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First interchangeability study for an adalimumab biosimilar has begun
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
Unresolved fatigue lingers for most PsA patients
MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.
A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.
“Pain is the most important symptom in patients with psoriatic arthritis, but fatigue is second-most important. It has a huge impact on patient quality of life,” she said.
“Just treating inflammation doesn’t do it all. We need to do more, think differently, think outside the box” of relying primarily on disease-modifying antirheumatic drugs, especially biological drugs, to resolve symptoms in PsA patients. “We should not think that biologicals do it all.”
The upshot is that PsA patients may have their inflammatory markers under control with treatment but still report that they don’t feel well, have pain, are tired, and have no energy.
But Dr. Jørgensen admitted that she couldn’t say with any certainty what additional interventions might help resolve pain and fatigue in PsA patients.
“I tell them to walk and be active; I think that may help. But we don’t really know what to do,” she said in an interview.
Her study included 1,062 PsA patients enrolled during December 2013-December 2014 in the Danish DANBIO registry of patients with inflammatory arthritides who received treatment with a biological drug. These participants also agreed to both complete a painDETECT Questionnaire and to rate their fatigue on a visual analog scale.
Dr. Jørgensen and her associates designated a visual analog scale score of at least 57 out of 100 as representing moderate or severe fatigue and found that 542 (51%) of the patients had fatigue self-ratings that fell in this range. Patients with this higher fatigue level also had significantly worse PsA with significantly higher numbers of swollen and tender joints, higher painDETECT scores, and higher scores on their Health Assessment Questionnaire and their 28-joint Disease Activity Score using C-reactive protein.
When the researchers ran a principal component analysis on these data, they identified three primary factors contributing to fatigue. Chronic inflammation contributed 31% of the fatigue effect, chronification contributed 17%, and chronic pain contributed 15%, Dr. Jørgensen reported.
Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.
A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.
“Pain is the most important symptom in patients with psoriatic arthritis, but fatigue is second-most important. It has a huge impact on patient quality of life,” she said.
“Just treating inflammation doesn’t do it all. We need to do more, think differently, think outside the box” of relying primarily on disease-modifying antirheumatic drugs, especially biological drugs, to resolve symptoms in PsA patients. “We should not think that biologicals do it all.”
The upshot is that PsA patients may have their inflammatory markers under control with treatment but still report that they don’t feel well, have pain, are tired, and have no energy.
But Dr. Jørgensen admitted that she couldn’t say with any certainty what additional interventions might help resolve pain and fatigue in PsA patients.
“I tell them to walk and be active; I think that may help. But we don’t really know what to do,” she said in an interview.
Her study included 1,062 PsA patients enrolled during December 2013-December 2014 in the Danish DANBIO registry of patients with inflammatory arthritides who received treatment with a biological drug. These participants also agreed to both complete a painDETECT Questionnaire and to rate their fatigue on a visual analog scale.
Dr. Jørgensen and her associates designated a visual analog scale score of at least 57 out of 100 as representing moderate or severe fatigue and found that 542 (51%) of the patients had fatigue self-ratings that fell in this range. Patients with this higher fatigue level also had significantly worse PsA with significantly higher numbers of swollen and tender joints, higher painDETECT scores, and higher scores on their Health Assessment Questionnaire and their 28-joint Disease Activity Score using C-reactive protein.
When the researchers ran a principal component analysis on these data, they identified three primary factors contributing to fatigue. Chronic inflammation contributed 31% of the fatigue effect, chronification contributed 17%, and chronic pain contributed 15%, Dr. Jørgensen reported.
Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.
A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.
“Pain is the most important symptom in patients with psoriatic arthritis, but fatigue is second-most important. It has a huge impact on patient quality of life,” she said.
“Just treating inflammation doesn’t do it all. We need to do more, think differently, think outside the box” of relying primarily on disease-modifying antirheumatic drugs, especially biological drugs, to resolve symptoms in PsA patients. “We should not think that biologicals do it all.”
The upshot is that PsA patients may have their inflammatory markers under control with treatment but still report that they don’t feel well, have pain, are tired, and have no energy.
But Dr. Jørgensen admitted that she couldn’t say with any certainty what additional interventions might help resolve pain and fatigue in PsA patients.
“I tell them to walk and be active; I think that may help. But we don’t really know what to do,” she said in an interview.
Her study included 1,062 PsA patients enrolled during December 2013-December 2014 in the Danish DANBIO registry of patients with inflammatory arthritides who received treatment with a biological drug. These participants also agreed to both complete a painDETECT Questionnaire and to rate their fatigue on a visual analog scale.
Dr. Jørgensen and her associates designated a visual analog scale score of at least 57 out of 100 as representing moderate or severe fatigue and found that 542 (51%) of the patients had fatigue self-ratings that fell in this range. Patients with this higher fatigue level also had significantly worse PsA with significantly higher numbers of swollen and tender joints, higher painDETECT scores, and higher scores on their Health Assessment Questionnaire and their 28-joint Disease Activity Score using C-reactive protein.
When the researchers ran a principal component analysis on these data, they identified three primary factors contributing to fatigue. Chronic inflammation contributed 31% of the fatigue effect, chronification contributed 17%, and chronic pain contributed 15%, Dr. Jørgensen reported.
Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Visual analog scoring showed 51% of patients rated their fatigue as 57 or higher on a 0-100 scale.
Data source: A review of 1,062 Danish psoriatic arthritis patients treated with a biological drug and enrolled in the DANBIO registry
Disclosures: Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
Children with psoriasis face multitude of comorbidities
CHICAGO – Children with psoriasis face a multitude of potential problems and comorbidities, ranging from anxiety and depression to obesity and metabolic disease, so early and proactive identification is key.
“These children are more likely to engage in high-risk behavior such as use of alcohol, tobacco, and drugs – a trend that continues into adult ages,” Kelly M. Cordoro, MD, said at the World Congress for Pediatric Dermatology. “They also have a higher association with inflammatory bowel disease, among other conditions. Those of us who care for pediatric psoriasis patients are on the front lines of recognition of these potential comorbidities, which allow for, ideally, prevention and certainly, early intervention.”
Obesity ranks as the most well understood comorbidity of psoriasis in children. Study after study has demonstrated this association. In addition, obese children with psoriasis may also harbor components of the metabolic syndrome – hypertension, dyslipidemia, and diabetes. “They’re not as much at risk for metabolic syndrome in the absence of obesity, but there’s still a small signal,” Dr. Cordoro said. “We ask ourselves this question as clinicians: Are these pediatric patients at risk for cardiovascular and cerebrovascular disease as they get older? In other words, what is the health of a 6-year-old, obese child with severe psoriasis, who may also have other components of the metabolic syndrome, going to be like when he is 35 or 40? Are these the children who go on to have cardiovascular events as documented in adult studies of psoriasis?”
To date, several studies have identified a clear link between psoriasis and obesity, and between psoriasis and hypertension, diabetes, and dyslipidemia in certain populations. “There is a dose-response effect,” Dr. Cordoro said. “The more severe the psoriasis, the more likely the patient is to be obese, and vice versa.” In one study, researchers analyzed 409 psoriasis patients up to age 17 years in nine countries (JAMA Dermatol. 2013;149:166-76). They concluded that globally, children with psoriasis have excess adiposity and increased central adiposity regardless of psoriasis severity. The researchers used multiple measures of adiposity, not just body mass index, but also waist circumference and waist-to-height ratio. “Waist circumference and waist-to-height ratio are surrogates for central and visceral adiposity,” said Dr. Cordoro, who was involved with the study. “And central adiposity may be a more sensitive indicator of metabolic disease and cardiovascular risk than BMI [body mass index] alone.”
Another study demonstrated that high adiposity preceded psoriasis by up to 2 years in 93% of overweight or obese psoriatic children (JAMA Dermatol. 2014;150:573-4).
In a more recent analysis, researchers evaluated lipid function in 44 psoriatic children (J Invest Dermatol. 2016;136[1]:67-73). Compared with age-matched controls, children with psoriasis were found to have higher waist-to-hip ratio, higher insulin resistance, and 27% were obese. “There was no difference in fasting lipid levels but the blood profiles had atherogenic markers that are worrisome for ongoing risk for atherosclerosis, cardiovascular disease, and cerebrovascular disease,” Dr. Cordoro said.
Research among adults has demonstrated that psoriasis confers an independent risk of atherosclerosis, MI, stroke, and early cardiovascular-related mortality, the so-called “psoriatic march.” Theoretically, Dr. Cordoro said, severe psoriasis sets up a state of chronic systemic inflammation, which leads to insulin resistance, which predisposes affected individuals to endothelial dysfunction, and eventually can lead to atherosclerosis. “When atherosclerosis becomes unstable, now you’ve gone from having severe psoriasis into a situation where the chronic inflammation may have predisposed you to having a thrombotic event such as a heart attack or stroke,” she said. “Obesity replicates that same pattern. What does this all mean? Is this real or is this just a theory? We don’t know, but it’s certainly biologically plausible. It’s not been proven with long-term prospective studies, which we need.”
Dr. Cordoro went on to discuss the importance of assessing young psoriasis patients for psychiatric and emotional comorbidities, including anxiety, depression, and eating disorders. “These kids can become socially isolated, which can lead to more downstream effects: more anxiety, more depression, sometimes overeating and obesity,” she said. “It’s not only that the patient has situational anxiety or depression, the notion that ‘My skin looks terrible. I’m really depressed about it;’ it’s more than that. It turns out that the same inflammatory milieu in psoriasis lesions can be replicated in the brain inflammatory milieu in patients with depression and other psychiatric disorders. That’s fascinating to recognize that these comorbidities can be intrinsic. There’s a biological basis and not just a downstream effect.”
She advises clinicians who care for children with psoriasis to keep potential comorbidities in mind, and to make sure families understand that there can be psychiatric, emotional, and physical consequences to undertreated disease. “We do not yet know how to risk stratify these patients. At the very least, you want to identify overweight or obese children with moderate to severe disease for early intervention,” Dr. Cordoro said. “Weight loss and lifestyle interventions are the hardest goals to accomplish but are really critical. Prevention is the best strategy. We can help ourselves and help our patients by referring to obesity and nutrition experts who can not only help the child but get the entire family involved.”
In a consensus statement published online in JAMA Dermatology, a multidisciplinary panel of experts including Dr. Cordoro offer an evidence- and consensus-based approach to screening children with psoriasis, based on a review of 153 manuscripts in the medical literature. The panel recommends that all psoriasis patients 2-21 years of age should undergo annual measurements of blood pressure and BMI, and screenings for arthritis and mood disorders. “These don’t have to be formal mood disorder screens,” Dr. Cordoro said. “They can be informal questioning about anxiety and depression, like ‘How is your psoriasis impacting you? How do you feel about your psoriasis? What do you say when people ask you about your psoriasis?’ It’s also important to ask overweight patients what they’re doing to keep their weight in check. Oftentimes when you ask a question about mood or impact of disease or stigma or bullying, the child will be completely silent and either stay silent or start crying or start telling you their stories. It’s really important to ask, because it validates that their concerns are more than just about vanity but about their overall health, and that is a critical difference.”
Dr. Cordoro disclosed that she is a consultant for Pfizer and Valeant.
CHICAGO – Children with psoriasis face a multitude of potential problems and comorbidities, ranging from anxiety and depression to obesity and metabolic disease, so early and proactive identification is key.
“These children are more likely to engage in high-risk behavior such as use of alcohol, tobacco, and drugs – a trend that continues into adult ages,” Kelly M. Cordoro, MD, said at the World Congress for Pediatric Dermatology. “They also have a higher association with inflammatory bowel disease, among other conditions. Those of us who care for pediatric psoriasis patients are on the front lines of recognition of these potential comorbidities, which allow for, ideally, prevention and certainly, early intervention.”
