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Systemic sclerosis gastrointestinal symptoms helped by gut microbiota transplant
MADRID – compared with control subjects in a 16-week randomized, double-blind, placebo-controlled pilot study presented at the European Congress of Rheumatology.
The effects were most pronounced on lower GI symptoms, including bloating, diarrhea, and fecal incontinence, with improvement reported by three of five of the patients given the gut microbiota transplant, compared with two of the five patients who received placebo.
“We were surprised by the effect the patients reported, as all had longstanding SSc with GI symptoms,” Anna-Maria Hoffmann-Vold, MD, PhD, of Oslo University Hospital, said in an interview ahead of the congress. “We were especially surprised at the strong effect FMT had on fecal incontinence.”“Patients with systemic sclerosis are very prone to having gastrointestinal involvement – up to 90% of patients have GI symptoms, and it’s associated with very high morbidity and mortality,” she observed during her presentation at the Congress. Despite that, there currently are no disease-modifying treatments that specifically addresses GI involvement in SSc.
It’s been known for a while that patients with SSc have a different intestinal microbiota composition, or dysbiosis, compared with healthy controls, and the possibility of permanent modification of the microbiome through fecal microbiota transplant (FMT) from healthy to ill individuals has become a subject of increased attention in the scientific literature in recent years,. Dr. Hoffmann-Vold said.
In particular, FMT has shown promising results in the treatment of Clostridium difficile infections. While the current study did not focus on mechanistic pathways by which FMT might be exerting its effects, such studies are definitely warranted, she said. “One could speculate that there is a mechanistic link between dysmotility and dysbiosis in SSc, and that the manipulation of gut microbiota with FMT primarily affects motility patterns, which in turn leads to improvement of GI symptoms.”
Together with colleagues at the Oslo University Hospital, Dr. Hoffmann-Vold randomly assigned 10 patients – all women – with limited cutaneous SSc either to treatment with a commercially-available gut microbiota preparation known as anaerobic cultivated human intestinal microbiota (ACHIM) or to placebo. Both ACHIM and placebo were given via gastroduodenoscopy. Their aim was to determine the safety of the approach, as well as to obtain preliminary data on its therapeutic potential.
The UCLA GIT 2.0 score questionnaire was used to assess GI symptoms, with patients defined as responders if they met the questionnaire’s definition of a minimally clinically important difference.
Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16, and safety was assessed by observation, interviews, and a standardized safety form.
Results showed improvement in GI symptoms (total UCLA GIT score) in three of the five patients who received the gut microbiota transplant versus two of the five placebo-treated patients at 16 weeks. Two patients in the active treatment versus one in the placebo group had unchanged symptoms, and one patient in the placebo group had worsening symptoms.
Adverse events associated with treatment were “transient and mild”. However, one procedure-related serious adverse event occurred in a placebo-treated patient, which was a duodenal perforation.
Concluding her presentation, Dr. Hoffman-Vold said: “FMT of commercially-available ACHIM in patients with SSc appeared safe, had beneficial effects on lower GI symptoms, altered gut microbiota composition – richness and diversity – and appeared to affect the mucosal immune system.”
The research team has just received national funding for a larger randomized clinical trial that will involve 70 SSc patients and should start towards the end of the year.
The study was sponsored by Helse Sør-øst and NKS. Dr. Hoffmann-Vold has received research funding, consulting fees, or other remuneration from Boehringer Ingelheim, GlaxoSmithKline, and Actelion. A coauthor is the owner of the company that provided the gut microbiota.
SOURCE: Hoffmann-Vold AM et al., Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.4684 .
MADRID – compared with control subjects in a 16-week randomized, double-blind, placebo-controlled pilot study presented at the European Congress of Rheumatology.
The effects were most pronounced on lower GI symptoms, including bloating, diarrhea, and fecal incontinence, with improvement reported by three of five of the patients given the gut microbiota transplant, compared with two of the five patients who received placebo.
“We were surprised by the effect the patients reported, as all had longstanding SSc with GI symptoms,” Anna-Maria Hoffmann-Vold, MD, PhD, of Oslo University Hospital, said in an interview ahead of the congress. “We were especially surprised at the strong effect FMT had on fecal incontinence.”“Patients with systemic sclerosis are very prone to having gastrointestinal involvement – up to 90% of patients have GI symptoms, and it’s associated with very high morbidity and mortality,” she observed during her presentation at the Congress. Despite that, there currently are no disease-modifying treatments that specifically addresses GI involvement in SSc.
It’s been known for a while that patients with SSc have a different intestinal microbiota composition, or dysbiosis, compared with healthy controls, and the possibility of permanent modification of the microbiome through fecal microbiota transplant (FMT) from healthy to ill individuals has become a subject of increased attention in the scientific literature in recent years,. Dr. Hoffmann-Vold said.
In particular, FMT has shown promising results in the treatment of Clostridium difficile infections. While the current study did not focus on mechanistic pathways by which FMT might be exerting its effects, such studies are definitely warranted, she said. “One could speculate that there is a mechanistic link between dysmotility and dysbiosis in SSc, and that the manipulation of gut microbiota with FMT primarily affects motility patterns, which in turn leads to improvement of GI symptoms.”
Together with colleagues at the Oslo University Hospital, Dr. Hoffmann-Vold randomly assigned 10 patients – all women – with limited cutaneous SSc either to treatment with a commercially-available gut microbiota preparation known as anaerobic cultivated human intestinal microbiota (ACHIM) or to placebo. Both ACHIM and placebo were given via gastroduodenoscopy. Their aim was to determine the safety of the approach, as well as to obtain preliminary data on its therapeutic potential.
The UCLA GIT 2.0 score questionnaire was used to assess GI symptoms, with patients defined as responders if they met the questionnaire’s definition of a minimally clinically important difference.
Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16, and safety was assessed by observation, interviews, and a standardized safety form.
Results showed improvement in GI symptoms (total UCLA GIT score) in three of the five patients who received the gut microbiota transplant versus two of the five placebo-treated patients at 16 weeks. Two patients in the active treatment versus one in the placebo group had unchanged symptoms, and one patient in the placebo group had worsening symptoms.
Adverse events associated with treatment were “transient and mild”. However, one procedure-related serious adverse event occurred in a placebo-treated patient, which was a duodenal perforation.
Concluding her presentation, Dr. Hoffman-Vold said: “FMT of commercially-available ACHIM in patients with SSc appeared safe, had beneficial effects on lower GI symptoms, altered gut microbiota composition – richness and diversity – and appeared to affect the mucosal immune system.”
The research team has just received national funding for a larger randomized clinical trial that will involve 70 SSc patients and should start towards the end of the year.
The study was sponsored by Helse Sør-øst and NKS. Dr. Hoffmann-Vold has received research funding, consulting fees, or other remuneration from Boehringer Ingelheim, GlaxoSmithKline, and Actelion. A coauthor is the owner of the company that provided the gut microbiota.
SOURCE: Hoffmann-Vold AM et al., Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.4684 .
MADRID – compared with control subjects in a 16-week randomized, double-blind, placebo-controlled pilot study presented at the European Congress of Rheumatology.
The effects were most pronounced on lower GI symptoms, including bloating, diarrhea, and fecal incontinence, with improvement reported by three of five of the patients given the gut microbiota transplant, compared with two of the five patients who received placebo.
“We were surprised by the effect the patients reported, as all had longstanding SSc with GI symptoms,” Anna-Maria Hoffmann-Vold, MD, PhD, of Oslo University Hospital, said in an interview ahead of the congress. “We were especially surprised at the strong effect FMT had on fecal incontinence.”“Patients with systemic sclerosis are very prone to having gastrointestinal involvement – up to 90% of patients have GI symptoms, and it’s associated with very high morbidity and mortality,” she observed during her presentation at the Congress. Despite that, there currently are no disease-modifying treatments that specifically addresses GI involvement in SSc.
It’s been known for a while that patients with SSc have a different intestinal microbiota composition, or dysbiosis, compared with healthy controls, and the possibility of permanent modification of the microbiome through fecal microbiota transplant (FMT) from healthy to ill individuals has become a subject of increased attention in the scientific literature in recent years,. Dr. Hoffmann-Vold said.
In particular, FMT has shown promising results in the treatment of Clostridium difficile infections. While the current study did not focus on mechanistic pathways by which FMT might be exerting its effects, such studies are definitely warranted, she said. “One could speculate that there is a mechanistic link between dysmotility and dysbiosis in SSc, and that the manipulation of gut microbiota with FMT primarily affects motility patterns, which in turn leads to improvement of GI symptoms.”
Together with colleagues at the Oslo University Hospital, Dr. Hoffmann-Vold randomly assigned 10 patients – all women – with limited cutaneous SSc either to treatment with a commercially-available gut microbiota preparation known as anaerobic cultivated human intestinal microbiota (ACHIM) or to placebo. Both ACHIM and placebo were given via gastroduodenoscopy. Their aim was to determine the safety of the approach, as well as to obtain preliminary data on its therapeutic potential.
The UCLA GIT 2.0 score questionnaire was used to assess GI symptoms, with patients defined as responders if they met the questionnaire’s definition of a minimally clinically important difference.
Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16, and safety was assessed by observation, interviews, and a standardized safety form.
Results showed improvement in GI symptoms (total UCLA GIT score) in three of the five patients who received the gut microbiota transplant versus two of the five placebo-treated patients at 16 weeks. Two patients in the active treatment versus one in the placebo group had unchanged symptoms, and one patient in the placebo group had worsening symptoms.
Adverse events associated with treatment were “transient and mild”. However, one procedure-related serious adverse event occurred in a placebo-treated patient, which was a duodenal perforation.
Concluding her presentation, Dr. Hoffman-Vold said: “FMT of commercially-available ACHIM in patients with SSc appeared safe, had beneficial effects on lower GI symptoms, altered gut microbiota composition – richness and diversity – and appeared to affect the mucosal immune system.”
The research team has just received national funding for a larger randomized clinical trial that will involve 70 SSc patients and should start towards the end of the year.
The study was sponsored by Helse Sør-øst and NKS. Dr. Hoffmann-Vold has received research funding, consulting fees, or other remuneration from Boehringer Ingelheim, GlaxoSmithKline, and Actelion. A coauthor is the owner of the company that provided the gut microbiota.
