In the era of Ebola, COVID-19, and even Legionnaires, technicians and other staff working behind the scenes to ensure provider and patient safety continue to face a long-recognized but under addressed challenge: splashes and airborne droplets.

Granted, National Institute for Occupational Safety and Health (NIOSH) standards, industry standards, and professional guidelines are all in place to prevent unintentional exposure to pathogens. However, findings from a newly published study in the American Journal of Infection Control suggest they fall short.

In the study, researchers found that simulated manual cleaning of medical devices generated a drenching splash throughout the process with droplet dispersal exceeding 7 feet (2.1 meters).

“The guidelines say that droplets stop at 3 or 4 feet, and they don’t,” Cori L. Ofstead, MSPH, lead author and president/CEO of Ofstead & Associates, Bloomington, Minn., told this news organization. “That’s the problem with having standards and guidelines that are not based on relevant evidence, [which] in this case, is a single study that was done in an intensive care area where they had an infection outbreak.”

Ms. Ofstead was referring to a report in the journal Infection Control and Hospital Epidemiology, detailing a Canadian investigation involving a multidrug-resistant Pseudomonas aeruginosa outbreak in an ICU. The report implicated the faucets over the hand hygiene sinks, with fluorescent dye showing droplet dispersal roughly 3 feet away from the sinks.

“Somehow it [the 3-feet rule] got implemented in guidelines in sterile processing decontamination areas, which are not the same as hand hygiene,’’ Ms. Ofstead explained.

With a goal of providing more current evidence on droplet generation and dispersal, as well as personal protection equipment (PPE) exposure/effectiveness, she and her colleagues simulated manual cleaning of a decommissioned colonoscope and transvaginal ultrasound probe, using for the study location a new academic sterile processing unit.

To detect droplet generation and dispersal as well as splash following common technician activities (for example, colonoscope brushing, scrubbing, rinsing and transport to an automated endoscope reprocessor [AER] for sterilization), the researchers affixed blue moisture-detection paper to environmental surfaces, on carts positioned 4 feet (1.2 meters) from the sink (to simulate observers), and along a 15-foot pathway between the sink and AER.

They observed droplets everywhere.

Technician activities such as running the faucet and rinsing the probe under running water generated substantial splashing overall. Instrument rinsing in particular produced small and large droplets and confluent puddles of water around the sink and in the broad area surrounding the workspace. Droplets were also dispersed on the floor 7.25 feet (2.2 meters) away and along the entire 15-foot path from the sink to the AER.

At the sink, the technician risked drenching exposure from head to toe during most activities, and even observers positioned 3-4 feet away were found to have droplets on their gowns. In addition, saturated shoe covers reportedly tracked moisture away from the sink to the unit door – a distance of 13 feet (4 meters) – and 2 feet (0.6 meters) farther out into the PPE foyer for donning and doffing.

Although PPE gowns effectively repelled moisture during cleaning of a single device, Ms. Ofstead emphasized that technicians typically handle up to 10 instruments during a normal, 2-hour shift, further increasing exposure risk with each subsequent cleaning.

However, perhaps one of the most surprising findings was that despite an optimal unit design, including physical separation of clean and dirty activities and pressurized air flow to protect workers, droplets were still broadly dispersed.

Current efforts, however well-intentioned, might not be offering the degree of protection (and consideration) that sterile processing technicians need.

“The study was conducted in a new sterile processing area that had an extra excellent kind of distancing and three separate rooms, something that I think most of our hospitals are working toward,” Stella Hines, MD, associate professor at the University of Maryland School of Medicine, Baltimore, explained. Dr. Hines was not directly involved in the study.

“But it also really kind of highlighted what’s happening to workers potentially,” she added. “For example, we want to know if that spray or splatter has a live microbe it in that could cause a problem or ... in a highly wet environment, if that water has some kind of chemical in it that could pose an occupational hazard to the worker based on skin or mucous membrane exposure.”

Ms. Ofstead agreed. “We need to be thinking about the exposure of critically important workers and the environment in an era where we are worried about aerosol-generating procedures and superbugs,” she explained.

Dr. Hines and Ms. Ofstead also noted that the majority of staff involved in front-line patient care have never actually ventured into the sterile processing units nor do they recognize the risks that technicians working in these units face on a daily, or even hourly, basis.

“The people who run these operations are very well trained and knowledgeable. I think that it would be helpful for them to know that they’re appreciated and for the people upstairs on the front lines using the equipment to see what goes on downstairs and all of the painstaking steps that need to be in place for the equipment to come out of sterile processing and be ready to go,” said Dr. Hines.

In the meantime, hospital leaders need to address the challenges and danger posed by migrating infectious droplets, especially for workers involved in processes that stir them up in the first place – workers who by the end of their shifts are unavoidably drenched with infectious blood and tissue secretions.

“I think that it’s going to take a much bigger kind of worldview from hospital leadership,” Dr. Hines said.

The study was supported in part by a grant from Healthmark Industries. Ms. Ofstead reports research grants or consulting fees through her organization with 3M Company, Ambu, Boston Scientific, Cleanis, Fortive/Advanced Sterilization Products, Healthmark Industries, Pentax, and Steris/Cantel/Medviators. Dr. Hines reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the era of Ebola, COVID-19, and even Legionnaires, technicians and other staff working behind the scenes to ensure provider and patient safety continue to face a long-recognized but under addressed challenge: splashes and airborne droplets.

Granted, National Institute for Occupational Safety and Health (NIOSH) standards, industry standards, and professional guidelines are all in place to prevent unintentional exposure to pathogens. However, findings from a newly published study in the American Journal of Infection Control suggest they fall short.

In the study, researchers found that simulated manual cleaning of medical devices generated a drenching splash throughout the process with droplet dispersal exceeding 7 feet (2.1 meters).

“The guidelines say that droplets stop at 3 or 4 feet, and they don’t,” Cori L. Ofstead, MSPH, lead author and president/CEO of Ofstead & Associates, Bloomington, Minn., told this news organization. “That’s the problem with having standards and guidelines that are not based on relevant evidence, [which] in this case, is a single study that was done in an intensive care area where they had an infection outbreak.”

Ms. Ofstead was referring to a report in the journal Infection Control and Hospital Epidemiology, detailing a Canadian investigation involving a multidrug-resistant Pseudomonas aeruginosa outbreak in an ICU. The report implicated the faucets over the hand hygiene sinks, with fluorescent dye showing droplet dispersal roughly 3 feet away from the sinks.

“Somehow it [the 3-feet rule] got implemented in guidelines in sterile processing decontamination areas, which are not the same as hand hygiene,’’ Ms. Ofstead explained.

With a goal of providing more current evidence on droplet generation and dispersal, as well as personal protection equipment (PPE) exposure/effectiveness, she and her colleagues simulated manual cleaning of a decommissioned colonoscope and transvaginal ultrasound probe, using for the study location a new academic sterile processing unit.

To detect droplet generation and dispersal as well as splash following common technician activities (for example, colonoscope brushing, scrubbing, rinsing and transport to an automated endoscope reprocessor [AER] for sterilization), the researchers affixed blue moisture-detection paper to environmental surfaces, on carts positioned 4 feet (1.2 meters) from the sink (to simulate observers), and along a 15-foot pathway between the sink and AER.

They observed droplets everywhere.

Technician activities such as running the faucet and rinsing the probe under running water generated substantial splashing overall. Instrument rinsing in particular produced small and large droplets and confluent puddles of water around the sink and in the broad area surrounding the workspace. Droplets were also dispersed on the floor 7.25 feet (2.2 meters) away and along the entire 15-foot path from the sink to the AER.

At the sink, the technician risked drenching exposure from head to toe during most activities, and even observers positioned 3-4 feet away were found to have droplets on their gowns. In addition, saturated shoe covers reportedly tracked moisture away from the sink to the unit door – a distance of 13 feet (4 meters) – and 2 feet (0.6 meters) farther out into the PPE foyer for donning and doffing.

Although PPE gowns effectively repelled moisture during cleaning of a single device, Ms. Ofstead emphasized that technicians typically handle up to 10 instruments during a normal, 2-hour shift, further increasing exposure risk with each subsequent cleaning.

However, perhaps one of the most surprising findings was that despite an optimal unit design, including physical separation of clean and dirty activities and pressurized air flow to protect workers, droplets were still broadly dispersed.

Current efforts, however well-intentioned, might not be offering the degree of protection (and consideration) that sterile processing technicians need.

“The study was conducted in a new sterile processing area that had an extra excellent kind of distancing and three separate rooms, something that I think most of our hospitals are working toward,” Stella Hines, MD, associate professor at the University of Maryland School of Medicine, Baltimore, explained. Dr. Hines was not directly involved in the study.

“But it also really kind of highlighted what’s happening to workers potentially,” she added. “For example, we want to know if that spray or splatter has a live microbe it in that could cause a problem or ... in a highly wet environment, if that water has some kind of chemical in it that could pose an occupational hazard to the worker based on skin or mucous membrane exposure.”

Ms. Ofstead agreed. “We need to be thinking about the exposure of critically important workers and the environment in an era where we are worried about aerosol-generating procedures and superbugs,” she explained.

Dr. Hines and Ms. Ofstead also noted that the majority of staff involved in front-line patient care have never actually ventured into the sterile processing units nor do they recognize the risks that technicians working in these units face on a daily, or even hourly, basis.

“The people who run these operations are very well trained and knowledgeable. I think that it would be helpful for them to know that they’re appreciated and for the people upstairs on the front lines using the equipment to see what goes on downstairs and all of the painstaking steps that need to be in place for the equipment to come out of sterile processing and be ready to go,” said Dr. Hines.

In the meantime, hospital leaders need to address the challenges and danger posed by migrating infectious droplets, especially for workers involved in processes that stir them up in the first place – workers who by the end of their shifts are unavoidably drenched with infectious blood and tissue secretions.

“I think that it’s going to take a much bigger kind of worldview from hospital leadership,” Dr. Hines said.

The study was supported in part by a grant from Healthmark Industries. Ms. Ofstead reports research grants or consulting fees through her organization with 3M Company, Ambu, Boston Scientific, Cleanis, Fortive/Advanced Sterilization Products, Healthmark Industries, Pentax, and Steris/Cantel/Medviators. Dr. Hines reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the era of Ebola, COVID-19, and even Legionnaires, technicians and other staff working behind the scenes to ensure provider and patient safety continue to face a long-recognized but under addressed challenge: splashes and airborne droplets.

Granted, National Institute for Occupational Safety and Health (NIOSH) standards, industry standards, and professional guidelines are all in place to prevent unintentional exposure to pathogens. However, findings from a newly published study in the American Journal of Infection Control suggest they fall short.

In the study, researchers found that simulated manual cleaning of medical devices generated a drenching splash throughout the process with droplet dispersal exceeding 7 feet (2.1 meters).

“The guidelines say that droplets stop at 3 or 4 feet, and they don’t,” Cori L. Ofstead, MSPH, lead author and president/CEO of Ofstead & Associates, Bloomington, Minn., told this news organization. “That’s the problem with having standards and guidelines that are not based on relevant evidence, [which] in this case, is a single study that was done in an intensive care area where they had an infection outbreak.”

Ms. Ofstead was referring to a report in the journal Infection Control and Hospital Epidemiology, detailing a Canadian investigation involving a multidrug-resistant Pseudomonas aeruginosa outbreak in an ICU. The report implicated the faucets over the hand hygiene sinks, with fluorescent dye showing droplet dispersal roughly 3 feet away from the sinks.

“Somehow it [the 3-feet rule] got implemented in guidelines in sterile processing decontamination areas, which are not the same as hand hygiene,’’ Ms. Ofstead explained.

With a goal of providing more current evidence on droplet generation and dispersal, as well as personal protection equipment (PPE) exposure/effectiveness, she and her colleagues simulated manual cleaning of a decommissioned colonoscope and transvaginal ultrasound probe, using for the study location a new academic sterile processing unit.

To detect droplet generation and dispersal as well as splash following common technician activities (for example, colonoscope brushing, scrubbing, rinsing and transport to an automated endoscope reprocessor [AER] for sterilization), the researchers affixed blue moisture-detection paper to environmental surfaces, on carts positioned 4 feet (1.2 meters) from the sink (to simulate observers), and along a 15-foot pathway between the sink and AER.

They observed droplets everywhere.

Technician activities such as running the faucet and rinsing the probe under running water generated substantial splashing overall. Instrument rinsing in particular produced small and large droplets and confluent puddles of water around the sink and in the broad area surrounding the workspace. Droplets were also dispersed on the floor 7.25 feet (2.2 meters) away and along the entire 15-foot path from the sink to the AER.

At the sink, the technician risked drenching exposure from head to toe during most activities, and even observers positioned 3-4 feet away were found to have droplets on their gowns. In addition, saturated shoe covers reportedly tracked moisture away from the sink to the unit door – a distance of 13 feet (4 meters) – and 2 feet (0.6 meters) farther out into the PPE foyer for donning and doffing.

Although PPE gowns effectively repelled moisture during cleaning of a single device, Ms. Ofstead emphasized that technicians typically handle up to 10 instruments during a normal, 2-hour shift, further increasing exposure risk with each subsequent cleaning.