Obesity ranks as the most well understood comorbidity of psoriasis in children. Study after study has demonstrated this association. In addition, obese children with psoriasis may also harbor components of the metabolic syndrome – hypertension, dyslipidemia, and diabetes. “They’re not as much at risk for metabolic syndrome in the absence of obesity, but there’s still a small signal,” Dr. Cordoro said. “We ask ourselves this question as clinicians: Are these pediatric patients at risk for cardiovascular and cerebrovascular disease as they get older? In other words, what is the health of a 6-year-old, obese child with severe psoriasis, who may also have other components of the metabolic syndrome, going to be like when he is 35 or 40? Are these the children who go on to have cardiovascular events as documented in adult studies of psoriasis?”
To date, several studies have identified a clear link between psoriasis and obesity, and between psoriasis and hypertension, diabetes, and dyslipidemia in certain populations. “There is a dose-response effect,” Dr. Cordoro said. “The more severe the psoriasis, the more likely the patient is to be obese, and vice versa.” In one study, researchers analyzed 409 psoriasis patients up to age 17 years in nine countries (JAMA Dermatol. 2013;149:166-76). They concluded that globally, children with psoriasis have excess adiposity and increased central adiposity regardless of psoriasis severity. The researchers used multiple measures of adiposity, not just body mass index, but also waist circumference and waist-to-height ratio. “Waist circumference and waist-to-height ratio are surrogates for central and visceral adiposity,” said Dr. Cordoro, who was involved with the study. “And central adiposity may be a more sensitive indicator of metabolic disease and cardiovascular risk than BMI [body mass index] alone.”
Another study demonstrated that high adiposity preceded psoriasis by up to 2 years in 93% of overweight or obese psoriatic children (JAMA Dermatol. 2014;150:573-4).
In a more recent analysis, researchers evaluated lipid function in 44 psoriatic children (J Invest Dermatol. 2016;136[1]:67-73). Compared with age-matched controls, children with psoriasis were found to have higher waist-to-hip ratio, higher insulin resistance, and 27% were obese. “There was no difference in fasting lipid levels but the blood profiles had atherogenic markers that are worrisome for ongoing risk for atherosclerosis, cardiovascular disease, and cerebrovascular disease,” Dr. Cordoro said.
Research among adults has demonstrated that psoriasis confers an independent risk of atherosclerosis, MI, stroke, and early cardiovascular-related mortality, the so-called “psoriatic march.” Theoretically, Dr. Cordoro said, severe psoriasis sets up a state of chronic systemic inflammation, which leads to insulin resistance, which predisposes affected individuals to endothelial dysfunction, and eventually can lead to atherosclerosis. “When atherosclerosis becomes unstable, now you’ve gone from having severe psoriasis into a situation where the chronic inflammation may have predisposed you to having a thrombotic event such as a heart attack or stroke,” she said. “Obesity replicates that same pattern. What does this all mean? Is this real or is this just a theory? We don’t know, but it’s certainly biologically plausible. It’s not been proven with long-term prospective studies, which we need.”
Dr. Cordoro went on to discuss the importance of assessing young psoriasis patients for psychiatric and emotional comorbidities, including anxiety, depression, and eating disorders. “These kids can become socially isolated, which can lead to more downstream effects: more anxiety, more depression, sometimes overeating and obesity,” she said. “It’s not only that the patient has situational anxiety or depression, the notion that ‘My skin looks terrible. I’m really depressed about it;’ it’s more than that. It turns out that the same inflammatory milieu in psoriasis lesions can be replicated in the brain inflammatory milieu in patients with depression and other psychiatric disorders. That’s fascinating to recognize that these comorbidities can be intrinsic. There’s a biological basis and not just a downstream effect.”
She advises clinicians who care for children with psoriasis to keep potential comorbidities in mind, and to make sure families understand that there can be psychiatric, emotional, and physical consequences to undertreated disease. “We do not yet know how to risk stratify these patients. At the very least, you want to identify overweight or obese children with moderate to severe disease for early intervention,” Dr. Cordoro said. “Weight loss and lifestyle interventions are the hardest goals to accomplish but are really critical. Prevention is the best strategy. We can help ourselves and help our patients by referring to obesity and nutrition experts who can not only help the child but get the entire family involved.”
In a consensus statement published online in JAMA Dermatology, a multidisciplinary panel of experts including Dr. Cordoro offer an evidence- and consensus-based approach to screening children with psoriasis, based on a review of 153 manuscripts in the medical literature. The panel recommends that all psoriasis patients 2-21 years of age should undergo annual measurements of blood pressure and BMI, and screenings for arthritis and mood disorders. “These don’t have to be formal mood disorder screens,” Dr. Cordoro said. “They can be informal questioning about anxiety and depression, like ‘How is your psoriasis impacting you? How do you feel about your psoriasis? What do you say when people ask you about your psoriasis?’ It’s also important to ask overweight patients what they’re doing to keep their weight in check. Oftentimes when you ask a question about mood or impact of disease or stigma or bullying, the child will be completely silent and either stay silent or start crying or start telling you their stories. It’s really important to ask, because it validates that their concerns are more than just about vanity but about their overall health, and that is a critical difference.”
Dr. Cordoro disclosed that she is a consultant for Pfizer and Valeant.
CHICAGO – Children with psoriasis face a multitude of potential problems and comorbidities, ranging from anxiety and depression to obesity and metabolic disease, so early and proactive identification is key.
“These children are more likely to engage in high-risk behavior such as use of alcohol, tobacco, and drugs – a trend that continues into adult ages,” Kelly M. Cordoro, MD, said at the World Congress for Pediatric Dermatology. “They also have a higher association with inflammatory bowel disease, among other conditions. Those of us who care for pediatric psoriasis patients are on the front lines of recognition of these potential comorbidities, which allow for, ideally, prevention and certainly, early intervention.”
Obesity ranks as the most well understood comorbidity of psoriasis in children. Study after study has demonstrated this association. In addition, obese children with psoriasis may also harbor components of the metabolic syndrome – hypertension, dyslipidemia, and diabetes. “They’re not as much at risk for metabolic syndrome in the absence of obesity, but there’s still a small signal,” Dr. Cordoro said. “We ask ourselves this question as clinicians: Are these pediatric patients at risk for cardiovascular and cerebrovascular disease as they get older? In other words, what is the health of a 6-year-old, obese child with severe psoriasis, who may also have other components of the metabolic syndrome, going to be like when he is 35 or 40? Are these the children who go on to have cardiovascular events as documented in adult studies of psoriasis?”
To date, several studies have identified a clear link between psoriasis and obesity, and between psoriasis and hypertension, diabetes, and dyslipidemia in certain populations. “There is a dose-response effect,” Dr. Cordoro said. “The more severe the psoriasis, the more likely the patient is to be obese, and vice versa.” In one study, researchers analyzed 409 psoriasis patients up to age 17 years in nine countries (JAMA Dermatol. 2013;149:166-76). They concluded that globally, children with psoriasis have excess adiposity and increased central adiposity regardless of psoriasis severity. The researchers used multiple measures of adiposity, not just body mass index, but also waist circumference and waist-to-height ratio. “Waist circumference and waist-to-height ratio are surrogates for central and visceral adiposity,” said Dr. Cordoro, who was involved with the study. “And central adiposity may be a more sensitive indicator of metabolic disease and cardiovascular risk than BMI [body mass index] alone.”
Another study demonstrated that high adiposity preceded psoriasis by up to 2 years in 93% of overweight or obese psoriatic children (JAMA Dermatol. 2014;150:573-4).
In a more recent analysis, researchers evaluated lipid function in 44 psoriatic children (J Invest Dermatol. 2016;136[1]:67-73). Compared with age-matched controls, children with psoriasis were found to have higher waist-to-hip ratio, higher insulin resistance, and 27% were obese. “There was no difference in fasting lipid levels but the blood profiles had atherogenic markers that are worrisome for ongoing risk for atherosclerosis, cardiovascular disease, and cerebrovascular disease,” Dr. Cordoro said.
Research among adults has demonstrated that psoriasis confers an independent risk of atherosclerosis, MI, stroke, and early cardiovascular-related mortality, the so-called “psoriatic march.” Theoretically, Dr. Cordoro said, severe psoriasis sets up a state of chronic systemic inflammation, which leads to insulin resistance, which predisposes affected individuals to endothelial dysfunction, and eventually can lead to atherosclerosis. “When atherosclerosis becomes unstable, now you’ve gone from having severe psoriasis into a situation where the chronic inflammation may have predisposed you to having a thrombotic event such as a heart attack or stroke,” she said. “Obesity replicates that same pattern. What does this all mean? Is this real or is this just a theory? We don’t know, but it’s certainly biologically plausible. It’s not been proven with long-term prospective studies, which we need.”
Dr. Cordoro went on to discuss the importance of assessing young psoriasis patients for psychiatric and emotional comorbidities, including anxiety, depression, and eating disorders. “These kids can become socially isolated, which can lead to more downstream effects: more anxiety, more depression, sometimes overeating and obesity,” she said. “It’s not only that the patient has situational anxiety or depression, the notion that ‘My skin looks terrible. I’m really depressed about it;’ it’s more than that. It turns out that the same inflammatory milieu in psoriasis lesions can be replicated in the brain inflammatory milieu in patients with depression and other psychiatric disorders. That’s fascinating to recognize that these comorbidities can be intrinsic. There’s a biological basis and not just a downstream effect.”
She advises clinicians who care for children with psoriasis to keep potential comorbidities in mind, and to make sure families understand that there can be psychiatric, emotional, and physical consequences to undertreated disease. “We do not yet know how to risk stratify these patients. At the very least, you want to identify overweight or obese children with moderate to severe disease for early intervention,” Dr. Cordoro said. “Weight loss and lifestyle interventions are the hardest goals to accomplish but are really critical. Prevention is the best strategy. We can help ourselves and help our patients by referring to obesity and nutrition experts who can not only help the child but get the entire family involved.”
In a consensus statement published online in JAMA Dermatology, a multidisciplinary panel of experts including Dr. Cordoro offer an evidence- and consensus-based approach to screening children with psoriasis, based on a review of 153 manuscripts in the medical literature. The panel recommends that all psoriasis patients 2-21 years of age should undergo annual measurements of blood pressure and BMI, and screenings for arthritis and mood disorders. “These don’t have to be formal mood disorder screens,” Dr. Cordoro said. “They can be informal questioning about anxiety and depression, like ‘How is your psoriasis impacting you? How do you feel about your psoriasis? What do you say when people ask you about your psoriasis?’ It’s also important to ask overweight patients what they’re doing to keep their weight in check. Oftentimes when you ask a question about mood or impact of disease or stigma or bullying, the child will be completely silent and either stay silent or start crying or start telling you their stories. It’s really important to ask, because it validates that their concerns are more than just about vanity but about their overall health, and that is a critical difference.”
Dr. Cordoro disclosed that she is a consultant for Pfizer and Valeant.
AT WCPD 2017
Ixekizumab helps PsA patients who failed a TNFi
MADRID – The anti–interleukin-17 drug ixekizumab, already on the U.S. market for treating psoriasis, showed efficacy and safety for treating psoriatic arthritis in patients who previously failed to respond to or tolerate a tumor necrosis factor inhibitor in a pivotal, phase 3 trial with 363 patients.
Treatment of patients with psoriatic arthritis (PsA) with ixekizumab (Taltz) led to improvements, compared with placebo, in arthritis, physical function, and psoriasis. These patients were unresponsive to or intolerant of a tumor necrosis factor inhibitor (TNFi) at rates similar to previously reported response rates for PsA patients who were TNFi naive, Peter Nash, MD, said at the European Congress of Rheumatology.
A published report with the data presented by Dr. Nash also recently appeared (Lancet. 2017;389[10086]:2317-27).
