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FDA approves infliximab biosimilar Ixifi for all of Remicade’s indications
The Food and Drug Administration has approved Ixifi (infliximab-qbtx), a biosimilar of Remicade, the original infliximab product. Ixifi is the third infliximab biosimilar to be approved by the FDA, and it is approved for all the same indications as Remicade, according to an announcement from its manufacturer, Pfizer.
Ixifi and Remicade are approved for the treatment of rheumatoid arthritis in combination with methotrexate, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The most common adverse events associated with Ixifi are upper respiratory infections, sinusitis, pharyngitis, infusion-related reactions, headache, and abdominal pain.
The Food and Drug Administration has approved Ixifi (infliximab-qbtx), a biosimilar of Remicade, the original infliximab product. Ixifi is the third infliximab biosimilar to be approved by the FDA, and it is approved for all the same indications as Remicade, according to an announcement from its manufacturer, Pfizer.
Ixifi and Remicade are approved for the treatment of rheumatoid arthritis in combination with methotrexate, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The most common adverse events associated with Ixifi are upper respiratory infections, sinusitis, pharyngitis, infusion-related reactions, headache, and abdominal pain.
The Food and Drug Administration has approved Ixifi (infliximab-qbtx), a biosimilar of Remicade, the original infliximab product. Ixifi is the third infliximab biosimilar to be approved by the FDA, and it is approved for all the same indications as Remicade, according to an announcement from its manufacturer, Pfizer.
Ixifi and Remicade are approved for the treatment of rheumatoid arthritis in combination with methotrexate, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The most common adverse events associated with Ixifi are upper respiratory infections, sinusitis, pharyngitis, infusion-related reactions, headache, and abdominal pain.
Interleukin-23 inhibition for psoriasis shows ‘wow’ factor
GENEVA – The merits of addressing interleukin-23 as a novel therapeutic target in moderate to severe plaque psoriasis were abundantly displayed in 2-year outcomes data for two anti–IL-23 monoclonal antibodies – guselkumab and tildrakizumab – in studies presented back to back at the annual congress of the European Academy of Dermatology and Venereology.
These long-term, open-label extensions of previously reported phase 3, randomized, double-blind clinical trials provided evidence of multiple advantages for IL-23 inhibition. The story was similar for both agents: After 2 years of use in the extension studies, the two biologics demonstrated stellar treatment response rates that would have been unimaginable only a few years ago, maintenance of efficacy without drop-off over time, exceedingly low dropout rates, and a safety picture that remains reassuring as experience accumulates. Also, the subcutaneously administered IL-23 inhibitors are attractive from a patient convenience standpoint in that maintenance guselkumab is dosed at 100 mg once every 8 weeks, and tildrakizumab is given once every 12 weeks.
Still, there are differences between the two drugs, most notably in apparent effectiveness. While more than half of guselkumab-treated patients had a Psoriasis Area Severity Index (PASI) 100 response – that is, totally clear skin – at 2 years, that was the case for only one-quarter to one-third of patients on tildrakizumab.
Guselkumab (Tremfya) was approved by the Food and Drug Administration in July 2017 for treatment of adults with moderate to severe plaque psoriasis. Tildrakizumab remains investigational.
Guselkumab
The 2-year, open-label extension of the phase 3 VOYAGE 1 trial included 735 patients who were either on guselkumab continuously, crossed from adalimumab (Humira) to guselkumab after 48 weeks, or switched from placebo after 16 weeks.
PASI 100 rates at 2 years were 49%-55% in the three patient groups. Of the patients in these groups, 54%-59% achieved an Investigator’s Global Assessment (IGA) score of 0. IGA scores of 0 or 1, meaning clear or almost clear skin, were present in 82%-85% of patients at 2 years.
“Dropout rate is an important consideration in long-term studies,” observed Dr. Blauvelt, a dermatologist and president of Oregon Medical Research Center in Portland. “For patients on continuous guselkumab there was a 6% dropout rate in the first year and 6% in the second year, so 88% of patients that started guselkumab were still on guselkumab 2 years later. That’s impressive. In the other two groups, the dropout rate was 2% per year.”
A Dermatology Life Quality Index (DLQI) score of 0 or 1, meaning no disease effects on quality of life, was recorded in 62.5% of the continuous guselkumab group at 48 weeks and 71.1% at 2 years.
“The interesting thing here is that, even though the efficacy numbers are fairly constant between year 1 and year 2, the DLQI goes up and up. Surprising? Maybe not. I think it shows patients are getting happier and happier over time with their disease control,” Dr. Blauvelt continued.
Rates of serious adverse events remained low and stable, with no negative surprises during year 2. The serious infection rate was 1.02 cases/100 patient-years in year 1 and 0.84 cases/100 patient-years in year 2. No cases of tuberculosis, opportunistic infections, or serious hypersensitivity reactions occurred during 2 years of treatment.
Tildrakizumab
Two-year results from the ongoing 5-year extension of the phase 3 reSURFACE 1 and reSURFACE 2 trials were presented by Kim A. Papp, MD, PhD, president of Probity Medical Research, Waterloo, Ont. This presentation of 2-year outcomes for 1,237 study participants was a feat, considering that the 12-week results of the trials had been published less than 3 months earlier (Lancet. 2017 Jul 15;390[10091]:276-88).
“I think these data are very compelling that the loss of response over time is minimal,” according to the dermatologist. “We’ve also seen that safety over 2 years has no surprises; in fact, it’s remarkably quiet. The rate of severe infections, which is important to look at for any treatment suppressing the immune system, is low and occurs almost independent of dose, which is very hopeful. It’s a promising sign.”
Indeed, the serious infection rate was 0.8 cases/100 patient-years regardless of whether subjects were on tildrakizumab at 100 mg or 200 mg.
Controversy over how to report long-term outcomes
A hot topic among clinical trialists in dermatology concerns how to report study results. The traditional method in studies funded by pharmaceutical companies is known as the “last observation carried forward” analysis. It casts the study drug results in the most favorable possible light because, when a subject drops out of a trial for any reason, their last measured value for response to treatment is carried forward as though the patient completed the study. Thus, psoriasis patients who drop out because they couldn’t tolerate a therapy or developed a serious side effect dictating discontinuation will be scored on the basis of their last PASI response, creating a bias in favor of active treatment.
A more conservative analytic method is known as the “nonresponder imputation” analysis. By this method, a patient who drops out of a trial is automatically categorized as a treatment failure, even if the reason was that the patient moved and could no longer make visits to the study center.
The prespecified guselkumab analysis presented by Dr. Blauvelt involved nonresponder imputation through year 1 and imputation based on the reason for discontinuation in the second year. In contrast, the 2-year tildrakizumab analysis presented by Dr. Papp used the far more common last observation carried forward method.
To help the audience appreciate the importance of looking at the analytic methods used in a studies and help them understand the clinical significance of the results, Dr. Blauvelt provided a reanalysis of the 2-year guselkumab data using the last observation carried forward method. Across the board, the numbers became more favorable. For example, the PASI 75 rate of 95.7% using the prespecified nonresponder imputation analysis crept up to 96.8% under the last observation carried forward method; for comparison, the PASI 75 rates were 81%-84% in the tildrakizumab analysis.
“If you wanted to compare apples to apples with some other drugs, you would use these numbers – the as-observed analysis numbers used by most other companies with other drugs. If you wanted to determine what the true-life numbers are, they’d probably be something between the nonresponder imputation and as-observed numbers,” said to Dr. Blauvelt.
Dr. Papp was untroubled by the use of the last observation carried forward method in the particular case of the tildrakizumab long-term extension study.
“There is reason to believe the as-observed analysis doesn’t affect the integrity of the data because the dropout rate is extraordinarily low,” he said.
The guselkumab analysis was sponsored by Janssen Pharmaceutica; the tildrakizumab analysis was sponsored by Merck and by Sun Pharma. Dr. Blauvelt and Dr. Papp were paid investigators in both studies and serve as scientific advisers to virtually all companies invested in the psoriasis therapy developmental pipeline.
GENEVA – The merits of addressing interleukin-23 as a novel therapeutic target in moderate to severe plaque psoriasis were abundantly displayed in 2-year outcomes data for two anti–IL-23 monoclonal antibodies – guselkumab and tildrakizumab – in studies presented back to back at the annual congress of the European Academy of Dermatology and Venereology.
These long-term, open-label extensions of previously reported phase 3, randomized, double-blind clinical trials provided evidence of multiple advantages for IL-23 inhibition. The story was similar for both agents: After 2 years of use in the extension studies, the two biologics demonstrated stellar treatment response rates that would have been unimaginable only a few years ago, maintenance of efficacy without drop-off over time, exceedingly low dropout rates, and a safety picture that remains reassuring as experience accumulates. Also, the subcutaneously administered IL-23 inhibitors are attractive from a patient convenience standpoint in that maintenance guselkumab is dosed at 100 mg once every 8 weeks, and tildrakizumab is given once every 12 weeks.
