Psoriasis

Biologic-naive patients with psoriasis or psoriatic arthritis had a lower risk of serious infection with interleukin-12/23 (IL-12/23) inhibitors than they did with tumor necrosis factor (TNF) inhibitors, but this difference disappeared in patients with previous exposure to biologics, according to data from a retrospective study of nearly 10,000 adults.

Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.

The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.

Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.

The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.

After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).

The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.

However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.

The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
 

SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.

Biologic-naive patients with psoriasis or psoriatic arthritis had a lower risk of serious infection with interleukin-12/23 (IL-12/23) inhibitors than they did with tumor necrosis factor (TNF) inhibitors, but this difference disappeared in patients with previous exposure to biologics, according to data from a retrospective study of nearly 10,000 adults.

Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.

The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.

Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.

The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.

After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).

The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.

However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.

The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
 

SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.

Biologic-naive patients with psoriasis or psoriatic arthritis had a lower risk of serious infection with interleukin-12/23 (IL-12/23) inhibitors than they did with tumor necrosis factor (TNF) inhibitors, but this difference disappeared in patients with previous exposure to biologics, according to data from a retrospective study of nearly 10,000 adults.

Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.

The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.

Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.

The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.

After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).

The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.

However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.

The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
 

SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.

People with psoriasis appear to have both an increased risk of cancer and an increased risk of cancer-related mortality, according to a meta-analysis of cohort and case-control studies.

Compared with a psoriasis-free population, having a diagnosis of severe psoriasis was associated with a 22% increase in cancer risk, Alex Trafford of the University of Manchester (England) and colleagues reported in JAMA Dermatology. The risk of cancer mortality was also increased by 22% among those with severe psoriasis.

The site-specific risks ranged from a low of 18% for colon cancer to more than a twofold increased risk for oral and esophageal cancer, according to the investigators.

Since these were associations only, any underlying mechanism is still unclear, they wrote. The chronic inflammation that drives psoriasis can also drive the development of cancer, but immunomodulatory therapies may also play a part, they suggested.

“Of particular relevance in this regard are biological therapies, which are being increasingly used for the management of psoriasis,” they added. “Although preliminary studies have suggested little to no increased risk of cancer incidence in patients with psoriasis receiving these therapies, further study allowing greater follow-up and increased power is required to properly examine the potential cancer risk, particularly for site-specific cancers.”

The analysis included 58 studies, published between 1983 and 2017. Nine of these reported risks for cancer incidence among patients with severe psoriasis, and seven reported the risk of cancer mortality among patients with all severities of psoriasis.

Overall, severe psoriasis was associated with an increased cancer risk of 22%; for all severities of psoriasis combined, the risk increase was 18%. Relative risks for specific cancer types were as follows: colon, 1.18; colorectal, 1.34; kidney, 1.58; laryngeal, 1.79; liver, 1.83; lymphoma, 1.40; non-Hodgkin lymphoma, 1.28; keratinocyte cancers, 1.71; esophageal 2.05; oral cavity, 2.80; and pancreatic, 1.41.

Overall cancer mortality risk was 22% higher in patients with severe psoriasis than the general population. Site-specific relative mortality risks included liver, 1.43; esophageal 2.53; and pancreatic, 1.31.

In light of these findings, clinicians should stress lifestyle modifications known to decrease cancer risk, the investigators said. “Although it has been noted that lifestyle behavior change is challenging for healthcare professionals to implement, the importance of a more holistic approach to psoriasis care involving lifestyle behavior change is reinforced through the results of this meta-analysis.”

Among the coauthors were Darren M. Ashcroft, PhD, the senior author, and Christopher Griffiths, MD, both of the University of Manchester. Dr. Ashcroft reported receiving research grants from AbbVie, Almirall, Celgene, Eli Lilly, Novartis, UCB, and the Leo Foundation. Dr. Griffiths reported receiving honoraria and/or research grants from AbbVie, Almirall, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Sandoz, and UCB. The lead author and the other authors had no disclosures. The Global Psoriasis Atlas (GPA) Collaborating Organizations (the International Federation of Psoriasis Associations, the International League of Dermatological Societies, and the International Psoriasis Council) were involved with funding of the study.
 

[email protected]

SOURCE: Trafford A et al. JAMA Dermatol. 2019 Oct 16. doi:10.1001/jamadermatol.2019.3056.

People with psoriasis appear to have both an increased risk of cancer and an increased risk of cancer-related mortality, according to a meta-analysis of cohort and case-control studies.

Compared with a psoriasis-free population, having a diagnosis of severe psoriasis was associated with a 22% increase in cancer risk, Alex Trafford of the University of Manchester (England) and colleagues reported in JAMA Dermatology. The risk of cancer mortality was also increased by 22% among those with severe psoriasis.

The site-specific risks ranged from a low of 18% for colon cancer to more than a twofold increased risk for oral and esophageal cancer, according to the investigators.

Since these were associations only, any underlying mechanism is still unclear, they wrote. The chronic inflammation that drives psoriasis can also drive the development of cancer, but immunomodulatory therapies may also play a part, they suggested.

“Of particular relevance in this regard are biological therapies, which are being increasingly used for the management of psoriasis,” they added. “Although preliminary studies have suggested little to no increased risk of cancer incidence in patients with psoriasis receiving these therapies, further study allowing greater follow-up and increased power is required to properly examine the potential cancer risk, particularly for site-specific cancers.”

The analysis included 58 studies, published between 1983 and 2017. Nine of these reported risks for cancer incidence among patients with severe psoriasis, and seven reported the risk of cancer mortality among patients with all severities of psoriasis.

Overall, severe psoriasis was associated with an increased cancer risk of 22%; for all severities of psoriasis combined, the risk increase was 18%. Relative risks for specific cancer types were as follows: colon, 1.18; colorectal, 1.34; kidney, 1.58; laryngeal, 1.79; liver, 1.83; lymphoma, 1.40; non-Hodgkin lymphoma, 1.28; keratinocyte cancers, 1.71; esophageal 2.05; oral cavity, 2.80; and pancreatic, 1.41.

