Psoriasis

If apremilast (Otezla) works initially for psoriasis, it’s likely to keep on helping for at least a year, according to phase III results published by the drug’s maker, Celgene, in the Journal of the American Academy of Dermatology.

The trial randomized 562 patients with moderate to severe plaque psoriasis to apremilast 30 mg twice daily, and 282 to placebo (J Am Acad Dermatol. 2015 Jul;73[1]:37-49).

At week 16, 33% of apremilast patients, but only 5.3% of placebo patients, achieved a 75% or greater reduction from their baseline Psoriasis Area and Severity Index (PASI-75) scores (P less than .0001).

The placebo group was next switched to apremilast so that all the subjects were on the drug from weeks 16 to 32. By week 32, patients switched from placebo caught up with their apremilast peers on PASI-75 response rates and improved pruritus scores.

The study continued past week 32 with 154 patients who had been on apremilast since baseline and had reached PASI-75; half were rerandomized to placebo, half to the drug. At week 52, 47 (61%) of apremilast patients had maintained their PASI-75 response, versus 9 (12%) of placebo patients.

“PASI response was maintained over 52 weeks with continued apremilast treatment. In addition, apremilast demonstrated improvements in nail and scalp psoriasis, both difficult-to-treat forms of psoriasis. Most patients rerandomized to placebo who lost PASI-75 response regained it after apremilast reinitiation,” said the authors, led by Dr. Kim Papp of Probity Medical Research in Waterloo, Ont.

Apremilast, an oral phosphodiesterase 4 inhibitor, was approved by the Food and Drug Administration in 2014 for moderate to severe plaque psoriasis and psoriatic arthritis. The 16-week results are included in the drug’s label.

The label warns of weight loss and depression with apremilast. The new report doesn’t mention depression but does note a mean weight loss of 2.08 kg with the drug, and that 19% of patients lost more than 5% of their body weight. However, no one left the study because of it.

During the first 16 weeks of the trial, the most common side effects were diarrhea (7.1% placebo versus 19% apremilast); nausea (6.7% placebo versus 16% apremilast); upper respiratory tract infection (7.4% versus 10%); nasopharyngitis (8.2% versus 7.3%); and tension headache (4.3% versus 7.3%).

Side effects tended to present early with apremilast, and the incidence didn’t increase as treatment continued. To minimize side effects, the investigators titrated the drug in 10-mg increments over the first week of treatment. Discontinuations due to side effects were low.

Serious adverse events occurred in 2.8% of placebo and 2.1% of apremilast subjects. In the apremilast group, they included three cases of coronary artery disease and three cases of nephrolithiasis, plus two cases each of urinary tract infections, acute myocardial infarctions, and chronic obstructive pulmonary disease.

The investigators excluded patients with major uncontrolled comorbidities, significant infections, active or incompletely treated tuberculosis, biologic use within 12-24 months, use of active topical agents within 2 weeks, and prolonged sun or ultraviolet exposure. Most of the subjects were white, two-thirds were men, and the average age in the study was 45 years. Weak or low-potency topical corticosteroids, coal tar shampoo and salicylic acid for scalp lesions, and unmedicated moisturizers were allowed in the study.

Celgene Corporation, the maker of apremilast, funded the work. Three investigators are employees, and most of the rest reported financial relationships with the company.

[email protected]

If apremilast (Otezla) works initially for psoriasis, it’s likely to keep on helping for at least a year, according to phase III results published by the drug’s maker, Celgene, in the Journal of the American Academy of Dermatology.

The trial randomized 562 patients with moderate to severe plaque psoriasis to apremilast 30 mg twice daily, and 282 to placebo (J Am Acad Dermatol. 2015 Jul;73[1]:37-49).

At week 16, 33% of apremilast patients, but only 5.3% of placebo patients, achieved a 75% or greater reduction from their baseline Psoriasis Area and Severity Index (PASI-75) scores (P less than .0001).

The placebo group was next switched to apremilast so that all the subjects were on the drug from weeks 16 to 32. By week 32, patients switched from placebo caught up with their apremilast peers on PASI-75 response rates and improved pruritus scores.

The study continued past week 32 with 154 patients who had been on apremilast since baseline and had reached PASI-75; half were rerandomized to placebo, half to the drug. At week 52, 47 (61%) of apremilast patients had maintained their PASI-75 response, versus 9 (12%) of placebo patients.

“PASI response was maintained over 52 weeks with continued apremilast treatment. In addition, apremilast demonstrated improvements in nail and scalp psoriasis, both difficult-to-treat forms of psoriasis. Most patients rerandomized to placebo who lost PASI-75 response regained it after apremilast reinitiation,” said the authors, led by Dr. Kim Papp of Probity Medical Research in Waterloo, Ont.

Apremilast, an oral phosphodiesterase 4 inhibitor, was approved by the Food and Drug Administration in 2014 for moderate to severe plaque psoriasis and psoriatic arthritis. The 16-week results are included in the drug’s label.

The label warns of weight loss and depression with apremilast. The new report doesn’t mention depression but does note a mean weight loss of 2.08 kg with the drug, and that 19% of patients lost more than 5% of their body weight. However, no one left the study because of it.

During the first 16 weeks of the trial, the most common side effects were diarrhea (7.1% placebo versus 19% apremilast); nausea (6.7% placebo versus 16% apremilast); upper respiratory tract infection (7.4% versus 10%); nasopharyngitis (8.2% versus 7.3%); and tension headache (4.3% versus 7.3%).

Side effects tended to present early with apremilast, and the incidence didn’t increase as treatment continued. To minimize side effects, the investigators titrated the drug in 10-mg increments over the first week of treatment. Discontinuations due to side effects were low.

Serious adverse events occurred in 2.8% of placebo and 2.1% of apremilast subjects. In the apremilast group, they included three cases of coronary artery disease and three cases of nephrolithiasis, plus two cases each of urinary tract infections, acute myocardial infarctions, and chronic obstructive pulmonary disease.

The investigators excluded patients with major uncontrolled comorbidities, significant infections, active or incompletely treated tuberculosis, biologic use within 12-24 months, use of active topical agents within 2 weeks, and prolonged sun or ultraviolet exposure. Most of the subjects were white, two-thirds were men, and the average age in the study was 45 years. Weak or low-potency topical corticosteroids, coal tar shampoo and salicylic acid for scalp lesions, and unmedicated moisturizers were allowed in the study.

Celgene Corporation, the maker of apremilast, funded the work. Three investigators are employees, and most of the rest reported financial relationships with the company.

[email protected]

If apremilast (Otezla) works initially for psoriasis, it’s likely to keep on helping for at least a year, according to phase III results published by the drug’s maker, Celgene, in the Journal of the American Academy of Dermatology.

The trial randomized 562 patients with moderate to severe plaque psoriasis to apremilast 30 mg twice daily, and 282 to placebo (J Am Acad Dermatol. 2015 Jul;73[1]:37-49).

At week 16, 33% of apremilast patients, but only 5.3% of placebo patients, achieved a 75% or greater reduction from their baseline Psoriasis Area and Severity Index (PASI-75) scores (P less than .0001).

The placebo group was next switched to apremilast so that all the subjects were on the drug from weeks 16 to 32. By week 32, patients switched from placebo caught up with their apremilast peers on PASI-75 response rates and improved pruritus scores.

The study continued past week 32 with 154 patients who had been on apremilast since baseline and had reached PASI-75; half were rerandomized to placebo, half to the drug. At week 52, 47 (61%) of apremilast patients had maintained their PASI-75 response, versus 9 (12%) of placebo patients.

“PASI response was maintained over 52 weeks with continued apremilast treatment. In addition, apremilast demonstrated improvements in nail and scalp psoriasis, both difficult-to-treat forms of psoriasis. Most patients rerandomized to placebo who lost PASI-75 response regained it after apremilast reinitiation,” said the authors, led by Dr. Kim Papp of Probity Medical Research in Waterloo, Ont.

Apremilast, an oral phosphodiesterase 4 inhibitor, was approved by the Food and Drug Administration in 2014 for moderate to severe plaque psoriasis and psoriatic arthritis. The 16-week results are included in the drug’s label.

The label warns of weight loss and depression with apremilast. The new report doesn’t mention depression but does note a mean weight loss of 2.08 kg with the drug, and that 19% of patients lost more than 5% of their body weight. However, no one left the study because of it.

During the first 16 weeks of the trial, the most common side effects were diarrhea (7.1% placebo versus 19% apremilast); nausea (6.7% placebo versus 16% apremilast); upper respiratory tract infection (7.4% versus 10%); nasopharyngitis (8.2% versus 7.3%); and tension headache (4.3% versus 7.3%).

Side effects tended to present early with apremilast, and the incidence didn’t increase as treatment continued. To minimize side effects, the investigators titrated the drug in 10-mg increments over the first week of treatment. Discontinuations due to side effects were low.

Serious adverse events occurred in 2.8% of placebo and 2.1% of apremilast subjects. In the apremilast group, they included three cases of coronary artery disease and three cases of nephrolithiasis, plus two cases each of urinary tract infections, acute myocardial infarctions, and chronic obstructive pulmonary disease.

The investigators excluded patients with major uncontrolled comorbidities, significant infections, active or incompletely treated tuberculosis, biologic use within 12-24 months, use of active topical agents within 2 weeks, and prolonged sun or ultraviolet exposure. Most of the subjects were white, two-thirds were men, and the average age in the study was 45 years. Weak or low-potency topical corticosteroids, coal tar shampoo and salicylic acid for scalp lesions, and unmedicated moisturizers were allowed in the study.

Celgene Corporation, the maker of apremilast, funded the work. Three investigators are employees, and most of the rest reported financial relationships with the company.

[email protected]

Low cholesterol efflux capacity may be an important biomarker for subclinical coronary atherosclerosis in patients with psoriasis, based on findings from a prospective cohort study.

High-density lipoprotein cholesterol efflux capacity (CEC) was inversely correlated with the noncalcified burden (NCB) of coronary atherosclerosis in baseline data from the first 101 patients enrolled in the 4-year study, Dr. Taufiq Salahuddin of the National Heart, Lung, and Blood Institute and colleagues reported online in the European Heart Journal.

The relationship between CEC and NCB “suggests that higher CEC may promote reverse cholesterol transport from earlier, more lipid-rich plaques. … Others have found this noncalcified plaque to be the culprit lesion in acute coronary syndromes. Therefore, in the context of our study, there is strong biological plausibility for observing a relationship between CEC and NCB; psoriasis is associated with both increased future cardiovascular events and impaired HDL function, and our findings suggest that this may be due to predisposition toward formation of noncalcified plaque,” the researchers wrote.

The relationship between CEC (quantified using a cell-based ex vivo assay), and NCB plaque indexes (assessed by quantitative coronary computed tomography angiography) persisted after adjustment for cardiovascular risk factors, high-density lipoprotein cholesterol levels, and apolipoprotein A₁ levels.

Of note, the relationship between CEC and NCB was stronger in women than in men, with a statistically significant gender interaction, the investigators found (Eur Heart J. 2015 Jul 18. doi.org/10.1093/eurheartj/ehv339).

Cholesterol efflux capacity has been shown in prior studies to predict future cardiovascular events, and since psoriasis both increases cardiovascular risk and impairs CEC, the investigators sought to assess the cross-sectional relationship between coronary plaque burden and CEC.

Study subjects were adults over age 18 years with moderate skin disease severity (median psoriasis area severity index [PASI] score, 6.2), and a low 10-year pooled cohort equation risk score (median, 2.7%). Traditional lipid profiles were within normal limits, and the median CEC was 0.94.

In addition to the inverse correlation between CEC and NCB at baseline, significant relationships were seen between CEC and PASI score, body surface area affected by psoriasis, and HDL cholesterol level, and between noncalcified burden and CEC, psoriasis severity, body surface area affected by psoriasis, and HDL cholesterol.

“Stratified by the sample’s median CEC value, patients with low CEC had greater total burden of coronary plaque and greater NCB than did patients with high CEC (0.0131 and 0.0127 mm² in low CEC vs. 0.0106 and 0.0103 mm² with high CEC),” they wrote.

No differences were seen based on psoriasis treatment status or statin use, although systemic/biologic therapy was associated with a reduction in noncalcified burden.

The findings with respect to gender differences may suggest that greater CEC is more protective against noncalcified plaque in women than it is in men, the investigators added, concluding that “ongoing follow-up of these patients will inform whether aggressive treatment of psoriasis and lifestyle measures improve CEC and ultimately noncalcified burden within the coronary arteries in psoriasis.”

This study was supported by a National Institutes of Health intramural grant, and the NIH Medical Research Scholars Program. The investigators reported having no relevant financial disclosures.

[email protected]

Low cholesterol efflux capacity may be an important biomarker for subclinical coronary atherosclerosis in patients with psoriasis, based on findings from a prospective cohort study.

High-density lipoprotein cholesterol efflux capacity (CEC) was inversely correlated with the noncalcified burden (NCB) of coronary atherosclerosis in baseline data from the first 101 patients enrolled in the 4-year study, Dr. Taufiq Salahuddin of the National Heart, Lung, and Blood Institute and colleagues reported online in the European Heart Journal.

The relationship between CEC and NCB “suggests that higher CEC may promote reverse cholesterol transport from earlier, more lipid-rich plaques. … Others have found this noncalcified plaque to be the culprit lesion in acute coronary syndromes. Therefore, in the context of our study, there is strong biological plausibility for observing a relationship between CEC and NCB; psoriasis is associated with both increased future cardiovascular events and impaired HDL function, and our findings suggest that this may be due to predisposition toward formation of noncalcified plaque,” the researchers wrote.

The relationship between CEC (quantified using a cell-based ex vivo assay), and NCB plaque indexes (assessed by quantitative coronary computed tomography angiography) persisted after adjustment for cardiovascular risk factors, high-density lipoprotein cholesterol levels, and apolipoprotein A₁ levels.

Of note, the relationship between CEC and NCB was stronger in women than in men, with a statistically significant gender interaction, the investigators found (Eur Heart J. 2015 Jul 18. doi.org/10.1093/eurheartj/ehv339).

Cholesterol efflux capacity has been shown in prior studies to predict future cardiovascular events, and since psoriasis both increases cardiovascular risk and impairs CEC, the investigators sought to assess the cross-sectional relationship between coronary plaque burden and CEC.

Study subjects were adults over age 18 years with moderate skin disease severity (median psoriasis area severity index [PASI] score, 6.2), and a low 10-year pooled cohort equation risk score (median, 2.7%). Traditional lipid profiles were within normal limits, and the median CEC was 0.94.

In addition to the inverse correlation between CEC and NCB at baseline, significant relationships were seen between CEC and PASI score, body surface area affected by psoriasis, and HDL cholesterol level, and between noncalcified burden and CEC, psoriasis severity, body surface area affected by psoriasis, and HDL cholesterol.

“Stratified by the sample’s median CEC value, patients with low CEC had greater total burden of coronary plaque and greater NCB than did patients with high CEC (0.0131 and 0.0127 mm² in low CEC vs. 0.0106 and 0.0103 mm² with high CEC),” they wrote.

No differences were seen based on psoriasis treatment status or statin use, although systemic/biologic therapy was associated with a reduction in noncalcified burden.

The findings with respect to gender differences may suggest that greater CEC is more protective against noncalcified plaque in women than it is in men, the investigators added, concluding that “ongoing follow-up of these patients will inform whether aggressive treatment of psoriasis and lifestyle measures improve CEC and ultimately noncalcified burden within the coronary arteries in psoriasis.”

This study was supported by a National Institutes of Health intramural grant, and the NIH Medical Research Scholars Program. The investigators reported having no relevant financial disclosures.

[email protected]

Low cholesterol efflux capacity may be an important biomarker for subclinical coronary atherosclerosis in patients with psoriasis, based on findings from a prospective cohort study.