Still, there are differences between the two drugs, most notably in apparent effectiveness. While more than half of guselkumab-treated patients had a Psoriasis Area Severity Index (PASI) 100 response – that is, totally clear skin – at 2 years, that was the case for only one-quarter to one-third of patients on tildrakizumab.
Guselkumab (Tremfya) was approved by the Food and Drug Administration in July 2017 for treatment of adults with moderate to severe plaque psoriasis. Tildrakizumab remains investigational.
Guselkumab
The 2-year, open-label extension of the phase 3 VOYAGE 1 trial included 735 patients who were either on guselkumab continuously, crossed from adalimumab (Humira) to guselkumab after 48 weeks, or switched from placebo after 16 weeks.
PASI 100 rates at 2 years were 49%-55% in the three patient groups. Of the patients in these groups, 54%-59% achieved an Investigator’s Global Assessment (IGA) score of 0. IGA scores of 0 or 1, meaning clear or almost clear skin, were present in 82%-85% of patients at 2 years.
“Dropout rate is an important consideration in long-term studies,” observed Dr. Blauvelt, a dermatologist and president of Oregon Medical Research Center in Portland. “For patients on continuous guselkumab there was a 6% dropout rate in the first year and 6% in the second year, so 88% of patients that started guselkumab were still on guselkumab 2 years later. That’s impressive. In the other two groups, the dropout rate was 2% per year.”
A Dermatology Life Quality Index (DLQI) score of 0 or 1, meaning no disease effects on quality of life, was recorded in 62.5% of the continuous guselkumab group at 48 weeks and 71.1% at 2 years.
“The interesting thing here is that, even though the efficacy numbers are fairly constant between year 1 and year 2, the DLQI goes up and up. Surprising? Maybe not. I think it shows patients are getting happier and happier over time with their disease control,” Dr. Blauvelt continued.
Rates of serious adverse events remained low and stable, with no negative surprises during year 2. The serious infection rate was 1.02 cases/100 patient-years in year 1 and 0.84 cases/100 patient-years in year 2. No cases of tuberculosis, opportunistic infections, or serious hypersensitivity reactions occurred during 2 years of treatment.
Tildrakizumab
Two-year results from the ongoing 5-year extension of the phase 3 reSURFACE 1 and reSURFACE 2 trials were presented by Kim A. Papp, MD, PhD, president of Probity Medical Research, Waterloo, Ont. This presentation of 2-year outcomes for 1,237 study participants was a feat, considering that the 12-week results of the trials had been published less than 3 months earlier (Lancet. 2017 Jul 15;390[10091]:276-88).
“I think these data are very compelling that the loss of response over time is minimal,” according to the dermatologist. “We’ve also seen that safety over 2 years has no surprises; in fact, it’s remarkably quiet. The rate of severe infections, which is important to look at for any treatment suppressing the immune system, is low and occurs almost independent of dose, which is very hopeful. It’s a promising sign.”
Indeed, the serious infection rate was 0.8 cases/100 patient-years regardless of whether subjects were on tildrakizumab at 100 mg or 200 mg.
Controversy over how to report long-term outcomes
A hot topic among clinical trialists in dermatology concerns how to report study results. The traditional method in studies funded by pharmaceutical companies is known as the “last observation carried forward” analysis. It casts the study drug results in the most favorable possible light because, when a subject drops out of a trial for any reason, their last measured value for response to treatment is carried forward as though the patient completed the study. Thus, psoriasis patients who drop out because they couldn’t tolerate a therapy or developed a serious side effect dictating discontinuation will be scored on the basis of their last PASI response, creating a bias in favor of active treatment.
A more conservative analytic method is known as the “nonresponder imputation” analysis. By this method, a patient who drops out of a trial is automatically categorized as a treatment failure, even if the reason was that the patient moved and could no longer make visits to the study center.
The prespecified guselkumab analysis presented by Dr. Blauvelt involved nonresponder imputation through year 1 and imputation based on the reason for discontinuation in the second year. In contrast, the 2-year tildrakizumab analysis presented by Dr. Papp used the far more common last observation carried forward method.
To help the audience appreciate the importance of looking at the analytic methods used in a studies and help them understand the clinical significance of the results, Dr. Blauvelt provided a reanalysis of the 2-year guselkumab data using the last observation carried forward method. Across the board, the numbers became more favorable. For example, the PASI 75 rate of 95.7% using the prespecified nonresponder imputation analysis crept up to 96.8% under the last observation carried forward method; for comparison, the PASI 75 rates were 81%-84% in the tildrakizumab analysis.
“If you wanted to compare apples to apples with some other drugs, you would use these numbers – the as-observed analysis numbers used by most other companies with other drugs. If you wanted to determine what the true-life numbers are, they’d probably be something between the nonresponder imputation and as-observed numbers,” said to Dr. Blauvelt.
Dr. Papp was untroubled by the use of the last observation carried forward method in the particular case of the tildrakizumab long-term extension study.
“There is reason to believe the as-observed analysis doesn’t affect the integrity of the data because the dropout rate is extraordinarily low,” he said.
The guselkumab analysis was sponsored by Janssen Pharmaceutica; the tildrakizumab analysis was sponsored by Merck and by Sun Pharma. Dr. Blauvelt and Dr. Papp were paid investigators in both studies and serve as scientific advisers to virtually all companies invested in the psoriasis therapy developmental pipeline.
GENEVA – The merits of addressing interleukin-23 as a novel therapeutic target in moderate to severe plaque psoriasis were abundantly displayed in 2-year outcomes data for two anti–IL-23 monoclonal antibodies – guselkumab and tildrakizumab – in studies presented back to back at the annual congress of the European Academy of Dermatology and Venereology.
These long-term, open-label extensions of previously reported phase 3, randomized, double-blind clinical trials provided evidence of multiple advantages for IL-23 inhibition. The story was similar for both agents: After 2 years of use in the extension studies, the two biologics demonstrated stellar treatment response rates that would have been unimaginable only a few years ago, maintenance of efficacy without drop-off over time, exceedingly low dropout rates, and a safety picture that remains reassuring as experience accumulates. Also, the subcutaneously administered IL-23 inhibitors are attractive from a patient convenience standpoint in that maintenance guselkumab is dosed at 100 mg once every 8 weeks, and tildrakizumab is given once every 12 weeks.
Still, there are differences between the two drugs, most notably in apparent effectiveness. While more than half of guselkumab-treated patients had a Psoriasis Area Severity Index (PASI) 100 response – that is, totally clear skin – at 2 years, that was the case for only one-quarter to one-third of patients on tildrakizumab.
Guselkumab (Tremfya) was approved by the Food and Drug Administration in July 2017 for treatment of adults with moderate to severe plaque psoriasis. Tildrakizumab remains investigational.
Guselkumab
The 2-year, open-label extension of the phase 3 VOYAGE 1 trial included 735 patients who were either on guselkumab continuously, crossed from adalimumab (Humira) to guselkumab after 48 weeks, or switched from placebo after 16 weeks.
PASI 100 rates at 2 years were 49%-55% in the three patient groups. Of the patients in these groups, 54%-59% achieved an Investigator’s Global Assessment (IGA) score of 0. IGA scores of 0 or 1, meaning clear or almost clear skin, were present in 82%-85% of patients at 2 years.
“Dropout rate is an important consideration in long-term studies,” observed Dr. Blauvelt, a dermatologist and president of Oregon Medical Research Center in Portland. “For patients on continuous guselkumab there was a 6% dropout rate in the first year and 6% in the second year, so 88% of patients that started guselkumab were still on guselkumab 2 years later. That’s impressive. In the other two groups, the dropout rate was 2% per year.”
A Dermatology Life Quality Index (DLQI) score of 0 or 1, meaning no disease effects on quality of life, was recorded in 62.5% of the continuous guselkumab group at 48 weeks and 71.1% at 2 years.
“The interesting thing here is that, even though the efficacy numbers are fairly constant between year 1 and year 2, the DLQI goes up and up. Surprising? Maybe not. I think it shows patients are getting happier and happier over time with their disease control,” Dr. Blauvelt continued.
Rates of serious adverse events remained low and stable, with no negative surprises during year 2. The serious infection rate was 1.02 cases/100 patient-years in year 1 and 0.84 cases/100 patient-years in year 2. No cases of tuberculosis, opportunistic infections, or serious hypersensitivity reactions occurred during 2 years of treatment.
