SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

PARIS – Omalizumab is widely considered a breakthrough drug for treatment of chronic spontaneous urticaria (CSU) resistant to antihistamines, but ligelizumab leaves it in the dust, according to the results of a 382-patient phase 2b clinical trial.

“For sure, ligelizumab is the highlight of this year in urticariology,” Marcus Maurer, MD, declared at the annual congress of the European Academy of Dermatology and Venereology. An ongoing phase 3 trial will now compare more than 1,000 patients with CSU who will be randomized to ligelizumab, omalizumab, or placebo.

Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, and this translated into greater therapeutic efficacy in the multicenter, double-blind, placebo-controlled clinical trial, explained Dr. Maurer, professor of dermatology and allergy at Charité University in Berlin.

Study participants, all refractory to histamine₁ antihistamines and in many cases to leukotriene receptor antagonists as well, were randomized to omalizumab at 300 mg, placebo, or to ligelizumab at 24 mg, 72 mg, or 240 mg administered by subcutaneous injection every 4 weeks for 20 weeks. The study showed that the effective dose of ligelizumab lies somewhere between 72 and 240 mg; the 24-mg dose won’t be pursued in further studies.

“Three things are important in the comparison between ligelizumab and omalizumab: First, ligelizumab works faster – and omalizumab is a fast-working drug in urticaria. As early as week 4 after initiation of treatment, ligelizumab resulted in a significantly higher response rate,” he said.

Second, a complete response rate as defined by an Urticaria Activity Score over the past 7 days (UAS7) of 0 was achieved by more than 50% of patients on ligelizumab at 240 mg, a rate twice that seen in the omalizumab group. Indeed, more patients were symptom-free on ligelizumab at 72 mg or 240 mg than on omalizumab throughout the 20-week study.

And third, time to relapse after treatment discontinuation was markedly longer with ligelizumab.

“Once you stop the treatment, we expect patients to come back because we didn’t cure the disease, we blocked the signs and symptoms by blocking mast cell degranulation. Relapse after the last injection occurred at about 4 weeks with omalizumab versus 10 weeks for ligelizumab on average. That’s amazing,” Dr. Maurer said.

At week 20, the mean reductions from baseline in UAS7 scores were 13.6 points with placebo, 15.2 points with the lowest dose of ligelizumab, 18.2 points with omalizumab, 23.1 points with ligelizumab at 72 mg, and 22.5 points for ligelizumab at 240 mg.

The side effect profiles for both biologics were essentially the same as for placebo with the exception of a 5.9% rate of mild injection site reactions with ligelizumab at the 240-mg dose versus 2.3% with placebo.

Many clinicians have noticed a significant limitation of omalizumab: It is less effective in patients with more complex CSU having an autoimmune overlay, type 2b angioedema, and/or long disease duration.

“This does not seem to be the case with ligelizumab. Even for the difficult-to-treat subpopulations of CSU, ligelizumab appears to be a drug that can protect against mast cell degranulation. We see a reduction in angioedema activity; we see a reduction in wheal size and number; we see a reduction in the itch – so across all the symptoms in the difficult subpopulations, this is the better drug. Now we have to make it work in the phase 3 trials to bring it to clinical practice,” he said.

Dr. Maurer reported receiving research funding from and serving as an advisor to and paid speaker for Novartis, which markets omalizumab and is developing ligelizumab.

[email protected]

PARIS – Omalizumab is widely considered a breakthrough drug for treatment of chronic spontaneous urticaria (CSU) resistant to antihistamines, but ligelizumab leaves it in the dust, according to the results of a 382-patient phase 2b clinical trial.

“For sure, ligelizumab is the highlight of this year in urticariology,” Marcus Maurer, MD, declared at the annual congress of the European Academy of Dermatology and Venereology. An ongoing phase 3 trial will now compare more than 1,000 patients with CSU who will be randomized to ligelizumab, omalizumab, or placebo.

Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, and this translated into greater therapeutic efficacy in the multicenter, double-blind, placebo-controlled clinical trial, explained Dr. Maurer, professor of dermatology and allergy at Charité University in Berlin.

Study participants, all refractory to histamine₁ antihistamines and in many cases to leukotriene receptor antagonists as well, were randomized to omalizumab at 300 mg, placebo, or to ligelizumab at 24 mg, 72 mg, or 240 mg administered by subcutaneous injection every 4 weeks for 20 weeks. The study showed that the effective dose of ligelizumab lies somewhere between 72 and 240 mg; the 24-mg dose won’t be pursued in further studies.

“Three things are important in the comparison between ligelizumab and omalizumab: First, ligelizumab works faster – and omalizumab is a fast-working drug in urticaria. As early as week 4 after initiation of treatment, ligelizumab resulted in a significantly higher response rate,” he said.

Second, a complete response rate as defined by an Urticaria Activity Score over the past 7 days (UAS7) of 0 was achieved by more than 50% of patients on ligelizumab at 240 mg, a rate twice that seen in the omalizumab group. Indeed, more patients were symptom-free on ligelizumab at 72 mg or 240 mg than on omalizumab throughout the 20-week study.

And third, time to relapse after treatment discontinuation was markedly longer with ligelizumab.

“Once you stop the treatment, we expect patients to come back because we didn’t cure the disease, we blocked the signs and symptoms by blocking mast cell degranulation. Relapse after the last injection occurred at about 4 weeks with omalizumab versus 10 weeks for ligelizumab on average. That’s amazing,” Dr. Maurer said.

At week 20, the mean reductions from baseline in UAS7 scores were 13.6 points with placebo, 15.2 points with the lowest dose of ligelizumab, 18.2 points with omalizumab, 23.1 points with ligelizumab at 72 mg, and 22.5 points for ligelizumab at 240 mg.

The side effect profiles for both biologics were essentially the same as for placebo with the exception of a 5.9% rate of mild injection site reactions with ligelizumab at the 240-mg dose versus 2.3% with placebo.

Many clinicians have noticed a significant limitation of omalizumab: It is less effective in patients with more complex CSU having an autoimmune overlay, type 2b angioedema, and/or long disease duration.

“This does not seem to be the case with ligelizumab. Even for the difficult-to-treat subpopulations of CSU, ligelizumab appears to be a drug that can protect against mast cell degranulation. We see a reduction in angioedema activity; we see a reduction in wheal size and number; we see a reduction in the itch – so across all the symptoms in the difficult subpopulations, this is the better drug. Now we have to make it work in the phase 3 trials to bring it to clinical practice,” he said.

Dr. Maurer reported receiving research funding from and serving as an advisor to and paid speaker for Novartis, which markets omalizumab and is developing ligelizumab.

[email protected]

PARIS – Omalizumab is widely considered a breakthrough drug for treatment of chronic spontaneous urticaria (CSU) resistant to antihistamines, but ligelizumab leaves it in the dust, according to the results of a 382-patient phase 2b clinical trial.

“For sure, ligelizumab is the highlight of this year in urticariology,” Marcus Maurer, MD, declared at the annual congress of the European Academy of Dermatology and Venereology. An ongoing phase 3 trial will now compare more than 1,000 patients with CSU who will be randomized to ligelizumab, omalizumab, or placebo.

Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, and this translated into greater therapeutic efficacy in the multicenter, double-blind, placebo-controlled clinical trial, explained Dr. Maurer, professor of dermatology and allergy at Charité University in Berlin.

Study participants, all refractory to histamine₁ antihistamines and in many cases to leukotriene receptor antagonists as well, were randomized to omalizumab at 300 mg, placebo, or to ligelizumab at 24 mg, 72 mg, or 240 mg administered by subcutaneous injection every 4 weeks for 20 weeks. The study showed that the effective dose of ligelizumab lies somewhere between 72 and 240 mg; the 24-mg dose won’t be pursued in further studies.

“Three things are important in the comparison between ligelizumab and omalizumab: First, ligelizumab works faster – and omalizumab is a fast-working drug in urticaria. As early as week 4 after initiation of treatment, ligelizumab resulted in a significantly higher response rate,” he said.

Second, a complete response rate as defined by an Urticaria Activity Score over the past 7 days (UAS7) of 0 was achieved by more than 50% of patients on ligelizumab at 240 mg, a rate twice that seen in the omalizumab group. Indeed, more patients were symptom-free on ligelizumab at 72 mg or 240 mg than on omalizumab throughout the 20-week study.

And third, time to relapse after treatment discontinuation was markedly longer with ligelizumab.

“Once you stop the treatment, we expect patients to come back because we didn’t cure the disease, we blocked the signs and symptoms by blocking mast cell degranulation. Relapse after the last injection occurred at about 4 weeks with omalizumab versus 10 weeks for ligelizumab on average. That’s amazing,” Dr. Maurer said.

At week 20, the mean reductions from baseline in UAS7 scores were 13.6 points with placebo, 15.2 points with the lowest dose of ligelizumab, 18.2 points with omalizumab, 23.1 points with ligelizumab at 72 mg, and 22.5 points for ligelizumab at 240 mg.

The side effect profiles for both biologics were essentially the same as for placebo with the exception of a 5.9% rate of mild injection site reactions with ligelizumab at the 240-mg dose versus 2.3% with placebo.

Many clinicians have noticed a significant limitation of omalizumab: It is less effective in patients with more complex CSU having an autoimmune overlay, type 2b angioedema, and/or long disease duration.

“This does not seem to be the case with ligelizumab. Even for the difficult-to-treat subpopulations of CSU, ligelizumab appears to be a drug that can protect against mast cell degranulation. We see a reduction in angioedema activity; we see a reduction in wheal size and number; we see a reduction in the itch – so across all the symptoms in the difficult subpopulations, this is the better drug. Now we have to make it work in the phase 3 trials to bring it to clinical practice,” he said.

Dr. Maurer reported receiving research funding from and serving as an advisor to and paid speaker for Novartis, which markets omalizumab and is developing ligelizumab.

[email protected]

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

AGA is taking the lead in educating health care providers and patients about biosimilars and how they can be used for IBD patient care. Learn more at www.gastro.org/biosimilars.

[email protected]

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

AGA is taking the lead in educating health care providers and patients about biosimilars and how they can be used for IBD patient care. Learn more at www.gastro.org/biosimilars.

[email protected]

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

AGA is taking the lead in educating health care providers and patients about biosimilars and how they can be used for IBD patient care. Learn more at www.gastro.org/biosimilars.