High-density lipoprotein cholesterol efflux capacity (CEC) was inversely correlated with the noncalcified burden (NCB) of coronary atherosclerosis in baseline data from the first 101 patients enrolled in the 4-year study, Dr. Taufiq Salahuddin of the National Heart, Lung, and Blood Institute and colleagues reported online in the European Heart Journal.

The relationship between CEC and NCB “suggests that higher CEC may promote reverse cholesterol transport from earlier, more lipid-rich plaques. … Others have found this noncalcified plaque to be the culprit lesion in acute coronary syndromes. Therefore, in the context of our study, there is strong biological plausibility for observing a relationship between CEC and NCB; psoriasis is associated with both increased future cardiovascular events and impaired HDL function, and our findings suggest that this may be due to predisposition toward formation of noncalcified plaque,” the researchers wrote.

The relationship between CEC (quantified using a cell-based ex vivo assay), and NCB plaque indexes (assessed by quantitative coronary computed tomography angiography) persisted after adjustment for cardiovascular risk factors, high-density lipoprotein cholesterol levels, and apolipoprotein A₁ levels.

Of note, the relationship between CEC and NCB was stronger in women than in men, with a statistically significant gender interaction, the investigators found (Eur Heart J. 2015 Jul 18. doi.org/10.1093/eurheartj/ehv339).

Cholesterol efflux capacity has been shown in prior studies to predict future cardiovascular events, and since psoriasis both increases cardiovascular risk and impairs CEC, the investigators sought to assess the cross-sectional relationship between coronary plaque burden and CEC.

Study subjects were adults over age 18 years with moderate skin disease severity (median psoriasis area severity index [PASI] score, 6.2), and a low 10-year pooled cohort equation risk score (median, 2.7%). Traditional lipid profiles were within normal limits, and the median CEC was 0.94.

In addition to the inverse correlation between CEC and NCB at baseline, significant relationships were seen between CEC and PASI score, body surface area affected by psoriasis, and HDL cholesterol level, and between noncalcified burden and CEC, psoriasis severity, body surface area affected by psoriasis, and HDL cholesterol.

“Stratified by the sample’s median CEC value, patients with low CEC had greater total burden of coronary plaque and greater NCB than did patients with high CEC (0.0131 and 0.0127 mm² in low CEC vs. 0.0106 and 0.0103 mm² with high CEC),” they wrote.

No differences were seen based on psoriasis treatment status or statin use, although systemic/biologic therapy was associated with a reduction in noncalcified burden.

The findings with respect to gender differences may suggest that greater CEC is more protective against noncalcified plaque in women than it is in men, the investigators added, concluding that “ongoing follow-up of these patients will inform whether aggressive treatment of psoriasis and lifestyle measures improve CEC and ultimately noncalcified burden within the coronary arteries in psoriasis.”

This study was supported by a National Institutes of Health intramural grant, and the NIH Medical Research Scholars Program. The investigators reported having no relevant financial disclosures.

[email protected]

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) meeting was held in Stockholm this year on July 7 and 8. This year’s meeting was packed with updates regarding numerous projects, including, but not limited to, educational initiatives, research work streams, inclusion of patients in the research process in psoriasis and psoriatic arthritis (PsA), and updating of the core set of outcome measures to be included in both psoriasis and PsA clinical trials through Outcome Measures in Rheumatology (OMERACT) and International Dermatology Outcome Measures (IDEOM) initiatives.

Among the most exciting initiatives was the review of the 2015 GRAPPA PsA Treatment Recommendations. The new treatment recommendations began 2 years ago and have included extensive literature reviews, small group discussions, and large group surveys. The final manuscript includes overarching principles and specific recommendations broken down by disease manifestations (for example, peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail disease). Changes from the 2009 GRAPPA Treatment Recommendations (Ann. Rheum. Dis. 2009;68:1387-94) include addition of new therapies (for example, phosphodiesterase-4 inhibitors, interleukin (IL) 12/23 inhibitors, IL-17 inhibitors) and recommendations for screening for comorbidities, as well as a table noting the influence of comorbidities on therapy selection. Each recommendation is supported as “weak” or “strong” depending on the level of evidence. Patient research partners were involved in all steps of the process. The final manuscript has been submitted for publication.

In addition to treating the disease, better defining the disease is also of critical importance. In particular, defining a “flare” of rheumatoid arthritis or PsA has been quite difficult, and there has been great interest in building an assessment tool to measure the occurrence of flare. During the meeting, Dr. Anna Moverley and Dr. Philip Helliwell, both from the NIHR Musculoskeletal Biomedical Research Unit, Leeds (England) Institute of Rheumatic & Musculoskeletal Medicine, presented their work to date on defining PsA flares. They began their work by conducting a qualitative analysis of 18 patient interviews to identify themes related to having a PsA flare. Domains (or themes) identified included physical, psychological, social withdrawal, fatigue, and loss of function. In addition, patients described flare triggers, timing of flares, preflare management, and flare management. The results of this study were recently published in a paper titled, “It’s not just the joints, it’s the whole thing: qualitative analysis of patients’ experience of flare in psoriatic arthritis” (Rheumatology 2015;54:1448-54). The team then used these themes to create a Delphi survey, which was sent to both patients and physicians. Working groups at GRAPPA were used to determine the next steps, in particular whether a physician or patient tool (or both) should be developed.

Care of the patient with PsA from a multispecialty perspective was discussed in the “combined clinics” presentation. Several academic centers across North America have developed combined dermatology-rheumatology clinics. The functioning of these clinics varies widely from monthly dual clinics in which the dermatologist and rheumatologist see the patient together for virtual combined clinics in which time is set aside for discussion of shared patients. The advantages of these dual clinics include rich educational opportunities for medical students, residents, and fellows; the ideal clinical care model for patients; enhanced patient satisfaction with their care; improved patient care and quicker transition to a disease-modifying agent when indicated; and physician satisfaction and learning opportunities through collaborative work. Institutions using these collaborative models have combined to form the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN). The group has had two meetings and has developed research initiatives that are moving forward. Another goal of the group is to assist others centers interested in creating similar collaborative clinics.

The GRAPPA PsA BioDam (Psoriatic Arthritis Biomarkers for Joint Damage) initiative was also discussed at the meeting. The goal of this initiative is to examine soluble biomarkers as predictors of structural damage in PsA. Blood samples are taken at enrollment and then patients are followed prospectively. At 24 months of follow-up, repeat radiographs are obtained to monitor the development of new erosions. In addition to plain film radiographs, three sites are now also including MRI to assess for erosions. The study team, led by Dr. Oliver FitzGerald, hopes to begin analyzing some of the results from the study in the next 1-2 years.

Dr. Ogdie-Beatty is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the GRAPPA Steering Committee.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) meeting was held in Stockholm this year on July 7 and 8. This year’s meeting was packed with updates regarding numerous projects, including, but not limited to, educational initiatives, research work streams, inclusion of patients in the research process in psoriasis and psoriatic arthritis (PsA), and updating of the core set of outcome measures to be included in both psoriasis and PsA clinical trials through Outcome Measures in Rheumatology (OMERACT) and International Dermatology Outcome Measures (IDEOM) initiatives.

Among the most exciting initiatives was the review of the 2015 GRAPPA PsA Treatment Recommendations. The new treatment recommendations began 2 years ago and have included extensive literature reviews, small group discussions, and large group surveys. The final manuscript includes overarching principles and specific recommendations broken down by disease manifestations (for example, peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail disease). Changes from the 2009 GRAPPA Treatment Recommendations (Ann. Rheum. Dis. 2009;68:1387-94) include addition of new therapies (for example, phosphodiesterase-4 inhibitors, interleukin (IL) 12/23 inhibitors, IL-17 inhibitors) and recommendations for screening for comorbidities, as well as a table noting the influence of comorbidities on therapy selection. Each recommendation is supported as “weak” or “strong” depending on the level of evidence. Patient research partners were involved in all steps of the process. The final manuscript has been submitted for publication.

In addition to treating the disease, better defining the disease is also of critical importance. In particular, defining a “flare” of rheumatoid arthritis or PsA has been quite difficult, and there has been great interest in building an assessment tool to measure the occurrence of flare. During the meeting, Dr. Anna Moverley and Dr. Philip Helliwell, both from the NIHR Musculoskeletal Biomedical Research Unit, Leeds (England) Institute of Rheumatic & Musculoskeletal Medicine, presented their work to date on defining PsA flares. They began their work by conducting a qualitative analysis of 18 patient interviews to identify themes related to having a PsA flare. Domains (or themes) identified included physical, psychological, social withdrawal, fatigue, and loss of function. In addition, patients described flare triggers, timing of flares, preflare management, and flare management. The results of this study were recently published in a paper titled, “It’s not just the joints, it’s the whole thing: qualitative analysis of patients’ experience of flare in psoriatic arthritis” (Rheumatology 2015;54:1448-54). The team then used these themes to create a Delphi survey, which was sent to both patients and physicians. Working groups at GRAPPA were used to determine the next steps, in particular whether a physician or patient tool (or both) should be developed.

Care of the patient with PsA from a multispecialty perspective was discussed in the “combined clinics” presentation. Several academic centers across North America have developed combined dermatology-rheumatology clinics. The functioning of these clinics varies widely from monthly dual clinics in which the dermatologist and rheumatologist see the patient together for virtual combined clinics in which time is set aside for discussion of shared patients. The advantages of these dual clinics include rich educational opportunities for medical students, residents, and fellows; the ideal clinical care model for patients; enhanced patient satisfaction with their care; improved patient care and quicker transition to a disease-modifying agent when indicated; and physician satisfaction and learning opportunities through collaborative work. Institutions using these collaborative models have combined to form the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN). The group has had two meetings and has developed research initiatives that are moving forward. Another goal of the group is to assist others centers interested in creating similar collaborative clinics.

The GRAPPA PsA BioDam (Psoriatic Arthritis Biomarkers for Joint Damage) initiative was also discussed at the meeting. The goal of this initiative is to examine soluble biomarkers as predictors of structural damage in PsA. Blood samples are taken at enrollment and then patients are followed prospectively. At 24 months of follow-up, repeat radiographs are obtained to monitor the development of new erosions. In addition to plain film radiographs, three sites are now also including MRI to assess for erosions. The study team, led by Dr. Oliver FitzGerald, hopes to begin analyzing some of the results from the study in the next 1-2 years.

Dr. Ogdie-Beatty is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the GRAPPA Steering Committee.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) meeting was held in Stockholm this year on July 7 and 8. This year’s meeting was packed with updates regarding numerous projects, including, but not limited to, educational initiatives, research work streams, inclusion of patients in the research process in psoriasis and psoriatic arthritis (PsA), and updating of the core set of outcome measures to be included in both psoriasis and PsA clinical trials through Outcome Measures in Rheumatology (OMERACT) and International Dermatology Outcome Measures (IDEOM) initiatives.

Among the most exciting initiatives was the review of the 2015 GRAPPA PsA Treatment Recommendations. The new treatment recommendations began 2 years ago and have included extensive literature reviews, small group discussions, and large group surveys. The final manuscript includes overarching principles and specific recommendations broken down by disease manifestations (for example, peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail disease). Changes from the 2009 GRAPPA Treatment Recommendations (Ann. Rheum. Dis. 2009;68:1387-94) include addition of new therapies (for example, phosphodiesterase-4 inhibitors, interleukin (IL) 12/23 inhibitors, IL-17 inhibitors) and recommendations for screening for comorbidities, as well as a table noting the influence of comorbidities on therapy selection. Each recommendation is supported as “weak” or “strong” depending on the level of evidence. Patient research partners were involved in all steps of the process. The final manuscript has been submitted for publication.

In addition to treating the disease, better defining the disease is also of critical importance. In particular, defining a “flare” of rheumatoid arthritis or PsA has been quite difficult, and there has been great interest in building an assessment tool to measure the occurrence of flare. During the meeting, Dr. Anna Moverley and Dr. Philip Helliwell, both from the NIHR Musculoskeletal Biomedical Research Unit, Leeds (England) Institute of Rheumatic & Musculoskeletal Medicine, presented their work to date on defining PsA flares. They began their work by conducting a qualitative analysis of 18 patient interviews to identify themes related to having a PsA flare. Domains (or themes) identified included physical, psychological, social withdrawal, fatigue, and loss of function. In addition, patients described flare triggers, timing of flares, preflare management, and flare management. The results of this study were recently published in a paper titled, “It’s not just the joints, it’s the whole thing: qualitative analysis of patients’ experience of flare in psoriatic arthritis” (Rheumatology 2015;54:1448-54). The team then used these themes to create a Delphi survey, which was sent to both patients and physicians. Working groups at GRAPPA were used to determine the next steps, in particular whether a physician or patient tool (or both) should be developed.

Care of the patient with PsA from a multispecialty perspective was discussed in the “combined clinics” presentation. Several academic centers across North America have developed combined dermatology-rheumatology clinics. The functioning of these clinics varies widely from monthly dual clinics in which the dermatologist and rheumatologist see the patient together for virtual combined clinics in which time is set aside for discussion of shared patients. The advantages of these dual clinics include rich educational opportunities for medical students, residents, and fellows; the ideal clinical care model for patients; enhanced patient satisfaction with their care; improved patient care and quicker transition to a disease-modifying agent when indicated; and physician satisfaction and learning opportunities through collaborative work. Institutions using these collaborative models have combined to form the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN). The group has had two meetings and has developed research initiatives that are moving forward. Another goal of the group is to assist others centers interested in creating similar collaborative clinics.

The GRAPPA PsA BioDam (Psoriatic Arthritis Biomarkers for Joint Damage) initiative was also discussed at the meeting. The goal of this initiative is to examine soluble biomarkers as predictors of structural damage in PsA. Blood samples are taken at enrollment and then patients are followed prospectively. At 24 months of follow-up, repeat radiographs are obtained to monitor the development of new erosions. In addition to plain film radiographs, three sites are now also including MRI to assess for erosions. The study team, led by Dr. Oliver FitzGerald, hopes to begin analyzing some of the results from the study in the next 1-2 years.

Dr. Ogdie-Beatty is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the GRAPPA Steering Committee.

VANCOUVER – Dermatologists and primary care physicians working collaboratively have a golden opportunity to improve the long-term health of pediatric psoriasis patients by addressing their predisposition to components of the metabolic syndrome, Dr. Amy S. Paller declared at the World Congress of Dermatology.

“I think we as dermatologists should be in touch with the primary care doctors of every one of our children with psoriasis. Together, we should be thinking about whether the child has metabolic issues and working jointly to most effectively counsel and evaluate these children for their potential risk for these metabolic disorders,” said Dr. Paller, professor and chair of the department of dermatology and professor of pediatrics at Northwestern University, Chicago.

Pediatric psoriasis is commonly associated with other comorbid conditions in addition to metabolic disorders. But the metabolic syndrome has recently become the focus of increasing attention given that cardiovascular disease is the No. 1 cause of death in the United States, and it appears that children with psoriasis may be getting a jump start on the atherosclerotic process.

Bruce Jancin/Frontline Medical News

By now, it’s well established that plaque psoriasis in adults is strongly associated with increased risks of diabetes, obesity, dyslipidemia, the metabolic syndrome, and cardiovascular disease. Mounting evidence indicates children and adolescents with psoriasis face the same risks.

Everyone knows how difficult it can be to make the long-term lifestyle changes that reverse obesity and its related metabolic disorders. But dermatologists, pediatricians, and family physicians have some leverage when it comes to pediatric psoriasis.

“Think about the fact that 30% of children with psoriasis have a first-degree relative with psoriasis, usually a parent. I think we need to think about counseling young adults with psoriasis early on, especially if that adult is overweight or obese, about the need for adopting a healthy lifestyle. If they do that, it’s not just for themselves but for their children, and we just might prevent pediatric psoriasis in that family or temper its severity through that healthy lifestyle intervention,” Dr. Paller continued.

