Conference Coverage

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

NEW YORK – From clinical trials to textbooks, patients with darker skin types who have psoriasis overall – and Black patients in particular – are underrepresented, which might at least partially explain why clinicians are slow to recognize nail involvement, even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.

In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
 

Black patients largely unrepresented in photos

When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.

Ted Bosworth/MDedge News

“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.

“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”

Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.

In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
 

Patient characteristics similar by race

In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.

“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.

Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.

The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.

“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”

The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.

“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.

An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”

Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.

NEW YORK – From clinical trials to textbooks, patients with darker skin types who have psoriasis overall – and Black patients in particular – are underrepresented, which might at least partially explain why clinicians are slow to recognize nail involvement, even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.

In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
 

Black patients largely unrepresented in photos

When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.

Ted Bosworth/MDedge News

“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.

“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”

Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.

In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
 

Patient characteristics similar by race

In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.

“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.

Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.

The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.

“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”

The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.

“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.

An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”

Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.

NEW YORK – From clinical trials to textbooks, patients with darker skin types who have psoriasis overall – and Black patients in particular – are underrepresented, which might at least partially explain why clinicians are slow to recognize nail involvement, even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.

In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
 

Black patients largely unrepresented in photos

When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.

Ted Bosworth/MDedge News

“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.

“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”

Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.

In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
 

Patient characteristics similar by race

In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.

“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.

Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.

The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.

“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”

The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.

“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.

An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”

Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.

One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.

“I think the size of sonelokimab is important,” Brian Kirby, MD, a consultant dermatologist at St. Vincent’s Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. “We think the smaller size results in better penetration of inflamed tissue,” he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.

Ted Bosworth/MDedge News

The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
 

IL-17A/F trials

Both the 16-week phase 2 data with sonelokimab and the 48-week pooled phase 3 maintenance data with bimekizumab were presented as late-breakers at the EADV Congress.

In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.

The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.

At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.

For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P <.01), and 14.7% of those randomized to placebo.

For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.

On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P <.001 vs. P <.01).

However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.

For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P <.01).

The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.

Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.

The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
 

Forty-eight–week bimekizumab data

From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.

“Improvements in disease severity were seen over time,” Dr. Zouboulis reported. “The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification.”

To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.

On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.

BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.

One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.

“I think the size of sonelokimab is important,” Brian Kirby, MD, a consultant dermatologist at St. Vincent’s Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. “We think the smaller size results in better penetration of inflamed tissue,” he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.

Ted Bosworth/MDedge News

The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
 

IL-17A/F trials

Both the 16-week phase 2 data with sonelokimab and the 48-week pooled phase 3 maintenance data with bimekizumab were presented as late-breakers at the EADV Congress.

In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.

The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.

At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.

For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P <.01), and 14.7% of those randomized to placebo.

For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.

On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P <.001 vs. P <.01).

However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.

For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P <.01).

The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.

Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.

The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
 

Forty-eight–week bimekizumab data

From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.

“Improvements in disease severity were seen over time,” Dr. Zouboulis reported. “The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification.”

To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.

On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.

BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.

One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.

“I think the size of sonelokimab is important,” Brian Kirby, MD, a consultant dermatologist at St. Vincent’s Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. “We think the smaller size results in better penetration of inflamed tissue,” he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.

Ted Bosworth/MDedge News

The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
 

IL-17A/F trials

Both the 16-week phase 2 data with sonelokimab and the 48-week pooled phase 3 maintenance data with bimekizumab were presented as late-breakers at the EADV Congress.

In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.

The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.

At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.

For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P <.01), and 14.7% of those randomized to placebo.

For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.

On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P <.001 vs. P <.01).

However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.

For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P <.01).

The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.

Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.

The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
 

Forty-eight–week bimekizumab data

From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.

“Improvements in disease severity were seen over time,” Dr. Zouboulis reported. “The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification.”

To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.

On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

With the help of artificial intelligence (AI), arterial inflammation measured with coronary computed tomography angiography (CCTA) can predict fatal and nonfatal events in patients with nonobstructive coronary artery disease (CAD), according to a study that suggests this approach would change treatment about half the time.

