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Severe psoriasis, kidney disease linked
WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.
The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.
“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”
The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).
A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).
Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.
In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.
Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).
But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”
Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.
Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.
WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.
The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.
“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”
The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).
A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).
Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.
In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.
Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).
But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”
Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.
Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.
WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.
The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.
“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”
The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).
A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).
Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.
In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.
Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).
But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”
Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.
Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.
AT AAD 16
Key clinical point: Severe psoriasis appears to increase the risk of both immunoglobulin A glomerulonephritis and glomerular disease.
Major finding: The risk of glomerulonephritis was five-fold higher and the risk of glomerular disease doubled in those with severe psoriasis.
Data source: A population based cohort study comprised about 1.2 million subjects.
Disclosures: Ms. Sungat Grewal had no financial disclosures.
How to beat apremilast-induced diarrhea
MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.
“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.
Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.
Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.
“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.
It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.
Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.
Diphenoxylate/atropine (Lomotil) is another effective prescription option.
Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.
The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.
Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”
Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.
Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.
“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.
He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.
MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.
“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.
Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.
Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.
“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.
It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.
Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.
Diphenoxylate/atropine (Lomotil) is another effective prescription option.
Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.
The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.
Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”
Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.
Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.
“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.
He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.
MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.
“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.
Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.
Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.
“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.
It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.
Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.
Diphenoxylate/atropine (Lomotil) is another effective prescription option.
Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.
The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.
Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”
Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.
Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.
“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.
He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2016
How to beat apremilast-induced diarrhea
MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.
“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.
Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.
Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.
“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.
It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.
Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.
Diphenoxylate/atropine (Lomotil) is another effective prescription option.
Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.
The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.
Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”
Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.
Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.
“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.
He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.
MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.
“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.
Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.
Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.
“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.
It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.
Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.
Diphenoxylate/atropine (Lomotil) is another effective prescription option.
Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.
The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.
Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”
Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.
Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.
“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.
He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.
MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.
“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.
Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.
Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.
“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.
It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.
Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.
Diphenoxylate/atropine (Lomotil) is another effective prescription option.
Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.
The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.
Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”
Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.
Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.
“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.
He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2016
Biologics for Psoriasis
Review the PDF of the fact sheet on biologics for psoriasis with board-relevant, easy-to-review material. This month's fact sheet discusses the current US Food and Drug Administration–approved biologic medications for psoriasis and psoriatic arthritis, including the mechanism of action, dosing, and side effects.
Practice Questions
1. Which biologic is administered as an intravenous infusion?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
2. Which biologic is dosed based on body weight?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
3. Which biologic has been shown to worsen existing Crohn disease?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
4. Which biologic is a fusion protein?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
5. Which biologic has been shown to cause reversible posterior leukoencephalopathy syndrome?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
Answers to practice questions provided on next page
Practice Question Answers
1. Which biologic is administered as an intravenous infusion?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
2. Which biologic is dosed based on body weight?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
3. Which biologic has been shown to worsen existing Crohn disease?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
4. Which biologic is a fusion protein?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
5. Which biologic has been shown to cause reversible posterior leukoencephalopathy syndrome?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
Review the PDF of the fact sheet on biologics for psoriasis with board-relevant, easy-to-review material. This month's fact sheet discusses the current US Food and Drug Administration–approved biologic medications for psoriasis and psoriatic arthritis, including the mechanism of action, dosing, and side effects.
Practice Questions
1. Which biologic is administered as an intravenous infusion?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
2. Which biologic is dosed based on body weight?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
3. Which biologic has been shown to worsen existing Crohn disease?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
4. Which biologic is a fusion protein?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
5. Which biologic has been shown to cause reversible posterior leukoencephalopathy syndrome?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
Answers to practice questions provided on next page
Practice Question Answers
1. Which biologic is administered as an intravenous infusion?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
2. Which biologic is dosed based on body weight?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
3. Which biologic has been shown to worsen existing Crohn disease?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
4. Which biologic is a fusion protein?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
5. Which biologic has been shown to cause reversible posterior leukoencephalopathy syndrome?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
Review the PDF of the fact sheet on biologics for psoriasis with board-relevant, easy-to-review material. This month's fact sheet discusses the current US Food and Drug Administration–approved biologic medications for psoriasis and psoriatic arthritis, including the mechanism of action, dosing, and side effects.