[email protected]

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Pilonidal disease was first described by Mayo¹ in 1833 who hypothesized that the underlying etiology is incomplete separation of the mesoderm and ectoderm layers during embryogenesis. In 1880, Hodges² coined the term pilonidal sinus; he postulated that sinus formation was incited by hair.² Today, Hodges theory is known as the acquired theory: hair induces a foreign body response in surrounding tissue, leading to sinus formation. Although pilonidal cysts can occur anywhere on the body, they most commonly extend cephalad in the sacrococcygeal and upper gluteal cleft (Figure 1).^3,4 An acute pilonidal cyst typically presents with pain, tenderness, and swelling, similar to the presentation of a superficial abscess in other locations; however, a clue to the diagnosis is the presence of cutaneous pits along the midline of the gluteal cleft.⁵ Chronic pilonidal disease varies based on the extent of inflammation and scarring; the underlying cavity communicates with the overlying skin through sinuses and often drains with pressure.⁶

Pilonidal sinuses are rare before puberty or after 40 years of age⁷ and occur primarily in hirsute men. The ratio of men to women affected is between 3:1 and 4:1.⁸ Although pilonidal sinuses account for only 15% of anal suppurations, complications arising from pilonidal sinuses are a considerable cause of morbidity, resulting in loss of productivity in otherwise healthy individuals.⁹ Complications include chronic nonhealing wounds,¹⁰ as recurrent pilonidal sinuses tend to become colonized with gram-positive and facultative anaerobic bacteria, whereas primary pilonidal cysts more commonly become infected with anaerobic and gram-negative bacteria.¹¹ Long-standing disease increases the risk of squamous cell carcinoma arising within sinus tracts.^10,12

Histopathologically, pilonidal cysts are not true cysts because they lack an epithelial lining. Examination of the cavity commonly reveals hair, debris, and granulation tissue with surrounding foreign-body giant cells (Figure 2).⁵

The preferred treatment of pilonidal cysts continues to be debated. In this article, we review evidence supporting current modalities including conservative and surgical techniques as well as novel laser therapy for the treatment of pilonidal disease.

Conservative Management Techniques

Phenol Injections
Liquid or crystallized phenol injections have been used for treatment of mild to moderate pilonidal cysts.¹³ Excess debris is removed by curettage, and phenol is administered through the existing orifices or pits without pressure. The phenol remains in the cavity for 1 to 3 minutes before aspiration. Remaining cyst contents are removed through tissue manipulation, and the sinus is washed with saline. Mean healing time is 20 days (range, +/−14 days).¹³

Classically, phenol injections have a failure rate of 30% to 40%, especially with multiple sinuses and suppurative disease⁶; however, the success rate improves with limited disease (ie, no more than 1–3 sinus pits).³ With multiple treatment sessions, a recurrence rate as low as 2% over 25 months has been reported.¹⁴ Phenol injection also has been proposed as an adjuvant therapy to pit excision to minimize the need for extensive surgery.¹⁵

Simple Incision and Drainage
Simple incision and drainage has a crucial role in the treatment of acute pilonidal disease to decrease pain and relieve tension. Off-midline incisions have been recommended for because the resulting closures fared better against sheer forces applied by the gluteal muscles on the cleft.⁶ Therefore, the incision often is made off-midline from the gluteal cleft even when the cyst lies directly on the gluteal cleft.

Rates of healing vary widely after incision and drainage, ranging from 45% to 82%.⁶ Primary pilonidal cysts may respond well, particularly if the cavity is abraded; in one series, 79% (58/73) of patients did not have a recurrence at the average follow-up of 60 months.¹⁶

Excision and Unroofing
Techniques for excision and unroofing without primary closure include 2 variants: wide and limited. The wide technique consists of an inwardly slanted excision that is deepest in the center of the cavity. The inward sloping angle of the incision aids in healing because it allows granulation to progress evenly from the base of the wound upward. The depth of the incision should spare the fascia and leave as much fatty tissue as possible while still resecting the entire cavity and associated pits.⁶ Limited incision techniques aim to shorten the healing period by making smaller incisions into the sinuses, pits, and secondary tracts, and they are frequently supplemented with curettage.⁶ Noteworthy disadvantages include prolonged healing time, need for professional wound management, and extended medical observation.⁵ The average duration of wound healing in a study of 300 patients was 5.4 weeks (range, +/−1.1 weeks),¹⁷ and the recurrence rate has ranged from 5% to 13%.^18,19 Care must be taken to respond to numerous possible complications, including excessive exudation and granulation, superinfection, and walling off.⁶

Although the cost of treatment varies by hospital, location, and a patient’s insurance coverage, patient reports to the Pilonidal Support Alliance indicate that the cost of conservative management ranges from $500 to $2000.²⁰

Excision and Primary Closure
An elliptical excision that includes some of the lateral margin is excised down to the level of the fascia. Adjacent lateral tracts may be excised by expanding the incision. To close the wound, edges are approximated with placement of deep and superficial sutures. Wound healing typically occurs faster than secondary granulation, as seen in one randomized controlled trial with a mean of 10 days for primary closure compared to 13 weeks for secondary intention.²¹ However, as with any surgical procedure, postoperative complications can delay wound healing.¹⁹ The recurrence rate after primary closure varies considerably, ranging from 10% to 38%.^18,21-23 The average cost of an excision ranges from $3000 to $6000.²⁰

A Cochrane review evaluated 26 studies comparing primary and secondary closure. This large analysis showed no clear benefit for open healing over surgical closure²⁴; however, off-midline closure showed statistically significant benefit over midline closure (mean difference, 5.4 days; 95% CI, 2.3-8.5), and many experts now consider off-midline closure the standard of care in pilonidal sinus management (Figure 3).^24,25

Surgical Techniques

For severe or recurrent pilonidal disease, skin flaps often are required. Several flaps have been developed, including advancement, Bascom cleft lift, Karydakis, and modified Limberg flap. Flaps require a vascular pedicle but allow for closure without tension.²⁶ The cost of a flap procedure, ranging from $10,000 to $30,000, is greater than the cost of excision or other conservative therapy²⁰; however, with a lower recurrence rate of pilonidal disease following flap procedures compared to other treatments, patients may save more on treatment over the long-term.

Advancement Flaps
The most commonly used advancement flaps are the V-Y advancement flap and Z-plasty. The V-Y advancement flap creates a full-thickness V-shaped incision down to gluteal fascia that is closed to form a postrepair suture line in the shape of a Y.⁵ Depending on the size of the defect, the flaps may be utilized unilaterally or bilaterally. A defect as large as 8 to 10 cm can be covered unilaterally; however, defects larger than 10 cm commonly require a bilateral flap.²⁶ The V-Y advancement flap failed to show superiority to primary closure techniques based on complications, recurrence, and patient satisfaction in a large randomized controlled trial.²⁷

Performing a Z-plasty requires excision of diseased tissue with recruitment of lateral flaps incised down to the level of the fascia. The lateral edges are transposed to increase transverse length.²⁶ No statistically significant difference in infection or recurrence rates was noted between excision alone and excision plus Z-plasty; however, wounds were reported to heal faster in patients receiving excision plus Z-plasty (41 vs 15 days).²⁸

Cleft Lift Closure
In 1987, Bascom²⁹ introduced the cleft lift closure for recurrent pilonidal disease. This technique aims to reduce or eliminate lateral gluteal forces on the wounds by filling the gluteal cleft.⁵ The sinus tracts are excised and a full-thickness skin flap is extended across the cleft and closed off-midline. The adipose tissue fills in the previous space of the gluteal cleft. In the initial study, no recurrences were reported in 30 patients who underwent this procedure at 2-year follow-up; similarly, in another case series of 26 patients who underwent the procedure, no recurrences were noted at a median follow-up of 3 years.³⁰ Compared to excision with secondary wound healing and primary closure on the midline, the Bascom cleft lift demonstrated a decrease in wound healing time (62, 52, and 29 days, respectively).³¹

The classic Karydakis flap consists of an oblique elliptical excision of diseased tissue with fixation of the flap base to the sacral fascia (Figures 4 and 5). The flap is closed by suturing the edge off-midline.³² This technique prevents a midline wound and aims to remodel and flatten the natal cleft. Karydakis³³ performed the most important study for treatment of pilonidal disease with the Karydakis flap, which included more than 5000 patients. The results showed a 0.9% recurrence rate and an 8.5% wound complication rate over a 2- to 20-year follow-up.³³ These results have been substantiated by more recent studies, which produced similar results: a 1.8% to 5.3% infection rate and a recurrence rate of 0.9% to 4.4%.^34,35

In the modified Karydakis flap, the same excision and closure is performed without tacking the flap to the sacral fascia, aiming to prevent formation of a new vulnerable raphe by flattening the natal cleft. The infection rate was similar to the classic Karydakis flap, and no recurrences were noted during a 20-month follow-up.³⁶

Limberg Flap
The Limberg flap is derived from a rhomboid flap. In the classic Limberg flap, a midline rhomboid incision to the presacral fascia including the sinus is performed. The flap gains mobility by extending the excision laterally to the fascia of the gluteus maximus muscle. A variant of the original flap includes the modified Limberg flap, which lateralizes the midline sutures and flattens the intergluteal sulcus. Compared to the traditional Limberg approach, the modified Limberg flap was associated with a lower failure rate at both early and late time points and a lower rate of infection^37,38; however, based on the data it is unclear when primary closure should be favored over a Limberg flap. Several studies show the recurrence rate to be identical; however, hospital stay and pain were reduced in the Limberg flap group compared to primary closure.^39,40

Results from randomized controlled trials comparing the modified Limberg flap to the Karydakis flap vary. One of the largest prospective, randomized, controlled trials comparing the 2 flaps included 269 patients.Results showed a lower postoperative complication rate, lower pain scores, shorter operation time, and shorter hospital stay with the Karydakis flap compared to the Limberg flap, though no difference in recurrence was noted between the 2 groups.⁴¹

Two randomized controlled trials comprising 145 and 120 patients, respectively, showed no statistically significant difference between the Limberg flap and Karydakis flap with regard to complication rate, length of stay, and recurrence rate^36,42; however, patients in the Karydakis group reported subjectively feeling healed more quickly than patients in the modified Limberg flap group,⁴² and 1 of the 2 studies showed an increase in patient satisfaction with the modified Karydakis flap compared to modified Limberg flap.³⁶ In contrast to earlier studies, a 2009 study showed the Karydakis flap was associated with a higher wound infection rate than the Limberg flap group in a randomized trial of 100 patients (13/50 vs 4/50 patients).⁴³

Overall, larger prospective trials are needed to clarify the differences in outcomes between flap techniques. In our opinion, variations in postoperative complication and recurrence rates likely are due to differences in surgeon comfort and surgical technique. The Table provides a comprehensive list of trials comparing flap techniques.

Laser Therapy

Lasers are emerging as primary and adjuvant treatment options for pilonidal sinuses. Depilation with alexandrite, diode, and Nd:YAG lasers has demonstrated the most consistent evidence.^50-54 The firm texture and quality of the hair is proposed to incite an inflammatory response with sinus formation; therefore, using a laser to permaently remove this factor may help prevent future disease.

Large randomized controlled trials are needed to fully determine the utility of laser therapy as a primary or adjuvant treatment in pilonidal disease; however, given that laser therapies address the core pathogenesis of pilonidal disease and generally are well tolerated, their use may be strongly considered.

Conclusion

With mild pilonidal disease, more conservative measures can be employed; however, in cases of recurrent or suppurative disease or extensive scarring, excision with flap closure typically is required. Although no single surgical procedure has been identified as superior, one review demonstrated that off-midline procedures are statistically superior to midline closure in healing time, surgical site infection, and recurrence rate.²⁴ Novel techniques continue to emerge in the management of pilonidal disease, including laser therapy. This modality shows promise as either a primary or adjuvant treatment; however, large randomized controlled trials are needed to confirm early findings.

