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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Boxed warning for JAK inhibitors belies their durability in real-world registry studies
Several relatively large real-world analyses of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis appear to show that the oral small-molecule drugs are discontinued and retained at rates similar to or better than biologic disease-modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi), according to studies presented at the annual meeting of the Canadian Rheumatology Association.
The findings of these studies, although conducted prior to the Food and Drug Administration’s September 2021 announcement of a boxed warning for JAKi, do not lend support to the warning’s message of higher risks of major adverse cardiovascular events (MACE), blood clots, cancer, and death associated with JAKi.
In one study, discontinuation of JAKi-class drugs was less common than discontinuation of bDMARD-class drugs, including tumor necrosis factor inhibitors (TNFi), according to a multicenter team of investigators led by Janet Pope, MD, a professor in the division of rheumatology at the University of Western Ontario, London.
The greater durability of the JAKi relative to TNFi “seem to be driven by a greater loss of efficacy in bDMARDs over time,” reported Samir Magdy Iskander, a medical student at the university, who presented the data.
JAKi rival bDMARDs for long-term retention
In a separate but larger analysis, the retention rates with the JAKi tofacitinib (Xeljanz) and TNFi in two RA registries in Canada were about the same after a mean follow-up of 23.2 months (36.9% vs. 37.5%), but the tofacitinib group was at a relative disadvantage. Relative to the bDMARD group, patients taking JAKi were more likely to have had prior treatment with a bDMARD (66.9% vs. 33.9%), to have a higher median baseline Clinical Disease Activity Index (CDAI) score (22.1 vs. 20.0; P < .05), and to be older (59.5 vs. 57.6 years).
In this study, 1,318 patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) or a Quebec cohort called RHUMADATA were evaluated, reported Mohammad Movahedi, MD, PhD, of the Institute of Health Policy, Management, and Evaluation at the University of Toronto.
“We have not yet analyzed the reasons for discontinuation, but the data show that retention is about the same, meaning that selection of one agent over the other should be tailored according to patient characteristics,” Dr. Movahedi said.
Reasons for discontinuation were presented in the other observational study, which included 333 adult patients with RA from two centers in Ontario. The discontinuation rate for adverse events was approximately 20% in both groups (HR, 1.0005; P = .98). However, the discontinuation rate for lack of efficacy favored the JAKi, reaching statistical significance.
TNFi failure for lack of efficacy is higher
“For lack of efficacy, the discontinuation rate was about 35% lower on the JAKi [HR, 0.6543; P = .029],” Mr. Iskander reported. Relative to those taking a TNFi, those on a JAKi demonstrated “greater durability regardless of gender, age, disease duration, and prior lines of therapy.”
In a population of patients who have not achieved an adequate response to conventional synthetic DMARDs (csDMARDs), which describes the study population from the two Ontario centers, JAKi “may be considered as a preferable method of treatment,” Mr. Iskander said.
Pointing out that many clinicians have interpreted the boxed warning as a relative contraindication for use of JAKi as first-line therapy in patients with an inadequate response to csDMARDs, Marinka Twilt, MD, PhD, the moderator of the scientific session where these data were presented, questioned the conclusion. In the boxed warning, clinicians and patients are advised to consider an increased risk of serious infections, malignancy, and cardiovascular-related mortality in individuals older than 50 years.
In response, Mr. Iskander said that the data were collected and analyzed prior to the change in labeling. He acknowledged that this study was not designed to capture long-term risks, such as cardiovascular disease or malignancy. In this analysis, the safety and tolerability of JAKi and bDMARDs appeared comparable.
NEJM published study leading to boxed warning
Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).
The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.
Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.
Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.
Several relatively large real-world analyses of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis appear to show that the oral small-molecule drugs are discontinued and retained at rates similar to or better than biologic disease-modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi), according to studies presented at the annual meeting of the Canadian Rheumatology Association.
The findings of these studies, although conducted prior to the Food and Drug Administration’s September 2021 announcement of a boxed warning for JAKi, do not lend support to the warning’s message of higher risks of major adverse cardiovascular events (MACE), blood clots, cancer, and death associated with JAKi.
In one study, discontinuation of JAKi-class drugs was less common than discontinuation of bDMARD-class drugs, including tumor necrosis factor inhibitors (TNFi), according to a multicenter team of investigators led by Janet Pope, MD, a professor in the division of rheumatology at the University of Western Ontario, London.
The greater durability of the JAKi relative to TNFi “seem to be driven by a greater loss of efficacy in bDMARDs over time,” reported Samir Magdy Iskander, a medical student at the university, who presented the data.
JAKi rival bDMARDs for long-term retention
In a separate but larger analysis, the retention rates with the JAKi tofacitinib (Xeljanz) and TNFi in two RA registries in Canada were about the same after a mean follow-up of 23.2 months (36.9% vs. 37.5%), but the tofacitinib group was at a relative disadvantage. Relative to the bDMARD group, patients taking JAKi were more likely to have had prior treatment with a bDMARD (66.9% vs. 33.9%), to have a higher median baseline Clinical Disease Activity Index (CDAI) score (22.1 vs. 20.0; P < .05), and to be older (59.5 vs. 57.6 years).
In this study, 1,318 patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) or a Quebec cohort called RHUMADATA were evaluated, reported Mohammad Movahedi, MD, PhD, of the Institute of Health Policy, Management, and Evaluation at the University of Toronto.