However, perhaps one of the most surprising findings was that despite an optimal unit design, including physical separation of clean and dirty activities and pressurized air flow to protect workers, droplets were still broadly dispersed.

Current efforts, however well-intentioned, might not be offering the degree of protection (and consideration) that sterile processing technicians need.

“The study was conducted in a new sterile processing area that had an extra excellent kind of distancing and three separate rooms, something that I think most of our hospitals are working toward,” Stella Hines, MD, associate professor at the University of Maryland School of Medicine, Baltimore, explained. Dr. Hines was not directly involved in the study.

“But it also really kind of highlighted what’s happening to workers potentially,” she added. “For example, we want to know if that spray or splatter has a live microbe it in that could cause a problem or ... in a highly wet environment, if that water has some kind of chemical in it that could pose an occupational hazard to the worker based on skin or mucous membrane exposure.”

Ms. Ofstead agreed. “We need to be thinking about the exposure of critically important workers and the environment in an era where we are worried about aerosol-generating procedures and superbugs,” she explained.

Dr. Hines and Ms. Ofstead also noted that the majority of staff involved in front-line patient care have never actually ventured into the sterile processing units nor do they recognize the risks that technicians working in these units face on a daily, or even hourly, basis.

“The people who run these operations are very well trained and knowledgeable. I think that it would be helpful for them to know that they’re appreciated and for the people upstairs on the front lines using the equipment to see what goes on downstairs and all of the painstaking steps that need to be in place for the equipment to come out of sterile processing and be ready to go,” said Dr. Hines.

In the meantime, hospital leaders need to address the challenges and danger posed by migrating infectious droplets, especially for workers involved in processes that stir them up in the first place – workers who by the end of their shifts are unavoidably drenched with infectious blood and tissue secretions.

“I think that it’s going to take a much bigger kind of worldview from hospital leadership,” Dr. Hines said.

The study was supported in part by a grant from Healthmark Industries. Ms. Ofstead reports research grants or consulting fees through her organization with 3M Company, Ambu, Boston Scientific, Cleanis, Fortive/Advanced Sterilization Products, Healthmark Industries, Pentax, and Steris/Cantel/Medviators. Dr. Hines reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Josie Tenore, MD, and Paul Hinds were introduced by a mutual friend in 2017 and hadn’t been going out long when she laid down the law: He had to get a physical.

“I don’t date people who don’t take care of their health,” said Dr. Tenore, who practices cosmetic dermatology and functional medicine in suburban Chicago.

One of Mr. Hinds’ blood tests that summer came back with an alarming result: His prostate-specific antigen (PSA), level was very high. A biopsy confirmed he had advanced prostate cancer.

There aren’t a lot of comfortable alternatives for treating prostate cancer, which generally progresses as long as testosterone levels remain high. Marijuana appears to lower testosterone levels, so after his diagnosis, he dosed a liquid form of cannabis for several weeks. That cut his PSA in half, but Mr. Hinds, a cybersecurity expert who likes yoga and bicycling, “was stoned out of his mind and couldn’t function,” Dr. Tenore recalled.

With Dr. Tenore guiding his decisions, Mr. Hinds next tried high-frequency ultrasound treatment, but it failed. And in the summer of 2019 doctors removed his prostate gland. Still, the PSA levels climbed again, and doctors assessed that the cancer had metastasized. The only alternative was to drastically lower Mr. Hinds’ testosterone levels – either via surgery or drugs that block all testosterone. In May 2021, he got his first intramuscular shot of Lupron Depot, a brand name for leuprolide, designed to suppress the prostate gland’s release of the hormone for 3 months. That August, he got his second shot.

And then the bills came.

The patient: Paul Hinds, now 60, is covered by United Healthcare through a COBRA plan from his former employer.

Medical service: Two 3-month Lupron Depot injections for metastatic prostate cancer.

Service provider: University of Chicago Medicine, a 900-physician nonprofit system that includes an 811-bed medical center, a suburban hospital, the Pritzker School of Medicine, and outpatient clinics and physician offices throughout the Chicago area.

Total bill: $73,812 for the two shots ($35,414 for the first, $38,398 for the second), including lab work and physician charges. United Healthcare’s negotiated rate for the two shots plus associated fees was $27,568, of which the insurer paid $19,567. After Mr. Hinds haggled with the hospital and insurer for more than a year, his share of the bills was determined to be nearly $7,000.

What gives: The first issue is unrelenting price increases on old drugs that have remained branded as manufacturers find ways to extend patents for decades and maintain sales through marketing.

Though Lupron was invented in 1973, its manufacturer got patent extensions in 1989 by offering a slow-release version. Drugmakers commonly use this tactic to extend their exclusive rights to sell a product.

The development of Lupron Depot as an intramuscular shot that suppressed testosterone for months at a time improved patient compliance and also enabled its maker, Abbott Laboratories, and its Japanese partner, Takeda, to extend their patents on the drug into the 2000s, said Gerald Weisberg, MD, a former Abbott scientist who has been critical of the company’s pricing policies.

In subsequent years, Abbott and Takeda, in a joint venture called TAP Pharmaceuticals, steadily marked up the price of their slow-release product. In 2000, the average wholesale U.S. price for a 3-month shot was $1,245; currently that figure is $5,866. (It is manufactured in the United States by AbbVie now.)

In the United Kingdom, where health care is generally free and Takeda sells the drug under the name Prostap, all physicians can purchase a 3-month dose for about $260.

It’s likely that Chicago Medicine, where Mr. Hinds got his shots, paid something close to the British price. That’s because the health system’s hospital on Chicago’s South Side participates in a federal program called 340B, which allows hospitals that serve low-income populations to purchase drugs at deep discounts.

Lupron Depot is given as a simple injection into the muscle. It takes minutes for a nurse or doctor to administer. Yet hospital systems like Chicago Medicine can and typically do charge lavishly for such services, to enhance revenue, said Morgan Henderson, principal data scientist at the Hilltop Institute at the University of Maryland-Baltimore County. Chicago Medicine declined to say what it paid for the drug.

While U.S. drugmakers can price their drugs however they please, TAP has gotten into trouble for its Lupron sales policies in the past. In 2001, after a Justice Department probe, it paid an $875 million settlement for illegally stimulating sales by giving urologists free and discounted vials of the drug while enabling them to charge Medicare full price.

Since then, many other drugs aimed at lowering testosterone levels have entered the market, including a pill, relugolix (Orgovyx). So why wouldn’t a patient use them?

Lupron Depot is long acting, is easy to prepare and store, and employs a small needle, which some patients prefer, said Brian McNeil, MD, chief of urology at University Hospital of Brooklyn. Orgovyx is convenient, but “a patient has to be very compliant. They have to take it every day around the same time,” he said. “Some people just forget.”

But there is another important factor that may well explain Lupron Depot’s ongoing popularity among medical providers: Doctors and hospitals can earn tens of thousands of dollars each visit by marking up its price and administration fees – as they did with Mr. Hinds. If they merely write a prescription for a drug that can be taken at home, they earn nothing.

Asked about this high patient charge and the possibility of using alternatives, United spokesperson Maria Gordon Shydlo said payment was “appropriately based on the hospital’s contract and the member’s benefit plan,” adding that the insurer encourages customers to shop around for the best quality and price.

Resolution: In addition to leaving Mr. Hinds listless, the Lupron Depot shots were, literally, a pain in the rear end. “Each time he was miserable for 2 weeks,” Dr. Tenore said. After looking over his first bill for the Lupron shot, Dr. Tenore told Mr. Hinds he should ask his doctor whether there was a less expensive drug that was easier to take.

After the second shot, in August 2021, a pharmacist told him he could instead receive the pill. His doctor prescribed Mr. Hinds 3 months’ worth of Orgovyx last November, for which he paid $216 and the insurer paid over $6,000. The drug’s list price is about $2,700 a month. There is evidence that Orgovyx works a little better than leuprolide.

Orgovyx was a “no-brainer,” Mr. Hinds said. “Why would you want a sore ass for two weeks when you can take a pill that kicks in sooner, functions the same way, and clears your body of testosterone faster?”

While Orgovyx is increasingly used for prostate cancer, Lupron and other injections usually remain the standard of care, hospital spokesperson Ashley Heher said. Clinicians “work with patients to determine what treatments are the most medically effective and, when necessary, to find reasonable alternatives that may be less financially burdensome due to insurance coverage limitations.”

Mr. Hinds was baffled by the size of the charges. During months of phone calls and emails, the hospital reversed and then reapplied part of the charge, and then in July agreed to a $666.34 monthly payment plan. After Hinds had made two payments, however, the hospital announced Aug. 29 it was canceling the agreement and sending the remainder of his bill to a collection agency. Two weeks later, the hospital reinstated the payment plan – after KHN asked about the cancellation.

As for Mr. Hinds, he remains active, though his bike rides have been shortened from 50 or 60 miles to about 30, he said.

He’s grateful to have Dr. Tenore as a free consultant and empathizes with those who lack a knowledgeable guide through their disease and health care’s financial maze.

“I’ve got Dr. Josie as an advocate who knows the system,” Mr. Hinds said.

The takeaway: First tip: If you are prescribed an infusion or injection, ask your physician if there are cheaper oral medications to treat your condition. Also, many drugs that are given by injection – ones that are given “subcutaneously,” rather than into a muscle – can be administered by a patient at home, avoiding hefty administration fees. Drugs like Dupixent for eczema fall into this category.

Keep in mind that where you get treatment could make a big difference in your charges: A study found that leading U.S. cancer centers charge enormous markups to private insurers for drug injections or infusions. Another study found that hospital systems charge an average of 86% more than private clinics for cancer drug infusions. And the percentage of cancer infusions done in hospital-operated clinics increased from 6% in 2004 to 43% in 2014, and has grown since.

Under a law that took effect in 2021, hospitals are required to list their charges, though they currently do so in a way that is not user friendly. But it’s worth taking a look at the price list – the hospital chargemaster – to try to decipher the pricing and markup for your medicine. If you’re about to get an injection, infusion, or procedure done in a hospital system, ask ahead of time for an estimate of what you will owe.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Josie Tenore, MD, and Paul Hinds were introduced by a mutual friend in 2017 and hadn’t been going out long when she laid down the law: He had to get a physical.

“I don’t date people who don’t take care of their health,” said Dr. Tenore, who practices cosmetic dermatology and functional medicine in suburban Chicago.

One of Mr. Hinds’ blood tests that summer came back with an alarming result: His prostate-specific antigen (PSA), level was very high. A biopsy confirmed he had advanced prostate cancer.

There aren’t a lot of comfortable alternatives for treating prostate cancer, which generally progresses as long as testosterone levels remain high. Marijuana appears to lower testosterone levels, so after his diagnosis, he dosed a liquid form of cannabis for several weeks. That cut his PSA in half, but Mr. Hinds, a cybersecurity expert who likes yoga and bicycling, “was stoned out of his mind and couldn’t function,” Dr. Tenore recalled.

With Dr. Tenore guiding his decisions, Mr. Hinds next tried high-frequency ultrasound treatment, but it failed. And in the summer of 2019 doctors removed his prostate gland. Still, the PSA levels climbed again, and doctors assessed that the cancer had metastasized. The only alternative was to drastically lower Mr. Hinds’ testosterone levels – either via surgery or drugs that block all testosterone. In May 2021, he got his first intramuscular shot of Lupron Depot, a brand name for leuprolide, designed to suppress the prostate gland’s release of the hormone for 3 months. That August, he got his second shot.

And then the bills came.

The patient: Paul Hinds, now 60, is covered by United Healthcare through a COBRA plan from his former employer.

Medical service: Two 3-month Lupron Depot injections for metastatic prostate cancer.

Service provider: University of Chicago Medicine, a 900-physician nonprofit system that includes an 811-bed medical center, a suburban hospital, the Pritzker School of Medicine, and outpatient clinics and physician offices throughout the Chicago area.

Total bill: $73,812 for the two shots ($35,414 for the first, $38,398 for the second), including lab work and physician charges. United Healthcare’s negotiated rate for the two shots plus associated fees was $27,568, of which the insurer paid $19,567. After Mr. Hinds haggled with the hospital and insurer for more than a year, his share of the bills was determined to be nearly $7,000.

What gives: The first issue is unrelenting price increases on old drugs that have remained branded as manufacturers find ways to extend patents for decades and maintain sales through marketing.

Though Lupron was invented in 1973, its manufacturer got patent extensions in 1989 by offering a slow-release version. Drugmakers commonly use this tactic to extend their exclusive rights to sell a product.

The development of Lupron Depot as an intramuscular shot that suppressed testosterone for months at a time improved patient compliance and also enabled its maker, Abbott Laboratories, and its Japanese partner, Takeda, to extend their patents on the drug into the 2000s, said Gerald Weisberg, MD, a former Abbott scientist who has been critical of the company’s pricing policies.

In subsequent years, Abbott and Takeda, in a joint venture called TAP Pharmaceuticals, steadily marked up the price of their slow-release product. In 2000, the average wholesale U.S. price for a 3-month shot was $1,245; currently that figure is $5,866. (It is manufactured in the United States by AbbVie now.)

In the United Kingdom, where health care is generally free and Takeda sells the drug under the name Prostap, all physicians can purchase a 3-month dose for about $260.