Practice Questions
1. Which biologic is administered as an intravenous infusion?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
2. Which biologic is dosed based on body weight?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
3. Which biologic has been shown to worsen existing Crohn disease?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
4. Which biologic is a fusion protein?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
5. Which biologic has been shown to cause reversible posterior leukoencephalopathy syndrome?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
Answers to practice questions provided on next page
Practice Question Answers
1. Which biologic is administered as an intravenous infusion?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
2. Which biologic is dosed based on body weight?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
3. Which biologic has been shown to worsen existing Crohn disease?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
4. Which biologic is a fusion protein?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
5. Which biologic has been shown to cause reversible posterior leukoencephalopathy syndrome?
a. adalimumab
b. etanercept
c. infliximab
d. secukinumab
e. ustekinumab
Biologics for Pediatric Psoriasis Patients?
Biologic agents for the treatment of psoriasis are approved for patients 18 years and older. Although some biologics are approved for juvenile idiopathic arthritis, the lack of approved biologic therapies for children with psoriasis has been a major gap in our treatment of the disease. The incidence of moderate to severe psoriasis in the pediatric population is much lower than in adults, but there are still many patients younger than 18 years who would benefit from systemic therapies.
A recent press release indicates that the US Food and Drug Administration has accepted for review a supplemental biologics license application for the expanded use of etanercept to treat pediatric patients with chronic severe plaque psoriasis.
In February 2016 Paller et al (J Am Acad Dermatol. 2016;74:280.e3-287.e3) published data evaluating long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. This 5-year, open-label extension study enrolled those patients aged 4 to 17 years who had participated in an initial 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections as well as rates of 75% and 90% improvement in psoriasis area and severity index (PASI) score and clear or almost clear status on the static physician global assessment.
Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks of treatment. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 Serious AEs (n=8) were reported in 7 patients, and only 1 case of cellulitis was considered treatment related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement (∼60%–70%) and 90% improvement (∼30%–40%) in PASI score were maintained through week 264 as well as static physician global assessment status of clear or almost clear (∼40%–50%).
What’s the issue?
If approved, etanercept would be the first US Food and Drug Administration–approved systemic drug for pediatric psoriasis patients, which would open up options for many patients in need. Would you be willing to treat your pediatric psoriasis patients with a biologic?
Biologic agents for the treatment of psoriasis are approved for patients 18 years and older. Although some biologics are approved for juvenile idiopathic arthritis, the lack of approved biologic therapies for children with psoriasis has been a major gap in our treatment of the disease. The incidence of moderate to severe psoriasis in the pediatric population is much lower than in adults, but there are still many patients younger than 18 years who would benefit from systemic therapies.
A recent press release indicates that the US Food and Drug Administration has accepted for review a supplemental biologics license application for the expanded use of etanercept to treat pediatric patients with chronic severe plaque psoriasis.
In February 2016 Paller et al (J Am Acad Dermatol. 2016;74:280.e3-287.e3) published data evaluating long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. This 5-year, open-label extension study enrolled those patients aged 4 to 17 years who had participated in an initial 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections as well as rates of 75% and 90% improvement in psoriasis area and severity index (PASI) score and clear or almost clear status on the static physician global assessment.
Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks of treatment. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 Serious AEs (n=8) were reported in 7 patients, and only 1 case of cellulitis was considered treatment related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement (∼60%–70%) and 90% improvement (∼30%–40%) in PASI score were maintained through week 264 as well as static physician global assessment status of clear or almost clear (∼40%–50%).
What’s the issue?
If approved, etanercept would be the first US Food and Drug Administration–approved systemic drug for pediatric psoriasis patients, which would open up options for many patients in need. Would you be willing to treat your pediatric psoriasis patients with a biologic?