“We have not yet analyzed the reasons for discontinuation, but the data show that retention is about the same, meaning that selection of one agent over the other should be tailored according to patient characteristics,” Dr. Movahedi said.
Reasons for discontinuation were presented in the other observational study, which included 333 adult patients with RA from two centers in Ontario. The discontinuation rate for adverse events was approximately 20% in both groups (HR, 1.0005; P = .98). However, the discontinuation rate for lack of efficacy favored the JAKi, reaching statistical significance.
TNFi failure for lack of efficacy is higher
“For lack of efficacy, the discontinuation rate was about 35% lower on the JAKi [HR, 0.6543; P = .029],” Mr. Iskander reported. Relative to those taking a TNFi, those on a JAKi demonstrated “greater durability regardless of gender, age, disease duration, and prior lines of therapy.”
In a population of patients who have not achieved an adequate response to conventional synthetic DMARDs (csDMARDs), which describes the study population from the two Ontario centers, JAKi “may be considered as a preferable method of treatment,” Mr. Iskander said.
Pointing out that many clinicians have interpreted the boxed warning as a relative contraindication for use of JAKi as first-line therapy in patients with an inadequate response to csDMARDs, Marinka Twilt, MD, PhD, the moderator of the scientific session where these data were presented, questioned the conclusion. In the boxed warning, clinicians and patients are advised to consider an increased risk of serious infections, malignancy, and cardiovascular-related mortality in individuals older than 50 years.
In response, Mr. Iskander said that the data were collected and analyzed prior to the change in labeling. He acknowledged that this study was not designed to capture long-term risks, such as cardiovascular disease or malignancy. In this analysis, the safety and tolerability of JAKi and bDMARDs appeared comparable.
NEJM published study leading to boxed warning
Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).
The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.
Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.
Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.
Several relatively large real-world analyses of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis appear to show that the oral small-molecule drugs are discontinued and retained at rates similar to or better than biologic disease-modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi), according to studies presented at the annual meeting of the Canadian Rheumatology Association.
The findings of these studies, although conducted prior to the Food and Drug Administration’s September 2021 announcement of a boxed warning for JAKi, do not lend support to the warning’s message of higher risks of major adverse cardiovascular events (MACE), blood clots, cancer, and death associated with JAKi.
In one study, discontinuation of JAKi-class drugs was less common than discontinuation of bDMARD-class drugs, including tumor necrosis factor inhibitors (TNFi), according to a multicenter team of investigators led by Janet Pope, MD, a professor in the division of rheumatology at the University of Western Ontario, London.
The greater durability of the JAKi relative to TNFi “seem to be driven by a greater loss of efficacy in bDMARDs over time,” reported Samir Magdy Iskander, a medical student at the university, who presented the data.
JAKi rival bDMARDs for long-term retention
In a separate but larger analysis, the retention rates with the JAKi tofacitinib (Xeljanz) and TNFi in two RA registries in Canada were about the same after a mean follow-up of 23.2 months (36.9% vs. 37.5%), but the tofacitinib group was at a relative disadvantage. Relative to the bDMARD group, patients taking JAKi were more likely to have had prior treatment with a bDMARD (66.9% vs. 33.9%), to have a higher median baseline Clinical Disease Activity Index (CDAI) score (22.1 vs. 20.0; P < .05), and to be older (59.5 vs. 57.6 years).
In this study, 1,318 patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) or a Quebec cohort called RHUMADATA were evaluated, reported Mohammad Movahedi, MD, PhD, of the Institute of Health Policy, Management, and Evaluation at the University of Toronto.
“We have not yet analyzed the reasons for discontinuation, but the data show that retention is about the same, meaning that selection of one agent over the other should be tailored according to patient characteristics,” Dr. Movahedi said.
Reasons for discontinuation were presented in the other observational study, which included 333 adult patients with RA from two centers in Ontario. The discontinuation rate for adverse events was approximately 20% in both groups (HR, 1.0005; P = .98). However, the discontinuation rate for lack of efficacy favored the JAKi, reaching statistical significance.
TNFi failure for lack of efficacy is higher
“For lack of efficacy, the discontinuation rate was about 35% lower on the JAKi [HR, 0.6543; P = .029],” Mr. Iskander reported. Relative to those taking a TNFi, those on a JAKi demonstrated “greater durability regardless of gender, age, disease duration, and prior lines of therapy.”
In a population of patients who have not achieved an adequate response to conventional synthetic DMARDs (csDMARDs), which describes the study population from the two Ontario centers, JAKi “may be considered as a preferable method of treatment,” Mr. Iskander said.
Pointing out that many clinicians have interpreted the boxed warning as a relative contraindication for use of JAKi as first-line therapy in patients with an inadequate response to csDMARDs, Marinka Twilt, MD, PhD, the moderator of the scientific session where these data were presented, questioned the conclusion. In the boxed warning, clinicians and patients are advised to consider an increased risk of serious infections, malignancy, and cardiovascular-related mortality in individuals older than 50 years.
In response, Mr. Iskander said that the data were collected and analyzed prior to the change in labeling. He acknowledged that this study was not designed to capture long-term risks, such as cardiovascular disease or malignancy. In this analysis, the safety and tolerability of JAKi and bDMARDs appeared comparable.
NEJM published study leading to boxed warning
Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).
The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.
Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.
Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.
