.

Clearly, long-term steroids cause a host of problems (eg, osteoporosis, diabetes). But I'm not sure that the dogma that systemic steroids should be avoided in patients with psoriasis is well supported. Systemic steroids are being widely used, and I don't see an epidemic of pustular flares.

Is it a mistake to give systemic steroids to psoriasis patients? I just don't know.
—Steven R. Feldman, MD, PhD (Winston-Salem, North Carolina)

Myth: Systemic steroids cause pustular psoriasis

The advent of biologic therapy for psoriasis has changed the landscape of treatments offered to patients. Nevertheless, systemic therapies still play an important role, according to the American Academy of Dermatology psoriasis treatment guidelines, due to their oral route of administration and low cost compared to biologics. They are options for patients with moderate to severe psoriasis that is unresponsive to topical therapies or phototherapy. However, many dermatologists feel that it is inappropriate to prescribe oral steroids to psoriasis patients due to the risk for steroid-induced conversion to pustular psoriasis, the long-term side effects of steroids, and deterioration of psoriasis after withdrawal of steroids.

Pustular psoriasis appears clinically as white pustules (blisters of noninfectious pus) surrounded by red skin. The pus consists of white blood cells. There are a number of triggers in addition to systemic steroids, such as internal medications, irritating topical agents, overexposure to UV light, and pregnancy. Stopping an oral steroid abruptly can cause serious disease flares, fatigue, and joint pain.

Westphal et al described the case of a 70-year-old woman with palmoplantar psoriasis who was diagnosed with acute generalized exanthematous pustulosis that was treated with corticotherapy by injection and then oral prednisone. She experienced improvement, but her symptoms worsened when she was in the process of reducing the prednisone dose. The dose was increased again, and the same worsening of symptoms was experienced when the dose was reduced. After completely abandoning oral steroid therapy, she developed a severe case of generalized pustular psoriasis that was treated with acitretin. This case illustrates the dangerous consequences of abruptly discontinuing oral steroids.

However, dermatologists may be using oral steroids for psoriasis more often than treatment guidelines suggest. In 2014, Al-Dabagh et al evaluated how frequently systemic corticosteroids are prescribed for psoriasis in the United States. The researchers reported, "Despite the absence or discouragement of systemic corticosteroids in psoriasis management guidelines, systemic corticosteroids are among the most common systemic treatments used for psoriasis." They found that systemic corticosteroids were prescribed at 650,000 of 21,020,000 psoriasis visits, of which 93% were visits to dermatologists. Prednisone was the most commonly prescribed systemic corticosteroid, followed by methylprednisolone and dexamethasone. To prevent rebound flares, systemic corticosteroids were prescribed with a topical corticosteroid in 45% of the visits in patients with psoriasis as the sole diagnosis. They concluded, "The striking contrast between the guidelines for psoriasis management and actual practice suggests that there is an acute need to better understand the use of systemic corticosteroids for psoriasis."

The benefits of systemic corticosteroids versus the frequency of adverse reactions should be weighed by dermatologists and patients to make evidence-based decisions about treatment. Patients should take oral steroids exactly as prescribed by physicians.

References

Al-Dabagh A, Al-Dabagh R, Davis SA, et al. Systemic corticosteroids are frequently prescribed for psoriasis. J Cutan Med Surg. 2014;18:195-199.

Delzell E. What you need to know about steroids. National Psoriasis Foundation website. https://www.psoriasis.org/advance/what-you-need-to-know-about-steroids. Published September 2, 2015. Accessed January 13, 2017.

Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.

Pustular psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/about-psoriasis/types/pustular. Accessed January 13, 2017.

Westphal DC, Schettini APM, de Souza PP, et al. Generalized pustular psoriasis induced by systemic steroid dose reduction. An Bras Dermatol. 2016;91:664-666.

Expert Commentaries on next page

Expert Commentaries

When I was a resident, I was trained not to use systemic steroids in psoriasis patients for the reasons noted above, and I have faithfully followed these instructions 9 years into practice. However, I see many patients with severe psoriasis who are given systemic steroids by other physicians (ie, rheumatologists for psoriatic arthritis, pulmonologists for asthma). I often tell patients afterwards of the dangers of systemic steroids and to have them tell their other doctors to be cautious when giving another course of systemic steroids. However, I have yet to see a generalized pustular psoriasis outbreak or flare in psoriasis vulgaris after a course of systemic steroids. While I do not recommend systemic steroids for psoriasis patients since we have so many other systemic agents, I wonder if the risks that we were all trained about are really that high.

—Jashin J. Wu, MD (Los Angeles, California)

How bad is it to give patients with psoriasis systemic steroids? Are psoriasis patients treated with systemic steroids likely to get a pustular flare? Are patients with psoriasis who suddenly stop their corticosteroids more likely to get a pustular flare than psoriasis patients who suddenly stop other systemic psoriasis treatments? I don't have the answers to these questions. My sense is that we have a lot of dogma and strong opinions but very little hard evidence to answer these questions.

I don't typically prescribe systemic steroids to psoriasis patients, but systemic steroids are widely used. Sometimes there are problems. I have seen patients who received systemic steroids for psoriasis and who went on to have a pustular flare, but it's possible the systemic steroid was given because those patients were headed toward the pustular flare already.

I once had a psoriasis patient who came to see me with a suddenly inflamed tender joint. Not knowing what to do, I called a rheumatologist to see the patient. The rheumatologist, too busy to work the patient in, told me to give the patient a 2-week prednisone taper. I did, and nothing untoward happened with the psoriasis. This one anecdote doesn't give me much confidence that systemic steroids are safe for psoriasis patients.

Clearly, long-term steroids cause a host of problems (eg, osteoporosis, diabetes). But I'm not sure that the dogma that systemic steroids should be avoided in patients with psoriasis is well supported. Systemic steroids are being widely used, and I don't see an epidemic of pustular flares.

Is it a mistake to give systemic steroids to psoriasis patients? I just don't know.
—Steven R. Feldman, MD, PhD (Winston-Salem, North Carolina)