Biologic agents for the treatment of psoriasis are approved for patients 18 years and older. Although some biologics are approved for juvenile idiopathic arthritis, the lack of approved biologic therapies for children with psoriasis has been a major gap in our treatment of the disease. The incidence of moderate to severe psoriasis in the pediatric population is much lower than in adults, but there are still many patients younger than 18 years who would benefit from systemic therapies.
A recent press release indicates that the US Food and Drug Administration has accepted for review a supplemental biologics license application for the expanded use of etanercept to treat pediatric patients with chronic severe plaque psoriasis.
In February 2016 Paller et al (J Am Acad Dermatol. 2016;74:280.e3-287.e3) published data evaluating long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. This 5-year, open-label extension study enrolled those patients aged 4 to 17 years who had participated in an initial 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections as well as rates of 75% and 90% improvement in psoriasis area and severity index (PASI) score and clear or almost clear status on the static physician global assessment.
Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks of treatment. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 Serious AEs (n=8) were reported in 7 patients, and only 1 case of cellulitis was considered treatment related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement (∼60%–70%) and 90% improvement (∼30%–40%) in PASI score were maintained through week 264 as well as static physician global assessment status of clear or almost clear (∼40%–50%).
What’s the issue?
If approved, etanercept would be the first US Food and Drug Administration–approved systemic drug for pediatric psoriasis patients, which would open up options for many patients in need. Would you be willing to treat your pediatric psoriasis patients with a biologic?
Ustekinumab Linked to More Outpatient Visits and Greater Pharmacy Costs Versus Adalimumab in Psoriasis Patients
Psoriasis patients who switched from etanercept (ETA) to ustekinumab (UST) incurred higher health care resource utilization and health care costs over 12 months compared to patients who switched from ETA to adalimumab (ADA), according to a study presented at the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC (March 4–8, 2016).
In the poster, Wu et al explained that although tumor necrosis factor (TNF) agents are effective therapies for psoriasis, treatment failure with anti-TNF agents may occur and switching to another anti-TNF agent or another biologic with a different mechanism of action may be needed. Both biologic therapies ADA and UST are effective therapies for psoriasis patients who previously received ETA. The investigators sought to compare health care resource utilization and health care costs in adult psoriasis patients who were switched from ETA to UST (n=365) versus from ETA to ADA (n=1335).
Health care resource utilization included the total number of days with medical services, including outpatient visits, inpatient days, emergency department visits, and other medical services measured over the 12-month study period. Health care costs included total pharmacy costs and total medical service costs incurred over the 12-month study period and were measured from a payer’s perspective.
The investigators reported that UST patients had statistically significantly more days with medical services (P=.02) compared to ADA patients, mainly driven by more outpatient visits (P<.01). Ustekinumab patients also had a greater total annual health care cost by $14,356 (P<.01). The cost difference was primarily driven by greater pharmacy costs (cost difference, $13,682; P<.01).
This study was funded by AbbVie Inc.
Data from: Wu JJ, Sundaram M, Guérin A, et al. Comparison of outcomes between psoriasis patients who switched from etanercept to adalimumab versus to ustekinumab. Posted presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC. P2524.
Psoriasis patients who switched from etanercept (ETA) to ustekinumab (UST) incurred higher health care resource utilization and health care costs over 12 months compared to patients who switched from ETA to adalimumab (ADA), according to a study presented at the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC (March 4–8, 2016).
In the poster, Wu et al explained that although tumor necrosis factor (TNF) agents are effective therapies for psoriasis, treatment failure with anti-TNF agents may occur and switching to another anti-TNF agent or another biologic with a different mechanism of action may be needed. Both biologic therapies ADA and UST are effective therapies for psoriasis patients who previously received ETA. The investigators sought to compare health care resource utilization and health care costs in adult psoriasis patients who were switched from ETA to UST (n=365) versus from ETA to ADA (n=1335).