FROM THE ANNUAL MEETING OF THE CANADIAN RHEUMATOLOGY ASSOCIATION
How to make the most of your time with psoriasis patients
In the clinical experience of George Han, MD, PhD, .
“They come in with bags of topical products to show you what they’ve tried,” Dr. Han, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said during the ODAC Dermatology, Aesthetic & Surgical Conference. “And you’re supposed to see this patient, talk to them, and counsel them in about 10 minutes. How do you make time to conduct an efficient psoriasis visit?”
Patients have a long-term battle to get clear, and spending a little longer on the initial visit “pays a lot of dividends,” he said. “Some of these patients are the most thankful patients in our practices, and it truly is gratifying” to see how much they can improve.
Questions about diet
Dr. Han said that psoriasis patients often ask him if, what, or how much they’re eating affects their disease. “But how do you counsel patients about diet when we’re not dietitians? We can at least give some guidance based on available data.”
He referred to a nationwide study of psoriasis patient-reported outcomes and dietary behaviors, which found that the percentage of patients who reported skin improvement was greatest after reducing intake of alcohol (53.8%); gluten (53.4%); and nightshade vegetables, such as tomatoes, potatoes, and peppers (52.1%); and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). He noted that there is a threefold increased incidence of celiac disease in patients with psoriasis.
As for nightshade vegetables, intake leads to increased alkaloids, “which have been known to worsen bowel inflammation such as in IBD [inflammatory bowel disease], but there is a lack of controlled trials examining this in the overall psoriasis population,” Dr. Han said. The Mediterranean diet, he added, “is sensible, and adding olive oil to your diet seems to have a positive effect on ... PASI, while fish oil seems to reduce C-reactive protein.” The data on the effect of vitamin D supplements are mixed, he said.
A separate randomized study evaluated the impact of weight loss in overweight or obese patients with psoriasis, who had not achieved clearance after 4 weeks of systemic treatment. Significantly more of those in the dietary intervention arm reached the weight loss goal of 5% at 20 weeks, and patients in this arm had a median reduction in the Psoriasis Area and Severity Index (PASI) score of almost 50%, compared with almost 26% among those without an active dietary intervention.
Joint pain, PsA
For psoriasis patients who complain of joint pain, he recommends administering quick measures like the five-question Psoriasis Epidemiology Screening Test (PEST) to screen for psoriatic arthritis (PsA), which is available on the National Psoriasis Foundation web site. “I ask patients about swollen, tender joints – specifically hands, wrists, ankles, feet, and toes,” Dr. Han said. Joint stiffness in the morning is a “concerning finding,” which is “more indicative of psoriatic arthritis than vague knee or back pain that worsens with use. If you have a younger patient with back pain who has a reduced ability to flex their spine, think axial disease.”
Tumor necrosis factor (TNF)–alpha inhibitors are considered first- and second-line treatment for PsA, but interleukin (IL)–17 inhibitors are generally considered just as effective overall. “The IL-23 inhibitors have mixed signals,” said Dr. Han, who is also on the NPF’s medical board. “We know that guselkumab is effective against psoriatic arthritis, but there is no inhibition of joint progression at the approved dosage on the label – though it was pretty close.”
Risankizumab (Skyrizi), an IL-23 inhibitor, was approved in January 2022 for adults with PsA and while the American College of Rheumatology response data “look reasonably good, the results for inhibition of radiographic progression are quite far off and it’s not in the label,” he said. Tildrakizumab (Ilumya), an IL-23 inhibitor, “looks impressive in phase 2b trials. It will be interesting to see if there is differentiation between the IL-23 agents in treating joint disease going forward.”
Dr. Han considers biologic therapy a good option for patients with questionable joint involvement or very limited joint disease. “If the patient has some evidence of PsA, as long as it’s a medication that has approval for that, I’m OK with starting it,” he said. “However, for patients whose joint pain dominates over the skin, or [who] have severe joint disease at presentation, I would prioritize the TNF-alpha inhibitors and IL-17s and refer them to rheumatology for shared management.”
Topical, oral treatments
As for topical approaches to treating psoriasis, adding halobetasol propionate 0.01% to tazarotene 0.045% may have a synergistic effect, while tapinarof 1% cream holds promise, he said. Tapinarof, which is expected to be approved this year, is an investigative aryl hydrocarbon agonist that inhibits an array of proinflammatory cytokines, including interferon-gamma and TNF-alpha. “It has been shown to have inhibitory effects both on Th17 cytokines and Th2 cytokines,” Dr. Han said. “What’s nice about this is that patients still appear to have treatment effect 1-2 months after stopping the drug.”
Another topical agent now under FDA review for psoriasis, is roflumilast, a phosphodiesterase type 4 (PDE4) inhibitor, which has been shown to have a treatment efficacy of 30% or more. “We’ll see how this works into our treatment regimen for psoriasis,” he said, as strategies targeting PDE4 have already been reported to help treat psoriasis.
With regards to oral therapies, he said that there are concerns about the efficacy of the oral PDE4 inhibitor apremilast, approved for psoriasis, compared with other biologics. Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor also under FDA review for psoriasis, “may fill this gap, because its efficacy seems much stronger and really capitalizes on blocking IL-23, which we know is a central pathway in the pathogenesis of psoriasis.”
Phototherapy is another treatment option. Home narrowband-UVB devices cost $3,000-$5,000, “which is a fraction of 1 year of biologic treatment,” Dr. Han said. Older data on phototherapy suggest that “lesions can clear within 2-3 months, depending on how often you do the phototherapy, while newer data suggest that 75% of patients can achieve clear or minimal disease” with phototherapy.