SOURCE: Hoffmann-Vold AM et al., Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.4684 .
REPORTING FROM THE EULAR 2019 CONGRESS
Retention rates comparable for biosimilars, original drug in spondyloarthritis
MADRID – judging from data drawn from registries in five Scandinavian countries in a study that evaluated retention rates after 1 year of therapy.
Bente Glintborg, MD, PhD, from the Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, explains in a video interview that the indication provided to biosimilars for spondyloarthritis was extended from comparisons conducted in rheumatoid arthritis (RA).
In the absence of a randomized trial in spondyloarthritis, she suggested that this comparison might be the best opportunity to evaluate whether biosimilars perform as well as their biologic originator. This is an important aim based on the theoretical possibility that equivalence in RA does not translate into equivalence in other rheumatic conditions where biologics are indicated.
As she explains, 1,015 biologic-naïve patients initiating etanercept, a tumor necrosis factor (TNF) inhibitor, or a biosimilar were assessed at baseline and at the end of 1 year of therapy. The patients were enrolled in biologic registries maintained in Denmark, Finland, Iceland, Norway, or Sweden.
Retention rates at 1 year were numerically lower on etanercept than the biosimilars, but the difference was not significant (66% vs. 73%; P = 0.18). There also were no significant differences between the biosimilars and etanercept when disease activity was compared at 6 months.
Retention rates are a reasonable surrogate for both efficacy and tolerability based on the expectation that more patients would switch or discontinue agents in the event of lack of efficacy or unacceptable side effects, Dr. Glintborg said at the European Congress of Rheumatology.
In this interview, she notes that a similar study from the Nordic registries led by a coinvestigator also showed equivalent retention rates among spondyloarthritis patients when biosimilars and infliximab were compared at 2 years.
Dr. Glintborg received research support from Biogen, Pfizer, and Abbievie.
MADRID – judging from data drawn from registries in five Scandinavian countries in a study that evaluated retention rates after 1 year of therapy.
Bente Glintborg, MD, PhD, from the Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, explains in a video interview that the indication provided to biosimilars for spondyloarthritis was extended from comparisons conducted in rheumatoid arthritis (RA).
In the absence of a randomized trial in spondyloarthritis, she suggested that this comparison might be the best opportunity to evaluate whether biosimilars perform as well as their biologic originator. This is an important aim based on the theoretical possibility that equivalence in RA does not translate into equivalence in other rheumatic conditions where biologics are indicated.
As she explains, 1,015 biologic-naïve patients initiating etanercept, a tumor necrosis factor (TNF) inhibitor, or a biosimilar were assessed at baseline and at the end of 1 year of therapy. The patients were enrolled in biologic registries maintained in Denmark, Finland, Iceland, Norway, or Sweden.
Retention rates at 1 year were numerically lower on etanercept than the biosimilars, but the difference was not significant (66% vs. 73%; P = 0.18). There also were no significant differences between the biosimilars and etanercept when disease activity was compared at 6 months.
Retention rates are a reasonable surrogate for both efficacy and tolerability based on the expectation that more patients would switch or discontinue agents in the event of lack of efficacy or unacceptable side effects, Dr. Glintborg said at the European Congress of Rheumatology.
In this interview, she notes that a similar study from the Nordic registries led by a coinvestigator also showed equivalent retention rates among spondyloarthritis patients when biosimilars and infliximab were compared at 2 years.
Dr. Glintborg received research support from Biogen, Pfizer, and Abbievie.
MADRID – judging from data drawn from registries in five Scandinavian countries in a study that evaluated retention rates after 1 year of therapy.
Bente Glintborg, MD, PhD, from the Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, explains in a video interview that the indication provided to biosimilars for spondyloarthritis was extended from comparisons conducted in rheumatoid arthritis (RA).
In the absence of a randomized trial in spondyloarthritis, she suggested that this comparison might be the best opportunity to evaluate whether biosimilars perform as well as their biologic originator. This is an important aim based on the theoretical possibility that equivalence in RA does not translate into equivalence in other rheumatic conditions where biologics are indicated.
As she explains, 1,015 biologic-naïve patients initiating etanercept, a tumor necrosis factor (TNF) inhibitor, or a biosimilar were assessed at baseline and at the end of 1 year of therapy. The patients were enrolled in biologic registries maintained in Denmark, Finland, Iceland, Norway, or Sweden.
Retention rates at 1 year were numerically lower on etanercept than the biosimilars, but the difference was not significant (66% vs. 73%; P = 0.18). There also were no significant differences between the biosimilars and etanercept when disease activity was compared at 6 months.
Retention rates are a reasonable surrogate for both efficacy and tolerability based on the expectation that more patients would switch or discontinue agents in the event of lack of efficacy or unacceptable side effects, Dr. Glintborg said at the European Congress of Rheumatology.
In this interview, she notes that a similar study from the Nordic registries led by a coinvestigator also showed equivalent retention rates among spondyloarthritis patients when biosimilars and infliximab were compared at 2 years.
Dr. Glintborg received research support from Biogen, Pfizer, and Abbievie.
REPORTING FROM EULAR 2019 Congress
Video program engages patients in treat-to-target concept
MADRID – according to data generated from a randomized trial.
One of the major goals of the video program is to inform patients about the treat-to-target concept of RA management, explained Maria I. Danila, MD, a rheumatologist at the University of Alabama at Birmingham.
Although physicians know this to be a guiding tenet for RA management, she explains in this video interview that 50% or more of patients are unaware of this therapeutic goal.
For patients who resist treatment escalation for fear of side effects, this lack of awareness might provide one explanation for failing to adhere to guideline-recommended therapy, Dr. Danila said at the European Congress of Rheumatology. She believes that patients need more information about the potential for treatment escalation to improve function.
To address this issue, a short video was developed to explain the treat-to-target concept. It was then tested in a randomized trial. Those who viewed the video expressed greater willingness to change intervention on the advice of their rheumatologist relative to those who did not (P = 0.01).
Further studies are planned, including studies to test whether willingness to escalate treatment results in better outcomes and whether linking patient behavioral goals such as being able to play golf again will enhance treatment adherence. Dr. Danila envisions wide distribution of this video if further studies demonstrate that it helps patients cooperate with treatment escalation when needed.
Dr. Danila received research support from Pfizer.
MADRID – according to data generated from a randomized trial.
One of the major goals of the video program is to inform patients about the treat-to-target concept of RA management, explained Maria I. Danila, MD, a rheumatologist at the University of Alabama at Birmingham.
Although physicians know this to be a guiding tenet for RA management, she explains in this video interview that 50% or more of patients are unaware of this therapeutic goal.
For patients who resist treatment escalation for fear of side effects, this lack of awareness might provide one explanation for failing to adhere to guideline-recommended therapy, Dr. Danila said at the European Congress of Rheumatology. She believes that patients need more information about the potential for treatment escalation to improve function.
To address this issue, a short video was developed to explain the treat-to-target concept. It was then tested in a randomized trial. Those who viewed the video expressed greater willingness to change intervention on the advice of their rheumatologist relative to those who did not (P = 0.01).
Further studies are planned, including studies to test whether willingness to escalate treatment results in better outcomes and whether linking patient behavioral goals such as being able to play golf again will enhance treatment adherence. Dr. Danila envisions wide distribution of this video if further studies demonstrate that it helps patients cooperate with treatment escalation when needed.
Dr. Danila received research support from Pfizer.
MADRID – according to data generated from a randomized trial.
One of the major goals of the video program is to inform patients about the treat-to-target concept of RA management, explained Maria I. Danila, MD, a rheumatologist at the University of Alabama at Birmingham.
Although physicians know this to be a guiding tenet for RA management, she explains in this video interview that 50% or more of patients are unaware of this therapeutic goal.
For patients who resist treatment escalation for fear of side effects, this lack of awareness might provide one explanation for failing to adhere to guideline-recommended therapy, Dr. Danila said at the European Congress of Rheumatology. She believes that patients need more information about the potential for treatment escalation to improve function.
To address this issue, a short video was developed to explain the treat-to-target concept. It was then tested in a randomized trial. Those who viewed the video expressed greater willingness to change intervention on the advice of their rheumatologist relative to those who did not (P = 0.01).
Further studies are planned, including studies to test whether willingness to escalate treatment results in better outcomes and whether linking patient behavioral goals such as being able to play golf again will enhance treatment adherence. Dr. Danila envisions wide distribution of this video if further studies demonstrate that it helps patients cooperate with treatment escalation when needed.
Dr. Danila received research support from Pfizer.
REPORTING FROM EULAR 2019 Congress
Cardiovascular events in U.S. RA patients fall to non-RA level
MADRID – U.S. patients with rheumatoid arthritis stopped having an excess of cardiovascular disease events during the 2000s.
During both the 1980s and 1990s, patients with rheumatoid arthritis (RA) residing in a 27-county region in southeastern Minnesota and northwestern Wisconsin had cardiovascular disease event rates that were more than twice the rates in similar adults without RA, but that changed during the 2000s, Elena Myasoedova, MD, said in a poster she presented at the European Congress of Rheumatology. During 2000-2009, RA patients enrolled in the Rochester (Minn.) Epidemiology Project had an incidence of cardiovascular disease events at a rate that was 12% lower, compared with matched adults without RA who were also enrolled in the same regional database, reported Dr. Myasoedova, a rheumatologist at the Mayo Clinic in Rochester, and her associates.
“We hypothesize that improved management of RA, including implementation of a treat-to-target strategy and the introduction of biological drugs could have influenced this, as well as increased awareness of and improved prevention of cardiovascular disease,” Dr. Myasoedova said in an interview. The findings “give us a hint that tight control of RA disease activity is also likely to help cardiovascular disease burden.”
She and her associates identified 906 people enrolled in the Rochester Epidemiology Project who had incident RA based on the 1987 criteria of the American College of Rheumatology and matched them by age, sex, and index year with 905 people in the registry without RA. These cohorts included roughly 200 people from each subgroup tracked during the 1980s, 300 from each subgroup tracked during the 1990s, and about 400 in each subgroup tracked during the 2000s. They averaged about 56 years old, and about two-thirds were women.
