Photo courtesy of the CDC

Clinical trials supporting the approval of drugs with breakthrough therapy designation¹ do not meet the same standards as trials for non-breakthrough drugs, according to researchers.

Between 2012 and 2017, the US Food and Drug Administration (FDA) approved 46 breakthrough therapeutics on the basis of 89 pivotal trials.

Researchers found these trials “commonly lacked randomization, double-blinding, and control groups, used surrogate markers as primary endpoints, and enrolled small numbers of patients.”

Joseph S. Ross, MD, of the Yale School of Medicine in New Haven, Connecticut, and his colleagues detailed these findings in a letter to JAMA.

“To be clear, I think the FDA, as directed by Congress, is doing everything it can to expedite the development and review of drugs that treat serious and life-threatening conditions,” Dr Ross said.

“Our research suggests that FDA approval of these breakthrough therapies is generally based on shorter and smaller clinical trials than those that support FDA approval of non-breakthrough therapy drugs.”

Analyzing the approvals

More than half of the 46 approvals analyzed were for cancer therapeutics (n=25; 54.3%), and an equal number were considered first-in-class.

All 46 products received priority review², 30 (65.2%) received orphan designation³, 24 qualified for fast track⁴ review (52.2%), and 18 received accelerated approval⁵ (39.1%).

The median time from an investigational new drug activation to final FDA approval was 4.9 years. The median time from the submission of the new drug application to FDA approval was 6.9 months.

The median number of pivotal trials per indication was 1, and the median number of patients supporting an indication was 222.

Of all the approvals, 27 (58.7%) were made based on randomized trials, 21 (45.7%) were based on double-blind allocation, and 25 (54.3%) used an active or placebo comparator. Only 10 (21.7%) used a clinical primary endpoint.

The analysis also showed that trials supporting breakthrough drugs with accelerated approval were significantly less likely to be randomized, double-blinded, or have an active/placebo control group.

Of 18 trials that were used to grant drugs accelerated approval, 3 (16.7%) trials were randomized, 1 (5.6%) was double-blinded, and 3 (16.7%) had an active/placebo control group.

Of 28 trials supporting drugs without accelerated approval, 24 (85.7%) trials were randomized, 20 (71.4%) were double-blinded, and 22 (78.6%) had an active/placebo control group.

All 18 accelerated approvals had at least 1 safety analysis or efficacy-focused postmarketing requirement.

Dr Ross pointed out that when approvals are based on shorter and smaller clinical trials, there is greater uncertainty at the time of approval.

For example, will effects observed in a small, single trial be observed in a larger population or in another independent study? Will effects observed over a short period persist over time? Will new risks (or benefits) be observed over a longer period? And will the effect observed on the outcomes used in these shorter trials—usually surrogate endpoints believed to predict a clinical benefit—be confirmed by clinical outcomes?

“If we are going to be making this trade-off to allow novel drugs to come to market on the basis of evidence that is generally accompanied by greater uncertainty, we must be committed as a clinical and scientific community to ensuring that high-quality, rigorous postmarketing trials are conducted within a reasonable period of time,” Dr Ross said.

He noted that postmarketing trials will resolve some of the uncertainty and will ensure that drugs are associated with the benefit/safety profile that is expected based on the initial clinical studies.

“This will allow clinicians and patients to make fully informed decisions about whether to use these novel treatments,” he said.

1. The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. Breakthrough designation entitles sponsors to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review. To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

2. The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

3. The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US. Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

4. The FDA’s fast track program is designed to expedite clinical development and submission of applications for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs. Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the drug’s development plan and written communications about issues such as trial design and use of biomarkers. Drugs that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Fast track drugs may also be eligible for rolling review, which allows a developer to submit individual sections of a drug’s application for review as they are ready, rather than waiting until all sections are complete.

5. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition. Accelerated approval is based on surrogate or intermediate endpoints that are reasonably likely to predict clinical benefit. Continued approval of drugs granted accelerated approval may be contingent upon verification of clinical benefit in confirmatory trials.

Photo courtesy of the CDC

Clinical trials supporting the approval of drugs with breakthrough therapy designation¹ do not meet the same standards as trials for non-breakthrough drugs, according to researchers.

Between 2012 and 2017, the US Food and Drug Administration (FDA) approved 46 breakthrough therapeutics on the basis of 89 pivotal trials.

Researchers found these trials “commonly lacked randomization, double-blinding, and control groups, used surrogate markers as primary endpoints, and enrolled small numbers of patients.”

Joseph S. Ross, MD, of the Yale School of Medicine in New Haven, Connecticut, and his colleagues detailed these findings in a letter to JAMA.

“To be clear, I think the FDA, as directed by Congress, is doing everything it can to expedite the development and review of drugs that treat serious and life-threatening conditions,” Dr Ross said.

“Our research suggests that FDA approval of these breakthrough therapies is generally based on shorter and smaller clinical trials than those that support FDA approval of non-breakthrough therapy drugs.”

Analyzing the approvals

More than half of the 46 approvals analyzed were for cancer therapeutics (n=25; 54.3%), and an equal number were considered first-in-class.

All 46 products received priority review², 30 (65.2%) received orphan designation³, 24 qualified for fast track⁴ review (52.2%), and 18 received accelerated approval⁵ (39.1%).

The median time from an investigational new drug activation to final FDA approval was 4.9 years. The median time from the submission of the new drug application to FDA approval was 6.9 months.

The median number of pivotal trials per indication was 1, and the median number of patients supporting an indication was 222.

Of all the approvals, 27 (58.7%) were made based on randomized trials, 21 (45.7%) were based on double-blind allocation, and 25 (54.3%) used an active or placebo comparator. Only 10 (21.7%) used a clinical primary endpoint.

The analysis also showed that trials supporting breakthrough drugs with accelerated approval were significantly less likely to be randomized, double-blinded, or have an active/placebo control group.

Of 18 trials that were used to grant drugs accelerated approval, 3 (16.7%) trials were randomized, 1 (5.6%) was double-blinded, and 3 (16.7%) had an active/placebo control group.

Of 28 trials supporting drugs without accelerated approval, 24 (85.7%) trials were randomized, 20 (71.4%) were double-blinded, and 22 (78.6%) had an active/placebo control group.

All 18 accelerated approvals had at least 1 safety analysis or efficacy-focused postmarketing requirement.

Dr Ross pointed out that when approvals are based on shorter and smaller clinical trials, there is greater uncertainty at the time of approval.

For example, will effects observed in a small, single trial be observed in a larger population or in another independent study? Will effects observed over a short period persist over time? Will new risks (or benefits) be observed over a longer period? And will the effect observed on the outcomes used in these shorter trials—usually surrogate endpoints believed to predict a clinical benefit—be confirmed by clinical outcomes?

“If we are going to be making this trade-off to allow novel drugs to come to market on the basis of evidence that is generally accompanied by greater uncertainty, we must be committed as a clinical and scientific community to ensuring that high-quality, rigorous postmarketing trials are conducted within a reasonable period of time,” Dr Ross said.

He noted that postmarketing trials will resolve some of the uncertainty and will ensure that drugs are associated with the benefit/safety profile that is expected based on the initial clinical studies.

“This will allow clinicians and patients to make fully informed decisions about whether to use these novel treatments,” he said.

