For heavily pretreated patients with BRCA-mutated ovarian cancer, olaparib is more effective than nonplatinum chemotherapy, according to results from the SOLO3 trial.

Both objective response rate and progression-free survival were significantly better in the olaparib group, reported lead author Richard T. Penson, MD, of Massachusetts General Hospital, Boston, and colleagues. These findings were published in the Journal of Clinical Oncology.

SOLO3 provides much-needed data for an understudied but common group of patients, according to Kathleen Moore, MD, lead author of the previous SOLO1 trial and associate director of clinical research at the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

“[Approximately] 50% of the women who participated in SOLO3 were on their fourth or more line of chemo,” Dr. Moore said in an interview. “That group of patients has not been studied in the past ... Even though we know many women receive many, many lines of chemotherapy, we really don’t have high quality clinical trial data to give women any indication of what to expect in terms of their response rate.”

SOLO3 is also notable, Dr. Moore said, because it is the first phase 3 trial to compare a PARP inhibitor with doctor’s choice chemotherapy.

SOLO3 involved 266 patients with BRCA-mutated, relapsed ovarian cancer who had received two or more lines of platinum-based chemotherapy. All patients were platinum sensitive (progression more than 12 months after last platinum-based treatment) or partially platinum sensitive (progression within 6-12 months of last platinum-based treatment).

After enrollment, participants were randomized in a 2:1 ratio to receive either olaparib (300 mg twice daily) or physician’s choice, single-agent, nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary endpoint was objective response rate, determined by blinded independent central review. Secondary endpoints included progression-free survival and overall survival.

At a median follow-up of 13.8 months in the olaparib group and 3.9 months in the chemotherapy group, olaparib showed a significant efficacy advantage. Among 223 patients with measurable disease, the objective response rate was 72.2% in the olaparib group and 51.4% in the chemotherapy group (odds ratio, 2.53; P = .002).

The superiority of olaparib was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Similar benefits were observed regardless of age.

Across all patients, the median progression-free survival was significantly better in the olaparib group, at 13.4 months, versus 9.2 months in the chemotherapy group (P = .013). Overall survival data were immature.

No new safety signals were encountered. The most common adverse events (AEs) in the olaparib group were nausea, fatigue/asthenia, anemia, vomiting, and diarrhea. The most common AEs in the chemotherapy group were fatigue/asthenia, palmar-plantar erythrodysesthesia, nausea, neutropenia, and anemia.

The rate of serious AEs was 23.6% in the olaparib group and 18.4% in the chemotherapy group. Three patients in the olaparib group, and none in the chemotherapy group, developed new primary malignancies. There were four patients with fatal AEs in the olaparib group (myelodysplastic syndrome, cardiopulmonary decompensation, sepsis, and acute myeloid leukemia and subarachnoid hemorrhage), and there was one fatal AE in the chemotherapy group (mesenteric vein thrombosis).

Dr. Moore pointed out that these findings are relevant to current clinical practice, but a shifting treatment landscape may soon render SOLO3 data obsolete.

“PARP [inhibitors] are likely moving into the frontline,” Dr. Moore said. “So this population of women who have not received a PARP [inhibitor] and are recurrent is still here, and they will be for several years, but there’s going to be a point when they’re not going to be here anymore, because they’ll all have received [a PARP inhibitor] front line.”

Concerning the broader research landscape for PARP inhibitors, Dr. Moore suggested that investigators are currently in a “waiting period” while the Food and Drug Administration and European Medicines Agency interpret major clinical trials, such as PAOLA-1 and PRIMA.

A variety of patient populations and clinical scenarios remain unevaluated, Dr. Moore said, including patients who don’t respond to PARP inhibitors, those who have disease recurrence while taking PARP inhibitors, and which drug combinations to use for which patients.

“There are a lot of irons in the fire right now, just getting ready to launch, but I think we need to see what the population is that’s going to be exposed to PARP [inhibitors] next, so we can design the next round of studies,” Dr. Moore said. “It’s an exciting time.”

SOLO3 was funded by AstraZeneca and Merck. The investigators reported additional relationships with Clovis Oncology, Eisai, Tesaro, and other companies. Dr. Moore disclosed relationships with Genentech, Immunogen, Mersana, and other companies.

SOURCE: Penson et al. J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745.

For heavily pretreated patients with BRCA-mutated ovarian cancer, olaparib is more effective than nonplatinum chemotherapy, according to results from the SOLO3 trial.

Both objective response rate and progression-free survival were significantly better in the olaparib group, reported lead author Richard T. Penson, MD, of Massachusetts General Hospital, Boston, and colleagues. These findings were published in the Journal of Clinical Oncology.

SOLO3 provides much-needed data for an understudied but common group of patients, according to Kathleen Moore, MD, lead author of the previous SOLO1 trial and associate director of clinical research at the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

“[Approximately] 50% of the women who participated in SOLO3 were on their fourth or more line of chemo,” Dr. Moore said in an interview. “That group of patients has not been studied in the past ... Even though we know many women receive many, many lines of chemotherapy, we really don’t have high quality clinical trial data to give women any indication of what to expect in terms of their response rate.”

SOLO3 is also notable, Dr. Moore said, because it is the first phase 3 trial to compare a PARP inhibitor with doctor’s choice chemotherapy.

SOLO3 involved 266 patients with BRCA-mutated, relapsed ovarian cancer who had received two or more lines of platinum-based chemotherapy. All patients were platinum sensitive (progression more than 12 months after last platinum-based treatment) or partially platinum sensitive (progression within 6-12 months of last platinum-based treatment).

After enrollment, participants were randomized in a 2:1 ratio to receive either olaparib (300 mg twice daily) or physician’s choice, single-agent, nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary endpoint was objective response rate, determined by blinded independent central review. Secondary endpoints included progression-free survival and overall survival.

At a median follow-up of 13.8 months in the olaparib group and 3.9 months in the chemotherapy group, olaparib showed a significant efficacy advantage. Among 223 patients with measurable disease, the objective response rate was 72.2% in the olaparib group and 51.4% in the chemotherapy group (odds ratio, 2.53; P = .002).

The superiority of olaparib was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Similar benefits were observed regardless of age.

Across all patients, the median progression-free survival was significantly better in the olaparib group, at 13.4 months, versus 9.2 months in the chemotherapy group (P = .013). Overall survival data were immature.

No new safety signals were encountered. The most common adverse events (AEs) in the olaparib group were nausea, fatigue/asthenia, anemia, vomiting, and diarrhea. The most common AEs in the chemotherapy group were fatigue/asthenia, palmar-plantar erythrodysesthesia, nausea, neutropenia, and anemia.

The rate of serious AEs was 23.6% in the olaparib group and 18.4% in the chemotherapy group. Three patients in the olaparib group, and none in the chemotherapy group, developed new primary malignancies. There were four patients with fatal AEs in the olaparib group (myelodysplastic syndrome, cardiopulmonary decompensation, sepsis, and acute myeloid leukemia and subarachnoid hemorrhage), and there was one fatal AE in the chemotherapy group (mesenteric vein thrombosis).

Dr. Moore pointed out that these findings are relevant to current clinical practice, but a shifting treatment landscape may soon render SOLO3 data obsolete.

“PARP [inhibitors] are likely moving into the frontline,” Dr. Moore said. “So this population of women who have not received a PARP [inhibitor] and are recurrent is still here, and they will be for several years, but there’s going to be a point when they’re not going to be here anymore, because they’ll all have received [a PARP inhibitor] front line.”

Concerning the broader research landscape for PARP inhibitors, Dr. Moore suggested that investigators are currently in a “waiting period” while the Food and Drug Administration and European Medicines Agency interpret major clinical trials, such as PAOLA-1 and PRIMA.

A variety of patient populations and clinical scenarios remain unevaluated, Dr. Moore said, including patients who don’t respond to PARP inhibitors, those who have disease recurrence while taking PARP inhibitors, and which drug combinations to use for which patients.

“There are a lot of irons in the fire right now, just getting ready to launch, but I think we need to see what the population is that’s going to be exposed to PARP [inhibitors] next, so we can design the next round of studies,” Dr. Moore said. “It’s an exciting time.”

SOLO3 was funded by AstraZeneca and Merck. The investigators reported additional relationships with Clovis Oncology, Eisai, Tesaro, and other companies. Dr. Moore disclosed relationships with Genentech, Immunogen, Mersana, and other companies.

SOURCE: Penson et al. J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745.

For heavily pretreated patients with BRCA-mutated ovarian cancer, olaparib is more effective than nonplatinum chemotherapy, according to results from the SOLO3 trial.