Health care resource utilization included the total number of days with medical services, including outpatient visits, inpatient days, emergency department visits, and other medical services measured over the 12-month study period. Health care costs included total pharmacy costs and total medical service costs incurred over the 12-month study period and were measured from a payer’s perspective.
The investigators reported that UST patients had statistically significantly more days with medical services (P=.02) compared to ADA patients, mainly driven by more outpatient visits (P<.01). Ustekinumab patients also had a greater total annual health care cost by $14,356 (P<.01). The cost difference was primarily driven by greater pharmacy costs (cost difference, $13,682; P<.01).
This study was funded by AbbVie Inc.
Psoriasis patients who switched from etanercept (ETA) to ustekinumab (UST) incurred higher health care resource utilization and health care costs over 12 months compared to patients who switched from ETA to adalimumab (ADA), according to a study presented at the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC (March 4–8, 2016).
In the poster, Wu et al explained that although tumor necrosis factor (TNF) agents are effective therapies for psoriasis, treatment failure with anti-TNF agents may occur and switching to another anti-TNF agent or another biologic with a different mechanism of action may be needed. Both biologic therapies ADA and UST are effective therapies for psoriasis patients who previously received ETA. The investigators sought to compare health care resource utilization and health care costs in adult psoriasis patients who were switched from ETA to UST (n=365) versus from ETA to ADA (n=1335).
Health care resource utilization included the total number of days with medical services, including outpatient visits, inpatient days, emergency department visits, and other medical services measured over the 12-month study period. Health care costs included total pharmacy costs and total medical service costs incurred over the 12-month study period and were measured from a payer’s perspective.
The investigators reported that UST patients had statistically significantly more days with medical services (P=.02) compared to ADA patients, mainly driven by more outpatient visits (P<.01). Ustekinumab patients also had a greater total annual health care cost by $14,356 (P<.01). The cost difference was primarily driven by greater pharmacy costs (cost difference, $13,682; P<.01).
This study was funded by AbbVie Inc.
Data from: Wu JJ, Sundaram M, Guérin A, et al. Comparison of outcomes between psoriasis patients who switched from etanercept to adalimumab versus to ustekinumab. Posted presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC. P2524.
Data from: Wu JJ, Sundaram M, Guérin A, et al. Comparison of outcomes between psoriasis patients who switched from etanercept to adalimumab versus to ustekinumab. Posted presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC. P2524.
Ixekizumab approved for plaque psoriasis
Ixekizumab is approved to treat moderate to severe plaque psoriasis in adults, according to an announcement from the Food and Drug Administration.
“Today’s approval provides patients suffering from plaque psoriasis with another important treatment option to help relieve the skin irritation and discomfort from the condition,” Dr. Julie Beitz, director of the FDA’s Office of Drug Evaluation III, said in a statement .
Ixekizumab is an IgG4 monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokines, inhibiting interaction with the IL-17 receptor. It is approved for patients who are candidates for systemic therapy, phototherapy, or a combination of both.
The safety and efficacy of ixekizumab were established in three randomized, placebo-controlled clinical trials with a total of 3,866 participants with plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients treated with ixekizumab achieved greater clinical response than did those who received placebo.
The therapy was approved with a medication guide to inform patients that they may have a greater risk of an infection, or an allergic or autoimmune condition, according to the FDA announcement. The agency advised that physicians should monitor patient for serious allergic reactions and development or worsening of inflammatory bowel disease.
The most common adverse events seen in clinical trials of ixekizumab were upper respiratory infections, injection site reactions, and tinea.
Ixekizumab will be marketed as Taltz by Eli Lilly and Company.
On Twitter @denisefulton
Ixekizumab is approved to treat moderate to severe plaque psoriasis in adults, according to an announcement from the Food and Drug Administration.