Based in part on the results from this trial, as well as results from a companion phase 3 trial that enrolled PsA patients naive to a TNFi (Ann Rheum Dis. 2017 Jan; 6[1]:79-87), the company that markets ixekizumab, Eli Lilly, filed an application with the Food and Drug Administration in early 2017 to have a new label indication for PsA, said a company spokeswoman.
“At least half of PsA patients don’t get at least a 20% improvement [an ACR20 response] on a TNFi, and so they are looking for something else,” explained Mark C. Genovese, MD, professor of medicine and director of the Rheumatology Clinic at Stanford (Calif.) University and a coinvestigator on the trial reported by Dr. Nash. “There is pent up demand” for an alternative to a TNFi for treating PsA, Dr. Genovese said in an interview.
The finding also sets ixekizumab apart from secukinumab (Cosentyx), another interleukin-17 inhibitor that already has FDA approval for treating PsA but that has not been specifically tested in PsA patients who failed or didn’t tolerate a TNFi, he noted.
The SPIRIT-P2 results also showed superior outcomes for patients treated with an ixekizumab injection once every 2 or 4 weeks, compared with placebo, by several secondary measures, including ACR50 and ACR70 rates and minimal disease activity. The ACR70 rate after 24 weeks on treatment was 23% with a dose of ixekizumab every 4 weeks and none with placebo. Minimal disease activity was reached by about a quarter of patients on either dosage of the active drug and by 3% of patients on placebo.
Despite the apparent role for ixekizumab when TNFi treatment fails, the TNFi drug class remains the clear first-line choice for PsA patients who are starting a biological drug for the first time. Not only do the TNFis have a much longer and more extensive track record but they also generally receive better insurance coverage that minimizes out-of-pocket expenses for patients, Dr. Genovese said.
SPIRIT-P2 was sponsored by Eli Lilly, the company that markets ixekizumab. Dr. Nash has been a speaker for or consultant to and has received research funding from Eli Lily and for several other companies. Dr. Genovese has been a consultant to and has received research funding from Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The anti–interleukin-17 drug ixekizumab, already on the U.S. market for treating psoriasis, showed efficacy and safety for treating psoriatic arthritis in patients who previously failed to respond to or tolerate a tumor necrosis factor inhibitor in a pivotal, phase 3 trial with 363 patients.
Treatment of patients with psoriatic arthritis (PsA) with ixekizumab (Taltz) led to improvements, compared with placebo, in arthritis, physical function, and psoriasis. These patients were unresponsive to or intolerant of a tumor necrosis factor inhibitor (TNFi) at rates similar to previously reported response rates for PsA patients who were TNFi naive, Peter Nash, MD, said at the European Congress of Rheumatology.
A published report with the data presented by Dr. Nash also recently appeared (Lancet. 2017;389[10086]:2317-27).
Based in part on the results from this trial, as well as results from a companion phase 3 trial that enrolled PsA patients naive to a TNFi (Ann Rheum Dis. 2017 Jan; 6[1]:79-87), the company that markets ixekizumab, Eli Lilly, filed an application with the Food and Drug Administration in early 2017 to have a new label indication for PsA, said a company spokeswoman.
“At least half of PsA patients don’t get at least a 20% improvement [an ACR20 response] on a TNFi, and so they are looking for something else,” explained Mark C. Genovese, MD, professor of medicine and director of the Rheumatology Clinic at Stanford (Calif.) University and a coinvestigator on the trial reported by Dr. Nash. “There is pent up demand” for an alternative to a TNFi for treating PsA, Dr. Genovese said in an interview.
The finding also sets ixekizumab apart from secukinumab (Cosentyx), another interleukin-17 inhibitor that already has FDA approval for treating PsA but that has not been specifically tested in PsA patients who failed or didn’t tolerate a TNFi, he noted.
The SPIRIT-P2 results also showed superior outcomes for patients treated with an ixekizumab injection once every 2 or 4 weeks, compared with placebo, by several secondary measures, including ACR50 and ACR70 rates and minimal disease activity. The ACR70 rate after 24 weeks on treatment was 23% with a dose of ixekizumab every 4 weeks and none with placebo. Minimal disease activity was reached by about a quarter of patients on either dosage of the active drug and by 3% of patients on placebo.
Despite the apparent role for ixekizumab when TNFi treatment fails, the TNFi drug class remains the clear first-line choice for PsA patients who are starting a biological drug for the first time. Not only do the TNFis have a much longer and more extensive track record but they also generally receive better insurance coverage that minimizes out-of-pocket expenses for patients, Dr. Genovese said.
SPIRIT-P2 was sponsored by Eli Lilly, the company that markets ixekizumab. Dr. Nash has been a speaker for or consultant to and has received research funding from Eli Lily and for several other companies. Dr. Genovese has been a consultant to and has received research funding from Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The anti–interleukin-17 drug ixekizumab, already on the U.S. market for treating psoriasis, showed efficacy and safety for treating psoriatic arthritis in patients who previously failed to respond to or tolerate a tumor necrosis factor inhibitor in a pivotal, phase 3 trial with 363 patients.
Treatment of patients with psoriatic arthritis (PsA) with ixekizumab (Taltz) led to improvements, compared with placebo, in arthritis, physical function, and psoriasis. These patients were unresponsive to or intolerant of a tumor necrosis factor inhibitor (TNFi) at rates similar to previously reported response rates for PsA patients who were TNFi naive, Peter Nash, MD, said at the European Congress of Rheumatology.
A published report with the data presented by Dr. Nash also recently appeared (Lancet. 2017;389[10086]:2317-27).
Based in part on the results from this trial, as well as results from a companion phase 3 trial that enrolled PsA patients naive to a TNFi (Ann Rheum Dis. 2017 Jan; 6[1]:79-87), the company that markets ixekizumab, Eli Lilly, filed an application with the Food and Drug Administration in early 2017 to have a new label indication for PsA, said a company spokeswoman.
“At least half of PsA patients don’t get at least a 20% improvement [an ACR20 response] on a TNFi, and so they are looking for something else,” explained Mark C. Genovese, MD, professor of medicine and director of the Rheumatology Clinic at Stanford (Calif.) University and a coinvestigator on the trial reported by Dr. Nash. “There is pent up demand” for an alternative to a TNFi for treating PsA, Dr. Genovese said in an interview.
The finding also sets ixekizumab apart from secukinumab (Cosentyx), another interleukin-17 inhibitor that already has FDA approval for treating PsA but that has not been specifically tested in PsA patients who failed or didn’t tolerate a TNFi, he noted.
The SPIRIT-P2 results also showed superior outcomes for patients treated with an ixekizumab injection once every 2 or 4 weeks, compared with placebo, by several secondary measures, including ACR50 and ACR70 rates and minimal disease activity. The ACR70 rate after 24 weeks on treatment was 23% with a dose of ixekizumab every 4 weeks and none with placebo. Minimal disease activity was reached by about a quarter of patients on either dosage of the active drug and by 3% of patients on placebo.
Despite the apparent role for ixekizumab when TNFi treatment fails, the TNFi drug class remains the clear first-line choice for PsA patients who are starting a biological drug for the first time. Not only do the TNFis have a much longer and more extensive track record but they also generally receive better insurance coverage that minimizes out-of-pocket expenses for patients, Dr. Genovese said.
SPIRIT-P2 was sponsored by Eli Lilly, the company that markets ixekizumab. Dr. Nash has been a speaker for or consultant to and has received research funding from Eli Lily and for several other companies. Dr. Genovese has been a consultant to and has received research funding from Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The ACR20 rate after 24 weeks of treatment was 53% with monthly ixekizumab and 20% on placebo.
Data source: The SPIRIT-P2 trial, a phase 3 multicenter trial with 363 patients.
Disclosures: SPIRIT-P2 was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Nash has been a speaker for or consultant to and has received research funding from Eli Lily and for several other companies. Dr. Genovese has been a consultant to and has received research funding from Eli Lilly, AbbVie, Astellas, Galapagos, Pfizer, and Vertex.
First IL-23 blocker, guselkumab, earns FDA approval for psoriasis
, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.
The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.
Results of one of the phase 3 trials, VOYAGE 1, included a significantly greater proportion of patients treated with guselkumab achieving at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) at 16 weeks, compared with placebo (73.3% vs. 2.9%). At 16 weeks, 85.1% of those treated with guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease), compared with 6.9% of those on placebo. Superior responses continued through 48 weeks.
In an active comparator arm of the study comparing guselkumab with the TNF blocker adalimumab (Humira), a significantly higher proportion of those treated with guselkumab achieved PASI 90 scores (76.3% vs. 47.9%) and IGA 0/1 scores (80.5% vs. 55.4%) at week 48. The results were published in March (J Am Acad Dermatol. 2017 Mar;76[3]:405-17).
Results of VOYAGE 2 comparing guselkumab with adalimumab included a PASI 90 rate of 66.1% at week 48 among adalimumab nonresponders who switched to guselkumab (J Am Acad Dermatol. 2017 Mar;76[3]:418-31).
The most common serious adverse effects associated with treatment included upper respiratory infections, headache, injection site reactions, arthralgias, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections, according to the company statement.
Phase 3 studies of guselkumab for active psoriatic arthritis and in comparison with secukinumab (Cosentyx) in patients with moderate to severe plaque psoriasis are underway, according to Janssen, which is marketing guselkumab as Tremfya.
, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.
The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.
Results of one of the phase 3 trials, VOYAGE 1, included a significantly greater proportion of patients treated with guselkumab achieving at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) at 16 weeks, compared with placebo (73.3% vs. 2.9%). At 16 weeks, 85.1% of those treated with guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease), compared with 6.9% of those on placebo. Superior responses continued through 48 weeks.
In an active comparator arm of the study comparing guselkumab with the TNF blocker adalimumab (Humira), a significantly higher proportion of those treated with guselkumab achieved PASI 90 scores (76.3% vs. 47.9%) and IGA 0/1 scores (80.5% vs. 55.4%) at week 48. The results were published in March (J Am Acad Dermatol. 2017 Mar;76[3]:405-17).
Results of VOYAGE 2 comparing guselkumab with adalimumab included a PASI 90 rate of 66.1% at week 48 among adalimumab nonresponders who switched to guselkumab (J Am Acad Dermatol. 2017 Mar;76[3]:418-31).
The most common serious adverse effects associated with treatment included upper respiratory infections, headache, injection site reactions, arthralgias, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections, according to the company statement.
Phase 3 studies of guselkumab for active psoriatic arthritis and in comparison with secukinumab (Cosentyx) in patients with moderate to severe plaque psoriasis are underway, according to Janssen, which is marketing guselkumab as Tremfya.
, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.
The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.
Results of one of the phase 3 trials, VOYAGE 1, included a significantly greater proportion of patients treated with guselkumab achieving at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) at 16 weeks, compared with placebo (73.3% vs. 2.9%). At 16 weeks, 85.1% of those treated with guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease), compared with 6.9% of those on placebo. Superior responses continued through 48 weeks.
In an active comparator arm of the study comparing guselkumab with the TNF blocker adalimumab (Humira), a significantly higher proportion of those treated with guselkumab achieved PASI 90 scores (76.3% vs. 47.9%) and IGA 0/1 scores (80.5% vs. 55.4%) at week 48. The results were published in March (J Am Acad Dermatol. 2017 Mar;76[3]:405-17).
Results of VOYAGE 2 comparing guselkumab with adalimumab included a PASI 90 rate of 66.1% at week 48 among adalimumab nonresponders who switched to guselkumab (J Am Acad Dermatol. 2017 Mar;76[3]:418-31).
The most common serious adverse effects associated with treatment included upper respiratory infections, headache, injection site reactions, arthralgias, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections, according to the company statement.
Phase 3 studies of guselkumab for active psoriatic arthritis and in comparison with secukinumab (Cosentyx) in patients with moderate to severe plaque psoriasis are underway, according to Janssen, which is marketing guselkumab as Tremfya.