Overall cancer mortality risk was 22% higher in patients with severe psoriasis than the general population. Site-specific relative mortality risks included liver, 1.43; esophageal 2.53; and pancreatic, 1.31.

In light of these findings, clinicians should stress lifestyle modifications known to decrease cancer risk, the investigators said. “Although it has been noted that lifestyle behavior change is challenging for healthcare professionals to implement, the importance of a more holistic approach to psoriasis care involving lifestyle behavior change is reinforced through the results of this meta-analysis.”

Among the coauthors were Darren M. Ashcroft, PhD, the senior author, and Christopher Griffiths, MD, both of the University of Manchester. Dr. Ashcroft reported receiving research grants from AbbVie, Almirall, Celgene, Eli Lilly, Novartis, UCB, and the Leo Foundation. Dr. Griffiths reported receiving honoraria and/or research grants from AbbVie, Almirall, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Sandoz, and UCB. The lead author and the other authors had no disclosures. The Global Psoriasis Atlas (GPA) Collaborating Organizations (the International Federation of Psoriasis Associations, the International League of Dermatological Societies, and the International Psoriasis Council) were involved with funding of the study.
 

[email protected]

SOURCE: Trafford A et al. JAMA Dermatol. 2019 Oct 16. doi:10.1001/jamadermatol.2019.3056.

People with psoriasis appear to have both an increased risk of cancer and an increased risk of cancer-related mortality, according to a meta-analysis of cohort and case-control studies.

Compared with a psoriasis-free population, having a diagnosis of severe psoriasis was associated with a 22% increase in cancer risk, Alex Trafford of the University of Manchester (England) and colleagues reported in JAMA Dermatology. The risk of cancer mortality was also increased by 22% among those with severe psoriasis.

The site-specific risks ranged from a low of 18% for colon cancer to more than a twofold increased risk for oral and esophageal cancer, according to the investigators.

Since these were associations only, any underlying mechanism is still unclear, they wrote. The chronic inflammation that drives psoriasis can also drive the development of cancer, but immunomodulatory therapies may also play a part, they suggested.

“Of particular relevance in this regard are biological therapies, which are being increasingly used for the management of psoriasis,” they added. “Although preliminary studies have suggested little to no increased risk of cancer incidence in patients with psoriasis receiving these therapies, further study allowing greater follow-up and increased power is required to properly examine the potential cancer risk, particularly for site-specific cancers.”

The analysis included 58 studies, published between 1983 and 2017. Nine of these reported risks for cancer incidence among patients with severe psoriasis, and seven reported the risk of cancer mortality among patients with all severities of psoriasis.

Overall, severe psoriasis was associated with an increased cancer risk of 22%; for all severities of psoriasis combined, the risk increase was 18%. Relative risks for specific cancer types were as follows: colon, 1.18; colorectal, 1.34; kidney, 1.58; laryngeal, 1.79; liver, 1.83; lymphoma, 1.40; non-Hodgkin lymphoma, 1.28; keratinocyte cancers, 1.71; esophageal 2.05; oral cavity, 2.80; and pancreatic, 1.41.

Overall cancer mortality risk was 22% higher in patients with severe psoriasis than the general population. Site-specific relative mortality risks included liver, 1.43; esophageal 2.53; and pancreatic, 1.31.

In light of these findings, clinicians should stress lifestyle modifications known to decrease cancer risk, the investigators said. “Although it has been noted that lifestyle behavior change is challenging for healthcare professionals to implement, the importance of a more holistic approach to psoriasis care involving lifestyle behavior change is reinforced through the results of this meta-analysis.”

Among the coauthors were Darren M. Ashcroft, PhD, the senior author, and Christopher Griffiths, MD, both of the University of Manchester. Dr. Ashcroft reported receiving research grants from AbbVie, Almirall, Celgene, Eli Lilly, Novartis, UCB, and the Leo Foundation. Dr. Griffiths reported receiving honoraria and/or research grants from AbbVie, Almirall, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Sandoz, and UCB. The lead author and the other authors had no disclosures. The Global Psoriasis Atlas (GPA) Collaborating Organizations (the International Federation of Psoriasis Associations, the International League of Dermatological Societies, and the International Psoriasis Council) were involved with funding of the study.
 

[email protected]

SOURCE: Trafford A et al. JAMA Dermatol. 2019 Oct 16. doi:10.1001/jamadermatol.2019.3056.

Psoriasis Associated with Tumor Necrosis Factor-Alpha Inhibitors in Children with Inflammatory Diseases.

Buckley, L. H., Xiao, R. , Perman, M. et al. Arthritis Care Res. 2019 Oct 23.

The study aimed to estimate the incidence rate (IR) of psoriasis in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic noninfectious osteomyelitis (CNO) with tumor necrosis factor‐alpha inhibitor (TNFi) exposure as compared to those without TNFi exposure and to the general pediatric population. Researchers found that children with IBD, JIA, and CNO had an increased rate of psoriasis compared to the general pediatric population, with the highest rate in those with TNFi exposure.

Skin Patterning in Psoriasis by Spatial Interactions between Pathogenic Cytokines.

Ringham, L, Prusinkiewicz, P, Gniadeck R. iScience. 2019 Oct 25;20:546-553.

This study shows that all known patterns of psoriasis, a common inflammatory skin disease, can be explained in terms of reaction-diffusion. Researchers constructed a computational model based on the known interactions between the main pathogenic cytokines: interleukins IL-17 and IL-23, and tumor necrosis factor TNF-α. Simulations revealed that the parameter space of the model contained all classes of psoriatic lesion patterns. They also faithfully reproduced the growth and evolution of the plaques and the response to treatment by cytokine targeting. Thus the pathogenesis of inflammatory diseases, such as psoriasis, may be readily understood in the framework of the stimulatory and inhibitory interactions between a few diffusing mediators.

SEfficacy of Secukinumab for Plaque Psoriasis in a Patient on Hemodialysis.