“Today’s approval provides patients suffering from plaque psoriasis with another important treatment option to help relieve the skin irritation and discomfort from the condition,” Dr. Julie Beitz, director of the FDA’s Office of Drug Evaluation III, said in a statement .
Ixekizumab is an IgG4 monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokines, inhibiting interaction with the IL-17 receptor. It is approved for patients who are candidates for systemic therapy, phototherapy, or a combination of both.
The safety and efficacy of ixekizumab were established in three randomized, placebo-controlled clinical trials with a total of 3,866 participants with plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients treated with ixekizumab achieved greater clinical response than did those who received placebo.
The therapy was approved with a medication guide to inform patients that they may have a greater risk of an infection, or an allergic or autoimmune condition, according to the FDA announcement. The agency advised that physicians should monitor patient for serious allergic reactions and development or worsening of inflammatory bowel disease.
The most common adverse events seen in clinical trials of ixekizumab were upper respiratory infections, injection site reactions, and tinea.
Ixekizumab will be marketed as Taltz by Eli Lilly and Company.
On Twitter @denisefulton
Ixekizumab is approved to treat moderate to severe plaque psoriasis in adults, according to an announcement from the Food and Drug Administration.
“Today’s approval provides patients suffering from plaque psoriasis with another important treatment option to help relieve the skin irritation and discomfort from the condition,” Dr. Julie Beitz, director of the FDA’s Office of Drug Evaluation III, said in a statement .
Ixekizumab is an IgG4 monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokines, inhibiting interaction with the IL-17 receptor. It is approved for patients who are candidates for systemic therapy, phototherapy, or a combination of both.
The safety and efficacy of ixekizumab were established in three randomized, placebo-controlled clinical trials with a total of 3,866 participants with plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients treated with ixekizumab achieved greater clinical response than did those who received placebo.
The therapy was approved with a medication guide to inform patients that they may have a greater risk of an infection, or an allergic or autoimmune condition, according to the FDA announcement. The agency advised that physicians should monitor patient for serious allergic reactions and development or worsening of inflammatory bowel disease.
The most common adverse events seen in clinical trials of ixekizumab were upper respiratory infections, injection site reactions, and tinea.
Ixekizumab will be marketed as Taltz by Eli Lilly and Company.
On Twitter @denisefulton
Atopic Dermatitis Treatments Moving Forward: Report From the AAD Meeting
Although psoriasis was once at the forefront of therapeutic advancements in dermatology, atopic dermatitis (AD) is now taking center stage with several new treatments in the pipeline. Dr. Emma Guttman-Yassky provides an overview of the future of AD treatment, which includes new topical and systemic agents that currently are moving forward in advanced clinical trials or are close to registration. She also discusses strategies for improving disease management in AD patients, noting that prevention and education of both patients and their caregivers are key to effective treatment.
Although psoriasis was once at the forefront of therapeutic advancements in dermatology, atopic dermatitis (AD) is now taking center stage with several new treatments in the pipeline. Dr. Emma Guttman-Yassky provides an overview of the future of AD treatment, which includes new topical and systemic agents that currently are moving forward in advanced clinical trials or are close to registration. She also discusses strategies for improving disease management in AD patients, noting that prevention and education of both patients and their caregivers are key to effective treatment.
Although psoriasis was once at the forefront of therapeutic advancements in dermatology, atopic dermatitis (AD) is now taking center stage with several new treatments in the pipeline. Dr. Emma Guttman-Yassky provides an overview of the future of AD treatment, which includes new topical and systemic agents that currently are moving forward in advanced clinical trials or are close to registration. She also discusses strategies for improving disease management in AD patients, noting that prevention and education of both patients and their caregivers are key to effective treatment.
Sparse, poor evidence supports fumarates for psoriasis
Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.
Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.
Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”
All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.
There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” (Br J Dermatol. 2016. doi: 10.1111/bjd.14500).
These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.
“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.
They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.
No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.
Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.
Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.
Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”
All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.
There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” (Br J Dermatol. 2016. doi: 10.1111/bjd.14500).