Given that pilonidal disease most commonly occurs in the actively employed population, we recommend that dermatologic surgeons discuss treatment options with patients who have pilonidal disease, taking into consideration cost, length of hospital stay, and recovery time when deciding on a treatment course.

Pilonidal disease was first described by Mayo¹ in 1833 who hypothesized that the underlying etiology is incomplete separation of the mesoderm and ectoderm layers during embryogenesis. In 1880, Hodges² coined the term pilonidal sinus; he postulated that sinus formation was incited by hair.² Today, Hodges theory is known as the acquired theory: hair induces a foreign body response in surrounding tissue, leading to sinus formation. Although pilonidal cysts can occur anywhere on the body, they most commonly extend cephalad in the sacrococcygeal and upper gluteal cleft (Figure 1).^3,4 An acute pilonidal cyst typically presents with pain, tenderness, and swelling, similar to the presentation of a superficial abscess in other locations; however, a clue to the diagnosis is the presence of cutaneous pits along the midline of the gluteal cleft.⁵ Chronic pilonidal disease varies based on the extent of inflammation and scarring; the underlying cavity communicates with the overlying skin through sinuses and often drains with pressure.⁶

Pilonidal sinuses are rare before puberty or after 40 years of age⁷ and occur primarily in hirsute men. The ratio of men to women affected is between 3:1 and 4:1.⁸ Although pilonidal sinuses account for only 15% of anal suppurations, complications arising from pilonidal sinuses are a considerable cause of morbidity, resulting in loss of productivity in otherwise healthy individuals.⁹ Complications include chronic nonhealing wounds,¹⁰ as recurrent pilonidal sinuses tend to become colonized with gram-positive and facultative anaerobic bacteria, whereas primary pilonidal cysts more commonly become infected with anaerobic and gram-negative bacteria.¹¹ Long-standing disease increases the risk of squamous cell carcinoma arising within sinus tracts.^10,12

Histopathologically, pilonidal cysts are not true cysts because they lack an epithelial lining. Examination of the cavity commonly reveals hair, debris, and granulation tissue with surrounding foreign-body giant cells (Figure 2).⁵

The preferred treatment of pilonidal cysts continues to be debated. In this article, we review evidence supporting current modalities including conservative and surgical techniques as well as novel laser therapy for the treatment of pilonidal disease.

Conservative Management Techniques

Phenol Injections
Liquid or crystallized phenol injections have been used for treatment of mild to moderate pilonidal cysts.¹³ Excess debris is removed by curettage, and phenol is administered through the existing orifices or pits without pressure. The phenol remains in the cavity for 1 to 3 minutes before aspiration. Remaining cyst contents are removed through tissue manipulation, and the sinus is washed with saline. Mean healing time is 20 days (range, +/−14 days).¹³

Classically, phenol injections have a failure rate of 30% to 40%, especially with multiple sinuses and suppurative disease⁶; however, the success rate improves with limited disease (ie, no more than 1–3 sinus pits).³ With multiple treatment sessions, a recurrence rate as low as 2% over 25 months has been reported.¹⁴ Phenol injection also has been proposed as an adjuvant therapy to pit excision to minimize the need for extensive surgery.¹⁵

Simple Incision and Drainage
Simple incision and drainage has a crucial role in the treatment of acute pilonidal disease to decrease pain and relieve tension. Off-midline incisions have been recommended for because the resulting closures fared better against sheer forces applied by the gluteal muscles on the cleft.⁶ Therefore, the incision often is made off-midline from the gluteal cleft even when the cyst lies directly on the gluteal cleft.

Rates of healing vary widely after incision and drainage, ranging from 45% to 82%.⁶ Primary pilonidal cysts may respond well, particularly if the cavity is abraded; in one series, 79% (58/73) of patients did not have a recurrence at the average follow-up of 60 months.¹⁶

Excision and Unroofing
Techniques for excision and unroofing without primary closure include 2 variants: wide and limited. The wide technique consists of an inwardly slanted excision that is deepest in the center of the cavity. The inward sloping angle of the incision aids in healing because it allows granulation to progress evenly from the base of the wound upward. The depth of the incision should spare the fascia and leave as much fatty tissue as possible while still resecting the entire cavity and associated pits.⁶ Limited incision techniques aim to shorten the healing period by making smaller incisions into the sinuses, pits, and secondary tracts, and they are frequently supplemented with curettage.⁶ Noteworthy disadvantages include prolonged healing time, need for professional wound management, and extended medical observation.⁵ The average duration of wound healing in a study of 300 patients was 5.4 weeks (range, +/−1.1 weeks),¹⁷ and the recurrence rate has ranged from 5% to 13%.^18,19 Care must be taken to respond to numerous possible complications, including excessive exudation and granulation, superinfection, and walling off.⁶

Although the cost of treatment varies by hospital, location, and a patient’s insurance coverage, patient reports to the Pilonidal Support Alliance indicate that the cost of conservative management ranges from $500 to $2000.²⁰

Excision and Primary Closure
An elliptical excision that includes some of the lateral margin is excised down to the level of the fascia. Adjacent lateral tracts may be excised by expanding the incision. To close the wound, edges are approximated with placement of deep and superficial sutures. Wound healing typically occurs faster than secondary granulation, as seen in one randomized controlled trial with a mean of 10 days for primary closure compared to 13 weeks for secondary intention.²¹ However, as with any surgical procedure, postoperative complications can delay wound healing.¹⁹ The recurrence rate after primary closure varies considerably, ranging from 10% to 38%.^18,21-23 The average cost of an excision ranges from $3000 to $6000.²⁰

A Cochrane review evaluated 26 studies comparing primary and secondary closure. This large analysis showed no clear benefit for open healing over surgical closure²⁴; however, off-midline closure showed statistically significant benefit over midline closure (mean difference, 5.4 days; 95% CI, 2.3-8.5), and many experts now consider off-midline closure the standard of care in pilonidal sinus management (Figure 3).^24,25

Surgical Techniques

For severe or recurrent pilonidal disease, skin flaps often are required. Several flaps have been developed, including advancement, Bascom cleft lift, Karydakis, and modified Limberg flap. Flaps require a vascular pedicle but allow for closure without tension.²⁶ The cost of a flap procedure, ranging from $10,000 to $30,000, is greater than the cost of excision or other conservative therapy²⁰; however, with a lower recurrence rate of pilonidal disease following flap procedures compared to other treatments, patients may save more on treatment over the long-term.

Advancement Flaps
The most commonly used advancement flaps are the V-Y advancement flap and Z-plasty. The V-Y advancement flap creates a full-thickness V-shaped incision down to gluteal fascia that is closed to form a postrepair suture line in the shape of a Y.⁵ Depending on the size of the defect, the flaps may be utilized unilaterally or bilaterally. A defect as large as 8 to 10 cm can be covered unilaterally; however, defects larger than 10 cm commonly require a bilateral flap.²⁶ The V-Y advancement flap failed to show superiority to primary closure techniques based on complications, recurrence, and patient satisfaction in a large randomized controlled trial.²⁷

Performing a Z-plasty requires excision of diseased tissue with recruitment of lateral flaps incised down to the level of the fascia. The lateral edges are transposed to increase transverse length.²⁶ No statistically significant difference in infection or recurrence rates was noted between excision alone and excision plus Z-plasty; however, wounds were reported to heal faster in patients receiving excision plus Z-plasty (41 vs 15 days).²⁸

Cleft Lift Closure
In 1987, Bascom²⁹ introduced the cleft lift closure for recurrent pilonidal disease. This technique aims to reduce or eliminate lateral gluteal forces on the wounds by filling the gluteal cleft.⁵ The sinus tracts are excised and a full-thickness skin flap is extended across the cleft and closed off-midline. The adipose tissue fills in the previous space of the gluteal cleft. In the initial study, no recurrences were reported in 30 patients who underwent this procedure at 2-year follow-up; similarly, in another case series of 26 patients who underwent the procedure, no recurrences were noted at a median follow-up of 3 years.³⁰ Compared to excision with secondary wound healing and primary closure on the midline, the Bascom cleft lift demonstrated a decrease in wound healing time (62, 52, and 29 days, respectively).³¹

The classic Karydakis flap consists of an oblique elliptical excision of diseased tissue with fixation of the flap base to the sacral fascia (Figures 4 and 5). The flap is closed by suturing the edge off-midline.³² This technique prevents a midline wound and aims to remodel and flatten the natal cleft. Karydakis³³ performed the most important study for treatment of pilonidal disease with the Karydakis flap, which included more than 5000 patients. The results showed a 0.9% recurrence rate and an 8.5% wound complication rate over a 2- to 20-year follow-up.³³ These results have been substantiated by more recent studies, which produced similar results: a 1.8% to 5.3% infection rate and a recurrence rate of 0.9% to 4.4%.^34,35

In the modified Karydakis flap, the same excision and closure is performed without tacking the flap to the sacral fascia, aiming to prevent formation of a new vulnerable raphe by flattening the natal cleft. The infection rate was similar to the classic Karydakis flap, and no recurrences were noted during a 20-month follow-up.³⁶

Limberg Flap
The Limberg flap is derived from a rhomboid flap. In the classic Limberg flap, a midline rhomboid incision to the presacral fascia including the sinus is performed. The flap gains mobility by extending the excision laterally to the fascia of the gluteus maximus muscle. A variant of the original flap includes the modified Limberg flap, which lateralizes the midline sutures and flattens the intergluteal sulcus. Compared to the traditional Limberg approach, the modified Limberg flap was associated with a lower failure rate at both early and late time points and a lower rate of infection^37,38; however, based on the data it is unclear when primary closure should be favored over a Limberg flap. Several studies show the recurrence rate to be identical; however, hospital stay and pain were reduced in the Limberg flap group compared to primary closure.^39,40

Results from randomized controlled trials comparing the modified Limberg flap to the Karydakis flap vary. One of the largest prospective, randomized, controlled trials comparing the 2 flaps included 269 patients.Results showed a lower postoperative complication rate, lower pain scores, shorter operation time, and shorter hospital stay with the Karydakis flap compared to the Limberg flap, though no difference in recurrence was noted between the 2 groups.⁴¹

Two randomized controlled trials comprising 145 and 120 patients, respectively, showed no statistically significant difference between the Limberg flap and Karydakis flap with regard to complication rate, length of stay, and recurrence rate^36,42; however, patients in the Karydakis group reported subjectively feeling healed more quickly than patients in the modified Limberg flap group,⁴² and 1 of the 2 studies showed an increase in patient satisfaction with the modified Karydakis flap compared to modified Limberg flap.³⁶ In contrast to earlier studies, a 2009 study showed the Karydakis flap was associated with a higher wound infection rate than the Limberg flap group in a randomized trial of 100 patients (13/50 vs 4/50 patients).⁴³

Overall, larger prospective trials are needed to clarify the differences in outcomes between flap techniques. In our opinion, variations in postoperative complication and recurrence rates likely are due to differences in surgeon comfort and surgical technique. The Table provides a comprehensive list of trials comparing flap techniques.