1. The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. Breakthrough designation entitles sponsors to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review. To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

2. The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

3. The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US. Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

4. The FDA’s fast track program is designed to expedite clinical development and submission of applications for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs. Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the drug’s development plan and written communications about issues such as trial design and use of biomarkers. Drugs that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Fast track drugs may also be eligible for rolling review, which allows a developer to submit individual sections of a drug’s application for review as they are ready, rather than waiting until all sections are complete.

5. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition. Accelerated approval is based on surrogate or intermediate endpoints that are reasonably likely to predict clinical benefit. Continued approval of drugs granted accelerated approval may be contingent upon verification of clinical benefit in confirmatory trials.

Photo courtesy of the CDC

Clinical trials supporting the approval of drugs with breakthrough therapy designation¹ do not meet the same standards as trials for non-breakthrough drugs, according to researchers.

Between 2012 and 2017, the US Food and Drug Administration (FDA) approved 46 breakthrough therapeutics on the basis of 89 pivotal trials.

Researchers found these trials “commonly lacked randomization, double-blinding, and control groups, used surrogate markers as primary endpoints, and enrolled small numbers of patients.”

Joseph S. Ross, MD, of the Yale School of Medicine in New Haven, Connecticut, and his colleagues detailed these findings in a letter to JAMA.

“To be clear, I think the FDA, as directed by Congress, is doing everything it can to expedite the development and review of drugs that treat serious and life-threatening conditions,” Dr Ross said.

“Our research suggests that FDA approval of these breakthrough therapies is generally based on shorter and smaller clinical trials than those that support FDA approval of non-breakthrough therapy drugs.”

Analyzing the approvals

More than half of the 46 approvals analyzed were for cancer therapeutics (n=25; 54.3%), and an equal number were considered first-in-class.

All 46 products received priority review², 30 (65.2%) received orphan designation³, 24 qualified for fast track⁴ review (52.2%), and 18 received accelerated approval⁵ (39.1%).

The median time from an investigational new drug activation to final FDA approval was 4.9 years. The median time from the submission of the new drug application to FDA approval was 6.9 months.

The median number of pivotal trials per indication was 1, and the median number of patients supporting an indication was 222.

Of all the approvals, 27 (58.7%) were made based on randomized trials, 21 (45.7%) were based on double-blind allocation, and 25 (54.3%) used an active or placebo comparator. Only 10 (21.7%) used a clinical primary endpoint.

The analysis also showed that trials supporting breakthrough drugs with accelerated approval were significantly less likely to be randomized, double-blinded, or have an active/placebo control group.

Of 18 trials that were used to grant drugs accelerated approval, 3 (16.7%) trials were randomized, 1 (5.6%) was double-blinded, and 3 (16.7%) had an active/placebo control group.

Of 28 trials supporting drugs without accelerated approval, 24 (85.7%) trials were randomized, 20 (71.4%) were double-blinded, and 22 (78.6%) had an active/placebo control group.

All 18 accelerated approvals had at least 1 safety analysis or efficacy-focused postmarketing requirement.

Dr Ross pointed out that when approvals are based on shorter and smaller clinical trials, there is greater uncertainty at the time of approval.

For example, will effects observed in a small, single trial be observed in a larger population or in another independent study? Will effects observed over a short period persist over time? Will new risks (or benefits) be observed over a longer period? And will the effect observed on the outcomes used in these shorter trials—usually surrogate endpoints believed to predict a clinical benefit—be confirmed by clinical outcomes?

“If we are going to be making this trade-off to allow novel drugs to come to market on the basis of evidence that is generally accompanied by greater uncertainty, we must be committed as a clinical and scientific community to ensuring that high-quality, rigorous postmarketing trials are conducted within a reasonable period of time,” Dr Ross said.

He noted that postmarketing trials will resolve some of the uncertainty and will ensure that drugs are associated with the benefit/safety profile that is expected based on the initial clinical studies.

“This will allow clinicians and patients to make fully informed decisions about whether to use these novel treatments,” he said.

1. The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. Breakthrough designation entitles sponsors to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review. To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

2. The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

3. The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US. Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

4. The FDA’s fast track program is designed to expedite clinical development and submission of applications for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs. Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the drug’s development plan and written communications about issues such as trial design and use of biomarkers. Drugs that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Fast track drugs may also be eligible for rolling review, which allows a developer to submit individual sections of a drug’s application for review as they are ready, rather than waiting until all sections are complete.

5. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition. Accelerated approval is based on surrogate or intermediate endpoints that are reasonably likely to predict clinical benefit. Continued approval of drugs granted accelerated approval may be contingent upon verification of clinical benefit in confirmatory trials.

A biopsy revealed a compound dysplastic nevus (DN) with no signs of malignancy. There was only mild atypia (if severe atypia is reported, then the lesion often is treated as a melanoma in-situ).

The FP was initially concerned about melanoma, given the size, growth, and other characteristics of the lesion. He performed dermoscopy and noted an irregular network with multiple asymmetrically placed dots off the network. His differential diagnosis included melanoma, melanoma in-situ, and dysplastic nevus. After informed consent, he performed a saucerization (deep shave) with a DermaBlade, taking 2-mm margins of clinically normal skin, which revealed the DN. (See the Watch & Learn video on “Shave biopsy.”)

Dysplastic nevi (with mild to moderate atypia) are benign acquired melanocytic lesions of the skin. Most are compound nevi possessing a junctional and intradermal component. While dysplastic nevi are not premalignant lesions, they do have some (small) potential for malignant transformation and patients with multiple DN have an increased risk for melanoma. Cutting out all the DN does not change that risk of melanoma.

The FP explained that no further treatment was needed and offered yearly skin exams to monitor for melanoma.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

A biopsy revealed a compound dysplastic nevus (DN) with no signs of malignancy. There was only mild atypia (if severe atypia is reported, then the lesion often is treated as a melanoma in-situ).

The FP was initially concerned about melanoma, given the size, growth, and other characteristics of the lesion. He performed dermoscopy and noted an irregular network with multiple asymmetrically placed dots off the network. His differential diagnosis included melanoma, melanoma in-situ, and dysplastic nevus. After informed consent, he performed a saucerization (deep shave) with a DermaBlade, taking 2-mm margins of clinically normal skin, which revealed the DN. (See the Watch & Learn video on “Shave biopsy.”)

Dysplastic nevi (with mild to moderate atypia) are benign acquired melanocytic lesions of the skin. Most are compound nevi possessing a junctional and intradermal component. While dysplastic nevi are not premalignant lesions, they do have some (small) potential for malignant transformation and patients with multiple DN have an increased risk for melanoma. Cutting out all the DN does not change that risk of melanoma.

The FP explained that no further treatment was needed and offered yearly skin exams to monitor for melanoma.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

A biopsy revealed a compound dysplastic nevus (DN) with no signs of malignancy. There was only mild atypia (if severe atypia is reported, then the lesion often is treated as a melanoma in-situ).

The FP was initially concerned about melanoma, given the size, growth, and other characteristics of the lesion. He performed dermoscopy and noted an irregular network with multiple asymmetrically placed dots off the network. His differential diagnosis included melanoma, melanoma in-situ, and dysplastic nevus. After informed consent, he performed a saucerization (deep shave) with a DermaBlade, taking 2-mm margins of clinically normal skin, which revealed the DN. (See the Watch & Learn video on “Shave biopsy.”)