These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.
“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.
They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.
No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.
Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.
Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.
Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”
All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.
There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” (Br J Dermatol. 2016. doi: 10.1111/bjd.14500).
These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.
“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.
They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.
No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.
FROM BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: Only sparse, low-quality evidence supports using fumaric acid esters as a treatment for psoriasis.
Major finding: Mean PASI scores decreased 42%-65% in patients treated with fumaric acid esters for 12-16 weeks in randomized controlled trials, but adverse events affected 69%-92% of patients.
Data source: A systematic review of 7 randomized clinical trials and 37 observational studies, involving a total of 3,906 patients.
Disclosures: No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.
Fresh evidence of methotrexate efficacy in psoriatic arthritis
MAUI, HAWAII – The effectiveness of methotrexate in psoriatic arthritis is a matter of debate, but Dr. Arthur Kavanaugh is a believer based in part upon a recent subanalysis of the TICOPA study.
Moreover, his new 5-year follow-up analysis from the GO-REVEAL study of golimumab (Simponi) with or without concomitant methotrexate suggests that methotrexate plus the tumor necrosis factor inhibitor provided synergistic efficacy, he said at the 2016 Rheumatology Winter Clinical Symposium.
The 5-year analysis doesn’t provide definitive proof of synergistic benefit because it wasn’t designed or powered with that endpoint in mind (Arthritis Care Res. 2016;68[2]:267–74). No randomized trial completed to date has been. But the first-ever trial set up to test the synergistic efficacy hypothesis is underway. It’s a 52-week, double-blind, multicenter, randomized trial of etanercept (Enbrel) and methotrexate versus either alone in combination with placebo. And while the Amgen-sponsored study won’t be completed until 2018, Dr. Kavanaugh is ready to predict the outcome based in part upon the message contained in his GO-REVEAL findings.
“I’m placing my bet down now that there will be synergy for the X-ray outcome of change in SHS [Sharp/van der Heijde Score] for sure, and maybe for clinical efficacy as well, both joints and skin,” declared Dr. Kavanaugh, the conference director and professor of medicine at the University of California, San Diego.
He pointed to a new subanalysis of the Tight Control of Psoriatic Arthritis (TICOPA) study reported by rheumatologists at the University of Leeds (England) as evidence that methotrexate is effective in psoriatic arthritis. Of the 188 patients in the tight control arm who received methotrexate in the first 12 weeks of the trial, 41% had an ACR 20 response, meaning a 20% improvement in disease signs and symptoms at 12 weeks. A total of 19% had an ACR 50 response. And 27% had at least a 75% improvement in Psoriasis Area and Severity Index, or PASI 75. A 63% reduction in the proportion of patients with dactylitis and a 26% decrease in the proportion of patients with enthesitis was observed in the early methotrexate group. There was a suggestion of a dose-response effect, with better outcomes seen in the 108 participants who received a mean dose greater than 15 mg/week (J Rheumatol. 2016 Feb;43[2]:356-61).
This is a more impressive result than earlier reported from the Methotrexate In Psoriatic Arthritis (MIPA) trial, where the ACR 20 response rate was only 34% (Rheumatology [Oxford]. 2012;51[8]:1368-77). That may well be because methotrexate was given at only 15 mg/week in MIPA, in Dr. Kavanaugh’s view.
“I think methotrexate can work for the peripheral arthritis. This TICOPA analysis gives us a sense of the extent of the improvement, and also the extent of improvement in the skin,” the rheumatologist commented.
Turning to the week 256 results of GO-REVEAL, he said there was no difference in clinical response between psoriatic arthritis patients on golimumab alone or golimumab plus methotrexate at baseline. But among patients who were doing well clinically, with an assessment of minimal disease activity (MDA) on three or more consecutive clinic visits, only those on golimumab plus methotrexate at baseline showed radiologic improvement. The 57 patients on combination therapy who achieved MDA on at least three consecutive visits showed a mean 1.29-point improvement in SHS; the 48 rated as having MDA on four or more consecutive occasions similarly had a mean 1.24-point improvement.