During the 1980s, the cumulative incidence of nonfatal MI, nonfatal stroke, or cardiovascular disease (CVD) death was 2.11-fold more common among the RA patients than in the matched controls without RA, and during the 1990s this ratio showed a 2.13-fold excess of CVD events among the RA patients. The between-group differences in both decades were statistically significant. During the 2000s, the RA patients actually had a nominally lower rate of CVD events, at 0.88 times the rate of the controls, a difference that was not statistically significant.
Dr. Myasoedova and her associates had previously reported a similar finding in an analysis that used a smaller number of people and focused exclusively on rates of CVD (J Rheumatol. 2017 Jun;44[6]:732-9).
A few factors limit the generalizability of the finding, Dr. Myasoedova cautioned. First, the population studied was about 90% white. Also, people in the Rochester Epidemiology Project receive their medical care from clinicians at the Mayo Clinic or an affiliated hospital in the region covered by the Project.
“These data are from a large, tertiary care center,” and so the findings are most directly applicable to patients who receive medical care in a similar setting that provides guideline-directed management of both RA and CVD risk.
A long-standing hypothesis is that CVD has an inflammatory component. These data support that concept by suggesting that when inflammatory disease is well controlled in RA patients, their CVD risk drops, Dr. Myasoedova said. “CVD has been seen as the number one comorbidity for RA patients, and it remains that way, but it’s very reassuring that the CVD rate has improved. It shows we’re doing something right.”
The study received no commercial funding. Dr. Myasoedova had no relevant disclosures.
SOURCE: Myasoedova E et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):1024-5. Abstract FRI0654. DOI: 10.1136/annrheumdis-2019-eular.4996.
MADRID – U.S. patients with rheumatoid arthritis stopped having an excess of cardiovascular disease events during the 2000s.
During both the 1980s and 1990s, patients with rheumatoid arthritis (RA) residing in a 27-county region in southeastern Minnesota and northwestern Wisconsin had cardiovascular disease event rates that were more than twice the rates in similar adults without RA, but that changed during the 2000s, Elena Myasoedova, MD, said in a poster she presented at the European Congress of Rheumatology. During 2000-2009, RA patients enrolled in the Rochester (Minn.) Epidemiology Project had an incidence of cardiovascular disease events at a rate that was 12% lower, compared with matched adults without RA who were also enrolled in the same regional database, reported Dr. Myasoedova, a rheumatologist at the Mayo Clinic in Rochester, and her associates.
“We hypothesize that improved management of RA, including implementation of a treat-to-target strategy and the introduction of biological drugs could have influenced this, as well as increased awareness of and improved prevention of cardiovascular disease,” Dr. Myasoedova said in an interview. The findings “give us a hint that tight control of RA disease activity is also likely to help cardiovascular disease burden.”
She and her associates identified 906 people enrolled in the Rochester Epidemiology Project who had incident RA based on the 1987 criteria of the American College of Rheumatology and matched them by age, sex, and index year with 905 people in the registry without RA. These cohorts included roughly 200 people from each subgroup tracked during the 1980s, 300 from each subgroup tracked during the 1990s, and about 400 in each subgroup tracked during the 2000s. They averaged about 56 years old, and about two-thirds were women.
During the 1980s, the cumulative incidence of nonfatal MI, nonfatal stroke, or cardiovascular disease (CVD) death was 2.11-fold more common among the RA patients than in the matched controls without RA, and during the 1990s this ratio showed a 2.13-fold excess of CVD events among the RA patients. The between-group differences in both decades were statistically significant. During the 2000s, the RA patients actually had a nominally lower rate of CVD events, at 0.88 times the rate of the controls, a difference that was not statistically significant.
Dr. Myasoedova and her associates had previously reported a similar finding in an analysis that used a smaller number of people and focused exclusively on rates of CVD (J Rheumatol. 2017 Jun;44[6]:732-9).
A few factors limit the generalizability of the finding, Dr. Myasoedova cautioned. First, the population studied was about 90% white. Also, people in the Rochester Epidemiology Project receive their medical care from clinicians at the Mayo Clinic or an affiliated hospital in the region covered by the Project.
“These data are from a large, tertiary care center,” and so the findings are most directly applicable to patients who receive medical care in a similar setting that provides guideline-directed management of both RA and CVD risk.
A long-standing hypothesis is that CVD has an inflammatory component. These data support that concept by suggesting that when inflammatory disease is well controlled in RA patients, their CVD risk drops, Dr. Myasoedova said. “CVD has been seen as the number one comorbidity for RA patients, and it remains that way, but it’s very reassuring that the CVD rate has improved. It shows we’re doing something right.”
The study received no commercial funding. Dr. Myasoedova had no relevant disclosures.
SOURCE: Myasoedova E et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):1024-5. Abstract FRI0654. DOI: 10.1136/annrheumdis-2019-eular.4996.
MADRID – U.S. patients with rheumatoid arthritis stopped having an excess of cardiovascular disease events during the 2000s.
During both the 1980s and 1990s, patients with rheumatoid arthritis (RA) residing in a 27-county region in southeastern Minnesota and northwestern Wisconsin had cardiovascular disease event rates that were more than twice the rates in similar adults without RA, but that changed during the 2000s, Elena Myasoedova, MD, said in a poster she presented at the European Congress of Rheumatology. During 2000-2009, RA patients enrolled in the Rochester (Minn.) Epidemiology Project had an incidence of cardiovascular disease events at a rate that was 12% lower, compared with matched adults without RA who were also enrolled in the same regional database, reported Dr. Myasoedova, a rheumatologist at the Mayo Clinic in Rochester, and her associates.
“We hypothesize that improved management of RA, including implementation of a treat-to-target strategy and the introduction of biological drugs could have influenced this, as well as increased awareness of and improved prevention of cardiovascular disease,” Dr. Myasoedova said in an interview. The findings “give us a hint that tight control of RA disease activity is also likely to help cardiovascular disease burden.”
She and her associates identified 906 people enrolled in the Rochester Epidemiology Project who had incident RA based on the 1987 criteria of the American College of Rheumatology and matched them by age, sex, and index year with 905 people in the registry without RA. These cohorts included roughly 200 people from each subgroup tracked during the 1980s, 300 from each subgroup tracked during the 1990s, and about 400 in each subgroup tracked during the 2000s. They averaged about 56 years old, and about two-thirds were women.
During the 1980s, the cumulative incidence of nonfatal MI, nonfatal stroke, or cardiovascular disease (CVD) death was 2.11-fold more common among the RA patients than in the matched controls without RA, and during the 1990s this ratio showed a 2.13-fold excess of CVD events among the RA patients. The between-group differences in both decades were statistically significant. During the 2000s, the RA patients actually had a nominally lower rate of CVD events, at 0.88 times the rate of the controls, a difference that was not statistically significant.
Dr. Myasoedova and her associates had previously reported a similar finding in an analysis that used a smaller number of people and focused exclusively on rates of CVD (J Rheumatol. 2017 Jun;44[6]:732-9).
A few factors limit the generalizability of the finding, Dr. Myasoedova cautioned. First, the population studied was about 90% white. Also, people in the Rochester Epidemiology Project receive their medical care from clinicians at the Mayo Clinic or an affiliated hospital in the region covered by the Project.
“These data are from a large, tertiary care center,” and so the findings are most directly applicable to patients who receive medical care in a similar setting that provides guideline-directed management of both RA and CVD risk.
A long-standing hypothesis is that CVD has an inflammatory component. These data support that concept by suggesting that when inflammatory disease is well controlled in RA patients, their CVD risk drops, Dr. Myasoedova said. “CVD has been seen as the number one comorbidity for RA patients, and it remains that way, but it’s very reassuring that the CVD rate has improved. It shows we’re doing something right.”
The study received no commercial funding. Dr. Myasoedova had no relevant disclosures.
SOURCE: Myasoedova E et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):1024-5. Abstract FRI0654. DOI: 10.1136/annrheumdis-2019-eular.4996.
REPORTING FROM EULAR 2019 CONGRESS
Sequential dermoscopy imaging helps find melanomas early
WAIKOLOA, HAWAII – Sequential dermoscopy imaging (SDI) is a valuable strategy for diagnosing melanomas early and with better sensitivity and specificity, compared with biopsy decisions based solely on the ugly duckling sign, the ABCDs of melanoma, or other aspects of lesion morphology, Michael A. Marchetti, MD, said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
SDI entails obtaining repeated dermoscopy images over time in order to detect subtle changes. It is typically done short term, over the course of 3-4 months, or longer term, over a period of 6 months to years, with long-term SDI being reserved for monitoring of less suspicious lesions, often in patients with an atypical mole syndrome.
SDI improves diagnostic specificity by dramatically reducing excision of benign pigmented lesions: in one large Belgian study, by up to 75% (Br J Dermatol. 2012 Oct;167[4]:778-86).
Short-term SDI also improves diagnostic sensitivity. That’s because it enables early identification of clinically featureless melanomas that are detected solely based upon change over a 3-month follow-up period. The operative principle here is that 93%-96% of melanomas will show change on dermoscopy within 3 months, while 99% of unchanged melanocytic lesions are benign. Since 16% of benign nevi will change within 3 months, that means 10%-30% of changed lesions are melanomas.
“If there is any change – it doesn’t matter what the change is, but the two images look different – that should lead to a biopsy,” explained Dr. Marchetti, a dermatologist at Memorial Sloan Kettering Cancer Center, New York.
As a result of this improved sensitivity and specificity, SDI has been shown to reduce the cost per melanoma diagnosis by about 40% (PLoS One. 2014 Oct 14;9[10]:e109339. doi: 10.1371/journal.pone.0109339).
Dr. Marchetti considers SDI a second-level diagnostic test for individual equivocal lesions. His first-level diagnostic tool is total-body photography.
SDI needs to be done by scrupulous examination of digital photographic images side-by-side on a computer monitor. A basic rule of SDI is that it should never be used to monitor raised or palpable lesions.
“The only thing you can monitor is something that’s flat,” he stressed.