Dysplastic nevi (with mild to moderate atypia) are benign acquired melanocytic lesions of the skin. Most are compound nevi possessing a junctional and intradermal component. While dysplastic nevi are not premalignant lesions, they do have some (small) potential for malignant transformation and patients with multiple DN have an increased risk for melanoma. Cutting out all the DN does not change that risk of melanoma.

The FP explained that no further treatment was needed and offered yearly skin exams to monitor for melanoma.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The Food and Drug Administration has approved ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer, as initial endocrine-based therapy.

The Food and Drug Administration has approved ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer, as initial endocrine-based therapy.

The Food and Drug Administration has approved ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer, as initial endocrine-based therapy.

ORLANDO – Obese black children are less likely than others to develop nonalcoholic fatty liver disease (NAFLD), but more likely to suffer its consequences if they do,according to a review of 503 adolescents at the Yale University pediatric obesity clinic in New Haven, Conn.

M. Alexander Otto/MDedge News

*This story was updated on 7/20/2018.

[email protected]

SOURCE: Trico D et al. ADA 2018, Abstract 313-OR.

ORLANDO – Obese black children are less likely than others to develop nonalcoholic fatty liver disease (NAFLD), but more likely to suffer its consequences if they do,according to a review of 503 adolescents at the Yale University pediatric obesity clinic in New Haven, Conn.

M. Alexander Otto/MDedge News

*This story was updated on 7/20/2018.

[email protected]

SOURCE: Trico D et al. ADA 2018, Abstract 313-OR.

ORLANDO – Obese black children are less likely than others to develop nonalcoholic fatty liver disease (NAFLD), but more likely to suffer its consequences if they do,according to a review of 503 adolescents at the Yale University pediatric obesity clinic in New Haven, Conn.

M. Alexander Otto/MDedge News

*This story was updated on 7/20/2018.

[email protected]

SOURCE: Trico D et al. ADA 2018, Abstract 313-OR.

The Food and Drug Administration issued its first-ever guidance on the development of human gene therapy for hemophilia.

The draft document provides a glimpse at the agency’s current thinking on clinical trial design and preclinical considerations in developing gene therapies. Specifically, it provides information to help companies set surrogate endpoints when seeking accelerated approval for hemophilia gene therapy products.

The hemophilia guidance is one of three disease-specific guidance documents. The other two clinical areas are retinal disorders and rare diseases.

FDA officials also issued updates to three more technical documents that deal with manufacturing of gene therapies.

The overall framework is similar to what FDA officials issued in 2017 for regenerative medicine. In a statement, FDA Commissioner Scott Gottlieb, MD, said the agency was responding to an increasing number of gene therapy approvals and anticipated development.

“Once just a theory, gene therapies are now a therapeutic reality for some patients,” Dr. Gottlieb said. “These platforms may have the potential to treat and cure some of our most intractable and vexing diseases. The policy framework we construct for how these products should be developed, reviewed by regulators, and reimbursed, will help set the stage for the continued advancement of this new market.”

[email protected]

The Food and Drug Administration issued its first-ever guidance on the development of human gene therapy for hemophilia.

The draft document provides a glimpse at the agency’s current thinking on clinical trial design and preclinical considerations in developing gene therapies. Specifically, it provides information to help companies set surrogate endpoints when seeking accelerated approval for hemophilia gene therapy products.

The hemophilia guidance is one of three disease-specific guidance documents. The other two clinical areas are retinal disorders and rare diseases.

FDA officials also issued updates to three more technical documents that deal with manufacturing of gene therapies.

The overall framework is similar to what FDA officials issued in 2017 for regenerative medicine. In a statement, FDA Commissioner Scott Gottlieb, MD, said the agency was responding to an increasing number of gene therapy approvals and anticipated development.

“Once just a theory, gene therapies are now a therapeutic reality for some patients,” Dr. Gottlieb said. “These platforms may have the potential to treat and cure some of our most intractable and vexing diseases. The policy framework we construct for how these products should be developed, reviewed by regulators, and reimbursed, will help set the stage for the continued advancement of this new market.”

[email protected]

The Food and Drug Administration issued its first-ever guidance on the development of human gene therapy for hemophilia.

The draft document provides a glimpse at the agency’s current thinking on clinical trial design and preclinical considerations in developing gene therapies. Specifically, it provides information to help companies set surrogate endpoints when seeking accelerated approval for hemophilia gene therapy products.

The hemophilia guidance is one of three disease-specific guidance documents. The other two clinical areas are retinal disorders and rare diseases.

FDA officials also issued updates to three more technical documents that deal with manufacturing of gene therapies.

The overall framework is similar to what FDA officials issued in 2017 for regenerative medicine. In a statement, FDA Commissioner Scott Gottlieb, MD, said the agency was responding to an increasing number of gene therapy approvals and anticipated development.

“Once just a theory, gene therapies are now a therapeutic reality for some patients,” Dr. Gottlieb said. “These platforms may have the potential to treat and cure some of our most intractable and vexing diseases. The policy framework we construct for how these products should be developed, reviewed by regulators, and reimbursed, will help set the stage for the continued advancement of this new market.”

[email protected]

Fish pedicures have recently received attention in the media because of a case report potentially linking a fish pedicure to onychomadesis. A letter published in JAMA Dermatology describes an otherwise healthy woman in her 20s who experienced nail abnormalities some months after having a fish pedicure. Onychomadesis, or transverse splitting of the nail plate, occurs when the nail matrix has arrested in producing the nail plate. It can be thought of as more severe form of Beau’s lines, in which the nail itself actually breaks and separates from the proximal nail plate and eventually sheds.

RomoloTavani/iStock/Getty Images Plus

Fish pedicures have a long-standing history in Mediterranean and Middle Eastern cultures for aiding such skin conditions as psoriasis and helping to remove scaly skin. The Garra rufa fish are nonmigratory freshwater fish native to the Persian Gulf and Eastern Mediterranean. Suction allows them to attach to rocks and eat plankton. These “doctor fish,” as they are nicknamed, when placed in a warm bath of 25°C to 30°C, will also eat human skin when starved of their natural food source. As the JAMA Dermatology letter mentions, this was demonstrated in a study in Kangal, Turkey, where Garra rufa fish were used to improve psoriasis by feeding on psoriasis plaques but not normal skin. After 3 weeks of therapy with Garra rufa in 67 patients, there was a 72% reduction in the Psoriasis Area and Severity Index (PASI) score from baseline (Evid Based Complement Alternat Med. 2006 Dec;3[4]:483-8).

Popular in the United States and Europe about a decade ago, fish pedicures have now been banned in 10 U.S. states and in some parts of Europe. While the trend in the United States has waned, fish pedicures have recently become more popular in vacation destinations, such as the Caribbean. The inherent concern of fish pedicures is risk of infection as the same fish are used successively and cannot be adequately sanitized between people.

Two cases of staphylococcus infections and one of Mycobacterium marinum have been reported after fish pedicures. Whether these infections were caused by the fish or the water source, however, remains to be determined. If the fish were transmitting infections, it seems that more infections would likely have been reported, considering the widespread popularity in the past. I, like Antonella Tosti, MD, who commented in a CNN report on the JAMA Dermatology case, also doubt that the fish pedicure alone caused onychomadesis in this woman. In order for onychomadesis to occur, there would have had to have been significant trauma to all 10 nails at the matrix. Would the fish been able to have caused the same amount of trauma to all 10 nails in one setting? While it is possible, I believe a more likely explanation would be an alternate endogenous or exogenous source.