Tildrakizumab
Two-year results from the ongoing 5-year extension of the phase 3 reSURFACE 1 and reSURFACE 2 trials were presented by Kim A. Papp, MD, PhD, president of Probity Medical Research, Waterloo, Ont. This presentation of 2-year outcomes for 1,237 study participants was a feat, considering that the 12-week results of the trials had been published less than 3 months earlier (Lancet. 2017 Jul 15;390[10091]:276-88).
“I think these data are very compelling that the loss of response over time is minimal,” according to the dermatologist. “We’ve also seen that safety over 2 years has no surprises; in fact, it’s remarkably quiet. The rate of severe infections, which is important to look at for any treatment suppressing the immune system, is low and occurs almost independent of dose, which is very hopeful. It’s a promising sign.”
Indeed, the serious infection rate was 0.8 cases/100 patient-years regardless of whether subjects were on tildrakizumab at 100 mg or 200 mg.
Controversy over how to report long-term outcomes
A hot topic among clinical trialists in dermatology concerns how to report study results. The traditional method in studies funded by pharmaceutical companies is known as the “last observation carried forward” analysis. It casts the study drug results in the most favorable possible light because, when a subject drops out of a trial for any reason, their last measured value for response to treatment is carried forward as though the patient completed the study. Thus, psoriasis patients who drop out because they couldn’t tolerate a therapy or developed a serious side effect dictating discontinuation will be scored on the basis of their last PASI response, creating a bias in favor of active treatment.
A more conservative analytic method is known as the “nonresponder imputation” analysis. By this method, a patient who drops out of a trial is automatically categorized as a treatment failure, even if the reason was that the patient moved and could no longer make visits to the study center.
The prespecified guselkumab analysis presented by Dr. Blauvelt involved nonresponder imputation through year 1 and imputation based on the reason for discontinuation in the second year. In contrast, the 2-year tildrakizumab analysis presented by Dr. Papp used the far more common last observation carried forward method.
To help the audience appreciate the importance of looking at the analytic methods used in a studies and help them understand the clinical significance of the results, Dr. Blauvelt provided a reanalysis of the 2-year guselkumab data using the last observation carried forward method. Across the board, the numbers became more favorable. For example, the PASI 75 rate of 95.7% using the prespecified nonresponder imputation analysis crept up to 96.8% under the last observation carried forward method; for comparison, the PASI 75 rates were 81%-84% in the tildrakizumab analysis.
“If you wanted to compare apples to apples with some other drugs, you would use these numbers – the as-observed analysis numbers used by most other companies with other drugs. If you wanted to determine what the true-life numbers are, they’d probably be something between the nonresponder imputation and as-observed numbers,” said to Dr. Blauvelt.
Dr. Papp was untroubled by the use of the last observation carried forward method in the particular case of the tildrakizumab long-term extension study.
“There is reason to believe the as-observed analysis doesn’t affect the integrity of the data because the dropout rate is extraordinarily low,” he said.
The guselkumab analysis was sponsored by Janssen Pharmaceutica; the tildrakizumab analysis was sponsored by Merck and by Sun Pharma. Dr. Blauvelt and Dr. Papp were paid investigators in both studies and serve as scientific advisers to virtually all companies invested in the psoriasis therapy developmental pipeline.
expert analysis from tHE EADV CONGRESS
Debunking Psoriasis Myths: Which Psoriasis Therapies Can Be Used in Pregnant Women?
Myth: Psoriasis Treatments Should Not Be Used During Pregnancy
It is likely that dermatologists will encounter female patients with psoriasis who are pregnant or wish to become pregnant during the course of their psoriasis treatment. Earlier this year Porter et al evaluated several psoriasis therapies and discussed their safety for patients with psoriasis during pregnancy. Because psoriasis is a risk factor for adverse pregnancy outcomes, control of disease prior to and during pregnancy may optimize maternal and fetal health, according to the authors. As a result, they outlined the following treatment recommendations:
- Consider anti–tumor necrosis factor (TNF) α agents over IL-12/IL-23 and IL-17 inhibitors.
- Anti–TNF-α agents can be used during the first half of pregnancy.
- Longer-term use of anti–TNF-α agents during pregnancy can be considered depending on psoriasis disease severity.
- If biologic therapy is required during pregnancy, use certolizumab because it does not cross the placenta in significant amounts; etanercept also may be a reasonable alternative.
- Babies born to mothers who are continually treated with biologic agents should not be administered live vaccinations for at least 6 months after birth due to the increased risk of infection; inactive vaccinations can be administered according to Centers for Disease Control and Prevention guidelines.
- Breastfeeding by mothers currently treated with anti–TNF-α agents is generally considered safe.
- Cotreatment with methotrexate and a biologic agent should be avoided.
However, the National Psoriasis Foundation guidelines for treating psoriasis in pregnant or breastfeeding women advise that topical treatments are the first choice of treatment, particularly moisturizers and emollients. Limited use of low- to moderate-potency topical steroids appears to be safe, but women should avoid applying topical steroids to the breasts. Second-line treatment is narrowband UVB phototherapy; if narrowband UVB is not available, use broadband UVB. Breastfeeding women should avoid psoralen plus UVA. The foundation also advises that systemic and biologic drugs should be avoided while pregnant or breastfeeding unless there is a clear medical need. Childbearing women should avoid oral retinoids, methotrexate, and cyclosporine due to a link to birth defects. A useful table of US Food and Drug Administration–approved psoriasis treatments and their category for use by pregnant and breastfeeding women is available online. Specifically, drugs that should absolutely be avoided in this patient population include acitretin, methotrexate, and tazarotene.
For some patients, discontinuing therapy may not be practical. Dermatologists should be prepared to weigh the risks and benefits of treatment to advise patients appropriately. According to Dr. Jeffrey M. Weinberg’s pearls for treating psoriasis in pregnant women in Cutis, “Most biologic therapies are pregnancy category B. We still use these drugs with caution in the setting of pregnancy. If a pregnant patient does wish to continue a biologic therapy, close monitoring and enrollment in a pregnancy registry would be good options.”
RELATED ARTICLE: How to Manage Psoriasis Safely in Pregnant Women
More research is necessary; however, pregnant women often are excluded from clinical trials. Therefore, adverse outcomes should be reported to registries such as the Organization of Teratology Information Specialists or others sponsored by drug manufacturers, which will aid in understanding the effects of psoriasis treatments in pregnant and breastfeeding women.
Expert Commentary
The treatment of psoriasis in pregnancy should be approached in a thoughtful manner. While we always want to minimize therapeutic interventions in pregnant individuals, we also want to maintain control of a disease such as psoriasis. As outlined in this article, there is good amount of flexibility in terms of therapies available to us. It is important to discuss the situation carefully, including the benefits and risks, with the patient and the obstetric professionals, in order to design the optimal regimen for each individual.
—Jeffrey M. Weinberg (New York, New York)
FDA determinations for pregnant and nursing women. National Psoriasis Foundation website. https://www.psoriasis.org/pregnancy/fda-determinations. Accessed December 4, 2017.
Porter ML, Lockwood SJ, Kimball AB. Update on biologic safety for patients with psoriasis during pregnancy. Int J Womens Dermatol. 2017;3:21-25.
Psoriasis and pregnancy: treatment options, psoriatic arthritis, and genetics. National Psoriasis Foundation website. https://www.psoriasis.org/pregnancy. Accessed December 4, 2017.
Weinberg JM. Treating psoriasis in pregnant women. Cutis. 2015;96:80.
Myth: Psoriasis Treatments Should Not Be Used During Pregnancy
It is likely that dermatologists will encounter female patients with psoriasis who are pregnant or wish to become pregnant during the course of their psoriasis treatment. Earlier this year Porter et al evaluated several psoriasis therapies and discussed their safety for patients with psoriasis during pregnancy. Because psoriasis is a risk factor for adverse pregnancy outcomes, control of disease prior to and during pregnancy may optimize maternal and fetal health, according to the authors. As a result, they outlined the following treatment recommendations:
- Consider anti–tumor necrosis factor (TNF) α agents over IL-12/IL-23 and IL-17 inhibitors.
- Anti–TNF-α agents can be used during the first half of pregnancy.
- Longer-term use of anti–TNF-α agents during pregnancy can be considered depending on psoriasis disease severity.
- If biologic therapy is required during pregnancy, use certolizumab because it does not cross the placenta in significant amounts; etanercept also may be a reasonable alternative.
- Babies born to mothers who are continually treated with biologic agents should not be administered live vaccinations for at least 6 months after birth due to the increased risk of infection; inactive vaccinations can be administered according to Centers for Disease Control and Prevention guidelines.