Nor should SDI be used to monitor lesions with a peripheral globular pattern. And very slow-growing melanomas could potentially be missed by short-term SDI, so suspected lentigo maligna should be monitored for a minimum of 12 months, according to Dr. Marchetti.
Not every patient with an equivocal melanocytic lesion is a good candidate for SDI. It’s a monitoring strategy that should be reserved for reliable patients who will come back in 3 months. “If a patient doesn’t come back I take that very seriously. We call or send a letter,” Dr. Marchetti said.
Moreover, even in a patient who is a good candidate for SDI, he always offers the option of biopsy today rather than short-term monitoring.
SDI employed in conjunction with total-body photography is an extremely effective means of monitoring patients at very high risk for melanoma, Dr. Marchetti said. The power of this combination was illustrated in a prospective Australian study of 311 patients with a history of invasive melanoma plus either a high-risk genetic mutation or a strong family history. During a median follow-up of 3.5 years, 75 melanomas were detected, 14 of them at the baseline visit. The median thickness of melanomas detected post baseline was in situ. Thirty-nine percent of melanomas were detected using SDI and 38% via total body photography. Roughly one in five biopsied melanocytic lesions proved to be melanoma. Of note, five of the melanomas were more than 1 mm in Breslow thickness: Three of them were histologically desmoplastic, and the other two had nodular components (JAMA Dermatol. 2014 Aug;150(8):819-27).
For dermatologists who need to brush up on their dermoscopy skills, Dr. Marchetti recommended dermoscopedia as a useful, free resource.
Legal implications of monitoring via photography
“People often get worked up about this, but I’m not aware of a lawsuit alleging missed melanoma using baseline photography as evidence. And patients, in my experience, are universally appreciative of the use of imaging, although admittedly my experience is biased because people generally come to me for imaging,” Dr. Marchetti said.
He makes a point of telling every patient who opts for short-term SDI that, although the lesion has no features of concern now, it’s important to return promptly for reexamination should any changes occur.
Dr. Marchetti reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Sequential dermoscopy imaging (SDI) is a valuable strategy for diagnosing melanomas early and with better sensitivity and specificity, compared with biopsy decisions based solely on the ugly duckling sign, the ABCDs of melanoma, or other aspects of lesion morphology, Michael A. Marchetti, MD, said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
SDI entails obtaining repeated dermoscopy images over time in order to detect subtle changes. It is typically done short term, over the course of 3-4 months, or longer term, over a period of 6 months to years, with long-term SDI being reserved for monitoring of less suspicious lesions, often in patients with an atypical mole syndrome.
SDI improves diagnostic specificity by dramatically reducing excision of benign pigmented lesions: in one large Belgian study, by up to 75% (Br J Dermatol. 2012 Oct;167[4]:778-86).
Short-term SDI also improves diagnostic sensitivity. That’s because it enables early identification of clinically featureless melanomas that are detected solely based upon change over a 3-month follow-up period. The operative principle here is that 93%-96% of melanomas will show change on dermoscopy within 3 months, while 99% of unchanged melanocytic lesions are benign. Since 16% of benign nevi will change within 3 months, that means 10%-30% of changed lesions are melanomas.
“If there is any change – it doesn’t matter what the change is, but the two images look different – that should lead to a biopsy,” explained Dr. Marchetti, a dermatologist at Memorial Sloan Kettering Cancer Center, New York.
As a result of this improved sensitivity and specificity, SDI has been shown to reduce the cost per melanoma diagnosis by about 40% (PLoS One. 2014 Oct 14;9[10]:e109339. doi: 10.1371/journal.pone.0109339).
Dr. Marchetti considers SDI a second-level diagnostic test for individual equivocal lesions. His first-level diagnostic tool is total-body photography.
SDI needs to be done by scrupulous examination of digital photographic images side-by-side on a computer monitor. A basic rule of SDI is that it should never be used to monitor raised or palpable lesions.
“The only thing you can monitor is something that’s flat,” he stressed.
Nor should SDI be used to monitor lesions with a peripheral globular pattern. And very slow-growing melanomas could potentially be missed by short-term SDI, so suspected lentigo maligna should be monitored for a minimum of 12 months, according to Dr. Marchetti.
Not every patient with an equivocal melanocytic lesion is a good candidate for SDI. It’s a monitoring strategy that should be reserved for reliable patients who will come back in 3 months. “If a patient doesn’t come back I take that very seriously. We call or send a letter,” Dr. Marchetti said.
Moreover, even in a patient who is a good candidate for SDI, he always offers the option of biopsy today rather than short-term monitoring.
SDI employed in conjunction with total-body photography is an extremely effective means of monitoring patients at very high risk for melanoma, Dr. Marchetti said. The power of this combination was illustrated in a prospective Australian study of 311 patients with a history of invasive melanoma plus either a high-risk genetic mutation or a strong family history. During a median follow-up of 3.5 years, 75 melanomas were detected, 14 of them at the baseline visit. The median thickness of melanomas detected post baseline was in situ. Thirty-nine percent of melanomas were detected using SDI and 38% via total body photography. Roughly one in five biopsied melanocytic lesions proved to be melanoma. Of note, five of the melanomas were more than 1 mm in Breslow thickness: Three of them were histologically desmoplastic, and the other two had nodular components (JAMA Dermatol. 2014 Aug;150(8):819-27).
For dermatologists who need to brush up on their dermoscopy skills, Dr. Marchetti recommended dermoscopedia as a useful, free resource.
Legal implications of monitoring via photography
“People often get worked up about this, but I’m not aware of a lawsuit alleging missed melanoma using baseline photography as evidence. And patients, in my experience, are universally appreciative of the use of imaging, although admittedly my experience is biased because people generally come to me for imaging,” Dr. Marchetti said.
He makes a point of telling every patient who opts for short-term SDI that, although the lesion has no features of concern now, it’s important to return promptly for reexamination should any changes occur.
Dr. Marchetti reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Sequential dermoscopy imaging (SDI) is a valuable strategy for diagnosing melanomas early and with better sensitivity and specificity, compared with biopsy decisions based solely on the ugly duckling sign, the ABCDs of melanoma, or other aspects of lesion morphology, Michael A. Marchetti, MD, said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
SDI entails obtaining repeated dermoscopy images over time in order to detect subtle changes. It is typically done short term, over the course of 3-4 months, or longer term, over a period of 6 months to years, with long-term SDI being reserved for monitoring of less suspicious lesions, often in patients with an atypical mole syndrome.
SDI improves diagnostic specificity by dramatically reducing excision of benign pigmented lesions: in one large Belgian study, by up to 75% (Br J Dermatol. 2012 Oct;167[4]:778-86).
Short-term SDI also improves diagnostic sensitivity. That’s because it enables early identification of clinically featureless melanomas that are detected solely based upon change over a 3-month follow-up period. The operative principle here is that 93%-96% of melanomas will show change on dermoscopy within 3 months, while 99% of unchanged melanocytic lesions are benign. Since 16% of benign nevi will change within 3 months, that means 10%-30% of changed lesions are melanomas.
“If there is any change – it doesn’t matter what the change is, but the two images look different – that should lead to a biopsy,” explained Dr. Marchetti, a dermatologist at Memorial Sloan Kettering Cancer Center, New York.
As a result of this improved sensitivity and specificity, SDI has been shown to reduce the cost per melanoma diagnosis by about 40% (PLoS One. 2014 Oct 14;9[10]:e109339. doi: 10.1371/journal.pone.0109339).
Dr. Marchetti considers SDI a second-level diagnostic test for individual equivocal lesions. His first-level diagnostic tool is total-body photography.
SDI needs to be done by scrupulous examination of digital photographic images side-by-side on a computer monitor. A basic rule of SDI is that it should never be used to monitor raised or palpable lesions.
“The only thing you can monitor is something that’s flat,” he stressed.
Nor should SDI be used to monitor lesions with a peripheral globular pattern. And very slow-growing melanomas could potentially be missed by short-term SDI, so suspected lentigo maligna should be monitored for a minimum of 12 months, according to Dr. Marchetti.
Not every patient with an equivocal melanocytic lesion is a good candidate for SDI. It’s a monitoring strategy that should be reserved for reliable patients who will come back in 3 months. “If a patient doesn’t come back I take that very seriously. We call or send a letter,” Dr. Marchetti said.
Moreover, even in a patient who is a good candidate for SDI, he always offers the option of biopsy today rather than short-term monitoring.
SDI employed in conjunction with total-body photography is an extremely effective means of monitoring patients at very high risk for melanoma, Dr. Marchetti said. The power of this combination was illustrated in a prospective Australian study of 311 patients with a history of invasive melanoma plus either a high-risk genetic mutation or a strong family history. During a median follow-up of 3.5 years, 75 melanomas were detected, 14 of them at the baseline visit. The median thickness of melanomas detected post baseline was in situ. Thirty-nine percent of melanomas were detected using SDI and 38% via total body photography. Roughly one in five biopsied melanocytic lesions proved to be melanoma. Of note, five of the melanomas were more than 1 mm in Breslow thickness: Three of them were histologically desmoplastic, and the other two had nodular components (JAMA Dermatol. 2014 Aug;150(8):819-27).
For dermatologists who need to brush up on their dermoscopy skills, Dr. Marchetti recommended dermoscopedia as a useful, free resource.
Legal implications of monitoring via photography
“People often get worked up about this, but I’m not aware of a lawsuit alleging missed melanoma using baseline photography as evidence. And patients, in my experience, are universally appreciative of the use of imaging, although admittedly my experience is biased because people generally come to me for imaging,” Dr. Marchetti said.
He makes a point of telling every patient who opts for short-term SDI that, although the lesion has no features of concern now, it’s important to return promptly for reexamination should any changes occur.
Dr. Marchetti reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
Rapid assay distinguishes viral from bacterial infection
LJUBLJANA, SLOVENIA – assessing RNA expression of a single patient gene, according to a proof-of-concept study presented by Ruth Barral-Arca at the annual meeting of the European Society for Paediatric Infectious Diseases.
The gene of interest – IFI44L – is entwined in a child’s response to infection. It’s upregulated in the presence of viral infection and suppressed in bacterial infection, explained Ms. Barral-Arca, a PhD student at the University of Santiago de Compostela (Spain).