Ikuma D, Oguro M, Hoshino J, et al. CEN Case Rep. 2019 Oct 25.

The case report discusses the safety and efficiency of secukinumab on a 60-year-old patient on hemodialysis. The psoriasis area and severity index (PASI) score decreased from 49.8 to 14.8 after 2 weeks and to 0 after 6 weeks, with remission being maintained after 28 months. No adverse reactions were seen. This case indicates that secukinumab may be effective for severe psoriasis in patients on hemodialysis for end-stage renal disease.

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients.

Bruin, G, Hockey, H‐UP, La Stella, P, et al. Br J Clin Pharmacol. 2019.

The aim of the study was to compare the pharmacokinetics, safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. Collective evidence from both studies demonstrated that 2 mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticable local reactions.

Dual biologic therapy for recalcitrant psoriasis and psoriatic arthritis

Thibodeaux, Quinn et al. JAAD Case Reports, Volume 5, Issue 10, 928 – 930.

This study presents a patient with severe psoriatic skin and joint disease who has been treated with multiple combinations of dual biologic therapy, including ustekinumab plus etanercept for 12 months, secukinumab plus etanercept for 6 months, and guselkumab plus etanercept for 15 months. Throughout the patient's treatment, adverse events only occurred with the ustekinumab plus etanercept combination and consisted of an increased incidence of urinary tract and upper respiratory infections, including a hospitalization for H2N1 flu.

Psoriasis Associated with Tumor Necrosis Factor-Alpha Inhibitors in Children with Inflammatory Diseases.

Buckley, L. H., Xiao, R. , Perman, M. et al. Arthritis Care Res. 2019 Oct 23.

The study aimed to estimate the incidence rate (IR) of psoriasis in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic noninfectious osteomyelitis (CNO) with tumor necrosis factor‐alpha inhibitor (TNFi) exposure as compared to those without TNFi exposure and to the general pediatric population. Researchers found that children with IBD, JIA, and CNO had an increased rate of psoriasis compared to the general pediatric population, with the highest rate in those with TNFi exposure.

Skin Patterning in Psoriasis by Spatial Interactions between Pathogenic Cytokines.

Ringham, L, Prusinkiewicz, P, Gniadeck R. iScience. 2019 Oct 25;20:546-553.

This study shows that all known patterns of psoriasis, a common inflammatory skin disease, can be explained in terms of reaction-diffusion. Researchers constructed a computational model based on the known interactions between the main pathogenic cytokines: interleukins IL-17 and IL-23, and tumor necrosis factor TNF-α. Simulations revealed that the parameter space of the model contained all classes of psoriatic lesion patterns. They also faithfully reproduced the growth and evolution of the plaques and the response to treatment by cytokine targeting. Thus the pathogenesis of inflammatory diseases, such as psoriasis, may be readily understood in the framework of the stimulatory and inhibitory interactions between a few diffusing mediators.

SEfficacy of Secukinumab for Plaque Psoriasis in a Patient on Hemodialysis.

Ikuma D, Oguro M, Hoshino J, et al. CEN Case Rep. 2019 Oct 25.

The case report discusses the safety and efficiency of secukinumab on a 60-year-old patient on hemodialysis. The psoriasis area and severity index (PASI) score decreased from 49.8 to 14.8 after 2 weeks and to 0 after 6 weeks, with remission being maintained after 28 months. No adverse reactions were seen. This case indicates that secukinumab may be effective for severe psoriasis in patients on hemodialysis for end-stage renal disease.

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients.

Bruin, G, Hockey, H‐UP, La Stella, P, et al. Br J Clin Pharmacol. 2019.

The aim of the study was to compare the pharmacokinetics, safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. Collective evidence from both studies demonstrated that 2 mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticable local reactions.

Dual biologic therapy for recalcitrant psoriasis and psoriatic arthritis

Thibodeaux, Quinn et al. JAAD Case Reports, Volume 5, Issue 10, 928 – 930.

This study presents a patient with severe psoriatic skin and joint disease who has been treated with multiple combinations of dual biologic therapy, including ustekinumab plus etanercept for 12 months, secukinumab plus etanercept for 6 months, and guselkumab plus etanercept for 15 months. Throughout the patient's treatment, adverse events only occurred with the ustekinumab plus etanercept combination and consisted of an increased incidence of urinary tract and upper respiratory infections, including a hospitalization for H2N1 flu.

Psoriasis Associated with Tumor Necrosis Factor-Alpha Inhibitors in Children with Inflammatory Diseases.

Buckley, L. H., Xiao, R. , Perman, M. et al. Arthritis Care Res. 2019 Oct 23.

The study aimed to estimate the incidence rate (IR) of psoriasis in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic noninfectious osteomyelitis (CNO) with tumor necrosis factor‐alpha inhibitor (TNFi) exposure as compared to those without TNFi exposure and to the general pediatric population. Researchers found that children with IBD, JIA, and CNO had an increased rate of psoriasis compared to the general pediatric population, with the highest rate in those with TNFi exposure.

Skin Patterning in Psoriasis by Spatial Interactions between Pathogenic Cytokines.

Ringham, L, Prusinkiewicz, P, Gniadeck R. iScience. 2019 Oct 25;20:546-553.

This study shows that all known patterns of psoriasis, a common inflammatory skin disease, can be explained in terms of reaction-diffusion. Researchers constructed a computational model based on the known interactions between the main pathogenic cytokines: interleukins IL-17 and IL-23, and tumor necrosis factor TNF-α. Simulations revealed that the parameter space of the model contained all classes of psoriatic lesion patterns. They also faithfully reproduced the growth and evolution of the plaques and the response to treatment by cytokine targeting. Thus the pathogenesis of inflammatory diseases, such as psoriasis, may be readily understood in the framework of the stimulatory and inhibitory interactions between a few diffusing mediators.

SEfficacy of Secukinumab for Plaque Psoriasis in a Patient on Hemodialysis.