- Breastfeeding by mothers currently treated with anti–TNF-α agents is generally considered safe.
- Cotreatment with methotrexate and a biologic agent should be avoided.
However, the National Psoriasis Foundation guidelines for treating psoriasis in pregnant or breastfeeding women advise that topical treatments are the first choice of treatment, particularly moisturizers and emollients. Limited use of low- to moderate-potency topical steroids appears to be safe, but women should avoid applying topical steroids to the breasts. Second-line treatment is narrowband UVB phototherapy; if narrowband UVB is not available, use broadband UVB. Breastfeeding women should avoid psoralen plus UVA. The foundation also advises that systemic and biologic drugs should be avoided while pregnant or breastfeeding unless there is a clear medical need. Childbearing women should avoid oral retinoids, methotrexate, and cyclosporine due to a link to birth defects. A useful table of US Food and Drug Administration–approved psoriasis treatments and their category for use by pregnant and breastfeeding women is available online. Specifically, drugs that should absolutely be avoided in this patient population include acitretin, methotrexate, and tazarotene.
For some patients, discontinuing therapy may not be practical. Dermatologists should be prepared to weigh the risks and benefits of treatment to advise patients appropriately. According to Dr. Jeffrey M. Weinberg’s pearls for treating psoriasis in pregnant women in Cutis, “Most biologic therapies are pregnancy category B. We still use these drugs with caution in the setting of pregnancy. If a pregnant patient does wish to continue a biologic therapy, close monitoring and enrollment in a pregnancy registry would be good options.”
RELATED ARTICLE: How to Manage Psoriasis Safely in Pregnant Women
More research is necessary; however, pregnant women often are excluded from clinical trials. Therefore, adverse outcomes should be reported to registries such as the Organization of Teratology Information Specialists or others sponsored by drug manufacturers, which will aid in understanding the effects of psoriasis treatments in pregnant and breastfeeding women.
Expert Commentary
The treatment of psoriasis in pregnancy should be approached in a thoughtful manner. While we always want to minimize therapeutic interventions in pregnant individuals, we also want to maintain control of a disease such as psoriasis. As outlined in this article, there is good amount of flexibility in terms of therapies available to us. It is important to discuss the situation carefully, including the benefits and risks, with the patient and the obstetric professionals, in order to design the optimal regimen for each individual.
—Jeffrey M. Weinberg (New York, New York)
Myth: Psoriasis Treatments Should Not Be Used During Pregnancy
It is likely that dermatologists will encounter female patients with psoriasis who are pregnant or wish to become pregnant during the course of their psoriasis treatment. Earlier this year Porter et al evaluated several psoriasis therapies and discussed their safety for patients with psoriasis during pregnancy. Because psoriasis is a risk factor for adverse pregnancy outcomes, control of disease prior to and during pregnancy may optimize maternal and fetal health, according to the authors. As a result, they outlined the following treatment recommendations:
- Consider anti–tumor necrosis factor (TNF) α agents over IL-12/IL-23 and IL-17 inhibitors.
- Anti–TNF-α agents can be used during the first half of pregnancy.
- Longer-term use of anti–TNF-α agents during pregnancy can be considered depending on psoriasis disease severity.
- If biologic therapy is required during pregnancy, use certolizumab because it does not cross the placenta in significant amounts; etanercept also may be a reasonable alternative.
- Babies born to mothers who are continually treated with biologic agents should not be administered live vaccinations for at least 6 months after birth due to the increased risk of infection; inactive vaccinations can be administered according to Centers for Disease Control and Prevention guidelines.
- Breastfeeding by mothers currently treated with anti–TNF-α agents is generally considered safe.
- Cotreatment with methotrexate and a biologic agent should be avoided.
However, the National Psoriasis Foundation guidelines for treating psoriasis in pregnant or breastfeeding women advise that topical treatments are the first choice of treatment, particularly moisturizers and emollients. Limited use of low- to moderate-potency topical steroids appears to be safe, but women should avoid applying topical steroids to the breasts. Second-line treatment is narrowband UVB phototherapy; if narrowband UVB is not available, use broadband UVB. Breastfeeding women should avoid psoralen plus UVA. The foundation also advises that systemic and biologic drugs should be avoided while pregnant or breastfeeding unless there is a clear medical need. Childbearing women should avoid oral retinoids, methotrexate, and cyclosporine due to a link to birth defects. A useful table of US Food and Drug Administration–approved psoriasis treatments and their category for use by pregnant and breastfeeding women is available online. Specifically, drugs that should absolutely be avoided in this patient population include acitretin, methotrexate, and tazarotene.
For some patients, discontinuing therapy may not be practical. Dermatologists should be prepared to weigh the risks and benefits of treatment to advise patients appropriately. According to Dr. Jeffrey M. Weinberg’s pearls for treating psoriasis in pregnant women in Cutis, “Most biologic therapies are pregnancy category B. We still use these drugs with caution in the setting of pregnancy. If a pregnant patient does wish to continue a biologic therapy, close monitoring and enrollment in a pregnancy registry would be good options.”
RELATED ARTICLE: How to Manage Psoriasis Safely in Pregnant Women
More research is necessary; however, pregnant women often are excluded from clinical trials. Therefore, adverse outcomes should be reported to registries such as the Organization of Teratology Information Specialists or others sponsored by drug manufacturers, which will aid in understanding the effects of psoriasis treatments in pregnant and breastfeeding women.
Expert Commentary
The treatment of psoriasis in pregnancy should be approached in a thoughtful manner. While we always want to minimize therapeutic interventions in pregnant individuals, we also want to maintain control of a disease such as psoriasis. As outlined in this article, there is good amount of flexibility in terms of therapies available to us. It is important to discuss the situation carefully, including the benefits and risks, with the patient and the obstetric professionals, in order to design the optimal regimen for each individual.
—Jeffrey M. Weinberg (New York, New York)
FDA determinations for pregnant and nursing women. National Psoriasis Foundation website. https://www.psoriasis.org/pregnancy/fda-determinations. Accessed December 4, 2017.
Porter ML, Lockwood SJ, Kimball AB. Update on biologic safety for patients with psoriasis during pregnancy. Int J Womens Dermatol. 2017;3:21-25.
Psoriasis and pregnancy: treatment options, psoriatic arthritis, and genetics. National Psoriasis Foundation website. https://www.psoriasis.org/pregnancy. Accessed December 4, 2017.
Weinberg JM. Treating psoriasis in pregnant women. Cutis. 2015;96:80.
FDA determinations for pregnant and nursing women. National Psoriasis Foundation website. https://www.psoriasis.org/pregnancy/fda-determinations. Accessed December 4, 2017.
Porter ML, Lockwood SJ, Kimball AB. Update on biologic safety for patients with psoriasis during pregnancy. Int J Womens Dermatol. 2017;3:21-25.
Psoriasis and pregnancy: treatment options, psoriatic arthritis, and genetics. National Psoriasis Foundation website. https://www.psoriasis.org/pregnancy. Accessed December 4, 2017.
Weinberg JM. Treating psoriasis in pregnant women. Cutis. 2015;96:80.
Biosimilars and sources show mostly parallel safety profiles
Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.
“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.
In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).
Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.
Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).
For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity
The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.
The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.
The researchers had no financial conflicts to disclose.
Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.
“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.
In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).
Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.
Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).
For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity
The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.
The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.
The researchers had no financial conflicts to disclose.
Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.
“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.
In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).
Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.
Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).
For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity
The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.
The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.
The researchers had no financial conflicts to disclose.
FROM THE BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Key clinical point: Most biosimilars show safety profiles comparable to their originators.
Major finding: Infliximab biosimilars demonstrated three more general safety concerns than the originator.
Data source: The data come from a cross-sectional analysis 19 biosimilars and 6 originators.
Disclosures: The researchers had no financial conflicts to disclose.
FDA approves IL-17A antagonist for treating psoriatic arthritis
The interleukin-17A antagonist ixekizumab has been approved by the Food and Drug Administration for treating adults with active psoriatic arthritis (PsA), based on two phase 3 studies, the manufacturer announced in a written statement Dec. 1.
The Eli Lilly statement noted that the approval is based on two randomized, double-blind, placebo-controlled studies; one compared ixekizumab to placebo in patients with active PsA never treated with a biologic (SPIRIT-P1) and another tested the drug in those who had been treated with a tumor necrosis factor inhibitor (TNFi) previously (SPIRIT-P2).
Ixekizumab, marketed as Taltz by Eli Lilly, was first approved by the FDA in 2016 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The statement did not provide information on dermatologic endpoints, but treatment with ixekizumab “resulted in an improvement in psoriatic skin lesions in patients with PsA,” as well as “in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis,” according to the prescribing information.