It’s likely that Chicago Medicine, where Mr. Hinds got his shots, paid something close to the British price. That’s because the health system’s hospital on Chicago’s South Side participates in a federal program called 340B, which allows hospitals that serve low-income populations to purchase drugs at deep discounts.

Lupron Depot is given as a simple injection into the muscle. It takes minutes for a nurse or doctor to administer. Yet hospital systems like Chicago Medicine can and typically do charge lavishly for such services, to enhance revenue, said Morgan Henderson, principal data scientist at the Hilltop Institute at the University of Maryland-Baltimore County. Chicago Medicine declined to say what it paid for the drug.

While U.S. drugmakers can price their drugs however they please, TAP has gotten into trouble for its Lupron sales policies in the past. In 2001, after a Justice Department probe, it paid an $875 million settlement for illegally stimulating sales by giving urologists free and discounted vials of the drug while enabling them to charge Medicare full price.

Since then, many other drugs aimed at lowering testosterone levels have entered the market, including a pill, relugolix (Orgovyx). So why wouldn’t a patient use them?

Lupron Depot is long acting, is easy to prepare and store, and employs a small needle, which some patients prefer, said Brian McNeil, MD, chief of urology at University Hospital of Brooklyn. Orgovyx is convenient, but “a patient has to be very compliant. They have to take it every day around the same time,” he said. “Some people just forget.”

But there is another important factor that may well explain Lupron Depot’s ongoing popularity among medical providers: Doctors and hospitals can earn tens of thousands of dollars each visit by marking up its price and administration fees – as they did with Mr. Hinds. If they merely write a prescription for a drug that can be taken at home, they earn nothing.

Asked about this high patient charge and the possibility of using alternatives, United spokesperson Maria Gordon Shydlo said payment was “appropriately based on the hospital’s contract and the member’s benefit plan,” adding that the insurer encourages customers to shop around for the best quality and price.

Resolution: In addition to leaving Mr. Hinds listless, the Lupron Depot shots were, literally, a pain in the rear end. “Each time he was miserable for 2 weeks,” Dr. Tenore said. After looking over his first bill for the Lupron shot, Dr. Tenore told Mr. Hinds he should ask his doctor whether there was a less expensive drug that was easier to take.

After the second shot, in August 2021, a pharmacist told him he could instead receive the pill. His doctor prescribed Mr. Hinds 3 months’ worth of Orgovyx last November, for which he paid $216 and the insurer paid over $6,000. The drug’s list price is about $2,700 a month. There is evidence that Orgovyx works a little better than leuprolide.

Orgovyx was a “no-brainer,” Mr. Hinds said. “Why would you want a sore ass for two weeks when you can take a pill that kicks in sooner, functions the same way, and clears your body of testosterone faster?”

While Orgovyx is increasingly used for prostate cancer, Lupron and other injections usually remain the standard of care, hospital spokesperson Ashley Heher said. Clinicians “work with patients to determine what treatments are the most medically effective and, when necessary, to find reasonable alternatives that may be less financially burdensome due to insurance coverage limitations.”

Mr. Hinds was baffled by the size of the charges. During months of phone calls and emails, the hospital reversed and then reapplied part of the charge, and then in July agreed to a $666.34 monthly payment plan. After Hinds had made two payments, however, the hospital announced Aug. 29 it was canceling the agreement and sending the remainder of his bill to a collection agency. Two weeks later, the hospital reinstated the payment plan – after KHN asked about the cancellation.

As for Mr. Hinds, he remains active, though his bike rides have been shortened from 50 or 60 miles to about 30, he said.

He’s grateful to have Dr. Tenore as a free consultant and empathizes with those who lack a knowledgeable guide through their disease and health care’s financial maze.

“I’ve got Dr. Josie as an advocate who knows the system,” Mr. Hinds said.

The takeaway: First tip: If you are prescribed an infusion or injection, ask your physician if there are cheaper oral medications to treat your condition. Also, many drugs that are given by injection – ones that are given “subcutaneously,” rather than into a muscle – can be administered by a patient at home, avoiding hefty administration fees. Drugs like Dupixent for eczema fall into this category.

Keep in mind that where you get treatment could make a big difference in your charges: A study found that leading U.S. cancer centers charge enormous markups to private insurers for drug injections or infusions. Another study found that hospital systems charge an average of 86% more than private clinics for cancer drug infusions. And the percentage of cancer infusions done in hospital-operated clinics increased from 6% in 2004 to 43% in 2014, and has grown since.

Under a law that took effect in 2021, hospitals are required to list their charges, though they currently do so in a way that is not user friendly. But it’s worth taking a look at the price list – the hospital chargemaster – to try to decipher the pricing and markup for your medicine. If you’re about to get an injection, infusion, or procedure done in a hospital system, ask ahead of time for an estimate of what you will owe.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Josie Tenore, MD, and Paul Hinds were introduced by a mutual friend in 2017 and hadn’t been going out long when she laid down the law: He had to get a physical.

“I don’t date people who don’t take care of their health,” said Dr. Tenore, who practices cosmetic dermatology and functional medicine in suburban Chicago.

One of Mr. Hinds’ blood tests that summer came back with an alarming result: His prostate-specific antigen (PSA), level was very high. A biopsy confirmed he had advanced prostate cancer.

There aren’t a lot of comfortable alternatives for treating prostate cancer, which generally progresses as long as testosterone levels remain high. Marijuana appears to lower testosterone levels, so after his diagnosis, he dosed a liquid form of cannabis for several weeks. That cut his PSA in half, but Mr. Hinds, a cybersecurity expert who likes yoga and bicycling, “was stoned out of his mind and couldn’t function,” Dr. Tenore recalled.

With Dr. Tenore guiding his decisions, Mr. Hinds next tried high-frequency ultrasound treatment, but it failed. And in the summer of 2019 doctors removed his prostate gland. Still, the PSA levels climbed again, and doctors assessed that the cancer had metastasized. The only alternative was to drastically lower Mr. Hinds’ testosterone levels – either via surgery or drugs that block all testosterone. In May 2021, he got his first intramuscular shot of Lupron Depot, a brand name for leuprolide, designed to suppress the prostate gland’s release of the hormone for 3 months. That August, he got his second shot.

And then the bills came.

The patient: Paul Hinds, now 60, is covered by United Healthcare through a COBRA plan from his former employer.

Medical service: Two 3-month Lupron Depot injections for metastatic prostate cancer.

Service provider: University of Chicago Medicine, a 900-physician nonprofit system that includes an 811-bed medical center, a suburban hospital, the Pritzker School of Medicine, and outpatient clinics and physician offices throughout the Chicago area.

Total bill: $73,812 for the two shots ($35,414 for the first, $38,398 for the second), including lab work and physician charges. United Healthcare’s negotiated rate for the two shots plus associated fees was $27,568, of which the insurer paid $19,567. After Mr. Hinds haggled with the hospital and insurer for more than a year, his share of the bills was determined to be nearly $7,000.

What gives: The first issue is unrelenting price increases on old drugs that have remained branded as manufacturers find ways to extend patents for decades and maintain sales through marketing.

Though Lupron was invented in 1973, its manufacturer got patent extensions in 1989 by offering a slow-release version. Drugmakers commonly use this tactic to extend their exclusive rights to sell a product.

The development of Lupron Depot as an intramuscular shot that suppressed testosterone for months at a time improved patient compliance and also enabled its maker, Abbott Laboratories, and its Japanese partner, Takeda, to extend their patents on the drug into the 2000s, said Gerald Weisberg, MD, a former Abbott scientist who has been critical of the company’s pricing policies.

In subsequent years, Abbott and Takeda, in a joint venture called TAP Pharmaceuticals, steadily marked up the price of their slow-release product. In 2000, the average wholesale U.S. price for a 3-month shot was $1,245; currently that figure is $5,866. (It is manufactured in the United States by AbbVie now.)

In the United Kingdom, where health care is generally free and Takeda sells the drug under the name Prostap, all physicians can purchase a 3-month dose for about $260.

It’s likely that Chicago Medicine, where Mr. Hinds got his shots, paid something close to the British price. That’s because the health system’s hospital on Chicago’s South Side participates in a federal program called 340B, which allows hospitals that serve low-income populations to purchase drugs at deep discounts.

Lupron Depot is given as a simple injection into the muscle. It takes minutes for a nurse or doctor to administer. Yet hospital systems like Chicago Medicine can and typically do charge lavishly for such services, to enhance revenue, said Morgan Henderson, principal data scientist at the Hilltop Institute at the University of Maryland-Baltimore County. Chicago Medicine declined to say what it paid for the drug.

While U.S. drugmakers can price their drugs however they please, TAP has gotten into trouble for its Lupron sales policies in the past. In 2001, after a Justice Department probe, it paid an $875 million settlement for illegally stimulating sales by giving urologists free and discounted vials of the drug while enabling them to charge Medicare full price.

Since then, many other drugs aimed at lowering testosterone levels have entered the market, including a pill, relugolix (Orgovyx). So why wouldn’t a patient use them?

Lupron Depot is long acting, is easy to prepare and store, and employs a small needle, which some patients prefer, said Brian McNeil, MD, chief of urology at University Hospital of Brooklyn. Orgovyx is convenient, but “a patient has to be very compliant. They have to take it every day around the same time,” he said. “Some people just forget.”

But there is another important factor that may well explain Lupron Depot’s ongoing popularity among medical providers: Doctors and hospitals can earn tens of thousands of dollars each visit by marking up its price and administration fees – as they did with Mr. Hinds. If they merely write a prescription for a drug that can be taken at home, they earn nothing.

Asked about this high patient charge and the possibility of using alternatives, United spokesperson Maria Gordon Shydlo said payment was “appropriately based on the hospital’s contract and the member’s benefit plan,” adding that the insurer encourages customers to shop around for the best quality and price.

Resolution: In addition to leaving Mr. Hinds listless, the Lupron Depot shots were, literally, a pain in the rear end. “Each time he was miserable for 2 weeks,” Dr. Tenore said. After looking over his first bill for the Lupron shot, Dr. Tenore told Mr. Hinds he should ask his doctor whether there was a less expensive drug that was easier to take.

After the second shot, in August 2021, a pharmacist told him he could instead receive the pill. His doctor prescribed Mr. Hinds 3 months’ worth of Orgovyx last November, for which he paid $216 and the insurer paid over $6,000. The drug’s list price is about $2,700 a month. There is evidence that Orgovyx works a little better than leuprolide.

Orgovyx was a “no-brainer,” Mr. Hinds said. “Why would you want a sore ass for two weeks when you can take a pill that kicks in sooner, functions the same way, and clears your body of testosterone faster?”

While Orgovyx is increasingly used for prostate cancer, Lupron and other injections usually remain the standard of care, hospital spokesperson Ashley Heher said. Clinicians “work with patients to determine what treatments are the most medically effective and, when necessary, to find reasonable alternatives that may be less financially burdensome due to insurance coverage limitations.”

Mr. Hinds was baffled by the size of the charges. During months of phone calls and emails, the hospital reversed and then reapplied part of the charge, and then in July agreed to a $666.34 monthly payment plan. After Hinds had made two payments, however, the hospital announced Aug. 29 it was canceling the agreement and sending the remainder of his bill to a collection agency. Two weeks later, the hospital reinstated the payment plan – after KHN asked about the cancellation.

As for Mr. Hinds, he remains active, though his bike rides have been shortened from 50 or 60 miles to about 30, he said.

He’s grateful to have Dr. Tenore as a free consultant and empathizes with those who lack a knowledgeable guide through their disease and health care’s financial maze.

“I’ve got Dr. Josie as an advocate who knows the system,” Mr. Hinds said.

The takeaway: First tip: If you are prescribed an infusion or injection, ask your physician if there are cheaper oral medications to treat your condition. Also, many drugs that are given by injection – ones that are given “subcutaneously,” rather than into a muscle – can be administered by a patient at home, avoiding hefty administration fees. Drugs like Dupixent for eczema fall into this category.

Keep in mind that where you get treatment could make a big difference in your charges: A study found that leading U.S. cancer centers charge enormous markups to private insurers for drug injections or infusions. Another study found that hospital systems charge an average of 86% more than private clinics for cancer drug infusions. And the percentage of cancer infusions done in hospital-operated clinics increased from 6% in 2004 to 43% in 2014, and has grown since.

Under a law that took effect in 2021, hospitals are required to list their charges, though they currently do so in a way that is not user friendly. But it’s worth taking a look at the price list – the hospital chargemaster – to try to decipher the pricing and markup for your medicine. If you’re about to get an injection, infusion, or procedure done in a hospital system, ask ahead of time for an estimate of what you will owe.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In a survey taken before the Supreme Court’s Dobbs ruling regarding abortion rights, two-thirds of assisted reproduction technology (ART) physicians who don’t offer mifepristone/misoprostol to patients with early pregnancy loss (EPL) reported that they lack access to the drugs.

The numbers are likely higher now. In the wake of the court ruling, some physicians in states with new abortion restrictions fear they won’t be able to properly treat women with miscarriages. Access to mifepristone, a component of medication abortions along with misoprostol, is at the center of their concerns.