Biologic therapy
If patients meet criteria for treatment with a biologic, he begins the conversation by saying, “I don’t want to give you an immunosuppressant, but your psoriasis represents an overactivation of inflammation in your body, so in some way we have to bring that down. Ideally, we would target your immune system in a way that targets psoriasis very narrowly, while leaving it to do what it needs to: protecting against infections and neoplasia.”
XXXIL-17 inhibitors generally have the fastest onset of action, Dr. Han noted. Authors of a review paper found that achievement of Psoriasis Area and Severity Index (PASI) 50 was 1.8 weeks with brodalumab, 1.9 weeks for ixekizumab, 3 weeks for high-dose secukinumab, 3.5 weeks for adalimumab, 3.7 weeks for infliximab, 5.1 weeks for low-dose ustekinumab, 6.5 weeks for high-dose etanercept, and 10.9 weeks with low-dose etanercept, while achievement of PASI 50 was closer to 1 month for IL-23 inhibitors.
“The conversation I have with patients on IL-23 inhibitors is, ‘we’re in this for the long haul,’ otherwise they come in 2 months later,” he said. “They may have gotten clearer but we’re talking about getting well over half of our patients to PASI 100, or to clear or minimal disease, and they may not have gotten there yet. It helps to frame expectations.”
Dr. Han disclosed that he is a consultant to, a speaker for, or has received research support from Beiersdorf, CeraVe, Celgene, Janssen, Lilly, MC2, Pfizer, UCB, Boehringer Ingelheim, Bond Avillion, Athenex, Amgen, AbbVie, Regeneron/Sanofi, LEO Pharma, Ortho Dermatologics, BMS, Sun Pharma, Dermavant, Dermtech, MedX, Novartis, and Castle Biosciences.
In the clinical experience of George Han, MD, PhD, .
“They come in with bags of topical products to show you what they’ve tried,” Dr. Han, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said during the ODAC Dermatology, Aesthetic & Surgical Conference. “And you’re supposed to see this patient, talk to them, and counsel them in about 10 minutes. How do you make time to conduct an efficient psoriasis visit?”
Patients have a long-term battle to get clear, and spending a little longer on the initial visit “pays a lot of dividends,” he said. “Some of these patients are the most thankful patients in our practices, and it truly is gratifying” to see how much they can improve.
Questions about diet
Dr. Han said that psoriasis patients often ask him if, what, or how much they’re eating affects their disease. “But how do you counsel patients about diet when we’re not dietitians? We can at least give some guidance based on available data.”
He referred to a nationwide study of psoriasis patient-reported outcomes and dietary behaviors, which found that the percentage of patients who reported skin improvement was greatest after reducing intake of alcohol (53.8%); gluten (53.4%); and nightshade vegetables, such as tomatoes, potatoes, and peppers (52.1%); and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). He noted that there is a threefold increased incidence of celiac disease in patients with psoriasis.
As for nightshade vegetables, intake leads to increased alkaloids, “which have been known to worsen bowel inflammation such as in IBD [inflammatory bowel disease], but there is a lack of controlled trials examining this in the overall psoriasis population,” Dr. Han said. The Mediterranean diet, he added, “is sensible, and adding olive oil to your diet seems to have a positive effect on ... PASI, while fish oil seems to reduce C-reactive protein.” The data on the effect of vitamin D supplements are mixed, he said.
A separate randomized study evaluated the impact of weight loss in overweight or obese patients with psoriasis, who had not achieved clearance after 4 weeks of systemic treatment. Significantly more of those in the dietary intervention arm reached the weight loss goal of 5% at 20 weeks, and patients in this arm had a median reduction in the Psoriasis Area and Severity Index (PASI) score of almost 50%, compared with almost 26% among those without an active dietary intervention.
Joint pain, PsA
For psoriasis patients who complain of joint pain, he recommends administering quick measures like the five-question Psoriasis Epidemiology Screening Test (PEST) to screen for psoriatic arthritis (PsA), which is available on the National Psoriasis Foundation web site. “I ask patients about swollen, tender joints – specifically hands, wrists, ankles, feet, and toes,” Dr. Han said. Joint stiffness in the morning is a “concerning finding,” which is “more indicative of psoriatic arthritis than vague knee or back pain that worsens with use. If you have a younger patient with back pain who has a reduced ability to flex their spine, think axial disease.”
Tumor necrosis factor (TNF)–alpha inhibitors are considered first- and second-line treatment for PsA, but interleukin (IL)–17 inhibitors are generally considered just as effective overall. “The IL-23 inhibitors have mixed signals,” said Dr. Han, who is also on the NPF’s medical board. “We know that guselkumab is effective against psoriatic arthritis, but there is no inhibition of joint progression at the approved dosage on the label – though it was pretty close.”
Risankizumab (Skyrizi), an IL-23 inhibitor, was approved in January 2022 for adults with PsA and while the American College of Rheumatology response data “look reasonably good, the results for inhibition of radiographic progression are quite far off and it’s not in the label,” he said. Tildrakizumab (Ilumya), an IL-23 inhibitor, “looks impressive in phase 2b trials. It will be interesting to see if there is differentiation between the IL-23 agents in treating joint disease going forward.”