The recommended dose for patients with psoriatic arthritis is 160 mg by subcutaneous injection (two 80 mg injections) at baseline, followed by 80 mg every 4 weeks. When patients with psoriatic arthritis also have moderate-to-severe plaque psoriasis, then the prescribing information recommends following the dosing for psoriasis, which is 160 mg (two 80 mg injections) at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
The most common adverse reactions associated with ixekizumab are injection site reactions, upper respiratory tract infections, nausea, and tinea infections, according to the warnings and precautions section of the drug’s prescribing information, which lists the potential for serious infections, tuberculosis, and serious allergic reactions. Prescriptions come with a Medication Guide for patients.
The interleukin-17A antagonist ixekizumab has been approved by the Food and Drug Administration for treating adults with active psoriatic arthritis (PsA), based on two phase 3 studies, the manufacturer announced in a written statement Dec. 1.
The Eli Lilly statement noted that the approval is based on two randomized, double-blind, placebo-controlled studies; one compared ixekizumab to placebo in patients with active PsA never treated with a biologic (SPIRIT-P1) and another tested the drug in those who had been treated with a tumor necrosis factor inhibitor (TNFi) previously (SPIRIT-P2).
Ixekizumab, marketed as Taltz by Eli Lilly, was first approved by the FDA in 2016 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The statement did not provide information on dermatologic endpoints, but treatment with ixekizumab “resulted in an improvement in psoriatic skin lesions in patients with PsA,” as well as “in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis,” according to the prescribing information.
The recommended dose for patients with psoriatic arthritis is 160 mg by subcutaneous injection (two 80 mg injections) at baseline, followed by 80 mg every 4 weeks. When patients with psoriatic arthritis also have moderate-to-severe plaque psoriasis, then the prescribing information recommends following the dosing for psoriasis, which is 160 mg (two 80 mg injections) at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
The most common adverse reactions associated with ixekizumab are injection site reactions, upper respiratory tract infections, nausea, and tinea infections, according to the warnings and precautions section of the drug’s prescribing information, which lists the potential for serious infections, tuberculosis, and serious allergic reactions. Prescriptions come with a Medication Guide for patients.
The interleukin-17A antagonist ixekizumab has been approved by the Food and Drug Administration for treating adults with active psoriatic arthritis (PsA), based on two phase 3 studies, the manufacturer announced in a written statement Dec. 1.
The Eli Lilly statement noted that the approval is based on two randomized, double-blind, placebo-controlled studies; one compared ixekizumab to placebo in patients with active PsA never treated with a biologic (SPIRIT-P1) and another tested the drug in those who had been treated with a tumor necrosis factor inhibitor (TNFi) previously (SPIRIT-P2).
Ixekizumab, marketed as Taltz by Eli Lilly, was first approved by the FDA in 2016 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The statement did not provide information on dermatologic endpoints, but treatment with ixekizumab “resulted in an improvement in psoriatic skin lesions in patients with PsA,” as well as “in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis,” according to the prescribing information.
The recommended dose for patients with psoriatic arthritis is 160 mg by subcutaneous injection (two 80 mg injections) at baseline, followed by 80 mg every 4 weeks. When patients with psoriatic arthritis also have moderate-to-severe plaque psoriasis, then the prescribing information recommends following the dosing for psoriasis, which is 160 mg (two 80 mg injections) at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
The most common adverse reactions associated with ixekizumab are injection site reactions, upper respiratory tract infections, nausea, and tinea infections, according to the warnings and precautions section of the drug’s prescribing information, which lists the potential for serious infections, tuberculosis, and serious allergic reactions. Prescriptions come with a Medication Guide for patients.
Oral and Injectable Medications for Psoriasis: Benefits and Downsides Requiring Patient Support
Approximately three-quarters of respondents indicated that they have used oral or injectable medications (eg, methotrexate, acitretin, cyclosporine, apremilast, biologics) to control their psoriasis, according to a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.
Patients universally spoke about the benefits of their current treatments, especially the biologics, but variable experiences regarding the effectiveness of the therapies were reported, ranging from excellent improvement, to improvement that lasted only a few months, to a near-complete clearance. However, limitations to these therapies also were mentioned, which are areas where dermatologists can provide counseling and alternatives. For example, treatments were reported to be effective in clearing cutaneous psoriasis symptoms such as flaking and scaling, but pruritus, burning, and pain were still problematic and mostly limited to areas where the cutaneous symptoms had been located.
Other treatment downsides that dermatologists should discuss with patients are side effects, including fatigue, nausea, fluctuations in weight, increased facial hair growth, nosebleeds, increased blood pressure, headaches, and palpitations, according to the patients present at the meeting. Patients also expressed concern about immune compromise from the biologics. Others reported concerns that the treatments addressed specific psoriasis symptoms but led to worsening of other symptoms or development of new conditions such as uveitis and psoriatic arthritis. The burden of treatment infusions or required blood work also were discussed. These are areas in which dermatologists may be best suited to provide more patient education or support when prescribing these therapies. The National Psoriasis Foundation’s Patient Navigation Center is a tool for patients to access information and interact with members of the psoriasis patient community.
The psoriasis public meeting in March 2016 was the FDA’s 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.
Approximately three-quarters of respondents indicated that they have used oral or injectable medications (eg, methotrexate, acitretin, cyclosporine, apremilast, biologics) to control their psoriasis, according to a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.
Patients universally spoke about the benefits of their current treatments, especially the biologics, but variable experiences regarding the effectiveness of the therapies were reported, ranging from excellent improvement, to improvement that lasted only a few months, to a near-complete clearance. However, limitations to these therapies also were mentioned, which are areas where dermatologists can provide counseling and alternatives. For example, treatments were reported to be effective in clearing cutaneous psoriasis symptoms such as flaking and scaling, but pruritus, burning, and pain were still problematic and mostly limited to areas where the cutaneous symptoms had been located.
Other treatment downsides that dermatologists should discuss with patients are side effects, including fatigue, nausea, fluctuations in weight, increased facial hair growth, nosebleeds, increased blood pressure, headaches, and palpitations, according to the patients present at the meeting. Patients also expressed concern about immune compromise from the biologics. Others reported concerns that the treatments addressed specific psoriasis symptoms but led to worsening of other symptoms or development of new conditions such as uveitis and psoriatic arthritis. The burden of treatment infusions or required blood work also were discussed. These are areas in which dermatologists may be best suited to provide more patient education or support when prescribing these therapies. The National Psoriasis Foundation’s Patient Navigation Center is a tool for patients to access information and interact with members of the psoriasis patient community.
The psoriasis public meeting in March 2016 was the FDA’s 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.
Approximately three-quarters of respondents indicated that they have used oral or injectable medications (eg, methotrexate, acitretin, cyclosporine, apremilast, biologics) to control their psoriasis, according to a public meeting hosted by the US Food and Drug Administration (FDA) to hear patient perspectives on psoriasis. Approximately 70 psoriasis patients or patient representatives attended the meeting in person and others attended through a live webcast.
Patients universally spoke about the benefits of their current treatments, especially the biologics, but variable experiences regarding the effectiveness of the therapies were reported, ranging from excellent improvement, to improvement that lasted only a few months, to a near-complete clearance. However, limitations to these therapies also were mentioned, which are areas where dermatologists can provide counseling and alternatives. For example, treatments were reported to be effective in clearing cutaneous psoriasis symptoms such as flaking and scaling, but pruritus, burning, and pain were still problematic and mostly limited to areas where the cutaneous symptoms had been located.
Other treatment downsides that dermatologists should discuss with patients are side effects, including fatigue, nausea, fluctuations in weight, increased facial hair growth, nosebleeds, increased blood pressure, headaches, and palpitations, according to the patients present at the meeting. Patients also expressed concern about immune compromise from the biologics. Others reported concerns that the treatments addressed specific psoriasis symptoms but led to worsening of other symptoms or development of new conditions such as uveitis and psoriatic arthritis. The burden of treatment infusions or required blood work also were discussed. These are areas in which dermatologists may be best suited to provide more patient education or support when prescribing these therapies. The National Psoriasis Foundation’s Patient Navigation Center is a tool for patients to access information and interact with members of the psoriasis patient community.
The psoriasis public meeting in March 2016 was the FDA’s 18th patient-focused drug development meeting. The FDA sought this information to have a greater understanding of the burden of psoriasis on patients and the treatments currently used to treat psoriasis and its symptoms. This information will help guide the FDA as they consider future drug approvals.