Ikuma D, Oguro M, Hoshino J, et al. CEN Case Rep. 2019 Oct 25.

The case report discusses the safety and efficiency of secukinumab on a 60-year-old patient on hemodialysis. The psoriasis area and severity index (PASI) score decreased from 49.8 to 14.8 after 2 weeks and to 0 after 6 weeks, with remission being maintained after 28 months. No adverse reactions were seen. This case indicates that secukinumab may be effective for severe psoriasis in patients on hemodialysis for end-stage renal disease.

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients.

Bruin, G, Hockey, H‐UP, La Stella, P, et al. Br J Clin Pharmacol. 2019.

The aim of the study was to compare the pharmacokinetics, safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. Collective evidence from both studies demonstrated that 2 mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticable local reactions.

Dual biologic therapy for recalcitrant psoriasis and psoriatic arthritis

Thibodeaux, Quinn et al. JAAD Case Reports, Volume 5, Issue 10, 928 – 930.

This study presents a patient with severe psoriatic skin and joint disease who has been treated with multiple combinations of dual biologic therapy, including ustekinumab plus etanercept for 12 months, secukinumab plus etanercept for 6 months, and guselkumab plus etanercept for 15 months. Throughout the patient's treatment, adverse events only occurred with the ustekinumab plus etanercept combination and consisted of an increased incidence of urinary tract and upper respiratory infections, including a hospitalization for H2N1 flu.

Psoriasis is nearly four times more likely to develop in children who were exposed to tumor necrosis factor inhibitors for inflammatory disorders than in unexposed children, a retrospective cohort study has determined.

“The incidence rate and risk factors of psoriasis in children with IBD [inflammatory bowel disease], JIA [juvenile idiopathic arthritis], or CNO [chronic nonbacterial osteomyelitis] who are exposed to TNFi [tumor necrosis factor inhibitors] are unknown. Additionally, there is a well-established association between these inflammatory conditions and psoriasis development. Yet, as TNFi can both treat and trigger psoriasis, it is not clear how TNFi exposure affects this relationship,” wrote Lisa H. Buckley, MD, of Children’s Hospital at Vanderbilt, Nashville, Tenn., and colleagues. Their report is in Arthritis Care & Research.

The team examined the relationship in children who were treated for an inflammatory disorder at Children’s Hospital of Philadelphia during 2008-2018. IBD was most common at 74%, followed by JIA at 24% and CNO at 2%.

Among 4,111 children with those inflammatory disorders, the psoriasis incidence was 12.3 per 1,000 person-years in exposed children and 3.8 per 1,000 person-years in unexposed. This significant difference equated to a hazard ratio of 3.84 for developing psoriasis after TNFi exposure.

“These data reflect the established association between inflammatory conditions and psoriasis development and suggest that TNFi exposure further increases the risk of psoriasis,” Dr. Buckley and coauthors wrote.

The median duration of follow-up in this study was about 2.5 years for patients exposed to TNFi and 2 years for those unexposed. Among the entire cohort, 39% had been exposed to a TNFi, with 4,705 person-years of follow-up. Among the unexposed children (61%), there were 6,604 person-years of follow-up.

In all, 83 cases of psoriasis developed: 58 in the exposed group and 25 in the unexposed group. Psoriasis incidence varied by disorder. Exposed children with IBD had a higher incidence than did unexposed children (10.9 vs. 2.6 per 1,000 person-years; HR = 4.52). Exposed children with JIA also had a higher incidence than did unexposed children (14.7 vs. 5.5 per 1,000 person-years; HR = 2.90). Among those with CNO, incidences were similar for exposed and unexposed children (33.5 and 38.9 per 1,000 person-years).

A family history of psoriasis significantly increased the risk of psoriasis with a hazard ratio of 3.11, the authors noted. But none of the other covariates (age, sex, race, obesity, methotrexate exposure, and underlying diagnosis) exerted a significant additional risk.

The study had no outside funding source. The authors had no financial disclosures. Dr. Buckley conducted the research when she was a pediatric rheumatology fellow at Children’s Hospital of Philadelphia.

[email protected]

SOURCE: Buckley LH et al. Arthritis Care Res. 2019 Oct 23. doi: 10.1002/ACR.24100

Psoriasis is nearly four times more likely to develop in children who were exposed to tumor necrosis factor inhibitors for inflammatory disorders than in unexposed children, a retrospective cohort study has determined.

“The incidence rate and risk factors of psoriasis in children with IBD [inflammatory bowel disease], JIA [juvenile idiopathic arthritis], or CNO [chronic nonbacterial osteomyelitis] who are exposed to TNFi [tumor necrosis factor inhibitors] are unknown. Additionally, there is a well-established association between these inflammatory conditions and psoriasis development. Yet, as TNFi can both treat and trigger psoriasis, it is not clear how TNFi exposure affects this relationship,” wrote Lisa H. Buckley, MD, of Children’s Hospital at Vanderbilt, Nashville, Tenn., and colleagues. Their report is in Arthritis Care & Research.

The team examined the relationship in children who were treated for an inflammatory disorder at Children’s Hospital of Philadelphia during 2008-2018. IBD was most common at 74%, followed by JIA at 24% and CNO at 2%.

Among 4,111 children with those inflammatory disorders, the psoriasis incidence was 12.3 per 1,000 person-years in exposed children and 3.8 per 1,000 person-years in unexposed. This significant difference equated to a hazard ratio of 3.84 for developing psoriasis after TNFi exposure.

“These data reflect the established association between inflammatory conditions and psoriasis development and suggest that TNFi exposure further increases the risk of psoriasis,” Dr. Buckley and coauthors wrote.

The median duration of follow-up in this study was about 2.5 years for patients exposed to TNFi and 2 years for those unexposed. Among the entire cohort, 39% had been exposed to a TNFi, with 4,705 person-years of follow-up. Among the unexposed children (61%), there were 6,604 person-years of follow-up.