The hope is that effectively addressing the metabolic comorbidities of pediatric psoriasis will modulate and improve the skin disease; in other words, that weight loss could improve psoriasis. As yet, however, that’s just a hope, as there is no persuasive supporting evidence.

“We’re looking towards ongoing adult trials to give us some clues about whether that’s the case,” she said.

Evidence for comorbidities

Some of the key evidence regarding the metabolic comorbidities of pediatric psoriasis comes from a landmark German epidemiologic study involving 33,981 pediatric psoriasis patients. The prevalence of psoriasis in German youth rose linearly from 0.12% at age 1 year to 1.2% at age 18. Pediatric psoriasis patients had significantly higher rates of diabetes, hyperlipidemia, obesity, and hypertension than did nonpsoriatic controls (Br. J. Dermatol. 2010;162:633-6).

A Kaiser Permanente study of nearly 711,000 youths aged 2-19 years showed that those who were overweight were 2.8-fold more likely than normal-weight youth to have severe or widespread psoriasis, while those who were moderately obese were at 2.9-fold increased risk and extremely obese youth were at 4.2-fold increased risk. Among adolescents, having psoriasis was associated with significantly higher mean total and LDL cholesterol, triglycerides, and alanine aminotransferase levels (J. Pediatr. 2011;159:577-83).

Recent evidence suggests that even before increased levels of LDL cholesterol and triglycerides are apparent in children with psoriasis, abnormalities in lipid function are present and may potentially serve as a novel marker for early cardiovascular risk. Dr. Paller cited a study presented by Dr. Wynnis L. Tom of Rady Children’s Hospital, San Diego, at the 2015 annual meeting of the Society for Investigative Dermatology. The case-control study included 50 children with psoriasis and 50 matched controls with a mean age of 13 years.

Like other investigators, Dr. Tom found that the psoriatic children had higher waist/hip ratios and more insulin resistance. While fasting lipid levels didn’t differ between the two groups, the psoriasis patients had significantly higher levels of atherogenic apolipoprotein B, fewer of the particularly cardioprotective large-size HDL particles, and reduced HDL efflux capacity. Stay tuned regarding these potential early markers, Dr. Paller advised.

She was lead author of a 409-patient international study that showed the risks of obesity and a high waist circumference rise with greater severity of pediatric psoriasis. Children with severe psoriasis were at 4.92-fold increased risk of obesity, compared with controls, while even those with mild psoriasis were at 3.6-fold increased risk (JAMA Dermatol. 2013;149:166-76).

Which comes first?

The question arises: Which comes first in children, the excess adiposity or the psoriasis? Dr. Paller said that although the final word isn’t in, she and her coworkers found in a pilot study of 27 overweight or obese children with psoriasis that excess adiposity typically came first. Moreover, among the roughly one-half of children with a family history of obesity, onset of psoriasis occurred a full 3 years earlier than in those without a positive family history (JAMA Dermatol. 2014;150:573-4).

In another small study, this by investigators at Tufts University, Boston, 6 of 20 children with psoriasis (30%) met criteria for the metabolic syndrome, compared with just 1 of 20 matched nonpsoriatic controls (Pediatr. Dermatol. 2013;30:700-5).

Dr. Paller said that if dermatologists and primary care physicians are to successfully collaborate in tackling the comorbid metabolic disorders associated with pediatric psoriasis, a prerequisite is that dermatologists are going to have to do a better job of educating their primary care colleagues about the skin disease as manifest in children.

“I think it’s very important that pediatricians are aware that psoriasis is a risk factor for metabolic syndrome. But pediatric psoriasis is often misdiagnosed by primary care physicians who mistake it for eczema or tinea infection or contact dermatitis,” according to the pediatric dermatologist.

In one eye-catching Australian study, she noted, a mere 9% of patients with pediatric psoriasis were correctly diagnosed before referral to a dermatologist (Australas. J. Dermatol. 2012;53:98-105).

Pediatric psoriasis: not just skin deep

In addition to the increased risk of metabolic disorders faced by pediatric psoriasis patients, other common comorbidities include depression, anxiety disorders, impaired self-esteem and quality of life, arthritis, and Crohn’s disease, Dr. Paller observed.

• Quality of life. “The quality of life impact of psoriasis is profound. It’s a highly visible disorder, which affects the development of self-esteem and social relationships,” Dr. Paller said.

Investigators at Texas A&M University applied the Pediatric Quality of Life Inventory Version 4.0 to 208 patients aged 2-17 years with moderate to severe psoriasis and compared the results to published data on children with arthritis, asthma, diabetes, and psychiatric disorders. Health-related quality of life turned out to be more impaired in the psoriasis patients than in those with diabetes. The quality-of-life impairment associated with pediatric psoriasis was comparable to that of having asthma or arthritis, albeit not as severe as for pediatric psychiatric disorders (Eur. J. Pediatr. 2012;171:485-92).

• Psychiatric disorders. A study of more than 7,400 pediatric psoriasis patients concluded they had an adjusted 25% increased risk of developing depression, compared with psoriasis-free controls, as well as a 32% increased risk of anxiety disorders and a 55% greater risk of bipolar disorder (J. Am. Acad. Dermatol. 2012;67:651-7.e2).

• Psoriatic arthritis. An estimated 1 in 10 U.S. children with psoriasis report having arthritis, often classified as juvenile idiopathic arthritis (JAMA Dermatol. 2013;149:1180-5).

• Crohn’s disease. A large German epidemiologic study concluded that psoriasis was associated with a 3.69-fold increased risk of Crohn’s disease. There was no increased risk of ulcerative colitis (Br. J. Dermatol. 2010;162:633-6).

Dr. Paller reported receiving research grants from Amgen and Leo and serving as a consultant to AbbVie.

[email protected]

VANCOUVER – Dermatologists and primary care physicians working collaboratively have a golden opportunity to improve the long-term health of pediatric psoriasis patients by addressing their predisposition to components of the metabolic syndrome, Dr. Amy S. Paller declared at the World Congress of Dermatology.

“I think we as dermatologists should be in touch with the primary care doctors of every one of our children with psoriasis. Together, we should be thinking about whether the child has metabolic issues and working jointly to most effectively counsel and evaluate these children for their potential risk for these metabolic disorders,” said Dr. Paller, professor and chair of the department of dermatology and professor of pediatrics at Northwestern University, Chicago.

Pediatric psoriasis is commonly associated with other comorbid conditions in addition to metabolic disorders. But the metabolic syndrome has recently become the focus of increasing attention given that cardiovascular disease is the No. 1 cause of death in the United States, and it appears that children with psoriasis may be getting a jump start on the atherosclerotic process.

Bruce Jancin/Frontline Medical News

By now, it’s well established that plaque psoriasis in adults is strongly associated with increased risks of diabetes, obesity, dyslipidemia, the metabolic syndrome, and cardiovascular disease. Mounting evidence indicates children and adolescents with psoriasis face the same risks.

Everyone knows how difficult it can be to make the long-term lifestyle changes that reverse obesity and its related metabolic disorders. But dermatologists, pediatricians, and family physicians have some leverage when it comes to pediatric psoriasis.

“Think about the fact that 30% of children with psoriasis have a first-degree relative with psoriasis, usually a parent. I think we need to think about counseling young adults with psoriasis early on, especially if that adult is overweight or obese, about the need for adopting a healthy lifestyle. If they do that, it’s not just for themselves but for their children, and we just might prevent pediatric psoriasis in that family or temper its severity through that healthy lifestyle intervention,” Dr. Paller continued.

The hope is that effectively addressing the metabolic comorbidities of pediatric psoriasis will modulate and improve the skin disease; in other words, that weight loss could improve psoriasis. As yet, however, that’s just a hope, as there is no persuasive supporting evidence.

“We’re looking towards ongoing adult trials to give us some clues about whether that’s the case,” she said.

Evidence for comorbidities

Some of the key evidence regarding the metabolic comorbidities of pediatric psoriasis comes from a landmark German epidemiologic study involving 33,981 pediatric psoriasis patients. The prevalence of psoriasis in German youth rose linearly from 0.12% at age 1 year to 1.2% at age 18. Pediatric psoriasis patients had significantly higher rates of diabetes, hyperlipidemia, obesity, and hypertension than did nonpsoriatic controls (Br. J. Dermatol. 2010;162:633-6).

A Kaiser Permanente study of nearly 711,000 youths aged 2-19 years showed that those who were overweight were 2.8-fold more likely than normal-weight youth to have severe or widespread psoriasis, while those who were moderately obese were at 2.9-fold increased risk and extremely obese youth were at 4.2-fold increased risk. Among adolescents, having psoriasis was associated with significantly higher mean total and LDL cholesterol, triglycerides, and alanine aminotransferase levels (J. Pediatr. 2011;159:577-83).

Recent evidence suggests that even before increased levels of LDL cholesterol and triglycerides are apparent in children with psoriasis, abnormalities in lipid function are present and may potentially serve as a novel marker for early cardiovascular risk. Dr. Paller cited a study presented by Dr. Wynnis L. Tom of Rady Children’s Hospital, San Diego, at the 2015 annual meeting of the Society for Investigative Dermatology. The case-control study included 50 children with psoriasis and 50 matched controls with a mean age of 13 years.

Like other investigators, Dr. Tom found that the psoriatic children had higher waist/hip ratios and more insulin resistance. While fasting lipid levels didn’t differ between the two groups, the psoriasis patients had significantly higher levels of atherogenic apolipoprotein B, fewer of the particularly cardioprotective large-size HDL particles, and reduced HDL efflux capacity. Stay tuned regarding these potential early markers, Dr. Paller advised.

She was lead author of a 409-patient international study that showed the risks of obesity and a high waist circumference rise with greater severity of pediatric psoriasis. Children with severe psoriasis were at 4.92-fold increased risk of obesity, compared with controls, while even those with mild psoriasis were at 3.6-fold increased risk (JAMA Dermatol. 2013;149:166-76).

Which comes first?

The question arises: Which comes first in children, the excess adiposity or the psoriasis? Dr. Paller said that although the final word isn’t in, she and her coworkers found in a pilot study of 27 overweight or obese children with psoriasis that excess adiposity typically came first. Moreover, among the roughly one-half of children with a family history of obesity, onset of psoriasis occurred a full 3 years earlier than in those without a positive family history (JAMA Dermatol. 2014;150:573-4).

In another small study, this by investigators at Tufts University, Boston, 6 of 20 children with psoriasis (30%) met criteria for the metabolic syndrome, compared with just 1 of 20 matched nonpsoriatic controls (Pediatr. Dermatol. 2013;30:700-5).

Dr. Paller said that if dermatologists and primary care physicians are to successfully collaborate in tackling the comorbid metabolic disorders associated with pediatric psoriasis, a prerequisite is that dermatologists are going to have to do a better job of educating their primary care colleagues about the skin disease as manifest in children.

“I think it’s very important that pediatricians are aware that psoriasis is a risk factor for metabolic syndrome. But pediatric psoriasis is often misdiagnosed by primary care physicians who mistake it for eczema or tinea infection or contact dermatitis,” according to the pediatric dermatologist.

In one eye-catching Australian study, she noted, a mere 9% of patients with pediatric psoriasis were correctly diagnosed before referral to a dermatologist (Australas. J. Dermatol. 2012;53:98-105).

Pediatric psoriasis: not just skin deep

In addition to the increased risk of metabolic disorders faced by pediatric psoriasis patients, other common comorbidities include depression, anxiety disorders, impaired self-esteem and quality of life, arthritis, and Crohn’s disease, Dr. Paller observed.

• Quality of life. “The quality of life impact of psoriasis is profound. It’s a highly visible disorder, which affects the development of self-esteem and social relationships,” Dr. Paller said.

Investigators at Texas A&M University applied the Pediatric Quality of Life Inventory Version 4.0 to 208 patients aged 2-17 years with moderate to severe psoriasis and compared the results to published data on children with arthritis, asthma, diabetes, and psychiatric disorders. Health-related quality of life turned out to be more impaired in the psoriasis patients than in those with diabetes. The quality-of-life impairment associated with pediatric psoriasis was comparable to that of having asthma or arthritis, albeit not as severe as for pediatric psychiatric disorders (Eur. J. Pediatr. 2012;171:485-92).

• Psychiatric disorders. A study of more than 7,400 pediatric psoriasis patients concluded they had an adjusted 25% increased risk of developing depression, compared with psoriasis-free controls, as well as a 32% increased risk of anxiety disorders and a 55% greater risk of bipolar disorder (J. Am. Acad. Dermatol. 2012;67:651-7.e2).

• Psoriatic arthritis. An estimated 1 in 10 U.S. children with psoriasis report having arthritis, often classified as juvenile idiopathic arthritis (JAMA Dermatol. 2013;149:1180-5).

• Crohn’s disease. A large German epidemiologic study concluded that psoriasis was associated with a 3.69-fold increased risk of Crohn’s disease. There was no increased risk of ulcerative colitis (Br. J. Dermatol. 2010;162:633-6).

Dr. Paller reported receiving research grants from Amgen and Leo and serving as a consultant to AbbVie.

[email protected]

VANCOUVER – Dermatologists and primary care physicians working collaboratively have a golden opportunity to improve the long-term health of pediatric psoriasis patients by addressing their predisposition to components of the metabolic syndrome, Dr. Amy S. Paller declared at the World Congress of Dermatology.

“I think we as dermatologists should be in touch with the primary care doctors of every one of our children with psoriasis. Together, we should be thinking about whether the child has metabolic issues and working jointly to most effectively counsel and evaluate these children for their potential risk for these metabolic disorders,” said Dr. Paller, professor and chair of the department of dermatology and professor of pediatrics at Northwestern University, Chicago.

Pediatric psoriasis is commonly associated with other comorbid conditions in addition to metabolic disorders. But the metabolic syndrome has recently become the focus of increasing attention given that cardiovascular disease is the No. 1 cause of death in the United States, and it appears that children with psoriasis may be getting a jump start on the atherosclerotic process.

Bruce Jancin/Frontline Medical News

By now, it’s well established that plaque psoriasis in adults is strongly associated with increased risks of diabetes, obesity, dyslipidemia, the metabolic syndrome, and cardiovascular disease. Mounting evidence indicates children and adolescents with psoriasis face the same risks.

Everyone knows how difficult it can be to make the long-term lifestyle changes that reverse obesity and its related metabolic disorders. But dermatologists, pediatricians, and family physicians have some leverage when it comes to pediatric psoriasis.

“Think about the fact that 30% of children with psoriasis have a first-degree relative with psoriasis, usually a parent. I think we need to think about counseling young adults with psoriasis early on, especially if that adult is overweight or obese, about the need for adopting a healthy lifestyle. If they do that, it’s not just for themselves but for their children, and we just might prevent pediatric psoriasis in that family or temper its severity through that healthy lifestyle intervention,” Dr. Paller continued.

The hope is that effectively addressing the metabolic comorbidities of pediatric psoriasis will modulate and improve the skin disease; in other words, that weight loss could improve psoriasis. As yet, however, that’s just a hope, as there is no persuasive supporting evidence.

“We’re looking towards ongoing adult trials to give us some clues about whether that’s the case,” she said.

Evidence for comorbidities

Some of the key evidence regarding the metabolic comorbidities of pediatric psoriasis comes from a landmark German epidemiologic study involving 33,981 pediatric psoriasis patients. The prevalence of psoriasis in German youth rose linearly from 0.12% at age 1 year to 1.2% at age 18. Pediatric psoriasis patients had significantly higher rates of diabetes, hyperlipidemia, obesity, and hypertension than did nonpsoriatic controls (Br. J. Dermatol. 2010;162:633-6).