Both objective response rate and progression-free survival were significantly better in the olaparib group, reported lead author Richard T. Penson, MD, of Massachusetts General Hospital, Boston, and colleagues. These findings were published in the Journal of Clinical Oncology.

SOLO3 provides much-needed data for an understudied but common group of patients, according to Kathleen Moore, MD, lead author of the previous SOLO1 trial and associate director of clinical research at the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

“[Approximately] 50% of the women who participated in SOLO3 were on their fourth or more line of chemo,” Dr. Moore said in an interview. “That group of patients has not been studied in the past ... Even though we know many women receive many, many lines of chemotherapy, we really don’t have high quality clinical trial data to give women any indication of what to expect in terms of their response rate.”

SOLO3 is also notable, Dr. Moore said, because it is the first phase 3 trial to compare a PARP inhibitor with doctor’s choice chemotherapy.

SOLO3 involved 266 patients with BRCA-mutated, relapsed ovarian cancer who had received two or more lines of platinum-based chemotherapy. All patients were platinum sensitive (progression more than 12 months after last platinum-based treatment) or partially platinum sensitive (progression within 6-12 months of last platinum-based treatment).

After enrollment, participants were randomized in a 2:1 ratio to receive either olaparib (300 mg twice daily) or physician’s choice, single-agent, nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary endpoint was objective response rate, determined by blinded independent central review. Secondary endpoints included progression-free survival and overall survival.

At a median follow-up of 13.8 months in the olaparib group and 3.9 months in the chemotherapy group, olaparib showed a significant efficacy advantage. Among 223 patients with measurable disease, the objective response rate was 72.2% in the olaparib group and 51.4% in the chemotherapy group (odds ratio, 2.53; P = .002).

The superiority of olaparib was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Similar benefits were observed regardless of age.

Across all patients, the median progression-free survival was significantly better in the olaparib group, at 13.4 months, versus 9.2 months in the chemotherapy group (P = .013). Overall survival data were immature.

No new safety signals were encountered. The most common adverse events (AEs) in the olaparib group were nausea, fatigue/asthenia, anemia, vomiting, and diarrhea. The most common AEs in the chemotherapy group were fatigue/asthenia, palmar-plantar erythrodysesthesia, nausea, neutropenia, and anemia.

The rate of serious AEs was 23.6% in the olaparib group and 18.4% in the chemotherapy group. Three patients in the olaparib group, and none in the chemotherapy group, developed new primary malignancies. There were four patients with fatal AEs in the olaparib group (myelodysplastic syndrome, cardiopulmonary decompensation, sepsis, and acute myeloid leukemia and subarachnoid hemorrhage), and there was one fatal AE in the chemotherapy group (mesenteric vein thrombosis).

Dr. Moore pointed out that these findings are relevant to current clinical practice, but a shifting treatment landscape may soon render SOLO3 data obsolete.

“PARP [inhibitors] are likely moving into the frontline,” Dr. Moore said. “So this population of women who have not received a PARP [inhibitor] and are recurrent is still here, and they will be for several years, but there’s going to be a point when they’re not going to be here anymore, because they’ll all have received [a PARP inhibitor] front line.”

Concerning the broader research landscape for PARP inhibitors, Dr. Moore suggested that investigators are currently in a “waiting period” while the Food and Drug Administration and European Medicines Agency interpret major clinical trials, such as PAOLA-1 and PRIMA.

A variety of patient populations and clinical scenarios remain unevaluated, Dr. Moore said, including patients who don’t respond to PARP inhibitors, those who have disease recurrence while taking PARP inhibitors, and which drug combinations to use for which patients.

“There are a lot of irons in the fire right now, just getting ready to launch, but I think we need to see what the population is that’s going to be exposed to PARP [inhibitors] next, so we can design the next round of studies,” Dr. Moore said. “It’s an exciting time.”

SOLO3 was funded by AstraZeneca and Merck. The investigators reported additional relationships with Clovis Oncology, Eisai, Tesaro, and other companies. Dr. Moore disclosed relationships with Genentech, Immunogen, Mersana, and other companies.

SOURCE: Penson et al. J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745.

MAUI, HAWAII – Osteoporosis affects about 15% of people with inflammatory bowel disease (IBD), but the disease pattern is different than in the general population, said gastroenterologist Millie Long, MD, from the Department of Medicine at the University of North Carolina in Chapel Hill.

In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.

But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.

A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
 

Preventing fractures

Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.

Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.

“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”

Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.

“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
 

Higher risk for herpes zoster

The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.

In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.

Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.

But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.

However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.

“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
 

Screening for TB

Screening to rule out latent tuberculosis (TB) is also important in IBD.

“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”

The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.

“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.

He said he is particularly struck by the collective risks for younger patients with IBD.

“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.

And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.

“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.

This article first appeared on Medscape.com.

MAUI, HAWAII – Osteoporosis affects about 15% of people with inflammatory bowel disease (IBD), but the disease pattern is different than in the general population, said gastroenterologist Millie Long, MD, from the Department of Medicine at the University of North Carolina in Chapel Hill.

In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.

But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.

A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
 

Preventing fractures

Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.

Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.

“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”

Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.

“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
 

Higher risk for herpes zoster

The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.

In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.

Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.

But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.

However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.

“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
 

Screening for TB

Screening to rule out latent tuberculosis (TB) is also important in IBD.

“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”

The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.

“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.

He said he is particularly struck by the collective risks for younger patients with IBD.

“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.

And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.

“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.

This article first appeared on Medscape.com.

MAUI, HAWAII – Osteoporosis affects about 15% of people with inflammatory bowel disease (IBD), but the disease pattern is different than in the general population, said gastroenterologist Millie Long, MD, from the Department of Medicine at the University of North Carolina in Chapel Hill.

In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.

But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.

A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
 

Preventing fractures

Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.

Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.

“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”

Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.

“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
 

Higher risk for herpes zoster

The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.

In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.

Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.

But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.

However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.

“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
 

Screening for TB

Screening to rule out latent tuberculosis (TB) is also important in IBD.

“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”

The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.

“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.

He said he is particularly struck by the collective risks for younger patients with IBD.

“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.

And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.

“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.

This article first appeared on Medscape.com.

SAN FRANCISCO – A large share of men with testicular cancer undergoing postchemotherapy retroperitoneal lymph node dissection (RPLND) may be having organs unnecessarily removed at the time, a retrospective analysis suggests.

However, determining which of these patients do not require adjunct resection remains challenging, according to Tim Nestler, MD, of the University Hospital of Cologne in Germany.

Dr. Nestler presented the retrospective analysis at the the 2020 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Nestler and his colleagues analyzed the frequency and pathologic findings of adjunctive organ resection (encompassing organs, blood vessels, and bones) among 1,181 men undergoing postchemotherapy RPLND during 2008-2018.

Adjunctive organ resection was performed in 20% of patients. Pathologic evaluation of the resection specimens showed viable germ cell tumors in 21.7% of these patients, teratomas in 38.7%, and necrosis or fibrosis in 39.6%. The prevalence of necrosis/fibrosis was generally similar across various organs, blood vessels, and bones.

At a median follow-up of 22 months, 27% of the study cohort experienced a relapse. The 5-year rate of relapse-free survival was 18% for patients with viable germ cell tumors in adjunctively resected organs, 54% for those with teratomas, and 81% for those with necrosis/fibrosis.

“Within this cohort, about 40% of all resections finally showed necrosis/fibrosis, and these are patients that were kind of unnecessarily treated from the oncological standpoint,” Dr. Nestler said, although he noted that such resections should continue until there is a reliable way to identify this subset of patients.

“We are thinking of increasing the rate of frozen sections within surgery, especially to avoid nephrectomies, hepatectomies, and vascular resections,” he said. “Or, if we are thinking about bone metastasis, then we also might think about presurgical biopsies.”

Stepping back even further, clinicians could do “a more accurate presurgical work-up to identify those patients that are really in need of postchemotherapy RPLND, compared to those who will have a high chance of showing necrosis/fibrosis,” Dr. Nestler said. “Here, we are currently working on means like radiomics and molecular markers.”
 

Implications for patient counseling

“The problem is, and this is the central crux of the issue, that we cannot accurately identify ‘cancer or teratoma’ from ‘not cancer or teratoma’ prior to surgery,” said session cochair Brant A. Inman, MD, of the Duke Prostate and Urologic Cancer Center in Durham, N.C.

Preoperative biopsies are not helpful in differentiating these groups because of their technical difficulty and very high false-negative rate, Dr. Inman said. And intraoperative biopsies with frozen sections have the same sampling problem, plus problems of diagnostic accuracy and differentiation of live from dead tumor.