Topical tapinarof heads for phase 3 in atopic dermatitis and psoriasis
GENEVA – Tapinarof cream, a first-in-class topical nonsteroidal anti-inflammatory agent, successfully met its primary and secondary efficacy endpoints in a large international, phase 2, dose-ranging study and is moving on to a phase 3 trial for atopic dermatitis.
Tapinarof is a naturally derived compound whose therapeutic mechanism of action has recently been shown to involve activation of the aryl hydrocarbon receptor, Johnny Peppers, PhD, said at the annual congress of the European Academy of Dermatology and Venereology.
GlaxoSmithKline is also developing tapinarof cream for mild to moderate plaque psoriasis, a disease that hasn’t seen a novel nonsteroidal topical therapy approved in more than 25 years. After a strong showing in a phase 2 study, a phase 3 trial in psoriasis is now scheduled.
Dr. Peppers presented a phase 2, double-blind, vehicle-controlled randomized trial including 247 adolescent and adult patients with mild, moderate, or severe atopic dermatitis. The six study arms were tapinarof cream at 1% or 0.5% or vehicle, self-administered at a frequency of either once or twice daily. Participants had a mean baseline Investigator’s Global Assessment (IGA) score of 3.1 on a 5-point scale, an Eczema Area and Severity Index (EASI) score of 9.8-13.1 in the various study arms, and a 5.1-5.8 score on an 11-point self-rated itch severity score recorded weekly.
“The 1% tapinarof arm showed higher efficacy and had a quicker onset of action than the 0.5% arm or vehicle,” he reported.
Indeed, the 1% tapinarof cream groups separated from controls in terms of the efficacy endpoints as early as week 1, with the maximum treatment effect seen at weeks 8-12, Dr. Peppers added.
The primary endpoint was a composite requiring both an IGA of 0 or 1, meaning clear or almost clear, at 12 weeks, along with a minimum 2-point improvement on the IGA from baseline to week 12. This was achieved in 46% of patients on tapinarof cream 1% applied once daily, 53% of those on tapinarof cream 1% twice a day, and in about 25% of controls on vehicle.
Eighty percent of subjects who achieved the primary endpoint maintained that level of treatment effect 2 weeks post treatment, and 70% still held their treatment response 4 weeks after they stopped using the medication.
There were two secondary endpoints. One was achievement of a 75% improvement from baseline on EASI scores (EASI-75) response. This was seen in 51% of the tapinarof 1% once-daily group, 60% on twice a day therapy, and 26% and 25% of controls. Onset of action was fastest with tapinarof cream 1% once daily.
The other secondary endpoint was at least a 3-point improvement from baseline to week 4 on the 11-point self-rated itch scale. This was achieved by 37% and 33% of patients on tapinarof cream 1% once daily and twice daily, respectively, a success rate twice that seen in controls.
Four percent of patients on tapinarof cream and 7% on vehicle discontinued the trial because of treatment-emergent adverse events. There were no serious treatment-related adverse events. The most frequent adverse events associated with tapinarof were folliculitis and contact dermatitis. The phase 3 trial will incorporate patch testing for contact dermatitis.
“We are very excited about this program. This will be the first topical therapy – if we’re able to achieve treatment success and ultimately regulatory approval – that would be able to treat both psoriasis and atopic dermatitis since topical steroids,” Dr. Peppers said.
The study was funded by GlaxoSmithKline and presented by a company employee.
[email protected]
GENEVA – Tapinarof cream, a first-in-class topical nonsteroidal anti-inflammatory agent, successfully met its primary and secondary efficacy endpoints in a large international, phase 2, dose-ranging study and is moving on to a phase 3 trial for atopic dermatitis.
Tapinarof is a naturally derived compound whose therapeutic mechanism of action has recently been shown to involve activation of the aryl hydrocarbon receptor, Johnny Peppers, PhD, said at the annual congress of the European Academy of Dermatology and Venereology.
GlaxoSmithKline is also developing tapinarof cream for mild to moderate plaque psoriasis, a disease that hasn’t seen a novel nonsteroidal topical therapy approved in more than 25 years. After a strong showing in a phase 2 study, a phase 3 trial in psoriasis is now scheduled.
Dr. Peppers presented a phase 2, double-blind, vehicle-controlled randomized trial including 247 adolescent and adult patients with mild, moderate, or severe atopic dermatitis. The six study arms were tapinarof cream at 1% or 0.5% or vehicle, self-administered at a frequency of either once or twice daily. Participants had a mean baseline Investigator’s Global Assessment (IGA) score of 3.1 on a 5-point scale, an Eczema Area and Severity Index (EASI) score of 9.8-13.1 in the various study arms, and a 5.1-5.8 score on an 11-point self-rated itch severity score recorded weekly.
“The 1% tapinarof arm showed higher efficacy and had a quicker onset of action than the 0.5% arm or vehicle,” he reported.
Indeed, the 1% tapinarof cream groups separated from controls in terms of the efficacy endpoints as early as week 1, with the maximum treatment effect seen at weeks 8-12, Dr. Peppers added.
The primary endpoint was a composite requiring both an IGA of 0 or 1, meaning clear or almost clear, at 12 weeks, along with a minimum 2-point improvement on the IGA from baseline to week 12. This was achieved in 46% of patients on tapinarof cream 1% applied once daily, 53% of those on tapinarof cream 1% twice a day, and in about 25% of controls on vehicle.
Eighty percent of subjects who achieved the primary endpoint maintained that level of treatment effect 2 weeks post treatment, and 70% still held their treatment response 4 weeks after they stopped using the medication.
There were two secondary endpoints. One was achievement of a 75% improvement from baseline on EASI scores (EASI-75) response. This was seen in 51% of the tapinarof 1% once-daily group, 60% on twice a day therapy, and 26% and 25% of controls. Onset of action was fastest with tapinarof cream 1% once daily.
The other secondary endpoint was at least a 3-point improvement from baseline to week 4 on the 11-point self-rated itch scale. This was achieved by 37% and 33% of patients on tapinarof cream 1% once daily and twice daily, respectively, a success rate twice that seen in controls.
Four percent of patients on tapinarof cream and 7% on vehicle discontinued the trial because of treatment-emergent adverse events. There were no serious treatment-related adverse events. The most frequent adverse events associated with tapinarof were folliculitis and contact dermatitis. The phase 3 trial will incorporate patch testing for contact dermatitis.
“We are very excited about this program. This will be the first topical therapy – if we’re able to achieve treatment success and ultimately regulatory approval – that would be able to treat both psoriasis and atopic dermatitis since topical steroids,” Dr. Peppers said.
The study was funded by GlaxoSmithKline and presented by a company employee.
[email protected]
GENEVA – Tapinarof cream, a first-in-class topical nonsteroidal anti-inflammatory agent, successfully met its primary and secondary efficacy endpoints in a large international, phase 2, dose-ranging study and is moving on to a phase 3 trial for atopic dermatitis.
Tapinarof is a naturally derived compound whose therapeutic mechanism of action has recently been shown to involve activation of the aryl hydrocarbon receptor, Johnny Peppers, PhD, said at the annual congress of the European Academy of Dermatology and Venereology.
GlaxoSmithKline is also developing tapinarof cream for mild to moderate plaque psoriasis, a disease that hasn’t seen a novel nonsteroidal topical therapy approved in more than 25 years. After a strong showing in a phase 2 study, a phase 3 trial in psoriasis is now scheduled.
Dr. Peppers presented a phase 2, double-blind, vehicle-controlled randomized trial including 247 adolescent and adult patients with mild, moderate, or severe atopic dermatitis. The six study arms were tapinarof cream at 1% or 0.5% or vehicle, self-administered at a frequency of either once or twice daily. Participants had a mean baseline Investigator’s Global Assessment (IGA) score of 3.1 on a 5-point scale, an Eczema Area and Severity Index (EASI) score of 9.8-13.1 in the various study arms, and a 5.1-5.8 score on an 11-point self-rated itch severity score recorded weekly.
“The 1% tapinarof arm showed higher efficacy and had a quicker onset of action than the 0.5% arm or vehicle,” he reported.
Indeed, the 1% tapinarof cream groups separated from controls in terms of the efficacy endpoints as early as week 1, with the maximum treatment effect seen at weeks 8-12, Dr. Peppers added.
The primary endpoint was a composite requiring both an IGA of 0 or 1, meaning clear or almost clear, at 12 weeks, along with a minimum 2-point improvement on the IGA from baseline to week 12. This was achieved in 46% of patients on tapinarof cream 1% applied once daily, 53% of those on tapinarof cream 1% twice a day, and in about 25% of controls on vehicle.
Eighty percent of subjects who achieved the primary endpoint maintained that level of treatment effect 2 weeks post treatment, and 70% still held their treatment response 4 weeks after they stopped using the medication.
