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Expert offers clinical pearls on leg ulcer therapy
Elena Conde Montero, MD, PhD, asserted at the virtual annual congress of the European Academy of Dermatology and Venereology.
In addition to delving into the finer points of compression therapy, she offered other clinical pearls for the treatment of chronic leg ulcers. These included the use of autologous punch grafting to reduce pain as well as promote healing, when to employ adjunctive negative pressure therapy, and the benefits of liquid sevoflurane for highly effective topical analgesia during wound cleansing and debridement.
Compression therapy
“If no contraindications exist, compression therapy is the best antihypertensive and anti-inflammatory treatment for all leg ulcers, not only venous leg ulcers,” according to Dr. Conde, a dermatologist at Infanta Leonor University Hospital in Madrid.
The list of absolute contraindications to compression treatment is brief, as highlighted in a recent international consensus statement. The expert writing panel named only four: severe peripheral artery disease, the presence of an epifascial arterial bypass, severe cardiac insufficiency, and true allergy to compression material.
Compression therapy provides multiple salutary effects. These include reduced capillary filtration of fluids to tissue, decreased swelling, enhanced tissue remodeling, better lymphatic drainage, reduced inflammatory cell counts, and increased arterial flow.
“This means that people with mild arterial disease will benefit from active compression because perfusion will improve,” Dr. Conde said.
Similarly, leg ulcers secondary to pyoderma gangrenosum will benefit from the anti-inflammatory effects of compression therapy in conjunction with standard immunotherapy, added the dermatologist, who coauthored a recent publication by the European Wound Management Association entitled “Atypical Wounds: Best Clinical Practices and Challenges.”
Four broad types of compression therapy are available: compression stockings, short-stretch bandages, multicomponent bandage systems, and self-adjusting compression wrap devices. The best clinical outcomes are achieved by individualized selection of a compression method based upon patient characteristics.
Short-stretch, low-elasticity bandages – such as the classic Unna boot loaded with zinc paste and topical corticosteroids – are well suited for patients with large leg ulcers. These bandages feature high working pressures during muscle contraction. They also provide low resting pressures, which is advantageous in patients with peripheral artery disease. The major disadvantage of short-stretch bandages is the need for frequent dressing changes by a nurse or other trained professional, since the compression is quickly lost as an unwanted consequence of the welcome reduction in swelling.
Multicomponent bandage systems feature two to four layers of bandages of differing stiffness, as well as padding material and in many cases pressure indicators. These bandages can often be worn for up to a week without needing to be changed, since they maintain adequate pressure long term. “These are very easy to use by nonexperts,” Dr. Conde noted.
A caveat regarding both short-stretch bandages and the multicomponent bandage systems: before applying them, it’s important to pad at-risk areas against injury caused by high pressures. These high-risk areas include the Achilles tendon, the pretibial region, and the lateral foot.
Self-adjusting compression systems are comprised of strips of short-stretch, low-elasticity fabric, which wrap around the leg and are fixed with Velcro closures. Dr. Conde hailed these devices as “a great innovation in compression therapy, without doubt.” Their major advantage is ease of application and removal by the patient. They are best-suited for treatment of small ulcers in patients who find it difficult to use compression stockings because of obesity or osteoarthritis, in patients who can’t tolerate such stockings because they have peripheral artery disease and the stockings’ high resting pressure is uncomfortable, or in individuals ill-suited for compression bandages because they lack adequate access to nursing care for the required frequent dressing changes.
Compression stockings are a good option for small ulcers. It’s easier for patients to wear shoes with compression stockings and thereby engage in normal everyday activities than with short-stretch bandages. A tip: Many patients find it arduous to don and remove a high-compression stocking that achieves the recommended pressure of 30-40 mm Hg at the point of transition between the Achilles tendon and the calf muscle, but the same effect can be achieved by overlapping two easier-to-use lower-compression stockings.
Punch grafting
This simple, cost-effective outpatient procedure was first described as a means of enhancing wound healing 150 years ago. The method involves utilizing a scalpel, curette, or punch to obtain a series of thin split-thickness skin grafts that contain epidermis and dermis down to the superficial papillary dermis. The grafts, usually harvested from the anterior thigh, are placed on the wound. This is followed by at least 5 days of local pressure and rest to promote graft uptake.
Sequential punch grafting is an excellent option for particularly challenging chronic ulcers, including Martorell hypertensive ischemic leg ulcers and other arteriolopathic ulcers in the elderly.
“Sequential punch grafting of wounds is very common in our clinics, especially for wounds that lack perfect grafting conditions,” Dr. Conde said.
She considers Martorell hypertensive ischemic leg ulcers to be underdiagnosed and undertreated. The Martorell leg ulcer is an exceedingly painful, rapidly progressive ischemic lesion, or bilateral lesions, with inflamed irregular margins. The disorder is caused by obstruction of subcutaneous arterioles in the absence of signs of vasculitis, and generally occurs in older individuals who have had well-controlled hypertension for many years. Diabetes, obesity, dyslipidemia, and peripheral artery disease are common comorbid conditions. The most common form of treatment – bioactive dressings in a moist environment – produces unsatisfactory results because it doesn’t address the inflammatory process.
Dr. Conde and coworkers have published the full details of how they achieved complete healing of Martorell hypertensive ischemic leg ulcers 3-8 weeks after punch grafting in three affected patients, all of whom presented with pain scores of 10/10 refractory even to opioid analgesics. The punch grafting was preceded by 15 days of topical corticosteroids and low-elasticity compression bandages in order to create adequate granulation tissue in the wound bed, which had the added benefit of achieving a 2- to 3-point reduction in pain scores even before the surgical procedure.