Traditional medicine has been used to enhance beauty and cure ailments for thousands of years before the advent of modern medicine as demonstrated by the Kangal study. Before discounting fish pedicures completely, perhaps some thought should also be given to how this practice affects wildlife and the fish. The CNN report refers to a 2011 investigation by the U.K.’s Fish Health Inspectorate, which “found a bacterial outbreak among thousands of these fish, which had been transported from Indonesia to the United Kingdom pedicure spas. Fish were found with bulging eyes, many hemorrhaging around the gills and mouth. The culprit was found to be a streptococcal bacteria, a strain that is associated with fish like tilapia, according to David Verner-Jeffreys, a senior microbiologist at the Centre for Environment, Fisheries and Aquaculture Science in the U.K.”

Whether or not these fish would pose any risk to humans is unknown, but certainly, this practice adversely affects the welfare of the fish and their environment. The overharvesting of these fish has led the Turkish government to introduce legal protections for the country’s Garra rufa in an attempt to combat overfishing and exploitation.

Perhaps fish pedicures solely for aesthetic reasons should not be practiced because of the potential infection risk – as well as the harm (to both humans and fish) and overharvesting of the fish. If used properly, these fish, however, could be an aid in treating certain skin pathologies.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

Fish pedicures have recently received attention in the media because of a case report potentially linking a fish pedicure to onychomadesis. A letter published in JAMA Dermatology describes an otherwise healthy woman in her 20s who experienced nail abnormalities some months after having a fish pedicure. Onychomadesis, or transverse splitting of the nail plate, occurs when the nail matrix has arrested in producing the nail plate. It can be thought of as more severe form of Beau’s lines, in which the nail itself actually breaks and separates from the proximal nail plate and eventually sheds.

RomoloTavani/iStock/Getty Images Plus

Fish pedicures have a long-standing history in Mediterranean and Middle Eastern cultures for aiding such skin conditions as psoriasis and helping to remove scaly skin. The Garra rufa fish are nonmigratory freshwater fish native to the Persian Gulf and Eastern Mediterranean. Suction allows them to attach to rocks and eat plankton. These “doctor fish,” as they are nicknamed, when placed in a warm bath of 25°C to 30°C, will also eat human skin when starved of their natural food source. As the JAMA Dermatology letter mentions, this was demonstrated in a study in Kangal, Turkey, where Garra rufa fish were used to improve psoriasis by feeding on psoriasis plaques but not normal skin. After 3 weeks of therapy with Garra rufa in 67 patients, there was a 72% reduction in the Psoriasis Area and Severity Index (PASI) score from baseline (Evid Based Complement Alternat Med. 2006 Dec;3[4]:483-8).

Popular in the United States and Europe about a decade ago, fish pedicures have now been banned in 10 U.S. states and in some parts of Europe. While the trend in the United States has waned, fish pedicures have recently become more popular in vacation destinations, such as the Caribbean. The inherent concern of fish pedicures is risk of infection as the same fish are used successively and cannot be adequately sanitized between people.

Two cases of staphylococcus infections and one of Mycobacterium marinum have been reported after fish pedicures. Whether these infections were caused by the fish or the water source, however, remains to be determined. If the fish were transmitting infections, it seems that more infections would likely have been reported, considering the widespread popularity in the past. I, like Antonella Tosti, MD, who commented in a CNN report on the JAMA Dermatology case, also doubt that the fish pedicure alone caused onychomadesis in this woman. In order for onychomadesis to occur, there would have had to have been significant trauma to all 10 nails at the matrix. Would the fish been able to have caused the same amount of trauma to all 10 nails in one setting? While it is possible, I believe a more likely explanation would be an alternate endogenous or exogenous source.

Traditional medicine has been used to enhance beauty and cure ailments for thousands of years before the advent of modern medicine as demonstrated by the Kangal study. Before discounting fish pedicures completely, perhaps some thought should also be given to how this practice affects wildlife and the fish. The CNN report refers to a 2011 investigation by the U.K.’s Fish Health Inspectorate, which “found a bacterial outbreak among thousands of these fish, which had been transported from Indonesia to the United Kingdom pedicure spas. Fish were found with bulging eyes, many hemorrhaging around the gills and mouth. The culprit was found to be a streptococcal bacteria, a strain that is associated with fish like tilapia, according to David Verner-Jeffreys, a senior microbiologist at the Centre for Environment, Fisheries and Aquaculture Science in the U.K.”

Whether or not these fish would pose any risk to humans is unknown, but certainly, this practice adversely affects the welfare of the fish and their environment. The overharvesting of these fish has led the Turkish government to introduce legal protections for the country’s Garra rufa in an attempt to combat overfishing and exploitation.

Perhaps fish pedicures solely for aesthetic reasons should not be practiced because of the potential infection risk – as well as the harm (to both humans and fish) and overharvesting of the fish. If used properly, these fish, however, could be an aid in treating certain skin pathologies.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

Fish pedicures have recently received attention in the media because of a case report potentially linking a fish pedicure to onychomadesis. A letter published in JAMA Dermatology describes an otherwise healthy woman in her 20s who experienced nail abnormalities some months after having a fish pedicure. Onychomadesis, or transverse splitting of the nail plate, occurs when the nail matrix has arrested in producing the nail plate. It can be thought of as more severe form of Beau’s lines, in which the nail itself actually breaks and separates from the proximal nail plate and eventually sheds.

RomoloTavani/iStock/Getty Images Plus

Fish pedicures have a long-standing history in Mediterranean and Middle Eastern cultures for aiding such skin conditions as psoriasis and helping to remove scaly skin. The Garra rufa fish are nonmigratory freshwater fish native to the Persian Gulf and Eastern Mediterranean. Suction allows them to attach to rocks and eat plankton. These “doctor fish,” as they are nicknamed, when placed in a warm bath of 25°C to 30°C, will also eat human skin when starved of their natural food source. As the JAMA Dermatology letter mentions, this was demonstrated in a study in Kangal, Turkey, where Garra rufa fish were used to improve psoriasis by feeding on psoriasis plaques but not normal skin. After 3 weeks of therapy with Garra rufa in 67 patients, there was a 72% reduction in the Psoriasis Area and Severity Index (PASI) score from baseline (Evid Based Complement Alternat Med. 2006 Dec;3[4]:483-8).

Popular in the United States and Europe about a decade ago, fish pedicures have now been banned in 10 U.S. states and in some parts of Europe. While the trend in the United States has waned, fish pedicures have recently become more popular in vacation destinations, such as the Caribbean. The inherent concern of fish pedicures is risk of infection as the same fish are used successively and cannot be adequately sanitized between people.

Two cases of staphylococcus infections and one of Mycobacterium marinum have been reported after fish pedicures. Whether these infections were caused by the fish or the water source, however, remains to be determined. If the fish were transmitting infections, it seems that more infections would likely have been reported, considering the widespread popularity in the past. I, like Antonella Tosti, MD, who commented in a CNN report on the JAMA Dermatology case, also doubt that the fish pedicure alone caused onychomadesis in this woman. In order for onychomadesis to occur, there would have had to have been significant trauma to all 10 nails at the matrix. Would the fish been able to have caused the same amount of trauma to all 10 nails in one setting? While it is possible, I believe a more likely explanation would be an alternate endogenous or exogenous source.