Laser Therapy

Lasers are emerging as primary and adjuvant treatment options for pilonidal sinuses. Depilation with alexandrite, diode, and Nd:YAG lasers has demonstrated the most consistent evidence.^50-54 The firm texture and quality of the hair is proposed to incite an inflammatory response with sinus formation; therefore, using a laser to permaently remove this factor may help prevent future disease.

Large randomized controlled trials are needed to fully determine the utility of laser therapy as a primary or adjuvant treatment in pilonidal disease; however, given that laser therapies address the core pathogenesis of pilonidal disease and generally are well tolerated, their use may be strongly considered.

Conclusion

With mild pilonidal disease, more conservative measures can be employed; however, in cases of recurrent or suppurative disease or extensive scarring, excision with flap closure typically is required. Although no single surgical procedure has been identified as superior, one review demonstrated that off-midline procedures are statistically superior to midline closure in healing time, surgical site infection, and recurrence rate.²⁴ Novel techniques continue to emerge in the management of pilonidal disease, including laser therapy. This modality shows promise as either a primary or adjuvant treatment; however, large randomized controlled trials are needed to confirm early findings.

Given that pilonidal disease most commonly occurs in the actively employed population, we recommend that dermatologic surgeons discuss treatment options with patients who have pilonidal disease, taking into consideration cost, length of hospital stay, and recovery time when deciding on a treatment course.

Pilonidal disease was first described by Mayo¹ in 1833 who hypothesized that the underlying etiology is incomplete separation of the mesoderm and ectoderm layers during embryogenesis. In 1880, Hodges² coined the term pilonidal sinus; he postulated that sinus formation was incited by hair.² Today, Hodges theory is known as the acquired theory: hair induces a foreign body response in surrounding tissue, leading to sinus formation. Although pilonidal cysts can occur anywhere on the body, they most commonly extend cephalad in the sacrococcygeal and upper gluteal cleft (Figure 1).^3,4 An acute pilonidal cyst typically presents with pain, tenderness, and swelling, similar to the presentation of a superficial abscess in other locations; however, a clue to the diagnosis is the presence of cutaneous pits along the midline of the gluteal cleft.⁵ Chronic pilonidal disease varies based on the extent of inflammation and scarring; the underlying cavity communicates with the overlying skin through sinuses and often drains with pressure.⁶

Pilonidal sinuses are rare before puberty or after 40 years of age⁷ and occur primarily in hirsute men. The ratio of men to women affected is between 3:1 and 4:1.⁸ Although pilonidal sinuses account for only 15% of anal suppurations, complications arising from pilonidal sinuses are a considerable cause of morbidity, resulting in loss of productivity in otherwise healthy individuals.⁹ Complications include chronic nonhealing wounds,¹⁰ as recurrent pilonidal sinuses tend to become colonized with gram-positive and facultative anaerobic bacteria, whereas primary pilonidal cysts more commonly become infected with anaerobic and gram-negative bacteria.¹¹ Long-standing disease increases the risk of squamous cell carcinoma arising within sinus tracts.^10,12

Histopathologically, pilonidal cysts are not true cysts because they lack an epithelial lining. Examination of the cavity commonly reveals hair, debris, and granulation tissue with surrounding foreign-body giant cells (Figure 2).⁵

The preferred treatment of pilonidal cysts continues to be debated. In this article, we review evidence supporting current modalities including conservative and surgical techniques as well as novel laser therapy for the treatment of pilonidal disease.

Conservative Management Techniques

Phenol Injections
Liquid or crystallized phenol injections have been used for treatment of mild to moderate pilonidal cysts.¹³ Excess debris is removed by curettage, and phenol is administered through the existing orifices or pits without pressure. The phenol remains in the cavity for 1 to 3 minutes before aspiration. Remaining cyst contents are removed through tissue manipulation, and the sinus is washed with saline. Mean healing time is 20 days (range, +/−14 days).¹³

Classically, phenol injections have a failure rate of 30% to 40%, especially with multiple sinuses and suppurative disease⁶; however, the success rate improves with limited disease (ie, no more than 1–3 sinus pits).³ With multiple treatment sessions, a recurrence rate as low as 2% over 25 months has been reported.¹⁴ Phenol injection also has been proposed as an adjuvant therapy to pit excision to minimize the need for extensive surgery.¹⁵

Simple Incision and Drainage
Simple incision and drainage has a crucial role in the treatment of acute pilonidal disease to decrease pain and relieve tension. Off-midline incisions have been recommended for because the resulting closures fared better against sheer forces applied by the gluteal muscles on the cleft.⁶ Therefore, the incision often is made off-midline from the gluteal cleft even when the cyst lies directly on the gluteal cleft.

Rates of healing vary widely after incision and drainage, ranging from 45% to 82%.⁶ Primary pilonidal cysts may respond well, particularly if the cavity is abraded; in one series, 79% (58/73) of patients did not have a recurrence at the average follow-up of 60 months.¹⁶

Excision and Unroofing
Techniques for excision and unroofing without primary closure include 2 variants: wide and limited. The wide technique consists of an inwardly slanted excision that is deepest in the center of the cavity. The inward sloping angle of the incision aids in healing because it allows granulation to progress evenly from the base of the wound upward. The depth of the incision should spare the fascia and leave as much fatty tissue as possible while still resecting the entire cavity and associated pits.⁶ Limited incision techniques aim to shorten the healing period by making smaller incisions into the sinuses, pits, and secondary tracts, and they are frequently supplemented with curettage.⁶ Noteworthy disadvantages include prolonged healing time, need for professional wound management, and extended medical observation.⁵ The average duration of wound healing in a study of 300 patients was 5.4 weeks (range, +/−1.1 weeks),¹⁷ and the recurrence rate has ranged from 5% to 13%.^18,19 Care must be taken to respond to numerous possible complications, including excessive exudation and granulation, superinfection, and walling off.⁶

Although the cost of treatment varies by hospital, location, and a patient’s insurance coverage, patient reports to the Pilonidal Support Alliance indicate that the cost of conservative management ranges from $500 to $2000.²⁰

Excision and Primary Closure
An elliptical excision that includes some of the lateral margin is excised down to the level of the fascia. Adjacent lateral tracts may be excised by expanding the incision. To close the wound, edges are approximated with placement of deep and superficial sutures. Wound healing typically occurs faster than secondary granulation, as seen in one randomized controlled trial with a mean of 10 days for primary closure compared to 13 weeks for secondary intention.²¹ However, as with any surgical procedure, postoperative complications can delay wound healing.¹⁹ The recurrence rate after primary closure varies considerably, ranging from 10% to 38%.^18,21-23 The average cost of an excision ranges from $3000 to $6000.²⁰

A Cochrane review evaluated 26 studies comparing primary and secondary closure. This large analysis showed no clear benefit for open healing over surgical closure²⁴; however, off-midline closure showed statistically significant benefit over midline closure (mean difference, 5.4 days; 95% CI, 2.3-8.5), and many experts now consider off-midline closure the standard of care in pilonidal sinus management (Figure 3).^24,25

Surgical Techniques

For severe or recurrent pilonidal disease, skin flaps often are required. Several flaps have been developed, including advancement, Bascom cleft lift, Karydakis, and modified Limberg flap. Flaps require a vascular pedicle but allow for closure without tension.²⁶ The cost of a flap procedure, ranging from $10,000 to $30,000, is greater than the cost of excision or other conservative therapy²⁰; however, with a lower recurrence rate of pilonidal disease following flap procedures compared to other treatments, patients may save more on treatment over the long-term.

Advancement Flaps
The most commonly used advancement flaps are the V-Y advancement flap and Z-plasty. The V-Y advancement flap creates a full-thickness V-shaped incision down to gluteal fascia that is closed to form a postrepair suture line in the shape of a Y.⁵ Depending on the size of the defect, the flaps may be utilized unilaterally or bilaterally. A defect as large as 8 to 10 cm can be covered unilaterally; however, defects larger than 10 cm commonly require a bilateral flap.²⁶ The V-Y advancement flap failed to show superiority to primary closure techniques based on complications, recurrence, and patient satisfaction in a large randomized controlled trial.²⁷

Performing a Z-plasty requires excision of diseased tissue with recruitment of lateral flaps incised down to the level of the fascia. The lateral edges are transposed to increase transverse length.²⁶ No statistically significant difference in infection or recurrence rates was noted between excision alone and excision plus Z-plasty; however, wounds were reported to heal faster in patients receiving excision plus Z-plasty (41 vs 15 days).²⁸

Cleft Lift Closure
In 1987, Bascom²⁹ introduced the cleft lift closure for recurrent pilonidal disease. This technique aims to reduce or eliminate lateral gluteal forces on the wounds by filling the gluteal cleft.⁵ The sinus tracts are excised and a full-thickness skin flap is extended across the cleft and closed off-midline. The adipose tissue fills in the previous space of the gluteal cleft. In the initial study, no recurrences were reported in 30 patients who underwent this procedure at 2-year follow-up; similarly, in another case series of 26 patients who underwent the procedure, no recurrences were noted at a median follow-up of 3 years.³⁰ Compared to excision with secondary wound healing and primary closure on the midline, the Bascom cleft lift demonstrated a decrease in wound healing time (62, 52, and 29 days, respectively).³¹

The classic Karydakis flap consists of an oblique elliptical excision of diseased tissue with fixation of the flap base to the sacral fascia (Figures 4 and 5). The flap is closed by suturing the edge off-midline.³² This technique prevents a midline wound and aims to remodel and flatten the natal cleft. Karydakis³³ performed the most important study for treatment of pilonidal disease with the Karydakis flap, which included more than 5000 patients. The results showed a 0.9% recurrence rate and an 8.5% wound complication rate over a 2- to 20-year follow-up.³³ These results have been substantiated by more recent studies, which produced similar results: a 1.8% to 5.3% infection rate and a recurrence rate of 0.9% to 4.4%.^34,35

In the modified Karydakis flap, the same excision and closure is performed without tacking the flap to the sacral fascia, aiming to prevent formation of a new vulnerable raphe by flattening the natal cleft. The infection rate was similar to the classic Karydakis flap, and no recurrences were noted during a 20-month follow-up.³⁶

Limberg Flap
The Limberg flap is derived from a rhomboid flap. In the classic Limberg flap, a midline rhomboid incision to the presacral fascia including the sinus is performed. The flap gains mobility by extending the excision laterally to the fascia of the gluteus maximus muscle. A variant of the original flap includes the modified Limberg flap, which lateralizes the midline sutures and flattens the intergluteal sulcus. Compared to the traditional Limberg approach, the modified Limberg flap was associated with a lower failure rate at both early and late time points and a lower rate of infection^37,38; however, based on the data it is unclear when primary closure should be favored over a Limberg flap. Several studies show the recurrence rate to be identical; however, hospital stay and pain were reduced in the Limberg flap group compared to primary closure.^39,40

Results from randomized controlled trials comparing the modified Limberg flap to the Karydakis flap vary. One of the largest prospective, randomized, controlled trials comparing the 2 flaps included 269 patients.Results showed a lower postoperative complication rate, lower pain scores, shorter operation time, and shorter hospital stay with the Karydakis flap compared to the Limberg flap, though no difference in recurrence was noted between the 2 groups.⁴¹

Two randomized controlled trials comprising 145 and 120 patients, respectively, showed no statistically significant difference between the Limberg flap and Karydakis flap with regard to complication rate, length of stay, and recurrence rate^36,42; however, patients in the Karydakis group reported subjectively feeling healed more quickly than patients in the modified Limberg flap group,⁴² and 1 of the 2 studies showed an increase in patient satisfaction with the modified Karydakis flap compared to modified Limberg flap.³⁶ In contrast to earlier studies, a 2009 study showed the Karydakis flap was associated with a higher wound infection rate than the Limberg flap group in a randomized trial of 100 patients (13/50 vs 4/50 patients).⁴³

Overall, larger prospective trials are needed to clarify the differences in outcomes between flap techniques. In our opinion, variations in postoperative complication and recurrence rates likely are due to differences in surgeon comfort and surgical technique. The Table provides a comprehensive list of trials comparing flap techniques.