The pain-reducing effect of punch grafting isn’t as well appreciated as the wound-healing effect. Dr. Conde was first author of a recent study in which investigators systematically measured pain reduction in 136 patients with hard-to-heal leg ulcers of various etiologies treated with punch grafting. Nearly three-quarters of those who presented with painful ulcers were pain free after punch grafting, and the rest experienced greater than 70% pain reduction.
Pain suppression wasn’t dependent upon the percentage of graft uptake in this study. That’s because, as long as the wound isn’t overcleaned during dressing changes, even grafts that haven’t attached to the wound will release growth factors that promote wound healing, Dr. Conde explained.
Adjunctive negative pressure therapy
Portable vacuum-based negative pressure therapy devices are easy to use as a means to promote punch graft uptake. Negative pressure is best employed as an adjunct to punch grafting in suboptimal wound beds, longstanding ulcers, in patients with previous graft failure, or in challenging anatomic locations, such as the Achilles tendon or ankle. Dr. Conde has found the combination of punch grafting and negative pressure therapy especially helpful in patients with clinically inactive pyoderma gangrenosum.
Topical sevoflurane for analgesia
Most of the literature on topical sevoflurane for ulcer care has been published by Spanish researchers, but this form of analgesia deserves much more widespread use, according to Dr. Conde.
Sevoflurane is most often used as a gas in general anesthesia. In liquid form, however, it not only has a rapid, long-lasting analgesic effect when applied to painful leg ulcers, it also promotes healing because it is both antibacterial and a vasodilator. So before performing a potentially painful ulcer or wound cleaning, Dr. Conde recommended protecting perilesional skin with petroleum jelly, then irrigating the ulcer site with liquid sevoflurane. After that, it’s advisable to wait just 5-10 minutes before proceeding.
“It takes effect in much less time than EMLA cream,” she noted.
In one study of 30 adults aged over age 65 years with painful chronic venous ulcers refractory to conventional analgesics who underwent ulcer cleaning supported by topical sevoflurane at a dose of roughly 1 mL/cm2 of ulcer area every 2 days for a month, Spanish investigators documented onset of analgesic effect in 2-7 minutes, with a duration of 8-18 hours. The researchers found that the use of backup conventional analgesics ranging from acetaminophen to opioids was diminished. Side effects were limited to mild, transient itching and redness.
Dr. Conde reported having no financial conflicts of interest regarding her presentation.
Elena Conde Montero, MD, PhD, asserted at the virtual annual congress of the European Academy of Dermatology and Venereology.
In addition to delving into the finer points of compression therapy, she offered other clinical pearls for the treatment of chronic leg ulcers. These included the use of autologous punch grafting to reduce pain as well as promote healing, when to employ adjunctive negative pressure therapy, and the benefits of liquid sevoflurane for highly effective topical analgesia during wound cleansing and debridement.
Compression therapy
“If no contraindications exist, compression therapy is the best antihypertensive and anti-inflammatory treatment for all leg ulcers, not only venous leg ulcers,” according to Dr. Conde, a dermatologist at Infanta Leonor University Hospital in Madrid.
The list of absolute contraindications to compression treatment is brief, as highlighted in a recent international consensus statement. The expert writing panel named only four: severe peripheral artery disease, the presence of an epifascial arterial bypass, severe cardiac insufficiency, and true allergy to compression material.
Compression therapy provides multiple salutary effects. These include reduced capillary filtration of fluids to tissue, decreased swelling, enhanced tissue remodeling, better lymphatic drainage, reduced inflammatory cell counts, and increased arterial flow.
“This means that people with mild arterial disease will benefit from active compression because perfusion will improve,” Dr. Conde said.
Similarly, leg ulcers secondary to pyoderma gangrenosum will benefit from the anti-inflammatory effects of compression therapy in conjunction with standard immunotherapy, added the dermatologist, who coauthored a recent publication by the European Wound Management Association entitled “Atypical Wounds: Best Clinical Practices and Challenges.”
Four broad types of compression therapy are available: compression stockings, short-stretch bandages, multicomponent bandage systems, and self-adjusting compression wrap devices. The best clinical outcomes are achieved by individualized selection of a compression method based upon patient characteristics.
Short-stretch, low-elasticity bandages – such as the classic Unna boot loaded with zinc paste and topical corticosteroids – are well suited for patients with large leg ulcers. These bandages feature high working pressures during muscle contraction. They also provide low resting pressures, which is advantageous in patients with peripheral artery disease. The major disadvantage of short-stretch bandages is the need for frequent dressing changes by a nurse or other trained professional, since the compression is quickly lost as an unwanted consequence of the welcome reduction in swelling.
Multicomponent bandage systems feature two to four layers of bandages of differing stiffness, as well as padding material and in many cases pressure indicators. These bandages can often be worn for up to a week without needing to be changed, since they maintain adequate pressure long term. “These are very easy to use by nonexperts,” Dr. Conde noted.
A caveat regarding both short-stretch bandages and the multicomponent bandage systems: before applying them, it’s important to pad at-risk areas against injury caused by high pressures. These high-risk areas include the Achilles tendon, the pretibial region, and the lateral foot.