Comorbidities in psoriatic arthritis flag worse prognosis
MADRID – Comorbidities are relatively common in psoriatic arthritis patients, and they are more prevalent in patients with a worse disease course while on initial treatment with a tumor necrosis factor inhibitor, based on data from more than 1,700 Danish patients.
The presence of comorbidities in psoriatic arthritis (PsA) patients on initial tumor necrosis factor inhibitor (TNFi) treatment “was associated with higher disease activity, shorter adherence to the first TNFi, and reduced clinical response,” Lars Erik Kristensen, MD, said at the European Congress of Rheumatology.
To better understand the possible impact of comorbidities on PsA, he and his associates reviewed 1,750 Danish patients with PsA enrolled in a national registry at the time they began treatment with a TNFi. At the time they started treatment, 1,066 (61%) had no comorbidities, 493 (28%) had one comorbidity, and 191 (11%) had two or more comorbidities.
A comparison of the subgroups with no comorbidities and those with two or more showed several important and statistically significant differences in their baseline characteristics. Patients with at least two comorbidities had longer disease duration, and they had more active disease as measured by parameters including the Disease Activity Score 28 and the Health Assessment Questionnaire. Patients with two or more comorbidities also were older and had a higher average body mass index.
Further analyses showed that patients with two or more comorbidities were 72% more like to discontinue their TNFi treatment, compared with patients with no comorbidities – a statistically significant difference, Dr. Kristensen reported.
After 6 months of TNFi treatment, patients with two or more comorbidities had lower rates of achieving the American College of Rheumatology 20%, 50%, or 70% improvement criteria compared with patients with no comorbidities. For example, an ACR20 response occurred in 40% of patients with no comorbidities and in 31% of patients with two or more comorbidities after 6 months in an adjusted analysis.
Dr. Kristensen has been a consultant to or a speaker for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Comorbidities are relatively common in psoriatic arthritis patients, and they are more prevalent in patients with a worse disease course while on initial treatment with a tumor necrosis factor inhibitor, based on data from more than 1,700 Danish patients.
The presence of comorbidities in psoriatic arthritis (PsA) patients on initial tumor necrosis factor inhibitor (TNFi) treatment “was associated with higher disease activity, shorter adherence to the first TNFi, and reduced clinical response,” Lars Erik Kristensen, MD, said at the European Congress of Rheumatology.
To better understand the possible impact of comorbidities on PsA, he and his associates reviewed 1,750 Danish patients with PsA enrolled in a national registry at the time they began treatment with a TNFi. At the time they started treatment, 1,066 (61%) had no comorbidities, 493 (28%) had one comorbidity, and 191 (11%) had two or more comorbidities.
A comparison of the subgroups with no comorbidities and those with two or more showed several important and statistically significant differences in their baseline characteristics. Patients with at least two comorbidities had longer disease duration, and they had more active disease as measured by parameters including the Disease Activity Score 28 and the Health Assessment Questionnaire. Patients with two or more comorbidities also were older and had a higher average body mass index.
Further analyses showed that patients with two or more comorbidities were 72% more like to discontinue their TNFi treatment, compared with patients with no comorbidities – a statistically significant difference, Dr. Kristensen reported.
After 6 months of TNFi treatment, patients with two or more comorbidities had lower rates of achieving the American College of Rheumatology 20%, 50%, or 70% improvement criteria compared with patients with no comorbidities. For example, an ACR20 response occurred in 40% of patients with no comorbidities and in 31% of patients with two or more comorbidities after 6 months in an adjusted analysis.
Dr. Kristensen has been a consultant to or a speaker for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Comorbidities are relatively common in psoriatic arthritis patients, and they are more prevalent in patients with a worse disease course while on initial treatment with a tumor necrosis factor inhibitor, based on data from more than 1,700 Danish patients.
The presence of comorbidities in psoriatic arthritis (PsA) patients on initial tumor necrosis factor inhibitor (TNFi) treatment “was associated with higher disease activity, shorter adherence to the first TNFi, and reduced clinical response,” Lars Erik Kristensen, MD, said at the European Congress of Rheumatology.
To better understand the possible impact of comorbidities on PsA, he and his associates reviewed 1,750 Danish patients with PsA enrolled in a national registry at the time they began treatment with a TNFi. At the time they started treatment, 1,066 (61%) had no comorbidities, 493 (28%) had one comorbidity, and 191 (11%) had two or more comorbidities.
A comparison of the subgroups with no comorbidities and those with two or more showed several important and statistically significant differences in their baseline characteristics. Patients with at least two comorbidities had longer disease duration, and they had more active disease as measured by parameters including the Disease Activity Score 28 and the Health Assessment Questionnaire. Patients with two or more comorbidities also were older and had a higher average body mass index.
Further analyses showed that patients with two or more comorbidities were 72% more like to discontinue their TNFi treatment, compared with patients with no comorbidities – a statistically significant difference, Dr. Kristensen reported.
After 6 months of TNFi treatment, patients with two or more comorbidities had lower rates of achieving the American College of Rheumatology 20%, 50%, or 70% improvement criteria compared with patients with no comorbidities. For example, an ACR20 response occurred in 40% of patients with no comorbidities and in 31% of patients with two or more comorbidities after 6 months in an adjusted analysis.
Dr. Kristensen has been a consultant to or a speaker for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point: , compared with patients with no comorbidities.
Major finding: An ACR20 response occurred in 40% of patients with no comorbidities but only 31% of those with two or more comorbidities.
Data source: Review of national registry data for 1,750 Danish psoriatic arthritis patients.
Disclosures: Dr. Kristensen has been a consultant to or a speaker for several drug companies.
FDA approves abatacept for adults with psoriatic arthritis
The Food and Drug Administration has approved abatacept, a selective T-cell costimulation modulator, for treating adults with active psoriatic arthritis (PsA), the manufacturer, Bristol-Myers Squibb, has announced.
Approval of abatacept (Orencia) was based on two randomized, double-blind, placebo-controlled studies (PsA-I and PsA-II) in 594 adults with PsA for more than 7 years, according to the July 6 announcement. Patients had active PsA (at least three swollen joints and at least three tender joints), despite previous disease-modifying antirheumatic drug (DMARD) therapy and had one qualifying psoriatic skin lesion measuring at least 2 cm in diameter. The studies included patients treated with TNF inhibitors (TNFi) previously.
In the PsA-II trial, 424 patients received weekly doses of placebo or abatacept 25 mg administered subcutaneously (SC) without a loading dose for 24 weeks, followed by open-label abatacept at a dose of 125 mg SC weekly.
Compared with those on placebo, more patients treated with abatacept 10 mg/kg IV or 125 mg SC achieved an ACR 20 (American College of Rheumatology 20) response at 24 weeks: 47.5% vs. 19.0% and 39.4% vs. 22.3%, respectively (P less than .05).
Other results included a greater proportion of abatacept SC patients with at least a 0.35 decrease from baseline on the Health Assessment Questionnaire-Disability Index: 31% vs. 24% on placebo at 24 weeks. Responses were seen regardless of prior anti-TNFi treatment and regardless of concomitant non-biologic DMARD treatment. In addition, patients on abatacept IV and SC had improvements in enthesitis and dactylitis at 24 weeks.
The safety profile of abatacept in the two studies was “consistent with the safety profile” in rheumatoid arthritis, according to the company release.
Abatacept, initially approved in 2005, was previously approved for RA in adults and for juvenile idiopathic arthritis
Find the updated prescribing information for abatacept here.
The Food and Drug Administration has approved abatacept, a selective T-cell costimulation modulator, for treating adults with active psoriatic arthritis (PsA), the manufacturer, Bristol-Myers Squibb, has announced.
Approval of abatacept (Orencia) was based on two randomized, double-blind, placebo-controlled studies (PsA-I and PsA-II) in 594 adults with PsA for more than 7 years, according to the July 6 announcement. Patients had active PsA (at least three swollen joints and at least three tender joints), despite previous disease-modifying antirheumatic drug (DMARD) therapy and had one qualifying psoriatic skin lesion measuring at least 2 cm in diameter. The studies included patients treated with TNF inhibitors (TNFi) previously.
In the PsA-II trial, 424 patients received weekly doses of placebo or abatacept 25 mg administered subcutaneously (SC) without a loading dose for 24 weeks, followed by open-label abatacept at a dose of 125 mg SC weekly.
Compared with those on placebo, more patients treated with abatacept 10 mg/kg IV or 125 mg SC achieved an ACR 20 (American College of Rheumatology 20) response at 24 weeks: 47.5% vs. 19.0% and 39.4% vs. 22.3%, respectively (P less than .05).
Other results included a greater proportion of abatacept SC patients with at least a 0.35 decrease from baseline on the Health Assessment Questionnaire-Disability Index: 31% vs. 24% on placebo at 24 weeks. Responses were seen regardless of prior anti-TNFi treatment and regardless of concomitant non-biologic DMARD treatment. In addition, patients on abatacept IV and SC had improvements in enthesitis and dactylitis at 24 weeks.
The safety profile of abatacept in the two studies was “consistent with the safety profile” in rheumatoid arthritis, according to the company release.
Abatacept, initially approved in 2005, was previously approved for RA in adults and for juvenile idiopathic arthritis
Find the updated prescribing information for abatacept here.
The Food and Drug Administration has approved abatacept, a selective T-cell costimulation modulator, for treating adults with active psoriatic arthritis (PsA), the manufacturer, Bristol-Myers Squibb, has announced.
Approval of abatacept (Orencia) was based on two randomized, double-blind, placebo-controlled studies (PsA-I and PsA-II) in 594 adults with PsA for more than 7 years, according to the July 6 announcement. Patients had active PsA (at least three swollen joints and at least three tender joints), despite previous disease-modifying antirheumatic drug (DMARD) therapy and had one qualifying psoriatic skin lesion measuring at least 2 cm in diameter. The studies included patients treated with TNF inhibitors (TNFi) previously.
In the PsA-II trial, 424 patients received weekly doses of placebo or abatacept 25 mg administered subcutaneously (SC) without a loading dose for 24 weeks, followed by open-label abatacept at a dose of 125 mg SC weekly.
Compared with those on placebo, more patients treated with abatacept 10 mg/kg IV or 125 mg SC achieved an ACR 20 (American College of Rheumatology 20) response at 24 weeks: 47.5% vs. 19.0% and 39.4% vs. 22.3%, respectively (P less than .05).
Other results included a greater proportion of abatacept SC patients with at least a 0.35 decrease from baseline on the Health Assessment Questionnaire-Disability Index: 31% vs. 24% on placebo at 24 weeks. Responses were seen regardless of prior anti-TNFi treatment and regardless of concomitant non-biologic DMARD treatment. In addition, patients on abatacept IV and SC had improvements in enthesitis and dactylitis at 24 weeks.
The safety profile of abatacept in the two studies was “consistent with the safety profile” in rheumatoid arthritis, according to the company release.
Abatacept, initially approved in 2005, was previously approved for RA in adults and for juvenile idiopathic arthritis
Find the updated prescribing information for abatacept here.