Dr. Han considers biologic therapy a good option for patients with questionable joint involvement or very limited joint disease. “If the patient has some evidence of PsA, as long as it’s a medication that has approval for that, I’m OK with starting it,” he said. “However, for patients whose joint pain dominates over the skin, or [who] have severe joint disease at presentation, I would prioritize the TNF-alpha inhibitors and IL-17s and refer them to rheumatology for shared management.”
Topical, oral treatments
As for topical approaches to treating psoriasis, adding halobetasol propionate 0.01% to tazarotene 0.045% may have a synergistic effect, while tapinarof 1% cream holds promise, he said. Tapinarof, which is expected to be approved this year, is an investigative aryl hydrocarbon agonist that inhibits an array of proinflammatory cytokines, including interferon-gamma and TNF-alpha. “It has been shown to have inhibitory effects both on Th17 cytokines and Th2 cytokines,” Dr. Han said. “What’s nice about this is that patients still appear to have treatment effect 1-2 months after stopping the drug.”
Another topical agent now under FDA review for psoriasis, is roflumilast, a phosphodiesterase type 4 (PDE4) inhibitor, which has been shown to have a treatment efficacy of 30% or more. “We’ll see how this works into our treatment regimen for psoriasis,” he said, as strategies targeting PDE4 have already been reported to help treat psoriasis.
With regards to oral therapies, he said that there are concerns about the efficacy of the oral PDE4 inhibitor apremilast, approved for psoriasis, compared with other biologics. Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor also under FDA review for psoriasis, “may fill this gap, because its efficacy seems much stronger and really capitalizes on blocking IL-23, which we know is a central pathway in the pathogenesis of psoriasis.”
Phototherapy is another treatment option. Home narrowband-UVB devices cost $3,000-$5,000, “which is a fraction of 1 year of biologic treatment,” Dr. Han said. Older data on phototherapy suggest that “lesions can clear within 2-3 months, depending on how often you do the phototherapy, while newer data suggest that 75% of patients can achieve clear or minimal disease” with phototherapy.
Biologic therapy
If patients meet criteria for treatment with a biologic, he begins the conversation by saying, “I don’t want to give you an immunosuppressant, but your psoriasis represents an overactivation of inflammation in your body, so in some way we have to bring that down. Ideally, we would target your immune system in a way that targets psoriasis very narrowly, while leaving it to do what it needs to: protecting against infections and neoplasia.”
XXXIL-17 inhibitors generally have the fastest onset of action, Dr. Han noted. Authors of a review paper found that achievement of Psoriasis Area and Severity Index (PASI) 50 was 1.8 weeks with brodalumab, 1.9 weeks for ixekizumab, 3 weeks for high-dose secukinumab, 3.5 weeks for adalimumab, 3.7 weeks for infliximab, 5.1 weeks for low-dose ustekinumab, 6.5 weeks for high-dose etanercept, and 10.9 weeks with low-dose etanercept, while achievement of PASI 50 was closer to 1 month for IL-23 inhibitors.
“The conversation I have with patients on IL-23 inhibitors is, ‘we’re in this for the long haul,’ otherwise they come in 2 months later,” he said. “They may have gotten clearer but we’re talking about getting well over half of our patients to PASI 100, or to clear or minimal disease, and they may not have gotten there yet. It helps to frame expectations.”
Dr. Han disclosed that he is a consultant to, a speaker for, or has received research support from Beiersdorf, CeraVe, Celgene, Janssen, Lilly, MC2, Pfizer, UCB, Boehringer Ingelheim, Bond Avillion, Athenex, Amgen, AbbVie, Regeneron/Sanofi, LEO Pharma, Ortho Dermatologics, BMS, Sun Pharma, Dermavant, Dermtech, MedX, Novartis, and Castle Biosciences.
In the clinical experience of George Han, MD, PhD, .
“They come in with bags of topical products to show you what they’ve tried,” Dr. Han, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said during the ODAC Dermatology, Aesthetic & Surgical Conference. “And you’re supposed to see this patient, talk to them, and counsel them in about 10 minutes. How do you make time to conduct an efficient psoriasis visit?”
Patients have a long-term battle to get clear, and spending a little longer on the initial visit “pays a lot of dividends,” he said. “Some of these patients are the most thankful patients in our practices, and it truly is gratifying” to see how much they can improve.
Questions about diet
Dr. Han said that psoriasis patients often ask him if, what, or how much they’re eating affects their disease. “But how do you counsel patients about diet when we’re not dietitians? We can at least give some guidance based on available data.”
He referred to a nationwide study of psoriasis patient-reported outcomes and dietary behaviors, which found that the percentage of patients who reported skin improvement was greatest after reducing intake of alcohol (53.8%); gluten (53.4%); and nightshade vegetables, such as tomatoes, potatoes, and peppers (52.1%); and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). He noted that there is a threefold increased incidence of celiac disease in patients with psoriasis.
As for nightshade vegetables, intake leads to increased alkaloids, “which have been known to worsen bowel inflammation such as in IBD [inflammatory bowel disease], but there is a lack of controlled trials examining this in the overall psoriasis population,” Dr. Han said. The Mediterranean diet, he added, “is sensible, and adding olive oil to your diet seems to have a positive effect on ... PASI, while fish oil seems to reduce C-reactive protein.” The data on the effect of vitamin D supplements are mixed, he said.