Traditional medicine has been used to enhance beauty and cure ailments for thousands of years before the advent of modern medicine as demonstrated by the Kangal study. Before discounting fish pedicures completely, perhaps some thought should also be given to how this practice affects wildlife and the fish. The CNN report refers to a 2011 investigation by the U.K.’s Fish Health Inspectorate, which “found a bacterial outbreak among thousands of these fish, which had been transported from Indonesia to the United Kingdom pedicure spas. Fish were found with bulging eyes, many hemorrhaging around the gills and mouth. The culprit was found to be a streptococcal bacteria, a strain that is associated with fish like tilapia, according to David Verner-Jeffreys, a senior microbiologist at the Centre for Environment, Fisheries and Aquaculture Science in the U.K.”

Whether or not these fish would pose any risk to humans is unknown, but certainly, this practice adversely affects the welfare of the fish and their environment. The overharvesting of these fish has led the Turkish government to introduce legal protections for the country’s Garra rufa in an attempt to combat overfishing and exploitation.

Perhaps fish pedicures solely for aesthetic reasons should not be practiced because of the potential infection risk – as well as the harm (to both humans and fish) and overharvesting of the fish. If used properly, these fish, however, could be an aid in treating certain skin pathologies.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

Participation in Medicare’s bundled payments initiative didn’t significantly change payments per episode or care outcomes for the top five medical conditions selected under the program, a new analysis shows.

Payments for the common conditions remained around $24,000 per episode before and during participation in the Bundled Payments for Care Improvement (BPCI) initiative for the 125 participating hospitals evaluated in this study, conducted by Karen E. Joynt Maddox, MD, of Washington University, St. Louis, and her coauthors.

The finding contrasts with a previous study showing that hospitals in BPCI successfully lowered overall Medicare payments for patients who underwent joint replacement.

“Bundling of services to encourage more efficient care has great face validity and enjoys bipartisan support,” Dr. Joynt Maddox and her colleagues wrote. “For such bundling to work for medical conditions, however, more time, new care strategies and partnerships, or additional incentives may be required.”

The Center for Medicare & Medicaid Innovation initiated the voluntary BPCI demonstration project in 2013. The program targets 48 conditions that account for about 70% of Medicare spending. Hospitals that achieve cost targets for a specific condition get to keep a portion of the savings, and they reimburse Medicare for part of the difference when costs are exceeded.

The present study focused on 2013-2015 Medicare claims for the five medical conditions that account for two-thirds of patients enrolled in medical bundles: congestive heart failure, pneumonia, chronic obstructive pulmonary disease, sepsis, and acute myocardial infarction.

Mean baseline payments per episode for those conditions were $24,280 before participation in the BPCI. After hospitals joined, their average payments per episode were $23,993 (P = .41). For a set of matched control hospitals, payments were a mean of $23,901 at baseline and $23,503 in the corresponding follow-up period (P = .08).

That amounted to a $286 payment reduction for BPCI hospitals and a $398 reduction for controls, a difference of $112 (P = .79), the study investigators reported.

Changes in length of stay, readmissions, emergency department use, and clinical complexity of cases from baseline to follow-up periods was not significantly different between BPCI and control hospitals. For example, 90-day mortality increases were seen in both groups, and the degree of increase was not statistically different between the groups.

Those data help fill a gap in research on the BPCI program and BPCI Advanced, a related version of the demonstration project that will have its first cohort of participants starting Oct. 1, 2018.

“Despite the importance of episode-based payment, there has been little research examining its efficacy or determining whether it has unintended consequences, such as hospitals’ selecting patients with relatively less complex conditions to reduce costs and improve outcomes,” Dr. Joynt Maddox and her colleagues cautioned.

It’s unclear why the previous joint replacement study showed a successful reduction in costs under BPCI, while the new study did not. However, patients in the new analysis of the most common bundled conditions were older and had higher rates of poverty and disability.

“As a result of these complexities, patients admitted for medical conditions may have had post-acute care needs that were less amenable to intervention,” Dr. Joynt Maddox said.

The investigators added that hospitals’ lack of effective influence on post–acute-care services may blunt their ability to achieve greater savings under BPCI. Better relationships with skilled nursing facilities, long-term care hospitals, home health agencies, and inpatient rehabilitation facilities could make a difference.

The Commonwealth Fund supported the study. One study author reported personal fees from HHS outside the submitted work, and another reported that he is an associate editor for the New England Journal of Medicine. No other disclosures were reported.

SOURCE: Joynt Maddox KE et al. N Engl J Med. 2018 Jul 19;379(3):260-9.

Participation in Medicare’s bundled payments initiative didn’t significantly change payments per episode or care outcomes for the top five medical conditions selected under the program, a new analysis shows.

Payments for the common conditions remained around $24,000 per episode before and during participation in the Bundled Payments for Care Improvement (BPCI) initiative for the 125 participating hospitals evaluated in this study, conducted by Karen E. Joynt Maddox, MD, of Washington University, St. Louis, and her coauthors.

The finding contrasts with a previous study showing that hospitals in BPCI successfully lowered overall Medicare payments for patients who underwent joint replacement.

“Bundling of services to encourage more efficient care has great face validity and enjoys bipartisan support,” Dr. Joynt Maddox and her colleagues wrote. “For such bundling to work for medical conditions, however, more time, new care strategies and partnerships, or additional incentives may be required.”

The Center for Medicare & Medicaid Innovation initiated the voluntary BPCI demonstration project in 2013. The program targets 48 conditions that account for about 70% of Medicare spending. Hospitals that achieve cost targets for a specific condition get to keep a portion of the savings, and they reimburse Medicare for part of the difference when costs are exceeded.

The present study focused on 2013-2015 Medicare claims for the five medical conditions that account for two-thirds of patients enrolled in medical bundles: congestive heart failure, pneumonia, chronic obstructive pulmonary disease, sepsis, and acute myocardial infarction.

Mean baseline payments per episode for those conditions were $24,280 before participation in the BPCI. After hospitals joined, their average payments per episode were $23,993 (P = .41). For a set of matched control hospitals, payments were a mean of $23,901 at baseline and $23,503 in the corresponding follow-up period (P = .08).

That amounted to a $286 payment reduction for BPCI hospitals and a $398 reduction for controls, a difference of $112 (P = .79), the study investigators reported.

Changes in length of stay, readmissions, emergency department use, and clinical complexity of cases from baseline to follow-up periods was not significantly different between BPCI and control hospitals. For example, 90-day mortality increases were seen in both groups, and the degree of increase was not statistically different between the groups.

Those data help fill a gap in research on the BPCI program and BPCI Advanced, a related version of the demonstration project that will have its first cohort of participants starting Oct. 1, 2018.

“Despite the importance of episode-based payment, there has been little research examining its efficacy or determining whether it has unintended consequences, such as hospitals’ selecting patients with relatively less complex conditions to reduce costs and improve outcomes,” Dr. Joynt Maddox and her colleagues cautioned.

It’s unclear why the previous joint replacement study showed a successful reduction in costs under BPCI, while the new study did not. However, patients in the new analysis of the most common bundled conditions were older and had higher rates of poverty and disability.

“As a result of these complexities, patients admitted for medical conditions may have had post-acute care needs that were less amenable to intervention,” Dr. Joynt Maddox said.