“This research is mainly helpful for preoperative patient counseling,” Dr. Inman said. “You have to tell your patient prior to RPLND, especially if they have a large postchemotherapy mass, several things.”

Specifically, patients should be informed about the probability of needing adjunctive resection and what that entails, he said. If this additional surgery is needed, patients should be informed of the probability that the tissues removed will not contain any cancer or teratoma. Moreover, “if this is the case, the blood vessel or organ will likely have been removed without benefit to you,” he added.

Finally, patients should be told that “there is no accurate way presently to distinguish cancer/teratoma from necrosis/fibrosis preoperatively or intraoperatively, including imaging and biopsies,” Dr. Inman said. “New technologies, like microRNA tests, are being developed to help sort this out.”

There was no funding for this research. Dr. Nestler disclosed no relevant conflicts of interest. Dr. Inman disclosed relationships with several pharmaceutical companies as well as patents or royalties for soluble B7-H1.

SOURCE: Nestler T et al. GUCS 2020, Abstract 388.

SAN FRANCISCO – A large share of men with testicular cancer undergoing postchemotherapy retroperitoneal lymph node dissection (RPLND) may be having organs unnecessarily removed at the time, a retrospective analysis suggests.

However, determining which of these patients do not require adjunct resection remains challenging, according to Tim Nestler, MD, of the University Hospital of Cologne in Germany.

Dr. Nestler presented the retrospective analysis at the the 2020 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Nestler and his colleagues analyzed the frequency and pathologic findings of adjunctive organ resection (encompassing organs, blood vessels, and bones) among 1,181 men undergoing postchemotherapy RPLND during 2008-2018.

Adjunctive organ resection was performed in 20% of patients. Pathologic evaluation of the resection specimens showed viable germ cell tumors in 21.7% of these patients, teratomas in 38.7%, and necrosis or fibrosis in 39.6%. The prevalence of necrosis/fibrosis was generally similar across various organs, blood vessels, and bones.

At a median follow-up of 22 months, 27% of the study cohort experienced a relapse. The 5-year rate of relapse-free survival was 18% for patients with viable germ cell tumors in adjunctively resected organs, 54% for those with teratomas, and 81% for those with necrosis/fibrosis.

“Within this cohort, about 40% of all resections finally showed necrosis/fibrosis, and these are patients that were kind of unnecessarily treated from the oncological standpoint,” Dr. Nestler said, although he noted that such resections should continue until there is a reliable way to identify this subset of patients.

“We are thinking of increasing the rate of frozen sections within surgery, especially to avoid nephrectomies, hepatectomies, and vascular resections,” he said. “Or, if we are thinking about bone metastasis, then we also might think about presurgical biopsies.”

Stepping back even further, clinicians could do “a more accurate presurgical work-up to identify those patients that are really in need of postchemotherapy RPLND, compared to those who will have a high chance of showing necrosis/fibrosis,” Dr. Nestler said. “Here, we are currently working on means like radiomics and molecular markers.”
 

Implications for patient counseling

“The problem is, and this is the central crux of the issue, that we cannot accurately identify ‘cancer or teratoma’ from ‘not cancer or teratoma’ prior to surgery,” said session cochair Brant A. Inman, MD, of the Duke Prostate and Urologic Cancer Center in Durham, N.C.

Preoperative biopsies are not helpful in differentiating these groups because of their technical difficulty and very high false-negative rate, Dr. Inman said. And intraoperative biopsies with frozen sections have the same sampling problem, plus problems of diagnostic accuracy and differentiation of live from dead tumor.

“This research is mainly helpful for preoperative patient counseling,” Dr. Inman said. “You have to tell your patient prior to RPLND, especially if they have a large postchemotherapy mass, several things.”

Specifically, patients should be informed about the probability of needing adjunctive resection and what that entails, he said. If this additional surgery is needed, patients should be informed of the probability that the tissues removed will not contain any cancer or teratoma. Moreover, “if this is the case, the blood vessel or organ will likely have been removed without benefit to you,” he added.

Finally, patients should be told that “there is no accurate way presently to distinguish cancer/teratoma from necrosis/fibrosis preoperatively or intraoperatively, including imaging and biopsies,” Dr. Inman said. “New technologies, like microRNA tests, are being developed to help sort this out.”

There was no funding for this research. Dr. Nestler disclosed no relevant conflicts of interest. Dr. Inman disclosed relationships with several pharmaceutical companies as well as patents or royalties for soluble B7-H1.

SOURCE: Nestler T et al. GUCS 2020, Abstract 388.

SAN FRANCISCO – A large share of men with testicular cancer undergoing postchemotherapy retroperitoneal lymph node dissection (RPLND) may be having organs unnecessarily removed at the time, a retrospective analysis suggests.

However, determining which of these patients do not require adjunct resection remains challenging, according to Tim Nestler, MD, of the University Hospital of Cologne in Germany.

Dr. Nestler presented the retrospective analysis at the the 2020 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Nestler and his colleagues analyzed the frequency and pathologic findings of adjunctive organ resection (encompassing organs, blood vessels, and bones) among 1,181 men undergoing postchemotherapy RPLND during 2008-2018.

Adjunctive organ resection was performed in 20% of patients. Pathologic evaluation of the resection specimens showed viable germ cell tumors in 21.7% of these patients, teratomas in 38.7%, and necrosis or fibrosis in 39.6%. The prevalence of necrosis/fibrosis was generally similar across various organs, blood vessels, and bones.

At a median follow-up of 22 months, 27% of the study cohort experienced a relapse. The 5-year rate of relapse-free survival was 18% for patients with viable germ cell tumors in adjunctively resected organs, 54% for those with teratomas, and 81% for those with necrosis/fibrosis.

“Within this cohort, about 40% of all resections finally showed necrosis/fibrosis, and these are patients that were kind of unnecessarily treated from the oncological standpoint,” Dr. Nestler said, although he noted that such resections should continue until there is a reliable way to identify this subset of patients.

“We are thinking of increasing the rate of frozen sections within surgery, especially to avoid nephrectomies, hepatectomies, and vascular resections,” he said. “Or, if we are thinking about bone metastasis, then we also might think about presurgical biopsies.”

Stepping back even further, clinicians could do “a more accurate presurgical work-up to identify those patients that are really in need of postchemotherapy RPLND, compared to those who will have a high chance of showing necrosis/fibrosis,” Dr. Nestler said. “Here, we are currently working on means like radiomics and molecular markers.”
 

Implications for patient counseling

“The problem is, and this is the central crux of the issue, that we cannot accurately identify ‘cancer or teratoma’ from ‘not cancer or teratoma’ prior to surgery,” said session cochair Brant A. Inman, MD, of the Duke Prostate and Urologic Cancer Center in Durham, N.C.

Preoperative biopsies are not helpful in differentiating these groups because of their technical difficulty and very high false-negative rate, Dr. Inman said. And intraoperative biopsies with frozen sections have the same sampling problem, plus problems of diagnostic accuracy and differentiation of live from dead tumor.

“This research is mainly helpful for preoperative patient counseling,” Dr. Inman said. “You have to tell your patient prior to RPLND, especially if they have a large postchemotherapy mass, several things.”

Specifically, patients should be informed about the probability of needing adjunctive resection and what that entails, he said. If this additional surgery is needed, patients should be informed of the probability that the tissues removed will not contain any cancer or teratoma. Moreover, “if this is the case, the blood vessel or organ will likely have been removed without benefit to you,” he added.

Finally, patients should be told that “there is no accurate way presently to distinguish cancer/teratoma from necrosis/fibrosis preoperatively or intraoperatively, including imaging and biopsies,” Dr. Inman said. “New technologies, like microRNA tests, are being developed to help sort this out.”

There was no funding for this research. Dr. Nestler disclosed no relevant conflicts of interest. Dr. Inman disclosed relationships with several pharmaceutical companies as well as patents or royalties for soluble B7-H1.

SOURCE: Nestler T et al. GUCS 2020, Abstract 388.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

While preparing to write this technology column, I received a great deal of insight from the unlikeliest of sources: my mother-in-law.

Now don’t get me wrong – she’s a truly lovely, intelligent, and capable woman. I have sought her advice often on many things and have always been impressed by her wisdom and pragmatism, but I’ve just never thought of asking her for her opinion on medicine or technology, as I considered her knowledge of both subjects to be limited.

This occasion changed my opinion. In fact, I believe that, as health care IT becomes more complex, people like my mother-in-law may be exactly who we should be looking to for answers.