In contrast, the 59 participants who achieved MDA on three or more consecutive visits but were on golimumab without methotrexate at baseline had a 0.25-point increase in SHS, and the 47 who had MDA on at least four consecutive visits had a 0.38-point SHS bump.
Dr. Kavanaugh reported having financial relationships with roughly a dozen pharmaceutical companies
MAUI, HAWAII – The effectiveness of methotrexate in psoriatic arthritis is a matter of debate, but Dr. Arthur Kavanaugh is a believer based in part upon a recent subanalysis of the TICOPA study.
Moreover, his new 5-year follow-up analysis from the GO-REVEAL study of golimumab (Simponi) with or without concomitant methotrexate suggests that methotrexate plus the tumor necrosis factor inhibitor provided synergistic efficacy, he said at the 2016 Rheumatology Winter Clinical Symposium.
The 5-year analysis doesn’t provide definitive proof of synergistic benefit because it wasn’t designed or powered with that endpoint in mind (Arthritis Care Res. 2016;68[2]:267–74). No randomized trial completed to date has been. But the first-ever trial set up to test the synergistic efficacy hypothesis is underway. It’s a 52-week, double-blind, multicenter, randomized trial of etanercept (Enbrel) and methotrexate versus either alone in combination with placebo. And while the Amgen-sponsored study won’t be completed until 2018, Dr. Kavanaugh is ready to predict the outcome based in part upon the message contained in his GO-REVEAL findings.
“I’m placing my bet down now that there will be synergy for the X-ray outcome of change in SHS [Sharp/van der Heijde Score] for sure, and maybe for clinical efficacy as well, both joints and skin,” declared Dr. Kavanaugh, the conference director and professor of medicine at the University of California, San Diego.
He pointed to a new subanalysis of the Tight Control of Psoriatic Arthritis (TICOPA) study reported by rheumatologists at the University of Leeds (England) as evidence that methotrexate is effective in psoriatic arthritis. Of the 188 patients in the tight control arm who received methotrexate in the first 12 weeks of the trial, 41% had an ACR 20 response, meaning a 20% improvement in disease signs and symptoms at 12 weeks. A total of 19% had an ACR 50 response. And 27% had at least a 75% improvement in Psoriasis Area and Severity Index, or PASI 75. A 63% reduction in the proportion of patients with dactylitis and a 26% decrease in the proportion of patients with enthesitis was observed in the early methotrexate group. There was a suggestion of a dose-response effect, with better outcomes seen in the 108 participants who received a mean dose greater than 15 mg/week (J Rheumatol. 2016 Feb;43[2]:356-61).
This is a more impressive result than earlier reported from the Methotrexate In Psoriatic Arthritis (MIPA) trial, where the ACR 20 response rate was only 34% (Rheumatology [Oxford]. 2012;51[8]:1368-77). That may well be because methotrexate was given at only 15 mg/week in MIPA, in Dr. Kavanaugh’s view.
“I think methotrexate can work for the peripheral arthritis. This TICOPA analysis gives us a sense of the extent of the improvement, and also the extent of improvement in the skin,” the rheumatologist commented.
Turning to the week 256 results of GO-REVEAL, he said there was no difference in clinical response between psoriatic arthritis patients on golimumab alone or golimumab plus methotrexate at baseline. But among patients who were doing well clinically, with an assessment of minimal disease activity (MDA) on three or more consecutive clinic visits, only those on golimumab plus methotrexate at baseline showed radiologic improvement. The 57 patients on combination therapy who achieved MDA on at least three consecutive visits showed a mean 1.29-point improvement in SHS; the 48 rated as having MDA on four or more consecutive occasions similarly had a mean 1.24-point improvement.
In contrast, the 59 participants who achieved MDA on three or more consecutive visits but were on golimumab without methotrexate at baseline had a 0.25-point increase in SHS, and the 47 who had MDA on at least four consecutive visits had a 0.38-point SHS bump.