In all, 83 cases of psoriasis developed: 58 in the exposed group and 25 in the unexposed group. Psoriasis incidence varied by disorder. Exposed children with IBD had a higher incidence than did unexposed children (10.9 vs. 2.6 per 1,000 person-years; HR = 4.52). Exposed children with JIA also had a higher incidence than did unexposed children (14.7 vs. 5.5 per 1,000 person-years; HR = 2.90). Among those with CNO, incidences were similar for exposed and unexposed children (33.5 and 38.9 per 1,000 person-years).

A family history of psoriasis significantly increased the risk of psoriasis with a hazard ratio of 3.11, the authors noted. But none of the other covariates (age, sex, race, obesity, methotrexate exposure, and underlying diagnosis) exerted a significant additional risk.

The study had no outside funding source. The authors had no financial disclosures. Dr. Buckley conducted the research when she was a pediatric rheumatology fellow at Children’s Hospital of Philadelphia.

[email protected]

SOURCE: Buckley LH et al. Arthritis Care Res. 2019 Oct 23. doi: 10.1002/ACR.24100

Psoriasis is nearly four times more likely to develop in children who were exposed to tumor necrosis factor inhibitors for inflammatory disorders than in unexposed children, a retrospective cohort study has determined.

“The incidence rate and risk factors of psoriasis in children with IBD [inflammatory bowel disease], JIA [juvenile idiopathic arthritis], or CNO [chronic nonbacterial osteomyelitis] who are exposed to TNFi [tumor necrosis factor inhibitors] are unknown. Additionally, there is a well-established association between these inflammatory conditions and psoriasis development. Yet, as TNFi can both treat and trigger psoriasis, it is not clear how TNFi exposure affects this relationship,” wrote Lisa H. Buckley, MD, of Children’s Hospital at Vanderbilt, Nashville, Tenn., and colleagues. Their report is in Arthritis Care & Research.

The team examined the relationship in children who were treated for an inflammatory disorder at Children’s Hospital of Philadelphia during 2008-2018. IBD was most common at 74%, followed by JIA at 24% and CNO at 2%.

Among 4,111 children with those inflammatory disorders, the psoriasis incidence was 12.3 per 1,000 person-years in exposed children and 3.8 per 1,000 person-years in unexposed. This significant difference equated to a hazard ratio of 3.84 for developing psoriasis after TNFi exposure.

“These data reflect the established association between inflammatory conditions and psoriasis development and suggest that TNFi exposure further increases the risk of psoriasis,” Dr. Buckley and coauthors wrote.

The median duration of follow-up in this study was about 2.5 years for patients exposed to TNFi and 2 years for those unexposed. Among the entire cohort, 39% had been exposed to a TNFi, with 4,705 person-years of follow-up. Among the unexposed children (61%), there were 6,604 person-years of follow-up.

In all, 83 cases of psoriasis developed: 58 in the exposed group and 25 in the unexposed group. Psoriasis incidence varied by disorder. Exposed children with IBD had a higher incidence than did unexposed children (10.9 vs. 2.6 per 1,000 person-years; HR = 4.52). Exposed children with JIA also had a higher incidence than did unexposed children (14.7 vs. 5.5 per 1,000 person-years; HR = 2.90). Among those with CNO, incidences were similar for exposed and unexposed children (33.5 and 38.9 per 1,000 person-years).

A family history of psoriasis significantly increased the risk of psoriasis with a hazard ratio of 3.11, the authors noted. But none of the other covariates (age, sex, race, obesity, methotrexate exposure, and underlying diagnosis) exerted a significant additional risk.

The study had no outside funding source. The authors had no financial disclosures. Dr. Buckley conducted the research when she was a pediatric rheumatology fellow at Children’s Hospital of Philadelphia.

[email protected]

SOURCE: Buckley LH et al. Arthritis Care Res. 2019 Oct 23. doi: 10.1002/ACR.24100

MADRID – Psoriasis patients aged 65 years and older are at more than twice the risk of serious bacterial and opportunistic infections, compared with younger patients, but that risk is not further elevated by being on biologic agents, Joseph F. Merola, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

He presented a large, propensity score–matched comparative safety study, which demonstrated that the infection risk of older psoriasis patients on biologics was not significantly different from that of similar patients on nonbiologic systemic medications or phototherapy. The study implications, he said, are clear: When moderate to severe psoriasis warrants consideration of highly effective biologic therapies, that therapeutic option shouldn’t be taken off the table on the basis of a mistaken belief that biologics pose a greater infection risk just because the affected patient is over age 65 years.

“We really think that older patients should be offered treatments at the same level of disease control as all the rest of our psoriasis patients, in the context of shared decision making,” said Dr. Merola, a dermatologist and rheumatologist who is the director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston.

The study utilized longitudinal claims data from a very large U.S. database covering the years 2003-2017. Among the 185 million covered lives were 1.1 million individuals with psoriasis, including 150,000 aged 65 years or older. After excluding older psoriasis patients with comorbid cancer or autoimmune disease, the investigators were left with 11,218 older psoriasis patients initiating systemic therapy for the first time and therefore eligible for propensity score matching using a highly accurate proprietary platform. The final study population consisted of 2,795 older psoriasis patients newly initiating biologic therapy, 2,795 others newly initiating nonbiologic systemic agents, and 2,529 seniors starting phototherapy. The matching was based upon factors including age, sex, prior infections, comorbid psoriatic arthritis, diabetes, and obesity.

The primary study endpoint was the rate of serious bacterial or opportunistic infections requiring hospitalization during the first 6 months of treatment. The bottom line: The rates were closely similar across all three groups, with the most common serious infections being pneumonia and cellulitis.

In contrast, among a population of 115,047 senior psoriasis patients who never used systemic therapy, the risk of serious infection was 12.2 events per 1,000 patients over 6 months, compared with 5.3 events in 120,174 matched controls without psoriasis. That translates to a 2.24-fold increased risk.