A Kaiser Permanente study of nearly 711,000 youths aged 2-19 years showed that those who were overweight were 2.8-fold more likely than normal-weight youth to have severe or widespread psoriasis, while those who were moderately obese were at 2.9-fold increased risk and extremely obese youth were at 4.2-fold increased risk. Among adolescents, having psoriasis was associated with significantly higher mean total and LDL cholesterol, triglycerides, and alanine aminotransferase levels (J. Pediatr. 2011;159:577-83).

Recent evidence suggests that even before increased levels of LDL cholesterol and triglycerides are apparent in children with psoriasis, abnormalities in lipid function are present and may potentially serve as a novel marker for early cardiovascular risk. Dr. Paller cited a study presented by Dr. Wynnis L. Tom of Rady Children’s Hospital, San Diego, at the 2015 annual meeting of the Society for Investigative Dermatology. The case-control study included 50 children with psoriasis and 50 matched controls with a mean age of 13 years.

Like other investigators, Dr. Tom found that the psoriatic children had higher waist/hip ratios and more insulin resistance. While fasting lipid levels didn’t differ between the two groups, the psoriasis patients had significantly higher levels of atherogenic apolipoprotein B, fewer of the particularly cardioprotective large-size HDL particles, and reduced HDL efflux capacity. Stay tuned regarding these potential early markers, Dr. Paller advised.

She was lead author of a 409-patient international study that showed the risks of obesity and a high waist circumference rise with greater severity of pediatric psoriasis. Children with severe psoriasis were at 4.92-fold increased risk of obesity, compared with controls, while even those with mild psoriasis were at 3.6-fold increased risk (JAMA Dermatol. 2013;149:166-76).

Which comes first?

The question arises: Which comes first in children, the excess adiposity or the psoriasis? Dr. Paller said that although the final word isn’t in, she and her coworkers found in a pilot study of 27 overweight or obese children with psoriasis that excess adiposity typically came first. Moreover, among the roughly one-half of children with a family history of obesity, onset of psoriasis occurred a full 3 years earlier than in those without a positive family history (JAMA Dermatol. 2014;150:573-4).

In another small study, this by investigators at Tufts University, Boston, 6 of 20 children with psoriasis (30%) met criteria for the metabolic syndrome, compared with just 1 of 20 matched nonpsoriatic controls (Pediatr. Dermatol. 2013;30:700-5).

Dr. Paller said that if dermatologists and primary care physicians are to successfully collaborate in tackling the comorbid metabolic disorders associated with pediatric psoriasis, a prerequisite is that dermatologists are going to have to do a better job of educating their primary care colleagues about the skin disease as manifest in children.

“I think it’s very important that pediatricians are aware that psoriasis is a risk factor for metabolic syndrome. But pediatric psoriasis is often misdiagnosed by primary care physicians who mistake it for eczema or tinea infection or contact dermatitis,” according to the pediatric dermatologist.

In one eye-catching Australian study, she noted, a mere 9% of patients with pediatric psoriasis were correctly diagnosed before referral to a dermatologist (Australas. J. Dermatol. 2012;53:98-105).

Pediatric psoriasis: not just skin deep

In addition to the increased risk of metabolic disorders faced by pediatric psoriasis patients, other common comorbidities include depression, anxiety disorders, impaired self-esteem and quality of life, arthritis, and Crohn’s disease, Dr. Paller observed.

• Quality of life. “The quality of life impact of psoriasis is profound. It’s a highly visible disorder, which affects the development of self-esteem and social relationships,” Dr. Paller said.

Investigators at Texas A&M University applied the Pediatric Quality of Life Inventory Version 4.0 to 208 patients aged 2-17 years with moderate to severe psoriasis and compared the results to published data on children with arthritis, asthma, diabetes, and psychiatric disorders. Health-related quality of life turned out to be more impaired in the psoriasis patients than in those with diabetes. The quality-of-life impairment associated with pediatric psoriasis was comparable to that of having asthma or arthritis, albeit not as severe as for pediatric psychiatric disorders (Eur. J. Pediatr. 2012;171:485-92).

• Psychiatric disorders. A study of more than 7,400 pediatric psoriasis patients concluded they had an adjusted 25% increased risk of developing depression, compared with psoriasis-free controls, as well as a 32% increased risk of anxiety disorders and a 55% greater risk of bipolar disorder (J. Am. Acad. Dermatol. 2012;67:651-7.e2).

• Psoriatic arthritis. An estimated 1 in 10 U.S. children with psoriasis report having arthritis, often classified as juvenile idiopathic arthritis (JAMA Dermatol. 2013;149:1180-5).

• Crohn’s disease. A large German epidemiologic study concluded that psoriasis was associated with a 3.69-fold increased risk of Crohn’s disease. There was no increased risk of ulcerative colitis (Br. J. Dermatol. 2010;162:633-6).

Dr. Paller reported receiving research grants from Amgen and Leo and serving as a consultant to AbbVie.

[email protected]

Treatment of psoriatic arthritis over 24 weeks with the human anti-interleukin-17A monoclonal antibody secukinumab allowed a significantly higher percentage of patients who received 150-mg and 300-mg doses to achieve at least 20% improvement in the American College of Rheumatology response criteria than did placebo.

The results of the multicenter, double-blind, randomized, placebo-controlled FUTURE 2 trial hinted at the effectiveness of the 300-mg dosing regimen in treating patients who previously had not responded to treatment with tumor necrosis factor (TNF) inhibitors and did not show differences in effectiveness when used together with methotrexate. The drug did not have any particularly worrisome treatment-related adverse events, Dr. Iain McInnes of the University of Glasgow (Scotland) and his colleagues reported (Lancet 2015 June 28 [doi:10.1016/S0140-6736(15)61134-5]).

At week 24, ACR20 responses occurred in 54 of 100 patients who received secukinumab 300 mg, 51 of 100 who took the 150-mg dosing regimen, 29 of 99 on the 75-mg dosing regimen, and 15 of 98 on placebo. The odds for achieving ACR20 at 24 weeks were nearly sevenfold higher for the 300-mg dose (odds ratio, 6.81; 95% confidence interval, 3.42-13.56; P < .0001) and 150-mg doses (OR, 6.52; 95% CI, 3.25-13.08; P < .0001) than with placebo.

In an editorial accompanying the report, Dr. Philip Helliwell and Dr. Laura Coates of the University of Leeds (England) said that it is important to note that responses at week 24 were similar to those observed at weeks 12 and 16 so that patients and physicians can “get an idea of response (or non-response) at an early timepoint” (Lancet 2015 June 28 [doi:10.1016/S0140-6736(15)61170-9]).

Although radiographic progression wasn’t assessed in the FUTURE 2 trial, Dr. Helliwell and Dr. Coates noted that secukinumab inhibited radiographic damage in the unpublished FUTURE-1 trial, so “in view of its position in the cytokine hierarchy, interleukin-17 inhibition might prevent both of these features, and future studies with this class of drug should investigate this issue in detail.”

The lower response that seemed to have occurred in the secukinumab-treated patients who had previously used TNF inhibitors vs. those who had not “is in keeping with data for other treatments such as ustekinumab,” they wrote. The fact that there appeared to be a dose-response effect between the patients who received 150 mg secukinumab vs. 300 mg and had previously used TNF inhibitors suggests that the 300-mg dose might be more appropriate for patients who did not respond to TNF inhibitors and/or have moderate to severe psoriasis, for whom the 300-mg dose is already approved and recommended.

Read our meeting coverage of the FUTURE 2 trial at ACR 2014 here.

[email protected]

Treatment of psoriatic arthritis over 24 weeks with the human anti-interleukin-17A monoclonal antibody secukinumab allowed a significantly higher percentage of patients who received 150-mg and 300-mg doses to achieve at least 20% improvement in the American College of Rheumatology response criteria than did placebo.

The results of the multicenter, double-blind, randomized, placebo-controlled FUTURE 2 trial hinted at the effectiveness of the 300-mg dosing regimen in treating patients who previously had not responded to treatment with tumor necrosis factor (TNF) inhibitors and did not show differences in effectiveness when used together with methotrexate. The drug did not have any particularly worrisome treatment-related adverse events, Dr. Iain McInnes of the University of Glasgow (Scotland) and his colleagues reported (Lancet 2015 June 28 [doi:10.1016/S0140-6736(15)61134-5]).

At week 24, ACR20 responses occurred in 54 of 100 patients who received secukinumab 300 mg, 51 of 100 who took the 150-mg dosing regimen, 29 of 99 on the 75-mg dosing regimen, and 15 of 98 on placebo. The odds for achieving ACR20 at 24 weeks were nearly sevenfold higher for the 300-mg dose (odds ratio, 6.81; 95% confidence interval, 3.42-13.56; P < .0001) and 150-mg doses (OR, 6.52; 95% CI, 3.25-13.08; P < .0001) than with placebo.

In an editorial accompanying the report, Dr. Philip Helliwell and Dr. Laura Coates of the University of Leeds (England) said that it is important to note that responses at week 24 were similar to those observed at weeks 12 and 16 so that patients and physicians can “get an idea of response (or non-response) at an early timepoint” (Lancet 2015 June 28 [doi:10.1016/S0140-6736(15)61170-9]).

Although radiographic progression wasn’t assessed in the FUTURE 2 trial, Dr. Helliwell and Dr. Coates noted that secukinumab inhibited radiographic damage in the unpublished FUTURE-1 trial, so “in view of its position in the cytokine hierarchy, interleukin-17 inhibition might prevent both of these features, and future studies with this class of drug should investigate this issue in detail.”

The lower response that seemed to have occurred in the secukinumab-treated patients who had previously used TNF inhibitors vs. those who had not “is in keeping with data for other treatments such as ustekinumab,” they wrote. The fact that there appeared to be a dose-response effect between the patients who received 150 mg secukinumab vs. 300 mg and had previously used TNF inhibitors suggests that the 300-mg dose might be more appropriate for patients who did not respond to TNF inhibitors and/or have moderate to severe psoriasis, for whom the 300-mg dose is already approved and recommended.

Read our meeting coverage of the FUTURE 2 trial at ACR 2014 here.

[email protected]

Treatment of psoriatic arthritis over 24 weeks with the human anti-interleukin-17A monoclonal antibody secukinumab allowed a significantly higher percentage of patients who received 150-mg and 300-mg doses to achieve at least 20% improvement in the American College of Rheumatology response criteria than did placebo.

The results of the multicenter, double-blind, randomized, placebo-controlled FUTURE 2 trial hinted at the effectiveness of the 300-mg dosing regimen in treating patients who previously had not responded to treatment with tumor necrosis factor (TNF) inhibitors and did not show differences in effectiveness when used together with methotrexate. The drug did not have any particularly worrisome treatment-related adverse events, Dr. Iain McInnes of the University of Glasgow (Scotland) and his colleagues reported (Lancet 2015 June 28 [doi:10.1016/S0140-6736(15)61134-5]).

At week 24, ACR20 responses occurred in 54 of 100 patients who received secukinumab 300 mg, 51 of 100 who took the 150-mg dosing regimen, 29 of 99 on the 75-mg dosing regimen, and 15 of 98 on placebo. The odds for achieving ACR20 at 24 weeks were nearly sevenfold higher for the 300-mg dose (odds ratio, 6.81; 95% confidence interval, 3.42-13.56; P < .0001) and 150-mg doses (OR, 6.52; 95% CI, 3.25-13.08; P < .0001) than with placebo.

In an editorial accompanying the report, Dr. Philip Helliwell and Dr. Laura Coates of the University of Leeds (England) said that it is important to note that responses at week 24 were similar to those observed at weeks 12 and 16 so that patients and physicians can “get an idea of response (or non-response) at an early timepoint” (Lancet 2015 June 28 [doi:10.1016/S0140-6736(15)61170-9]).

Although radiographic progression wasn’t assessed in the FUTURE 2 trial, Dr. Helliwell and Dr. Coates noted that secukinumab inhibited radiographic damage in the unpublished FUTURE-1 trial, so “in view of its position in the cytokine hierarchy, interleukin-17 inhibition might prevent both of these features, and future studies with this class of drug should investigate this issue in detail.”

The lower response that seemed to have occurred in the secukinumab-treated patients who had previously used TNF inhibitors vs. those who had not “is in keeping with data for other treatments such as ustekinumab,” they wrote. The fact that there appeared to be a dose-response effect between the patients who received 150 mg secukinumab vs. 300 mg and had previously used TNF inhibitors suggests that the 300-mg dose might be more appropriate for patients who did not respond to TNF inhibitors and/or have moderate to severe psoriasis, for whom the 300-mg dose is already approved and recommended.

Read our meeting coverage of the FUTURE 2 trial at ACR 2014 here.

[email protected]

Evolving knowledge of the underlying pathogenesis of psoriasis has afforded the development of a broad spectrum of nonbiologic systemic medications with therapeutic potential in moderate to severe psoriasis and psoriatic arthritis (PsA). The targets for these medications are antagonists of proinflammatory mediators such as tyrosine kinase, protein kinase, Janus kinase (JAK), p38α mitogen-activated protein (MAP) kinase, phosphodiesterase 4 (PDE-4), calcineurin, Rho-associated kinase (ROCK) 2, cytochrome P450 26 (CYP26), and purine nucleoside phosphorylase (PNP); agonists of anti-inflammatory mediators such as sphingosine-1-phosphate receptor 1 (S1P₁) and adeno-sine A₃ receptor; and myriad other mechanisms. A brief introduction to some of these therapies presently in phase 2 and phase 3 clinical trials are presented (Table).¹

Masitinib (Tyrosine Kinase Inhibitor)

Masitinib (formerly known as AB1010)(AB Sciences) is a tyrosine kinase inhibitor that is purported to decrease inflammation by inhibiting stem cell factor receptor (c-kit) and consequently limiting mast cell degranulation.² A randomized, placebo-controlled, double-blind phase 3 study evaluating its efficacy as an oral formulation was completed, but the results were not available at the time of publication (registered at www.clinicaltrials.gov with the identifier NCT01045577).

Ponesimod (S1P₁ Receptor Agonist)

Ponesimod (formerly known as ACT-128800)(Actelion Pharmaceuticals US, Inc) is an orally formulated S1P₁ receptor agonist. Sphingosine-1-phosphate receptor 1 is necessary for lymphoid chemotaxis.³ A randomized, placebo-controlled, double-blind phase 2 trial of 326 patients demonstrated 75% improvement in psoriasis area and severity index (PASI) score at week 16 in 13.4%, 46.0%, and 48.1% of participants receiving placebo, ponesimod 20 mg, and ponesimod 40 mg, respectively.⁴ At week 28, PASI 75 scores for participants transitioned from ponesimod 40 mg to placebo or ponesimod 20 mg to placebo and those maintained on ponesimod 20 mg and 40 mg were 40.4%, 42.2%, 77.4%, and 71.4%, respectively. This study demonstrated benefit of treatment with ponesimod versus placebo with increased efficacy using maintenance therapy.⁴

Sotrastaurin (Protein Kinase C Inhibitor)

Sotrastaurin (formerly known as AEB071)(Novartis AG) is an oral medication that inhibitsprotein kinase C, thereby limiting CD28-induced activation of T cells. Furthermore, it increases forkhead box P3 expression, which is important, as proinflammatory IL-17 production is stimulated in regulatory T cells with lost forkhead box P3 expression.⁵ In a study of 32 patients who received placebo or sotrastaurin 25, 100, 200, or 300 mg twice daily for 2 weeks, the mean PASI score was reduced by 69% for the 300-mg group versus 5.3% for placebo.⁶ A randomized, placebo-controlled, double-blind phase 2 study was completed for patients with moderate to severe psoriasis, but the results were not available at the time of publication (NCT00885196).