Self-adjusting compression systems are comprised of strips of short-stretch, low-elasticity fabric, which wrap around the leg and are fixed with Velcro closures. Dr. Conde hailed these devices as “a great innovation in compression therapy, without doubt.” Their major advantage is ease of application and removal by the patient. They are best-suited for treatment of small ulcers in patients who find it difficult to use compression stockings because of obesity or osteoarthritis, in patients who can’t tolerate such stockings because they have peripheral artery disease and the stockings’ high resting pressure is uncomfortable, or in individuals ill-suited for compression bandages because they lack adequate access to nursing care for the required frequent dressing changes.
Compression stockings are a good option for small ulcers. It’s easier for patients to wear shoes with compression stockings and thereby engage in normal everyday activities than with short-stretch bandages. A tip: Many patients find it arduous to don and remove a high-compression stocking that achieves the recommended pressure of 30-40 mm Hg at the point of transition between the Achilles tendon and the calf muscle, but the same effect can be achieved by overlapping two easier-to-use lower-compression stockings.
Punch grafting
This simple, cost-effective outpatient procedure was first described as a means of enhancing wound healing 150 years ago. The method involves utilizing a scalpel, curette, or punch to obtain a series of thin split-thickness skin grafts that contain epidermis and dermis down to the superficial papillary dermis. The grafts, usually harvested from the anterior thigh, are placed on the wound. This is followed by at least 5 days of local pressure and rest to promote graft uptake.
Sequential punch grafting is an excellent option for particularly challenging chronic ulcers, including Martorell hypertensive ischemic leg ulcers and other arteriolopathic ulcers in the elderly.
“Sequential punch grafting of wounds is very common in our clinics, especially for wounds that lack perfect grafting conditions,” Dr. Conde said.
She considers Martorell hypertensive ischemic leg ulcers to be underdiagnosed and undertreated. The Martorell leg ulcer is an exceedingly painful, rapidly progressive ischemic lesion, or bilateral lesions, with inflamed irregular margins. The disorder is caused by obstruction of subcutaneous arterioles in the absence of signs of vasculitis, and generally occurs in older individuals who have had well-controlled hypertension for many years. Diabetes, obesity, dyslipidemia, and peripheral artery disease are common comorbid conditions. The most common form of treatment – bioactive dressings in a moist environment – produces unsatisfactory results because it doesn’t address the inflammatory process.
Dr. Conde and coworkers have published the full details of how they achieved complete healing of Martorell hypertensive ischemic leg ulcers 3-8 weeks after punch grafting in three affected patients, all of whom presented with pain scores of 10/10 refractory even to opioid analgesics. The punch grafting was preceded by 15 days of topical corticosteroids and low-elasticity compression bandages in order to create adequate granulation tissue in the wound bed, which had the added benefit of achieving a 2- to 3-point reduction in pain scores even before the surgical procedure.
The pain-reducing effect of punch grafting isn’t as well appreciated as the wound-healing effect. Dr. Conde was first author of a recent study in which investigators systematically measured pain reduction in 136 patients with hard-to-heal leg ulcers of various etiologies treated with punch grafting. Nearly three-quarters of those who presented with painful ulcers were pain free after punch grafting, and the rest experienced greater than 70% pain reduction.
Pain suppression wasn’t dependent upon the percentage of graft uptake in this study. That’s because, as long as the wound isn’t overcleaned during dressing changes, even grafts that haven’t attached to the wound will release growth factors that promote wound healing, Dr. Conde explained.
Adjunctive negative pressure therapy
Portable vacuum-based negative pressure therapy devices are easy to use as a means to promote punch graft uptake. Negative pressure is best employed as an adjunct to punch grafting in suboptimal wound beds, longstanding ulcers, in patients with previous graft failure, or in challenging anatomic locations, such as the Achilles tendon or ankle. Dr. Conde has found the combination of punch grafting and negative pressure therapy especially helpful in patients with clinically inactive pyoderma gangrenosum.
Topical sevoflurane for analgesia
Most of the literature on topical sevoflurane for ulcer care has been published by Spanish researchers, but this form of analgesia deserves much more widespread use, according to Dr. Conde.
Sevoflurane is most often used as a gas in general anesthesia. In liquid form, however, it not only has a rapid, long-lasting analgesic effect when applied to painful leg ulcers, it also promotes healing because it is both antibacterial and a vasodilator. So before performing a potentially painful ulcer or wound cleaning, Dr. Conde recommended protecting perilesional skin with petroleum jelly, then irrigating the ulcer site with liquid sevoflurane. After that, it’s advisable to wait just 5-10 minutes before proceeding.
“It takes effect in much less time than EMLA cream,” she noted.
In one study of 30 adults aged over age 65 years with painful chronic venous ulcers refractory to conventional analgesics who underwent ulcer cleaning supported by topical sevoflurane at a dose of roughly 1 mL/cm2 of ulcer area every 2 days for a month, Spanish investigators documented onset of analgesic effect in 2-7 minutes, with a duration of 8-18 hours. The researchers found that the use of backup conventional analgesics ranging from acetaminophen to opioids was diminished. Side effects were limited to mild, transient itching and redness.
Dr. Conde reported having no financial conflicts of interest regarding her presentation.
Elena Conde Montero, MD, PhD, asserted at the virtual annual congress of the European Academy of Dermatology and Venereology.
In addition to delving into the finer points of compression therapy, she offered other clinical pearls for the treatment of chronic leg ulcers. These included the use of autologous punch grafting to reduce pain as well as promote healing, when to employ adjunctive negative pressure therapy, and the benefits of liquid sevoflurane for highly effective topical analgesia during wound cleansing and debridement.