A separate randomized study evaluated the impact of weight loss in overweight or obese patients with psoriasis, who had not achieved clearance after 4 weeks of systemic treatment. Significantly more of those in the dietary intervention arm reached the weight loss goal of 5% at 20 weeks, and patients in this arm had a median reduction in the Psoriasis Area and Severity Index (PASI) score of almost 50%, compared with almost 26% among those without an active dietary intervention.
Joint pain, PsA
For psoriasis patients who complain of joint pain, he recommends administering quick measures like the five-question Psoriasis Epidemiology Screening Test (PEST) to screen for psoriatic arthritis (PsA), which is available on the National Psoriasis Foundation web site. “I ask patients about swollen, tender joints – specifically hands, wrists, ankles, feet, and toes,” Dr. Han said. Joint stiffness in the morning is a “concerning finding,” which is “more indicative of psoriatic arthritis than vague knee or back pain that worsens with use. If you have a younger patient with back pain who has a reduced ability to flex their spine, think axial disease.”
Tumor necrosis factor (TNF)–alpha inhibitors are considered first- and second-line treatment for PsA, but interleukin (IL)–17 inhibitors are generally considered just as effective overall. “The IL-23 inhibitors have mixed signals,” said Dr. Han, who is also on the NPF’s medical board. “We know that guselkumab is effective against psoriatic arthritis, but there is no inhibition of joint progression at the approved dosage on the label – though it was pretty close.”
Risankizumab (Skyrizi), an IL-23 inhibitor, was approved in January 2022 for adults with PsA and while the American College of Rheumatology response data “look reasonably good, the results for inhibition of radiographic progression are quite far off and it’s not in the label,” he said. Tildrakizumab (Ilumya), an IL-23 inhibitor, “looks impressive in phase 2b trials. It will be interesting to see if there is differentiation between the IL-23 agents in treating joint disease going forward.”
Dr. Han considers biologic therapy a good option for patients with questionable joint involvement or very limited joint disease. “If the patient has some evidence of PsA, as long as it’s a medication that has approval for that, I’m OK with starting it,” he said. “However, for patients whose joint pain dominates over the skin, or [who] have severe joint disease at presentation, I would prioritize the TNF-alpha inhibitors and IL-17s and refer them to rheumatology for shared management.”
Topical, oral treatments
As for topical approaches to treating psoriasis, adding halobetasol propionate 0.01% to tazarotene 0.045% may have a synergistic effect, while tapinarof 1% cream holds promise, he said. Tapinarof, which is expected to be approved this year, is an investigative aryl hydrocarbon agonist that inhibits an array of proinflammatory cytokines, including interferon-gamma and TNF-alpha. “It has been shown to have inhibitory effects both on Th17 cytokines and Th2 cytokines,” Dr. Han said. “What’s nice about this is that patients still appear to have treatment effect 1-2 months after stopping the drug.”
Another topical agent now under FDA review for psoriasis, is roflumilast, a phosphodiesterase type 4 (PDE4) inhibitor, which has been shown to have a treatment efficacy of 30% or more. “We’ll see how this works into our treatment regimen for psoriasis,” he said, as strategies targeting PDE4 have already been reported to help treat psoriasis.
With regards to oral therapies, he said that there are concerns about the efficacy of the oral PDE4 inhibitor apremilast, approved for psoriasis, compared with other biologics. Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor also under FDA review for psoriasis, “may fill this gap, because its efficacy seems much stronger and really capitalizes on blocking IL-23, which we know is a central pathway in the pathogenesis of psoriasis.”
Phototherapy is another treatment option. Home narrowband-UVB devices cost $3,000-$5,000, “which is a fraction of 1 year of biologic treatment,” Dr. Han said. Older data on phototherapy suggest that “lesions can clear within 2-3 months, depending on how often you do the phototherapy, while newer data suggest that 75% of patients can achieve clear or minimal disease” with phototherapy.
Biologic therapy
If patients meet criteria for treatment with a biologic, he begins the conversation by saying, “I don’t want to give you an immunosuppressant, but your psoriasis represents an overactivation of inflammation in your body, so in some way we have to bring that down. Ideally, we would target your immune system in a way that targets psoriasis very narrowly, while leaving it to do what it needs to: protecting against infections and neoplasia.”
XXXIL-17 inhibitors generally have the fastest onset of action, Dr. Han noted. Authors of a review paper found that achievement of Psoriasis Area and Severity Index (PASI) 50 was 1.8 weeks with brodalumab, 1.9 weeks for ixekizumab, 3 weeks for high-dose secukinumab, 3.5 weeks for adalimumab, 3.7 weeks for infliximab, 5.1 weeks for low-dose ustekinumab, 6.5 weeks for high-dose etanercept, and 10.9 weeks with low-dose etanercept, while achievement of PASI 50 was closer to 1 month for IL-23 inhibitors.
“The conversation I have with patients on IL-23 inhibitors is, ‘we’re in this for the long haul,’ otherwise they come in 2 months later,” he said. “They may have gotten clearer but we’re talking about getting well over half of our patients to PASI 100, or to clear or minimal disease, and they may not have gotten there yet. It helps to frame expectations.”
Dr. Han disclosed that he is a consultant to, a speaker for, or has received research support from Beiersdorf, CeraVe, Celgene, Janssen, Lilly, MC2, Pfizer, UCB, Boehringer Ingelheim, Bond Avillion, Athenex, Amgen, AbbVie, Regeneron/Sanofi, LEO Pharma, Ortho Dermatologics, BMS, Sun Pharma, Dermavant, Dermtech, MedX, Novartis, and Castle Biosciences.