“These restrictions that were put in place to restrict abortion care have far-reaching implications regarding miscarriages and early pregnancy loss and the assisted reproduction community is not immune,” obstetrics and gynecology specialist Zachary Anderson, MD, a resident physician at the University of Southern California, Los Angeles, said in an interview. He presented the findings at the American Society for Reproductive Medicine’s 2022 meeting.

Early pregnancy loss – defined as a miscarriage within 12 weeks and 6 days of conception – is common in all pregnancies and affects an estimated 15% of those who rely on in vitro fertilization (IVF). In women who conceive through intrauterine insemination or IVF, “an abnormal karyotype embryo/fetus is the cause of miscarriage in more than two-thirds of cases,” Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview. “The options of management are observation – with no ability to determine when passage of the products of conception will occur – vs. mifepristone/misoprostol or suction D&C.”

Dr. Trolice added that “most woman select the medical treatment protocol, which is 200 mg mifepristone orally followed by 800 mcg misoprostol vaginally 24 hours later. If no signs of heavy bleeding occur after 3 hours following misoprostol, the patient should repeat the dose of 800 micrograms vaginally.”

According to the Reuters news service, some abortion bans target mifepristone. In October 2022, the American College of Obstetricians and Gynecologists asked the Food and Drug Administration to approve mifepristone for use in miscarriage management; such use is now off label, although it is approved to end early pregnancies in conjunction with misoprostol.

For the new study, researchers sent anonymous surveys to 826 members of the Society of Reproductive Endocrinology and Infertility and received 101 responses (12% response rate, 51% women, 86% non-Hispanic White, average age 52, 52% urban, and 51% in private practice).

More than two-thirds (70%) said they diagnosed early pregnancy loss at least once a week; 47% prefer treatment with misoprostol alone, 18% surgery in an operating room, 15% expectant management (monitoring a miscarriage as it occurs without medical intervention), 10% surgery in the office, and 3% mifepristone-misoprostol.

Of those who don’t offer mifepristone-misoprostol, 68% said they lack access, and 26% said they lack familiarity with the treatment.

Study coauthor Brian T. Nguyen, MD, MSc, assistant professor of obstetrics and gynecology at USC, said in an interview that mifepristone, a highly effective drug, is treated differently from other medications “for no good reason.”

Dr. Anderson, who led the study, urged colleagues to get the appropriate certification to prescribe mifepristone. “Providers overestimate how difficult it is to become certified to prescribe it,” he said.

Dr. Trolice, who is familiar with the study findings, said the response rate is low, and the results might be biased because those with preconceived opinions may be more likely to respond.

However, he said, “The results are not surprising in that medication is more commonly preferred (nearly 50%) given the devastation of a miscarriage and the desire to expedite resolution. Approximately one-third prefer surgical management, which would allow for genetic testing of the embryo/fetus to potentially determine a cause of the pregnancy loss.”

As for the medications used to treat early pregnancy loss, many ART physicians “treat pregnancy loss with misoprostol both pre- and post Dobbs,” he said. “The difficulty in obtaining mifepristone remains.”

The study authors and Dr. Trolice report no disclosures.

In a survey taken before the Supreme Court’s Dobbs ruling regarding abortion rights, two-thirds of assisted reproduction technology (ART) physicians who don’t offer mifepristone/misoprostol to patients with early pregnancy loss (EPL) reported that they lack access to the drugs.

The numbers are likely higher now. In the wake of the court ruling, some physicians in states with new abortion restrictions fear they won’t be able to properly treat women with miscarriages. Access to mifepristone, a component of medication abortions along with misoprostol, is at the center of their concerns.

“These restrictions that were put in place to restrict abortion care have far-reaching implications regarding miscarriages and early pregnancy loss and the assisted reproduction community is not immune,” obstetrics and gynecology specialist Zachary Anderson, MD, a resident physician at the University of Southern California, Los Angeles, said in an interview. He presented the findings at the American Society for Reproductive Medicine’s 2022 meeting.

Early pregnancy loss – defined as a miscarriage within 12 weeks and 6 days of conception – is common in all pregnancies and affects an estimated 15% of those who rely on in vitro fertilization (IVF). In women who conceive through intrauterine insemination or IVF, “an abnormal karyotype embryo/fetus is the cause of miscarriage in more than two-thirds of cases,” Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview. “The options of management are observation – with no ability to determine when passage of the products of conception will occur – vs. mifepristone/misoprostol or suction D&C.”

Dr. Trolice added that “most woman select the medical treatment protocol, which is 200 mg mifepristone orally followed by 800 mcg misoprostol vaginally 24 hours later. If no signs of heavy bleeding occur after 3 hours following misoprostol, the patient should repeat the dose of 800 micrograms vaginally.”

According to the Reuters news service, some abortion bans target mifepristone. In October 2022, the American College of Obstetricians and Gynecologists asked the Food and Drug Administration to approve mifepristone for use in miscarriage management; such use is now off label, although it is approved to end early pregnancies in conjunction with misoprostol.

For the new study, researchers sent anonymous surveys to 826 members of the Society of Reproductive Endocrinology and Infertility and received 101 responses (12% response rate, 51% women, 86% non-Hispanic White, average age 52, 52% urban, and 51% in private practice).

More than two-thirds (70%) said they diagnosed early pregnancy loss at least once a week; 47% prefer treatment with misoprostol alone, 18% surgery in an operating room, 15% expectant management (monitoring a miscarriage as it occurs without medical intervention), 10% surgery in the office, and 3% mifepristone-misoprostol.

Of those who don’t offer mifepristone-misoprostol, 68% said they lack access, and 26% said they lack familiarity with the treatment.

Study coauthor Brian T. Nguyen, MD, MSc, assistant professor of obstetrics and gynecology at USC, said in an interview that mifepristone, a highly effective drug, is treated differently from other medications “for no good reason.”

Dr. Anderson, who led the study, urged colleagues to get the appropriate certification to prescribe mifepristone. “Providers overestimate how difficult it is to become certified to prescribe it,” he said.

Dr. Trolice, who is familiar with the study findings, said the response rate is low, and the results might be biased because those with preconceived opinions may be more likely to respond.

However, he said, “The results are not surprising in that medication is more commonly preferred (nearly 50%) given the devastation of a miscarriage and the desire to expedite resolution. Approximately one-third prefer surgical management, which would allow for genetic testing of the embryo/fetus to potentially determine a cause of the pregnancy loss.”

As for the medications used to treat early pregnancy loss, many ART physicians “treat pregnancy loss with misoprostol both pre- and post Dobbs,” he said. “The difficulty in obtaining mifepristone remains.”

The study authors and Dr. Trolice report no disclosures.

In a survey taken before the Supreme Court’s Dobbs ruling regarding abortion rights, two-thirds of assisted reproduction technology (ART) physicians who don’t offer mifepristone/misoprostol to patients with early pregnancy loss (EPL) reported that they lack access to the drugs.

The numbers are likely higher now. In the wake of the court ruling, some physicians in states with new abortion restrictions fear they won’t be able to properly treat women with miscarriages. Access to mifepristone, a component of medication abortions along with misoprostol, is at the center of their concerns.

“These restrictions that were put in place to restrict abortion care have far-reaching implications regarding miscarriages and early pregnancy loss and the assisted reproduction community is not immune,” obstetrics and gynecology specialist Zachary Anderson, MD, a resident physician at the University of Southern California, Los Angeles, said in an interview. He presented the findings at the American Society for Reproductive Medicine’s 2022 meeting.

Early pregnancy loss – defined as a miscarriage within 12 weeks and 6 days of conception – is common in all pregnancies and affects an estimated 15% of those who rely on in vitro fertilization (IVF). In women who conceive through intrauterine insemination or IVF, “an abnormal karyotype embryo/fetus is the cause of miscarriage in more than two-thirds of cases,” Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview. “The options of management are observation – with no ability to determine when passage of the products of conception will occur – vs. mifepristone/misoprostol or suction D&C.”

Dr. Trolice added that “most woman select the medical treatment protocol, which is 200 mg mifepristone orally followed by 800 mcg misoprostol vaginally 24 hours later. If no signs of heavy bleeding occur after 3 hours following misoprostol, the patient should repeat the dose of 800 micrograms vaginally.”

According to the Reuters news service, some abortion bans target mifepristone. In October 2022, the American College of Obstetricians and Gynecologists asked the Food and Drug Administration to approve mifepristone for use in miscarriage management; such use is now off label, although it is approved to end early pregnancies in conjunction with misoprostol.

For the new study, researchers sent anonymous surveys to 826 members of the Society of Reproductive Endocrinology and Infertility and received 101 responses (12% response rate, 51% women, 86% non-Hispanic White, average age 52, 52% urban, and 51% in private practice).

More than two-thirds (70%) said they diagnosed early pregnancy loss at least once a week; 47% prefer treatment with misoprostol alone, 18% surgery in an operating room, 15% expectant management (monitoring a miscarriage as it occurs without medical intervention), 10% surgery in the office, and 3% mifepristone-misoprostol.

Of those who don’t offer mifepristone-misoprostol, 68% said they lack access, and 26% said they lack familiarity with the treatment.

Study coauthor Brian T. Nguyen, MD, MSc, assistant professor of obstetrics and gynecology at USC, said in an interview that mifepristone, a highly effective drug, is treated differently from other medications “for no good reason.”

Dr. Anderson, who led the study, urged colleagues to get the appropriate certification to prescribe mifepristone. “Providers overestimate how difficult it is to become certified to prescribe it,” he said.

Dr. Trolice, who is familiar with the study findings, said the response rate is low, and the results might be biased because those with preconceived opinions may be more likely to respond.

However, he said, “The results are not surprising in that medication is more commonly preferred (nearly 50%) given the devastation of a miscarriage and the desire to expedite resolution. Approximately one-third prefer surgical management, which would allow for genetic testing of the embryo/fetus to potentially determine a cause of the pregnancy loss.”

As for the medications used to treat early pregnancy loss, many ART physicians “treat pregnancy loss with misoprostol both pre- and post Dobbs,” he said. “The difficulty in obtaining mifepristone remains.”

The study authors and Dr. Trolice report no disclosures.

Just when we thought this holiday season, finally, would be the back-to-normal one, some infectious disease experts are warning that a so-called “tripledemic” – influenza, COVID-19, and RSV – may be in the forecast.

The warning isn’t without basis. 

The flu season has gotten an early start. As of Oct. 21, early increases in seasonal flu activity have been reported in most of the country, the Centers for Disease Control and Prevention said, with the southeast and south-central areas having the highest activity levels. 

Children’s hospitals and EDs are seeing a surge in children with RSV.

COVID-19 cases are trending down, according to the CDC, but epidemiologists – scientists who study disease outbreaks – always have their eyes on emerging variants. 

Predicting exactly when cases will peak is difficult, said Justin Lessler, PhD, a professor of epidemiology at the University of North Carolina at Chapel Hill. Dr. Lessler is on the coordinating team for the COVID-19 Scenario Modeling Hub, which aims to predict the course COVID-19, and the Flu Scenario Modeling Hub, which does the same for influenza.

For COVID-19, some models are predicting some spikes before Christmas, he said, and others see a new wave in 2023. For the flu, the model is predicting an earlier-than-usual start, as the CDC has reported.  

While flu activity is relatively low, the CDC said, the season is off to an early start. For the week ending Oct. 21, 1,674 patients were hospitalized for flu, higher than in the summer months but fewer than the 2,675 hospitalizations for the week of May 15, 2022. 

As of Oct. 20, COVID-19 cases have declined 12% over the last 2 weeks, nationwide. But hospitalizations are up 10% in much of the Northeast, The New York Times reports, and the improvement in cases and deaths has been slowing down. 

As of Oct. 15, 15% of RSV tests reported nationwide were positive, compared with about 11% at that time in 2021, the CDC said. The surveillance collects information from 75 counties in 12 states. 

Experts point out that the viruses – all three are respiratory viruses – are simply playing catchup. 

“They spread the same way and along with lots of other viruses, and you tend to see an increase in them during the cold months,” said Timothy Brewer, MD, professor of medicine and epidemiology at UCLA.

The increase in all three viruses “is almost predictable at this point in the pandemic,” said Dean Blumberg, MD, a professor and chief of pediatric infectious diseases at the University of California Davis Health. “All the respiratory viruses are out of whack.” 

Last year, RSV cases were up, too, and began to appear very early, he said, in the summer instead of in the cooler months. Flu also appeared early in 2021, as it has in 2022. 

That contrasts with the flu season of 2020-2021, when COVID precautions were nearly universal, and cases were down. At UC Davis, “we didn’t have one pediatric admission due to influenza in the 2020-2021 [flu] season,” Dr. Blumberg said. 

The number of pediatric flu deaths usually range from 37 to 199 per year, according to CDC records. But in the 2020-2021 season, the CDC recorded one pediatric flu death in the U.S.

Both children and adults have had less contact with others the past two seasons, Dr. Blumberg said, “and they don’t get the immunity they got with those infections [previously]. That’s why we are seeing out-of-season, early season [viruses].” 

Eventually, he said, the cases of flu and RSV will return to previous levels. “It could be as soon as next year,” Dr. Blumberg said. And COVID-19, hopefully, will become like influenza, he said.