Laser Therapy

Lasers are emerging as primary and adjuvant treatment options for pilonidal sinuses. Depilation with alexandrite, diode, and Nd:YAG lasers has demonstrated the most consistent evidence.^50-54 The firm texture and quality of the hair is proposed to incite an inflammatory response with sinus formation; therefore, using a laser to permaently remove this factor may help prevent future disease.

Large randomized controlled trials are needed to fully determine the utility of laser therapy as a primary or adjuvant treatment in pilonidal disease; however, given that laser therapies address the core pathogenesis of pilonidal disease and generally are well tolerated, their use may be strongly considered.

Conclusion

With mild pilonidal disease, more conservative measures can be employed; however, in cases of recurrent or suppurative disease or extensive scarring, excision with flap closure typically is required. Although no single surgical procedure has been identified as superior, one review demonstrated that off-midline procedures are statistically superior to midline closure in healing time, surgical site infection, and recurrence rate.²⁴ Novel techniques continue to emerge in the management of pilonidal disease, including laser therapy. This modality shows promise as either a primary or adjuvant treatment; however, large randomized controlled trials are needed to confirm early findings.

Given that pilonidal disease most commonly occurs in the actively employed population, we recommend that dermatologic surgeons discuss treatment options with patients who have pilonidal disease, taking into consideration cost, length of hospital stay, and recovery time when deciding on a treatment course.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Children with autism who also have an abnormal EEG or epilepsy are more likely to experience problems with developmental and adaptive functioning, according to an analysis of 443 patients with autism spectrum disorder (ASD).

• The medical records of children with autism were reviewed by researchers at Cincinnati Children’s Hospital Medical Center.
• The children were divided into 3 categories: those with ASD, no epilepsy, and abnormal EEG results; those with ASD, no epilepsy, and normal EEG; and those with ASD and epilepsy.
• Among 372 patients with ASD without epilepsy, 25.5% had an abnormal EEG; these patients were more likely to have more impaired adaptive functioning when compared to patients with normal EEG readings.
• Children with abnormal EEG readings presented with similar abnormalities to the group with epilepsy.
• Patients with epilepsy had lower scores on all the tests that measure developmental and adaptive functioning, when compared to those with normal EEG readings.

Capal JK, Carosella C, Corbin E, et al. EEG endophenotypes in autism spectrum disorder [published online ahead of print Oct 17, 2018]. Epilepsy Behav.  

Children with autism who also have an abnormal EEG or epilepsy are more likely to experience problems with developmental and adaptive functioning, according to an analysis of 443 patients with autism spectrum disorder (ASD).

• The medical records of children with autism were reviewed by researchers at Cincinnati Children’s Hospital Medical Center.
• The children were divided into 3 categories: those with ASD, no epilepsy, and abnormal EEG results; those with ASD, no epilepsy, and normal EEG; and those with ASD and epilepsy.
• Among 372 patients with ASD without epilepsy, 25.5% had an abnormal EEG; these patients were more likely to have more impaired adaptive functioning when compared to patients with normal EEG readings.
• Children with abnormal EEG readings presented with similar abnormalities to the group with epilepsy.
• Patients with epilepsy had lower scores on all the tests that measure developmental and adaptive functioning, when compared to those with normal EEG readings.

Capal JK, Carosella C, Corbin E, et al. EEG endophenotypes in autism spectrum disorder [published online ahead of print Oct 17, 2018]. Epilepsy Behav.  

Children with autism who also have an abnormal EEG or epilepsy are more likely to experience problems with developmental and adaptive functioning, according to an analysis of 443 patients with autism spectrum disorder (ASD).

• The medical records of children with autism were reviewed by researchers at Cincinnati Children’s Hospital Medical Center.
• The children were divided into 3 categories: those with ASD, no epilepsy, and abnormal EEG results; those with ASD, no epilepsy, and normal EEG; and those with ASD and epilepsy.
• Among 372 patients with ASD without epilepsy, 25.5% had an abnormal EEG; these patients were more likely to have more impaired adaptive functioning when compared to patients with normal EEG readings.
• Children with abnormal EEG readings presented with similar abnormalities to the group with epilepsy.
• Patients with epilepsy had lower scores on all the tests that measure developmental and adaptive functioning, when compared to those with normal EEG readings.

Capal JK, Carosella C, Corbin E, et al. EEG endophenotypes in autism spectrum disorder [published online ahead of print Oct 17, 2018]. Epilepsy Behav.  

PARIS – Secukinumab racked up impressive results for the treatment of moderate to severe hidradenitis suppurativa in 18 patients in an open-label, proof-of-concept study, David Rosmarin, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“It was especially notable that secukinumab was effective in five of the six patients who had previously failed anti-TNF [tumor necrosis factor] therapy,” said Dr. Rosmarin, a dermatologist at Tufts University, Boston.

At present, the sole medication approved for treatment of hidradenitis suppurativa (HS) is the TNF inhibitor adalimumab (Humira). The rationale for investigating secukinumab (Cosentyx), a biologic that blocks the interleukin-17A receptor and is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, lies in the observation that HS lesions exhibit an increased ratio of Th17- to T-regulatory cells, compared with normal skin. Lesional skin also features elevated IL-17 levels. These abnormalities can be reversed by anti-TNF therapy, he explained.

Dr. Rosmarin presented a 28-week, open-label study in which 18 patients with moderate to severe HS received an induction regimen consisting of 300 mg secukinumab given subcutaneously once weekly for 5 weeks and were then randomized to the same dose of the biologic given either every 2 or 4 weeks until week 24.

The primary endpoint was achievement of a Hidradenitis Suppurativa Clinical Response (HiSCR) at 24 weeks. This requires no increase in the number of draining fistulae or abscesses, compared with baseline, plus at least a 50% reduction in total inflammatory nodules. Secondary endpoints were the mean change from baseline in the Sartorius Scale as well as on the Dermatology Life Quality Index (DLQI).

“The other thing we noticed was the rapidity of response, which is important to a lot of our patients. It took an average of 7 weeks to achieve HiSCR, and eight patients achieved HiSCR during the induction phase of treatment,” the dermatologist said.

Mean scores on the Sartorius Scale dropped by 28%. Similarly, scores on the DLQI improved by a mean of 3.6 points, or 26%. Nine patients experienced a reduction of 5 points or more on the DLQI. “This happened largely in the first 1-2 months of therapy,” Dr. Rosmarin continued.

Secukinumab was well tolerated. There were no treatment discontinuations because of adverse events. Four patients, all in the biweekly dosing arm, developed Candida infections, all easily cured using topical ketoconazole.

The next step will be to conduct a large, placebo-controlled, randomized trial to firmly establish the efficacy of secukinumab for HS. Also, the optimal dosing of the biologic for induction and long-term maintenance therapy have yet to be determined. Over the long term, it will be important to see whether marked improvement in HS is accompanied by a reduction in the elevated cardiovascular risk associated with this inflammatory disease, he added.

In 2019, a trial will get underway to compare two doses of secukinumab for patients with HS. Based on a search of clinical trials at ClinicalTrials.gov, a wide range of monoclonal antibody therapies are being investigated for the treatment of HS.

The results of this preliminary study of secukinumab emphasize the importance of the Th17 pathway in HS and open the door to alternative strategies targeting this pathway. Dr. Rosmarin noted that he and his coinvestigators have collected a case series of positive responses to guselkumab (Tremfya), which targets the IL-23 p19 subunit, which also lies along the Th17 pathway.

The secukinumab study was sponsored by Novartis. Dr. Rosmarin reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

[email protected]

PARIS – Secukinumab racked up impressive results for the treatment of moderate to severe hidradenitis suppurativa in 18 patients in an open-label, proof-of-concept study, David Rosmarin, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“It was especially notable that secukinumab was effective in five of the six patients who had previously failed anti-TNF [tumor necrosis factor] therapy,” said Dr. Rosmarin, a dermatologist at Tufts University, Boston.

At present, the sole medication approved for treatment of hidradenitis suppurativa (HS) is the TNF inhibitor adalimumab (Humira). The rationale for investigating secukinumab (Cosentyx), a biologic that blocks the interleukin-17A receptor and is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, lies in the observation that HS lesions exhibit an increased ratio of Th17- to T-regulatory cells, compared with normal skin. Lesional skin also features elevated IL-17 levels. These abnormalities can be reversed by anti-TNF therapy, he explained.

Dr. Rosmarin presented a 28-week, open-label study in which 18 patients with moderate to severe HS received an induction regimen consisting of 300 mg secukinumab given subcutaneously once weekly for 5 weeks and were then randomized to the same dose of the biologic given either every 2 or 4 weeks until week 24.

The primary endpoint was achievement of a Hidradenitis Suppurativa Clinical Response (HiSCR) at 24 weeks. This requires no increase in the number of draining fistulae or abscesses, compared with baseline, plus at least a 50% reduction in total inflammatory nodules. Secondary endpoints were the mean change from baseline in the Sartorius Scale as well as on the Dermatology Life Quality Index (DLQI).

“The other thing we noticed was the rapidity of response, which is important to a lot of our patients. It took an average of 7 weeks to achieve HiSCR, and eight patients achieved HiSCR during the induction phase of treatment,” the dermatologist said.

Mean scores on the Sartorius Scale dropped by 28%. Similarly, scores on the DLQI improved by a mean of 3.6 points, or 26%. Nine patients experienced a reduction of 5 points or more on the DLQI. “This happened largely in the first 1-2 months of therapy,” Dr. Rosmarin continued.

Secukinumab was well tolerated. There were no treatment discontinuations because of adverse events. Four patients, all in the biweekly dosing arm, developed Candida infections, all easily cured using topical ketoconazole.

The next step will be to conduct a large, placebo-controlled, randomized trial to firmly establish the efficacy of secukinumab for HS. Also, the optimal dosing of the biologic for induction and long-term maintenance therapy have yet to be determined. Over the long term, it will be important to see whether marked improvement in HS is accompanied by a reduction in the elevated cardiovascular risk associated with this inflammatory disease, he added.

In 2019, a trial will get underway to compare two doses of secukinumab for patients with HS. Based on a search of clinical trials at ClinicalTrials.gov, a wide range of monoclonal antibody therapies are being investigated for the treatment of HS.