This investigational real-time PCR assay could provide a major advance over current routine practice, which is to admit a sick febrile child to the hospital, order bacterial cultures, and start parenteral antibiotics presumptively while awaiting the culture results, which usually don’t come back for more than 24 hours. This practice is a step backwards in terms of antibiotic stewardship, because the majority of febrile children have a self-resolving viral infection.
“This is a big problem because a lot of children with viral infections are inappropriately given antibiotics, leading to antimicrobial resistance,” she noted.
Also, misleadingly false-negative bacterial cultures can occur if the causative pathogen wasn’t included in the test, the infection is in a nonaccessible site, or the child has recently been on antibiotics.
All of these shortcomings have led to a new diagnostic strategy based upon measuring the pattern of key host genes upregulated or suppressed during the inflammatory response.
“We’ve seen that, instead of analyzing the bugs, analyzing the host transcriptome response during infection is proving to be a promising tool for disease biomarker identification. And it’s faster. An early differentiation between viral and bacterial patients will help improve triage in emergency departments, decrease the misuse of antibiotics, and guide clinics to a more precise diagnosis. A lot of big hospitals are already doing PCR. They could quickly adopt this kind of analysis,” Ms. Barral-Arca continued.
She presented a pilot study in which the assay was put to the test using multiple blood samples from 14 febrile infants and children up to 6 years of age with microbiologically confirmed bacterial infection, 11 febrile children with confirmed viral infection, and 10 healthy controls.
“I know the numbers seem small, but we did a sample-size power calculation and it’s just fine,” according to the researcher.
The initial study goal was to confirm earlier promising findings from a study of 370 febrile children in the United Kingdom, Spain, and the United States, conducted by the Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium, a study in which several of Ms. Barral-Arca’s senior coinvestigators participated. The IRIS investigators demonstrated that the combined expression pattern of two genes – IFI44L and FAM89A – distinguished the bacterial from viral infections with impressive sensitivity and specificity (JAMA. 2016 Aug 23-30;316[8]:835-45).
The two-gene signature performed similarly well in Ms. Barral-Arca’s study. However, when she and her coinvestigators tested the discriminatory power of the two genes individually, they got a surprise: The real-time PCR analysis assessing expression of IFI44L alone performed even better than the two-gene combination, discriminating viral from bacterial infections with 91% sensitivity, 93% specificity, and an area under the curve of 94%. In contrast, the two-gene signature based upon IFI44L and FAM89A had a sensitivity of 91%, a specificity of 86%, and an area under the curve of 92%. While those differences in performance are small, a single-gene assay saves time, work, and cost, according to Ms. Barral-Arca.
Her group then validated their findings regarding the performance of the IFI44L single-gene signature in two independent cohorts: stored blood samples from the children in the earlier IRIS study, and a group of children with diarrhea of viral or bacterial etiology.
“One gene seems to be enough,” she said. “We have demonstrated in a real-life scenario that host gene expression microarray data can be successfully translated into a fast, highly accurate, and relatively inexpensive in vitro assay that could be implemented in the clinical routine.”
Planned future work includes investigation of how the gene expression evolves over time from fever onset, the possible utility of the assay in noninfectious febrile illnesses such as rheumatoid arthritis, and whether the test discriminates viral from bacterial infection in adults.
Ms. Barral-Arca reported having no financial conflicts regarding her study, supported by institutional funding.
LJUBLJANA, SLOVENIA – assessing RNA expression of a single patient gene, according to a proof-of-concept study presented by Ruth Barral-Arca at the annual meeting of the European Society for Paediatric Infectious Diseases.
The gene of interest – IFI44L – is entwined in a child’s response to infection. It’s upregulated in the presence of viral infection and suppressed in bacterial infection, explained Ms. Barral-Arca, a PhD student at the University of Santiago de Compostela (Spain).
This investigational real-time PCR assay could provide a major advance over current routine practice, which is to admit a sick febrile child to the hospital, order bacterial cultures, and start parenteral antibiotics presumptively while awaiting the culture results, which usually don’t come back for more than 24 hours. This practice is a step backwards in terms of antibiotic stewardship, because the majority of febrile children have a self-resolving viral infection.
“This is a big problem because a lot of children with viral infections are inappropriately given antibiotics, leading to antimicrobial resistance,” she noted.
Also, misleadingly false-negative bacterial cultures can occur if the causative pathogen wasn’t included in the test, the infection is in a nonaccessible site, or the child has recently been on antibiotics.
All of these shortcomings have led to a new diagnostic strategy based upon measuring the pattern of key host genes upregulated or suppressed during the inflammatory response.
“We’ve seen that, instead of analyzing the bugs, analyzing the host transcriptome response during infection is proving to be a promising tool for disease biomarker identification. And it’s faster. An early differentiation between viral and bacterial patients will help improve triage in emergency departments, decrease the misuse of antibiotics, and guide clinics to a more precise diagnosis. A lot of big hospitals are already doing PCR. They could quickly adopt this kind of analysis,” Ms. Barral-Arca continued.
She presented a pilot study in which the assay was put to the test using multiple blood samples from 14 febrile infants and children up to 6 years of age with microbiologically confirmed bacterial infection, 11 febrile children with confirmed viral infection, and 10 healthy controls.
“I know the numbers seem small, but we did a sample-size power calculation and it’s just fine,” according to the researcher.
The initial study goal was to confirm earlier promising findings from a study of 370 febrile children in the United Kingdom, Spain, and the United States, conducted by the Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium, a study in which several of Ms. Barral-Arca’s senior coinvestigators participated. The IRIS investigators demonstrated that the combined expression pattern of two genes – IFI44L and FAM89A – distinguished the bacterial from viral infections with impressive sensitivity and specificity (JAMA. 2016 Aug 23-30;316[8]:835-45).
The two-gene signature performed similarly well in Ms. Barral-Arca’s study. However, when she and her coinvestigators tested the discriminatory power of the two genes individually, they got a surprise: The real-time PCR analysis assessing expression of IFI44L alone performed even better than the two-gene combination, discriminating viral from bacterial infections with 91% sensitivity, 93% specificity, and an area under the curve of 94%. In contrast, the two-gene signature based upon IFI44L and FAM89A had a sensitivity of 91%, a specificity of 86%, and an area under the curve of 92%. While those differences in performance are small, a single-gene assay saves time, work, and cost, according to Ms. Barral-Arca.
Her group then validated their findings regarding the performance of the IFI44L single-gene signature in two independent cohorts: stored blood samples from the children in the earlier IRIS study, and a group of children with diarrhea of viral or bacterial etiology.
“One gene seems to be enough,” she said. “We have demonstrated in a real-life scenario that host gene expression microarray data can be successfully translated into a fast, highly accurate, and relatively inexpensive in vitro assay that could be implemented in the clinical routine.”
Planned future work includes investigation of how the gene expression evolves over time from fever onset, the possible utility of the assay in noninfectious febrile illnesses such as rheumatoid arthritis, and whether the test discriminates viral from bacterial infection in adults.
Ms. Barral-Arca reported having no financial conflicts regarding her study, supported by institutional funding.
LJUBLJANA, SLOVENIA – assessing RNA expression of a single patient gene, according to a proof-of-concept study presented by Ruth Barral-Arca at the annual meeting of the European Society for Paediatric Infectious Diseases.
The gene of interest – IFI44L – is entwined in a child’s response to infection. It’s upregulated in the presence of viral infection and suppressed in bacterial infection, explained Ms. Barral-Arca, a PhD student at the University of Santiago de Compostela (Spain).
This investigational real-time PCR assay could provide a major advance over current routine practice, which is to admit a sick febrile child to the hospital, order bacterial cultures, and start parenteral antibiotics presumptively while awaiting the culture results, which usually don’t come back for more than 24 hours. This practice is a step backwards in terms of antibiotic stewardship, because the majority of febrile children have a self-resolving viral infection.
“This is a big problem because a lot of children with viral infections are inappropriately given antibiotics, leading to antimicrobial resistance,” she noted.
Also, misleadingly false-negative bacterial cultures can occur if the causative pathogen wasn’t included in the test, the infection is in a nonaccessible site, or the child has recently been on antibiotics.
All of these shortcomings have led to a new diagnostic strategy based upon measuring the pattern of key host genes upregulated or suppressed during the inflammatory response.
“We’ve seen that, instead of analyzing the bugs, analyzing the host transcriptome response during infection is proving to be a promising tool for disease biomarker identification. And it’s faster. An early differentiation between viral and bacterial patients will help improve triage in emergency departments, decrease the misuse of antibiotics, and guide clinics to a more precise diagnosis. A lot of big hospitals are already doing PCR. They could quickly adopt this kind of analysis,” Ms. Barral-Arca continued.
She presented a pilot study in which the assay was put to the test using multiple blood samples from 14 febrile infants and children up to 6 years of age with microbiologically confirmed bacterial infection, 11 febrile children with confirmed viral infection, and 10 healthy controls.
“I know the numbers seem small, but we did a sample-size power calculation and it’s just fine,” according to the researcher.
The initial study goal was to confirm earlier promising findings from a study of 370 febrile children in the United Kingdom, Spain, and the United States, conducted by the Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium, a study in which several of Ms. Barral-Arca’s senior coinvestigators participated. The IRIS investigators demonstrated that the combined expression pattern of two genes – IFI44L and FAM89A – distinguished the bacterial from viral infections with impressive sensitivity and specificity (JAMA. 2016 Aug 23-30;316[8]:835-45).
The two-gene signature performed similarly well in Ms. Barral-Arca’s study. However, when she and her coinvestigators tested the discriminatory power of the two genes individually, they got a surprise: The real-time PCR analysis assessing expression of IFI44L alone performed even better than the two-gene combination, discriminating viral from bacterial infections with 91% sensitivity, 93% specificity, and an area under the curve of 94%. In contrast, the two-gene signature based upon IFI44L and FAM89A had a sensitivity of 91%, a specificity of 86%, and an area under the curve of 92%. While those differences in performance are small, a single-gene assay saves time, work, and cost, according to Ms. Barral-Arca.
Her group then validated their findings regarding the performance of the IFI44L single-gene signature in two independent cohorts: stored blood samples from the children in the earlier IRIS study, and a group of children with diarrhea of viral or bacterial etiology.