There were two secondary endpoints. One was achievement of a 75% improvement from baseline on EASI scores (EASI-75) response. This was seen in 51% of the tapinarof 1% once-daily group, 60% on twice a day therapy, and 26% and 25% of controls. Onset of action was fastest with tapinarof cream 1% once daily.
The other secondary endpoint was at least a 3-point improvement from baseline to week 4 on the 11-point self-rated itch scale. This was achieved by 37% and 33% of patients on tapinarof cream 1% once daily and twice daily, respectively, a success rate twice that seen in controls.
Four percent of patients on tapinarof cream and 7% on vehicle discontinued the trial because of treatment-emergent adverse events. There were no serious treatment-related adverse events. The most frequent adverse events associated with tapinarof were folliculitis and contact dermatitis. The phase 3 trial will incorporate patch testing for contact dermatitis.
“We are very excited about this program. This will be the first topical therapy – if we’re able to achieve treatment success and ultimately regulatory approval – that would be able to treat both psoriasis and atopic dermatitis since topical steroids,” Dr. Peppers said.
The study was funded by GlaxoSmithKline and presented by a company employee.
[email protected]
AT THE EADV CONGRESS
Key clinical point:
Major finding: Forty-six percent of atopic dermatitis patients on tapinarof cream 1% applied once daily, and 53% of atopic dermatitis patients on tapinarof cream applied twice daily, met the primary study endpoint, rates twice those in vehicle-treated controls.
Data source: A phase 2, double-blind, vehicle-controlled, international 12-week clinical trial in 247 adolescents and adults with moderate to severe atopic dermatitis.
Disclosures: The study was funded by GlaxoSmithKline and presented by a company employee.
VIDEO: Consider depression in patients with psoriasis
LAS VEGAS – When treating patients with psoriasis, “it is very important for us to treat the entire patient,” and consider the comorbidities, including depression, associated with psoriasis, Jeffrey M. Sobell, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Depression can be a particular concern for younger patients with more severe psoriasis, said Dr. Sobell of Tufts University, Boston.
When he sees patients aged 18-35 years with significant psoriasis in his practice, he has made it a habit to ask them about depression “and if they’ve ever had thoughts of hurting themselves,” and arranges for mental health follow-up visits for patients about whom he is concerned. “It’s something that’s hard to talk about, but so important,” he said.
Dr. Sobell disclosed relationships with multiple companies including AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, Sanofi, and Sun Pharma.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LAS VEGAS – When treating patients with psoriasis, “it is very important for us to treat the entire patient,” and consider the comorbidities, including depression, associated with psoriasis, Jeffrey M. Sobell, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Depression can be a particular concern for younger patients with more severe psoriasis, said Dr. Sobell of Tufts University, Boston.
When he sees patients aged 18-35 years with significant psoriasis in his practice, he has made it a habit to ask them about depression “and if they’ve ever had thoughts of hurting themselves,” and arranges for mental health follow-up visits for patients about whom he is concerned. “It’s something that’s hard to talk about, but so important,” he said.
Dr. Sobell disclosed relationships with multiple companies including AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, Sanofi, and Sun Pharma.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LAS VEGAS – When treating patients with psoriasis, “it is very important for us to treat the entire patient,” and consider the comorbidities, including depression, associated with psoriasis, Jeffrey M. Sobell, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Depression can be a particular concern for younger patients with more severe psoriasis, said Dr. Sobell of Tufts University, Boston.
When he sees patients aged 18-35 years with significant psoriasis in his practice, he has made it a habit to ask them about depression “and if they’ve ever had thoughts of hurting themselves,” and arranges for mental health follow-up visits for patients about whom he is concerned. “It’s something that’s hard to talk about, but so important,” he said.
Dr. Sobell disclosed relationships with multiple companies including AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, Sanofi, and Sun Pharma.
SDEF and this news organization are owned by the same parent company.
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AT SDEF LAS VEGAS DERMATOLOGY SEMINAR
Ustekinumab may reduce risk of nonmelanoma skin cancer
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology. 
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
GENEVA – Ustekinumab therapy appears to protect psoriasis patients against nonmelanoma skin cancer (NMSC), according to a new analysis from the PSOLAR registry.
Compared with psoriasis patients on methotrexate, the risk of developing on-treatment NMSC was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry – infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). The lower risk was statistically significant only for ustekinumab, although there was a favorable trend with the TNF inhibitors showing a 19% relative risk reduction, Bhaskar Srivastava, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
PSOLAR (Psoriasis Longitudinal Assessment and Registry) is an ongoing international prospective observational study evaluating long-term safety and clinical outcomes in psoriasis patients eligible for systemic therapies. The study is now fully enrolled, with 12,090 psoriasis patients and 48,870 patient-years of follow-up and climbing, noted Dr. Srivastava, an employee of Janssen Scientific Affairs, Spring House, Pa.
This analysis focused on 6,782 PSOLAR participants with a mean 18-year history of psoriasis and no history of NMSC at enrollment: 2,623 patients on ustekinumab with 7,900 patient-years of prospective follow-up, 3,727 on a TNF inhibitor with 10,580 patient-years of follow-up, and 432 controls on methotrexate with 781 patient-years of follow-up.
Patients on a biologic were significantly younger, with a mean age of 46.7 years, versus 53.6 years for those on methotrexate. Rates of past or current smoking were similar, in the 55%-60% range, regardless of which systemic agent patients were using.
The crude unadjusted incidence rate for NMSC among all patients on a biologic was 0.33 cancers/100 patient-years, compared with 1.41/100 patient-years for psoriasis patients on methotrexate.
Patients on ustekinumab had an NMSC incidence rate of 0.19/100 patient-years, with a basal cell carcinoma rate of 0.13/100 patient-years and a squamous cell carcinoma rate of 0.06/100 patient-years. Psoriasis patients on a TNF inhibitor had an NMSC incidence rate of 0.43/100 patient-years, with a basal cell carcinoma rate of 0.26/100 patient-years and a squamous cell carcinoma rate of 0.17/100 patient-years.
In a multivariate analysis adjusted for age, sex, race, location, duration of psoriasis, smoking, prior malignancy, skin type, and history of treatment with cyclosporine, methotrexate, other systemic agents, or phototherapy, patients taking ustekinumab had a statistically significant 65% reduction in the risk of NMSC compared with patients on methotrexate and a 74% relative risk reduction for basal cell carcinoma; however, the squamous cell carcinoma risk in the two patient groups was similar.
Dr. Srivastava said the PSOLAR data shouldn’t be taken as the final word regarding NMSC risk and the use of biologics. He noted that psoriasis itself is associated with an increased risk of NMSC. And methotrexate, which was used as the reference standard in this analysis, may alter the risk of NMSC.
“Overall, these results require further validation in psoriasis populations with larger numbers of exposed patients,” he said.
The PSOLAR registry is funded by Janssen, where Dr. Srivastava is employed.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Psoriasis patients on ustekinumab had an adjusted 65% reduction in the risk of developing nonmelanoma skin cancer compared with patients on methotrexate.
Data source: An analysis of 6,782 psoriasis patients participating in an international prospective observational registry evaluating the long-term safety and clinical outcomes of systemic therapies.
Disclosures: The PSOLAR registry is funded by ustekinumab manufacturer Janssen; the study presenter is a company employee.
Moderate psoriasis: the new frontier for systemic therapies
GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.
“A large percentage of my patients who are on biologic therapy have less than 10% involved body surface area and would have a PASI [Psoriasis Area Severity Index] score, if I were to measure it, of under 12. Therefore they couldn’t get into a typical registration study for moderate to severe psoriasis,” he continued.
The UNVEIL trial included a 16-week, double-blind, placebo-controlled phase in which 221 systemic therapy–naive patients with plaque psoriasis on 5%-10% of their body surface area (BSA) were randomized 2:1 to apremilast at 30 mg twice a day or placebo. Thereafter, the placebo group was switched over to apremilast and the trial continued in open-label fashion out to 52 weeks. Apremilast (Otezla) is approved only for use in moderate to severe psoriasis.
At baseline, participants had a mean 15-year duration of psoriasis, an involved BSA of 7.1%, a PASI score of 8.1, a static Physician’s Global Assessment (PGA) score of 3 on a 0-5 scale, and a Dermatology Life Quality Index (DLQI) score of 11.
UNVEIL not only targeted a new population for a modern systemic therapy, it also debuted as its primary endpoint a novel metric for disease severity. Because PASI score is a relatively crude measure of change in a population with moderate psoriasis, Dr. Strober and his coinvestigators developed and employed as the primary outcome measure PGA+BSA, which can range from 15 to 30.