The investigators added that hospitals’ lack of effective influence on post–acute-care services may blunt their ability to achieve greater savings under BPCI. Better relationships with skilled nursing facilities, long-term care hospitals, home health agencies, and inpatient rehabilitation facilities could make a difference.

The Commonwealth Fund supported the study. One study author reported personal fees from HHS outside the submitted work, and another reported that he is an associate editor for the New England Journal of Medicine. No other disclosures were reported.

SOURCE: Joynt Maddox KE et al. N Engl J Med. 2018 Jul 19;379(3):260-9.

Participation in Medicare’s bundled payments initiative didn’t significantly change payments per episode or care outcomes for the top five medical conditions selected under the program, a new analysis shows.

Payments for the common conditions remained around $24,000 per episode before and during participation in the Bundled Payments for Care Improvement (BPCI) initiative for the 125 participating hospitals evaluated in this study, conducted by Karen E. Joynt Maddox, MD, of Washington University, St. Louis, and her coauthors.

The finding contrasts with a previous study showing that hospitals in BPCI successfully lowered overall Medicare payments for patients who underwent joint replacement.

“Bundling of services to encourage more efficient care has great face validity and enjoys bipartisan support,” Dr. Joynt Maddox and her colleagues wrote. “For such bundling to work for medical conditions, however, more time, new care strategies and partnerships, or additional incentives may be required.”

The Center for Medicare & Medicaid Innovation initiated the voluntary BPCI demonstration project in 2013. The program targets 48 conditions that account for about 70% of Medicare spending. Hospitals that achieve cost targets for a specific condition get to keep a portion of the savings, and they reimburse Medicare for part of the difference when costs are exceeded.

The present study focused on 2013-2015 Medicare claims for the five medical conditions that account for two-thirds of patients enrolled in medical bundles: congestive heart failure, pneumonia, chronic obstructive pulmonary disease, sepsis, and acute myocardial infarction.

Mean baseline payments per episode for those conditions were $24,280 before participation in the BPCI. After hospitals joined, their average payments per episode were $23,993 (P = .41). For a set of matched control hospitals, payments were a mean of $23,901 at baseline and $23,503 in the corresponding follow-up period (P = .08).

That amounted to a $286 payment reduction for BPCI hospitals and a $398 reduction for controls, a difference of $112 (P = .79), the study investigators reported.

Changes in length of stay, readmissions, emergency department use, and clinical complexity of cases from baseline to follow-up periods was not significantly different between BPCI and control hospitals. For example, 90-day mortality increases were seen in both groups, and the degree of increase was not statistically different between the groups.

Those data help fill a gap in research on the BPCI program and BPCI Advanced, a related version of the demonstration project that will have its first cohort of participants starting Oct. 1, 2018.

“Despite the importance of episode-based payment, there has been little research examining its efficacy or determining whether it has unintended consequences, such as hospitals’ selecting patients with relatively less complex conditions to reduce costs and improve outcomes,” Dr. Joynt Maddox and her colleagues cautioned.

It’s unclear why the previous joint replacement study showed a successful reduction in costs under BPCI, while the new study did not. However, patients in the new analysis of the most common bundled conditions were older and had higher rates of poverty and disability.

“As a result of these complexities, patients admitted for medical conditions may have had post-acute care needs that were less amenable to intervention,” Dr. Joynt Maddox said.

The investigators added that hospitals’ lack of effective influence on post–acute-care services may blunt their ability to achieve greater savings under BPCI. Better relationships with skilled nursing facilities, long-term care hospitals, home health agencies, and inpatient rehabilitation facilities could make a difference.

The Commonwealth Fund supported the study. One study author reported personal fees from HHS outside the submitted work, and another reported that he is an associate editor for the New England Journal of Medicine. No other disclosures were reported.

SOURCE: Joynt Maddox KE et al. N Engl J Med. 2018 Jul 19;379(3):260-9.

LAKE TAHOE, CALIF. – Morphea lesions on the extensor extremities, face, and superior head are associated with higher rates of extracutaneous involvement, results from a multicenter retrospective study showed.

Doug Brunk/MDedge News

“We know that risk is highest with linear morphea,” lead study author Yvonne E. Chiu, MD, said at the annual meeting of the Society for Pediatric Dermatology. “Specifically, linear morphea on the head and neck is associated with neurologic issues, and linear morphea on a limb is associated with musculoskeletal issues. However, risk stratification within each of those sites has never really been studied before.”

Dr. Chiu, who is a pediatric dermatologist at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Milwaukee, and her associates carried out a 14-site retrospective study in an effort to characterize morphea lesional distribution and to determine which sites had the highest risk for extracutaneous manifestations. They limited the analysis to patients with pediatric-onset morphea before the age of 18 and adequate lesional photographs in their clinical record. Patients with extragenital lichen sclerosis and atrophoderma were included in the analysis, but those with pansclerotic morphea and eosinophilic fasciitis were excluded. The researchers used custom web-based software to map the morphea lesions, and linked those data to a REDCap database where demographic and clinical information was stored. From this, the researchers tracked neurologic symptoms such as seizures, migraine headaches, other headaches, or any other neurologic signs or symptoms; neurologic testing results from those who underwent MRI, CT, and EEG; musculoskeletal symptoms such as arthritis, arthralgias, joint contracture, leg length discrepancy, and other musculoskeletal issues, as well as ophthalmologic manifestations including uveitis and other ophthalmologic symptoms. Logistic regression was used to analyze association of body sites with extracutaneous involvement.

Dr. Chiu, who also directs the dermatology residency program at the Medical College of Wisconsin, reported findings from 826 patients with 2,467 skin lesions of morphea, or an average of about 1.92 lesions per patient. Consistent with prior reports, most patients were female (73%), and the most prevalent subtype was linear morphea (56%), followed by plaque (29%), generalized (8%), and mixed (7%).

The trunk was the single most commonly affected body site, seen in 36% of cases. “However, if you lumped all body sites together, the extremities were the most commonly affected site (44%), while 16% of lesions involved the head and 4% involved the neck,” Dr. Chiu said. Patients with linear morphea had the highest rate of extracutaneous involvement. Specifically, 34% had musculoskeletal involvement, 24% had neurologic involvement, and 10% had ophthalmologic involvement. There were small rates of extracutaneous manifestations in the other types of morphea as well.

The most common musculoskeletal complications among patients with linear morphea were arthralgias (20%) and joint contractures (17%), followed by other musculoskeletal complications (15%), leg length discrepancy (5%), and arthritis (2%). Contrary to previously published reports, nonmigraine headaches were more common than seizures among patients with linear morphea (17% vs. 4%, respectively), while 4% of subjects had migraine headaches. Of the 134 subjects who underwent neuroimaging, 19% had abnormal results. Ophthalmologic complications were rare among patients overall, with the exception of those who had linear morphea. Of these cases, 1% had uveitis, and 9% had some other ophthalmologic condition.

Among all patients, the researchers found that left-extremity and extensor-extremity lesions had a stronger association with musculoskeletal involvement (odds ratios of 1.26 and 1.94, respectively). “The reasons for this are unclear,” Dr. Chiu said. “We didn’t assess handedness in our study, but that perhaps could explain it; 90% of the general population is right-hand dominant, so perhaps there’s some sort of protective effect if you’re using an extremity more. Joint contractures showed the greatest discrepancy between left and right extremity. So perhaps if you’re using that one side more, you’re less likely to have a joint contracture.”