A few weeks ago, my mother-in-law and I were discussing her recent trip to the doctor. When she mentioned some lab tests, I suggested that we log in to her patient portal to view the results. This elicited several questions and a declaration of frustration.

“Which portal?” she asked. “I have so many and can’t keep all of the websites and passwords straight! Why can’t all of my doctors use the same portal, and why do they all have different password requirements?”

As she spoke these words, I was immediately struck with an unfortunate reality of EHRs: We have done a brilliant job creating state-of-the-art digital castles and have filled them with the data needed to revolutionize care and improve population health – but we haven’t given our patients the keys to get inside.

We must ask ourselves if, in trying to construct fortresses of information around our patients, we have lost sight of the individuals in the center. I believe that we can answer this question and improve the benefits of patient portals, but we all must agree to a few simple steps to streamline the experience for everyone.
 

Make it easy

A study recently published in the Journal of General Internal Medicine surveyed several hospitals on their usage of patient portals. After determining whether or not the institutions had such portals, the authors then investigated to find out what, if any, guidance was provided to patients about how to use them.

Their findings are frustrating, though not surprising. While 89% of hospitals had some form of patient portal, only 65% of those “had links that were easily found, defined as links accessible within two clicks from the home page.”

Furthermore, even in cases where portals were easily found, good instructions on how to use them were missing. Those instructions that did exist centered on rules and restrictions and laying out “terms and conditions” and informing patients on “what not to do,” rather than explaining how to make the most of the experience.

According to the authors, “this focus on curtailing behavior, and the hurdles placed on finding and understanding guidance, suggest that some hospitals may be prioritizing reducing liability over improving the patient experience with portals.”

If we want our patients to use them, portals must be easy to access and intuitive to use. They also must provide value.
 

Make it meaningful

Patient portals have proliferated exponentially over the last 10 years, thanks to government incentive programs. One such program, known as “meaningful use,” is primarily responsible for this, as it made implementation of a patient portal one of its core requirements.

Sadly, in spite of its oft-reviled name, the meaningful use program never defined patient-friendly standards of usability for patient portals. As a result, current portals just aren’t very good. Patients like my mother-in-law find them to be too numerous, too unfriendly to use, and too limited, so they are not being used to their full potential.

In fact, many institutions may choose not to enable all of the available features in order to limit technical issues and reduce the burden on providers. In the study referenced above, only 63% of portals offered the ability for patients to communicate directly with their physicians, and only 43% offered the ability to refill prescriptions.

When enabled, these functions improve patient engagement and efficiency. Without them, patients are less likely to log on, and physicians are forced to rely on less-efficient telephone calls or traditional letters to communicate results to their patients.
 

Put the patient, not the portal, at the center

History has all but forgotten the attempts by tech giants such as Google and Microsoft to create personal health records. While these initially seemed like a wonderful concept, they sadly proved to be a total flop. Some patients embraced the idea, but security concerns and the lack of buy-in from EHR vendors significantly limited their uptake.

They may simply have been ahead of their time.

A decade later, wearable technology and telemedicine are ushering in a new era of patient-centric care. Individuals have been embracing a greater share of the responsibility for their own personal health information, yet most EHRs lack the ability to easily incorporate data acquired outside physicians’ offices.

It’s time for EHR vendors to go all in and change that. Instead of enslaving patients to the tyranny of fragmented health records, they should prioritize the creation of a robust, standardized, and portable health record that travels with the patient, not the other way around.

Have any other ideas on how to improve patient engagement? We’d love to hear about them and share them in a future column.

If you want to contribute but don’t have any ideas, we have a suggestion: Ask your mother-in-law. You may be surprised at what you learn!

Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Hospital–Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health.

Reference

Lee JL et al. J Gen Intern Med. 2019 Nov 12. doi: 10.1007/s11606-019-05528-z.

While preparing to write this technology column, I received a great deal of insight from the unlikeliest of sources: my mother-in-law.

Now don’t get me wrong – she’s a truly lovely, intelligent, and capable woman. I have sought her advice often on many things and have always been impressed by her wisdom and pragmatism, but I’ve just never thought of asking her for her opinion on medicine or technology, as I considered her knowledge of both subjects to be limited.

This occasion changed my opinion. In fact, I believe that, as health care IT becomes more complex, people like my mother-in-law may be exactly who we should be looking to for answers.

A few weeks ago, my mother-in-law and I were discussing her recent trip to the doctor. When she mentioned some lab tests, I suggested that we log in to her patient portal to view the results. This elicited several questions and a declaration of frustration.

“Which portal?” she asked. “I have so many and can’t keep all of the websites and passwords straight! Why can’t all of my doctors use the same portal, and why do they all have different password requirements?”

As she spoke these words, I was immediately struck with an unfortunate reality of EHRs: We have done a brilliant job creating state-of-the-art digital castles and have filled them with the data needed to revolutionize care and improve population health – but we haven’t given our patients the keys to get inside.

We must ask ourselves if, in trying to construct fortresses of information around our patients, we have lost sight of the individuals in the center. I believe that we can answer this question and improve the benefits of patient portals, but we all must agree to a few simple steps to streamline the experience for everyone.
 

Make it easy

A study recently published in the Journal of General Internal Medicine surveyed several hospitals on their usage of patient portals. After determining whether or not the institutions had such portals, the authors then investigated to find out what, if any, guidance was provided to patients about how to use them.

Their findings are frustrating, though not surprising. While 89% of hospitals had some form of patient portal, only 65% of those “had links that were easily found, defined as links accessible within two clicks from the home page.”

Furthermore, even in cases where portals were easily found, good instructions on how to use them were missing. Those instructions that did exist centered on rules and restrictions and laying out “terms and conditions” and informing patients on “what not to do,” rather than explaining how to make the most of the experience.

According to the authors, “this focus on curtailing behavior, and the hurdles placed on finding and understanding guidance, suggest that some hospitals may be prioritizing reducing liability over improving the patient experience with portals.”

If we want our patients to use them, portals must be easy to access and intuitive to use. They also must provide value.
 

Make it meaningful

Patient portals have proliferated exponentially over the last 10 years, thanks to government incentive programs. One such program, known as “meaningful use,” is primarily responsible for this, as it made implementation of a patient portal one of its core requirements.

Sadly, in spite of its oft-reviled name, the meaningful use program never defined patient-friendly standards of usability for patient portals. As a result, current portals just aren’t very good. Patients like my mother-in-law find them to be too numerous, too unfriendly to use, and too limited, so they are not being used to their full potential.

In fact, many institutions may choose not to enable all of the available features in order to limit technical issues and reduce the burden on providers. In the study referenced above, only 63% of portals offered the ability for patients to communicate directly with their physicians, and only 43% offered the ability to refill prescriptions.

When enabled, these functions improve patient engagement and efficiency. Without them, patients are less likely to log on, and physicians are forced to rely on less-efficient telephone calls or traditional letters to communicate results to their patients.
 

Put the patient, not the portal, at the center

History has all but forgotten the attempts by tech giants such as Google and Microsoft to create personal health records. While these initially seemed like a wonderful concept, they sadly proved to be a total flop. Some patients embraced the idea, but security concerns and the lack of buy-in from EHR vendors significantly limited their uptake.

They may simply have been ahead of their time.

A decade later, wearable technology and telemedicine are ushering in a new era of patient-centric care. Individuals have been embracing a greater share of the responsibility for their own personal health information, yet most EHRs lack the ability to easily incorporate data acquired outside physicians’ offices.

It’s time for EHR vendors to go all in and change that. Instead of enslaving patients to the tyranny of fragmented health records, they should prioritize the creation of a robust, standardized, and portable health record that travels with the patient, not the other way around.

Have any other ideas on how to improve patient engagement? We’d love to hear about them and share them in a future column.

If you want to contribute but don’t have any ideas, we have a suggestion: Ask your mother-in-law. You may be surprised at what you learn!

Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Hospital–Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health.

Reference

Lee JL et al. J Gen Intern Med. 2019 Nov 12. doi: 10.1007/s11606-019-05528-z.

While preparing to write this technology column, I received a great deal of insight from the unlikeliest of sources: my mother-in-law.

Now don’t get me wrong – she’s a truly lovely, intelligent, and capable woman. I have sought her advice often on many things and have always been impressed by her wisdom and pragmatism, but I’ve just never thought of asking her for her opinion on medicine or technology, as I considered her knowledge of both subjects to be limited.

This occasion changed my opinion. In fact, I believe that, as health care IT becomes more complex, people like my mother-in-law may be exactly who we should be looking to for answers.