Phototherapy Coding and Documentation in the Time of Biologics
In this era of biologics for psoriasis with ever-increasing effectiveness and safety as well as patients who have less and less time to visit the physician's office, it would seem that the days of in-office UV treatments would be numbered. However, rumors of the demise of phototherapy may be greatly exaggerated. Phototherapy is still one of the safest and most cost-effective treatments for psoriasis and other dermatoses.1 Its use often is a prerequisite for biologic therapy, and it may be the only therapeutic option for certain subsets of patients, such as children, pregnant women, and immunosuppressed patients. Moreover, narrowband UVB technology has breathed new life into phototherapy, with better efficacy and less long-term risk. Although the utilization of psoralen plus UVA (PUVA) light therapy has indeed decreased over the last 2 decades, the use of UVB therapies continues to increase dramatically.2
Phototherapy Codes
There are 4 chief Current Procedural Terminology (CPT) codes for reporting phototherapy services: (1) 96900: actinotherapy (UV light treatment); (2) 96910: photochemotherapy, tar, and UVB (Goeckerman treatment) or petrolatum and UVB; (3) 96912: photochemotherapy and PUVA; and (4) 96913: photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4 to 8 hours of care under direct supervision of the physician.3
There is lack of specificity of the CPT code descriptions for phototherapy. Moreover, insurer guidance for documentation for phototherapy is vague to nonexistent, and of course whenever the use of any medical service increases, insurer scrutiny is sure to follow. Therefore, it is not surprising that dermatology practices have reported that private insurers as well as Medicare are auditing medical records for phototherapy treatments.4 In fact, recently we have seen a Midwest private insurer demand payment from dermatologists for hundreds of 96910 phototherapy services, which the insurer asserted should have been coded as 96900 because topical therapies were not applied by the dermatology staff. The insurer did not just evaluate medical records but also contacted patients directly and asked how services had been provided. Clearly, more detailed guidance for dermatologists and insurers on documentation and performance standards for each phototherapy service is needed.
Existing coding guidance for phototherapy indicates that actinotherapy (96900) defines the basic service of treating a patient with a UV light unit.5 Actinotherapy does not involve application of topical medications while the patient is in the office.
In contrast, photochemotherapy (96910) implies addition of a chemo agent to phototherapy. Despite the somewhat nonspecific nature of the code descriptor, it is apparent that application of photoenhancing agents such as tar, petrolatum, or distillates of petrolatum meet the requirements of 96910. The Coder's Desk Reference for Procedures 2017 describes 96910 as "the physician uses photosensitizing chemicals and light rays to treat skin ailments."6 Application of light-enhancing topical products should occur within the office by either staff or the patient. In fact, examination of practice expense data from the Centers for Medicare & Medicaid Services indicated that the 96910 code includes payment for clinical staff time to apply topical products as well as the cost of the topical agent(s).7
The PUVA code 96912 is defined by the use of photosensitizing psoralen medication, which can be administered topically or orally, followed by UVA treatment. In my experience, PUVA has similar performance standards with in-office application of psoralen, if applicable. If application of topical photoenhancing products occurs outside the office, the requirements of photochemotherapy are not met, and 96900 should be reported.
The 96913 code defines prolonged phototherapy service with intensive topical therapy requirements and multiple phototherapy sessions per day.3 This code is rarely reported (average of fewer than 100 times in the Medicare population per year), and most insurers do not reimburse this service.
Protecting Yourself From an Audit
In my experience, review of private insurer audits of phototherapy services has yielded important lessons. First, having a written standard operating procedure in place regarding the performance of phototherapy services and how application of topicals will be handled has been helpful in audit defense. The other key to beating audits for phototherapy services is to have detailed documentation or a flowchart in the medical record regarding the topical agent and the light administration. The medical record should include what topical agent was applied, if any; whether the topical agent was applied in the office; where the topical product was applied; and who applied the topical product. Sometimes topical product application by a physician or staff is not feasible because of patient preference or the site of application. If the patient applied the topical, document that assistance was offered and refused, along with what type of UV light was used and the dosage. Inclusion of these elements in the medical record provides a clear picture of the delivery of the phototherapy service and will aid in responding to medical record audit.
Final Thoughts
Phototherapy is a critical treatment modality that continues to be utilized frequently in the expanding armamentarium of treatments for dermatoses. Phototherapy is performed almost exclusively by dermatologists and allows dermatologists to offer a unique level of care and value in the treatment of skin disease. Careful documentation, a written standard operating procedure, and adherence to proper performance standards will allow dermatologists to be compensated fairly for this important treatment modality and pass audits that are likely to occur.
- Lapolla W, Yentzer BA, Bagel J, et al. A review of phototherapy protocols for psoriasis treatment. J Am Acad Dermatol. 2011;64:936-949.
- Simpson GL, Yelverton CB, Rittenberg S, et al. Do utilization management controls for phototherapy increase the prescription of biologics? J Dermatolog Treat. 2006;17:359-361.
- Current Procedural Terminology 2017, Professional Edition. Chicago IL: American Medical Association; 2016.
- American Academy of Dermatology Association. Insurers review billing for photochemotherapy (CPT 96910). Derm Coding Consult. Spring 2009;13:4.
- American Academy of Dermatology Association. Coding Q&A's. Derm Coding Consult. Spring 2007;11:5, 7, 8.
- Coders' Desk Reference for Procedures 2017. Chicago, IL: Optum360; 2017.
- Relative Value Scale Update Committee Database. Chicago, IL: American Medical Association; 2016.
In this era of biologics for psoriasis with ever-increasing effectiveness and safety as well as patients who have less and less time to visit the physician's office, it would seem that the days of in-office UV treatments would be numbered. However, rumors of the demise of phototherapy may be greatly exaggerated. Phototherapy is still one of the safest and most cost-effective treatments for psoriasis and other dermatoses.1 Its use often is a prerequisite for biologic therapy, and it may be the only therapeutic option for certain subsets of patients, such as children, pregnant women, and immunosuppressed patients. Moreover, narrowband UVB technology has breathed new life into phototherapy, with better efficacy and less long-term risk. Although the utilization of psoralen plus UVA (PUVA) light therapy has indeed decreased over the last 2 decades, the use of UVB therapies continues to increase dramatically.2
Phototherapy Codes
There are 4 chief Current Procedural Terminology (CPT) codes for reporting phototherapy services: (1) 96900: actinotherapy (UV light treatment); (2) 96910: photochemotherapy, tar, and UVB (Goeckerman treatment) or petrolatum and UVB; (3) 96912: photochemotherapy and PUVA; and (4) 96913: photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4 to 8 hours of care under direct supervision of the physician.3
There is lack of specificity of the CPT code descriptions for phototherapy. Moreover, insurer guidance for documentation for phototherapy is vague to nonexistent, and of course whenever the use of any medical service increases, insurer scrutiny is sure to follow. Therefore, it is not surprising that dermatology practices have reported that private insurers as well as Medicare are auditing medical records for phototherapy treatments.4 In fact, recently we have seen a Midwest private insurer demand payment from dermatologists for hundreds of 96910 phototherapy services, which the insurer asserted should have been coded as 96900 because topical therapies were not applied by the dermatology staff. The insurer did not just evaluate medical records but also contacted patients directly and asked how services had been provided. Clearly, more detailed guidance for dermatologists and insurers on documentation and performance standards for each phototherapy service is needed.
Existing coding guidance for phototherapy indicates that actinotherapy (96900) defines the basic service of treating a patient with a UV light unit.5 Actinotherapy does not involve application of topical medications while the patient is in the office.
In contrast, photochemotherapy (96910) implies addition of a chemo agent to phototherapy. Despite the somewhat nonspecific nature of the code descriptor, it is apparent that application of photoenhancing agents such as tar, petrolatum, or distillates of petrolatum meet the requirements of 96910. The Coder's Desk Reference for Procedures 2017 describes 96910 as "the physician uses photosensitizing chemicals and light rays to treat skin ailments."6 Application of light-enhancing topical products should occur within the office by either staff or the patient. In fact, examination of practice expense data from the Centers for Medicare & Medicaid Services indicated that the 96910 code includes payment for clinical staff time to apply topical products as well as the cost of the topical agent(s).7
The PUVA code 96912 is defined by the use of photosensitizing psoralen medication, which can be administered topically or orally, followed by UVA treatment. In my experience, PUVA has similar performance standards with in-office application of psoralen, if applicable. If application of topical photoenhancing products occurs outside the office, the requirements of photochemotherapy are not met, and 96900 should be reported.
The 96913 code defines prolonged phototherapy service with intensive topical therapy requirements and multiple phototherapy sessions per day.3 This code is rarely reported (average of fewer than 100 times in the Medicare population per year), and most insurers do not reimburse this service.
Protecting Yourself From an Audit
In my experience, review of private insurer audits of phototherapy services has yielded important lessons. First, having a written standard operating procedure in place regarding the performance of phototherapy services and how application of topicals will be handled has been helpful in audit defense. The other key to beating audits for phototherapy services is to have detailed documentation or a flowchart in the medical record regarding the topical agent and the light administration. The medical record should include what topical agent was applied, if any; whether the topical agent was applied in the office; where the topical product was applied; and who applied the topical product. Sometimes topical product application by a physician or staff is not feasible because of patient preference or the site of application. If the patient applied the topical, document that assistance was offered and refused, along with what type of UV light was used and the dosage. Inclusion of these elements in the medical record provides a clear picture of the delivery of the phototherapy service and will aid in responding to medical record audit.
Final Thoughts
Phototherapy is a critical treatment modality that continues to be utilized frequently in the expanding armamentarium of treatments for dermatoses. Phototherapy is performed almost exclusively by dermatologists and allows dermatologists to offer a unique level of care and value in the treatment of skin disease. Careful documentation, a written standard operating procedure, and adherence to proper performance standards will allow dermatologists to be compensated fairly for this important treatment modality and pass audits that are likely to occur.
In this era of biologics for psoriasis with ever-increasing effectiveness and safety as well as patients who have less and less time to visit the physician's office, it would seem that the days of in-office UV treatments would be numbered. However, rumors of the demise of phototherapy may be greatly exaggerated. Phototherapy is still one of the safest and most cost-effective treatments for psoriasis and other dermatoses.1 Its use often is a prerequisite for biologic therapy, and it may be the only therapeutic option for certain subsets of patients, such as children, pregnant women, and immunosuppressed patients. Moreover, narrowband UVB technology has breathed new life into phototherapy, with better efficacy and less long-term risk. Although the utilization of psoralen plus UVA (PUVA) light therapy has indeed decreased over the last 2 decades, the use of UVB therapies continues to increase dramatically.2
Phototherapy Codes
There are 4 chief Current Procedural Terminology (CPT) codes for reporting phototherapy services: (1) 96900: actinotherapy (UV light treatment); (2) 96910: photochemotherapy, tar, and UVB (Goeckerman treatment) or petrolatum and UVB; (3) 96912: photochemotherapy and PUVA; and (4) 96913: photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4 to 8 hours of care under direct supervision of the physician.3
There is lack of specificity of the CPT code descriptions for phototherapy. Moreover, insurer guidance for documentation for phototherapy is vague to nonexistent, and of course whenever the use of any medical service increases, insurer scrutiny is sure to follow. Therefore, it is not surprising that dermatology practices have reported that private insurers as well as Medicare are auditing medical records for phototherapy treatments.4 In fact, recently we have seen a Midwest private insurer demand payment from dermatologists for hundreds of 96910 phototherapy services, which the insurer asserted should have been coded as 96900 because topical therapies were not applied by the dermatology staff. The insurer did not just evaluate medical records but also contacted patients directly and asked how services had been provided. Clearly, more detailed guidance for dermatologists and insurers on documentation and performance standards for each phototherapy service is needed.
Existing coding guidance for phototherapy indicates that actinotherapy (96900) defines the basic service of treating a patient with a UV light unit.5 Actinotherapy does not involve application of topical medications while the patient is in the office.
In contrast, photochemotherapy (96910) implies addition of a chemo agent to phototherapy. Despite the somewhat nonspecific nature of the code descriptor, it is apparent that application of photoenhancing agents such as tar, petrolatum, or distillates of petrolatum meet the requirements of 96910. The Coder's Desk Reference for Procedures 2017 describes 96910 as "the physician uses photosensitizing chemicals and light rays to treat skin ailments."6 Application of light-enhancing topical products should occur within the office by either staff or the patient. In fact, examination of practice expense data from the Centers for Medicare & Medicaid Services indicated that the 96910 code includes payment for clinical staff time to apply topical products as well as the cost of the topical agent(s).7
The PUVA code 96912 is defined by the use of photosensitizing psoralen medication, which can be administered topically or orally, followed by UVA treatment. In my experience, PUVA has similar performance standards with in-office application of psoralen, if applicable. If application of topical photoenhancing products occurs outside the office, the requirements of photochemotherapy are not met, and 96900 should be reported.