When the researchers limited the analysis to head lesions, they observed no significant difference in the lesions between the left and right head (OR, 0.72), but anterior head lesions had a stronger association with neurologic signs or symptoms, compared with posterior head lesions (OR, 2.56), as did superior head lesions, compared with inferior head lesions (OR, 2.23). The association between head lesion location and ophthalmologic involvement was not significant.

“The odds of extracutaneous manifestations vary by site of morphea lesions, with higher odds seen on the left extremity, extensor extremity, the anterior head, and the superior head,” Dr. Chiu concluded. “Further research can be done to perhaps help us decide whether this necessitates difference in management or screening.”

The project was funded by the Pediatric Dermatology Research Alliance and the SPD. Dr. Chiu reported having no relevant financial disclosures.

[email protected]

LAKE TAHOE, CALIF. – Morphea lesions on the extensor extremities, face, and superior head are associated with higher rates of extracutaneous involvement, results from a multicenter retrospective study showed.

Doug Brunk/MDedge News

“We know that risk is highest with linear morphea,” lead study author Yvonne E. Chiu, MD, said at the annual meeting of the Society for Pediatric Dermatology. “Specifically, linear morphea on the head and neck is associated with neurologic issues, and linear morphea on a limb is associated with musculoskeletal issues. However, risk stratification within each of those sites has never really been studied before.”

Dr. Chiu, who is a pediatric dermatologist at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Milwaukee, and her associates carried out a 14-site retrospective study in an effort to characterize morphea lesional distribution and to determine which sites had the highest risk for extracutaneous manifestations. They limited the analysis to patients with pediatric-onset morphea before the age of 18 and adequate lesional photographs in their clinical record. Patients with extragenital lichen sclerosis and atrophoderma were included in the analysis, but those with pansclerotic morphea and eosinophilic fasciitis were excluded. The researchers used custom web-based software to map the morphea lesions, and linked those data to a REDCap database where demographic and clinical information was stored. From this, the researchers tracked neurologic symptoms such as seizures, migraine headaches, other headaches, or any other neurologic signs or symptoms; neurologic testing results from those who underwent MRI, CT, and EEG; musculoskeletal symptoms such as arthritis, arthralgias, joint contracture, leg length discrepancy, and other musculoskeletal issues, as well as ophthalmologic manifestations including uveitis and other ophthalmologic symptoms. Logistic regression was used to analyze association of body sites with extracutaneous involvement.

Dr. Chiu, who also directs the dermatology residency program at the Medical College of Wisconsin, reported findings from 826 patients with 2,467 skin lesions of morphea, or an average of about 1.92 lesions per patient. Consistent with prior reports, most patients were female (73%), and the most prevalent subtype was linear morphea (56%), followed by plaque (29%), generalized (8%), and mixed (7%).

The trunk was the single most commonly affected body site, seen in 36% of cases. “However, if you lumped all body sites together, the extremities were the most commonly affected site (44%), while 16% of lesions involved the head and 4% involved the neck,” Dr. Chiu said. Patients with linear morphea had the highest rate of extracutaneous involvement. Specifically, 34% had musculoskeletal involvement, 24% had neurologic involvement, and 10% had ophthalmologic involvement. There were small rates of extracutaneous manifestations in the other types of morphea as well.

The most common musculoskeletal complications among patients with linear morphea were arthralgias (20%) and joint contractures (17%), followed by other musculoskeletal complications (15%), leg length discrepancy (5%), and arthritis (2%). Contrary to previously published reports, nonmigraine headaches were more common than seizures among patients with linear morphea (17% vs. 4%, respectively), while 4% of subjects had migraine headaches. Of the 134 subjects who underwent neuroimaging, 19% had abnormal results. Ophthalmologic complications were rare among patients overall, with the exception of those who had linear morphea. Of these cases, 1% had uveitis, and 9% had some other ophthalmologic condition.

Among all patients, the researchers found that left-extremity and extensor-extremity lesions had a stronger association with musculoskeletal involvement (odds ratios of 1.26 and 1.94, respectively). “The reasons for this are unclear,” Dr. Chiu said. “We didn’t assess handedness in our study, but that perhaps could explain it; 90% of the general population is right-hand dominant, so perhaps there’s some sort of protective effect if you’re using an extremity more. Joint contractures showed the greatest discrepancy between left and right extremity. So perhaps if you’re using that one side more, you’re less likely to have a joint contracture.”

When the researchers limited the analysis to head lesions, they observed no significant difference in the lesions between the left and right head (OR, 0.72), but anterior head lesions had a stronger association with neurologic signs or symptoms, compared with posterior head lesions (OR, 2.56), as did superior head lesions, compared with inferior head lesions (OR, 2.23). The association between head lesion location and ophthalmologic involvement was not significant.

“The odds of extracutaneous manifestations vary by site of morphea lesions, with higher odds seen on the left extremity, extensor extremity, the anterior head, and the superior head,” Dr. Chiu concluded. “Further research can be done to perhaps help us decide whether this necessitates difference in management or screening.”

The project was funded by the Pediatric Dermatology Research Alliance and the SPD. Dr. Chiu reported having no relevant financial disclosures.

[email protected]

LAKE TAHOE, CALIF. – Morphea lesions on the extensor extremities, face, and superior head are associated with higher rates of extracutaneous involvement, results from a multicenter retrospective study showed.

Doug Brunk/MDedge News

“We know that risk is highest with linear morphea,” lead study author Yvonne E. Chiu, MD, said at the annual meeting of the Society for Pediatric Dermatology. “Specifically, linear morphea on the head and neck is associated with neurologic issues, and linear morphea on a limb is associated with musculoskeletal issues. However, risk stratification within each of those sites has never really been studied before.”

Dr. Chiu, who is a pediatric dermatologist at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Milwaukee, and her associates carried out a 14-site retrospective study in an effort to characterize morphea lesional distribution and to determine which sites had the highest risk for extracutaneous manifestations. They limited the analysis to patients with pediatric-onset morphea before the age of 18 and adequate lesional photographs in their clinical record. Patients with extragenital lichen sclerosis and atrophoderma were included in the analysis, but those with pansclerotic morphea and eosinophilic fasciitis were excluded. The researchers used custom web-based software to map the morphea lesions, and linked those data to a REDCap database where demographic and clinical information was stored. From this, the researchers tracked neurologic symptoms such as seizures, migraine headaches, other headaches, or any other neurologic signs or symptoms; neurologic testing results from those who underwent MRI, CT, and EEG; musculoskeletal symptoms such as arthritis, arthralgias, joint contracture, leg length discrepancy, and other musculoskeletal issues, as well as ophthalmologic manifestations including uveitis and other ophthalmologic symptoms. Logistic regression was used to analyze association of body sites with extracutaneous involvement.

Dr. Chiu, who also directs the dermatology residency program at the Medical College of Wisconsin, reported findings from 826 patients with 2,467 skin lesions of morphea, or an average of about 1.92 lesions per patient. Consistent with prior reports, most patients were female (73%), and the most prevalent subtype was linear morphea (56%), followed by plaque (29%), generalized (8%), and mixed (7%).