Alitretinoin (Retinoid)

Alitretinoin (9-cis-retinoic acid; Stiefel, a GSK company) is an oral retinoid with purported promise for patients with palmoplantar pustular psoriasis recalcitrant to conventional therapies. In one study, 7 participants with palmoplantar psoriasis received alitretinoin 30 mg daily for 12 weeks with 60% to 90% clinical improvement noted using the visual analog scale and palmoplantar pustular PASI to assess response.⁷ A randomized, placebo-controlled, double-blind phase 2 trial of alitretinoin assessing the success of alitretinoin in patients with palmoplantar psoriasis recalcitrant to topical treatments was completed, but the results were not available at the time of publication (NCT01245140).

Apo805K1 (Unknown Mechanism of Action)

Apo805K1 (ApoPharma Inc) is an oral agent whose mechanism of action has not been disclosed. A randomized, placebo-controlled, double-blind phase 2 trial in patients with moderate to severe psoriasis with a treatment duration of 14 days has been completed. For 12 weeks there was a daily dosing regimen of Apo805K1 10, 30, 60, or 100 mg or placebo, with 12 patients in each treatment group. The proportion of patients achieving PASI 75 was 16.7%, 0%, 0%, 8.3%, and 16.7%, respectively (P=.1975). The number of participants with adverse events reported ranged between 4 to 7, with the greatest number of adverse events reported in the 30-mg subset.⁸ It may be of interest to repeat the study with a larger sample size.

ASP015K (JAK 1 and JAK 3 Inhibitor)

ASP015K (Astellas Pharma US, Inc) is the first of the JAK inhibitors that will be discussed in this section. Janus kinase inhibitors represent a group of tyrosine kinases that regulate cytokine-mediated signaling pathways through the activation of signal transducer and activator of transcription proteins via phosphorylation in the cytoplasm, which in turn control the transcription of genes that generate inflammation. ASP015K and tofacitinib (formerly known as CP-690550)(Pfizer, Inc) inhibit JAK 1 and JAK 3, whereas GSK2586184 (GlaxoSmithKline) inhibits JAK 1 and baricitinib (formerly known as LY3009104 or INCB28050)(Eli Lilly and Company) inhibits JAK 1 and JAK 2.⁹ In a 6-week, dose-escalation phase 2 trial in patients with moderate to severe psoriasis, ASP015K showed a dose-dependent decline in PASI, psoriasis static global assessment, and body surface area.¹⁰

BMS-582949 (p38α MAP Kinase Inhibitor)

BMS-582949 (Bristol-Myers Squibb Company) is an oral p38α MAP kinase inhibitor.¹¹ Along with c-Jun N-terminal kinase and extracellular signal-regulated protein kinases 1 and 2, MAP kinase plays a role in the pathogenesis of psoriasis.¹² A randomized, placebo-controlled, double-blind, 12-week phase 2a study of placebo versus BMS-582949 dosed at 10, 30, and 100 mg has been completed, but the results were not available at the time of publication (NCT00399906).

Apremilast (PDE-4 Inhibitor)

Apremilast (formerly known as CC-10004)(Celgene Corporation) is an oral PDE-4 inhibitor that acts to inhibit the degradation of cyclic adenosine monophosphate. It is approved by the US Food and Drug Administration for moderate to severe plaque psoriasis¹³ and is a particularly good treatment for patients with recalcitrant disease.¹⁴ Several studies on apremilast have been published, including a phase 2 trial of 204 participants receiving placebo or apremilast 20 mg or 40 mg twice daily with American College of Rheumatology (ACR) 20% improvement response of 11.8%, 35.8%, and 43.5%, respectively.¹⁵ The phase 3 PALACE 1, 2, 3, and 4 trials also demonstrated therapeutic efficacy.¹⁶ In PALACE 1, 504 patients receiving placebo or apremilast 20 mg and 30 mg twice daily had an ACR20 of 19%, 31%, and 40%, respectively. In the PALACE 4 study, ACR20 was achieved by 58% of participants at week 52, but the ACR50 and ACR70 rates were less impressive.¹⁶

Lestaurtinib (Multikinase Inhibitor)

Lestaurtinib (formerly known as CEP-701)(Teva Pharmaceutical Industries) is an oral multikinase inhibitor for which a 12-week, nonrandomized, dose-escalation phase 2 study was completed, but the results were not available at the time of publication (NCT00236119).

CF101 (Adenosine A₃ Receptor Agonist)

CF101 (IB-MECA; Can-Fite BioPharma Ltd) is an oral adenosine A₃ receptor agonist. Adenosine A₃ is a G protein–coupled receptor that has an anti-inflammatory role, which lends itself to the treatment of inflammatory conditions such as rheumatoid arthritis.¹⁷ In a randomized, placebo-controlled, double-blind phase 2 trial of 75 patients who received placebo or CF101 1, 2, or 4 mg twice daily for 12 weeks, PASI 50 or greater was reported in 35.3% of participants in the 2-mg group, which was statistically significant at weeks 8 (P=.047) and 12 (P=.031).¹⁸ A randomized, placebo-controlled, double-blind, 16-week phase 2/phase 3 trial in patients with moderate to severe psoriasis treated with CF101 2 mg twice daily versus placebo is ongoing but not recruiting participants (NCT01265667).

Tofacitinib (JAK 1 and JAK 3 Inhibitor)

Tofacitinib is a JAK 1 and JAK 3 inhibitor that is available in both topical and oral formulations. Many studies have been published on tofacitinib, including a dose-ranging phase 2b trial of 197 patients randomized to placebo or tofacitinib 2, 5, or 15 mg daily in which 2.0%, 25.0% (P<.001), 40.8% (P<.0001), and 66.7% (P<.0001) of participants in each treatment group, respectively, achieved PASI 75 at week 12.¹⁹ Another 12-week phase 2b trial in patients with moderate to severe psoriasis explored the effectiveness of oral formulations of tofacitinib based on body location, namely the head and neck, arms, trunk, and legs.²⁰ Designed with twice-daily placebo and tofacitinib 2-, 5-, and 15-mg treatment arms, the target plaque severity score demonstrated a statistically significant dose-responsive improvement in each of the 4 anatomic regions (P<.01).

Two randomized, double-blinded, placebo-controlled phase 3 trials of tofacitinib have been completed. One trial compared the safety and effectiveness of tofacitinib and etanercept in patients with moderate to severe psoriasis.²¹ The 329 participants were randomized to treatment with oral tofacitinib 5 mg or 10 mg twice daily with placebo subcutaneous (SQ) injections twice weekly; oral placebo twice daily with etanercept 50-mg SQ injections twice weekly; or oral placebo twice daily with placebo SQ injection twice weekly. At week 12, PASI 75 was achieved in 39.51%, 63.64%, 58.81%, and 5.61% of participants in each treatment group, respectively. Thus, tofacitinib 10 mg and etanercept 50 mg were the first and second best performers in this study design.²¹

In the other phase 3 trial, the efficacy and safety of treatment, treatment withdrawal, and subsequent resumption of treatment with tofacitinib was examined in 290 patients who received either tofacitinib 5 mg or 10 mg or placebo twice daily for 24 weeks.²² In the withdrawal period, the percentage of patients who maintained a PASI 75 response in the tofacitinib 5-mg group was 56.2% versus 23.3% in the placebo group at week 16 (P<.0008). In the 10-mg group, 62.3% of participants maintained PASI 75 at week 16 versus 26.1% in the placebo group (P<.0001). During the re-treatment period for those who showed a greater than 50% reduction in week 24 PASI during treatment withdrawal (N=102), 50.0% of the tofacitinib 5-mg group showed PASI 75 versus 31.58% of the placebo group at week 16. In the tofacitinib 10-mg group, PASI 75 was seen in 0% versus 50.85% in the placebo group. Of note, only 5 participants who demonstrated a greater than 50% reduction in week 24 PASI response following withdrawal of therapy were in the tofacitinib 5- or 10-mg groups, as the rest were in the placebo group.²²

FP187 (Fumaric Acid Ester)

FP187 (Forward Pharma A/S) is an oral fumaric acid ester whose underlying mechanism is thought to be elevation of glutathione levels that decreases the amount of inflammatory cytokines by blocking the translocation of nuclear factor κB. Other fumaric acid esters such as monoethyl fumarate and dimethyl fumarate have been used in Europe for the management of psoriasis.²³ A phase 2 study of the safety and effectiveness of FP187 for moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01230138). A phase 3 trial examining the efficacy of FP187 in managing moderate to severe psoriasis was not yet open for participant recruitment at the time of publication (NCT01815723).

Doxercalciferol (Vitamin D₂ Analogue)

Doxercalciferol (1α-hydroxyvitamin D₂; Genzyme Corporation, a Sanofi company) is an oral prodrug of vitamin D.²⁴ Topical preparations of vitamin D analogues approved by the US Food and Drug Administration such as calcipotriene are mainstays in psoriasis management. Doxercalciferol has been used for other therapeutic applications such as decreasing elevated parathyroid hormone levels.²⁵ Research has demonstrated that CYP24A1 can extrahepatically regulate the activation of vitamin D prodrugs in cutaneous tissues.²⁶ In a phase 2 study examining the efficacy and safety of doxercalciferol in patients with moderate to severe psoriasis, 111 patients were randomized to placebo or doxercalciferol 2.5, 5, or 7.5 mg daily for 24 weeks (NCT00601107). At week 12, PASI 50 was similar regardless of the treatment administered, reported at 20.0%, 20.0%, 17.9%, and 20.0%, respectively (P=1.000).²⁷

GSK2586184 (JAK 1 Inhibitor)

GSK2586184 is an oral JAK 1 inhibitor. A placebo-controlled, double-blind, dose-dependent phase 2 study of GSK2586184 in patients with chronic plaque psoriasis who were randomized to placebo or GSK2586184 100, 200, and 400 mg twice daily for 84 days has been completed, but the results were not available at the time of publication (NCT01782664). Of note, despite clinical promise, due to potential adverse effects of the medication that included a possible interaction with statin medication, the manufacturer decided against pursuing GSK2586184 as a treatment in the management of psoriasis.²⁸

Voclosporin (Calcineurin Inhibitor)

Voclosporin (formerly known as ISA247)(Aurinia Pharmaceuticals Inc) is an oral calcineurin inhibitor that is purported to be as effective as cyclospor-ine A with less associated toxicity. A 12-week randomized, placebo-controlled, double-blind phase 2 trial demonstrated PASI 75 in 0%, 18.2%, and 66.7% of 201 participants receiving placebo, voclospo-rin 0.5 mg/kg, and voclosporin 1.5 mg/kg twice daily, respectively (P<.0001). Elevated serum creatinine levels within the high range of normal were noted in the 1.5-mg/kg group.²⁹ A 12-week phase 3 study of 451 patients randomized to placebo or voclospo-rin 0.2-, 0.3-, or 0.4-mg/kg treatment groups similarly demonstrated a dose-responsive PASI 75 of 4%, 16%, 25%, and 47%, respectively, that was maintained at week 24. Mild to moderate decreases in glomerular filtration rates were noted in 8 patients in the 0.3- and 0.4-mg/kg subsets.³⁰ Another phase 2 study of voclosporin in patients with moderate to severe psoriasis showed improvements according to the psoriasis disability index and dermatology life quality index.³¹

Three randomized, placebo-controlled, double-blind phase 3 trials have been completed for voclosporin, but the results were not available at the time of publication. The phase 3 ESSENCE trial compared voclosporin to placebo and ciclosporin controls (NCT00408187). Two phase 3 trials known as the SPIRIT trials—one a 12-week study (NCT00244842) and the other a 36-week extension trial (NCT00258713)—compared the efficacy of placebo to voclosporin administered at 0.2-, 0.3-, and 0.4-mg/kg doses.

KD025 (ROCK 2 Inhibitor)

KD025 (Kadmon Corporation, LLC) is an oral ROCK 2 inhibitor. The inhibition of ROCK in the ras homolog gene family, member A/ROCK pathway has been targeted therapeutically for pulmonary arterial hypertension,³² glaucoma,³³ and many other uses. A phase 2a study assessing the tolerability and safety profile of KD025 in patients with moderate to severe psoriasis was completed, but the results were not available at the time of publication (NCT02106195).

LAS41008 (Fumaric Acid Ester)

LAS41008 (Almirall, S.A.) is purported to be an oral dimethyl fumarate that inhibits endothelial cell proliferation, migration, and differentiation.³⁴ A phase 3 trial comparing the safety and effectiveness of LAS41008, LASW1835 (an active comparator), and placebo in patients with moderate to severe psoriasis is ongoing but not recruiting participants (NCT01726933).

LEO 22811 (Anti-inflammatory)

LEO 22811 (LEO Pharma) is an oral anti-inflammatory agent for the treatment of psoriasis. Two clinical trials have been completed, the results of which have not yet been published. A phase 1 trial assessing the tolerability and safety profile of LEO 22811 (NCT00833872) and a phase 2 proof-of-concept study assessing dose response of LEO 22811 versus placebo (NCT01116895) were completed, but the results were not available at the time of publication.

Baricitinib (JAK 1 and JAK 2 Inhibitor)

As noted above, baricitinib (LY3009104 or INCB28050) is a JAK 1 and JAK 2 inhibitor. A phase 2b trial examining dose response for LY3009104 or baricitinib administration in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01490632).

Talarozole (CYP26 Inhibitor)

Talarozole (formerly known as R115866)(GlaxoSmithKline) is a selective oral CYP26 inhibitor that could serve to regulate the degradation of all-trans retinoic acid in the management of conditions such as acne and psoriasis. One phase 2 nonrandomized, open-label study (NCT00725348) and another phase 2 randomized, placebo-controlled, double-blind, dose-dependent trial examining the effectiveness and safety profile of 12-week talarozole treatment in patients with severe plaque psoriasis have been completed, but the results were not available at the time of publication (NCT00716144).

R3421 or BCX-4208 (PNP Inhibitor)

R3421 or BCX-4208 (BioCryst Pharmaceuticals, Inc/Hoffman–La Roche) is an oral PNP inhibitor that may help regulate apoptosis of T cells and B cells.³⁵ A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT00504270).

RWJ-445380 (Cathepsin S Inhibitor)

RWJ-445380 (Alza Corporation, DE) is an oral cathepsin S inhibitor. Cathepsin S is produced by antigen-presenting cells and activates CD4⁺ T cells via presentation of antigen by class II major histocompatibility complex.³⁶ A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial evaluating the tolerability, safety, pharmacodynamics, and pharmacokinetics of RWJ-445380 in patients with plaque psoriasis has been completed, but the results were not available at the time of publication (NCT00396422).

SRT2104 (Sirtuin 1 Activator)

SRT2104 (GlaxoSmithKline) is a selective oral NAD⁺-dependent deacetylase sirtuin 1 activator. Sirtuins help regulate apoptosis, inflammation, and other important cellular mechanisms.³⁷ A randomized, open-label phase 1 trial examining drug bioavailability (NCT01702493) and a randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial studying the efficacy, tolerability, and safety of SRT2104 in patients with moderate to severe psoriasis have been completed (NCT01154101), but the results were not available at the time of publication.

VB-201 (Oxidized Phospholipid)

VB-201 (VBL Therapeutics) is an orally administered oxidized phospholipid analogue with anti-inflammatory effects.³⁸ Oxidized phospholipids are another element in the intricate spectrum of inflammatory mediators. A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial of VB-201 20 mg or 80 mg daily in patients with moderate to severe psoriasis was completed, but the results were not available at the time of publication (NCT01001468). Another randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial of VB-201 80 mg and 160 mg twice daily in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01837420).