One audience member commented that a limitation of the study was that all biologics were lumped together. He would expect that the tumor necrosis factor inhibitors, for example, would be associated with a significantly higher serious infection risk than biologics with other targets.

Dr. Merola conceded the point, adding that the investigators are trying to reanalyze the data in a more granular way to address that shortcoming. Other study limitations included an inability to access the specific doses of systemic treatments used or to stratify patients by disease severity.

Another audience member noted that dermatologists often reassure surgeons that there’s no increased risk of infection associated with psoriasis when in fact there is increased risk in older psoriasis patients, according to these new data.

“We’re not trying to send a message to surgeons to withhold a knee transplant because of a psoriasis plaque over the knee,” Dr. Merola replied. “I think we’ve all been there; we’ve all fought that battle.” Based on the data, he said, he would advise that “our patients who need to be on systemics should remain appropriately on systemics as we see fit.”

The study was entirely funded by Brigham and Women’s Hospital. Dr. Merola reported serving as a consultant to and/or recipient of research grants from nearly two dozen pharmaceutical companies.

[email protected]

MADRID – Psoriasis patients aged 65 years and older are at more than twice the risk of serious bacterial and opportunistic infections, compared with younger patients, but that risk is not further elevated by being on biologic agents, Joseph F. Merola, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

He presented a large, propensity score–matched comparative safety study, which demonstrated that the infection risk of older psoriasis patients on biologics was not significantly different from that of similar patients on nonbiologic systemic medications or phototherapy. The study implications, he said, are clear: When moderate to severe psoriasis warrants consideration of highly effective biologic therapies, that therapeutic option shouldn’t be taken off the table on the basis of a mistaken belief that biologics pose a greater infection risk just because the affected patient is over age 65 years.

“We really think that older patients should be offered treatments at the same level of disease control as all the rest of our psoriasis patients, in the context of shared decision making,” said Dr. Merola, a dermatologist and rheumatologist who is the director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston.

The study utilized longitudinal claims data from a very large U.S. database covering the years 2003-2017. Among the 185 million covered lives were 1.1 million individuals with psoriasis, including 150,000 aged 65 years or older. After excluding older psoriasis patients with comorbid cancer or autoimmune disease, the investigators were left with 11,218 older psoriasis patients initiating systemic therapy for the first time and therefore eligible for propensity score matching using a highly accurate proprietary platform. The final study population consisted of 2,795 older psoriasis patients newly initiating biologic therapy, 2,795 others newly initiating nonbiologic systemic agents, and 2,529 seniors starting phototherapy. The matching was based upon factors including age, sex, prior infections, comorbid psoriatic arthritis, diabetes, and obesity.

The primary study endpoint was the rate of serious bacterial or opportunistic infections requiring hospitalization during the first 6 months of treatment. The bottom line: The rates were closely similar across all three groups, with the most common serious infections being pneumonia and cellulitis.

In contrast, among a population of 115,047 senior psoriasis patients who never used systemic therapy, the risk of serious infection was 12.2 events per 1,000 patients over 6 months, compared with 5.3 events in 120,174 matched controls without psoriasis. That translates to a 2.24-fold increased risk.

One audience member commented that a limitation of the study was that all biologics were lumped together. He would expect that the tumor necrosis factor inhibitors, for example, would be associated with a significantly higher serious infection risk than biologics with other targets.

Dr. Merola conceded the point, adding that the investigators are trying to reanalyze the data in a more granular way to address that shortcoming. Other study limitations included an inability to access the specific doses of systemic treatments used or to stratify patients by disease severity.

Another audience member noted that dermatologists often reassure surgeons that there’s no increased risk of infection associated with psoriasis when in fact there is increased risk in older psoriasis patients, according to these new data.

“We’re not trying to send a message to surgeons to withhold a knee transplant because of a psoriasis plaque over the knee,” Dr. Merola replied. “I think we’ve all been there; we’ve all fought that battle.” Based on the data, he said, he would advise that “our patients who need to be on systemics should remain appropriately on systemics as we see fit.”

The study was entirely funded by Brigham and Women’s Hospital. Dr. Merola reported serving as a consultant to and/or recipient of research grants from nearly two dozen pharmaceutical companies.

[email protected]

MADRID – Psoriasis patients aged 65 years and older are at more than twice the risk of serious bacterial and opportunistic infections, compared with younger patients, but that risk is not further elevated by being on biologic agents, Joseph F. Merola, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

He presented a large, propensity score–matched comparative safety study, which demonstrated that the infection risk of older psoriasis patients on biologics was not significantly different from that of similar patients on nonbiologic systemic medications or phototherapy. The study implications, he said, are clear: When moderate to severe psoriasis warrants consideration of highly effective biologic therapies, that therapeutic option shouldn’t be taken off the table on the basis of a mistaken belief that biologics pose a greater infection risk just because the affected patient is over age 65 years.

“We really think that older patients should be offered treatments at the same level of disease control as all the rest of our psoriasis patients, in the context of shared decision making,” said Dr. Merola, a dermatologist and rheumatologist who is the director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston.

The study utilized longitudinal claims data from a very large U.S. database covering the years 2003-2017. Among the 185 million covered lives were 1.1 million individuals with psoriasis, including 150,000 aged 65 years or older. After excluding older psoriasis patients with comorbid cancer or autoimmune disease, the investigators were left with 11,218 older psoriasis patients initiating systemic therapy for the first time and therefore eligible for propensity score matching using a highly accurate proprietary platform. The final study population consisted of 2,795 older psoriasis patients newly initiating biologic therapy, 2,795 others newly initiating nonbiologic systemic agents, and 2,529 seniors starting phototherapy. The matching was based upon factors including age, sex, prior infections, comorbid psoriatic arthritis, diabetes, and obesity.

The primary study endpoint was the rate of serious bacterial or opportunistic infections requiring hospitalization during the first 6 months of treatment. The bottom line: The rates were closely similar across all three groups, with the most common serious infections being pneumonia and cellulitis.