The trunk was the single most commonly affected body site, seen in 36% of cases. “However, if you lumped all body sites together, the extremities were the most commonly affected site (44%), while 16% of lesions involved the head and 4% involved the neck,” Dr. Chiu said. Patients with linear morphea had the highest rate of extracutaneous involvement. Specifically, 34% had musculoskeletal involvement, 24% had neurologic involvement, and 10% had ophthalmologic involvement. There were small rates of extracutaneous manifestations in the other types of morphea as well.

The most common musculoskeletal complications among patients with linear morphea were arthralgias (20%) and joint contractures (17%), followed by other musculoskeletal complications (15%), leg length discrepancy (5%), and arthritis (2%). Contrary to previously published reports, nonmigraine headaches were more common than seizures among patients with linear morphea (17% vs. 4%, respectively), while 4% of subjects had migraine headaches. Of the 134 subjects who underwent neuroimaging, 19% had abnormal results. Ophthalmologic complications were rare among patients overall, with the exception of those who had linear morphea. Of these cases, 1% had uveitis, and 9% had some other ophthalmologic condition.

Among all patients, the researchers found that left-extremity and extensor-extremity lesions had a stronger association with musculoskeletal involvement (odds ratios of 1.26 and 1.94, respectively). “The reasons for this are unclear,” Dr. Chiu said. “We didn’t assess handedness in our study, but that perhaps could explain it; 90% of the general population is right-hand dominant, so perhaps there’s some sort of protective effect if you’re using an extremity more. Joint contractures showed the greatest discrepancy between left and right extremity. So perhaps if you’re using that one side more, you’re less likely to have a joint contracture.”

When the researchers limited the analysis to head lesions, they observed no significant difference in the lesions between the left and right head (OR, 0.72), but anterior head lesions had a stronger association with neurologic signs or symptoms, compared with posterior head lesions (OR, 2.56), as did superior head lesions, compared with inferior head lesions (OR, 2.23). The association between head lesion location and ophthalmologic involvement was not significant.

“The odds of extracutaneous manifestations vary by site of morphea lesions, with higher odds seen on the left extremity, extensor extremity, the anterior head, and the superior head,” Dr. Chiu concluded. “Further research can be done to perhaps help us decide whether this necessitates difference in management or screening.”

The project was funded by the Pediatric Dermatology Research Alliance and the SPD. Dr. Chiu reported having no relevant financial disclosures.

[email protected]

Pfizer has begun early work on a phase 3 study of an investigational gene therapy to treat hemophilia B.

Pfizer, along with Spark Therapeutics, launched a phase 3 lead-in study at multiple centers to evaluate the efficacy and safety of current factor IX prophylaxis replacement therapy in the usual care setting. The efficacy data from the lead-in study will become the within-subject control group for patients who enroll in the next part of the phase 3 study, which will evaluate fidanacogene elaparvovec (formerly SPK-9001) for the treatment of hemophilia B.

Fidanacogene elaparvovec is a vector containing a bioengineered adeno-associated virus capsid and a high-activity human coagulation factor IX gene. In an ongoing phase 1/2 trial of fidanacogene elaparvovec, all 15 participants with hemophilia B were able to discontinue routine infusion of factor IX concentrates without serious adverse events, according to data released by Pfizer and Spark Therapeutics in May 2018.

[email protected]

Pfizer has begun early work on a phase 3 study of an investigational gene therapy to treat hemophilia B.

Pfizer, along with Spark Therapeutics, launched a phase 3 lead-in study at multiple centers to evaluate the efficacy and safety of current factor IX prophylaxis replacement therapy in the usual care setting. The efficacy data from the lead-in study will become the within-subject control group for patients who enroll in the next part of the phase 3 study, which will evaluate fidanacogene elaparvovec (formerly SPK-9001) for the treatment of hemophilia B.

Fidanacogene elaparvovec is a vector containing a bioengineered adeno-associated virus capsid and a high-activity human coagulation factor IX gene. In an ongoing phase 1/2 trial of fidanacogene elaparvovec, all 15 participants with hemophilia B were able to discontinue routine infusion of factor IX concentrates without serious adverse events, according to data released by Pfizer and Spark Therapeutics in May 2018.

[email protected]

Pfizer has begun early work on a phase 3 study of an investigational gene therapy to treat hemophilia B.

Pfizer, along with Spark Therapeutics, launched a phase 3 lead-in study at multiple centers to evaluate the efficacy and safety of current factor IX prophylaxis replacement therapy in the usual care setting. The efficacy data from the lead-in study will become the within-subject control group for patients who enroll in the next part of the phase 3 study, which will evaluate fidanacogene elaparvovec (formerly SPK-9001) for the treatment of hemophilia B.

Fidanacogene elaparvovec is a vector containing a bioengineered adeno-associated virus capsid and a high-activity human coagulation factor IX gene. In an ongoing phase 1/2 trial of fidanacogene elaparvovec, all 15 participants with hemophilia B were able to discontinue routine infusion of factor IX concentrates without serious adverse events, according to data released by Pfizer and Spark Therapeutics in May 2018.

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A total of 82% of psoriasis patients achieved PASI 75 during long-term treatment with ixekizumab (Taltz), based on interim data from 120 patients followed over a 4-year extension of a randomized trial.

James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.

At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.

A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).

The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.

However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”

The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.

SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.

A total of 82% of psoriasis patients achieved PASI 75 during long-term treatment with ixekizumab (Taltz), based on interim data from 120 patients followed over a 4-year extension of a randomized trial.

James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.

At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.

A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).

The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.

However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”

The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.

SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.

A total of 82% of psoriasis patients achieved PASI 75 during long-term treatment with ixekizumab (Taltz), based on interim data from 120 patients followed over a 4-year extension of a randomized trial.

James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

Patients from a previous study of ixekizumab were treated with 120 mg at the start of the extension, and then 80 mg subcutaneously every 4 weeks, Claus Zachariae, MD, of the University Hospital of Copenhagen Gentofte, and his coauthors reported in the Journal of the American Academy of Dermatology.

At week 208, 82% of the patients achieved Psoriasis Area and Severity Index (PASI) 75, 65% achieved PASI 90, and 45% achieved PASI 100; 65% scored a 0 or 1 on the Physician’s Global Assessment Scale. In addition, 45% of patients reported a score of 0 on the Physician Global Assessment. Patients also reported a decrease in itching from baseline.

A total of 17% of patients experienced a serious adverse event and 87% of the patients experienced at least one treatment-related adverse event by the end of the 4-year extension period. Most of the reported events were mild to moderate; the most common were nasopharyngitis (23%), sinusitis (13%), upper respiratory tract infection (13%), and headache (10%).

The study findings were limited by several factors including the lack of blinding and lack of a placebo, the researchers noted.

However, the results demonstrate “that efficacy can be maintained at high levels for up to 4 years of ixekizumab therapy without apparent increases in health risks or safety issues,” for psoriasis patients, Dr. Zachariae and his associates said. “Longer treatment periods in larger numbers of patients will be reported for patients enrolled in the 5-year phase 3 ixekizumab studies.”

The study was supported by Eli Lilly. Dr. Zachariae disclosed relationships with Eli Lilly and other companies including Janssen, Novartis, AbbVie, and Amgen. His coauthors had financial relationships with multiple companies.

SOURCE: Zachariae C et al. J Am Acad Dermatol. 2018 Aug;79(2):294-301.e6.