The results of this preliminary study of secukinumab emphasize the importance of the Th17 pathway in HS and open the door to alternative strategies targeting this pathway. Dr. Rosmarin noted that he and his coinvestigators have collected a case series of positive responses to guselkumab (Tremfya), which targets the IL-23 p19 subunit, which also lies along the Th17 pathway.

The secukinumab study was sponsored by Novartis. Dr. Rosmarin reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

[email protected]

PARIS – Secukinumab racked up impressive results for the treatment of moderate to severe hidradenitis suppurativa in 18 patients in an open-label, proof-of-concept study, David Rosmarin, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“It was especially notable that secukinumab was effective in five of the six patients who had previously failed anti-TNF [tumor necrosis factor] therapy,” said Dr. Rosmarin, a dermatologist at Tufts University, Boston.

At present, the sole medication approved for treatment of hidradenitis suppurativa (HS) is the TNF inhibitor adalimumab (Humira). The rationale for investigating secukinumab (Cosentyx), a biologic that blocks the interleukin-17A receptor and is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, lies in the observation that HS lesions exhibit an increased ratio of Th17- to T-regulatory cells, compared with normal skin. Lesional skin also features elevated IL-17 levels. These abnormalities can be reversed by anti-TNF therapy, he explained.

Dr. Rosmarin presented a 28-week, open-label study in which 18 patients with moderate to severe HS received an induction regimen consisting of 300 mg secukinumab given subcutaneously once weekly for 5 weeks and were then randomized to the same dose of the biologic given either every 2 or 4 weeks until week 24.

The primary endpoint was achievement of a Hidradenitis Suppurativa Clinical Response (HiSCR) at 24 weeks. This requires no increase in the number of draining fistulae or abscesses, compared with baseline, plus at least a 50% reduction in total inflammatory nodules. Secondary endpoints were the mean change from baseline in the Sartorius Scale as well as on the Dermatology Life Quality Index (DLQI).

“The other thing we noticed was the rapidity of response, which is important to a lot of our patients. It took an average of 7 weeks to achieve HiSCR, and eight patients achieved HiSCR during the induction phase of treatment,” the dermatologist said.

Mean scores on the Sartorius Scale dropped by 28%. Similarly, scores on the DLQI improved by a mean of 3.6 points, or 26%. Nine patients experienced a reduction of 5 points or more on the DLQI. “This happened largely in the first 1-2 months of therapy,” Dr. Rosmarin continued.

Secukinumab was well tolerated. There were no treatment discontinuations because of adverse events. Four patients, all in the biweekly dosing arm, developed Candida infections, all easily cured using topical ketoconazole.

The next step will be to conduct a large, placebo-controlled, randomized trial to firmly establish the efficacy of secukinumab for HS. Also, the optimal dosing of the biologic for induction and long-term maintenance therapy have yet to be determined. Over the long term, it will be important to see whether marked improvement in HS is accompanied by a reduction in the elevated cardiovascular risk associated with this inflammatory disease, he added.

In 2019, a trial will get underway to compare two doses of secukinumab for patients with HS. Based on a search of clinical trials at ClinicalTrials.gov, a wide range of monoclonal antibody therapies are being investigated for the treatment of HS.

The results of this preliminary study of secukinumab emphasize the importance of the Th17 pathway in HS and open the door to alternative strategies targeting this pathway. Dr. Rosmarin noted that he and his coinvestigators have collected a case series of positive responses to guselkumab (Tremfya), which targets the IL-23 p19 subunit, which also lies along the Th17 pathway.

The secukinumab study was sponsored by Novartis. Dr. Rosmarin reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

[email protected]

Young adults with elevated blood pressure or hypertension, as it is defined in recent U.S. guidelines, may be at increased risk of cardiovascular disease, a pair of recent studies published in JAMA suggest.

GlobalStock/Getty Images

In one study, investigators applied the 2017 American College of Cardiology/American Heart Association blood pressure criteria to nearly 5,000 U.S. young adults followed for approximately 20 years and who had up to a 3.5-fold risk associated with hypertension versus normal blood pressure.

The second study of almost 2.5 million Korean young adults, followed for 10 years, similarly found increased risks of cardiovascular disease later in life for those who had stage 1 or 2 hypertension between the ages of 20 and 39 years.

“These findings from a second country on the opposite side of the globe are consistent with those of the U.S. study, providing further support for the ACC/AHA guideline definitions of hypertension,” Naomi D.L. Fisher, MD, deputy editor, JAMA, and Gregory Curfman, MD, Brigham and Women’s Hospital, Boston, said in an editorial also appearing in JAMA.

Disagreement over the ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults threatens to distract from their potential benefits, Dr. Fisher and Dr. Curfman wrote in that editorial.

By redefining stage 1 hypertension as 130/80 mm Hg or higher, down from 140/90 mm Hg or higher, the 2017 ACC/AHA increased the prevalence of hypertension in the United States from 31.9% to 45.6%, they noted.

“Given the magnitude and reach of the global problem of hypertension, it is imperative that dedicated control efforts at the population level intensify,” they said.
 

U.S. study

The U.S. study, described in JAMA by Yuichiro Yano, MD, PhD, department of community and family medicine, Duke University, Durham, N.C., and his colleagues, was based on analysis of a prospective cohort study, CARDIA (Coronary Artery Risk Development in Young Adults Study), which started in 1985 and enrolled 5,115 black and white adults aged 18-30 years.

They applied the ACC/AHA blood pressure criteria based on each participants’ highest measurement before the age of 40 years, and correlated that with incident cardiovascular disease events that occurred over a median follow-up of 18.8 years.

Patients with normal blood pressure had a cardiovascular disease incidence rate of 1.37/1,000 person-years, compared with 2.74/1,000 person-years for those with elevated blood pressure, 3.15 for stage 1 hypertension, and 8.04 for stage 2 hypertension, investigators found.

That translated into increased risks of cardiovascular disease for those with elevated blood pressure versus those with normal blood pressure. After multivariable adjustment, the hazard ratio for cardiovascular disease was 1.67 (95% confidence interval, 1.01-2.77) for elevated blood pressure, 1.75 (95% CI, 1.22-2.53) for stage 1 hypertension, and 3.49 (95% CI, 2.42-5.05) for stage 2, Dr. Yano and his colleagues reported.

“The ACC/AHA blood pressure classification system may help identify young adults at higher risk for CVD events,” they concluded.
 

South Korean study

Similar findings were shown in a population-based cohort study, also published in JAMA, that included 2,488,101 adults aged 20-39 years in Korean National Health Insurance Service records.

The investigators looked at mean blood pressure levels from an initial health examination that took place during 2002-2003 and a second examination during 2004-2005.

Follow-up was shorter than the U.S. study, with a median duration of 10 years, reported Joung Sik Son, MD, department of family medicine and biomedical sciences, Seoul (South Korea) National University, and coauthors.

Even so, investigators detected an elevated risk of cardiovascular events for individuals with stage 1 or 2 hypertension versus those with normal blood pressure.

For men with baseline stage 1 hypertension based on the mean values and using the latest ACC/AHA blood pressure criteria, the incidence of cardiovascular disease was 215/100,000 person-years, versus 164 for those with normal blood pressure, with an adjusted hazard ratio of 1.25 (95% CI, 1.21-1.28), the authors said. Likewise, women with stage 1 hypertension had an incidence of 131/100,000 person-years versus 40 for women with normal blood pressure, with a hazard ratio of 1.27 (95% CI, 1.21-1.34).

Men with stage 2 hypertension likewise had a higher cardiovascular disease incidence than did those with normal blood pressure (336 vs. 164 per 100,000 person-years; adjusted HR 1.76), with similar findings seen in women, the report shows.

“Despite the relatively low absolute risk, the difference in absolute risk and the fact that sustained hypertension during longer durations is associated with higher risk of CVD [cardiovascular disease] indicate that early blood pressure management among young adults may lead to significant public health benefits by reducing CVD risk later in life,” Dr. Son and colleagues wrote in a discussion of the results.

Authors of the U.S. study reported disclosures related to Amarin, Amgen, and Novartis outside of the submitted work, as well as grants from the National Heart, Lung, and Blood Institute and National Institutes of Health during the conduct of the study.

Authors of the South Korean study reported no conflict of interest disclosures. That study was supported by the Ministry of Health and Welfare and the Ministry of Education of Korea, along with grants from the National Research Foundation of Korea.

SOURCES: Yano Y et al. JAMA. 2018;302(17):1774-82; Son JS et al. JAMA. 2018;302(17):1783-92.

Young adults with elevated blood pressure or hypertension, as it is defined in recent U.S. guidelines, may be at increased risk of cardiovascular disease, a pair of recent studies published in JAMA suggest.

GlobalStock/Getty Images

In one study, investigators applied the 2017 American College of Cardiology/American Heart Association blood pressure criteria to nearly 5,000 U.S. young adults followed for approximately 20 years and who had up to a 3.5-fold risk associated with hypertension versus normal blood pressure.

The second study of almost 2.5 million Korean young adults, followed for 10 years, similarly found increased risks of cardiovascular disease later in life for those who had stage 1 or 2 hypertension between the ages of 20 and 39 years.

“These findings from a second country on the opposite side of the globe are consistent with those of the U.S. study, providing further support for the ACC/AHA guideline definitions of hypertension,” Naomi D.L. Fisher, MD, deputy editor, JAMA, and Gregory Curfman, MD, Brigham and Women’s Hospital, Boston, said in an editorial also appearing in JAMA.

Disagreement over the ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults threatens to distract from their potential benefits, Dr. Fisher and Dr. Curfman wrote in that editorial.

By redefining stage 1 hypertension as 130/80 mm Hg or higher, down from 140/90 mm Hg or higher, the 2017 ACC/AHA increased the prevalence of hypertension in the United States from 31.9% to 45.6%, they noted.

“Given the magnitude and reach of the global problem of hypertension, it is imperative that dedicated control efforts at the population level intensify,” they said.
 

U.S. study

The U.S. study, described in JAMA by Yuichiro Yano, MD, PhD, department of community and family medicine, Duke University, Durham, N.C., and his colleagues, was based on analysis of a prospective cohort study, CARDIA (Coronary Artery Risk Development in Young Adults Study), which started in 1985 and enrolled 5,115 black and white adults aged 18-30 years.

They applied the ACC/AHA blood pressure criteria based on each participants’ highest measurement before the age of 40 years, and correlated that with incident cardiovascular disease events that occurred over a median follow-up of 18.8 years.

Patients with normal blood pressure had a cardiovascular disease incidence rate of 1.37/1,000 person-years, compared with 2.74/1,000 person-years for those with elevated blood pressure, 3.15 for stage 1 hypertension, and 8.04 for stage 2 hypertension, investigators found.

That translated into increased risks of cardiovascular disease for those with elevated blood pressure versus those with normal blood pressure. After multivariable adjustment, the hazard ratio for cardiovascular disease was 1.67 (95% confidence interval, 1.01-2.77) for elevated blood pressure, 1.75 (95% CI, 1.22-2.53) for stage 1 hypertension, and 3.49 (95% CI, 2.42-5.05) for stage 2, Dr. Yano and his colleagues reported.