FROM ODAC 2022
Prophylactic meds may prevent cesarean bleeding
Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.
The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.
“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.
Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”
Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).
Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.
“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.
Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.
“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”
Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”
Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.
“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.
The researchers reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.
The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.
“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.
Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”
Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).
Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.
“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.
Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.
“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”
Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”
Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.
“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.
The researchers reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.
The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.
“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.
Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”
Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).
Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.
“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.
Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.
“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”
Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”
Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.
“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.
The researchers reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
Study questions reliability of maternal drug testing
A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.
The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”
Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.
The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.
Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.
Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.
Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.
Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.
“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”
The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.
“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”
Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.
“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
Lack of standards
Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.
“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”
High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.
Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”
Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”
The researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.
The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”
Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.
The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.
Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.
Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.
Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.
Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.
“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”
The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.
“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”
Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.
“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
Lack of standards
Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.
“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”
High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.
Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”
Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”
The researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.
The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”
Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.
The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.
Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.
Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.
Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.
Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.
“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”
The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.
“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”
Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.
“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
Lack of standards
Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.
“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”
High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.
Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”
Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”
The researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE PREGNANCY MEETING
ctDNA identifies CRC patients who benefit from adjuvant therapy
SAN FRANCISCO — A
The team used a personalized tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay) to measure molecular residual disease (MRD) 4 weeks after surgery.
Among patients who were ctDNA positive at 4 weeks post-op, those who received adjuvant chemotherapy had significantly longer disease-free survival (DFS) at 6 months, compared with patients who didn’t receive it.
The adjuvant chemotherapy was able to clear ctDNA in 68% of that subgroup by 24 weeks, noted study author Masahito Kotaka, MD, PhD, from the gastrointestinal cancer center, Sano Hospital, Hyogo, Japan
“Even with an extended follow-up time, ctDNA positivity at 4 weeks post-op was significantly associated with inferior disease-free survival,” he said.
“Two out of three post-op patients who were positive at 4 weeks recurred, even in stage I or low-risk stage II.”
However, he noted that “patients who were 4 weeks post-op and ctDNA negative did not derive significant benefit from adjuvant chemotherapy in high- risk stage II and III.”
Overall, the study shows that stratifying postsurgical treatment decisions using the assay can identify patients likely to benefit from adjuvant chemotherapy across all stages of the disease, explained Dr. Kotaka.
Dr. Kotaka presented the new results at the Gastrointestinal Cancers Symposium.
“ctDNA dynamics from 4-week post-op positivity to 12 weeks afterwards could become new surrogate endpoints beyond disease-free survival,” he suggested.
However, the discussant for this abstract, Rona Yaeger, MD, from Memorial Sloan Kettering Cancer Center in New York, cautioned that this is not yet ready for clinical use.
“There was a clear prognostic effect,” she said. “This was a very large sample size and validates some of the earlier studies showing that ctDNA is a very important prognostic marker.” This study “gives us a tighter confidence interval due to the large size.”
However, there are limitations, one being that it was not a randomized study so it is unknown who received adjuvant therapy, she pointed out. “Since it is not randomized, the groups are not equal.”
Summarizing, she said that ctDNA is a strong prognostic marker that identifies MRD. “But it is expensive and currently doesn’t guide our adjuvant decisions,” she said. “It is not ready yet for standard evaluation of early-stage colorectal cancer patients, and we don’t know yet if additional therapy after adjuvant therapy in ctDNA-positive patients will change outcomes.”
Study details
The new results come from the GALAXY study, which is part of a large platform in Japan, called CIRCULATE, that is evaluating the clinical utility of ctDNA in patients with resectable colorectal cancer. Aside from GALAXY, which is a prospective observational trial, CIRCULATE also includes two phase 3 randomized trials: VEGA and ALTAIR.
For their study, Dr. Kotaka and colleagues monitored ctDNA status in patients with clinical stage l to IV colorectal cancer who underwent complete surgical resection and then evaluated the association of ctDNA dynamics with a short-term clinical outcome and adjuvant therapy efficacy.
A total of 1,040 patients were included in the current analysis. They were stratified into subgroups that were either ctDNA positive (n = 183) or ctDNA negative (n = 531) 4 weeks post surgery. The cohort included 116 patients with stage I disease, 478 with stage II, 503 with stage III, and 268 patients with oligomet resectable stage IV (of whom 16% received neoadjuvant chemotherapy).
Blood samples were collected before surgery and at 4, 12, 24, 36, 48, 72, and 96 weeks following resection.
The team looked at 6-month disease-free survival rates. Among patients with high-risk stage II disease and with a positive ctDNA assay at 4 weeks post-op, those who received adjuvant chemotherapy had a 6-month DFS rate of 100% vs. 53.8% who did not receive adjuvant chemotherapy.
For stage III disease, those rates were 89.2% vs. 32.0%, and for stage IV disease, they were 72.7% vs. 28.3%.
At a median follow-up of 11.4 months, the 6- and 12-month DFS was 96.5% and 92.7% for all patients who were ctDNA negative at 4 weeks post-op. Outcomes for patients who were ctDNA positive were significantly poorer, at 62.8% and 47.5% (hazard ratio, 10.9; P <.001; sensitivity for recurrence, 63.6%).