Conclusion

We are living in an exciting time in the treatment of psoriasis and PsA, with promising novel therapies afforded by the discovery of new therapeutic targets. In this 3-part series, we have reviewed topical, systemic, and biologic therapies that currently are in phase 2 through phase 4 clinical trials or have recently been approved by the US Food and Drug Administration for the management of psoriasis and PsA. These treatments offer patients and their caregivers the prospect of more targeted therapeutic regimens that offer enhanced clinical outcomes with more favorable side-effect profiles. As clinicians and researchers build upon this knowledge in the years to come, we can offer psoriasis patients an increasingly diverse and powerful therapeutic armamentarium.

Evolving knowledge of the underlying pathogenesis of psoriasis has afforded the development of a broad spectrum of nonbiologic systemic medications with therapeutic potential in moderate to severe psoriasis and psoriatic arthritis (PsA). The targets for these medications are antagonists of proinflammatory mediators such as tyrosine kinase, protein kinase, Janus kinase (JAK), p38α mitogen-activated protein (MAP) kinase, phosphodiesterase 4 (PDE-4), calcineurin, Rho-associated kinase (ROCK) 2, cytochrome P450 26 (CYP26), and purine nucleoside phosphorylase (PNP); agonists of anti-inflammatory mediators such as sphingosine-1-phosphate receptor 1 (S1P₁) and adeno-sine A₃ receptor; and myriad other mechanisms. A brief introduction to some of these therapies presently in phase 2 and phase 3 clinical trials are presented (Table).¹

Masitinib (Tyrosine Kinase Inhibitor)

Masitinib (formerly known as AB1010)(AB Sciences) is a tyrosine kinase inhibitor that is purported to decrease inflammation by inhibiting stem cell factor receptor (c-kit) and consequently limiting mast cell degranulation.² A randomized, placebo-controlled, double-blind phase 3 study evaluating its efficacy as an oral formulation was completed, but the results were not available at the time of publication (registered at www.clinicaltrials.gov with the identifier NCT01045577).

Ponesimod (S1P₁ Receptor Agonist)

Ponesimod (formerly known as ACT-128800)(Actelion Pharmaceuticals US, Inc) is an orally formulated S1P₁ receptor agonist. Sphingosine-1-phosphate receptor 1 is necessary for lymphoid chemotaxis.³ A randomized, placebo-controlled, double-blind phase 2 trial of 326 patients demonstrated 75% improvement in psoriasis area and severity index (PASI) score at week 16 in 13.4%, 46.0%, and 48.1% of participants receiving placebo, ponesimod 20 mg, and ponesimod 40 mg, respectively.⁴ At week 28, PASI 75 scores for participants transitioned from ponesimod 40 mg to placebo or ponesimod 20 mg to placebo and those maintained on ponesimod 20 mg and 40 mg were 40.4%, 42.2%, 77.4%, and 71.4%, respectively. This study demonstrated benefit of treatment with ponesimod versus placebo with increased efficacy using maintenance therapy.⁴

Sotrastaurin (Protein Kinase C Inhibitor)

Sotrastaurin (formerly known as AEB071)(Novartis AG) is an oral medication that inhibitsprotein kinase C, thereby limiting CD28-induced activation of T cells. Furthermore, it increases forkhead box P3 expression, which is important, as proinflammatory IL-17 production is stimulated in regulatory T cells with lost forkhead box P3 expression.⁵ In a study of 32 patients who received placebo or sotrastaurin 25, 100, 200, or 300 mg twice daily for 2 weeks, the mean PASI score was reduced by 69% for the 300-mg group versus 5.3% for placebo.⁶ A randomized, placebo-controlled, double-blind phase 2 study was completed for patients with moderate to severe psoriasis, but the results were not available at the time of publication (NCT00885196).

Alitretinoin (Retinoid)

Alitretinoin (9-cis-retinoic acid; Stiefel, a GSK company) is an oral retinoid with purported promise for patients with palmoplantar pustular psoriasis recalcitrant to conventional therapies. In one study, 7 participants with palmoplantar psoriasis received alitretinoin 30 mg daily for 12 weeks with 60% to 90% clinical improvement noted using the visual analog scale and palmoplantar pustular PASI to assess response.⁷ A randomized, placebo-controlled, double-blind phase 2 trial of alitretinoin assessing the success of alitretinoin in patients with palmoplantar psoriasis recalcitrant to topical treatments was completed, but the results were not available at the time of publication (NCT01245140).

Apo805K1 (Unknown Mechanism of Action)

Apo805K1 (ApoPharma Inc) is an oral agent whose mechanism of action has not been disclosed. A randomized, placebo-controlled, double-blind phase 2 trial in patients with moderate to severe psoriasis with a treatment duration of 14 days has been completed. For 12 weeks there was a daily dosing regimen of Apo805K1 10, 30, 60, or 100 mg or placebo, with 12 patients in each treatment group. The proportion of patients achieving PASI 75 was 16.7%, 0%, 0%, 8.3%, and 16.7%, respectively (P=.1975). The number of participants with adverse events reported ranged between 4 to 7, with the greatest number of adverse events reported in the 30-mg subset.⁸ It may be of interest to repeat the study with a larger sample size.

ASP015K (JAK 1 and JAK 3 Inhibitor)

ASP015K (Astellas Pharma US, Inc) is the first of the JAK inhibitors that will be discussed in this section. Janus kinase inhibitors represent a group of tyrosine kinases that regulate cytokine-mediated signaling pathways through the activation of signal transducer and activator of transcription proteins via phosphorylation in the cytoplasm, which in turn control the transcription of genes that generate inflammation. ASP015K and tofacitinib (formerly known as CP-690550)(Pfizer, Inc) inhibit JAK 1 and JAK 3, whereas GSK2586184 (GlaxoSmithKline) inhibits JAK 1 and baricitinib (formerly known as LY3009104 or INCB28050)(Eli Lilly and Company) inhibits JAK 1 and JAK 2.⁹ In a 6-week, dose-escalation phase 2 trial in patients with moderate to severe psoriasis, ASP015K showed a dose-dependent decline in PASI, psoriasis static global assessment, and body surface area.¹⁰

BMS-582949 (p38α MAP Kinase Inhibitor)

BMS-582949 (Bristol-Myers Squibb Company) is an oral p38α MAP kinase inhibitor.¹¹ Along with c-Jun N-terminal kinase and extracellular signal-regulated protein kinases 1 and 2, MAP kinase plays a role in the pathogenesis of psoriasis.¹² A randomized, placebo-controlled, double-blind, 12-week phase 2a study of placebo versus BMS-582949 dosed at 10, 30, and 100 mg has been completed, but the results were not available at the time of publication (NCT00399906).

Apremilast (PDE-4 Inhibitor)

Apremilast (formerly known as CC-10004)(Celgene Corporation) is an oral PDE-4 inhibitor that acts to inhibit the degradation of cyclic adenosine monophosphate. It is approved by the US Food and Drug Administration for moderate to severe plaque psoriasis¹³ and is a particularly good treatment for patients with recalcitrant disease.¹⁴ Several studies on apremilast have been published, including a phase 2 trial of 204 participants receiving placebo or apremilast 20 mg or 40 mg twice daily with American College of Rheumatology (ACR) 20% improvement response of 11.8%, 35.8%, and 43.5%, respectively.¹⁵ The phase 3 PALACE 1, 2, 3, and 4 trials also demonstrated therapeutic efficacy.¹⁶ In PALACE 1, 504 patients receiving placebo or apremilast 20 mg and 30 mg twice daily had an ACR20 of 19%, 31%, and 40%, respectively. In the PALACE 4 study, ACR20 was achieved by 58% of participants at week 52, but the ACR50 and ACR70 rates were less impressive.¹⁶

Lestaurtinib (Multikinase Inhibitor)

Lestaurtinib (formerly known as CEP-701)(Teva Pharmaceutical Industries) is an oral multikinase inhibitor for which a 12-week, nonrandomized, dose-escalation phase 2 study was completed, but the results were not available at the time of publication (NCT00236119).

CF101 (Adenosine A₃ Receptor Agonist)

CF101 (IB-MECA; Can-Fite BioPharma Ltd) is an oral adenosine A₃ receptor agonist. Adenosine A₃ is a G protein–coupled receptor that has an anti-inflammatory role, which lends itself to the treatment of inflammatory conditions such as rheumatoid arthritis.¹⁷ In a randomized, placebo-controlled, double-blind phase 2 trial of 75 patients who received placebo or CF101 1, 2, or 4 mg twice daily for 12 weeks, PASI 50 or greater was reported in 35.3% of participants in the 2-mg group, which was statistically significant at weeks 8 (P=.047) and 12 (P=.031).¹⁸ A randomized, placebo-controlled, double-blind, 16-week phase 2/phase 3 trial in patients with moderate to severe psoriasis treated with CF101 2 mg twice daily versus placebo is ongoing but not recruiting participants (NCT01265667).

Tofacitinib (JAK 1 and JAK 3 Inhibitor)

Tofacitinib is a JAK 1 and JAK 3 inhibitor that is available in both topical and oral formulations. Many studies have been published on tofacitinib, including a dose-ranging phase 2b trial of 197 patients randomized to placebo or tofacitinib 2, 5, or 15 mg daily in which 2.0%, 25.0% (P<.001), 40.8% (P<.0001), and 66.7% (P<.0001) of participants in each treatment group, respectively, achieved PASI 75 at week 12.¹⁹ Another 12-week phase 2b trial in patients with moderate to severe psoriasis explored the effectiveness of oral formulations of tofacitinib based on body location, namely the head and neck, arms, trunk, and legs.²⁰ Designed with twice-daily placebo and tofacitinib 2-, 5-, and 15-mg treatment arms, the target plaque severity score demonstrated a statistically significant dose-responsive improvement in each of the 4 anatomic regions (P<.01).

Two randomized, double-blinded, placebo-controlled phase 3 trials of tofacitinib have been completed. One trial compared the safety and effectiveness of tofacitinib and etanercept in patients with moderate to severe psoriasis.²¹ The 329 participants were randomized to treatment with oral tofacitinib 5 mg or 10 mg twice daily with placebo subcutaneous (SQ) injections twice weekly; oral placebo twice daily with etanercept 50-mg SQ injections twice weekly; or oral placebo twice daily with placebo SQ injection twice weekly. At week 12, PASI 75 was achieved in 39.51%, 63.64%, 58.81%, and 5.61% of participants in each treatment group, respectively. Thus, tofacitinib 10 mg and etanercept 50 mg were the first and second best performers in this study design.²¹

In the other phase 3 trial, the efficacy and safety of treatment, treatment withdrawal, and subsequent resumption of treatment with tofacitinib was examined in 290 patients who received either tofacitinib 5 mg or 10 mg or placebo twice daily for 24 weeks.²² In the withdrawal period, the percentage of patients who maintained a PASI 75 response in the tofacitinib 5-mg group was 56.2% versus 23.3% in the placebo group at week 16 (P<.0008). In the 10-mg group, 62.3% of participants maintained PASI 75 at week 16 versus 26.1% in the placebo group (P<.0001). During the re-treatment period for those who showed a greater than 50% reduction in week 24 PASI during treatment withdrawal (N=102), 50.0% of the tofacitinib 5-mg group showed PASI 75 versus 31.58% of the placebo group at week 16. In the tofacitinib 10-mg group, PASI 75 was seen in 0% versus 50.85% in the placebo group. Of note, only 5 participants who demonstrated a greater than 50% reduction in week 24 PASI response following withdrawal of therapy were in the tofacitinib 5- or 10-mg groups, as the rest were in the placebo group.²²

FP187 (Fumaric Acid Ester)

FP187 (Forward Pharma A/S) is an oral fumaric acid ester whose underlying mechanism is thought to be elevation of glutathione levels that decreases the amount of inflammatory cytokines by blocking the translocation of nuclear factor κB. Other fumaric acid esters such as monoethyl fumarate and dimethyl fumarate have been used in Europe for the management of psoriasis.²³ A phase 2 study of the safety and effectiveness of FP187 for moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01230138). A phase 3 trial examining the efficacy of FP187 in managing moderate to severe psoriasis was not yet open for participant recruitment at the time of publication (NCT01815723).

Doxercalciferol (Vitamin D₂ Analogue)

Doxercalciferol (1α-hydroxyvitamin D₂; Genzyme Corporation, a Sanofi company) is an oral prodrug of vitamin D.²⁴ Topical preparations of vitamin D analogues approved by the US Food and Drug Administration such as calcipotriene are mainstays in psoriasis management. Doxercalciferol has been used for other therapeutic applications such as decreasing elevated parathyroid hormone levels.²⁵ Research has demonstrated that CYP24A1 can extrahepatically regulate the activation of vitamin D prodrugs in cutaneous tissues.²⁶ In a phase 2 study examining the efficacy and safety of doxercalciferol in patients with moderate to severe psoriasis, 111 patients were randomized to placebo or doxercalciferol 2.5, 5, or 7.5 mg daily for 24 weeks (NCT00601107). At week 12, PASI 50 was similar regardless of the treatment administered, reported at 20.0%, 20.0%, 17.9%, and 20.0%, respectively (P=1.000).²⁷

GSK2586184 (JAK 1 Inhibitor)

GSK2586184 is an oral JAK 1 inhibitor. A placebo-controlled, double-blind, dose-dependent phase 2 study of GSK2586184 in patients with chronic plaque psoriasis who were randomized to placebo or GSK2586184 100, 200, and 400 mg twice daily for 84 days has been completed, but the results were not available at the time of publication (NCT01782664). Of note, despite clinical promise, due to potential adverse effects of the medication that included a possible interaction with statin medication, the manufacturer decided against pursuing GSK2586184 as a treatment in the management of psoriasis.²⁸

Voclosporin (Calcineurin Inhibitor)

Voclosporin (formerly known as ISA247)(Aurinia Pharmaceuticals Inc) is an oral calcineurin inhibitor that is purported to be as effective as cyclospor-ine A with less associated toxicity. A 12-week randomized, placebo-controlled, double-blind phase 2 trial demonstrated PASI 75 in 0%, 18.2%, and 66.7% of 201 participants receiving placebo, voclospo-rin 0.5 mg/kg, and voclosporin 1.5 mg/kg twice daily, respectively (P<.0001). Elevated serum creatinine levels within the high range of normal were noted in the 1.5-mg/kg group.²⁹ A 12-week phase 3 study of 451 patients randomized to placebo or voclospo-rin 0.2-, 0.3-, or 0.4-mg/kg treatment groups similarly demonstrated a dose-responsive PASI 75 of 4%, 16%, 25%, and 47%, respectively, that was maintained at week 24. Mild to moderate decreases in glomerular filtration rates were noted in 8 patients in the 0.3- and 0.4-mg/kg subsets.³⁰ Another phase 2 study of voclosporin in patients with moderate to severe psoriasis showed improvements according to the psoriasis disability index and dermatology life quality index.³¹

Three randomized, placebo-controlled, double-blind phase 3 trials have been completed for voclosporin, but the results were not available at the time of publication. The phase 3 ESSENCE trial compared voclosporin to placebo and ciclosporin controls (NCT00408187). Two phase 3 trials known as the SPIRIT trials—one a 12-week study (NCT00244842) and the other a 36-week extension trial (NCT00258713)—compared the efficacy of placebo to voclosporin administered at 0.2-, 0.3-, and 0.4-mg/kg doses.

KD025 (ROCK 2 Inhibitor)

KD025 (Kadmon Corporation, LLC) is an oral ROCK 2 inhibitor. The inhibition of ROCK in the ras homolog gene family, member A/ROCK pathway has been targeted therapeutically for pulmonary arterial hypertension,³² glaucoma,³³ and many other uses. A phase 2a study assessing the tolerability and safety profile of KD025 in patients with moderate to severe psoriasis was completed, but the results were not available at the time of publication (NCT02106195).

LAS41008 (Fumaric Acid Ester)

LAS41008 (Almirall, S.A.) is purported to be an oral dimethyl fumarate that inhibits endothelial cell proliferation, migration, and differentiation.³⁴ A phase 3 trial comparing the safety and effectiveness of LAS41008, LASW1835 (an active comparator), and placebo in patients with moderate to severe psoriasis is ongoing but not recruiting participants (NCT01726933).