A few weeks ago, my mother-in-law and I were discussing her recent trip to the doctor. When she mentioned some lab tests, I suggested that we log in to her patient portal to view the results. This elicited several questions and a declaration of frustration.

“Which portal?” she asked. “I have so many and can’t keep all of the websites and passwords straight! Why can’t all of my doctors use the same portal, and why do they all have different password requirements?”

As she spoke these words, I was immediately struck with an unfortunate reality of EHRs: We have done a brilliant job creating state-of-the-art digital castles and have filled them with the data needed to revolutionize care and improve population health – but we haven’t given our patients the keys to get inside.

We must ask ourselves if, in trying to construct fortresses of information around our patients, we have lost sight of the individuals in the center. I believe that we can answer this question and improve the benefits of patient portals, but we all must agree to a few simple steps to streamline the experience for everyone.
 

Make it easy

A study recently published in the Journal of General Internal Medicine surveyed several hospitals on their usage of patient portals. After determining whether or not the institutions had such portals, the authors then investigated to find out what, if any, guidance was provided to patients about how to use them.

Their findings are frustrating, though not surprising. While 89% of hospitals had some form of patient portal, only 65% of those “had links that were easily found, defined as links accessible within two clicks from the home page.”

Furthermore, even in cases where portals were easily found, good instructions on how to use them were missing. Those instructions that did exist centered on rules and restrictions and laying out “terms and conditions” and informing patients on “what not to do,” rather than explaining how to make the most of the experience.

According to the authors, “this focus on curtailing behavior, and the hurdles placed on finding and understanding guidance, suggest that some hospitals may be prioritizing reducing liability over improving the patient experience with portals.”

If we want our patients to use them, portals must be easy to access and intuitive to use. They also must provide value.
 

Make it meaningful

Patient portals have proliferated exponentially over the last 10 years, thanks to government incentive programs. One such program, known as “meaningful use,” is primarily responsible for this, as it made implementation of a patient portal one of its core requirements.

Sadly, in spite of its oft-reviled name, the meaningful use program never defined patient-friendly standards of usability for patient portals. As a result, current portals just aren’t very good. Patients like my mother-in-law find them to be too numerous, too unfriendly to use, and too limited, so they are not being used to their full potential.

In fact, many institutions may choose not to enable all of the available features in order to limit technical issues and reduce the burden on providers. In the study referenced above, only 63% of portals offered the ability for patients to communicate directly with their physicians, and only 43% offered the ability to refill prescriptions.

When enabled, these functions improve patient engagement and efficiency. Without them, patients are less likely to log on, and physicians are forced to rely on less-efficient telephone calls or traditional letters to communicate results to their patients.
 

Put the patient, not the portal, at the center

History has all but forgotten the attempts by tech giants such as Google and Microsoft to create personal health records. While these initially seemed like a wonderful concept, they sadly proved to be a total flop. Some patients embraced the idea, but security concerns and the lack of buy-in from EHR vendors significantly limited their uptake.

They may simply have been ahead of their time.

A decade later, wearable technology and telemedicine are ushering in a new era of patient-centric care. Individuals have been embracing a greater share of the responsibility for their own personal health information, yet most EHRs lack the ability to easily incorporate data acquired outside physicians’ offices.

It’s time for EHR vendors to go all in and change that. Instead of enslaving patients to the tyranny of fragmented health records, they should prioritize the creation of a robust, standardized, and portable health record that travels with the patient, not the other way around.

Have any other ideas on how to improve patient engagement? We’d love to hear about them and share them in a future column.

If you want to contribute but don’t have any ideas, we have a suggestion: Ask your mother-in-law. You may be surprised at what you learn!

Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Hospital–Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health.

Reference

Lee JL et al. J Gen Intern Med. 2019 Nov 12. doi: 10.1007/s11606-019-05528-z.

NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.

Mitchel L. Zoler/MDedge News

Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.

The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.

The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.

It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.

While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.

The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).

The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.

[email protected]

NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.

Mitchel L. Zoler/MDedge News

Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.

The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.

The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.

It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.

While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.

The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).

The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.

[email protected]

NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.

Mitchel L. Zoler/MDedge News

Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.

The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.

The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.

It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.

While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.

The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).

The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.

[email protected]

SAN FRANCISCO – A novel gene therapy may expand treatment options for non–muscle invasive bladder cancer that does not respond to Bacillus Calmette-Guerin (BCG), new research suggests.

Susan London/MDedge News

The therapy, nadofaragene firadenovec, is a recombinant adenovirus that is instilled into the bladder and delivers the human interferon alpha-2b gene, leading to expression of the immune cytokine.

At 3 months, nadofaragene firadenovec had produced a complete response in 53.4% of patients with carcinoma in situ (CIS), and the rate of high-grade recurrence-free survival was 59.6% in all patients. Although most patients (70.1%) experienced adverse events in this trial, few had serious events (1.9%).

Stephen A. Boorjian, MD, of the Mayo Clinic in Rochester, Minn., presented these results at the 2020 Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“The optimal management for patients with BCG-unresponsive non–muscle invasive bladder cancer remains to be established,” Dr. Boorjian said. “National and organizational guidelines recommend radical cystectomy in this setting, but we have to acknowledge that many of our patients will be either unwilling or unfit to undergo what is often a highly morbid operation.”

Dr. Boorjian and coinvestigators tested nadofaragene firadenovec in 107 patients with CIS, with or without high-grade Ta or T1 papillary disease, as well as 50 patients with high-grade Ta or T1 papillary disease only.

All patients received nadofaragene firadenovec once every 3 months for up four doses, with additional dosing at the investigator’s discretion. Although the trial was designated as phase 3, it did not have the typical randomized comparative design.

“The challenge in the BCG-unresponsive disease state is that, historically, there has been no validated good comparator to use here; there’s no standard of care for these patients,” Dr. Boorjian explained, noting that the design was chosen after discussion with the Food and Drug Administration.
 

Efficacy

The complete response rate among CIS patients at any time after instillation, the trial’s primary objective, was 53.4%. All of these responses occurred after a single dose of nadofaragene firadenovec. Responses were considered durable, as 45.5% of CIS patients who had a complete response at 3 months still had a complete response at 12 months.

The rate of high-grade recurrence-free survival at 3 months was 59.6% in the overall population, 53.4% in patients with CIS, and 72.9% in patients with papillary disease. At 12 months, the rate of high-grade recurrence-free survival was 30.5%, 24.3%, and 43.8%, respectively.

The rate of high-grade recurrence without muscle invasive bladder cancer was 71.8% in the CIS group and 52.1% in the papillary group. The rate of progression to muscle invasive bladder cancer or more advanced disease was 4.9% and 6.3%, respectively. The overall 2-year rate of cystectomy-free survival was 64%, and there were no bladder cancer deaths.
 

Safety

Nadofaragene firadenovec was considered safe and well tolerated. The most common study drug–related adverse events were irritative voiding symptoms, such as discharge, bladder spasm, micturition urgency, and hematuria.

Although 70.1% of patients experienced a local or systemic adverse event related to the study drug or procedure, few experienced serious adverse events (1.9%), grade 3 adverse events (3.8%), or treatment-emergent adverse events leading to discontinuation (1.9%). The serious adverse events were sepsis, syncope, and hematuria.
 

Next steps

“Nadofaragene firadenovec represents a promising option for patients with BCG-unresponsive [non–muscle invasive bladder cancer],” Dr. Boorjian said. “What we want to see going forward is durability of response, cystectomy-free survival, and metastasis-free and cancer-specific survival. Those are the harder endpoints that, as these data mature, we will want to see so that we are able to counsel our patients accordingly.”

Susan London/MDedge News

The FDA recently approved pembrolizumab for this patient population, noted session cochair Guru Sonpavde, MD, of the Dana-Farber Cancer Institute in Boston.

“But nadofaragene firadenovec is much less toxic, it is given intravesically, and it’s only given once every 3 months,” he said. “The outcomes at the 1-year point look similar in terms of the durable complete response rate. So we hope that this therapy will be able to get to the clinic, but we have to wait for the FDA to decide.”

It remains to be seen how nadofaragene firadenovec compares with other emerging therapies for high-risk BCG-unresponsive non–muscle invasive bladder cancer, including pembrolizumab and potentially intravesical oportuzumab monatox (a targeted immunotoxin) and intravesical combination BCG and superagonist interleukin-15 (ALT-803), according to Dr. Boorjian.

“A unique feature of the trial I presented was that the results were validated by a mandatory 12-month study biopsy, which has not been the case in other trials,” he pointed out. “So this separates it a little bit when you are looking at pathologic response rates and high-grade recurrence–free rates. They are based on pathologic confirmation.”