In contrast, among a population of 115,047 senior psoriasis patients who never used systemic therapy, the risk of serious infection was 12.2 events per 1,000 patients over 6 months, compared with 5.3 events in 120,174 matched controls without psoriasis. That translates to a 2.24-fold increased risk.

One audience member commented that a limitation of the study was that all biologics were lumped together. He would expect that the tumor necrosis factor inhibitors, for example, would be associated with a significantly higher serious infection risk than biologics with other targets.

Dr. Merola conceded the point, adding that the investigators are trying to reanalyze the data in a more granular way to address that shortcoming. Other study limitations included an inability to access the specific doses of systemic treatments used or to stratify patients by disease severity.

Another audience member noted that dermatologists often reassure surgeons that there’s no increased risk of infection associated with psoriasis when in fact there is increased risk in older psoriasis patients, according to these new data.

“We’re not trying to send a message to surgeons to withhold a knee transplant because of a psoriasis plaque over the knee,” Dr. Merola replied. “I think we’ve all been there; we’ve all fought that battle.” Based on the data, he said, he would advise that “our patients who need to be on systemics should remain appropriately on systemics as we see fit.”

The study was entirely funded by Brigham and Women’s Hospital. Dr. Merola reported serving as a consultant to and/or recipient of research grants from nearly two dozen pharmaceutical companies.

[email protected]

MADRID – The interleukin-17A inhibitor ixekizumab met all primary and secondary endpoints in a phase 3 trial in 6- to 18-year-olds with moderate to severe plaque psoriasis, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The results bode well for an underserved population.

“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.

At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.

The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.

The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.

An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.

The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.

More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.

And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.

“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.

He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.

Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.

Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.

[email protected]

SOURCE: Papp KA. EADV Late breaker.

MADRID – The interleukin-17A inhibitor ixekizumab met all primary and secondary endpoints in a phase 3 trial in 6- to 18-year-olds with moderate to severe plaque psoriasis, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The results bode well for an underserved population.

“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.

At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.

The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.

The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.

An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.

The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.

More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.

And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.

“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.

He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.

Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.

Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.

[email protected]

SOURCE: Papp KA. EADV Late breaker.

MADRID – The interleukin-17A inhibitor ixekizumab met all primary and secondary endpoints in a phase 3 trial in 6- to 18-year-olds with moderate to severe plaque psoriasis, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The results bode well for an underserved population.

“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.

At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.

The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.

The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.

An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.

The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.

More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.

And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.

“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.

He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.

Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.

Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.

[email protected]

SOURCE: Papp KA. EADV Late breaker.

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[email protected]

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[email protected]

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[email protected]

SEATTLE – Treatment of psoriasis has been profoundly impacted by the advent of biologic therapies, but “topical therapy is not dead,” Linda Stein Gold, MD, said at the annual Coastal Dermatology Symposium.

Jim Kling/MDedge News

“We have to remember when we think back to our practice, how many topical prescriptions do we write, compared to preventive prescriptions? Probably most are topical,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Hospital Center, Detroit.

Topical agents have a place when a patient is doing well on treatment with a biologic but is not responding completely, she noted. One open-label, single-arm study looked at adjunctive calcipotriene 0.005%/betamethasone dipropionate 0.064% (Enstilar) foam, applied once daily for 4 week, then twice a week on consecutive days for 12 weeks in 25 patients with psoriasis who had a mean body surface area (BSA) of less than 5% but significant remaining disease despite treatment with biologics.

At week 4, 76% achieved a BSA of 1% or less and Physician’s Global Assessment score of 1 or less at week 4, as did 68% at week 16. This was compared with 12% and 4%, respectively (J Drugs Dermatol. 2018 Aug 1;17[8]:845-50). “They found that a good potent topical on top of a biologic does really well. That can really kick up the last part of the efficacy to get the patients almost to clear,” she observed.

At the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education, Dr. Stein Gold also discussed tazarotene, a topical retinoid approved by the Food and Drug Administration for treating psoriasis and is available as a 0.1% and 0.05% cream and gel. About 10%-30% of patients experience side effects with tazarotene, such as pruritus, stinging, and burning. Topical corticosteroids can help, which prompted development of a combined product, she noted.

She referred to a phase 2 study of patients with moderate to severe plaque psoriasis, which compared the fixed combination lotion formulation of tazarotene plus halobetasol propionate to the two components alone. The investigators found almost a 9% rate of treatment success with tazarotene alone, versus about 23% with halobetasol propionate alone and about 43% with the combined product. The combined individual effect of the two drugs was about 32%, so the 43% efficacy of the combined product had an absolute synergistic effect of about 11%, Dr. Stein Gold pointed out.

Two phase 3 trials of adults with moderate to severe psoriasis supported the phase 2 results of the combined lotion formulation (halobetasol 0.01% with tazarotene 0.045%), said Dr. Stein Gold, the first author (J Am Acad Dermatol. 2018 Aug;79[2]:287-93). Treatment success was defined as at least a 2-grade Investigator’s Global Assessment score and improvement from baseline and a score of “clear” or “almost clear.” In one of the studies, 36% of those on the combination versus 7% of those on the vehicle met this endpoint at week 8, as did 45% versus 13%, respectively, in the second study (P less than .001 for both studies).

Patients also had less itching, drying, and stinging than typically seen with tazarotene alone, Dr. Stein Gold said. In the studies, contact dermatitis was the most common side effect associated with treatment, reported in 6.3%

Dr. Stein Gold has received research support from Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, and Foamix. She has been a consultant for Sol-gel, Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Promis, Anacor, and Medimetriks. She has been on the speakers bureau of Galderma, Leo, Valeant, Novartis, Celgene, and Allergan. She has been a member of scientific advisory boards for Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, and Promius.

This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Treatment of psoriasis has been profoundly impacted by the advent of biologic therapies, but “topical therapy is not dead,” Linda Stein Gold, MD, said at the annual Coastal Dermatology Symposium.

Jim Kling/MDedge News

“We have to remember when we think back to our practice, how many topical prescriptions do we write, compared to preventive prescriptions? Probably most are topical,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Hospital Center, Detroit.