The 96913 code defines prolonged phototherapy service with intensive topical therapy requirements and multiple phototherapy sessions per day.3 This code is rarely reported (average of fewer than 100 times in the Medicare population per year), and most insurers do not reimburse this service.
Protecting Yourself From an Audit
In my experience, review of private insurer audits of phototherapy services has yielded important lessons. First, having a written standard operating procedure in place regarding the performance of phototherapy services and how application of topicals will be handled has been helpful in audit defense. The other key to beating audits for phototherapy services is to have detailed documentation or a flowchart in the medical record regarding the topical agent and the light administration. The medical record should include what topical agent was applied, if any; whether the topical agent was applied in the office; where the topical product was applied; and who applied the topical product. Sometimes topical product application by a physician or staff is not feasible because of patient preference or the site of application. If the patient applied the topical, document that assistance was offered and refused, along with what type of UV light was used and the dosage. Inclusion of these elements in the medical record provides a clear picture of the delivery of the phototherapy service and will aid in responding to medical record audit.
Final Thoughts
Phototherapy is a critical treatment modality that continues to be utilized frequently in the expanding armamentarium of treatments for dermatoses. Phototherapy is performed almost exclusively by dermatologists and allows dermatologists to offer a unique level of care and value in the treatment of skin disease. Careful documentation, a written standard operating procedure, and adherence to proper performance standards will allow dermatologists to be compensated fairly for this important treatment modality and pass audits that are likely to occur.
- Lapolla W, Yentzer BA, Bagel J, et al. A review of phototherapy protocols for psoriasis treatment. J Am Acad Dermatol. 2011;64:936-949.
- Simpson GL, Yelverton CB, Rittenberg S, et al. Do utilization management controls for phototherapy increase the prescription of biologics? J Dermatolog Treat. 2006;17:359-361.
- Current Procedural Terminology 2017, Professional Edition. Chicago IL: American Medical Association; 2016.
- American Academy of Dermatology Association. Insurers review billing for photochemotherapy (CPT 96910). Derm Coding Consult. Spring 2009;13:4.
- American Academy of Dermatology Association. Coding Q&A's. Derm Coding Consult. Spring 2007;11:5, 7, 8.
- Coders' Desk Reference for Procedures 2017. Chicago, IL: Optum360; 2017.
- Relative Value Scale Update Committee Database. Chicago, IL: American Medical Association; 2016.
- Lapolla W, Yentzer BA, Bagel J, et al. A review of phototherapy protocols for psoriasis treatment. J Am Acad Dermatol. 2011;64:936-949.
- Simpson GL, Yelverton CB, Rittenberg S, et al. Do utilization management controls for phototherapy increase the prescription of biologics? J Dermatolog Treat. 2006;17:359-361.
- Current Procedural Terminology 2017, Professional Edition. Chicago IL: American Medical Association; 2016.
- American Academy of Dermatology Association. Insurers review billing for photochemotherapy (CPT 96910). Derm Coding Consult. Spring 2009;13:4.
- American Academy of Dermatology Association. Coding Q&A's. Derm Coding Consult. Spring 2007;11:5, 7, 8.
- Coders' Desk Reference for Procedures 2017. Chicago, IL: Optum360; 2017.
- Relative Value Scale Update Committee Database. Chicago, IL: American Medical Association; 2016.
Topical Cannabinoids in Dermatology
The prevalence of topical cannabinoids has risen sharply in recent years. Commercial advertisers promote their usage as a safe means to treat a multitude of skin disorders, including atopic dermatitis (AD), psoriasis, and acne. Topical compounds have garnered interest in laboratory studies, but the purchase of commercial formulations is limited to over-the-counter products from unregulated suppliers. In this article, we review the scientific evidence behind topical cannabinoids and evaluate their role in clinical dermatology.
Background
Cannabis is designated as a Schedule I drug, according to the Controlled Substances Act of 1970. This listing is given to substances with no therapeutic value and a high potential for abuse. However, as of 2017, 29 states and the District of Columbia have laws legalizing cannabis in some capacity. These regulations typically apply to medicinal use, though several states have now legalized recreational use.
Cannabinoids represent a broad class of chemical compounds derived from the cannabis plant. Originally, this class only comprised phytocannabinoids, cannabinoids produced by the cannabis plant. Tetrahydrocannabinol (THC) is the most well-known phytocannabinoid and leads to the psychoactive effects typically associated with cannabis use. Later investigation led to the discovery of endocannabinoids, cannabinoids that are naturally produced by human and animal bodies, as well as synthetic cannabinoids.1 Cannabidiol is a phytocannabinoid that has been investigated in neurologic and anti-inflammatory conditions.2-4
Cannabinoids act as agonists on 2 principal receptors— cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2)—which are both G protein–coupled receptors (Figure).5 Both have distinct distributions throughout different organ systems, to which cannabinoids (eg, THC, cannabidiol, endocannabinoids) show differential binding.6,7 Importantly, the expression of CB1 and CB2 has been identified on sensory nerve fibers, inflammatory cells, and adnexal structures of human skin.8 Based on these associations, topical application of cannabinoids has become a modality of interest for dermatological disorders. These formulations aim to influence cutaneous morphology without producing psychoactive effects.
Topical Cannabinoids in Inflammatory Disorders
Atopic dermatitis has emerged as an active area of investigation for cannabinoid receptors and topical agonists (Table 1). In an animal model, Kim et al9 examined the effects of CB1 agonism on skin inflammation. Mice treated with topical CB1 agonists showed greater recovery of epidermal barrier function in acutely abrogated skin relative to those treated with a vehicle preparation. In addition, agonism of CB1 led to significant (P<.001) decreases in skin fold thickness among models of acute and chronic skin inflammation.9
Nam et al10 also examined the role of topical CB1 agonists in mice with induced AD-like symptoms. Relative to treatment with vehicle, CB1 agonists significantly reduced the recruitment of mast cells (P<.01) and lowered the blood concentration of histamine (P<.05). Given the noted decrease in the release of inflammatory mediators, the authors speculated that topical agonsim of CB1 may prove useful in several conditions related to mast cell activation, such as AD, contact dermatitis, and psoriasis.10
The anti-inflammatory properties of topical THC were evaluated by Gaffal et al.11 In a mouse model of allergic contact dermatitis, mice treated with topical THC showed decreases in myeloid immune cell infiltration, with these beneficial effects existing even in mice with deficient CB1 and CB2 receptors. These results support a potentially wide anti-inflammatory activity of topical THC.11
Topical Cannabinoids in Pain Management
The effects of smoked cannabis in treating pain have undergone thorough investigation over recent years. Benefits have been noted in treating neuropathic pain, particularly in human immunodeficiency virus–associated sensory neuropathy.12-15 Smoked cannabis also may provide value as a synergistic therapy with opioids, thereby allowing for lower opioid doses.16
In contrast, research into the relationship between topical application of cannabinoids and nociception remains in preliminary stages (Table 2). In a mouse model, Dogrul et al17 assessed the topical antinociceptive potential of a mixed CB1-CB2 agonist. Results showed significant (P<.01) and dose-dependent antinociceptive effects relative to treatment with a vehicle.17 In a related study, Yesilyurt et al18 evaluated whether a mixed CB1-CB2 agonist could enhance the antinociceptive effects of topical opioids. Among mice treated with the combination of a cannabinoid agonist and topical morphine, a significantly (P<.05) greater analgesic effect was demonstrated relative to topical morphine alone.18
Studies in humans have been far more limited. Phan et al19 conducted a small, nonrandomized, open-label trial of a topical cannabinoid cream in patients with facial postherpetic neuralgia. Of 8 patients treated, 5 noted a mean pain reduction of 87.8%. No comparison vehicle was used. Based on this narrow study design, it is difficult to extrapolate these positive results to a broader patient population.19
Commercial Products
Although preliminary models with topical cannabinoids have shown potential, large-scale clinical trials in humans have yet to be performed. Despite this lack of investigation, commercial formulations of topical cannabinoids are available to dermatology patients. These formulations are nonstandardized, and no safety data exists regarding their use. Topical cannabinoids on the market may contain various amounts of active ingredient and may be combined with a range of other compounds.
In dermatology offices, it is not uncommon for patients to express an intention to use topical cannabinoid products following their planned treatment or procedure. Patients also have been known to use topical cannabinoid products prior to dermatologic procedures, sometimes in place of an approved topical anesthetic, without consulting the physician performing the procedure. With interventions that lead to active areas of wound healing, the application of such products may increase the risk for contamination and infection. Therefore, patients should be counseled that the use of commercial topical cannabinoids could jeopardize the success of their planned procedure, put them at risk for infection, and possibly lead to systemic absorption and/or changes in wound-healing capacities.
Conclusion
Based on the results from recent animal models, cannabinoids may have a role in future treatment algorithms for several inflammatory conditions. However, current efficacy and safety data are almost entirely limited to preliminary animal studies in rodents. In addition, the formulation of topical cannabinoid products is nonstandardized and poorly regulated. As such, the present evidence does not support the use of topical cannabinoids in dermatology practices. Dermatologists should ask patients about the use of any cannabinoid products as part of a treatment program, especially given the unsubstantiated claims often made by unscrupulous advertisers. This issue highlights the need for further research and regulation.
- Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389-462.
- Giacoppo S, Galuppo M, Pollastro F, et al. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. Daru. 2015;23:48.
- Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20:936-948.
- Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89:149-155.
- Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002;54:161-202.
- Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199-215.
- Svizenska I, Dubovy P, Sulcova A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures—a short review. Pharmacol Biochem Behav. 2008;90:501-511.
- Stander S, Schmelz M, Metze D, et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38:177-188.
- Kim HJ, Kim B, Park BM, et al. Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone-induced atopic dermatitis model. Int J Dermatol. 2015;54:E401-E408.
- Nam G, Jeong SK, Park BM, et al. Selective cannabinoid receptor-1 agonists regulate mast cell activation in an oxazolone-induced atopic dermatitis model. Ann Dermatol. 2016;28:22-29.
- Gaffal E, Cron M, Glodde N, et al. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013;68:994-1000.
- Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68:515-521.
- Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672-680.
- Wilsey B, Marcotte T, Deutsch R, et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136-148.
- Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9:506-521.
- Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90:844-851.
- Dogrul A, Gul H, Akar A, et al. Topical cannabinoid antinociception: synergy with spinal sites. Pain. 2003;105:11-16.
- Yesilyurt O, Dogrul A, Gul H, et al. Topical cannabinoid enhances topical morphine antinociception. Pain. 2003;105:303-308.
- Phan NQ, Siepmann D, Gralow I, et al. Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. J Dtsch Dermatol Ges. 2010;8:88-91.
The prevalence of topical cannabinoids has risen sharply in recent years. Commercial advertisers promote their usage as a safe means to treat a multitude of skin disorders, including atopic dermatitis (AD), psoriasis, and acne. Topical compounds have garnered interest in laboratory studies, but the purchase of commercial formulations is limited to over-the-counter products from unregulated suppliers. In this article, we review the scientific evidence behind topical cannabinoids and evaluate their role in clinical dermatology.
Background
Cannabis is designated as a Schedule I drug, according to the Controlled Substances Act of 1970. This listing is given to substances with no therapeutic value and a high potential for abuse. However, as of 2017, 29 states and the District of Columbia have laws legalizing cannabis in some capacity. These regulations typically apply to medicinal use, though several states have now legalized recreational use.