Evaluators will ultimately compare these therapies on safety, efficacy, ease of administration, delivery schedule, and cost, Dr. Boorjian said. “At this stage, it’s very difficult to start to say which agent is going to be placed where in our management paradigm. We have to go step by step: Do the trial that we did, show our data, put it out for review, and then allow the community to engage in a discussion about which agent, and why, for which patient.”

This trial was funded by FKD Therapies Oy. Dr. Boorjian disclosed relationships with Ferring and Sanofi. Dr. Sonpavde disclosed relationships with many companies.

SOURCE: Boorjian SA et al. GUCS 2020, Abstract 442.

SAN FRANCISCO – A novel gene therapy may expand treatment options for non–muscle invasive bladder cancer that does not respond to Bacillus Calmette-Guerin (BCG), new research suggests.

Susan London/MDedge News

The therapy, nadofaragene firadenovec, is a recombinant adenovirus that is instilled into the bladder and delivers the human interferon alpha-2b gene, leading to expression of the immune cytokine.

At 3 months, nadofaragene firadenovec had produced a complete response in 53.4% of patients with carcinoma in situ (CIS), and the rate of high-grade recurrence-free survival was 59.6% in all patients. Although most patients (70.1%) experienced adverse events in this trial, few had serious events (1.9%).

Stephen A. Boorjian, MD, of the Mayo Clinic in Rochester, Minn., presented these results at the 2020 Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“The optimal management for patients with BCG-unresponsive non–muscle invasive bladder cancer remains to be established,” Dr. Boorjian said. “National and organizational guidelines recommend radical cystectomy in this setting, but we have to acknowledge that many of our patients will be either unwilling or unfit to undergo what is often a highly morbid operation.”

Dr. Boorjian and coinvestigators tested nadofaragene firadenovec in 107 patients with CIS, with or without high-grade Ta or T1 papillary disease, as well as 50 patients with high-grade Ta or T1 papillary disease only.

All patients received nadofaragene firadenovec once every 3 months for up four doses, with additional dosing at the investigator’s discretion. Although the trial was designated as phase 3, it did not have the typical randomized comparative design.

“The challenge in the BCG-unresponsive disease state is that, historically, there has been no validated good comparator to use here; there’s no standard of care for these patients,” Dr. Boorjian explained, noting that the design was chosen after discussion with the Food and Drug Administration.
 

Efficacy

The complete response rate among CIS patients at any time after instillation, the trial’s primary objective, was 53.4%. All of these responses occurred after a single dose of nadofaragene firadenovec. Responses were considered durable, as 45.5% of CIS patients who had a complete response at 3 months still had a complete response at 12 months.

The rate of high-grade recurrence-free survival at 3 months was 59.6% in the overall population, 53.4% in patients with CIS, and 72.9% in patients with papillary disease. At 12 months, the rate of high-grade recurrence-free survival was 30.5%, 24.3%, and 43.8%, respectively.

The rate of high-grade recurrence without muscle invasive bladder cancer was 71.8% in the CIS group and 52.1% in the papillary group. The rate of progression to muscle invasive bladder cancer or more advanced disease was 4.9% and 6.3%, respectively. The overall 2-year rate of cystectomy-free survival was 64%, and there were no bladder cancer deaths.
 

Safety

Nadofaragene firadenovec was considered safe and well tolerated. The most common study drug–related adverse events were irritative voiding symptoms, such as discharge, bladder spasm, micturition urgency, and hematuria.

Although 70.1% of patients experienced a local or systemic adverse event related to the study drug or procedure, few experienced serious adverse events (1.9%), grade 3 adverse events (3.8%), or treatment-emergent adverse events leading to discontinuation (1.9%). The serious adverse events were sepsis, syncope, and hematuria.
 

Next steps

“Nadofaragene firadenovec represents a promising option for patients with BCG-unresponsive [non–muscle invasive bladder cancer],” Dr. Boorjian said. “What we want to see going forward is durability of response, cystectomy-free survival, and metastasis-free and cancer-specific survival. Those are the harder endpoints that, as these data mature, we will want to see so that we are able to counsel our patients accordingly.”

Susan London/MDedge News

The FDA recently approved pembrolizumab for this patient population, noted session cochair Guru Sonpavde, MD, of the Dana-Farber Cancer Institute in Boston.

“But nadofaragene firadenovec is much less toxic, it is given intravesically, and it’s only given once every 3 months,” he said. “The outcomes at the 1-year point look similar in terms of the durable complete response rate. So we hope that this therapy will be able to get to the clinic, but we have to wait for the FDA to decide.”

It remains to be seen how nadofaragene firadenovec compares with other emerging therapies for high-risk BCG-unresponsive non–muscle invasive bladder cancer, including pembrolizumab and potentially intravesical oportuzumab monatox (a targeted immunotoxin) and intravesical combination BCG and superagonist interleukin-15 (ALT-803), according to Dr. Boorjian.

“A unique feature of the trial I presented was that the results were validated by a mandatory 12-month study biopsy, which has not been the case in other trials,” he pointed out. “So this separates it a little bit when you are looking at pathologic response rates and high-grade recurrence–free rates. They are based on pathologic confirmation.”

Evaluators will ultimately compare these therapies on safety, efficacy, ease of administration, delivery schedule, and cost, Dr. Boorjian said. “At this stage, it’s very difficult to start to say which agent is going to be placed where in our management paradigm. We have to go step by step: Do the trial that we did, show our data, put it out for review, and then allow the community to engage in a discussion about which agent, and why, for which patient.”

This trial was funded by FKD Therapies Oy. Dr. Boorjian disclosed relationships with Ferring and Sanofi. Dr. Sonpavde disclosed relationships with many companies.

SOURCE: Boorjian SA et al. GUCS 2020, Abstract 442.

SAN FRANCISCO – A novel gene therapy may expand treatment options for non–muscle invasive bladder cancer that does not respond to Bacillus Calmette-Guerin (BCG), new research suggests.

Susan London/MDedge News

The therapy, nadofaragene firadenovec, is a recombinant adenovirus that is instilled into the bladder and delivers the human interferon alpha-2b gene, leading to expression of the immune cytokine.

At 3 months, nadofaragene firadenovec had produced a complete response in 53.4% of patients with carcinoma in situ (CIS), and the rate of high-grade recurrence-free survival was 59.6% in all patients. Although most patients (70.1%) experienced adverse events in this trial, few had serious events (1.9%).

Stephen A. Boorjian, MD, of the Mayo Clinic in Rochester, Minn., presented these results at the 2020 Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“The optimal management for patients with BCG-unresponsive non–muscle invasive bladder cancer remains to be established,” Dr. Boorjian said. “National and organizational guidelines recommend radical cystectomy in this setting, but we have to acknowledge that many of our patients will be either unwilling or unfit to undergo what is often a highly morbid operation.”

Dr. Boorjian and coinvestigators tested nadofaragene firadenovec in 107 patients with CIS, with or without high-grade Ta or T1 papillary disease, as well as 50 patients with high-grade Ta or T1 papillary disease only.

All patients received nadofaragene firadenovec once every 3 months for up four doses, with additional dosing at the investigator’s discretion. Although the trial was designated as phase 3, it did not have the typical randomized comparative design.

“The challenge in the BCG-unresponsive disease state is that, historically, there has been no validated good comparator to use here; there’s no standard of care for these patients,” Dr. Boorjian explained, noting that the design was chosen after discussion with the Food and Drug Administration.
 

Efficacy

The complete response rate among CIS patients at any time after instillation, the trial’s primary objective, was 53.4%. All of these responses occurred after a single dose of nadofaragene firadenovec. Responses were considered durable, as 45.5% of CIS patients who had a complete response at 3 months still had a complete response at 12 months.

The rate of high-grade recurrence-free survival at 3 months was 59.6% in the overall population, 53.4% in patients with CIS, and 72.9% in patients with papillary disease. At 12 months, the rate of high-grade recurrence-free survival was 30.5%, 24.3%, and 43.8%, respectively.

The rate of high-grade recurrence without muscle invasive bladder cancer was 71.8% in the CIS group and 52.1% in the papillary group. The rate of progression to muscle invasive bladder cancer or more advanced disease was 4.9% and 6.3%, respectively. The overall 2-year rate of cystectomy-free survival was 64%, and there were no bladder cancer deaths.
 

Safety

Nadofaragene firadenovec was considered safe and well tolerated. The most common study drug–related adverse events were irritative voiding symptoms, such as discharge, bladder spasm, micturition urgency, and hematuria.