“RSV has always come around in the fall and winter,” said Elizabeth Murray, DO, a pediatric emergency medicine doctor at the University of Rochester (N.Y.) Medical Center and a spokesperson for the American Academy of Pediatrics. In 2022, children are back in school and for the most part not masking. “It’s a perfect storm for all the germs to spread now. They’ve just been waiting for their opportunity to come back.”
 

Self-care vs. not

RSV can pose a risk for anyone, but most at risk are children under age 5, especially infants under age 1, and adults over age 65. There is no vaccine for it. Symptoms include a runny nose, decreased appetite, coughing, sneezing, fever, and wheezing. But in young infants, there may only be decreased activity, crankiness, and breathing issues, the CDC said.

Keep an eye on the breathing if RSV is suspected, Dr. Murray tells parents. If your child can’t breathe easily, is unable to lie down comfortably, can’t speak clearly, or is sucking in the chest muscles to breathe, get medical help. Most kids with RSV can stay home and recover, she said, but often will need to be checked by a medical professional.

She advises against getting an oximeter to measure oxygen levels for home use. “They are often not accurate,” she said. If in doubt about how serious your child’s symptoms are, “don’t wait it out,” and don’t hesitate to call 911.

Symptoms of flu, COVID, and RSV can overlap. But each can involve breathing problems, which can be an emergency. 

“It’s important to seek medical attention for any concerning symptoms, but especially severe shortness of breath or difficulty breathing, as these could signal the need for supplemental oxygen or other emergency interventions,” said Mandy De Vries, a respiratory therapist and director of education at the American Association for Respiratory Care. Inhalation treatment or mechanical ventilation may be needed for severe respiratory issues.
 

Precautions

To avoid the tripledemic – or any single infection – Timothy Brewer, MD, a professor of medicine and epidemiology at the University of California, Los Angeles, suggests some familiar measures: “Stay home if you’re feeling sick. Make sure you are up to date on your vaccinations. Wear a mask indoors.”

A version of this article first appeared on Medscape.com.

Just when we thought this holiday season, finally, would be the back-to-normal one, some infectious disease experts are warning that a so-called “tripledemic” – influenza, COVID-19, and RSV – may be in the forecast.

The warning isn’t without basis. 

The flu season has gotten an early start. As of Oct. 21, early increases in seasonal flu activity have been reported in most of the country, the Centers for Disease Control and Prevention said, with the southeast and south-central areas having the highest activity levels. 

Children’s hospitals and EDs are seeing a surge in children with RSV.

COVID-19 cases are trending down, according to the CDC, but epidemiologists – scientists who study disease outbreaks – always have their eyes on emerging variants. 

Predicting exactly when cases will peak is difficult, said Justin Lessler, PhD, a professor of epidemiology at the University of North Carolina at Chapel Hill. Dr. Lessler is on the coordinating team for the COVID-19 Scenario Modeling Hub, which aims to predict the course COVID-19, and the Flu Scenario Modeling Hub, which does the same for influenza.

For COVID-19, some models are predicting some spikes before Christmas, he said, and others see a new wave in 2023. For the flu, the model is predicting an earlier-than-usual start, as the CDC has reported.  

While flu activity is relatively low, the CDC said, the season is off to an early start. For the week ending Oct. 21, 1,674 patients were hospitalized for flu, higher than in the summer months but fewer than the 2,675 hospitalizations for the week of May 15, 2022. 

As of Oct. 20, COVID-19 cases have declined 12% over the last 2 weeks, nationwide. But hospitalizations are up 10% in much of the Northeast, The New York Times reports, and the improvement in cases and deaths has been slowing down. 

As of Oct. 15, 15% of RSV tests reported nationwide were positive, compared with about 11% at that time in 2021, the CDC said. The surveillance collects information from 75 counties in 12 states. 

Experts point out that the viruses – all three are respiratory viruses – are simply playing catchup. 

“They spread the same way and along with lots of other viruses, and you tend to see an increase in them during the cold months,” said Timothy Brewer, MD, professor of medicine and epidemiology at UCLA.

The increase in all three viruses “is almost predictable at this point in the pandemic,” said Dean Blumberg, MD, a professor and chief of pediatric infectious diseases at the University of California Davis Health. “All the respiratory viruses are out of whack.” 

Last year, RSV cases were up, too, and began to appear very early, he said, in the summer instead of in the cooler months. Flu also appeared early in 2021, as it has in 2022. 

That contrasts with the flu season of 2020-2021, when COVID precautions were nearly universal, and cases were down. At UC Davis, “we didn’t have one pediatric admission due to influenza in the 2020-2021 [flu] season,” Dr. Blumberg said. 

The number of pediatric flu deaths usually range from 37 to 199 per year, according to CDC records. But in the 2020-2021 season, the CDC recorded one pediatric flu death in the U.S.

Both children and adults have had less contact with others the past two seasons, Dr. Blumberg said, “and they don’t get the immunity they got with those infections [previously]. That’s why we are seeing out-of-season, early season [viruses].” 

Eventually, he said, the cases of flu and RSV will return to previous levels. “It could be as soon as next year,” Dr. Blumberg said. And COVID-19, hopefully, will become like influenza, he said.

“RSV has always come around in the fall and winter,” said Elizabeth Murray, DO, a pediatric emergency medicine doctor at the University of Rochester (N.Y.) Medical Center and a spokesperson for the American Academy of Pediatrics. In 2022, children are back in school and for the most part not masking. “It’s a perfect storm for all the germs to spread now. They’ve just been waiting for their opportunity to come back.”
 

Self-care vs. not

RSV can pose a risk for anyone, but most at risk are children under age 5, especially infants under age 1, and adults over age 65. There is no vaccine for it. Symptoms include a runny nose, decreased appetite, coughing, sneezing, fever, and wheezing. But in young infants, there may only be decreased activity, crankiness, and breathing issues, the CDC said.

Keep an eye on the breathing if RSV is suspected, Dr. Murray tells parents. If your child can’t breathe easily, is unable to lie down comfortably, can’t speak clearly, or is sucking in the chest muscles to breathe, get medical help. Most kids with RSV can stay home and recover, she said, but often will need to be checked by a medical professional.

She advises against getting an oximeter to measure oxygen levels for home use. “They are often not accurate,” she said. If in doubt about how serious your child’s symptoms are, “don’t wait it out,” and don’t hesitate to call 911.

Symptoms of flu, COVID, and RSV can overlap. But each can involve breathing problems, which can be an emergency. 

“It’s important to seek medical attention for any concerning symptoms, but especially severe shortness of breath or difficulty breathing, as these could signal the need for supplemental oxygen or other emergency interventions,” said Mandy De Vries, a respiratory therapist and director of education at the American Association for Respiratory Care. Inhalation treatment or mechanical ventilation may be needed for severe respiratory issues.
 

Precautions

To avoid the tripledemic – or any single infection – Timothy Brewer, MD, a professor of medicine and epidemiology at the University of California, Los Angeles, suggests some familiar measures: “Stay home if you’re feeling sick. Make sure you are up to date on your vaccinations. Wear a mask indoors.”

A version of this article first appeared on Medscape.com.

Just when we thought this holiday season, finally, would be the back-to-normal one, some infectious disease experts are warning that a so-called “tripledemic” – influenza, COVID-19, and RSV – may be in the forecast.

The warning isn’t without basis. 

The flu season has gotten an early start. As of Oct. 21, early increases in seasonal flu activity have been reported in most of the country, the Centers for Disease Control and Prevention said, with the southeast and south-central areas having the highest activity levels. 

Children’s hospitals and EDs are seeing a surge in children with RSV.

COVID-19 cases are trending down, according to the CDC, but epidemiologists – scientists who study disease outbreaks – always have their eyes on emerging variants. 

Predicting exactly when cases will peak is difficult, said Justin Lessler, PhD, a professor of epidemiology at the University of North Carolina at Chapel Hill. Dr. Lessler is on the coordinating team for the COVID-19 Scenario Modeling Hub, which aims to predict the course COVID-19, and the Flu Scenario Modeling Hub, which does the same for influenza.

For COVID-19, some models are predicting some spikes before Christmas, he said, and others see a new wave in 2023. For the flu, the model is predicting an earlier-than-usual start, as the CDC has reported.  

While flu activity is relatively low, the CDC said, the season is off to an early start. For the week ending Oct. 21, 1,674 patients were hospitalized for flu, higher than in the summer months but fewer than the 2,675 hospitalizations for the week of May 15, 2022. 

As of Oct. 20, COVID-19 cases have declined 12% over the last 2 weeks, nationwide. But hospitalizations are up 10% in much of the Northeast, The New York Times reports, and the improvement in cases and deaths has been slowing down. 

As of Oct. 15, 15% of RSV tests reported nationwide were positive, compared with about 11% at that time in 2021, the CDC said. The surveillance collects information from 75 counties in 12 states. 

Experts point out that the viruses – all three are respiratory viruses – are simply playing catchup. 

“They spread the same way and along with lots of other viruses, and you tend to see an increase in them during the cold months,” said Timothy Brewer, MD, professor of medicine and epidemiology at UCLA.

The increase in all three viruses “is almost predictable at this point in the pandemic,” said Dean Blumberg, MD, a professor and chief of pediatric infectious diseases at the University of California Davis Health. “All the respiratory viruses are out of whack.” 

Last year, RSV cases were up, too, and began to appear very early, he said, in the summer instead of in the cooler months. Flu also appeared early in 2021, as it has in 2022. 

That contrasts with the flu season of 2020-2021, when COVID precautions were nearly universal, and cases were down. At UC Davis, “we didn’t have one pediatric admission due to influenza in the 2020-2021 [flu] season,” Dr. Blumberg said. 

The number of pediatric flu deaths usually range from 37 to 199 per year, according to CDC records. But in the 2020-2021 season, the CDC recorded one pediatric flu death in the U.S.

Both children and adults have had less contact with others the past two seasons, Dr. Blumberg said, “and they don’t get the immunity they got with those infections [previously]. That’s why we are seeing out-of-season, early season [viruses].” 

Eventually, he said, the cases of flu and RSV will return to previous levels. “It could be as soon as next year,” Dr. Blumberg said. And COVID-19, hopefully, will become like influenza, he said.

“RSV has always come around in the fall and winter,” said Elizabeth Murray, DO, a pediatric emergency medicine doctor at the University of Rochester (N.Y.) Medical Center and a spokesperson for the American Academy of Pediatrics. In 2022, children are back in school and for the most part not masking. “It’s a perfect storm for all the germs to spread now. They’ve just been waiting for their opportunity to come back.”
 

Self-care vs. not

RSV can pose a risk for anyone, but most at risk are children under age 5, especially infants under age 1, and adults over age 65. There is no vaccine for it. Symptoms include a runny nose, decreased appetite, coughing, sneezing, fever, and wheezing. But in young infants, there may only be decreased activity, crankiness, and breathing issues, the CDC said.

Keep an eye on the breathing if RSV is suspected, Dr. Murray tells parents. If your child can’t breathe easily, is unable to lie down comfortably, can’t speak clearly, or is sucking in the chest muscles to breathe, get medical help. Most kids with RSV can stay home and recover, she said, but often will need to be checked by a medical professional.

She advises against getting an oximeter to measure oxygen levels for home use. “They are often not accurate,” she said. If in doubt about how serious your child’s symptoms are, “don’t wait it out,” and don’t hesitate to call 911.

Symptoms of flu, COVID, and RSV can overlap. But each can involve breathing problems, which can be an emergency. 

“It’s important to seek medical attention for any concerning symptoms, but especially severe shortness of breath or difficulty breathing, as these could signal the need for supplemental oxygen or other emergency interventions,” said Mandy De Vries, a respiratory therapist and director of education at the American Association for Respiratory Care. Inhalation treatment or mechanical ventilation may be needed for severe respiratory issues.
 

Precautions

To avoid the tripledemic – or any single infection – Timothy Brewer, MD, a professor of medicine and epidemiology at the University of California, Los Angeles, suggests some familiar measures: “Stay home if you’re feeling sick. Make sure you are up to date on your vaccinations. Wear a mask indoors.”

A version of this article first appeared on Medscape.com.

CHARLOTTE, N.C. – People with moderate to severe ulcerative colitis benefit from stronger treatment from the start – a combination of monoclonal antibodies – compared with induction with either agent alone, a phase 2a study demonstrates.

Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.

Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.

University of Western Ontario, London

The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv and a gastroenterologist at Western University in London, Ont.

The findings were presented at the annual meeting of the American College of Gastroenterology.
 

Study design

The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures, compared with monotherapy.

The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naive to TNF-alpha antagonists and refractory or intolerant to conventional therapy.

Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.

Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.

The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.

Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.

Dr. Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
 

Key findings through week 38

The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.

At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.

Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.

“Quite striking differences were maintained up to week 38,” Dr. Feagan said. “This combination treatment warrants further investigation, and phase 3 trials are underway.”

He added that, while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.

Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
 

Valuable data

“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic and the Kenneth Rainin Endowed Chair for IBD Research, said when asked to comment.

“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single-biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Dr. Achkar, who served as the session comoderator.

A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.

“I think they have to,” Dr. Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”

Dr. Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”

However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”

Another meeting attendee asked if the results might apply to other biologic combinations.