Compression therapy
“If no contraindications exist, compression therapy is the best antihypertensive and anti-inflammatory treatment for all leg ulcers, not only venous leg ulcers,” according to Dr. Conde, a dermatologist at Infanta Leonor University Hospital in Madrid.
The list of absolute contraindications to compression treatment is brief, as highlighted in a recent international consensus statement. The expert writing panel named only four: severe peripheral artery disease, the presence of an epifascial arterial bypass, severe cardiac insufficiency, and true allergy to compression material.
Compression therapy provides multiple salutary effects. These include reduced capillary filtration of fluids to tissue, decreased swelling, enhanced tissue remodeling, better lymphatic drainage, reduced inflammatory cell counts, and increased arterial flow.
“This means that people with mild arterial disease will benefit from active compression because perfusion will improve,” Dr. Conde said.
Similarly, leg ulcers secondary to pyoderma gangrenosum will benefit from the anti-inflammatory effects of compression therapy in conjunction with standard immunotherapy, added the dermatologist, who coauthored a recent publication by the European Wound Management Association entitled “Atypical Wounds: Best Clinical Practices and Challenges.”
Four broad types of compression therapy are available: compression stockings, short-stretch bandages, multicomponent bandage systems, and self-adjusting compression wrap devices. The best clinical outcomes are achieved by individualized selection of a compression method based upon patient characteristics.
Short-stretch, low-elasticity bandages – such as the classic Unna boot loaded with zinc paste and topical corticosteroids – are well suited for patients with large leg ulcers. These bandages feature high working pressures during muscle contraction. They also provide low resting pressures, which is advantageous in patients with peripheral artery disease. The major disadvantage of short-stretch bandages is the need for frequent dressing changes by a nurse or other trained professional, since the compression is quickly lost as an unwanted consequence of the welcome reduction in swelling.
Multicomponent bandage systems feature two to four layers of bandages of differing stiffness, as well as padding material and in many cases pressure indicators. These bandages can often be worn for up to a week without needing to be changed, since they maintain adequate pressure long term. “These are very easy to use by nonexperts,” Dr. Conde noted.
A caveat regarding both short-stretch bandages and the multicomponent bandage systems: before applying them, it’s important to pad at-risk areas against injury caused by high pressures. These high-risk areas include the Achilles tendon, the pretibial region, and the lateral foot.
Self-adjusting compression systems are comprised of strips of short-stretch, low-elasticity fabric, which wrap around the leg and are fixed with Velcro closures. Dr. Conde hailed these devices as “a great innovation in compression therapy, without doubt.” Their major advantage is ease of application and removal by the patient. They are best-suited for treatment of small ulcers in patients who find it difficult to use compression stockings because of obesity or osteoarthritis, in patients who can’t tolerate such stockings because they have peripheral artery disease and the stockings’ high resting pressure is uncomfortable, or in individuals ill-suited for compression bandages because they lack adequate access to nursing care for the required frequent dressing changes.
Compression stockings are a good option for small ulcers. It’s easier for patients to wear shoes with compression stockings and thereby engage in normal everyday activities than with short-stretch bandages. A tip: Many patients find it arduous to don and remove a high-compression stocking that achieves the recommended pressure of 30-40 mm Hg at the point of transition between the Achilles tendon and the calf muscle, but the same effect can be achieved by overlapping two easier-to-use lower-compression stockings.
Punch grafting
This simple, cost-effective outpatient procedure was first described as a means of enhancing wound healing 150 years ago. The method involves utilizing a scalpel, curette, or punch to obtain a series of thin split-thickness skin grafts that contain epidermis and dermis down to the superficial papillary dermis. The grafts, usually harvested from the anterior thigh, are placed on the wound. This is followed by at least 5 days of local pressure and rest to promote graft uptake.
Sequential punch grafting is an excellent option for particularly challenging chronic ulcers, including Martorell hypertensive ischemic leg ulcers and other arteriolopathic ulcers in the elderly.
“Sequential punch grafting of wounds is very common in our clinics, especially for wounds that lack perfect grafting conditions,” Dr. Conde said.
She considers Martorell hypertensive ischemic leg ulcers to be underdiagnosed and undertreated. The Martorell leg ulcer is an exceedingly painful, rapidly progressive ischemic lesion, or bilateral lesions, with inflamed irregular margins. The disorder is caused by obstruction of subcutaneous arterioles in the absence of signs of vasculitis, and generally occurs in older individuals who have had well-controlled hypertension for many years. Diabetes, obesity, dyslipidemia, and peripheral artery disease are common comorbid conditions. The most common form of treatment – bioactive dressings in a moist environment – produces unsatisfactory results because it doesn’t address the inflammatory process.
Dr. Conde and coworkers have published the full details of how they achieved complete healing of Martorell hypertensive ischemic leg ulcers 3-8 weeks after punch grafting in three affected patients, all of whom presented with pain scores of 10/10 refractory even to opioid analgesics. The punch grafting was preceded by 15 days of topical corticosteroids and low-elasticity compression bandages in order to create adequate granulation tissue in the wound bed, which had the added benefit of achieving a 2- to 3-point reduction in pain scores even before the surgical procedure.
The pain-reducing effect of punch grafting isn’t as well appreciated as the wound-healing effect. Dr. Conde was first author of a recent study in which investigators systematically measured pain reduction in 136 patients with hard-to-heal leg ulcers of various etiologies treated with punch grafting. Nearly three-quarters of those who presented with painful ulcers were pain free after punch grafting, and the rest experienced greater than 70% pain reduction.