“One gene seems to be enough,” she said. “We have demonstrated in a real-life scenario that host gene expression microarray data can be successfully translated into a fast, highly accurate, and relatively inexpensive in vitro assay that could be implemented in the clinical routine.”
Planned future work includes investigation of how the gene expression evolves over time from fever onset, the possible utility of the assay in noninfectious febrile illnesses such as rheumatoid arthritis, and whether the test discriminates viral from bacterial infection in adults.
Ms. Barral-Arca reported having no financial conflicts regarding her study, supported by institutional funding.
REPORTING FROM ESPID 2019
Key clinical point: A novel real-time single-gene–expression PCR test quickly distinguishes viral from bacterial infection in febrile children.
Major finding: The expression signature of the IFI44L gene rapidly distinguished bacterial from viral infection in febrile children with 91% sensitivity and 93% specificity.
Study details: This translational study included 25 febrile children with definite bacterial or viral infections and 10 healthy controls.
Disclosures: The presenter reported having no financial conflicts regarding her study, supported by institutional funding.
Cannabis withdrawal syndrome real but underrecognized
SAN FRANCISCO – Marijuana withdrawal syndrome is real, and physicians and patients should recognize the phenomenon and take it seriously as legalization rolls out across the United States, an investigation from Columbia University in New York suggests,
“Most clinicians don’t really believe there is a withdrawal syndrome, but there definitely is. The prevalence we found was 12% among frequent cannabis users,” meaning three or more times a week, said psychiatrist and lead investigator Ofir Livne, MD, who until recently was a research fellow at Columbia but now is affiliated with Tel Aviv University in Israel (Drug Alcohol Depend. 2019 Feb 1;195:170-7).
“Usually what happens is a cannabis user will feel a bit agitated, and they’ll take another joint without even realizing they are just perpetuating the addiction.”
Dr. Livne said the syndrome is seen with other substances but is underrecognized with cannabis. “The word needs to get out more,” he said at the annual meeting of the American Psychiatric Association.
The symptoms can last for several days – or longer.
To get an idea of the extent of the problem, he and his team analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions-III. The survey collected data on more than 36,000 adults about drug use, associated effects, and other issues in 2012-13.
The investigators focused on the 1,527 people who reported frequent use in the preceding 12 months, and looked to see whether the symptoms they reported when they stopped or cut back would qualify them for cannabis withdrawal syndrome (CWS) in the DSM-5, the first edition of the manual to include the diagnosis.
Overall, 12.1% made the cut. The most common symptoms were nervousness/anxiety (76%), irritability (72%), sleep difficulty (68%), and depressed mood (59%). CWS patients also had lower health-related quality of life scores than peers without CWS.
Physical symptoms associated with CWS included headache, tremors, and sweating, among others. Overall, 70% of people reported some sort of physical discomfort associated with withdrawal.
“We also saw that frequent cannabis users who experience withdrawal are a lot more prone to other psychiatric disorders,” Dr. Livne said, including mood disorders (adjusted odds ratio, 1.9-2.6), anxiety disorders (aOR, 2.4-2.5), and personality disorders (aOR, 1.7-2.2). They more often had a family history of depression (aOR, 2.5).
“This study provides the first nationally representative large-scale report on the DSM-5 cannabis withdrawal syndrome. ... Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it,” Dr. Livne and his colleagues concluded.
The work was adjusted for social demographics and other confounders, including tobacco withdrawal, which has overlapping symptoms.
It’s possible that in some cases, the survey simply caught a return of the anxiety and other issues that caused people to use in the first place, instead of true withdrawal, but Dr. Livne didn’t think so. “Some of them might have been prone to anxiety, but we controlled for that as much as we could,” he said.
The work was funded by the National Institute on Drug Abuse. Dr. Livne had no disclosures.
SAN FRANCISCO – Marijuana withdrawal syndrome is real, and physicians and patients should recognize the phenomenon and take it seriously as legalization rolls out across the United States, an investigation from Columbia University in New York suggests,
“Most clinicians don’t really believe there is a withdrawal syndrome, but there definitely is. The prevalence we found was 12% among frequent cannabis users,” meaning three or more times a week, said psychiatrist and lead investigator Ofir Livne, MD, who until recently was a research fellow at Columbia but now is affiliated with Tel Aviv University in Israel (Drug Alcohol Depend. 2019 Feb 1;195:170-7).
“Usually what happens is a cannabis user will feel a bit agitated, and they’ll take another joint without even realizing they are just perpetuating the addiction.”
Dr. Livne said the syndrome is seen with other substances but is underrecognized with cannabis. “The word needs to get out more,” he said at the annual meeting of the American Psychiatric Association.
The symptoms can last for several days – or longer.
To get an idea of the extent of the problem, he and his team analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions-III. The survey collected data on more than 36,000 adults about drug use, associated effects, and other issues in 2012-13.
The investigators focused on the 1,527 people who reported frequent use in the preceding 12 months, and looked to see whether the symptoms they reported when they stopped or cut back would qualify them for cannabis withdrawal syndrome (CWS) in the DSM-5, the first edition of the manual to include the diagnosis.
Overall, 12.1% made the cut. The most common symptoms were nervousness/anxiety (76%), irritability (72%), sleep difficulty (68%), and depressed mood (59%). CWS patients also had lower health-related quality of life scores than peers without CWS.
Physical symptoms associated with CWS included headache, tremors, and sweating, among others. Overall, 70% of people reported some sort of physical discomfort associated with withdrawal.
“We also saw that frequent cannabis users who experience withdrawal are a lot more prone to other psychiatric disorders,” Dr. Livne said, including mood disorders (adjusted odds ratio, 1.9-2.6), anxiety disorders (aOR, 2.4-2.5), and personality disorders (aOR, 1.7-2.2). They more often had a family history of depression (aOR, 2.5).
“This study provides the first nationally representative large-scale report on the DSM-5 cannabis withdrawal syndrome. ... Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it,” Dr. Livne and his colleagues concluded.
The work was adjusted for social demographics and other confounders, including tobacco withdrawal, which has overlapping symptoms.
It’s possible that in some cases, the survey simply caught a return of the anxiety and other issues that caused people to use in the first place, instead of true withdrawal, but Dr. Livne didn’t think so. “Some of them might have been prone to anxiety, but we controlled for that as much as we could,” he said.
The work was funded by the National Institute on Drug Abuse. Dr. Livne had no disclosures.
SAN FRANCISCO – Marijuana withdrawal syndrome is real, and physicians and patients should recognize the phenomenon and take it seriously as legalization rolls out across the United States, an investigation from Columbia University in New York suggests,
“Most clinicians don’t really believe there is a withdrawal syndrome, but there definitely is. The prevalence we found was 12% among frequent cannabis users,” meaning three or more times a week, said psychiatrist and lead investigator Ofir Livne, MD, who until recently was a research fellow at Columbia but now is affiliated with Tel Aviv University in Israel (Drug Alcohol Depend. 2019 Feb 1;195:170-7).
“Usually what happens is a cannabis user will feel a bit agitated, and they’ll take another joint without even realizing they are just perpetuating the addiction.”
Dr. Livne said the syndrome is seen with other substances but is underrecognized with cannabis. “The word needs to get out more,” he said at the annual meeting of the American Psychiatric Association.
The symptoms can last for several days – or longer.
To get an idea of the extent of the problem, he and his team analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions-III. The survey collected data on more than 36,000 adults about drug use, associated effects, and other issues in 2012-13.
The investigators focused on the 1,527 people who reported frequent use in the preceding 12 months, and looked to see whether the symptoms they reported when they stopped or cut back would qualify them for cannabis withdrawal syndrome (CWS) in the DSM-5, the first edition of the manual to include the diagnosis.
Overall, 12.1% made the cut. The most common symptoms were nervousness/anxiety (76%), irritability (72%), sleep difficulty (68%), and depressed mood (59%). CWS patients also had lower health-related quality of life scores than peers without CWS.
Physical symptoms associated with CWS included headache, tremors, and sweating, among others. Overall, 70% of people reported some sort of physical discomfort associated with withdrawal.
“We also saw that frequent cannabis users who experience withdrawal are a lot more prone to other psychiatric disorders,” Dr. Livne said, including mood disorders (adjusted odds ratio, 1.9-2.6), anxiety disorders (aOR, 2.4-2.5), and personality disorders (aOR, 1.7-2.2). They more often had a family history of depression (aOR, 2.5).
“This study provides the first nationally representative large-scale report on the DSM-5 cannabis withdrawal syndrome. ... Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it,” Dr. Livne and his colleagues concluded.
The work was adjusted for social demographics and other confounders, including tobacco withdrawal, which has overlapping symptoms.
It’s possible that in some cases, the survey simply caught a return of the anxiety and other issues that caused people to use in the first place, instead of true withdrawal, but Dr. Livne didn’t think so. “Some of them might have been prone to anxiety, but we controlled for that as much as we could,” he said.
The work was funded by the National Institute on Drug Abuse. Dr. Livne had no disclosures.
REPORTING FROM APA 2019
Sexual harassment: Prevention and defense
Unless you have been vacationing on some distant astral plane, you are well aware that sexual misconduct and harassment have dominated news coverage and social media forums over the past year or more. It has ended the careers of a number of formerly respectable celebrities, and the #MeToo movement has empowered many additional harassment victims to come forward with their stories.
Medical offices are far from immune from harassment, of course, and the problem is not limited to staff interactions. According to a Medscape poll, 27% of physicians have been targets of inappropriate behavior in a professional setting. In another poll, 47% of physicians and 71% of nurses reported being harassed (by stalking, persistent attempts at communication, or inappropriate social media contact) by a patient.
The reality is that , have an ethical and legal responsibility to provide a safe and respectful work environment for everyone involved.
The first step in meeting that responsibility is to develop a written policy, if you don’t already have one, starting with a clear definition of sexual harassment. The Equal Employment Opportunity Commission (EEOC) has a good summary on its website of what does and does not constitute harassment, and under what conditions employers may be liable. Once the problem has been defined, a good written policy will provide specific methods for reporting transgressions, along with outlines of investigative and corrective measures to be taken in response. Templates for such documents are available on many websites, if you don’t want to start from scratch.