“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Dr. Feagan said.

Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.

The study was funded by Janssen Research and Development. Dr. Feagan reports being a consultant for Janssen. Dr. Achkar reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHARLOTTE, N.C. – People with moderate to severe ulcerative colitis benefit from stronger treatment from the start – a combination of monoclonal antibodies – compared with induction with either agent alone, a phase 2a study demonstrates.

Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.

Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.

University of Western Ontario, London

The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv and a gastroenterologist at Western University in London, Ont.

The findings were presented at the annual meeting of the American College of Gastroenterology.
 

Study design

The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures, compared with monotherapy.

The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naive to TNF-alpha antagonists and refractory or intolerant to conventional therapy.

Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.

Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.

The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.

Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.

Dr. Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
 

Key findings through week 38

The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.

At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.

Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.

“Quite striking differences were maintained up to week 38,” Dr. Feagan said. “This combination treatment warrants further investigation, and phase 3 trials are underway.”

He added that, while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.

Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
 

Valuable data

“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic and the Kenneth Rainin Endowed Chair for IBD Research, said when asked to comment.

“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single-biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Dr. Achkar, who served as the session comoderator.

A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.

“I think they have to,” Dr. Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”

Dr. Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”

However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”

Another meeting attendee asked if the results might apply to other biologic combinations.

“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Dr. Feagan said.

Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.

The study was funded by Janssen Research and Development. Dr. Feagan reports being a consultant for Janssen. Dr. Achkar reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHARLOTTE, N.C. – People with moderate to severe ulcerative colitis benefit from stronger treatment from the start – a combination of monoclonal antibodies – compared with induction with either agent alone, a phase 2a study demonstrates.

Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.

Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.

University of Western Ontario, London

The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv and a gastroenterologist at Western University in London, Ont.

The findings were presented at the annual meeting of the American College of Gastroenterology.
 

Study design

The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures, compared with monotherapy.

The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naive to TNF-alpha antagonists and refractory or intolerant to conventional therapy.

Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.

Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.

The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.

Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.

Dr. Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
 

Key findings through week 38

The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.

At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.

Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.

“Quite striking differences were maintained up to week 38,” Dr. Feagan said. “This combination treatment warrants further investigation, and phase 3 trials are underway.”

He added that, while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.

Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
 

Valuable data

“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic and the Kenneth Rainin Endowed Chair for IBD Research, said when asked to comment.

“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single-biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Dr. Achkar, who served as the session comoderator.

A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.

“I think they have to,” Dr. Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”

Dr. Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”

However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”

Another meeting attendee asked if the results might apply to other biologic combinations.

“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Dr. Feagan said.

Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.

The study was funded by Janssen Research and Development. Dr. Feagan reports being a consultant for Janssen. Dr. Achkar reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .

“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.

According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.

“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”

Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”

For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.

The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.

Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.

The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.

What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”

Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.

What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.

In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”

She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”

Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”

The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.

A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .

“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.

According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.

“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”

Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”

For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.

The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.

Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.

The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.

What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”

Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.

What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.

In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”

She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”

Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”

The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.

A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .

“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.

According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.

“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”

Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”

For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.

The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.

Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.

The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.

What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”

Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.

What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.

In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”

She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”

Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”

The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.

High-efficacy therapies for multiple sclerosis (MS) have improved disease outcomes for many patients, but physicians are uncertain when to use them. Despite better long-term disease outcomes, there are concerns over long-term safety, and some physicians and patients remain wary of these medications.

High-efficacy therapies were the subject of a session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Key topics included patient selection, timing of escalation to high-efficacy therapies, and initial use of high-efficacy therapies. The session produced a compelling message, according to moderator Patricia Coyle, MD. “I think [the speakers provided] accumulating data that this is a smart thing to do: Use high-efficacy therapies early to get the maximum bang for the buck,” Dr. Coyle said in an interview. She is professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University.
 

Consider baseline characteristics

In the first talk, Xavier Montalban, MD, PhD, noted that a statement from the ECTRIMS/EAN (European Academy of Neurology) guideline update in 2021 said that a high-efficacy disease-modifying therapy (DMT) should be considered early in the disease course. A key question is whether any baseline characteristics can be used to select patients, and studies have shown worse prognosis with older age, male sex, low levels of vitamin D, and smoking status, among various other factors.

He presented subgroup analyses from trials of fingolimod and ozanimod, which showed that the drugs did not work as well in patients with poor prognostic factors such as an Expanded Disability Status Scale (EDSS) score of 4 or above and age over 40 years. Lower doses also tend to have less efficacy in males. “If you have [a patient with] bad baseline prognostic factors, you need high-efficacy medication at the right dose, because a lower dose will not work well. It is the same phenomenon for age,” Dr. Montalban said in his talk. On the other hand, he showed the results of a study of ofatumumab and ocrelizumab, both of which showed high efficacy even in patients with poor prognostic factors.

Among patients with secondary progressive MS, clinical or MRI evidence of inflammatory activity is the only poor prognostic factor that appears to be a good predictor of treatment response.

Dr. Montalban also addressed the timing of intervention with DMTs. A study from his group prospectively followed 1,015 patients treated with DMTs. “Interestingly, what we observed is that patients who were treated with DMTs just after the first attack did better than those who were treated after the second attack, and you have to take into consideration that we treat those patients after the first attack, those who had the worst prognostic factors, so treatment was very effective in that sense,” said Dr. Montalban, director of the Multiple Sclerosis Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona.
 

Switching DMTs

In the second presentation, Dalia Rotstein, MD, discussed how to incorporate prognostic factors when switching a patient to high-efficacy therapies as a result of new disease activity while on another therapy.

Patients with favorable prognostic factors at baseline may be started out on immunomodulatory therapy. “Essentially, we want to match the intensity of the therapy to the intensity of the disease of the patient in front of us,” Dr. Rotstein said in her talk. Nevertheless, the course of MS is unpredictable, and the first year or two of immunomodulatory therapy can give physicians clues about the longer-term course of the disease. “We need to observe closely for disease activity in the first year, but even up to 2 years on therapy to determine a need for early escalation,” said Dr. Rotstein, assistant professor of medicine at University of Toronto.

For switching to high-efficacy therapies, any relapse, disability progression, or an EDSS change of 1 point or more could be a consideration. MRI indicators are more controversial, but one to three new T2 lesions also could prompt a switch.

Serum neural filament light chain (sNFL) is a useful biomarker for monitoring disease activity as it correlates well with new disease activity within the next year. It can be monitored every 3-4 months and adjusted for clinical factors and monitored for changing levels. A concerning finding can be followed up with an MRI or in-person visit.

When switching to a high-efficacy therapy, it’s important to administer any vaccines well in advance to ensure a good immune response.

When it comes to a washout period, physicians need to consider both the risk of immunosuppression and breakthrough disease activity. “But in general, we’ve observed that we can minimize the duration of the washout when stopping initial immunomodulator therapy to reduce the risk of breakthrough disease activity. We need to pay particular attention to the risk of rebound activity with longer washouts after stopping sphingosine-1 phosphate (S1P) receptor modulators because the rebound activity can be devastating,” said Dr. Rotstein.

A study of timing of relapses after fingolimod washout, carried out by Dr. Rotstein’s group, found a stark signal. “We observed that when the washout after fingolimod discontinuation was 30 days or more, there is a very high risk of early relapse,” she said.
 

The case for induction therapy

In the third talk, Gavin Giovannoni, MBBCh, PhD, discussed “flipping the pyramid” – that is, starting patients off immediately with high-efficacy therapies rather than waiting until they progress on other therapies. He likened such a decision to a gambler, because MS patients on less-effective therapy can suffer irreversible, long-term physical consequences, as well as social consequences such as unemployment due to cognitive effects.

“We always tend to put up a graph about the risks and benefits of a specific treatment, and we forget about the risks of untreated or undertreated MS. Keep that in mind when making decisions about high-efficacy therapies,” said Dr. Giovannoni, professor of neurology at Queen Mary University of London.

About 80% of patients on tier 1, or low-efficacy therapies, will have breakthrough activity on MRI within 4 years. Moving up a tier gets to about a 60% rate of breakthrough activity. High-efficacy therapies attain an efficacy of about 80% at 6 months. “If you have MS, you’ve got to realize that if you had to roll the dice, which tier would you want to be in? By putting all of them [on high-efficacy therapies], you’re going to get the majority responding and a few of them will break through,” said Dr. Giovannoni.

He presented some real-world evidence to back up the argument: A study comparing outcomes in Sweden and Denmark, which have similar demographics. In Denmark, 7.6% of patients with MS received high-efficacy therapies initially, while in Sweden the proportion was 34.5%. Patients with MS treated in Sweden had a 29% lower probability of progressing to disability (P = .004) and there were 22% fewer discontinuations of DMTs (P < .001). Since that study, the proportion of patients receiving high-efficacy therapies to begin with is closer to 70%. “This is compelling evidence that you want to be on a [high-efficacy therapy] early. If I had MS, I would want to live in Sweden,” said Dr. Giovannoni.

Historical treatments focused on reducing relapses, and more recently on eliminating evidence of inflammatory disease. He said that physicians are prioritizing brain volume loss to improve long-term outcomes in MS, and some are studying long-term disability. “We know that brain volume loss in MS is a prognostic sign both at baseline and at follow-up. It predicts poor outcome, poor cognition and employment, poor quality of life, et cetera,” said Dr. Giovannoni.

He cited data from studies of alemtuzumab that showed a significant reduction in brain volume loss. “The rate is about 0.2% per annum, which is kind of getting into the normal range for age-matched controls. Those people who were started off on interferons in the study lost a lot of brain volume in those first 2 years, and that’s irreversible,” said Dr. Giovannoni.

He pointed out that studies of hematopoietic stem cell therapy showed similar brain-volume outcomes. “So flipping the pyramid with the two most highly effective therapies almost normalizes brain volume loss in people with MS,” said Dr. Giovannoni.

There is also evidence in other autoimmune diseases that early use of high-efficacy therapies improves outcomes. More aggressive therapy in rheumatoid arthritis has reduced joint replacements by 90%.

“I think you really, really need to give your patients the opportunity of flipping the pyramid. You shouldn’t decide that for them,” said Dr. Giovannoni.

Dr. Coyle has consulted for nearly all pharmaceutical companies developing drugs in the MS space. Dr. Montalban has financial relationships with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Celgene, Actelion, Mylan, BMS, and Sandoz. Dr. Rotstein has financial ties with Roche Canada, Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis. Dr. Giovannoni has financial ties with AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, GW Pharma, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co., Merck KGaA/EMD Serono, Moderna, Novartis, Sanofi, Roche/Genentech, and Teva.

High-efficacy therapies for multiple sclerosis (MS) have improved disease outcomes for many patients, but physicians are uncertain when to use them. Despite better long-term disease outcomes, there are concerns over long-term safety, and some physicians and patients remain wary of these medications.

High-efficacy therapies were the subject of a session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Key topics included patient selection, timing of escalation to high-efficacy therapies, and initial use of high-efficacy therapies. The session produced a compelling message, according to moderator Patricia Coyle, MD. “I think [the speakers provided] accumulating data that this is a smart thing to do: Use high-efficacy therapies early to get the maximum bang for the buck,” Dr. Coyle said in an interview. She is professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University.
 

Consider baseline characteristics

In the first talk, Xavier Montalban, MD, PhD, noted that a statement from the ECTRIMS/EAN (European Academy of Neurology) guideline update in 2021 said that a high-efficacy disease-modifying therapy (DMT) should be considered early in the disease course. A key question is whether any baseline characteristics can be used to select patients, and studies have shown worse prognosis with older age, male sex, low levels of vitamin D, and smoking status, among various other factors.

He presented subgroup analyses from trials of fingolimod and ozanimod, which showed that the drugs did not work as well in patients with poor prognostic factors such as an Expanded Disability Status Scale (EDSS) score of 4 or above and age over 40 years. Lower doses also tend to have less efficacy in males. “If you have [a patient with] bad baseline prognostic factors, you need high-efficacy medication at the right dose, because a lower dose will not work well. It is the same phenomenon for age,” Dr. Montalban said in his talk. On the other hand, he showed the results of a study of ofatumumab and ocrelizumab, both of which showed high efficacy even in patients with poor prognostic factors.

Among patients with secondary progressive MS, clinical or MRI evidence of inflammatory activity is the only poor prognostic factor that appears to be a good predictor of treatment response.

Dr. Montalban also addressed the timing of intervention with DMTs. A study from his group prospectively followed 1,015 patients treated with DMTs. “Interestingly, what we observed is that patients who were treated with DMTs just after the first attack did better than those who were treated after the second attack, and you have to take into consideration that we treat those patients after the first attack, those who had the worst prognostic factors, so treatment was very effective in that sense,” said Dr. Montalban, director of the Multiple Sclerosis Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona.
 

Switching DMTs

In the second presentation, Dalia Rotstein, MD, discussed how to incorporate prognostic factors when switching a patient to high-efficacy therapies as a result of new disease activity while on another therapy.