Pain suppression wasn’t dependent upon the percentage of graft uptake in this study. That’s because, as long as the wound isn’t overcleaned during dressing changes, even grafts that haven’t attached to the wound will release growth factors that promote wound healing, Dr. Conde explained.
Adjunctive negative pressure therapy
Portable vacuum-based negative pressure therapy devices are easy to use as a means to promote punch graft uptake. Negative pressure is best employed as an adjunct to punch grafting in suboptimal wound beds, longstanding ulcers, in patients with previous graft failure, or in challenging anatomic locations, such as the Achilles tendon or ankle. Dr. Conde has found the combination of punch grafting and negative pressure therapy especially helpful in patients with clinically inactive pyoderma gangrenosum.
Topical sevoflurane for analgesia
Most of the literature on topical sevoflurane for ulcer care has been published by Spanish researchers, but this form of analgesia deserves much more widespread use, according to Dr. Conde.
Sevoflurane is most often used as a gas in general anesthesia. In liquid form, however, it not only has a rapid, long-lasting analgesic effect when applied to painful leg ulcers, it also promotes healing because it is both antibacterial and a vasodilator. So before performing a potentially painful ulcer or wound cleaning, Dr. Conde recommended protecting perilesional skin with petroleum jelly, then irrigating the ulcer site with liquid sevoflurane. After that, it’s advisable to wait just 5-10 minutes before proceeding.
“It takes effect in much less time than EMLA cream,” she noted.
In one study of 30 adults aged over age 65 years with painful chronic venous ulcers refractory to conventional analgesics who underwent ulcer cleaning supported by topical sevoflurane at a dose of roughly 1 mL/cm2 of ulcer area every 2 days for a month, Spanish investigators documented onset of analgesic effect in 2-7 minutes, with a duration of 8-18 hours. The researchers found that the use of backup conventional analgesics ranging from acetaminophen to opioids was diminished. Side effects were limited to mild, transient itching and redness.
Dr. Conde reported having no financial conflicts of interest regarding her presentation.
FROM THE EADV CONGRESS
Early use of high-titer plasma may prevent severe COVID-19
Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.
In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.
“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.
“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.
The study was published online Jan. 6 in The New England Journal of Medicine.
“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.
Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.
“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.
Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.
Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”
A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.
“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.
However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”
A search for clear answers
Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”
To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.
In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).
The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).
Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.
The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.
“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.
The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.
Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”
Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
An inexpensive therapy with global potential?
“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”
Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”
Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”
Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.
“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.
“We are glad it worked,” he said.
The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.
A version of this article first appeared on Medscape.com.
Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.
In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.
“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.
“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.
The study was published online Jan. 6 in The New England Journal of Medicine.
“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.
Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.
“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.
Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.
Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”
A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.
“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.
However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”
A search for clear answers
Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”
To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.
In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).
The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).
Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.
The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.
“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.
The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.
Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”
Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
An inexpensive therapy with global potential?
“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”
Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”
Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”
Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.
“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.
“We are glad it worked,” he said.
The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.
A version of this article first appeared on Medscape.com.
Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.
In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.
“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.
“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.
The study was published online Jan. 6 in The New England Journal of Medicine.
“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.
Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.
“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.
Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.
Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”
A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.
“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.
However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”
A search for clear answers
Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”
To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.
In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).
The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).
Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.
The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.
“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.
The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.
Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”
Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
An inexpensive therapy with global potential?
“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”
Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”
Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”
Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.
“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.
“We are glad it worked,” he said.
The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.
A version of this article first appeared on Medscape.com.
Guidance issued on COVID vaccine use in patients with dermal fillers
outlining the potential risk and clinical relevance.
The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.
“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.
The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.
“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.
In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.
The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.
“The good news is that these will go away,” Dr. Cox said.
The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.
Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.
“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.
As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,
Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.
The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.
As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
This article was updated 1/7/21.
outlining the potential risk and clinical relevance.
The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.
“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.
The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.
“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.
In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.
The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.
“The good news is that these will go away,” Dr. Cox said.
The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.
Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.
“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.
As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,
Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.
The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.
As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
This article was updated 1/7/21.
outlining the potential risk and clinical relevance.
The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.
“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.
The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.
“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.
In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.
The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.
“The good news is that these will go away,” Dr. Cox said.
The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.
Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.
“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.
As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,
Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.
The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.
As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
This article was updated 1/7/21.
Inflammation of juxta-articular soft tissues could be an early feature of RA
Key clinical point: Intermetatarsal (IMB) and submetatarsal (SMB) bursitis are associated with and specific for early rheumatoid arthritis (RA), with IMB having the highest sensitivity.
Major finding: IMB (adjusted odds ratio [aOR], 4.5; P less than .001) and SMB (aOR, 2.2; P = .041) were associated with RA. Sensitivity for RA of IMB and SMB was 69% and 25%, respectively. Specificity of IMB vs. other arthritides and healthy controls was 70% and 84%, respectively. Specificity for SMB was 94% (vs. other arthritides) and 97% (vs. healthy controls).
Study details: The findings are based on a large case-controlled magnetic resonance imaging study of 157 patients presenting with early RA, 284 other arthritides, and 193 healthy controls.
Disclosures: The study was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.
Source: Dakkak Y et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02359-w.
Key clinical point: Intermetatarsal (IMB) and submetatarsal (SMB) bursitis are associated with and specific for early rheumatoid arthritis (RA), with IMB having the highest sensitivity.
Major finding: IMB (adjusted odds ratio [aOR], 4.5; P less than .001) and SMB (aOR, 2.2; P = .041) were associated with RA. Sensitivity for RA of IMB and SMB was 69% and 25%, respectively. Specificity of IMB vs. other arthritides and healthy controls was 70% and 84%, respectively. Specificity for SMB was 94% (vs. other arthritides) and 97% (vs. healthy controls).