LEO 22811 (Anti-inflammatory)

LEO 22811 (LEO Pharma) is an oral anti-inflammatory agent for the treatment of psoriasis. Two clinical trials have been completed, the results of which have not yet been published. A phase 1 trial assessing the tolerability and safety profile of LEO 22811 (NCT00833872) and a phase 2 proof-of-concept study assessing dose response of LEO 22811 versus placebo (NCT01116895) were completed, but the results were not available at the time of publication.

Baricitinib (JAK 1 and JAK 2 Inhibitor)

As noted above, baricitinib (LY3009104 or INCB28050) is a JAK 1 and JAK 2 inhibitor. A phase 2b trial examining dose response for LY3009104 or baricitinib administration in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01490632).

Talarozole (CYP26 Inhibitor)

Talarozole (formerly known as R115866)(GlaxoSmithKline) is a selective oral CYP26 inhibitor that could serve to regulate the degradation of all-trans retinoic acid in the management of conditions such as acne and psoriasis. One phase 2 nonrandomized, open-label study (NCT00725348) and another phase 2 randomized, placebo-controlled, double-blind, dose-dependent trial examining the effectiveness and safety profile of 12-week talarozole treatment in patients with severe plaque psoriasis have been completed, but the results were not available at the time of publication (NCT00716144).

R3421 or BCX-4208 (PNP Inhibitor)

R3421 or BCX-4208 (BioCryst Pharmaceuticals, Inc/Hoffman–La Roche) is an oral PNP inhibitor that may help regulate apoptosis of T cells and B cells.³⁵ A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT00504270).

RWJ-445380 (Cathepsin S Inhibitor)

RWJ-445380 (Alza Corporation, DE) is an oral cathepsin S inhibitor. Cathepsin S is produced by antigen-presenting cells and activates CD4⁺ T cells via presentation of antigen by class II major histocompatibility complex.³⁶ A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial evaluating the tolerability, safety, pharmacodynamics, and pharmacokinetics of RWJ-445380 in patients with plaque psoriasis has been completed, but the results were not available at the time of publication (NCT00396422).

SRT2104 (Sirtuin 1 Activator)

SRT2104 (GlaxoSmithKline) is a selective oral NAD⁺-dependent deacetylase sirtuin 1 activator. Sirtuins help regulate apoptosis, inflammation, and other important cellular mechanisms.³⁷ A randomized, open-label phase 1 trial examining drug bioavailability (NCT01702493) and a randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial studying the efficacy, tolerability, and safety of SRT2104 in patients with moderate to severe psoriasis have been completed (NCT01154101), but the results were not available at the time of publication.

VB-201 (Oxidized Phospholipid)

VB-201 (VBL Therapeutics) is an orally administered oxidized phospholipid analogue with anti-inflammatory effects.³⁸ Oxidized phospholipids are another element in the intricate spectrum of inflammatory mediators. A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial of VB-201 20 mg or 80 mg daily in patients with moderate to severe psoriasis was completed, but the results were not available at the time of publication (NCT01001468). Another randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial of VB-201 80 mg and 160 mg twice daily in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01837420).

Conclusion

We are living in an exciting time in the treatment of psoriasis and PsA, with promising novel therapies afforded by the discovery of new therapeutic targets. In this 3-part series, we have reviewed topical, systemic, and biologic therapies that currently are in phase 2 through phase 4 clinical trials or have recently been approved by the US Food and Drug Administration for the management of psoriasis and PsA. These treatments offer patients and their caregivers the prospect of more targeted therapeutic regimens that offer enhanced clinical outcomes with more favorable side-effect profiles. As clinicians and researchers build upon this knowledge in the years to come, we can offer psoriasis patients an increasingly diverse and powerful therapeutic armamentarium.

Evolving knowledge of the underlying pathogenesis of psoriasis has afforded the development of a broad spectrum of nonbiologic systemic medications with therapeutic potential in moderate to severe psoriasis and psoriatic arthritis (PsA). The targets for these medications are antagonists of proinflammatory mediators such as tyrosine kinase, protein kinase, Janus kinase (JAK), p38α mitogen-activated protein (MAP) kinase, phosphodiesterase 4 (PDE-4), calcineurin, Rho-associated kinase (ROCK) 2, cytochrome P450 26 (CYP26), and purine nucleoside phosphorylase (PNP); agonists of anti-inflammatory mediators such as sphingosine-1-phosphate receptor 1 (S1P₁) and adeno-sine A₃ receptor; and myriad other mechanisms. A brief introduction to some of these therapies presently in phase 2 and phase 3 clinical trials are presented (Table).¹

Masitinib (Tyrosine Kinase Inhibitor)

Masitinib (formerly known as AB1010)(AB Sciences) is a tyrosine kinase inhibitor that is purported to decrease inflammation by inhibiting stem cell factor receptor (c-kit) and consequently limiting mast cell degranulation.² A randomized, placebo-controlled, double-blind phase 3 study evaluating its efficacy as an oral formulation was completed, but the results were not available at the time of publication (registered at www.clinicaltrials.gov with the identifier NCT01045577).

Ponesimod (S1P₁ Receptor Agonist)

Ponesimod (formerly known as ACT-128800)(Actelion Pharmaceuticals US, Inc) is an orally formulated S1P₁ receptor agonist. Sphingosine-1-phosphate receptor 1 is necessary for lymphoid chemotaxis.³ A randomized, placebo-controlled, double-blind phase 2 trial of 326 patients demonstrated 75% improvement in psoriasis area and severity index (PASI) score at week 16 in 13.4%, 46.0%, and 48.1% of participants receiving placebo, ponesimod 20 mg, and ponesimod 40 mg, respectively.⁴ At week 28, PASI 75 scores for participants transitioned from ponesimod 40 mg to placebo or ponesimod 20 mg to placebo and those maintained on ponesimod 20 mg and 40 mg were 40.4%, 42.2%, 77.4%, and 71.4%, respectively. This study demonstrated benefit of treatment with ponesimod versus placebo with increased efficacy using maintenance therapy.⁴

Sotrastaurin (Protein Kinase C Inhibitor)

Sotrastaurin (formerly known as AEB071)(Novartis AG) is an oral medication that inhibitsprotein kinase C, thereby limiting CD28-induced activation of T cells. Furthermore, it increases forkhead box P3 expression, which is important, as proinflammatory IL-17 production is stimulated in regulatory T cells with lost forkhead box P3 expression.⁵ In a study of 32 patients who received placebo or sotrastaurin 25, 100, 200, or 300 mg twice daily for 2 weeks, the mean PASI score was reduced by 69% for the 300-mg group versus 5.3% for placebo.⁶ A randomized, placebo-controlled, double-blind phase 2 study was completed for patients with moderate to severe psoriasis, but the results were not available at the time of publication (NCT00885196).

Alitretinoin (Retinoid)

Alitretinoin (9-cis-retinoic acid; Stiefel, a GSK company) is an oral retinoid with purported promise for patients with palmoplantar pustular psoriasis recalcitrant to conventional therapies. In one study, 7 participants with palmoplantar psoriasis received alitretinoin 30 mg daily for 12 weeks with 60% to 90% clinical improvement noted using the visual analog scale and palmoplantar pustular PASI to assess response.⁷ A randomized, placebo-controlled, double-blind phase 2 trial of alitretinoin assessing the success of alitretinoin in patients with palmoplantar psoriasis recalcitrant to topical treatments was completed, but the results were not available at the time of publication (NCT01245140).

Apo805K1 (Unknown Mechanism of Action)

Apo805K1 (ApoPharma Inc) is an oral agent whose mechanism of action has not been disclosed. A randomized, placebo-controlled, double-blind phase 2 trial in patients with moderate to severe psoriasis with a treatment duration of 14 days has been completed. For 12 weeks there was a daily dosing regimen of Apo805K1 10, 30, 60, or 100 mg or placebo, with 12 patients in each treatment group. The proportion of patients achieving PASI 75 was 16.7%, 0%, 0%, 8.3%, and 16.7%, respectively (P=.1975). The number of participants with adverse events reported ranged between 4 to 7, with the greatest number of adverse events reported in the 30-mg subset.⁸ It may be of interest to repeat the study with a larger sample size.

ASP015K (JAK 1 and JAK 3 Inhibitor)

ASP015K (Astellas Pharma US, Inc) is the first of the JAK inhibitors that will be discussed in this section. Janus kinase inhibitors represent a group of tyrosine kinases that regulate cytokine-mediated signaling pathways through the activation of signal transducer and activator of transcription proteins via phosphorylation in the cytoplasm, which in turn control the transcription of genes that generate inflammation. ASP015K and tofacitinib (formerly known as CP-690550)(Pfizer, Inc) inhibit JAK 1 and JAK 3, whereas GSK2586184 (GlaxoSmithKline) inhibits JAK 1 and baricitinib (formerly known as LY3009104 or INCB28050)(Eli Lilly and Company) inhibits JAK 1 and JAK 2.⁹ In a 6-week, dose-escalation phase 2 trial in patients with moderate to severe psoriasis, ASP015K showed a dose-dependent decline in PASI, psoriasis static global assessment, and body surface area.¹⁰

BMS-582949 (p38α MAP Kinase Inhibitor)

BMS-582949 (Bristol-Myers Squibb Company) is an oral p38α MAP kinase inhibitor.¹¹ Along with c-Jun N-terminal kinase and extracellular signal-regulated protein kinases 1 and 2, MAP kinase plays a role in the pathogenesis of psoriasis.¹² A randomized, placebo-controlled, double-blind, 12-week phase 2a study of placebo versus BMS-582949 dosed at 10, 30, and 100 mg has been completed, but the results were not available at the time of publication (NCT00399906).

Apremilast (PDE-4 Inhibitor)

Apremilast (formerly known as CC-10004)(Celgene Corporation) is an oral PDE-4 inhibitor that acts to inhibit the degradation of cyclic adenosine monophosphate. It is approved by the US Food and Drug Administration for moderate to severe plaque psoriasis¹³ and is a particularly good treatment for patients with recalcitrant disease.¹⁴ Several studies on apremilast have been published, including a phase 2 trial of 204 participants receiving placebo or apremilast 20 mg or 40 mg twice daily with American College of Rheumatology (ACR) 20% improvement response of 11.8%, 35.8%, and 43.5%, respectively.¹⁵ The phase 3 PALACE 1, 2, 3, and 4 trials also demonstrated therapeutic efficacy.¹⁶ In PALACE 1, 504 patients receiving placebo or apremilast 20 mg and 30 mg twice daily had an ACR20 of 19%, 31%, and 40%, respectively. In the PALACE 4 study, ACR20 was achieved by 58% of participants at week 52, but the ACR50 and ACR70 rates were less impressive.¹⁶

Lestaurtinib (Multikinase Inhibitor)

Lestaurtinib (formerly known as CEP-701)(Teva Pharmaceutical Industries) is an oral multikinase inhibitor for which a 12-week, nonrandomized, dose-escalation phase 2 study was completed, but the results were not available at the time of publication (NCT00236119).

CF101 (Adenosine A₃ Receptor Agonist)

CF101 (IB-MECA; Can-Fite BioPharma Ltd) is an oral adenosine A₃ receptor agonist. Adenosine A₃ is a G protein–coupled receptor that has an anti-inflammatory role, which lends itself to the treatment of inflammatory conditions such as rheumatoid arthritis.¹⁷ In a randomized, placebo-controlled, double-blind phase 2 trial of 75 patients who received placebo or CF101 1, 2, or 4 mg twice daily for 12 weeks, PASI 50 or greater was reported in 35.3% of participants in the 2-mg group, which was statistically significant at weeks 8 (P=.047) and 12 (P=.031).¹⁸ A randomized, placebo-controlled, double-blind, 16-week phase 2/phase 3 trial in patients with moderate to severe psoriasis treated with CF101 2 mg twice daily versus placebo is ongoing but not recruiting participants (NCT01265667).

Tofacitinib (JAK 1 and JAK 3 Inhibitor)

Tofacitinib is a JAK 1 and JAK 3 inhibitor that is available in both topical and oral formulations. Many studies have been published on tofacitinib, including a dose-ranging phase 2b trial of 197 patients randomized to placebo or tofacitinib 2, 5, or 15 mg daily in which 2.0%, 25.0% (P<.001), 40.8% (P<.0001), and 66.7% (P<.0001) of participants in each treatment group, respectively, achieved PASI 75 at week 12.¹⁹ Another 12-week phase 2b trial in patients with moderate to severe psoriasis explored the effectiveness of oral formulations of tofacitinib based on body location, namely the head and neck, arms, trunk, and legs.²⁰ Designed with twice-daily placebo and tofacitinib 2-, 5-, and 15-mg treatment arms, the target plaque severity score demonstrated a statistically significant dose-responsive improvement in each of the 4 anatomic regions (P<.01).

Two randomized, double-blinded, placebo-controlled phase 3 trials of tofacitinib have been completed. One trial compared the safety and effectiveness of tofacitinib and etanercept in patients with moderate to severe psoriasis.²¹ The 329 participants were randomized to treatment with oral tofacitinib 5 mg or 10 mg twice daily with placebo subcutaneous (SQ) injections twice weekly; oral placebo twice daily with etanercept 50-mg SQ injections twice weekly; or oral placebo twice daily with placebo SQ injection twice weekly. At week 12, PASI 75 was achieved in 39.51%, 63.64%, 58.81%, and 5.61% of participants in each treatment group, respectively. Thus, tofacitinib 10 mg and etanercept 50 mg were the first and second best performers in this study design.²¹

In the other phase 3 trial, the efficacy and safety of treatment, treatment withdrawal, and subsequent resumption of treatment with tofacitinib was examined in 290 patients who received either tofacitinib 5 mg or 10 mg or placebo twice daily for 24 weeks.²² In the withdrawal period, the percentage of patients who maintained a PASI 75 response in the tofacitinib 5-mg group was 56.2% versus 23.3% in the placebo group at week 16 (P<.0008). In the 10-mg group, 62.3% of participants maintained PASI 75 at week 16 versus 26.1% in the placebo group (P<.0001). During the re-treatment period for those who showed a greater than 50% reduction in week 24 PASI during treatment withdrawal (N=102), 50.0% of the tofacitinib 5-mg group showed PASI 75 versus 31.58% of the placebo group at week 16. In the tofacitinib 10-mg group, PASI 75 was seen in 0% versus 50.85% in the placebo group. Of note, only 5 participants who demonstrated a greater than 50% reduction in week 24 PASI response following withdrawal of therapy were in the tofacitinib 5- or 10-mg groups, as the rest were in the placebo group.²²

FP187 (Fumaric Acid Ester)

FP187 (Forward Pharma A/S) is an oral fumaric acid ester whose underlying mechanism is thought to be elevation of glutathione levels that decreases the amount of inflammatory cytokines by blocking the translocation of nuclear factor κB. Other fumaric acid esters such as monoethyl fumarate and dimethyl fumarate have been used in Europe for the management of psoriasis.²³ A phase 2 study of the safety and effectiveness of FP187 for moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01230138). A phase 3 trial examining the efficacy of FP187 in managing moderate to severe psoriasis was not yet open for participant recruitment at the time of publication (NCT01815723).