The next step, once a written policy is in place (and vetted by your attorney), is training for your staff. In particular, you should ensure that those in supervisory roles understand their specific responsibilities, and that everyone knows how to report an incident.
Harassment prevention training is already mandated by law in some states, including New York, California (if you have five or more employees), Maine, Delaware, and Connecticut. Other states, such as Colorado, Florida, Massachusetts, Michigan, Oklahoma, Rhode Island, Tennessee, Utah, and Vermont, have laws that “encourage” employers to provide such training. Other legislation is pending; check for new laws in your state on a regular basis.
Federal EEOC guidelines suggest that all employers “conduct and reinforce” harassment prevention training, whether laws in your particular state require it or not. On a practical level, recent court decisions suggest that offices that do not train their employees may find it difficult to mount an effective defense of a harassment lawsuit, even when they have a written policy in place. They may also be more vulnerable to punitive damage awards.
OSHA and various private companies offer a variety of downloadable training videos at reasonable cost. (As always, I have no financial interest in any product or service mentioned here.)
Misconduct among office staff is a straightforward, zero-tolerance issue. Harassment by patients is more complex, and dealing with it often requires some creativity. No one in your office, however, should think it is something they must accept because it comes from a patient. Any physician or staffer should be empowered to speak up if anyone else’s behavior, including a patient’s, makes them uncomfortable. Even when there is a medical explanation – such as psychiatric or cognitive impairment – it is important (and in some states, mandatory) to call out the behavior and report the incident.
Once reported, it should be documented, so that colleagues and other providers will be aware of the problem, and to protect yourself should the patient ever make false accusations against your practice. At subsequent appointments, take common-sense precautions. Chaperones are always a good idea, but especially so in these situations.
With repeat offenders, everyone has their own barometer of what they can and cannot tolerate. My personal threshold is low; I give one polite warning, explaining that we must provide a respectful and welcoming environment for everyone in the office, and any unacceptable behavior in the future will be grounds for dismissal from my practice. Most get the message; those who don’t are dismissed, politely.
The central point is to prevent harassment whenever possible, and to take every complaint seriously and address it promptly. An effective misconduct policy goes beyond simply avoiding legal liability. Patients and staffers alike should be secure in the knowledge that inappropriate verbal or physical interactions are not acceptable in your office under any circumstances, and will not be ignored or tolerated.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected] .
Unless you have been vacationing on some distant astral plane, you are well aware that sexual misconduct and harassment have dominated news coverage and social media forums over the past year or more. It has ended the careers of a number of formerly respectable celebrities, and the #MeToo movement has empowered many additional harassment victims to come forward with their stories.
Medical offices are far from immune from harassment, of course, and the problem is not limited to staff interactions. According to a Medscape poll, 27% of physicians have been targets of inappropriate behavior in a professional setting. In another poll, 47% of physicians and 71% of nurses reported being harassed (by stalking, persistent attempts at communication, or inappropriate social media contact) by a patient.
The reality is that , have an ethical and legal responsibility to provide a safe and respectful work environment for everyone involved.
The first step in meeting that responsibility is to develop a written policy, if you don’t already have one, starting with a clear definition of sexual harassment. The Equal Employment Opportunity Commission (EEOC) has a good summary on its website of what does and does not constitute harassment, and under what conditions employers may be liable. Once the problem has been defined, a good written policy will provide specific methods for reporting transgressions, along with outlines of investigative and corrective measures to be taken in response. Templates for such documents are available on many websites, if you don’t want to start from scratch.
The next step, once a written policy is in place (and vetted by your attorney), is training for your staff. In particular, you should ensure that those in supervisory roles understand their specific responsibilities, and that everyone knows how to report an incident.
Harassment prevention training is already mandated by law in some states, including New York, California (if you have five or more employees), Maine, Delaware, and Connecticut. Other states, such as Colorado, Florida, Massachusetts, Michigan, Oklahoma, Rhode Island, Tennessee, Utah, and Vermont, have laws that “encourage” employers to provide such training. Other legislation is pending; check for new laws in your state on a regular basis.
Federal EEOC guidelines suggest that all employers “conduct and reinforce” harassment prevention training, whether laws in your particular state require it or not. On a practical level, recent court decisions suggest that offices that do not train their employees may find it difficult to mount an effective defense of a harassment lawsuit, even when they have a written policy in place. They may also be more vulnerable to punitive damage awards.
OSHA and various private companies offer a variety of downloadable training videos at reasonable cost. (As always, I have no financial interest in any product or service mentioned here.)
Misconduct among office staff is a straightforward, zero-tolerance issue. Harassment by patients is more complex, and dealing with it often requires some creativity. No one in your office, however, should think it is something they must accept because it comes from a patient. Any physician or staffer should be empowered to speak up if anyone else’s behavior, including a patient’s, makes them uncomfortable. Even when there is a medical explanation – such as psychiatric or cognitive impairment – it is important (and in some states, mandatory) to call out the behavior and report the incident.
Once reported, it should be documented, so that colleagues and other providers will be aware of the problem, and to protect yourself should the patient ever make false accusations against your practice. At subsequent appointments, take common-sense precautions. Chaperones are always a good idea, but especially so in these situations.
With repeat offenders, everyone has their own barometer of what they can and cannot tolerate. My personal threshold is low; I give one polite warning, explaining that we must provide a respectful and welcoming environment for everyone in the office, and any unacceptable behavior in the future will be grounds for dismissal from my practice. Most get the message; those who don’t are dismissed, politely.
The central point is to prevent harassment whenever possible, and to take every complaint seriously and address it promptly. An effective misconduct policy goes beyond simply avoiding legal liability. Patients and staffers alike should be secure in the knowledge that inappropriate verbal or physical interactions are not acceptable in your office under any circumstances, and will not be ignored or tolerated.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected] .
Unless you have been vacationing on some distant astral plane, you are well aware that sexual misconduct and harassment have dominated news coverage and social media forums over the past year or more. It has ended the careers of a number of formerly respectable celebrities, and the #MeToo movement has empowered many additional harassment victims to come forward with their stories.
Medical offices are far from immune from harassment, of course, and the problem is not limited to staff interactions. According to a Medscape poll, 27% of physicians have been targets of inappropriate behavior in a professional setting. In another poll, 47% of physicians and 71% of nurses reported being harassed (by stalking, persistent attempts at communication, or inappropriate social media contact) by a patient.
The reality is that , have an ethical and legal responsibility to provide a safe and respectful work environment for everyone involved.
The first step in meeting that responsibility is to develop a written policy, if you don’t already have one, starting with a clear definition of sexual harassment. The Equal Employment Opportunity Commission (EEOC) has a good summary on its website of what does and does not constitute harassment, and under what conditions employers may be liable. Once the problem has been defined, a good written policy will provide specific methods for reporting transgressions, along with outlines of investigative and corrective measures to be taken in response. Templates for such documents are available on many websites, if you don’t want to start from scratch.
The next step, once a written policy is in place (and vetted by your attorney), is training for your staff. In particular, you should ensure that those in supervisory roles understand their specific responsibilities, and that everyone knows how to report an incident.
Harassment prevention training is already mandated by law in some states, including New York, California (if you have five or more employees), Maine, Delaware, and Connecticut. Other states, such as Colorado, Florida, Massachusetts, Michigan, Oklahoma, Rhode Island, Tennessee, Utah, and Vermont, have laws that “encourage” employers to provide such training. Other legislation is pending; check for new laws in your state on a regular basis.
Federal EEOC guidelines suggest that all employers “conduct and reinforce” harassment prevention training, whether laws in your particular state require it or not. On a practical level, recent court decisions suggest that offices that do not train their employees may find it difficult to mount an effective defense of a harassment lawsuit, even when they have a written policy in place. They may also be more vulnerable to punitive damage awards.
OSHA and various private companies offer a variety of downloadable training videos at reasonable cost. (As always, I have no financial interest in any product or service mentioned here.)
Misconduct among office staff is a straightforward, zero-tolerance issue. Harassment by patients is more complex, and dealing with it often requires some creativity. No one in your office, however, should think it is something they must accept because it comes from a patient. Any physician or staffer should be empowered to speak up if anyone else’s behavior, including a patient’s, makes them uncomfortable. Even when there is a medical explanation – such as psychiatric or cognitive impairment – it is important (and in some states, mandatory) to call out the behavior and report the incident.
Once reported, it should be documented, so that colleagues and other providers will be aware of the problem, and to protect yourself should the patient ever make false accusations against your practice. At subsequent appointments, take common-sense precautions. Chaperones are always a good idea, but especially so in these situations.
With repeat offenders, everyone has their own barometer of what they can and cannot tolerate. My personal threshold is low; I give one polite warning, explaining that we must provide a respectful and welcoming environment for everyone in the office, and any unacceptable behavior in the future will be grounds for dismissal from my practice. Most get the message; those who don’t are dismissed, politely.
The central point is to prevent harassment whenever possible, and to take every complaint seriously and address it promptly. An effective misconduct policy goes beyond simply avoiding legal liability. Patients and staffers alike should be secure in the knowledge that inappropriate verbal or physical interactions are not acceptable in your office under any circumstances, and will not be ignored or tolerated.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected] .
Response endures in cemiplimab-treated patients with cutaneous SCC
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
REPORTING FROM WCD2019
Visual examinations yield signs to guide vitiligo treatment
MILAN – Subtle signs beyond depigmentation alone can guide management of vitiligo, Michelle Rodrigues, MBBS, said at the World Congress of Dermatology.
Signs of high disease activity can be visually observed and, when found, can compel urgent treatment, Dr. Rodrigues said. “If we identify and understand these [signs, they] can change our management plan, and the patient’s outcomes ... picking these up quickly, getting the best response you can, can help our patients tremendously.”
To assess clinical signs of severity in vitiligo, “use the tools that you have in your practice – your dermatoscope, your Wood’s lamp.”