The mean baseline PGA+BSA was 21.8. At week 16, the placebo group averaged a 10% decrease in this metric, while the apremilast group showed a 48% reduction. At week 52, the group switched from placebo to apremilast at 16 weeks had a 42% improvement in PGA+BSA and patients on apremilast for the full study had a 49% improvement.
“So you can assume about half of patients with moderate psoriasis will experience a 50% reduction in the product of PGA+BSA on apremilast,” Dr. Strober observed.
At week 52, a PGA score of 0 or 1, meaning clear or almost clear, was present in 36% of the switchover group and 29% of patients on apremilast for 52 weeks.
A 75% improvement in PGA+BSA, or a PGA+BSA–75 response, occurred at week 52 in 45% of the switchover group and 37% of those on apremilast for the entire study.
The mean improvement in the DLQI at week 16 was 2.4 points in the placebo arm and twice that amount with apremilast. At 52 weeks, the switchover group averaged a 5.1-point reduction in DLQI from baseline and the full-time apremilast group had a 4.3-point reduction.
The incidence of apremilast-related adverse events didn’t increase over time. The main issues were diarrhea, nausea, and headache, as is the case when the oral drug is prescribed for its approved indication in patients with moderate to severe psoriasis.
In an interview, Dr. Strober said that despite the encouraging results of UNVEIL, the study is not by itself sufficient evidence to win an expanded indication for apremilast from regulatory agencies and the drug’s manufacturer, Celgene, is not interested in pursuing that course.
UNVEIL, a phase 4 study, was funded by Celgene. Dr. Strober reported serving as a consultant to and/or receiving research funding from that company and more than a dozen others.
GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.
“A large percentage of my patients who are on biologic therapy have less than 10% involved body surface area and would have a PASI [Psoriasis Area Severity Index] score, if I were to measure it, of under 12. Therefore they couldn’t get into a typical registration study for moderate to severe psoriasis,” he continued.
The UNVEIL trial included a 16-week, double-blind, placebo-controlled phase in which 221 systemic therapy–naive patients with plaque psoriasis on 5%-10% of their body surface area (BSA) were randomized 2:1 to apremilast at 30 mg twice a day or placebo. Thereafter, the placebo group was switched over to apremilast and the trial continued in open-label fashion out to 52 weeks. Apremilast (Otezla) is approved only for use in moderate to severe psoriasis.
At baseline, participants had a mean 15-year duration of psoriasis, an involved BSA of 7.1%, a PASI score of 8.1, a static Physician’s Global Assessment (PGA) score of 3 on a 0-5 scale, and a Dermatology Life Quality Index (DLQI) score of 11.
UNVEIL not only targeted a new population for a modern systemic therapy, it also debuted as its primary endpoint a novel metric for disease severity. Because PASI score is a relatively crude measure of change in a population with moderate psoriasis, Dr. Strober and his coinvestigators developed and employed as the primary outcome measure PGA+BSA, which can range from 15 to 30.
The mean baseline PGA+BSA was 21.8. At week 16, the placebo group averaged a 10% decrease in this metric, while the apremilast group showed a 48% reduction. At week 52, the group switched from placebo to apremilast at 16 weeks had a 42% improvement in PGA+BSA and patients on apremilast for the full study had a 49% improvement.
“So you can assume about half of patients with moderate psoriasis will experience a 50% reduction in the product of PGA+BSA on apremilast,” Dr. Strober observed.
At week 52, a PGA score of 0 or 1, meaning clear or almost clear, was present in 36% of the switchover group and 29% of patients on apremilast for 52 weeks.
A 75% improvement in PGA+BSA, or a PGA+BSA–75 response, occurred at week 52 in 45% of the switchover group and 37% of those on apremilast for the entire study.
The mean improvement in the DLQI at week 16 was 2.4 points in the placebo arm and twice that amount with apremilast. At 52 weeks, the switchover group averaged a 5.1-point reduction in DLQI from baseline and the full-time apremilast group had a 4.3-point reduction.
The incidence of apremilast-related adverse events didn’t increase over time. The main issues were diarrhea, nausea, and headache, as is the case when the oral drug is prescribed for its approved indication in patients with moderate to severe psoriasis.
In an interview, Dr. Strober said that despite the encouraging results of UNVEIL, the study is not by itself sufficient evidence to win an expanded indication for apremilast from regulatory agencies and the drug’s manufacturer, Celgene, is not interested in pursuing that course.
UNVEIL, a phase 4 study, was funded by Celgene. Dr. Strober reported serving as a consultant to and/or receiving research funding from that company and more than a dozen others.
GENEVA – Apremilast showed substantial efficacy for patients with truly moderate psoriasis as defined by an involved body surface area of 5%-10% in the first-of-its-kind UNVEIL trial, Bruce Strober, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Patients with moderate psoriasis constitute a very large and underserved population, said Dr. Strober, professor and chair of the department of dermatology at the University of Connecticut, Farmington. “I would say the moderate psoriasis group defined by 5%-10% psoriasis-involved body surface area represents a gray area in our treatment. Often, people with this degree of psoriasis receive no treatment or are relegated to topical monotherapy, yet unfortunately do not respond to those treatments. Nevertheless, clinical trials for systemic therapies, including biologics, exclude this population solely because they’re under 10% involved body surface area,” he noted.
“A large percentage of my patients who are on biologic therapy have less than 10% involved body surface area and would have a PASI [Psoriasis Area Severity Index] score, if I were to measure it, of under 12. Therefore they couldn’t get into a typical registration study for moderate to severe psoriasis,” he continued.
The UNVEIL trial included a 16-week, double-blind, placebo-controlled phase in which 221 systemic therapy–naive patients with plaque psoriasis on 5%-10% of their body surface area (BSA) were randomized 2:1 to apremilast at 30 mg twice a day or placebo. Thereafter, the placebo group was switched over to apremilast and the trial continued in open-label fashion out to 52 weeks. Apremilast (Otezla) is approved only for use in moderate to severe psoriasis.
At baseline, participants had a mean 15-year duration of psoriasis, an involved BSA of 7.1%, a PASI score of 8.1, a static Physician’s Global Assessment (PGA) score of 3 on a 0-5 scale, and a Dermatology Life Quality Index (DLQI) score of 11.
UNVEIL not only targeted a new population for a modern systemic therapy, it also debuted as its primary endpoint a novel metric for disease severity. Because PASI score is a relatively crude measure of change in a population with moderate psoriasis, Dr. Strober and his coinvestigators developed and employed as the primary outcome measure PGA+BSA, which can range from 15 to 30.
The mean baseline PGA+BSA was 21.8. At week 16, the placebo group averaged a 10% decrease in this metric, while the apremilast group showed a 48% reduction. At week 52, the group switched from placebo to apremilast at 16 weeks had a 42% improvement in PGA+BSA and patients on apremilast for the full study had a 49% improvement.
“So you can assume about half of patients with moderate psoriasis will experience a 50% reduction in the product of PGA+BSA on apremilast,” Dr. Strober observed.
At week 52, a PGA score of 0 or 1, meaning clear or almost clear, was present in 36% of the switchover group and 29% of patients on apremilast for 52 weeks.
A 75% improvement in PGA+BSA, or a PGA+BSA–75 response, occurred at week 52 in 45% of the switchover group and 37% of those on apremilast for the entire study.
The mean improvement in the DLQI at week 16 was 2.4 points in the placebo arm and twice that amount with apremilast. At 52 weeks, the switchover group averaged a 5.1-point reduction in DLQI from baseline and the full-time apremilast group had a 4.3-point reduction.
The incidence of apremilast-related adverse events didn’t increase over time. The main issues were diarrhea, nausea, and headache, as is the case when the oral drug is prescribed for its approved indication in patients with moderate to severe psoriasis.
In an interview, Dr. Strober said that despite the encouraging results of UNVEIL, the study is not by itself sufficient evidence to win an expanded indication for apremilast from regulatory agencies and the drug’s manufacturer, Celgene, is not interested in pursuing that course.
UNVEIL, a phase 4 study, was funded by Celgene. Dr. Strober reported serving as a consultant to and/or receiving research funding from that company and more than a dozen others.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Roughly half of apremilast-treated patients with moderate psoriasis as defined by an involved body surface area of 5%-10% experienced a 50% reduction in a novel outcome metric: the product of the Physician’s Global Assessment plus the involved body surface area.
Data source: This 52-week study of 221 patients with truly moderate psoriasis featured a 16-week, double-blind, placebo-controlled phase, after which everyone continued on open-label apremilast out to 51 weeks.
Disclosures: The UNVEIL study was sponsored by Celgene. The presenter reported receiving research funding from and serving as a consultant to that company and numerous others.