Dr. Kavanaugh reported having financial relationships with roughly a dozen pharmaceutical companies
MAUI, HAWAII – The effectiveness of methotrexate in psoriatic arthritis is a matter of debate, but Dr. Arthur Kavanaugh is a believer based in part upon a recent subanalysis of the TICOPA study.
Moreover, his new 5-year follow-up analysis from the GO-REVEAL study of golimumab (Simponi) with or without concomitant methotrexate suggests that methotrexate plus the tumor necrosis factor inhibitor provided synergistic efficacy, he said at the 2016 Rheumatology Winter Clinical Symposium.
The 5-year analysis doesn’t provide definitive proof of synergistic benefit because it wasn’t designed or powered with that endpoint in mind (Arthritis Care Res. 2016;68[2]:267–74). No randomized trial completed to date has been. But the first-ever trial set up to test the synergistic efficacy hypothesis is underway. It’s a 52-week, double-blind, multicenter, randomized trial of etanercept (Enbrel) and methotrexate versus either alone in combination with placebo. And while the Amgen-sponsored study won’t be completed until 2018, Dr. Kavanaugh is ready to predict the outcome based in part upon the message contained in his GO-REVEAL findings.
“I’m placing my bet down now that there will be synergy for the X-ray outcome of change in SHS [Sharp/van der Heijde Score] for sure, and maybe for clinical efficacy as well, both joints and skin,” declared Dr. Kavanaugh, the conference director and professor of medicine at the University of California, San Diego.
He pointed to a new subanalysis of the Tight Control of Psoriatic Arthritis (TICOPA) study reported by rheumatologists at the University of Leeds (England) as evidence that methotrexate is effective in psoriatic arthritis. Of the 188 patients in the tight control arm who received methotrexate in the first 12 weeks of the trial, 41% had an ACR 20 response, meaning a 20% improvement in disease signs and symptoms at 12 weeks. A total of 19% had an ACR 50 response. And 27% had at least a 75% improvement in Psoriasis Area and Severity Index, or PASI 75. A 63% reduction in the proportion of patients with dactylitis and a 26% decrease in the proportion of patients with enthesitis was observed in the early methotrexate group. There was a suggestion of a dose-response effect, with better outcomes seen in the 108 participants who received a mean dose greater than 15 mg/week (J Rheumatol. 2016 Feb;43[2]:356-61).
This is a more impressive result than earlier reported from the Methotrexate In Psoriatic Arthritis (MIPA) trial, where the ACR 20 response rate was only 34% (Rheumatology [Oxford]. 2012;51[8]:1368-77). That may well be because methotrexate was given at only 15 mg/week in MIPA, in Dr. Kavanaugh’s view.
“I think methotrexate can work for the peripheral arthritis. This TICOPA analysis gives us a sense of the extent of the improvement, and also the extent of improvement in the skin,” the rheumatologist commented.
Turning to the week 256 results of GO-REVEAL, he said there was no difference in clinical response between psoriatic arthritis patients on golimumab alone or golimumab plus methotrexate at baseline. But among patients who were doing well clinically, with an assessment of minimal disease activity (MDA) on three or more consecutive clinic visits, only those on golimumab plus methotrexate at baseline showed radiologic improvement. The 57 patients on combination therapy who achieved MDA on at least three consecutive visits showed a mean 1.29-point improvement in SHS; the 48 rated as having MDA on four or more consecutive occasions similarly had a mean 1.24-point improvement.
In contrast, the 59 participants who achieved MDA on three or more consecutive visits but were on golimumab without methotrexate at baseline had a 0.25-point increase in SHS, and the 47 who had MDA on at least four consecutive visits had a 0.38-point SHS bump.
Dr. Kavanaugh reported having financial relationships with roughly a dozen pharmaceutical companies
EXPERT ANALYSIS FROM RWCS 2016