In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.

This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.

Ted Bosworth/MDedge News

Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
 

CCTA-based inflammation is promising

The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.

So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.

In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).

The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.

When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.

The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.

“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
 

Predictive value greater in nonobstructive CAD

When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.

When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.

When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.

When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.

Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.

“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
 

Imaging has potential for expanded risk assessment

The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.

“A registry is not a randomized trial,” she said.

Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.

Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.

“This is an incredibly intriguing idea that deserves continuing research,” she said.

Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.

With the help of artificial intelligence (AI), arterial inflammation measured with coronary computed tomography angiography (CCTA) can predict fatal and nonfatal events in patients with nonobstructive coronary artery disease (CAD), according to a study that suggests this approach would change treatment about half the time.

In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.

This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.

Ted Bosworth/MDedge News

Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
 

CCTA-based inflammation is promising

The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.

So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.

In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).

The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.

When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.

The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.

“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
 

Predictive value greater in nonobstructive CAD

When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.

When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.

When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.

When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.

Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.

“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
 

Imaging has potential for expanded risk assessment

The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.

“A registry is not a randomized trial,” she said.

Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.

Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.

“This is an incredibly intriguing idea that deserves continuing research,” she said.

Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.

With the help of artificial intelligence (AI), arterial inflammation measured with coronary computed tomography angiography (CCTA) can predict fatal and nonfatal events in patients with nonobstructive coronary artery disease (CAD), according to a study that suggests this approach would change treatment about half the time.

In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.

This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.

Ted Bosworth/MDedge News

Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
 

CCTA-based inflammation is promising

The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.

So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.

In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).

The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.

When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.

The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.

“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
 

Predictive value greater in nonobstructive CAD

When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.

When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.

When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.

When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.

Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.

“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
 

Imaging has potential for expanded risk assessment

The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.

“A registry is not a randomized trial,” she said.

Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.

Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.

“This is an incredibly intriguing idea that deserves continuing research,” she said.

Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

Screening with a “smart,” artificial-intelligence (AI)–enhanced investigational digital stethoscope (Eko Duo) that provides phonocardiogram and electrocardiogram (ECG) readings doubled the detection of peripartum cardiomyopathy in a large study of obstetric patients in Nigeria.

Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.

“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”

If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.

Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.

“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.

Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.

“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.

This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.

Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.

A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
 

Findings ‘absolutely startling’

The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”

Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.

“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.

“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”

“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.

The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.

With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.

“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?

“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”

However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.

Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.

“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
 

AI-guided screening study

Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.

In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.

The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).

In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.

In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.

The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.

The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).

For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.

Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.

A version of this article appeared on Medscape.com.

Screening with a “smart,” artificial-intelligence (AI)–enhanced investigational digital stethoscope (Eko Duo) that provides phonocardiogram and electrocardiogram (ECG) readings doubled the detection of peripartum cardiomyopathy in a large study of obstetric patients in Nigeria.

Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.

“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”

If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.

Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.

“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.

Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.

“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.

This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.

Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.

A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
 

Findings ‘absolutely startling’

The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”

Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.

“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.

“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”

“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.

The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.

With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.

“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?

“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”

However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.

Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.

“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
 

AI-guided screening study

Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.

In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.

The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).

In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.

In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.

The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.

The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).

For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.

Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.

A version of this article appeared on Medscape.com.

Screening with a “smart,” artificial-intelligence (AI)–enhanced investigational digital stethoscope (Eko Duo) that provides phonocardiogram and electrocardiogram (ECG) readings doubled the detection of peripartum cardiomyopathy in a large study of obstetric patients in Nigeria.

Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.

“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”

If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.

Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.

“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.

Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.

“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.

This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.

Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.

A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
 

Findings ‘absolutely startling’

The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”

Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.

“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.

“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”

“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.

The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.

With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.

“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?

“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”

However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.

Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.

“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
 

AI-guided screening study

Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.

In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.

The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).

In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.

In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.

The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.

The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).

For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.

Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.

A version of this article appeared on Medscape.com.