Although 70.1% of patients experienced a local or systemic adverse event related to the study drug or procedure, few experienced serious adverse events (1.9%), grade 3 adverse events (3.8%), or treatment-emergent adverse events leading to discontinuation (1.9%). The serious adverse events were sepsis, syncope, and hematuria.
 

Next steps

“Nadofaragene firadenovec represents a promising option for patients with BCG-unresponsive [non–muscle invasive bladder cancer],” Dr. Boorjian said. “What we want to see going forward is durability of response, cystectomy-free survival, and metastasis-free and cancer-specific survival. Those are the harder endpoints that, as these data mature, we will want to see so that we are able to counsel our patients accordingly.”

Susan London/MDedge News

The FDA recently approved pembrolizumab for this patient population, noted session cochair Guru Sonpavde, MD, of the Dana-Farber Cancer Institute in Boston.

“But nadofaragene firadenovec is much less toxic, it is given intravesically, and it’s only given once every 3 months,” he said. “The outcomes at the 1-year point look similar in terms of the durable complete response rate. So we hope that this therapy will be able to get to the clinic, but we have to wait for the FDA to decide.”

It remains to be seen how nadofaragene firadenovec compares with other emerging therapies for high-risk BCG-unresponsive non–muscle invasive bladder cancer, including pembrolizumab and potentially intravesical oportuzumab monatox (a targeted immunotoxin) and intravesical combination BCG and superagonist interleukin-15 (ALT-803), according to Dr. Boorjian.

“A unique feature of the trial I presented was that the results were validated by a mandatory 12-month study biopsy, which has not been the case in other trials,” he pointed out. “So this separates it a little bit when you are looking at pathologic response rates and high-grade recurrence–free rates. They are based on pathologic confirmation.”

Evaluators will ultimately compare these therapies on safety, efficacy, ease of administration, delivery schedule, and cost, Dr. Boorjian said. “At this stage, it’s very difficult to start to say which agent is going to be placed where in our management paradigm. We have to go step by step: Do the trial that we did, show our data, put it out for review, and then allow the community to engage in a discussion about which agent, and why, for which patient.”

This trial was funded by FKD Therapies Oy. Dr. Boorjian disclosed relationships with Ferring and Sanofi. Dr. Sonpavde disclosed relationships with many companies.

SOURCE: Boorjian SA et al. GUCS 2020, Abstract 442.

NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.

Ted Bosworth/MDedge News

“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.

The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.

“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.

“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”

Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.

However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.

SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.

Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”

Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.

If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.

It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.

“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.

Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.

Dr. Shinnar reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.

Ted Bosworth/MDedge News

“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.

The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.

“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.

“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”

Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.

However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.

SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.

Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”

Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.

If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.

It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.

“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.

Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.

Dr. Shinnar reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.

Ted Bosworth/MDedge News

“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.

The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.

“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.

“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”

Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.

However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.

SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.

Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”

Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.

If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.

It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.

“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.

Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.

Dr. Shinnar reported no potential financial conflicts of interest.

Adults with moderate to severe prurigo nodularis who were treated with the investigational drug nemolizumab showed significant improvement in itching, compared with patients treated with placebo, according to data from a phase 2 trial of 70 patients.

Prurigo nodularis (PN) is a chronic skin condition distinguished by hyperkeratotic red nodules and extreme pruritus, which contributes to crusting and excoriation of the lesions. Lesions can range in size from a few millimeters to 3 centimeters in diameter, and number from a handful to hundreds.

“The pathogenesis of prurigo nodularis is not well understood, but it has been considered to include a form of neuronal sensitization of itch-processing neurons and the development of an itch–scratch cycle,” wrote Sonja Ständer, MD, of the department of dermatology and Center for Chronic Pruritus, University Hospital Münster, Germany, and coauthors. “Interleukin-31, when bound to its receptor complex, has been shown to be a mediator of pruritus, especially in atopic dermatitis and prurigo nodularis,” they noted.

In a study published in the New England Journal of Medicine, the researchers randomized 70 adults with PN to nemolizumab, a monoclonal antibody targeting the interleukin-31 receptor, or a placebo. Patients received 0.5 mg/kg of the drug or placebo subcutaneously at baseline and again at 4 and 8 weeks; safety data were assessed through 18 weeks.

At week 4, the primary outcome of average peak pruritus score based on the numerical rating scale (PP-NRS) decreased by 4.5 points in the nemolizumab group, compared with 1.7 points in the placebo group (reductions of 53% and 20%, respectively). At baseline, weekly peak scores on the PP-NRS were 8.4 for both groups.

In addition, 24% of the nemolizumab patients reported 75% or more healed lesions at week 4, compared with 11% of the placebo group, and at the week 18 final follow-up visit, “the least-squares mean change in the lesion count was −13.3 in the nemolizumab group and − 7.5 in the placebo group,” the researchers said.

Adverse events were similar in both nemolizumab and placebo groups (68% and 67%, respectively) with the most common being gastrointestinal symptoms and musculoskeletal pain. Four nemolizumab patients and three placebo patients experienced serious adverse events. The serious adverse events in the nemolizumab patients included one case each of psoriasiform rash, clavicular fracture, fibromyalgia, and bladder lithiasis. Two patients in each group discontinued the study because of adverse events.

The study findings were limited by the small sample size and short duration, the researchers noted. However, the Food and Drug Administration granted nemolizumab a Breakthrough Therapy Designation in 2019, according to Galderma, and the company is planning a phase 3 trial of nemolizumab in adults with PN to begin later in 2020.

Galderma sponsored and designed the study. Lead author Dr. Ständer disclosed ties with Galderma, Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, LEO Pharma, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals. Several coauthors were Galderma employees.

SOURCE: Ständer S et al. N Engl J Med. 2020 Feb 20;382(8):706-16.

Adults with moderate to severe prurigo nodularis who were treated with the investigational drug nemolizumab showed significant improvement in itching, compared with patients treated with placebo, according to data from a phase 2 trial of 70 patients.

Prurigo nodularis (PN) is a chronic skin condition distinguished by hyperkeratotic red nodules and extreme pruritus, which contributes to crusting and excoriation of the lesions. Lesions can range in size from a few millimeters to 3 centimeters in diameter, and number from a handful to hundreds.

“The pathogenesis of prurigo nodularis is not well understood, but it has been considered to include a form of neuronal sensitization of itch-processing neurons and the development of an itch–scratch cycle,” wrote Sonja Ständer, MD, of the department of dermatology and Center for Chronic Pruritus, University Hospital Münster, Germany, and coauthors. “Interleukin-31, when bound to its receptor complex, has been shown to be a mediator of pruritus, especially in atopic dermatitis and prurigo nodularis,” they noted.

In a study published in the New England Journal of Medicine, the researchers randomized 70 adults with PN to nemolizumab, a monoclonal antibody targeting the interleukin-31 receptor, or a placebo. Patients received 0.5 mg/kg of the drug or placebo subcutaneously at baseline and again at 4 and 8 weeks; safety data were assessed through 18 weeks.

At week 4, the primary outcome of average peak pruritus score based on the numerical rating scale (PP-NRS) decreased by 4.5 points in the nemolizumab group, compared with 1.7 points in the placebo group (reductions of 53% and 20%, respectively). At baseline, weekly peak scores on the PP-NRS were 8.4 for both groups.

In addition, 24% of the nemolizumab patients reported 75% or more healed lesions at week 4, compared with 11% of the placebo group, and at the week 18 final follow-up visit, “the least-squares mean change in the lesion count was −13.3 in the nemolizumab group and − 7.5 in the placebo group,” the researchers said.

Adverse events were similar in both nemolizumab and placebo groups (68% and 67%, respectively) with the most common being gastrointestinal symptoms and musculoskeletal pain. Four nemolizumab patients and three placebo patients experienced serious adverse events. The serious adverse events in the nemolizumab patients included one case each of psoriasiform rash, clavicular fracture, fibromyalgia, and bladder lithiasis. Two patients in each group discontinued the study because of adverse events.

The study findings were limited by the small sample size and short duration, the researchers noted. However, the Food and Drug Administration granted nemolizumab a Breakthrough Therapy Designation in 2019, according to Galderma, and the company is planning a phase 3 trial of nemolizumab in adults with PN to begin later in 2020.

Galderma sponsored and designed the study. Lead author Dr. Ständer disclosed ties with Galderma, Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, LEO Pharma, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals. Several coauthors were Galderma employees.

SOURCE: Ständer S et al. N Engl J Med. 2020 Feb 20;382(8):706-16.