Doxercalciferol (Vitamin D₂ Analogue)

Doxercalciferol (1α-hydroxyvitamin D₂; Genzyme Corporation, a Sanofi company) is an oral prodrug of vitamin D.²⁴ Topical preparations of vitamin D analogues approved by the US Food and Drug Administration such as calcipotriene are mainstays in psoriasis management. Doxercalciferol has been used for other therapeutic applications such as decreasing elevated parathyroid hormone levels.²⁵ Research has demonstrated that CYP24A1 can extrahepatically regulate the activation of vitamin D prodrugs in cutaneous tissues.²⁶ In a phase 2 study examining the efficacy and safety of doxercalciferol in patients with moderate to severe psoriasis, 111 patients were randomized to placebo or doxercalciferol 2.5, 5, or 7.5 mg daily for 24 weeks (NCT00601107). At week 12, PASI 50 was similar regardless of the treatment administered, reported at 20.0%, 20.0%, 17.9%, and 20.0%, respectively (P=1.000).²⁷

GSK2586184 (JAK 1 Inhibitor)

GSK2586184 is an oral JAK 1 inhibitor. A placebo-controlled, double-blind, dose-dependent phase 2 study of GSK2586184 in patients with chronic plaque psoriasis who were randomized to placebo or GSK2586184 100, 200, and 400 mg twice daily for 84 days has been completed, but the results were not available at the time of publication (NCT01782664). Of note, despite clinical promise, due to potential adverse effects of the medication that included a possible interaction with statin medication, the manufacturer decided against pursuing GSK2586184 as a treatment in the management of psoriasis.²⁸

Voclosporin (Calcineurin Inhibitor)

Voclosporin (formerly known as ISA247)(Aurinia Pharmaceuticals Inc) is an oral calcineurin inhibitor that is purported to be as effective as cyclospor-ine A with less associated toxicity. A 12-week randomized, placebo-controlled, double-blind phase 2 trial demonstrated PASI 75 in 0%, 18.2%, and 66.7% of 201 participants receiving placebo, voclospo-rin 0.5 mg/kg, and voclosporin 1.5 mg/kg twice daily, respectively (P<.0001). Elevated serum creatinine levels within the high range of normal were noted in the 1.5-mg/kg group.²⁹ A 12-week phase 3 study of 451 patients randomized to placebo or voclospo-rin 0.2-, 0.3-, or 0.4-mg/kg treatment groups similarly demonstrated a dose-responsive PASI 75 of 4%, 16%, 25%, and 47%, respectively, that was maintained at week 24. Mild to moderate decreases in glomerular filtration rates were noted in 8 patients in the 0.3- and 0.4-mg/kg subsets.³⁰ Another phase 2 study of voclosporin in patients with moderate to severe psoriasis showed improvements according to the psoriasis disability index and dermatology life quality index.³¹

Three randomized, placebo-controlled, double-blind phase 3 trials have been completed for voclosporin, but the results were not available at the time of publication. The phase 3 ESSENCE trial compared voclosporin to placebo and ciclosporin controls (NCT00408187). Two phase 3 trials known as the SPIRIT trials—one a 12-week study (NCT00244842) and the other a 36-week extension trial (NCT00258713)—compared the efficacy of placebo to voclosporin administered at 0.2-, 0.3-, and 0.4-mg/kg doses.

KD025 (ROCK 2 Inhibitor)

KD025 (Kadmon Corporation, LLC) is an oral ROCK 2 inhibitor. The inhibition of ROCK in the ras homolog gene family, member A/ROCK pathway has been targeted therapeutically for pulmonary arterial hypertension,³² glaucoma,³³ and many other uses. A phase 2a study assessing the tolerability and safety profile of KD025 in patients with moderate to severe psoriasis was completed, but the results were not available at the time of publication (NCT02106195).

LAS41008 (Fumaric Acid Ester)

LAS41008 (Almirall, S.A.) is purported to be an oral dimethyl fumarate that inhibits endothelial cell proliferation, migration, and differentiation.³⁴ A phase 3 trial comparing the safety and effectiveness of LAS41008, LASW1835 (an active comparator), and placebo in patients with moderate to severe psoriasis is ongoing but not recruiting participants (NCT01726933).

LEO 22811 (Anti-inflammatory)

LEO 22811 (LEO Pharma) is an oral anti-inflammatory agent for the treatment of psoriasis. Two clinical trials have been completed, the results of which have not yet been published. A phase 1 trial assessing the tolerability and safety profile of LEO 22811 (NCT00833872) and a phase 2 proof-of-concept study assessing dose response of LEO 22811 versus placebo (NCT01116895) were completed, but the results were not available at the time of publication.

Baricitinib (JAK 1 and JAK 2 Inhibitor)

As noted above, baricitinib (LY3009104 or INCB28050) is a JAK 1 and JAK 2 inhibitor. A phase 2b trial examining dose response for LY3009104 or baricitinib administration in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01490632).

Talarozole (CYP26 Inhibitor)

Talarozole (formerly known as R115866)(GlaxoSmithKline) is a selective oral CYP26 inhibitor that could serve to regulate the degradation of all-trans retinoic acid in the management of conditions such as acne and psoriasis. One phase 2 nonrandomized, open-label study (NCT00725348) and another phase 2 randomized, placebo-controlled, double-blind, dose-dependent trial examining the effectiveness and safety profile of 12-week talarozole treatment in patients with severe plaque psoriasis have been completed, but the results were not available at the time of publication (NCT00716144).

R3421 or BCX-4208 (PNP Inhibitor)

R3421 or BCX-4208 (BioCryst Pharmaceuticals, Inc/Hoffman–La Roche) is an oral PNP inhibitor that may help regulate apoptosis of T cells and B cells.³⁵ A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT00504270).

RWJ-445380 (Cathepsin S Inhibitor)

RWJ-445380 (Alza Corporation, DE) is an oral cathepsin S inhibitor. Cathepsin S is produced by antigen-presenting cells and activates CD4⁺ T cells via presentation of antigen by class II major histocompatibility complex.³⁶ A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial evaluating the tolerability, safety, pharmacodynamics, and pharmacokinetics of RWJ-445380 in patients with plaque psoriasis has been completed, but the results were not available at the time of publication (NCT00396422).

SRT2104 (Sirtuin 1 Activator)

SRT2104 (GlaxoSmithKline) is a selective oral NAD⁺-dependent deacetylase sirtuin 1 activator. Sirtuins help regulate apoptosis, inflammation, and other important cellular mechanisms.³⁷ A randomized, open-label phase 1 trial examining drug bioavailability (NCT01702493) and a randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial studying the efficacy, tolerability, and safety of SRT2104 in patients with moderate to severe psoriasis have been completed (NCT01154101), but the results were not available at the time of publication.

VB-201 (Oxidized Phospholipid)

VB-201 (VBL Therapeutics) is an orally administered oxidized phospholipid analogue with anti-inflammatory effects.³⁸ Oxidized phospholipids are another element in the intricate spectrum of inflammatory mediators. A randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial of VB-201 20 mg or 80 mg daily in patients with moderate to severe psoriasis was completed, but the results were not available at the time of publication (NCT01001468). Another randomized, placebo-controlled, double-blind, dose-dependent phase 2 trial of VB-201 80 mg and 160 mg twice daily in patients with moderate to severe psoriasis has been completed, but the results were not available at the time of publication (NCT01837420).

Conclusion

We are living in an exciting time in the treatment of psoriasis and PsA, with promising novel therapies afforded by the discovery of new therapeutic targets. In this 3-part series, we have reviewed topical, systemic, and biologic therapies that currently are in phase 2 through phase 4 clinical trials or have recently been approved by the US Food and Drug Administration for the management of psoriasis and PsA. These treatments offer patients and their caregivers the prospect of more targeted therapeutic regimens that offer enhanced clinical outcomes with more favorable side-effect profiles. As clinicians and researchers build upon this knowledge in the years to come, we can offer psoriasis patients an increasingly diverse and powerful therapeutic armamentarium.

VANCOUVER – Touch impairment is an important but largely unappreciated aspect of quality-of-life impairment in psoriasis, Dr. April Armstrong said at the World Congress of Dermatology.

“Touch avoidance is a new concept in dermatology, and I think it’s great because it really brings home a humanistic aspect to research,” observed Dr. Armstrong, director of the psoriasis program at the University of Colorado, Denver.

“Touch is a fundamental human gesture that conveys understanding, connection, validation, as well as being cared for or caring for someone,” she added.

She presented an online study of 1,109 psoriasis patients, 70% of whom were female. When asked whether within the past 2 weeks they had avoided hugging, shaking hands, or other touching of others, or of being touched, because of how their skin looks or feels, 48% responded yes. On a 0-10 scale, 27% of the overall patient population rated themselves as having touch avoidance at the level of 4-10, corresponding to moderate to severe.

In a multivariate analysis, the prevalence or severity of touch avoidance didn’t vary by gender. However, touch avoidance was reported most often by patients under age 25 years. And touch avoidance was strongly associated with disease severity: Those with mild psoriasis as defined by body surface area of involvement were only about one-third as likely to report touch avoidance, compared with those with severe disease. Also, psoriatic itching was an important correlate of touch avoidance: Those with itch were roughly fivefold more likely to report recent touch avoidance.

In addition, patients with psoriasis on exposed areas such as the face and neck or in sensitive areas such as the genitalia were more likely to report touch avoidance.

Touch avoidance had a strong negative impact on quality of life. Scores on the Dermatology Life Quality Index averaged nearly threefold higher – indicating worse quality of life – in participants who reported touch avoidance. They were at similarly increased risk for mild or greater depressive symptoms based upon their scores on the Quick Inventory of Depressive Symptoms.

Thus, touch avoidance is an important new patient-reported outcome, and these study results open up a new area of psoriasis research, according to Dr. Armstrong.

“Future research may reveal that therapies offering clearance of psoriasis, particularly in sensitive areas, could lead to large improvements in the initiation and acceptance of interpersonal touch by patients with psoriasis,” she noted.

This study was supported by the National Psoriasis Foundation. Dr. Armstrong reported receiving research grants from and/or serving as a consultant to more than half a dozen pharmaceutical companies as well as the National Institutes of Health.

[email protected]

VANCOUVER – Touch impairment is an important but largely unappreciated aspect of quality-of-life impairment in psoriasis, Dr. April Armstrong said at the World Congress of Dermatology.

“Touch avoidance is a new concept in dermatology, and I think it’s great because it really brings home a humanistic aspect to research,” observed Dr. Armstrong, director of the psoriasis program at the University of Colorado, Denver.

“Touch is a fundamental human gesture that conveys understanding, connection, validation, as well as being cared for or caring for someone,” she added.

She presented an online study of 1,109 psoriasis patients, 70% of whom were female. When asked whether within the past 2 weeks they had avoided hugging, shaking hands, or other touching of others, or of being touched, because of how their skin looks or feels, 48% responded yes. On a 0-10 scale, 27% of the overall patient population rated themselves as having touch avoidance at the level of 4-10, corresponding to moderate to severe.

In a multivariate analysis, the prevalence or severity of touch avoidance didn’t vary by gender. However, touch avoidance was reported most often by patients under age 25 years. And touch avoidance was strongly associated with disease severity: Those with mild psoriasis as defined by body surface area of involvement were only about one-third as likely to report touch avoidance, compared with those with severe disease. Also, psoriatic itching was an important correlate of touch avoidance: Those with itch were roughly fivefold more likely to report recent touch avoidance.

In addition, patients with psoriasis on exposed areas such as the face and neck or in sensitive areas such as the genitalia were more likely to report touch avoidance.

Touch avoidance had a strong negative impact on quality of life. Scores on the Dermatology Life Quality Index averaged nearly threefold higher – indicating worse quality of life – in participants who reported touch avoidance. They were at similarly increased risk for mild or greater depressive symptoms based upon their scores on the Quick Inventory of Depressive Symptoms.

Thus, touch avoidance is an important new patient-reported outcome, and these study results open up a new area of psoriasis research, according to Dr. Armstrong.

“Future research may reveal that therapies offering clearance of psoriasis, particularly in sensitive areas, could lead to large improvements in the initiation and acceptance of interpersonal touch by patients with psoriasis,” she noted.

This study was supported by the National Psoriasis Foundation. Dr. Armstrong reported receiving research grants from and/or serving as a consultant to more than half a dozen pharmaceutical companies as well as the National Institutes of Health.

[email protected]

VANCOUVER – Touch impairment is an important but largely unappreciated aspect of quality-of-life impairment in psoriasis, Dr. April Armstrong said at the World Congress of Dermatology.

“Touch avoidance is a new concept in dermatology, and I think it’s great because it really brings home a humanistic aspect to research,” observed Dr. Armstrong, director of the psoriasis program at the University of Colorado, Denver.

“Touch is a fundamental human gesture that conveys understanding, connection, validation, as well as being cared for or caring for someone,” she added.

She presented an online study of 1,109 psoriasis patients, 70% of whom were female. When asked whether within the past 2 weeks they had avoided hugging, shaking hands, or other touching of others, or of being touched, because of how their skin looks or feels, 48% responded yes. On a 0-10 scale, 27% of the overall patient population rated themselves as having touch avoidance at the level of 4-10, corresponding to moderate to severe.

In a multivariate analysis, the prevalence or severity of touch avoidance didn’t vary by gender. However, touch avoidance was reported most often by patients under age 25 years. And touch avoidance was strongly associated with disease severity: Those with mild psoriasis as defined by body surface area of involvement were only about one-third as likely to report touch avoidance, compared with those with severe disease. Also, psoriatic itching was an important correlate of touch avoidance: Those with itch were roughly fivefold more likely to report recent touch avoidance.

In addition, patients with psoriasis on exposed areas such as the face and neck or in sensitive areas such as the genitalia were more likely to report touch avoidance.

Touch avoidance had a strong negative impact on quality of life. Scores on the Dermatology Life Quality Index averaged nearly threefold higher – indicating worse quality of life – in participants who reported touch avoidance. They were at similarly increased risk for mild or greater depressive symptoms based upon their scores on the Quick Inventory of Depressive Symptoms.

Thus, touch avoidance is an important new patient-reported outcome, and these study results open up a new area of psoriasis research, according to Dr. Armstrong.

“Future research may reveal that therapies offering clearance of psoriasis, particularly in sensitive areas, could lead to large improvements in the initiation and acceptance of interpersonal touch by patients with psoriasis,” she noted.

This study was supported by the National Psoriasis Foundation. Dr. Armstrong reported receiving research grants from and/or serving as a consultant to more than half a dozen pharmaceutical companies as well as the National Institutes of Health.

[email protected]

Delayed diagnosis of psoriatic arthritis (PsA) can have profound effects, such as irreversible joint damage, poor quality of life, and decreased response to treatment; however, many cases of PsA are not diagnosed until up to 2 years after onset of symptoms. Dr. Saakshi Khattri discusses screening questions for PsA that dermatologists should address when treating patients with psoriasis and emphasizes that collaboration between dermatologists and rheumatologists is essential to early diagnosis and treatment of PsA.

The psoriasis audiocast series is created in collaboration with Cutis^® and the National Psoriasis Foundation^®.

Delayed diagnosis of psoriatic arthritis (PsA) can have profound effects, such as irreversible joint damage, poor quality of life, and decreased response to treatment; however, many cases of PsA are not diagnosed until up to 2 years after onset of symptoms. Dr. Saakshi Khattri discusses screening questions for PsA that dermatologists should address when treating patients with psoriasis and emphasizes that collaboration between dermatologists and rheumatologists is essential to early diagnosis and treatment of PsA.

The psoriasis audiocast series is created in collaboration with Cutis^® and the National Psoriasis Foundation^®.

Delayed diagnosis of psoriatic arthritis (PsA) can have profound effects, such as irreversible joint damage, poor quality of life, and decreased response to treatment; however, many cases of PsA are not diagnosed until up to 2 years after onset of symptoms. Dr. Saakshi Khattri discusses screening questions for PsA that dermatologists should address when treating patients with psoriasis and emphasizes that collaboration between dermatologists and rheumatologists is essential to early diagnosis and treatment of PsA.

The psoriasis audiocast series is created in collaboration with Cutis^® and the National Psoriasis Foundation^®.