Cannabinoids represent a broad class of chemical compounds derived from the cannabis plant. Originally, this class only comprised phytocannabinoids, cannabinoids produced by the cannabis plant. Tetrahydrocannabinol (THC) is the most well-known phytocannabinoid and leads to the psychoactive effects typically associated with cannabis use. Later investigation led to the discovery of endocannabinoids, cannabinoids that are naturally produced by human and animal bodies, as well as synthetic cannabinoids.1 Cannabidiol is a phytocannabinoid that has been investigated in neurologic and anti-inflammatory conditions.2-4
Cannabinoids act as agonists on 2 principal receptors— cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2)—which are both G protein–coupled receptors (Figure).5 Both have distinct distributions throughout different organ systems, to which cannabinoids (eg, THC, cannabidiol, endocannabinoids) show differential binding.6,7 Importantly, the expression of CB1 and CB2 has been identified on sensory nerve fibers, inflammatory cells, and adnexal structures of human skin.8 Based on these associations, topical application of cannabinoids has become a modality of interest for dermatological disorders. These formulations aim to influence cutaneous morphology without producing psychoactive effects.
Topical Cannabinoids in Inflammatory Disorders
Atopic dermatitis has emerged as an active area of investigation for cannabinoid receptors and topical agonists (Table 1). In an animal model, Kim et al9 examined the effects of CB1 agonism on skin inflammation. Mice treated with topical CB1 agonists showed greater recovery of epidermal barrier function in acutely abrogated skin relative to those treated with a vehicle preparation. In addition, agonism of CB1 led to significant (P<.001) decreases in skin fold thickness among models of acute and chronic skin inflammation.9
Nam et al10 also examined the role of topical CB1 agonists in mice with induced AD-like symptoms. Relative to treatment with vehicle, CB1 agonists significantly reduced the recruitment of mast cells (P<.01) and lowered the blood concentration of histamine (P<.05). Given the noted decrease in the release of inflammatory mediators, the authors speculated that topical agonsim of CB1 may prove useful in several conditions related to mast cell activation, such as AD, contact dermatitis, and psoriasis.10
The anti-inflammatory properties of topical THC were evaluated by Gaffal et al.11 In a mouse model of allergic contact dermatitis, mice treated with topical THC showed decreases in myeloid immune cell infiltration, with these beneficial effects existing even in mice with deficient CB1 and CB2 receptors. These results support a potentially wide anti-inflammatory activity of topical THC.11
Topical Cannabinoids in Pain Management
The effects of smoked cannabis in treating pain have undergone thorough investigation over recent years. Benefits have been noted in treating neuropathic pain, particularly in human immunodeficiency virus–associated sensory neuropathy.12-15 Smoked cannabis also may provide value as a synergistic therapy with opioids, thereby allowing for lower opioid doses.16
In contrast, research into the relationship between topical application of cannabinoids and nociception remains in preliminary stages (Table 2). In a mouse model, Dogrul et al17 assessed the topical antinociceptive potential of a mixed CB1-CB2 agonist. Results showed significant (P<.01) and dose-dependent antinociceptive effects relative to treatment with a vehicle.17 In a related study, Yesilyurt et al18 evaluated whether a mixed CB1-CB2 agonist could enhance the antinociceptive effects of topical opioids. Among mice treated with the combination of a cannabinoid agonist and topical morphine, a significantly (P<.05) greater analgesic effect was demonstrated relative to topical morphine alone.18
Studies in humans have been far more limited. Phan et al19 conducted a small, nonrandomized, open-label trial of a topical cannabinoid cream in patients with facial postherpetic neuralgia. Of 8 patients treated, 5 noted a mean pain reduction of 87.8%. No comparison vehicle was used. Based on this narrow study design, it is difficult to extrapolate these positive results to a broader patient population.19
Commercial Products
Although preliminary models with topical cannabinoids have shown potential, large-scale clinical trials in humans have yet to be performed. Despite this lack of investigation, commercial formulations of topical cannabinoids are available to dermatology patients. These formulations are nonstandardized, and no safety data exists regarding their use. Topical cannabinoids on the market may contain various amounts of active ingredient and may be combined with a range of other compounds.
In dermatology offices, it is not uncommon for patients to express an intention to use topical cannabinoid products following their planned treatment or procedure. Patients also have been known to use topical cannabinoid products prior to dermatologic procedures, sometimes in place of an approved topical anesthetic, without consulting the physician performing the procedure. With interventions that lead to active areas of wound healing, the application of such products may increase the risk for contamination and infection. Therefore, patients should be counseled that the use of commercial topical cannabinoids could jeopardize the success of their planned procedure, put them at risk for infection, and possibly lead to systemic absorption and/or changes in wound-healing capacities.
Conclusion
Based on the results from recent animal models, cannabinoids may have a role in future treatment algorithms for several inflammatory conditions. However, current efficacy and safety data are almost entirely limited to preliminary animal studies in rodents. In addition, the formulation of topical cannabinoid products is nonstandardized and poorly regulated. As such, the present evidence does not support the use of topical cannabinoids in dermatology practices. Dermatologists should ask patients about the use of any cannabinoid products as part of a treatment program, especially given the unsubstantiated claims often made by unscrupulous advertisers. This issue highlights the need for further research and regulation.
The prevalence of topical cannabinoids has risen sharply in recent years. Commercial advertisers promote their usage as a safe means to treat a multitude of skin disorders, including atopic dermatitis (AD), psoriasis, and acne. Topical compounds have garnered interest in laboratory studies, but the purchase of commercial formulations is limited to over-the-counter products from unregulated suppliers. In this article, we review the scientific evidence behind topical cannabinoids and evaluate their role in clinical dermatology.
Background
Cannabis is designated as a Schedule I drug, according to the Controlled Substances Act of 1970. This listing is given to substances with no therapeutic value and a high potential for abuse. However, as of 2017, 29 states and the District of Columbia have laws legalizing cannabis in some capacity. These regulations typically apply to medicinal use, though several states have now legalized recreational use.
Cannabinoids represent a broad class of chemical compounds derived from the cannabis plant. Originally, this class only comprised phytocannabinoids, cannabinoids produced by the cannabis plant. Tetrahydrocannabinol (THC) is the most well-known phytocannabinoid and leads to the psychoactive effects typically associated with cannabis use. Later investigation led to the discovery of endocannabinoids, cannabinoids that are naturally produced by human and animal bodies, as well as synthetic cannabinoids.1 Cannabidiol is a phytocannabinoid that has been investigated in neurologic and anti-inflammatory conditions.2-4
Cannabinoids act as agonists on 2 principal receptors— cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2)—which are both G protein–coupled receptors (Figure).5 Both have distinct distributions throughout different organ systems, to which cannabinoids (eg, THC, cannabidiol, endocannabinoids) show differential binding.6,7 Importantly, the expression of CB1 and CB2 has been identified on sensory nerve fibers, inflammatory cells, and adnexal structures of human skin.8 Based on these associations, topical application of cannabinoids has become a modality of interest for dermatological disorders. These formulations aim to influence cutaneous morphology without producing psychoactive effects.
Topical Cannabinoids in Inflammatory Disorders
Atopic dermatitis has emerged as an active area of investigation for cannabinoid receptors and topical agonists (Table 1). In an animal model, Kim et al9 examined the effects of CB1 agonism on skin inflammation. Mice treated with topical CB1 agonists showed greater recovery of epidermal barrier function in acutely abrogated skin relative to those treated with a vehicle preparation. In addition, agonism of CB1 led to significant (P<.001) decreases in skin fold thickness among models of acute and chronic skin inflammation.9
Nam et al10 also examined the role of topical CB1 agonists in mice with induced AD-like symptoms. Relative to treatment with vehicle, CB1 agonists significantly reduced the recruitment of mast cells (P<.01) and lowered the blood concentration of histamine (P<.05). Given the noted decrease in the release of inflammatory mediators, the authors speculated that topical agonsim of CB1 may prove useful in several conditions related to mast cell activation, such as AD, contact dermatitis, and psoriasis.10
The anti-inflammatory properties of topical THC were evaluated by Gaffal et al.11 In a mouse model of allergic contact dermatitis, mice treated with topical THC showed decreases in myeloid immune cell infiltration, with these beneficial effects existing even in mice with deficient CB1 and CB2 receptors. These results support a potentially wide anti-inflammatory activity of topical THC.11
Topical Cannabinoids in Pain Management
The effects of smoked cannabis in treating pain have undergone thorough investigation over recent years. Benefits have been noted in treating neuropathic pain, particularly in human immunodeficiency virus–associated sensory neuropathy.12-15 Smoked cannabis also may provide value as a synergistic therapy with opioids, thereby allowing for lower opioid doses.16
In contrast, research into the relationship between topical application of cannabinoids and nociception remains in preliminary stages (Table 2). In a mouse model, Dogrul et al17 assessed the topical antinociceptive potential of a mixed CB1-CB2 agonist. Results showed significant (P<.01) and dose-dependent antinociceptive effects relative to treatment with a vehicle.17 In a related study, Yesilyurt et al18 evaluated whether a mixed CB1-CB2 agonist could enhance the antinociceptive effects of topical opioids. Among mice treated with the combination of a cannabinoid agonist and topical morphine, a significantly (P<.05) greater analgesic effect was demonstrated relative to topical morphine alone.18
Studies in humans have been far more limited. Phan et al19 conducted a small, nonrandomized, open-label trial of a topical cannabinoid cream in patients with facial postherpetic neuralgia. Of 8 patients treated, 5 noted a mean pain reduction of 87.8%. No comparison vehicle was used. Based on this narrow study design, it is difficult to extrapolate these positive results to a broader patient population.19
Commercial Products
Although preliminary models with topical cannabinoids have shown potential, large-scale clinical trials in humans have yet to be performed. Despite this lack of investigation, commercial formulations of topical cannabinoids are available to dermatology patients. These formulations are nonstandardized, and no safety data exists regarding their use. Topical cannabinoids on the market may contain various amounts of active ingredient and may be combined with a range of other compounds.
In dermatology offices, it is not uncommon for patients to express an intention to use topical cannabinoid products following their planned treatment or procedure. Patients also have been known to use topical cannabinoid products prior to dermatologic procedures, sometimes in place of an approved topical anesthetic, without consulting the physician performing the procedure. With interventions that lead to active areas of wound healing, the application of such products may increase the risk for contamination and infection. Therefore, patients should be counseled that the use of commercial topical cannabinoids could jeopardize the success of their planned procedure, put them at risk for infection, and possibly lead to systemic absorption and/or changes in wound-healing capacities.
Conclusion
Based on the results from recent animal models, cannabinoids may have a role in future treatment algorithms for several inflammatory conditions. However, current efficacy and safety data are almost entirely limited to preliminary animal studies in rodents. In addition, the formulation of topical cannabinoid products is nonstandardized and poorly regulated. As such, the present evidence does not support the use of topical cannabinoids in dermatology practices. Dermatologists should ask patients about the use of any cannabinoid products as part of a treatment program, especially given the unsubstantiated claims often made by unscrupulous advertisers. This issue highlights the need for further research and regulation.
- Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389-462.
- Giacoppo S, Galuppo M, Pollastro F, et al. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. Daru. 2015;23:48.
- Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20:936-948.
- Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89:149-155.
- Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002;54:161-202.
- Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199-215.
- Svizenska I, Dubovy P, Sulcova A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures—a short review. Pharmacol Biochem Behav. 2008;90:501-511.
- Stander S, Schmelz M, Metze D, et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38:177-188.
- Kim HJ, Kim B, Park BM, et al. Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone-induced atopic dermatitis model. Int J Dermatol. 2015;54:E401-E408.
- Nam G, Jeong SK, Park BM, et al. Selective cannabinoid receptor-1 agonists regulate mast cell activation in an oxazolone-induced atopic dermatitis model. Ann Dermatol. 2016;28:22-29.
- Gaffal E, Cron M, Glodde N, et al. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013;68:994-1000.
- Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68:515-521.
- Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672-680.
- Wilsey B, Marcotte T, Deutsch R, et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136-148.
- Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9:506-521.
- Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90:844-851.
- Dogrul A, Gul H, Akar A, et al. Topical cannabinoid antinociception: synergy with spinal sites. Pain. 2003;105:11-16.
- Yesilyurt O, Dogrul A, Gul H, et al. Topical cannabinoid enhances topical morphine antinociception. Pain. 2003;105:303-308.
- Phan NQ, Siepmann D, Gralow I, et al. Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. J Dtsch Dermatol Ges. 2010;8:88-91.
- Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389-462.
- Giacoppo S, Galuppo M, Pollastro F, et al. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. Daru. 2015;23:48.
- Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20:936-948.
- Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89:149-155.
- Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002;54:161-202.
- Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199-215.
- Svizenska I, Dubovy P, Sulcova A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures—a short review. Pharmacol Biochem Behav. 2008;90:501-511.
- Stander S, Schmelz M, Metze D, et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38:177-188.
- Kim HJ, Kim B, Park BM, et al. Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone-induced atopic dermatitis model. Int J Dermatol. 2015;54:E401-E408.
- Nam G, Jeong SK, Park BM, et al. Selective cannabinoid receptor-1 agonists regulate mast cell activation in an oxazolone-induced atopic dermatitis model. Ann Dermatol. 2016;28:22-29.
- Gaffal E, Cron M, Glodde N, et al. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013;68:994-1000.
- Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68:515-521.
- Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672-680.
- Wilsey B, Marcotte T, Deutsch R, et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136-148.
- Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9:506-521.
- Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90:844-851.
- Dogrul A, Gul H, Akar A, et al. Topical cannabinoid antinociception: synergy with spinal sites. Pain. 2003;105:11-16.
- Yesilyurt O, Dogrul A, Gul H, et al. Topical cannabinoid enhances topical morphine antinociception. Pain. 2003;105:303-308.
- Phan NQ, Siepmann D, Gralow I, et al. Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. J Dtsch Dermatol Ges. 2010;8:88-91.
Practice Points
- Topical cannabinoids are advertised by companies as treatment options for numerous dermatologic conditions.
- Despite promising data in rodent models, there have been no rigorous studies to date confirming efficacy or safety in humans.
- Dermatologists should therefore inquire with patients about the use of any topical cannabinoid products, especially around the time of planned procedures, as they may affect treatment outcomes.
Early phase III data positive for adalimumab biosimilar, for both psoriasis and PsA
MADRID – To date, an adalimumab biosimilar has proven itself in a large, phase III trial of patients with psoriasis, including a subset with mild to moderate psoriatic arthritis (PsA).
The biosimilar, known as CHS-1420, cleared psoriatic plaques and improved health-related quality of life just as well as adalimumab after 12 weeks of treatment, Barbara Finck, MD, said at the European Congress of Rheumatology. It also suppressed high-sensitivity C-reactive protein (CRP) as well as the originator molecule, she said.
Dr. Finck, the chief medical officer of Coherus Biosciences, the developer of CHS-1420, reported results from the first 16-week phase of the 48-week study. Data are still to come on a 6-week period during which half those taking adalimumab switched to CHS-1420 in a blinded fashion, and 26 weeks of open-label CHS-1420 for all patients.
The study’s primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) Two additional endpoints were evaluated in patients with PsA: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and changes in CRP.
Dr. Finck bemoaned the lack of the clinical rheumatologic endpoint, tender and swollen joint count. “I advocated for this but was unable to convince our dermatology colleagues” to conduct this exam, she said. “I think we have a ways to go to educate our colleagues in this regard.”
The study comprised 545 patients with mild to moderate psoriasis; of these, 127 had PsA. They received subcutaneous injections of either CHS-1420 or adalimumab at identical doses (80 mg at week 1, followed by 40 mg every other week). They were a mean of 44 years o
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In the entire study population, treatment with CHS-1420 and adalimumab followed almost identical response curves. By week 4, 22% of the CHS-1420 group and 20% of the adalimumab group had reached a PASI75 response. By week 8, those numbers were 57% and 61%, respectively, and by week 12, they were 69% and 72% – not significantly different.
Response was similar in the subgroup of PsA patients: By week 12, 82% of the CHS-1420 group and 77% of the adalimumab group had reached a PASI 75. PsA patients also responded equally well to both medications on the HAQ-DI by week 12. At baseline, the mean HAQ-DI was about 1 in each group. At 12 weeks, it was reduced by about half a point in both groups. High-sensitivity CRP decreased similarly in the CHS-1420 and adalimumab groups as well (reductions of 8.9 mg/L and 6.3 mg/L, respectively).
Adalimumab, a tumor necrosis factor blocker, is a highly immunogenic molecule, and as such, many patients developed antibodies to both it and to CHS-1420. By week 12, 84% of both treatment groups had developed anti-drug antibodies and 32%, neutralizing antibodies. Among those with PsA, 82% taking CHS-1420 and 88% of those taking adalimumab developed antidrug antibodies. Neutralizing antibodies developed in 33% and 30%, respectively. Neither of these differences was statistically significant.
Other adverse events were similar, Dr. Finck noted. These included nasopharyngitis (9% of both groups), upper respiratory tract infection (6%), injection site reaction (4%), headache (3%), and worsening of psoriasis (1% for CHS-1420, and 3% for adalimumab).
If the switching study data are similarly positive, Coherus expects to file a Biologics License Application with the Food and Drug Administration in early 2018, Dr. Finck said.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – To date, an adalimumab biosimilar has proven itself in a large, phase III trial of patients with psoriasis, including a subset with mild to moderate psoriatic arthritis (PsA).
The biosimilar, known as CHS-1420, cleared psoriatic plaques and improved health-related quality of life just as well as adalimumab after 12 weeks of treatment, Barbara Finck, MD, said at the European Congress of Rheumatology. It also suppressed high-sensitivity C-reactive protein (CRP) as well as the originator molecule, she said.
Dr. Finck, the chief medical officer of Coherus Biosciences, the developer of CHS-1420, reported results from the first 16-week phase of the 48-week study. Data are still to come on a 6-week period during which half those taking adalimumab switched to CHS-1420 in a blinded fashion, and 26 weeks of open-label CHS-1420 for all patients.
The study’s primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) Two additional endpoints were evaluated in patients with PsA: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and changes in CRP.
Dr. Finck bemoaned the lack of the clinical rheumatologic endpoint, tender and swollen joint count. “I advocated for this but was unable to convince our dermatology colleagues” to conduct this exam, she said. “I think we have a ways to go to educate our colleagues in this regard.”
The study comprised 545 patients with mild to moderate psoriasis; of these, 127 had PsA. They received subcutaneous injections of either CHS-1420 or adalimumab at identical doses (80 mg at week 1, followed by 40 mg every other week). They were a mean of 44 years o
In the entire study population, treatment with CHS-1420 and adalimumab followed almost identical response curves. By week 4, 22% of the CHS-1420 group and 20% of the adalimumab group had reached a PASI75 response. By week 8, those numbers were 57% and 61%, respectively, and by week 12, they were 69% and 72% – not significantly different.
Response was similar in the subgroup of PsA patients: By week 12, 82% of the CHS-1420 group and 77% of the adalimumab group had reached a PASI 75. PsA patients also responded equally well to both medications on the HAQ-DI by week 12. At baseline, the mean HAQ-DI was about 1 in each group. At 12 weeks, it was reduced by about half a point in both groups. High-sensitivity CRP decreased similarly in the CHS-1420 and adalimumab groups as well (reductions of 8.9 mg/L and 6.3 mg/L, respectively).
Adalimumab, a tumor necrosis factor blocker, is a highly immunogenic molecule, and as such, many patients developed antibodies to both it and to CHS-1420. By week 12, 84% of both treatment groups had developed anti-drug antibodies and 32%, neutralizing antibodies. Among those with PsA, 82% taking CHS-1420 and 88% of those taking adalimumab developed antidrug antibodies. Neutralizing antibodies developed in 33% and 30%, respectively. Neither of these differences was statistically significant.
Other adverse events were similar, Dr. Finck noted. These included nasopharyngitis (9% of both groups), upper respiratory tract infection (6%), injection site reaction (4%), headache (3%), and worsening of psoriasis (1% for CHS-1420, and 3% for adalimumab).
If the switching study data are similarly positive, Coherus expects to file a Biologics License Application with the Food and Drug Administration in early 2018, Dr. Finck said.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
MADRID – To date, an adalimumab biosimilar has proven itself in a large, phase III trial of patients with psoriasis, including a subset with mild to moderate psoriatic arthritis (PsA).
The biosimilar, known as CHS-1420, cleared psoriatic plaques and improved health-related quality of life just as well as adalimumab after 12 weeks of treatment, Barbara Finck, MD, said at the European Congress of Rheumatology. It also suppressed high-sensitivity C-reactive protein (CRP) as well as the originator molecule, she said.
Dr. Finck, the chief medical officer of Coherus Biosciences, the developer of CHS-1420, reported results from the first 16-week phase of the 48-week study. Data are still to come on a 6-week period during which half those taking adalimumab switched to CHS-1420 in a blinded fashion, and 26 weeks of open-label CHS-1420 for all patients.
The study’s primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) Two additional endpoints were evaluated in patients with PsA: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and changes in CRP.
Dr. Finck bemoaned the lack of the clinical rheumatologic endpoint, tender and swollen joint count. “I advocated for this but was unable to convince our dermatology colleagues” to conduct this exam, she said. “I think we have a ways to go to educate our colleagues in this regard.”
The study comprised 545 patients with mild to moderate psoriasis; of these, 127 had PsA. They received subcutaneous injections of either CHS-1420 or adalimumab at identical doses (80 mg at week 1, followed by 40 mg every other week). They were a mean of 44 years o
In the entire study population, treatment with CHS-1420 and adalimumab followed almost identical response curves. By week 4, 22% of the CHS-1420 group and 20% of the adalimumab group had reached a PASI75 response. By week 8, those numbers were 57% and 61%, respectively, and by week 12, they were 69% and 72% – not significantly different.
Response was similar in the subgroup of PsA patients: By week 12, 82% of the CHS-1420 group and 77% of the adalimumab group had reached a PASI 75. PsA patients also responded equally well to both medications on the HAQ-DI by week 12. At baseline, the mean HAQ-DI was about 1 in each group. At 12 weeks, it was reduced by about half a point in both groups. High-sensitivity CRP decreased similarly in the CHS-1420 and adalimumab groups as well (reductions of 8.9 mg/L and 6.3 mg/L, respectively).
Adalimumab, a tumor necrosis factor blocker, is a highly immunogenic molecule, and as such, many patients developed antibodies to both it and to CHS-1420. By week 12, 84% of both treatment groups had developed anti-drug antibodies and 32%, neutralizing antibodies. Among those with PsA, 82% taking CHS-1420 and 88% of those taking adalimumab developed antidrug antibodies. Neutralizing antibodies developed in 33% and 30%, respectively. Neither of these differences was statistically significant.
Other adverse events were similar, Dr. Finck noted. These included nasopharyngitis (9% of both groups), upper respiratory tract infection (6%), injection site reaction (4%), headache (3%), and worsening of psoriasis (1% for CHS-1420, and 3% for adalimumab).
If the switching study data are similarly positive, Coherus expects to file a Biologics License Application with the Food and Drug Administration in early 2018, Dr. Finck said.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: By week 12, 69% of those who received CHS-1420 and 72% of those who received adalimumab had reached a PASI75, response rates that were not significantly different.
Data source: The phase III trial randomized 545 patients with psoriasis, including 127 with PsA, to treatment with adalimumab or the biosimilar.
Disclosures: Dr. Finck is chief medical officer of Coherus Biosciences, which is developing CHS-1420.