Adults with moderate to severe prurigo nodularis who were treated with the investigational drug nemolizumab showed significant improvement in itching, compared with patients treated with placebo, according to data from a phase 2 trial of 70 patients.

Prurigo nodularis (PN) is a chronic skin condition distinguished by hyperkeratotic red nodules and extreme pruritus, which contributes to crusting and excoriation of the lesions. Lesions can range in size from a few millimeters to 3 centimeters in diameter, and number from a handful to hundreds.

“The pathogenesis of prurigo nodularis is not well understood, but it has been considered to include a form of neuronal sensitization of itch-processing neurons and the development of an itch–scratch cycle,” wrote Sonja Ständer, MD, of the department of dermatology and Center for Chronic Pruritus, University Hospital Münster, Germany, and coauthors. “Interleukin-31, when bound to its receptor complex, has been shown to be a mediator of pruritus, especially in atopic dermatitis and prurigo nodularis,” they noted.

In a study published in the New England Journal of Medicine, the researchers randomized 70 adults with PN to nemolizumab, a monoclonal antibody targeting the interleukin-31 receptor, or a placebo. Patients received 0.5 mg/kg of the drug or placebo subcutaneously at baseline and again at 4 and 8 weeks; safety data were assessed through 18 weeks.

At week 4, the primary outcome of average peak pruritus score based on the numerical rating scale (PP-NRS) decreased by 4.5 points in the nemolizumab group, compared with 1.7 points in the placebo group (reductions of 53% and 20%, respectively). At baseline, weekly peak scores on the PP-NRS were 8.4 for both groups.

In addition, 24% of the nemolizumab patients reported 75% or more healed lesions at week 4, compared with 11% of the placebo group, and at the week 18 final follow-up visit, “the least-squares mean change in the lesion count was −13.3 in the nemolizumab group and − 7.5 in the placebo group,” the researchers said.

Adverse events were similar in both nemolizumab and placebo groups (68% and 67%, respectively) with the most common being gastrointestinal symptoms and musculoskeletal pain. Four nemolizumab patients and three placebo patients experienced serious adverse events. The serious adverse events in the nemolizumab patients included one case each of psoriasiform rash, clavicular fracture, fibromyalgia, and bladder lithiasis. Two patients in each group discontinued the study because of adverse events.

The study findings were limited by the small sample size and short duration, the researchers noted. However, the Food and Drug Administration granted nemolizumab a Breakthrough Therapy Designation in 2019, according to Galderma, and the company is planning a phase 3 trial of nemolizumab in adults with PN to begin later in 2020.

Galderma sponsored and designed the study. Lead author Dr. Ständer disclosed ties with Galderma, Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, LEO Pharma, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals. Several coauthors were Galderma employees.

SOURCE: Ständer S et al. N Engl J Med. 2020 Feb 20;382(8):706-16.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy characterized by diffuse blanchable telangiectases that usually develop in late adulthood. It appears morphologically identical to generalized essential telangiectasia (GET), but skin biopsy characteristically shows dilated superficial blood vessels in the papillary dermis that are surrounded by a thickened layer of type IV collagen.¹ We report a case of CCV occurring in an elderly white man.

A 72-year-old man presented with an asymptomatic rash on the arms, legs, and abdomen of 3 years’ duration. His medical history was remarkable for hypothyroidism, hypertension, reflex sympathetic dystrophy syndrome, coronary artery disease, and nonmelanoma skin cancer. He denied any changes in medications or illnesses prior to onset of the rash. Physical examination revealed diffuse, erythematous, blanchable telangiectases on the arms, legs, and trunk (Figure 1). No petechiae, atrophy, or epidermal changes were appreciated. Darier sign was negative.

Skin biopsy is essential to differentiate CCV from GET, which appears morphologically identical. Cutaneous collagenous vasculopathy may be underreported as a result of clinician choice not to biopsy due to a presumptive diagnosis of GET.³ Successful treatment with a pulsed dye laser has been reported,⁷ though the extent of disease may make complete destruction of the lesions difficult to accomplish. Although it is theorized that CCV may be a marker for underlying systemic disease or even a genetic defect causing abnormal collagen deposition, its cause has yet to be ascertained.⁵ Previously reported patients have had a variety of comorbidities, including several cases of type 2 diabetes mellitus.⁶ Another patient was reported to have recently started treatment with an angiotensin receptor blocker prior to onset of CCV.⁵

Our case contributes to the small series of reported patients with this rare diagnosis and further suggests that it may be underreported at this time. Similar to previously reported cases, our patient was an elderly white individual. Although our patient had long-standing iatrogenic hypothyroidism, no recent medication changes or underlying comorbidities could be tied to the development of CCV. Further studies are needed to determine if this disease process is associated with any underlying systemic illnesses, medications, or family history.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy characterized by diffuse blanchable telangiectases that usually develop in late adulthood. It appears morphologically identical to generalized essential telangiectasia (GET), but skin biopsy characteristically shows dilated superficial blood vessels in the papillary dermis that are surrounded by a thickened layer of type IV collagen.¹ We report a case of CCV occurring in an elderly white man.

A 72-year-old man presented with an asymptomatic rash on the arms, legs, and abdomen of 3 years’ duration. His medical history was remarkable for hypothyroidism, hypertension, reflex sympathetic dystrophy syndrome, coronary artery disease, and nonmelanoma skin cancer. He denied any changes in medications or illnesses prior to onset of the rash. Physical examination revealed diffuse, erythematous, blanchable telangiectases on the arms, legs, and trunk (Figure 1). No petechiae, atrophy, or epidermal changes were appreciated. Darier sign was negative.

Skin biopsy is essential to differentiate CCV from GET, which appears morphologically identical. Cutaneous collagenous vasculopathy may be underreported as a result of clinician choice not to biopsy due to a presumptive diagnosis of GET.³ Successful treatment with a pulsed dye laser has been reported,⁷ though the extent of disease may make complete destruction of the lesions difficult to accomplish. Although it is theorized that CCV may be a marker for underlying systemic disease or even a genetic defect causing abnormal collagen deposition, its cause has yet to be ascertained.⁵ Previously reported patients have had a variety of comorbidities, including several cases of type 2 diabetes mellitus.⁶ Another patient was reported to have recently started treatment with an angiotensin receptor blocker prior to onset of CCV.⁵

Our case contributes to the small series of reported patients with this rare diagnosis and further suggests that it may be underreported at this time. Similar to previously reported cases, our patient was an elderly white individual. Although our patient had long-standing iatrogenic hypothyroidism, no recent medication changes or underlying comorbidities could be tied to the development of CCV. Further studies are needed to determine if this disease process is associated with any underlying systemic illnesses, medications, or family history.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy characterized by diffuse blanchable telangiectases that usually develop in late adulthood. It appears morphologically identical to generalized essential telangiectasia (GET), but skin biopsy characteristically shows dilated superficial blood vessels in the papillary dermis that are surrounded by a thickened layer of type IV collagen.¹ We report a case of CCV occurring in an elderly white man.

A 72-year-old man presented with an asymptomatic rash on the arms, legs, and abdomen of 3 years’ duration. His medical history was remarkable for hypothyroidism, hypertension, reflex sympathetic dystrophy syndrome, coronary artery disease, and nonmelanoma skin cancer. He denied any changes in medications or illnesses prior to onset of the rash. Physical examination revealed diffuse, erythematous, blanchable telangiectases on the arms, legs, and trunk (Figure 1). No petechiae, atrophy, or epidermal changes were appreciated. Darier sign was negative.

Skin biopsy is essential to differentiate CCV from GET, which appears morphologically identical. Cutaneous collagenous vasculopathy may be underreported as a result of clinician choice not to biopsy due to a presumptive diagnosis of GET.³ Successful treatment with a pulsed dye laser has been reported,⁷ though the extent of disease may make complete destruction of the lesions difficult to accomplish. Although it is theorized that CCV may be a marker for underlying systemic disease or even a genetic defect causing abnormal collagen deposition, its cause has yet to be ascertained.⁵ Previously reported patients have had a variety of comorbidities, including several cases of type 2 diabetes mellitus.⁶ Another patient was reported to have recently started treatment with an angiotensin receptor blocker prior to onset of CCV.⁵

Our case contributes to the small series of reported patients with this rare diagnosis and further suggests that it may be underreported at this time. Similar to previously reported cases, our patient was an elderly white individual. Although our patient had long-standing iatrogenic hypothyroidism, no recent medication changes or underlying comorbidities could be tied to the development of CCV. Further studies are needed to determine if this disease process is associated with any underlying systemic illnesses, medications, or family history.