“The ACC/AHA blood pressure classification system may help identify young adults at higher risk for CVD events,” they concluded.
 

South Korean study

Similar findings were shown in a population-based cohort study, also published in JAMA, that included 2,488,101 adults aged 20-39 years in Korean National Health Insurance Service records.

The investigators looked at mean blood pressure levels from an initial health examination that took place during 2002-2003 and a second examination during 2004-2005.

Follow-up was shorter than the U.S. study, with a median duration of 10 years, reported Joung Sik Son, MD, department of family medicine and biomedical sciences, Seoul (South Korea) National University, and coauthors.

Even so, investigators detected an elevated risk of cardiovascular events for individuals with stage 1 or 2 hypertension versus those with normal blood pressure.

For men with baseline stage 1 hypertension based on the mean values and using the latest ACC/AHA blood pressure criteria, the incidence of cardiovascular disease was 215/100,000 person-years, versus 164 for those with normal blood pressure, with an adjusted hazard ratio of 1.25 (95% CI, 1.21-1.28), the authors said. Likewise, women with stage 1 hypertension had an incidence of 131/100,000 person-years versus 40 for women with normal blood pressure, with a hazard ratio of 1.27 (95% CI, 1.21-1.34).

Men with stage 2 hypertension likewise had a higher cardiovascular disease incidence than did those with normal blood pressure (336 vs. 164 per 100,000 person-years; adjusted HR 1.76), with similar findings seen in women, the report shows.

“Despite the relatively low absolute risk, the difference in absolute risk and the fact that sustained hypertension during longer durations is associated with higher risk of CVD [cardiovascular disease] indicate that early blood pressure management among young adults may lead to significant public health benefits by reducing CVD risk later in life,” Dr. Son and colleagues wrote in a discussion of the results.

Authors of the U.S. study reported disclosures related to Amarin, Amgen, and Novartis outside of the submitted work, as well as grants from the National Heart, Lung, and Blood Institute and National Institutes of Health during the conduct of the study.

Authors of the South Korean study reported no conflict of interest disclosures. That study was supported by the Ministry of Health and Welfare and the Ministry of Education of Korea, along with grants from the National Research Foundation of Korea.

SOURCES: Yano Y et al. JAMA. 2018;302(17):1774-82; Son JS et al. JAMA. 2018;302(17):1783-92.

Young adults with elevated blood pressure or hypertension, as it is defined in recent U.S. guidelines, may be at increased risk of cardiovascular disease, a pair of recent studies published in JAMA suggest.

GlobalStock/Getty Images

In one study, investigators applied the 2017 American College of Cardiology/American Heart Association blood pressure criteria to nearly 5,000 U.S. young adults followed for approximately 20 years and who had up to a 3.5-fold risk associated with hypertension versus normal blood pressure.

The second study of almost 2.5 million Korean young adults, followed for 10 years, similarly found increased risks of cardiovascular disease later in life for those who had stage 1 or 2 hypertension between the ages of 20 and 39 years.

“These findings from a second country on the opposite side of the globe are consistent with those of the U.S. study, providing further support for the ACC/AHA guideline definitions of hypertension,” Naomi D.L. Fisher, MD, deputy editor, JAMA, and Gregory Curfman, MD, Brigham and Women’s Hospital, Boston, said in an editorial also appearing in JAMA.

Disagreement over the ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults threatens to distract from their potential benefits, Dr. Fisher and Dr. Curfman wrote in that editorial.

By redefining stage 1 hypertension as 130/80 mm Hg or higher, down from 140/90 mm Hg or higher, the 2017 ACC/AHA increased the prevalence of hypertension in the United States from 31.9% to 45.6%, they noted.

“Given the magnitude and reach of the global problem of hypertension, it is imperative that dedicated control efforts at the population level intensify,” they said.
 

U.S. study

The U.S. study, described in JAMA by Yuichiro Yano, MD, PhD, department of community and family medicine, Duke University, Durham, N.C., and his colleagues, was based on analysis of a prospective cohort study, CARDIA (Coronary Artery Risk Development in Young Adults Study), which started in 1985 and enrolled 5,115 black and white adults aged 18-30 years.

They applied the ACC/AHA blood pressure criteria based on each participants’ highest measurement before the age of 40 years, and correlated that with incident cardiovascular disease events that occurred over a median follow-up of 18.8 years.

Patients with normal blood pressure had a cardiovascular disease incidence rate of 1.37/1,000 person-years, compared with 2.74/1,000 person-years for those with elevated blood pressure, 3.15 for stage 1 hypertension, and 8.04 for stage 2 hypertension, investigators found.

That translated into increased risks of cardiovascular disease for those with elevated blood pressure versus those with normal blood pressure. After multivariable adjustment, the hazard ratio for cardiovascular disease was 1.67 (95% confidence interval, 1.01-2.77) for elevated blood pressure, 1.75 (95% CI, 1.22-2.53) for stage 1 hypertension, and 3.49 (95% CI, 2.42-5.05) for stage 2, Dr. Yano and his colleagues reported.

“The ACC/AHA blood pressure classification system may help identify young adults at higher risk for CVD events,” they concluded.
 

South Korean study

Similar findings were shown in a population-based cohort study, also published in JAMA, that included 2,488,101 adults aged 20-39 years in Korean National Health Insurance Service records.

The investigators looked at mean blood pressure levels from an initial health examination that took place during 2002-2003 and a second examination during 2004-2005.

Follow-up was shorter than the U.S. study, with a median duration of 10 years, reported Joung Sik Son, MD, department of family medicine and biomedical sciences, Seoul (South Korea) National University, and coauthors.

Even so, investigators detected an elevated risk of cardiovascular events for individuals with stage 1 or 2 hypertension versus those with normal blood pressure.

For men with baseline stage 1 hypertension based on the mean values and using the latest ACC/AHA blood pressure criteria, the incidence of cardiovascular disease was 215/100,000 person-years, versus 164 for those with normal blood pressure, with an adjusted hazard ratio of 1.25 (95% CI, 1.21-1.28), the authors said. Likewise, women with stage 1 hypertension had an incidence of 131/100,000 person-years versus 40 for women with normal blood pressure, with a hazard ratio of 1.27 (95% CI, 1.21-1.34).

Men with stage 2 hypertension likewise had a higher cardiovascular disease incidence than did those with normal blood pressure (336 vs. 164 per 100,000 person-years; adjusted HR 1.76), with similar findings seen in women, the report shows.

“Despite the relatively low absolute risk, the difference in absolute risk and the fact that sustained hypertension during longer durations is associated with higher risk of CVD [cardiovascular disease] indicate that early blood pressure management among young adults may lead to significant public health benefits by reducing CVD risk later in life,” Dr. Son and colleagues wrote in a discussion of the results.

Authors of the U.S. study reported disclosures related to Amarin, Amgen, and Novartis outside of the submitted work, as well as grants from the National Heart, Lung, and Blood Institute and National Institutes of Health during the conduct of the study.

Authors of the South Korean study reported no conflict of interest disclosures. That study was supported by the Ministry of Health and Welfare and the Ministry of Education of Korea, along with grants from the National Research Foundation of Korea.

SOURCES: Yano Y et al. JAMA. 2018;302(17):1774-82; Son JS et al. JAMA. 2018;302(17):1783-92.

SAN DIEGO – Patients undergoing transcatheter edge-to-edge valve repair for symptomatic tricuspid regurgitation have good outcomes at 1 year, based on a subgroup analysis of the TriValve Registry. Findings were reported in a session and press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.

Susan London/MDedge News

Research on the tricuspid valve, “the so-called forgotten valve,” is limited, commented lead investigator Jörg Hausleiter, MD, of the Medizinische Klinik und Poliklinik I at the Klinikum der Universität München and the Munich Heart Alliance. But there is unmet need for transcatheter treatment of high-risk patients having symptomatic tricuspid regurgitation (TR).

“The MitraClip has been used in several sites in off-label and compassionate-use programs to treat these patients,” he noted. “But the data which are available so far are really just looking at the early outcome, like 30 days.”

Dr. Hausleiter and his colleagues undertook a retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic TR from the international, multidevice TriValve Registry. All received conventional MitraClips (Abbott Vascular) through off-label or compassionate-use programs.

The procedure was successful, reducing regurgitation to mild or moderate levels in nearly four-fifths of patients by discharge. And procedural success was associated with lower risk of rehospitalization and death.

At 1 year, more than two-thirds of all patients had achieved a New York Heart Association (NYHA) functional class of I or II. In addition, prevalence of peripheral edema had fallen dramatically.

“We were able to demonstrate that the TR reduction is durable and that this also improves the clinical outcome at 1 year,” Dr. Hausleiter concluded.

Uptake and applicability

This procedure will likely be increasingly used in Europe and will find its way into U.S. practice in the not-so-distant future, Dr. Hausleiter predicted. “The MitraClip actually is being used now in a modified version in trials, so that this edge-to-edge therapy is applied for TR. And the TRILUMINATE trial has just finished its enrollment in Europe. I guess that we are going to see EU Mark approval for this therapy also next year. At the same time, a U.S. study is currently being planned and will start very soon with this device, so you are going to see this type of therapy at least being investigated within the next few months.”

The procedure is applicable to a large proportion of patients with TR, including the sizable share having comorbid mitral regurgitation (MR), according to Dr. Hausleiter. In fact, more than half of the study patients had treatment of MR during the same procedure for their tricuspid valve.

Susan London/MDedge News

“How were outcomes compared, mitral clip plus tricuspid clip, versus tricuspid clip alone? Could some of this benefit be attributed to the mitral clip procedure?” asked press conference panelist Mayra Guerrero, MD, a senior associate consultant in interventional cardiology in the department of cardiovascular medicine at the Mayo Clinic Hospital, Rochester, Minn.

The two groups had essentially the same mortality rates and improvements in NYHA class, Dr. Hausleiter said. “So we did not observe any difference between those patients who were just treated on the tricuspid side and those patients who had combined treatment. Of course the patients differed a bit in their baseline characteristics, but the outcome was very much the same.”

“With the new data we have, operators and teams may be encouraged to start treating functional MR. I personally think that, if we do that, we should probably evaluate the response and reevaluate the severity of TR after all therapies to the mitral valve have been provided, before we intervene on the tricuspid valve, until we have more data,” Dr. Guerrero further commented. “Do you agree?”

“The tricuspid regurgitation can also improve after treatment of the mitral side. However, when we look at least at the published data, in at least 50% of patients who have severe TR, this TR is not improving,” Dr. Hausleiter replied. In addition, registry data suggest that these patients with severe TR have higher in-hospital, 30-day, and 1-year mortality, compared with patients whose TR is not severe. “Since these are frail patients and you don’t want to bring them too often back to the hospital, if the procedure can be performed very easily, I think there might be a good rationale to combine this.”

Study details

The patients Dr. Hausleiter and his coinvestigators studied had symptomatic TR, predominantly of grade 3+ or 4+, despite receiving adequate medical therapy, as well as a high operative risk, with an average EuroSCORE II of 11.2%. On average, two MitraClips were placed in their tricuspid valve during the procedure.