Study details: The findings are based on a large case-controlled magnetic resonance imaging study of 157 patients presenting with early RA, 284 other arthritides, and 193 healthy controls.
Disclosures: The study was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.
Source: Dakkak Y et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02359-w.
Key clinical point: Intermetatarsal (IMB) and submetatarsal (SMB) bursitis are associated with and specific for early rheumatoid arthritis (RA), with IMB having the highest sensitivity.
Major finding: IMB (adjusted odds ratio [aOR], 4.5; P less than .001) and SMB (aOR, 2.2; P = .041) were associated with RA. Sensitivity for RA of IMB and SMB was 69% and 25%, respectively. Specificity of IMB vs. other arthritides and healthy controls was 70% and 84%, respectively. Specificity for SMB was 94% (vs. other arthritides) and 97% (vs. healthy controls).
Study details: The findings are based on a large case-controlled magnetic resonance imaging study of 157 patients presenting with early RA, 284 other arthritides, and 193 healthy controls.
Disclosures: The study was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.
Source: Dakkak Y et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02359-w.
Younger adults present with more advanced esophageal adenocarcinoma
The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.
Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”
In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older
Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
Younger patients show more advanced illness
Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.
In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.
“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.
The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.
However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
Reasons for increase remain unclear
“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.
“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.
“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.
“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”
The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.
SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.
The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.
Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”
In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older
Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
Younger patients show more advanced illness
Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.
In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.
“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.
The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.
However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
Reasons for increase remain unclear
“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.
“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.
“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.
“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”
The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.
SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.
The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.
Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”
In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older
Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
Younger patients show more advanced illness
Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.
In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.
“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.
The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.
However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
Reasons for increase remain unclear
“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.
“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.
“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.
“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”
The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.
SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.
FROM CANCER EPIDEMIOLOGY, BIOMARKERS & PREVENTION
RA: Depression tied to greater disease activity and pain
Key clinical point: Depression was associated with greater short-term disease activity and more severe and persistent pain in US veterans with early rheumatoid arthritis (RA) receiving methotrexate.
Major finding: Depression was associated with significantly higher 28-joint count disease activity scores at 6 months (β, 0.345; P = .045) but not at 1- (P = .477) and 2- (P = .804) year follow-up. Moreover, depression was significantly associated with higher patient-reported pain at 6 months (β, 0.385; P = .029) and 1 year (β, 0.396; P = .028).
Study details: The study included 268 US veterans (89.2% males) with early RA (duration less than 2 years) prescribed methotrexate, identified from the Veterans Affairs Rheumatoid Arthritis Registry.
Disclosures: The study was supported by the Rheumatology Research Foundation’s Scientist Development Award, the National Institute on Ageing, VA Clinical Science Research and Development Service, and the National Institute of General Medical Sciences. The authors reported receiving grants from various organizations and/or pharmaceutical companies.
Source: Rathbun AM et al. J Rheumatol. 2020 Nov 15. doi: 10.3899/jrheum.200743.
Key clinical point: Depression was associated with greater short-term disease activity and more severe and persistent pain in US veterans with early rheumatoid arthritis (RA) receiving methotrexate.
Major finding: Depression was associated with significantly higher 28-joint count disease activity scores at 6 months (β, 0.345; P = .045) but not at 1- (P = .477) and 2- (P = .804) year follow-up. Moreover, depression was significantly associated with higher patient-reported pain at 6 months (β, 0.385; P = .029) and 1 year (β, 0.396; P = .028).
Study details: The study included 268 US veterans (89.2% males) with early RA (duration less than 2 years) prescribed methotrexate, identified from the Veterans Affairs Rheumatoid Arthritis Registry.
Disclosures: The study was supported by the Rheumatology Research Foundation’s Scientist Development Award, the National Institute on Ageing, VA Clinical Science Research and Development Service, and the National Institute of General Medical Sciences. The authors reported receiving grants from various organizations and/or pharmaceutical companies.
Source: Rathbun AM et al. J Rheumatol. 2020 Nov 15. doi: 10.3899/jrheum.200743.
Key clinical point: Depression was associated with greater short-term disease activity and more severe and persistent pain in US veterans with early rheumatoid arthritis (RA) receiving methotrexate.
Major finding: Depression was associated with significantly higher 28-joint count disease activity scores at 6 months (β, 0.345; P = .045) but not at 1- (P = .477) and 2- (P = .804) year follow-up. Moreover, depression was significantly associated with higher patient-reported pain at 6 months (β, 0.385; P = .029) and 1 year (β, 0.396; P = .028).
Study details: The study included 268 US veterans (89.2% males) with early RA (duration less than 2 years) prescribed methotrexate, identified from the Veterans Affairs Rheumatoid Arthritis Registry.
Disclosures: The study was supported by the Rheumatology Research Foundation’s Scientist Development Award, the National Institute on Ageing, VA Clinical Science Research and Development Service, and the National Institute of General Medical Sciences. The authors reported receiving grants from various organizations and/or pharmaceutical companies.
Source: Rathbun AM et al. J Rheumatol. 2020 Nov 15. doi: 10.3899/jrheum.200743.
Oral glucocorticoids plus PPIs raise osteoporotic fracture risk in patients with RA
Key clinical point: The concomitant use of oral glucocorticoids and proton pump inhibitors (PPIs) is associated with a higher risk of osteoporotic fractures in patients with rheumatoid arthritis (RA).