Topical agents have a place when a patient is doing well on treatment with a biologic but is not responding completely, she noted. One open-label, single-arm study looked at adjunctive calcipotriene 0.005%/betamethasone dipropionate 0.064% (Enstilar) foam, applied once daily for 4 week, then twice a week on consecutive days for 12 weeks in 25 patients with psoriasis who had a mean body surface area (BSA) of less than 5% but significant remaining disease despite treatment with biologics.

At week 4, 76% achieved a BSA of 1% or less and Physician’s Global Assessment score of 1 or less at week 4, as did 68% at week 16. This was compared with 12% and 4%, respectively (J Drugs Dermatol. 2018 Aug 1;17[8]:845-50). “They found that a good potent topical on top of a biologic does really well. That can really kick up the last part of the efficacy to get the patients almost to clear,” she observed.

At the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education, Dr. Stein Gold also discussed tazarotene, a topical retinoid approved by the Food and Drug Administration for treating psoriasis and is available as a 0.1% and 0.05% cream and gel. About 10%-30% of patients experience side effects with tazarotene, such as pruritus, stinging, and burning. Topical corticosteroids can help, which prompted development of a combined product, she noted.

She referred to a phase 2 study of patients with moderate to severe plaque psoriasis, which compared the fixed combination lotion formulation of tazarotene plus halobetasol propionate to the two components alone. The investigators found almost a 9% rate of treatment success with tazarotene alone, versus about 23% with halobetasol propionate alone and about 43% with the combined product. The combined individual effect of the two drugs was about 32%, so the 43% efficacy of the combined product had an absolute synergistic effect of about 11%, Dr. Stein Gold pointed out.

Two phase 3 trials of adults with moderate to severe psoriasis supported the phase 2 results of the combined lotion formulation (halobetasol 0.01% with tazarotene 0.045%), said Dr. Stein Gold, the first author (J Am Acad Dermatol. 2018 Aug;79[2]:287-93). Treatment success was defined as at least a 2-grade Investigator’s Global Assessment score and improvement from baseline and a score of “clear” or “almost clear.” In one of the studies, 36% of those on the combination versus 7% of those on the vehicle met this endpoint at week 8, as did 45% versus 13%, respectively, in the second study (P less than .001 for both studies).

Patients also had less itching, drying, and stinging than typically seen with tazarotene alone, Dr. Stein Gold said. In the studies, contact dermatitis was the most common side effect associated with treatment, reported in 6.3%

Dr. Stein Gold has received research support from Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, and Foamix. She has been a consultant for Sol-gel, Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Promis, Anacor, and Medimetriks. She has been on the speakers bureau of Galderma, Leo, Valeant, Novartis, Celgene, and Allergan. She has been a member of scientific advisory boards for Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, and Promius.

This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Treatment of psoriasis has been profoundly impacted by the advent of biologic therapies, but “topical therapy is not dead,” Linda Stein Gold, MD, said at the annual Coastal Dermatology Symposium.

Jim Kling/MDedge News

“We have to remember when we think back to our practice, how many topical prescriptions do we write, compared to preventive prescriptions? Probably most are topical,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Hospital Center, Detroit.

Topical agents have a place when a patient is doing well on treatment with a biologic but is not responding completely, she noted. One open-label, single-arm study looked at adjunctive calcipotriene 0.005%/betamethasone dipropionate 0.064% (Enstilar) foam, applied once daily for 4 week, then twice a week on consecutive days for 12 weeks in 25 patients with psoriasis who had a mean body surface area (BSA) of less than 5% but significant remaining disease despite treatment with biologics.

At week 4, 76% achieved a BSA of 1% or less and Physician’s Global Assessment score of 1 or less at week 4, as did 68% at week 16. This was compared with 12% and 4%, respectively (J Drugs Dermatol. 2018 Aug 1;17[8]:845-50). “They found that a good potent topical on top of a biologic does really well. That can really kick up the last part of the efficacy to get the patients almost to clear,” she observed.

At the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education, Dr. Stein Gold also discussed tazarotene, a topical retinoid approved by the Food and Drug Administration for treating psoriasis and is available as a 0.1% and 0.05% cream and gel. About 10%-30% of patients experience side effects with tazarotene, such as pruritus, stinging, and burning. Topical corticosteroids can help, which prompted development of a combined product, she noted.

She referred to a phase 2 study of patients with moderate to severe plaque psoriasis, which compared the fixed combination lotion formulation of tazarotene plus halobetasol propionate to the two components alone. The investigators found almost a 9% rate of treatment success with tazarotene alone, versus about 23% with halobetasol propionate alone and about 43% with the combined product. The combined individual effect of the two drugs was about 32%, so the 43% efficacy of the combined product had an absolute synergistic effect of about 11%, Dr. Stein Gold pointed out.

Two phase 3 trials of adults with moderate to severe psoriasis supported the phase 2 results of the combined lotion formulation (halobetasol 0.01% with tazarotene 0.045%), said Dr. Stein Gold, the first author (J Am Acad Dermatol. 2018 Aug;79[2]:287-93). Treatment success was defined as at least a 2-grade Investigator’s Global Assessment score and improvement from baseline and a score of “clear” or “almost clear.” In one of the studies, 36% of those on the combination versus 7% of those on the vehicle met this endpoint at week 8, as did 45% versus 13%, respectively, in the second study (P less than .001 for both studies).

Patients also had less itching, drying, and stinging than typically seen with tazarotene alone, Dr. Stein Gold said. In the studies, contact dermatitis was the most common side effect associated with treatment, reported in 6.3%

Dr. Stein Gold has received research support from Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, and Foamix. She has been a consultant for Sol-gel, Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Promis, Anacor, and Medimetriks. She has been on the speakers bureau of Galderma, Leo, Valeant, Novartis, Celgene, and Allergan. She has been a member of scientific advisory boards for Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, and Promius.

This publication and Global Academy for Medical Education are owned by the same parent company.