“We were able to demonstrate that this procedure can be performed very safely. There was a mortality of only 2% in the first 30 days, and one conversion to surgery,” Dr. Hausleiter reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. “We were able to reduce the TR by at least one grade in 89% of patients, and concomitant treatment for mitral regurgitation was also performed in the same procedure in 52%.”

The rate of procedural success, defined as achievement of TR grade of 1+ or 2+ at discharge, was 77%. Independent predictors of procedural failure were noncentral/nonanteroseptal TR jet location and larger TR effective regurgitant orifice area, tenting area, and leaflet gap.

With a mean follow-up of about 10 months, compared with peers in whom the procedure failed, patients in whom it was successful had a higher 1-year rate of freedom from unplanned rehospitalization or death (70.1% vs. 49.7%; P less than .0001).

The 77% rate of procedural success at discharge was largely maintained at 1 year, when it was 72%. There was also a significant improvement in NYHA class distribution in the entire cohort (P less than .001), with 69% of patients attaining class I or II at this time point, compared with virtually none at baseline. Prevalence of peripheral edema fell from 84% to 26% (P less than .001).

Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.

SAN DIEGO – Patients undergoing transcatheter edge-to-edge valve repair for symptomatic tricuspid regurgitation have good outcomes at 1 year, based on a subgroup analysis of the TriValve Registry. Findings were reported in a session and press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.

Susan London/MDedge News

Research on the tricuspid valve, “the so-called forgotten valve,” is limited, commented lead investigator Jörg Hausleiter, MD, of the Medizinische Klinik und Poliklinik I at the Klinikum der Universität München and the Munich Heart Alliance. But there is unmet need for transcatheter treatment of high-risk patients having symptomatic tricuspid regurgitation (TR).

“The MitraClip has been used in several sites in off-label and compassionate-use programs to treat these patients,” he noted. “But the data which are available so far are really just looking at the early outcome, like 30 days.”

Dr. Hausleiter and his colleagues undertook a retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic TR from the international, multidevice TriValve Registry. All received conventional MitraClips (Abbott Vascular) through off-label or compassionate-use programs.

The procedure was successful, reducing regurgitation to mild or moderate levels in nearly four-fifths of patients by discharge. And procedural success was associated with lower risk of rehospitalization and death.

At 1 year, more than two-thirds of all patients had achieved a New York Heart Association (NYHA) functional class of I or II. In addition, prevalence of peripheral edema had fallen dramatically.

“We were able to demonstrate that the TR reduction is durable and that this also improves the clinical outcome at 1 year,” Dr. Hausleiter concluded.

Uptake and applicability

This procedure will likely be increasingly used in Europe and will find its way into U.S. practice in the not-so-distant future, Dr. Hausleiter predicted. “The MitraClip actually is being used now in a modified version in trials, so that this edge-to-edge therapy is applied for TR. And the TRILUMINATE trial has just finished its enrollment in Europe. I guess that we are going to see EU Mark approval for this therapy also next year. At the same time, a U.S. study is currently being planned and will start very soon with this device, so you are going to see this type of therapy at least being investigated within the next few months.”

The procedure is applicable to a large proportion of patients with TR, including the sizable share having comorbid mitral regurgitation (MR), according to Dr. Hausleiter. In fact, more than half of the study patients had treatment of MR during the same procedure for their tricuspid valve.

Susan London/MDedge News

“How were outcomes compared, mitral clip plus tricuspid clip, versus tricuspid clip alone? Could some of this benefit be attributed to the mitral clip procedure?” asked press conference panelist Mayra Guerrero, MD, a senior associate consultant in interventional cardiology in the department of cardiovascular medicine at the Mayo Clinic Hospital, Rochester, Minn.

The two groups had essentially the same mortality rates and improvements in NYHA class, Dr. Hausleiter said. “So we did not observe any difference between those patients who were just treated on the tricuspid side and those patients who had combined treatment. Of course the patients differed a bit in their baseline characteristics, but the outcome was very much the same.”

“With the new data we have, operators and teams may be encouraged to start treating functional MR. I personally think that, if we do that, we should probably evaluate the response and reevaluate the severity of TR after all therapies to the mitral valve have been provided, before we intervene on the tricuspid valve, until we have more data,” Dr. Guerrero further commented. “Do you agree?”

“The tricuspid regurgitation can also improve after treatment of the mitral side. However, when we look at least at the published data, in at least 50% of patients who have severe TR, this TR is not improving,” Dr. Hausleiter replied. In addition, registry data suggest that these patients with severe TR have higher in-hospital, 30-day, and 1-year mortality, compared with patients whose TR is not severe. “Since these are frail patients and you don’t want to bring them too often back to the hospital, if the procedure can be performed very easily, I think there might be a good rationale to combine this.”

Study details

The patients Dr. Hausleiter and his coinvestigators studied had symptomatic TR, predominantly of grade 3+ or 4+, despite receiving adequate medical therapy, as well as a high operative risk, with an average EuroSCORE II of 11.2%. On average, two MitraClips were placed in their tricuspid valve during the procedure.

“We were able to demonstrate that this procedure can be performed very safely. There was a mortality of only 2% in the first 30 days, and one conversion to surgery,” Dr. Hausleiter reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. “We were able to reduce the TR by at least one grade in 89% of patients, and concomitant treatment for mitral regurgitation was also performed in the same procedure in 52%.”

The rate of procedural success, defined as achievement of TR grade of 1+ or 2+ at discharge, was 77%. Independent predictors of procedural failure were noncentral/nonanteroseptal TR jet location and larger TR effective regurgitant orifice area, tenting area, and leaflet gap.

With a mean follow-up of about 10 months, compared with peers in whom the procedure failed, patients in whom it was successful had a higher 1-year rate of freedom from unplanned rehospitalization or death (70.1% vs. 49.7%; P less than .0001).

The 77% rate of procedural success at discharge was largely maintained at 1 year, when it was 72%. There was also a significant improvement in NYHA class distribution in the entire cohort (P less than .001), with 69% of patients attaining class I or II at this time point, compared with virtually none at baseline. Prevalence of peripheral edema fell from 84% to 26% (P less than .001).

Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.

SAN DIEGO – Patients undergoing transcatheter edge-to-edge valve repair for symptomatic tricuspid regurgitation have good outcomes at 1 year, based on a subgroup analysis of the TriValve Registry. Findings were reported in a session and press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.

Susan London/MDedge News

Research on the tricuspid valve, “the so-called forgotten valve,” is limited, commented lead investigator Jörg Hausleiter, MD, of the Medizinische Klinik und Poliklinik I at the Klinikum der Universität München and the Munich Heart Alliance. But there is unmet need for transcatheter treatment of high-risk patients having symptomatic tricuspid regurgitation (TR).

“The MitraClip has been used in several sites in off-label and compassionate-use programs to treat these patients,” he noted. “But the data which are available so far are really just looking at the early outcome, like 30 days.”

Dr. Hausleiter and his colleagues undertook a retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic TR from the international, multidevice TriValve Registry. All received conventional MitraClips (Abbott Vascular) through off-label or compassionate-use programs.

The procedure was successful, reducing regurgitation to mild or moderate levels in nearly four-fifths of patients by discharge. And procedural success was associated with lower risk of rehospitalization and death.

At 1 year, more than two-thirds of all patients had achieved a New York Heart Association (NYHA) functional class of I or II. In addition, prevalence of peripheral edema had fallen dramatically.

“We were able to demonstrate that the TR reduction is durable and that this also improves the clinical outcome at 1 year,” Dr. Hausleiter concluded.

Uptake and applicability

This procedure will likely be increasingly used in Europe and will find its way into U.S. practice in the not-so-distant future, Dr. Hausleiter predicted. “The MitraClip actually is being used now in a modified version in trials, so that this edge-to-edge therapy is applied for TR. And the TRILUMINATE trial has just finished its enrollment in Europe. I guess that we are going to see EU Mark approval for this therapy also next year. At the same time, a U.S. study is currently being planned and will start very soon with this device, so you are going to see this type of therapy at least being investigated within the next few months.”

The procedure is applicable to a large proportion of patients with TR, including the sizable share having comorbid mitral regurgitation (MR), according to Dr. Hausleiter. In fact, more than half of the study patients had treatment of MR during the same procedure for their tricuspid valve.

Susan London/MDedge News

“How were outcomes compared, mitral clip plus tricuspid clip, versus tricuspid clip alone? Could some of this benefit be attributed to the mitral clip procedure?” asked press conference panelist Mayra Guerrero, MD, a senior associate consultant in interventional cardiology in the department of cardiovascular medicine at the Mayo Clinic Hospital, Rochester, Minn.

The two groups had essentially the same mortality rates and improvements in NYHA class, Dr. Hausleiter said. “So we did not observe any difference between those patients who were just treated on the tricuspid side and those patients who had combined treatment. Of course the patients differed a bit in their baseline characteristics, but the outcome was very much the same.”

“With the new data we have, operators and teams may be encouraged to start treating functional MR. I personally think that, if we do that, we should probably evaluate the response and reevaluate the severity of TR after all therapies to the mitral valve have been provided, before we intervene on the tricuspid valve, until we have more data,” Dr. Guerrero further commented. “Do you agree?”

“The tricuspid regurgitation can also improve after treatment of the mitral side. However, when we look at least at the published data, in at least 50% of patients who have severe TR, this TR is not improving,” Dr. Hausleiter replied. In addition, registry data suggest that these patients with severe TR have higher in-hospital, 30-day, and 1-year mortality, compared with patients whose TR is not severe. “Since these are frail patients and you don’t want to bring them too often back to the hospital, if the procedure can be performed very easily, I think there might be a good rationale to combine this.”

Study details

The patients Dr. Hausleiter and his coinvestigators studied had symptomatic TR, predominantly of grade 3+ or 4+, despite receiving adequate medical therapy, as well as a high operative risk, with an average EuroSCORE II of 11.2%. On average, two MitraClips were placed in their tricuspid valve during the procedure.

“We were able to demonstrate that this procedure can be performed very safely. There was a mortality of only 2% in the first 30 days, and one conversion to surgery,” Dr. Hausleiter reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. “We were able to reduce the TR by at least one grade in 89% of patients, and concomitant treatment for mitral regurgitation was also performed in the same procedure in 52%.”

The rate of procedural success, defined as achievement of TR grade of 1+ or 2+ at discharge, was 77%. Independent predictors of procedural failure were noncentral/nonanteroseptal TR jet location and larger TR effective regurgitant orifice area, tenting area, and leaflet gap.

With a mean follow-up of about 10 months, compared with peers in whom the procedure failed, patients in whom it was successful had a higher 1-year rate of freedom from unplanned rehospitalization or death (70.1% vs. 49.7%; P less than .0001).

The 77% rate of procedural success at discharge was largely maintained at 1 year, when it was 72%. There was also a significant improvement in NYHA class distribution in the entire cohort (P less than .001), with 69% of patients attaining class I or II at this time point, compared with virtually none at baseline. Prevalence of peripheral edema fell from 84% to 26% (P less than .001).

Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.