Major finding: The risk of osteoporotic fractures was significantly higher in concomitant users of oral glucocorticoids and PPIs (adjusted hazard ratio [aHR] 1.60; 95% confidence interval [CI] 1.35-1.89). Among current concomitant users, an increased risk was observed for fractures of the hip (aHR, 1.45; 95% CI, 1.11-1.91), clinical vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and ribs (aHR, 4.03; 95% CI, 2.13-7.63).
Study details: The data come from a retrospective study of 12,351 patients with RA aged 50 years or older in the United Kingdom.
Disclosures: Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.
Source: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.
Key clinical point: The concomitant use of oral glucocorticoids and proton pump inhibitors (PPIs) is associated with a higher risk of osteoporotic fractures in patients with rheumatoid arthritis (RA).
Major finding: The risk of osteoporotic fractures was significantly higher in concomitant users of oral glucocorticoids and PPIs (adjusted hazard ratio [aHR] 1.60; 95% confidence interval [CI] 1.35-1.89). Among current concomitant users, an increased risk was observed for fractures of the hip (aHR, 1.45; 95% CI, 1.11-1.91), clinical vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and ribs (aHR, 4.03; 95% CI, 2.13-7.63).
Study details: The data come from a retrospective study of 12,351 patients with RA aged 50 years or older in the United Kingdom.
Disclosures: Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.
Source: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.
Key clinical point: The concomitant use of oral glucocorticoids and proton pump inhibitors (PPIs) is associated with a higher risk of osteoporotic fractures in patients with rheumatoid arthritis (RA).
Major finding: The risk of osteoporotic fractures was significantly higher in concomitant users of oral glucocorticoids and PPIs (adjusted hazard ratio [aHR] 1.60; 95% confidence interval [CI] 1.35-1.89). Among current concomitant users, an increased risk was observed for fractures of the hip (aHR, 1.45; 95% CI, 1.11-1.91), clinical vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and ribs (aHR, 4.03; 95% CI, 2.13-7.63).
Study details: The data come from a retrospective study of 12,351 patients with RA aged 50 years or older in the United Kingdom.
Disclosures: Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.
Source: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.
Tocilizumab + methotrexate vs. tocilizumab alone for preventing radiographic progression in RA
Key clinical point: Tocilizumab (TCZ) and methotrexate (MTX) combination therapy was generally more effective than TCZ monotherapy in preventing radiographic progression in patients with early and established rheumatoid arthritis. However, effect modifiers were more joint damage or lower disease activity score (DAS) in early RA and longer disease duration in established RA.
Major finding: Overall, TCZ monotherapy was less effective in preventing radiographic progression (relative risk; 95% confidence interval) than TCZ+MTX combination therapy in patients with early (0.96; 0.90 to –1.03) and established (0.96; 0.87 to –1.07) RA. These effects were modified by baseline joint damage (P less than .01), DAS assessing 28 joints (P = .04) in early RA, and disease duration (P = .04) in established RA.
Study details: Analysis of individual patient data from randomized controlled trials comparing TCZ monotherapy and TCZ+MTX combination therapy in patients with early (n=1,089) and established (n=417) RA.
Disclosures: No study sponsor was identified. Some of the investigators reported ties with various pharmaceutical companies.
Source: Verhoeven MMA et al. Arthritis Care Res (Hoboken). 2020 Nov 30. doi: 10.1002/acr.24524.
Key clinical point: Tocilizumab (TCZ) and methotrexate (MTX) combination therapy was generally more effective than TCZ monotherapy in preventing radiographic progression in patients with early and established rheumatoid arthritis. However, effect modifiers were more joint damage or lower disease activity score (DAS) in early RA and longer disease duration in established RA.
Major finding: Overall, TCZ monotherapy was less effective in preventing radiographic progression (relative risk; 95% confidence interval) than TCZ+MTX combination therapy in patients with early (0.96; 0.90 to –1.03) and established (0.96; 0.87 to –1.07) RA. These effects were modified by baseline joint damage (P less than .01), DAS assessing 28 joints (P = .04) in early RA, and disease duration (P = .04) in established RA.
Study details: Analysis of individual patient data from randomized controlled trials comparing TCZ monotherapy and TCZ+MTX combination therapy in patients with early (n=1,089) and established (n=417) RA.
Disclosures: No study sponsor was identified. Some of the investigators reported ties with various pharmaceutical companies.
Source: Verhoeven MMA et al. Arthritis Care Res (Hoboken). 2020 Nov 30. doi: 10.1002/acr.24524.
Key clinical point: Tocilizumab (TCZ) and methotrexate (MTX) combination therapy was generally more effective than TCZ monotherapy in preventing radiographic progression in patients with early and established rheumatoid arthritis. However, effect modifiers were more joint damage or lower disease activity score (DAS) in early RA and longer disease duration in established RA.
Major finding: Overall, TCZ monotherapy was less effective in preventing radiographic progression (relative risk; 95% confidence interval) than TCZ+MTX combination therapy in patients with early (0.96; 0.90 to –1.03) and established (0.96; 0.87 to –1.07) RA. These effects were modified by baseline joint damage (P less than .01), DAS assessing 28 joints (P = .04) in early RA, and disease duration (P = .04) in established RA.
Study details: Analysis of individual patient data from randomized controlled trials comparing TCZ monotherapy and TCZ+MTX combination therapy in patients with early (n=1,089) and established (n=417) RA.
Disclosures: No study sponsor was identified. Some of the investigators reported ties with various pharmaceutical companies.