Patients with favorable prognostic factors at baseline may be started out on immunomodulatory therapy. “Essentially, we want to match the intensity of the therapy to the intensity of the disease of the patient in front of us,” Dr. Rotstein said in her talk. Nevertheless, the course of MS is unpredictable, and the first year or two of immunomodulatory therapy can give physicians clues about the longer-term course of the disease. “We need to observe closely for disease activity in the first year, but even up to 2 years on therapy to determine a need for early escalation,” said Dr. Rotstein, assistant professor of medicine at University of Toronto.

For switching to high-efficacy therapies, any relapse, disability progression, or an EDSS change of 1 point or more could be a consideration. MRI indicators are more controversial, but one to three new T2 lesions also could prompt a switch.

Serum neural filament light chain (sNFL) is a useful biomarker for monitoring disease activity as it correlates well with new disease activity within the next year. It can be monitored every 3-4 months and adjusted for clinical factors and monitored for changing levels. A concerning finding can be followed up with an MRI or in-person visit.

When switching to a high-efficacy therapy, it’s important to administer any vaccines well in advance to ensure a good immune response.

When it comes to a washout period, physicians need to consider both the risk of immunosuppression and breakthrough disease activity. “But in general, we’ve observed that we can minimize the duration of the washout when stopping initial immunomodulator therapy to reduce the risk of breakthrough disease activity. We need to pay particular attention to the risk of rebound activity with longer washouts after stopping sphingosine-1 phosphate (S1P) receptor modulators because the rebound activity can be devastating,” said Dr. Rotstein.

A study of timing of relapses after fingolimod washout, carried out by Dr. Rotstein’s group, found a stark signal. “We observed that when the washout after fingolimod discontinuation was 30 days or more, there is a very high risk of early relapse,” she said.
 

The case for induction therapy

In the third talk, Gavin Giovannoni, MBBCh, PhD, discussed “flipping the pyramid” – that is, starting patients off immediately with high-efficacy therapies rather than waiting until they progress on other therapies. He likened such a decision to a gambler, because MS patients on less-effective therapy can suffer irreversible, long-term physical consequences, as well as social consequences such as unemployment due to cognitive effects.

“We always tend to put up a graph about the risks and benefits of a specific treatment, and we forget about the risks of untreated or undertreated MS. Keep that in mind when making decisions about high-efficacy therapies,” said Dr. Giovannoni, professor of neurology at Queen Mary University of London.

About 80% of patients on tier 1, or low-efficacy therapies, will have breakthrough activity on MRI within 4 years. Moving up a tier gets to about a 60% rate of breakthrough activity. High-efficacy therapies attain an efficacy of about 80% at 6 months. “If you have MS, you’ve got to realize that if you had to roll the dice, which tier would you want to be in? By putting all of them [on high-efficacy therapies], you’re going to get the majority responding and a few of them will break through,” said Dr. Giovannoni.

He presented some real-world evidence to back up the argument: A study comparing outcomes in Sweden and Denmark, which have similar demographics. In Denmark, 7.6% of patients with MS received high-efficacy therapies initially, while in Sweden the proportion was 34.5%. Patients with MS treated in Sweden had a 29% lower probability of progressing to disability (P = .004) and there were 22% fewer discontinuations of DMTs (P < .001). Since that study, the proportion of patients receiving high-efficacy therapies to begin with is closer to 70%. “This is compelling evidence that you want to be on a [high-efficacy therapy] early. If I had MS, I would want to live in Sweden,” said Dr. Giovannoni.

Historical treatments focused on reducing relapses, and more recently on eliminating evidence of inflammatory disease. He said that physicians are prioritizing brain volume loss to improve long-term outcomes in MS, and some are studying long-term disability. “We know that brain volume loss in MS is a prognostic sign both at baseline and at follow-up. It predicts poor outcome, poor cognition and employment, poor quality of life, et cetera,” said Dr. Giovannoni.

He cited data from studies of alemtuzumab that showed a significant reduction in brain volume loss. “The rate is about 0.2% per annum, which is kind of getting into the normal range for age-matched controls. Those people who were started off on interferons in the study lost a lot of brain volume in those first 2 years, and that’s irreversible,” said Dr. Giovannoni.

He pointed out that studies of hematopoietic stem cell therapy showed similar brain-volume outcomes. “So flipping the pyramid with the two most highly effective therapies almost normalizes brain volume loss in people with MS,” said Dr. Giovannoni.

There is also evidence in other autoimmune diseases that early use of high-efficacy therapies improves outcomes. More aggressive therapy in rheumatoid arthritis has reduced joint replacements by 90%.

“I think you really, really need to give your patients the opportunity of flipping the pyramid. You shouldn’t decide that for them,” said Dr. Giovannoni.

Dr. Coyle has consulted for nearly all pharmaceutical companies developing drugs in the MS space. Dr. Montalban has financial relationships with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Celgene, Actelion, Mylan, BMS, and Sandoz. Dr. Rotstein has financial ties with Roche Canada, Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis. Dr. Giovannoni has financial ties with AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, GW Pharma, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co., Merck KGaA/EMD Serono, Moderna, Novartis, Sanofi, Roche/Genentech, and Teva.

High-efficacy therapies for multiple sclerosis (MS) have improved disease outcomes for many patients, but physicians are uncertain when to use them. Despite better long-term disease outcomes, there are concerns over long-term safety, and some physicians and patients remain wary of these medications.

High-efficacy therapies were the subject of a session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Key topics included patient selection, timing of escalation to high-efficacy therapies, and initial use of high-efficacy therapies. The session produced a compelling message, according to moderator Patricia Coyle, MD. “I think [the speakers provided] accumulating data that this is a smart thing to do: Use high-efficacy therapies early to get the maximum bang for the buck,” Dr. Coyle said in an interview. She is professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University.
 

Consider baseline characteristics

In the first talk, Xavier Montalban, MD, PhD, noted that a statement from the ECTRIMS/EAN (European Academy of Neurology) guideline update in 2021 said that a high-efficacy disease-modifying therapy (DMT) should be considered early in the disease course. A key question is whether any baseline characteristics can be used to select patients, and studies have shown worse prognosis with older age, male sex, low levels of vitamin D, and smoking status, among various other factors.

He presented subgroup analyses from trials of fingolimod and ozanimod, which showed that the drugs did not work as well in patients with poor prognostic factors such as an Expanded Disability Status Scale (EDSS) score of 4 or above and age over 40 years. Lower doses also tend to have less efficacy in males. “If you have [a patient with] bad baseline prognostic factors, you need high-efficacy medication at the right dose, because a lower dose will not work well. It is the same phenomenon for age,” Dr. Montalban said in his talk. On the other hand, he showed the results of a study of ofatumumab and ocrelizumab, both of which showed high efficacy even in patients with poor prognostic factors.

Among patients with secondary progressive MS, clinical or MRI evidence of inflammatory activity is the only poor prognostic factor that appears to be a good predictor of treatment response.

Dr. Montalban also addressed the timing of intervention with DMTs. A study from his group prospectively followed 1,015 patients treated with DMTs. “Interestingly, what we observed is that patients who were treated with DMTs just after the first attack did better than those who were treated after the second attack, and you have to take into consideration that we treat those patients after the first attack, those who had the worst prognostic factors, so treatment was very effective in that sense,” said Dr. Montalban, director of the Multiple Sclerosis Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona.
 

Switching DMTs

In the second presentation, Dalia Rotstein, MD, discussed how to incorporate prognostic factors when switching a patient to high-efficacy therapies as a result of new disease activity while on another therapy.

Patients with favorable prognostic factors at baseline may be started out on immunomodulatory therapy. “Essentially, we want to match the intensity of the therapy to the intensity of the disease of the patient in front of us,” Dr. Rotstein said in her talk. Nevertheless, the course of MS is unpredictable, and the first year or two of immunomodulatory therapy can give physicians clues about the longer-term course of the disease. “We need to observe closely for disease activity in the first year, but even up to 2 years on therapy to determine a need for early escalation,” said Dr. Rotstein, assistant professor of medicine at University of Toronto.

For switching to high-efficacy therapies, any relapse, disability progression, or an EDSS change of 1 point or more could be a consideration. MRI indicators are more controversial, but one to three new T2 lesions also could prompt a switch.

Serum neural filament light chain (sNFL) is a useful biomarker for monitoring disease activity as it correlates well with new disease activity within the next year. It can be monitored every 3-4 months and adjusted for clinical factors and monitored for changing levels. A concerning finding can be followed up with an MRI or in-person visit.

When switching to a high-efficacy therapy, it’s important to administer any vaccines well in advance to ensure a good immune response.

When it comes to a washout period, physicians need to consider both the risk of immunosuppression and breakthrough disease activity. “But in general, we’ve observed that we can minimize the duration of the washout when stopping initial immunomodulator therapy to reduce the risk of breakthrough disease activity. We need to pay particular attention to the risk of rebound activity with longer washouts after stopping sphingosine-1 phosphate (S1P) receptor modulators because the rebound activity can be devastating,” said Dr. Rotstein.

A study of timing of relapses after fingolimod washout, carried out by Dr. Rotstein’s group, found a stark signal. “We observed that when the washout after fingolimod discontinuation was 30 days or more, there is a very high risk of early relapse,” she said.
 

The case for induction therapy

In the third talk, Gavin Giovannoni, MBBCh, PhD, discussed “flipping the pyramid” – that is, starting patients off immediately with high-efficacy therapies rather than waiting until they progress on other therapies. He likened such a decision to a gambler, because MS patients on less-effective therapy can suffer irreversible, long-term physical consequences, as well as social consequences such as unemployment due to cognitive effects.

“We always tend to put up a graph about the risks and benefits of a specific treatment, and we forget about the risks of untreated or undertreated MS. Keep that in mind when making decisions about high-efficacy therapies,” said Dr. Giovannoni, professor of neurology at Queen Mary University of London.

About 80% of patients on tier 1, or low-efficacy therapies, will have breakthrough activity on MRI within 4 years. Moving up a tier gets to about a 60% rate of breakthrough activity. High-efficacy therapies attain an efficacy of about 80% at 6 months. “If you have MS, you’ve got to realize that if you had to roll the dice, which tier would you want to be in? By putting all of them [on high-efficacy therapies], you’re going to get the majority responding and a few of them will break through,” said Dr. Giovannoni.

He presented some real-world evidence to back up the argument: A study comparing outcomes in Sweden and Denmark, which have similar demographics. In Denmark, 7.6% of patients with MS received high-efficacy therapies initially, while in Sweden the proportion was 34.5%. Patients with MS treated in Sweden had a 29% lower probability of progressing to disability (P = .004) and there were 22% fewer discontinuations of DMTs (P < .001). Since that study, the proportion of patients receiving high-efficacy therapies to begin with is closer to 70%. “This is compelling evidence that you want to be on a [high-efficacy therapy] early. If I had MS, I would want to live in Sweden,” said Dr. Giovannoni.

Historical treatments focused on reducing relapses, and more recently on eliminating evidence of inflammatory disease. He said that physicians are prioritizing brain volume loss to improve long-term outcomes in MS, and some are studying long-term disability. “We know that brain volume loss in MS is a prognostic sign both at baseline and at follow-up. It predicts poor outcome, poor cognition and employment, poor quality of life, et cetera,” said Dr. Giovannoni.

He cited data from studies of alemtuzumab that showed a significant reduction in brain volume loss. “The rate is about 0.2% per annum, which is kind of getting into the normal range for age-matched controls. Those people who were started off on interferons in the study lost a lot of brain volume in those first 2 years, and that’s irreversible,” said Dr. Giovannoni.

He pointed out that studies of hematopoietic stem cell therapy showed similar brain-volume outcomes. “So flipping the pyramid with the two most highly effective therapies almost normalizes brain volume loss in people with MS,” said Dr. Giovannoni.

There is also evidence in other autoimmune diseases that early use of high-efficacy therapies improves outcomes. More aggressive therapy in rheumatoid arthritis has reduced joint replacements by 90%.

“I think you really, really need to give your patients the opportunity of flipping the pyramid. You shouldn’t decide that for them,” said Dr. Giovannoni.

Dr. Coyle has consulted for nearly all pharmaceutical companies developing drugs in the MS space. Dr. Montalban has financial relationships with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Celgene, Actelion, Mylan, BMS, and Sandoz. Dr. Rotstein has financial ties with Roche Canada, Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis. Dr. Giovannoni has financial ties with AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, GW Pharma, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co., Merck KGaA/EMD Serono, Moderna, Novartis, Sanofi, Roche/Genentech, and Teva.

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

DENVER – Use of subcutaneous ropivacaine for Mohs surgery in highly vascularized anatomical regions such as the nose results in significantly shorter duration of anesthesia compared with less vascularized regions such as the shin, results from a single-center study showed.

Ropivacaine is a long-acting anesthetic that may be used as a substitute for the more commonly local anesthetics such as lidocaine or bupivacaine in dermatologic surgery, lead study author Kira Minkis, MD, PhD, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the study results were presented during an oral abstract session. By comparison, ropivacaine has been reported to have a faster onset, similar duration in the range of 6-14 hours, less pain upon injection, and inherent vasoconstrictive properties.