Showing an image of the leg of a patient with vitiligo, Dr. Rodrigues said, “I know this patient’s vitiligo is very, very active. Why?” Clues come when there are areas of hypopigmentation at the rim of lesions, with depigmentation at the center. The presence of pigmentation, hypopigmentation, and depigmentation within the same lesion indicates high disease activity. This finding is the trichrome sign, also called the “blurry borders” sign in some regions, said Dr. Rodrigues, a dermatologist in Melbourne and the founder of Chroma Dermatology, which specializes in treating pigment problems and diagnosing and managing skin conditions in patients with skin of color.
Next, Dr. Rodrigues said, look at hair growth within the vitiliginous area. “If you’re unable to see that clinically, it’s really important to get that dermatoscope onto the patient, and look within a patch, to see whether or not you can actually see white hairs or normal colored hairs,” she said. This finding will help to determine both treatment plan and prognosis, since leukotrichia is a marker of disease severity in vitiligo.
Be alert to Koebnerization, said Dr. Rodrigues; the presentation may be subtle. As an example, she shared an image of a patient with depigmented patches on the dorsum of each foot. It wasn’t until the patient removed her foot gear – rubber slide-type sandals with a single broad strap over the dorsum – that Dr. Rodrigues recognized that “there was clear Koebnerization from the constant friction as a result of the wearing of the shoes.
“This can also be seen when patients scratch themselves, as can be seen with the itch that vitiligo can sometimes cause,” she said.
She noted that about 10% of patients with vitiligo have pruritus as a prominent symptom. Here, she said, is where a Wood’s lamp can be helpful as well. “Sometimes we can’t appreciate the very, very subtle Koebnerization, especially in patients with lighter skin. Getting out that Wood’s lamp and looking at other areas of involvement is really important,” she said. Areas of high disease activity and signs of progression that might otherwise be missed will be more obvious under the ultraviolet light.
It’s important to look beyond the obvious patches of vitiligo to examine the surrounding skin. Searching for “confetti depigmentation” – tiny white dots of depigmentation scattered over the otherwise normally pigmented skin – also marks high disease activity. An area with these dots – each often only a few millimeters in diameter – is likely destined for rapid depigmentation unless aggressive treatment is started. “We know that without treating these areas there will be very, very rapid and aggressive depigmentation. And remember that in areas that have a paucity of hair follicles, it might be irreversible ... so recognizing these signs is absolutely critical.”
The final clue to highly active disease that’s likely to move quickly without intervention can be found at the border of a vitiligo lesion. Look for a fine rim of erythema and some scale, Dr. Rodrigues said. This sign is common, and often seen early in the disease course. When this erythematous region is biopsied, ”You’ll see an intense inflammatory response, with an interface dermatitis. Again, this tells us that the patient may have a poorer prognosis if we don’t commence treatment early on.”
As a final clinical tip, Dr. Rodrigues reminded attendees that when one sign of disease activity is seen, others are often present. A thorough clinical examination is needed to document aggressive disease. “Please make sure that if you find one, you’re looking for other signs of disease severity as well.”
Dr. Rodrigues reported that she had no disclosures relevant to her presentation.
MILAN – Subtle signs beyond depigmentation alone can guide management of vitiligo, Michelle Rodrigues, MBBS, said at the World Congress of Dermatology.
Signs of high disease activity can be visually observed and, when found, can compel urgent treatment, Dr. Rodrigues said. “If we identify and understand these [signs, they] can change our management plan, and the patient’s outcomes ... picking these up quickly, getting the best response you can, can help our patients tremendously.”
To assess clinical signs of severity in vitiligo, “use the tools that you have in your practice – your dermatoscope, your Wood’s lamp.”
Showing an image of the leg of a patient with vitiligo, Dr. Rodrigues said, “I know this patient’s vitiligo is very, very active. Why?” Clues come when there are areas of hypopigmentation at the rim of lesions, with depigmentation at the center. The presence of pigmentation, hypopigmentation, and depigmentation within the same lesion indicates high disease activity. This finding is the trichrome sign, also called the “blurry borders” sign in some regions, said Dr. Rodrigues, a dermatologist in Melbourne and the founder of Chroma Dermatology, which specializes in treating pigment problems and diagnosing and managing skin conditions in patients with skin of color.
Next, Dr. Rodrigues said, look at hair growth within the vitiliginous area. “If you’re unable to see that clinically, it’s really important to get that dermatoscope onto the patient, and look within a patch, to see whether or not you can actually see white hairs or normal colored hairs,” she said. This finding will help to determine both treatment plan and prognosis, since leukotrichia is a marker of disease severity in vitiligo.
Be alert to Koebnerization, said Dr. Rodrigues; the presentation may be subtle. As an example, she shared an image of a patient with depigmented patches on the dorsum of each foot. It wasn’t until the patient removed her foot gear – rubber slide-type sandals with a single broad strap over the dorsum – that Dr. Rodrigues recognized that “there was clear Koebnerization from the constant friction as a result of the wearing of the shoes.
“This can also be seen when patients scratch themselves, as can be seen with the itch that vitiligo can sometimes cause,” she said.
She noted that about 10% of patients with vitiligo have pruritus as a prominent symptom. Here, she said, is where a Wood’s lamp can be helpful as well. “Sometimes we can’t appreciate the very, very subtle Koebnerization, especially in patients with lighter skin. Getting out that Wood’s lamp and looking at other areas of involvement is really important,” she said. Areas of high disease activity and signs of progression that might otherwise be missed will be more obvious under the ultraviolet light.
It’s important to look beyond the obvious patches of vitiligo to examine the surrounding skin. Searching for “confetti depigmentation” – tiny white dots of depigmentation scattered over the otherwise normally pigmented skin – also marks high disease activity. An area with these dots – each often only a few millimeters in diameter – is likely destined for rapid depigmentation unless aggressive treatment is started. “We know that without treating these areas there will be very, very rapid and aggressive depigmentation. And remember that in areas that have a paucity of hair follicles, it might be irreversible ... so recognizing these signs is absolutely critical.”
The final clue to highly active disease that’s likely to move quickly without intervention can be found at the border of a vitiligo lesion. Look for a fine rim of erythema and some scale, Dr. Rodrigues said. This sign is common, and often seen early in the disease course. When this erythematous region is biopsied, ”You’ll see an intense inflammatory response, with an interface dermatitis. Again, this tells us that the patient may have a poorer prognosis if we don’t commence treatment early on.”
As a final clinical tip, Dr. Rodrigues reminded attendees that when one sign of disease activity is seen, others are often present. A thorough clinical examination is needed to document aggressive disease. “Please make sure that if you find one, you’re looking for other signs of disease severity as well.”
Dr. Rodrigues reported that she had no disclosures relevant to her presentation.
MILAN – Subtle signs beyond depigmentation alone can guide management of vitiligo, Michelle Rodrigues, MBBS, said at the World Congress of Dermatology.
Signs of high disease activity can be visually observed and, when found, can compel urgent treatment, Dr. Rodrigues said. “If we identify and understand these [signs, they] can change our management plan, and the patient’s outcomes ... picking these up quickly, getting the best response you can, can help our patients tremendously.”
To assess clinical signs of severity in vitiligo, “use the tools that you have in your practice – your dermatoscope, your Wood’s lamp.”
Showing an image of the leg of a patient with vitiligo, Dr. Rodrigues said, “I know this patient’s vitiligo is very, very active. Why?” Clues come when there are areas of hypopigmentation at the rim of lesions, with depigmentation at the center. The presence of pigmentation, hypopigmentation, and depigmentation within the same lesion indicates high disease activity. This finding is the trichrome sign, also called the “blurry borders” sign in some regions, said Dr. Rodrigues, a dermatologist in Melbourne and the founder of Chroma Dermatology, which specializes in treating pigment problems and diagnosing and managing skin conditions in patients with skin of color.
Next, Dr. Rodrigues said, look at hair growth within the vitiliginous area. “If you’re unable to see that clinically, it’s really important to get that dermatoscope onto the patient, and look within a patch, to see whether or not you can actually see white hairs or normal colored hairs,” she said. This finding will help to determine both treatment plan and prognosis, since leukotrichia is a marker of disease severity in vitiligo.
Be alert to Koebnerization, said Dr. Rodrigues; the presentation may be subtle. As an example, she shared an image of a patient with depigmented patches on the dorsum of each foot. It wasn’t until the patient removed her foot gear – rubber slide-type sandals with a single broad strap over the dorsum – that Dr. Rodrigues recognized that “there was clear Koebnerization from the constant friction as a result of the wearing of the shoes.
“This can also be seen when patients scratch themselves, as can be seen with the itch that vitiligo can sometimes cause,” she said.
She noted that about 10% of patients with vitiligo have pruritus as a prominent symptom. Here, she said, is where a Wood’s lamp can be helpful as well. “Sometimes we can’t appreciate the very, very subtle Koebnerization, especially in patients with lighter skin. Getting out that Wood’s lamp and looking at other areas of involvement is really important,” she said. Areas of high disease activity and signs of progression that might otherwise be missed will be more obvious under the ultraviolet light.
It’s important to look beyond the obvious patches of vitiligo to examine the surrounding skin. Searching for “confetti depigmentation” – tiny white dots of depigmentation scattered over the otherwise normally pigmented skin – also marks high disease activity. An area with these dots – each often only a few millimeters in diameter – is likely destined for rapid depigmentation unless aggressive treatment is started. “We know that without treating these areas there will be very, very rapid and aggressive depigmentation. And remember that in areas that have a paucity of hair follicles, it might be irreversible ... so recognizing these signs is absolutely critical.”
The final clue to highly active disease that’s likely to move quickly without intervention can be found at the border of a vitiligo lesion. Look for a fine rim of erythema and some scale, Dr. Rodrigues said. This sign is common, and often seen early in the disease course. When this erythematous region is biopsied, ”You’ll see an intense inflammatory response, with an interface dermatitis. Again, this tells us that the patient may have a poorer prognosis if we don’t commence treatment early on.”
As a final clinical tip, Dr. Rodrigues reminded attendees that when one sign of disease activity is seen, others are often present. A thorough clinical examination is needed to document aggressive disease. “Please make sure that if you find one, you’re looking for other signs of disease severity as well.”
Dr. Rodrigues reported that she had no disclosures relevant to her presentation.
EXPERT ANALYSIS FROM WCD2019