Source: Verhoeven MMA et al. Arthritis Care Res (Hoboken). 2020 Nov 30. doi: 10.1002/acr.24524.
Prognostic factors for short-term mortality in RA patients admitted to ICU
Key clinical point: Nonuse of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), high updated Charlson’s comorbidity index (CCI), elevated acute physiology and chronic health evaluation (APACHE) II score, and coagulation abnormalities predicted poorer prognosis in patients with rheumatoid arthritis admitted to the intensive care unit (ICU).
Major finding: The 30-day, 90-day, and 1-year mortality rates were 22%, 27%, and 37%, respectively. Factors associated with an increased mortality risk after ICU admission were nonuse of csDMARDs (hazard ratio [HR], 0.413; P = .0229), elevated updated CCI (HR, 1.522; P = .0007), high APACHE II score (HR, 1.045; P = .0008), and extended prothrombin time-international normalized ratio (HR, 2.670; P = .0051). The liver (P = .0004) and renal (P = .0009) disease scores were significantly higher in nonsurvivors vs. survivors.
Study details: The findings are based on a single-center retrospective study of 67 patients (mean age at admission, 68±13 years) with RA (median duration, 14±15 years) admitted to the ICU.
Disclosures: The study was supported by grants from JSPS KAKENHI. The authors declared no conflicts of interest.
Source: Fujiwara T et al. BMC Rheumatol. 2020 Dec 4. doi: 10.1186/s41927-020-00164-1.
Key clinical point: Nonuse of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), high updated Charlson’s comorbidity index (CCI), elevated acute physiology and chronic health evaluation (APACHE) II score, and coagulation abnormalities predicted poorer prognosis in patients with rheumatoid arthritis admitted to the intensive care unit (ICU).
Major finding: The 30-day, 90-day, and 1-year mortality rates were 22%, 27%, and 37%, respectively. Factors associated with an increased mortality risk after ICU admission were nonuse of csDMARDs (hazard ratio [HR], 0.413; P = .0229), elevated updated CCI (HR, 1.522; P = .0007), high APACHE II score (HR, 1.045; P = .0008), and extended prothrombin time-international normalized ratio (HR, 2.670; P = .0051). The liver (P = .0004) and renal (P = .0009) disease scores were significantly higher in nonsurvivors vs. survivors.
Study details: The findings are based on a single-center retrospective study of 67 patients (mean age at admission, 68±13 years) with RA (median duration, 14±15 years) admitted to the ICU.
Disclosures: The study was supported by grants from JSPS KAKENHI. The authors declared no conflicts of interest.
Source: Fujiwara T et al. BMC Rheumatol. 2020 Dec 4. doi: 10.1186/s41927-020-00164-1.
Key clinical point: Nonuse of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), high updated Charlson’s comorbidity index (CCI), elevated acute physiology and chronic health evaluation (APACHE) II score, and coagulation abnormalities predicted poorer prognosis in patients with rheumatoid arthritis admitted to the intensive care unit (ICU).
Major finding: The 30-day, 90-day, and 1-year mortality rates were 22%, 27%, and 37%, respectively. Factors associated with an increased mortality risk after ICU admission were nonuse of csDMARDs (hazard ratio [HR], 0.413; P = .0229), elevated updated CCI (HR, 1.522; P = .0007), high APACHE II score (HR, 1.045; P = .0008), and extended prothrombin time-international normalized ratio (HR, 2.670; P = .0051). The liver (P = .0004) and renal (P = .0009) disease scores were significantly higher in nonsurvivors vs. survivors.
Study details: The findings are based on a single-center retrospective study of 67 patients (mean age at admission, 68±13 years) with RA (median duration, 14±15 years) admitted to the ICU.
Disclosures: The study was supported by grants from JSPS KAKENHI. The authors declared no conflicts of interest.
Source: Fujiwara T et al. BMC Rheumatol. 2020 Dec 4. doi: 10.1186/s41927-020-00164-1.
Gut microbiome influences response to methotrexate in new-onset RA patients
Key clinical point: Nonresponse to methotrexate (MTX) therapy can be predicted based on the gut microbiome of an individual patient newly diagnosed with rheumatoid arthritis.
Major finding: A model developed using machine learning predicted 83.3% of patients who did not respond to MTX and 78% of MTX responders.
Study details: An analysis of DNA from fecal samples obtained from a training cohort of 26 patients with new-onset RA (NORA), a validation cohort of 21 patients with NORA, and a control group of 20 patients with RA.
Disclosures: This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.
Source: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.
Key clinical point: Nonresponse to methotrexate (MTX) therapy can be predicted based on the gut microbiome of an individual patient newly diagnosed with rheumatoid arthritis.
Major finding: A model developed using machine learning predicted 83.3% of patients who did not respond to MTX and 78% of MTX responders.
Study details: An analysis of DNA from fecal samples obtained from a training cohort of 26 patients with new-onset RA (NORA), a validation cohort of 21 patients with NORA, and a control group of 20 patients with RA.
Disclosures: This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.
Source: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.
Key clinical point: Nonresponse to methotrexate (MTX) therapy can be predicted based on the gut microbiome of an individual patient newly diagnosed with rheumatoid arthritis.
Major finding: A model developed using machine learning predicted 83.3% of patients who did not respond to MTX and 78% of MTX responders.
Study details: An analysis of DNA from fecal samples obtained from a training cohort of 26 patients with new-onset RA (NORA), a validation cohort of 21 patients with NORA, and a control group of 20 patients with RA.
Disclosures: This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.
Source: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.