“With tumescent anesthesia, studies have previously shown that the rate and absorption of anesthetics is influenced by the site of administration,” said Dr. Minkis, director of Mohs and dermatologic surgery at Weill Cornell Medicine, New York. “In studies comparing absorption of local anesthetics in tumescent anesthesia by regions that differ in vascularity, peak serum concentrations are greater and rise more rapidly after use in the head and neck compared to the trunk and extremities. However, no studies to date have compared the duration of ropivacaine in highly vascularized tissue or compared duration between regions that differ in vascularity.” The aim of the study, she noted, was to characterize the difference in duration of ropivacaine’s effects between anatomic regions of rich and comparably poor vascularity, such as the face and extremities, respectively.

Dr. Minkis and her colleagues recruited 17 women and 12 men with a mean age of 72 years who underwent Mohs surgery on the nose or the shin at Weill Cornell Medicine. Patients were anesthetized at each site with a subcutaneous injection of 0.5 mL of ropivacaine, 0.2%. Sensation was determined by pinprick prior to injection, at baseline, and every 15 minutes until sensation returned or surgery concluded. The primary endpoint was time to return of pinprick sensation.

The researchers found that the duration of ropivacaine was significantly shorter on the nose (a median of 60 minutes) than on the shin (a median of 210 minutes). In fact, the upper limit of the range of duration at the shin was not determinable because 22 of the 29 (76%) of participants did not regain sensation on the shin prior to leaving the surgical suite and concluding the study. The proportion of study participants who regained sensation within 1 hour was 76% among those who were treated on the nose vs. 3% of those who were treated on the shin (P < .0001).

“With durations of up to 6-14 hours reported, our results indicate a strikingly shorter duration of local anesthesia in highly vascularized tissue,” Dr. Minkis said. “The brevity of local anesthesia is even more surprising given the intrinsic vasoconstrictive properties of ropivacaine. Often, we co-administer epinephrine to achieve vasoconstriction and reduce local blood flow, thus prolonging local concentrations of the anesthetic with the added benefit of reducing bleeding during surgery. The short duration we’ve observed in our study is emphasized in using a potent, long-acting local anesthetic with vasoconstrictive properties that otherwise should attenuate the effects of high local vascularity.”

In other findings, patients with history of hypertension were more likely to regain sensation on the nose by 60 minutes but this did not reach statistical significance (P = .079). Other comorbidities including underlying anxiety/depression, diabetes, and kidney disease did not significantly impact duration of ropivacaine action on the nose. The same held true for patients who were treated on the shin.

“We highlight an inconsistency between the reported duration of a long-lasting local anesthetic and the short-lived anesthesia experienced by our patients in a highly vascularized region,” Dr. Minkis said. “In practice, adjunctive use of a long-acting anesthetic to prolong anesthesia is common, which may provide relief from multiple injections of shorter-acting lidocaine. However, the duration of Mohs surgery can be unpredictable. Extended wait times between stages may exceed the duration we’ve observed in this study.”

In addition, she continued, “pain is frequently reported on postoperative days 0 to 3, leading some to recommend the use of long-acting local anesthetics to prevent overprescription or a gap in pain coverage. This emphasizes a gap in effective pain control, but also an opportunity to improve our patients’ surgical and recovery experiences.”

 

Impact on practice

Keith L. Duffy, MD, associate professor of dermatology at the University of Utah, Salt Lake City, who was asked to comment on the study, said that in light of current local anesthetic shortages and back orders, “we dermatologic surgeons have been experimenting with different anesthetics and concentrations that we can use in our patients. Ropivacaine may become the anesthetic of choice for many of our practices given its inherent properties.”

The duration of anesthetic effects by anatomic location in this study is “actually more impressive than I would have suspected as a practicing Mohs surgeon. The results of this study will immediately impact my Mohs surgery clinic,” he said, adding that he hoped that Dr. Minkis and others “will expand on this study to include more patients, different anesthetics, and more anatomic locations.”

Dr. Minkis acknowledged certain limitations of the study, including its single-center design and the fact that there were too few observations of medical and clinical characteristics for subgroup analysis.

She and Dr. Duffy reported having no financial disclosures.

DENVER – Use of subcutaneous ropivacaine for Mohs surgery in highly vascularized anatomical regions such as the nose results in significantly shorter duration of anesthesia compared with less vascularized regions such as the shin, results from a single-center study showed.

Ropivacaine is a long-acting anesthetic that may be used as a substitute for the more commonly local anesthetics such as lidocaine or bupivacaine in dermatologic surgery, lead study author Kira Minkis, MD, PhD, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the study results were presented during an oral abstract session. By comparison, ropivacaine has been reported to have a faster onset, similar duration in the range of 6-14 hours, less pain upon injection, and inherent vasoconstrictive properties.

“With tumescent anesthesia, studies have previously shown that the rate and absorption of anesthetics is influenced by the site of administration,” said Dr. Minkis, director of Mohs and dermatologic surgery at Weill Cornell Medicine, New York. “In studies comparing absorption of local anesthetics in tumescent anesthesia by regions that differ in vascularity, peak serum concentrations are greater and rise more rapidly after use in the head and neck compared to the trunk and extremities. However, no studies to date have compared the duration of ropivacaine in highly vascularized tissue or compared duration between regions that differ in vascularity.” The aim of the study, she noted, was to characterize the difference in duration of ropivacaine’s effects between anatomic regions of rich and comparably poor vascularity, such as the face and extremities, respectively.

Dr. Minkis and her colleagues recruited 17 women and 12 men with a mean age of 72 years who underwent Mohs surgery on the nose or the shin at Weill Cornell Medicine. Patients were anesthetized at each site with a subcutaneous injection of 0.5 mL of ropivacaine, 0.2%. Sensation was determined by pinprick prior to injection, at baseline, and every 15 minutes until sensation returned or surgery concluded. The primary endpoint was time to return of pinprick sensation.

The researchers found that the duration of ropivacaine was significantly shorter on the nose (a median of 60 minutes) than on the shin (a median of 210 minutes). In fact, the upper limit of the range of duration at the shin was not determinable because 22 of the 29 (76%) of participants did not regain sensation on the shin prior to leaving the surgical suite and concluding the study. The proportion of study participants who regained sensation within 1 hour was 76% among those who were treated on the nose vs. 3% of those who were treated on the shin (P < .0001).

“With durations of up to 6-14 hours reported, our results indicate a strikingly shorter duration of local anesthesia in highly vascularized tissue,” Dr. Minkis said. “The brevity of local anesthesia is even more surprising given the intrinsic vasoconstrictive properties of ropivacaine. Often, we co-administer epinephrine to achieve vasoconstriction and reduce local blood flow, thus prolonging local concentrations of the anesthetic with the added benefit of reducing bleeding during surgery. The short duration we’ve observed in our study is emphasized in using a potent, long-acting local anesthetic with vasoconstrictive properties that otherwise should attenuate the effects of high local vascularity.”

In other findings, patients with history of hypertension were more likely to regain sensation on the nose by 60 minutes but this did not reach statistical significance (P = .079). Other comorbidities including underlying anxiety/depression, diabetes, and kidney disease did not significantly impact duration of ropivacaine action on the nose. The same held true for patients who were treated on the shin.

“We highlight an inconsistency between the reported duration of a long-lasting local anesthetic and the short-lived anesthesia experienced by our patients in a highly vascularized region,” Dr. Minkis said. “In practice, adjunctive use of a long-acting anesthetic to prolong anesthesia is common, which may provide relief from multiple injections of shorter-acting lidocaine. However, the duration of Mohs surgery can be unpredictable. Extended wait times between stages may exceed the duration we’ve observed in this study.”

In addition, she continued, “pain is frequently reported on postoperative days 0 to 3, leading some to recommend the use of long-acting local anesthetics to prevent overprescription or a gap in pain coverage. This emphasizes a gap in effective pain control, but also an opportunity to improve our patients’ surgical and recovery experiences.”

 

Impact on practice

Keith L. Duffy, MD, associate professor of dermatology at the University of Utah, Salt Lake City, who was asked to comment on the study, said that in light of current local anesthetic shortages and back orders, “we dermatologic surgeons have been experimenting with different anesthetics and concentrations that we can use in our patients. Ropivacaine may become the anesthetic of choice for many of our practices given its inherent properties.”

The duration of anesthetic effects by anatomic location in this study is “actually more impressive than I would have suspected as a practicing Mohs surgeon. The results of this study will immediately impact my Mohs surgery clinic,” he said, adding that he hoped that Dr. Minkis and others “will expand on this study to include more patients, different anesthetics, and more anatomic locations.”

Dr. Minkis acknowledged certain limitations of the study, including its single-center design and the fact that there were too few observations of medical and clinical characteristics for subgroup analysis.

She and Dr. Duffy reported having no financial disclosures.

DENVER – Use of subcutaneous ropivacaine for Mohs surgery in highly vascularized anatomical regions such as the nose results in significantly shorter duration of anesthesia compared with less vascularized regions such as the shin, results from a single-center study showed.

Ropivacaine is a long-acting anesthetic that may be used as a substitute for the more commonly local anesthetics such as lidocaine or bupivacaine in dermatologic surgery, lead study author Kira Minkis, MD, PhD, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the study results were presented during an oral abstract session. By comparison, ropivacaine has been reported to have a faster onset, similar duration in the range of 6-14 hours, less pain upon injection, and inherent vasoconstrictive properties.

“With tumescent anesthesia, studies have previously shown that the rate and absorption of anesthetics is influenced by the site of administration,” said Dr. Minkis, director of Mohs and dermatologic surgery at Weill Cornell Medicine, New York. “In studies comparing absorption of local anesthetics in tumescent anesthesia by regions that differ in vascularity, peak serum concentrations are greater and rise more rapidly after use in the head and neck compared to the trunk and extremities. However, no studies to date have compared the duration of ropivacaine in highly vascularized tissue or compared duration between regions that differ in vascularity.” The aim of the study, she noted, was to characterize the difference in duration of ropivacaine’s effects between anatomic regions of rich and comparably poor vascularity, such as the face and extremities, respectively.

Dr. Minkis and her colleagues recruited 17 women and 12 men with a mean age of 72 years who underwent Mohs surgery on the nose or the shin at Weill Cornell Medicine. Patients were anesthetized at each site with a subcutaneous injection of 0.5 mL of ropivacaine, 0.2%. Sensation was determined by pinprick prior to injection, at baseline, and every 15 minutes until sensation returned or surgery concluded. The primary endpoint was time to return of pinprick sensation.

The researchers found that the duration of ropivacaine was significantly shorter on the nose (a median of 60 minutes) than on the shin (a median of 210 minutes). In fact, the upper limit of the range of duration at the shin was not determinable because 22 of the 29 (76%) of participants did not regain sensation on the shin prior to leaving the surgical suite and concluding the study. The proportion of study participants who regained sensation within 1 hour was 76% among those who were treated on the nose vs. 3% of those who were treated on the shin (P < .0001).

“With durations of up to 6-14 hours reported, our results indicate a strikingly shorter duration of local anesthesia in highly vascularized tissue,” Dr. Minkis said. “The brevity of local anesthesia is even more surprising given the intrinsic vasoconstrictive properties of ropivacaine. Often, we co-administer epinephrine to achieve vasoconstriction and reduce local blood flow, thus prolonging local concentrations of the anesthetic with the added benefit of reducing bleeding during surgery. The short duration we’ve observed in our study is emphasized in using a potent, long-acting local anesthetic with vasoconstrictive properties that otherwise should attenuate the effects of high local vascularity.”

In other findings, patients with history of hypertension were more likely to regain sensation on the nose by 60 minutes but this did not reach statistical significance (P = .079). Other comorbidities including underlying anxiety/depression, diabetes, and kidney disease did not significantly impact duration of ropivacaine action on the nose. The same held true for patients who were treated on the shin.

“We highlight an inconsistency between the reported duration of a long-lasting local anesthetic and the short-lived anesthesia experienced by our patients in a highly vascularized region,” Dr. Minkis said. “In practice, adjunctive use of a long-acting anesthetic to prolong anesthesia is common, which may provide relief from multiple injections of shorter-acting lidocaine. However, the duration of Mohs surgery can be unpredictable. Extended wait times between stages may exceed the duration we’ve observed in this study.”

In addition, she continued, “pain is frequently reported on postoperative days 0 to 3, leading some to recommend the use of long-acting local anesthetics to prevent overprescription or a gap in pain coverage. This emphasizes a gap in effective pain control, but also an opportunity to improve our patients’ surgical and recovery experiences.”

 

Impact on practice

Keith L. Duffy, MD, associate professor of dermatology at the University of Utah, Salt Lake City, who was asked to comment on the study, said that in light of current local anesthetic shortages and back orders, “we dermatologic surgeons have been experimenting with different anesthetics and concentrations that we can use in our patients. Ropivacaine may become the anesthetic of choice for many of our practices given its inherent properties.”

The duration of anesthetic effects by anatomic location in this study is “actually more impressive than I would have suspected as a practicing Mohs surgeon. The results of this study will immediately impact my Mohs surgery clinic,” he said, adding that he hoped that Dr. Minkis and others “will expand on this study to include more patients, different anesthetics, and more anatomic locations.”

Dr. Minkis acknowledged certain limitations of the study, including its single-center design and the fact that there were too few observations of medical and clinical characteristics for subgroup analysis.

She and Dr. Duffy reported having no financial disclosures.