Of the 188 patients who were MRD positive at 4 weeks post-op with available MRD status at 12 weeks, 95 received adjuvant therapy. The ctDNA clearance rate at 12 weeks was significantly higher in the adjuvant therapy group vs. no adjuvant therapy; 57% vs. 8% in stage I-IV (P < .001), and 58% vs. 11% (4/37) in stage II–III (P < .001).
Additionally, the ctDNA clearance rate at 24 weeks was also significantly higher in adjuvant vs. no adjuvant therapy arms; 26% vs. 0% in patients with stage I-IV disease (P = .003), and 33% vs. 0% in patients with stage II-III disease (P = .03).
Cumulative clearance of ctDNA at 6 months post-op was significantly higher in the adjuvant vs. no adjuvant therapy arms (67% vs. 7% by 24 weeks; cumulative HR, 17.1; P < .001). For patients MRD positive at 4 weeks, the 6-month DFS was also significantly higher in adjuvant vs. no adjuvant therapy arms; 84% vs 34% (HR, 0.15; P < .001), which was observed across all stages.
Upon multivariate analysis, the highest risk of recurrence for patients with stage II-III cancer correlated with ctDNA-positive vs. ctDNA-negative status (HR, 15.3; P <. 001), mutant vs. wild-type RAS (HR, 1.8; P = .04), or mutant vs. wild-type BRAF (HR, 5.2; P < .001).
The group is continuing with its research into a ctDNA-guided adjuvant strategy. More data will be available soon from the ongoing randomized VEGA and ALTAIR studies and will be presented at future conference, Dr. Kotaka commented.
CIRCULATE‐Japan receives financial supports from the Japan Agency for Medical Research and Development and from Taiho Pharmaceutical, through Alpha‐A. Dr. Kotaka reported relationships with Chugai, Lilly Japan, Taiho, Takeda, and Yakult Honsha. Dr. Yaeger reported relationships with Array BioPharma, Boehringer Ingelheim, Mirati Therapeutics, Natera, and Pfizer.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO — A
The team used a personalized tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay) to measure molecular residual disease (MRD) 4 weeks after surgery.
Among patients who were ctDNA positive at 4 weeks post-op, those who received adjuvant chemotherapy had significantly longer disease-free survival (DFS) at 6 months, compared with patients who didn’t receive it.
The adjuvant chemotherapy was able to clear ctDNA in 68% of that subgroup by 24 weeks, noted study author Masahito Kotaka, MD, PhD, from the gastrointestinal cancer center, Sano Hospital, Hyogo, Japan
“Even with an extended follow-up time, ctDNA positivity at 4 weeks post-op was significantly associated with inferior disease-free survival,” he said.
“Two out of three post-op patients who were positive at 4 weeks recurred, even in stage I or low-risk stage II.”
However, he noted that “patients who were 4 weeks post-op and ctDNA negative did not derive significant benefit from adjuvant chemotherapy in high- risk stage II and III.”
Overall, the study shows that stratifying postsurgical treatment decisions using the assay can identify patients likely to benefit from adjuvant chemotherapy across all stages of the disease, explained Dr. Kotaka.
Dr. Kotaka presented the new results at the Gastrointestinal Cancers Symposium.
“ctDNA dynamics from 4-week post-op positivity to 12 weeks afterwards could become new surrogate endpoints beyond disease-free survival,” he suggested.
However, the discussant for this abstract, Rona Yaeger, MD, from Memorial Sloan Kettering Cancer Center in New York, cautioned that this is not yet ready for clinical use.
“There was a clear prognostic effect,” she said. “This was a very large sample size and validates some of the earlier studies showing that ctDNA is a very important prognostic marker.” This study “gives us a tighter confidence interval due to the large size.”
However, there are limitations, one being that it was not a randomized study so it is unknown who received adjuvant therapy, she pointed out. “Since it is not randomized, the groups are not equal.”
Summarizing, she said that ctDNA is a strong prognostic marker that identifies MRD. “But it is expensive and currently doesn’t guide our adjuvant decisions,” she said. “It is not ready yet for standard evaluation of early-stage colorectal cancer patients, and we don’t know yet if additional therapy after adjuvant therapy in ctDNA-positive patients will change outcomes.”
Study details
The new results come from the GALAXY study, which is part of a large platform in Japan, called CIRCULATE, that is evaluating the clinical utility of ctDNA in patients with resectable colorectal cancer. Aside from GALAXY, which is a prospective observational trial, CIRCULATE also includes two phase 3 randomized trials: VEGA and ALTAIR.
For their study, Dr. Kotaka and colleagues monitored ctDNA status in patients with clinical stage l to IV colorectal cancer who underwent complete surgical resection and then evaluated the association of ctDNA dynamics with a short-term clinical outcome and adjuvant therapy efficacy.
A total of 1,040 patients were included in the current analysis. They were stratified into subgroups that were either ctDNA positive (n = 183) or ctDNA negative (n = 531) 4 weeks post surgery. The cohort included 116 patients with stage I disease, 478 with stage II, 503 with stage III, and 268 patients with oligomet resectable stage IV (of whom 16% received neoadjuvant chemotherapy).
Blood samples were collected before surgery and at 4, 12, 24, 36, 48, 72, and 96 weeks following resection.
The team looked at 6-month disease-free survival rates. Among patients with high-risk stage II disease and with a positive ctDNA assay at 4 weeks post-op, those who received adjuvant chemotherapy had a 6-month DFS rate of 100% vs. 53.8% who did not receive adjuvant chemotherapy.
For stage III disease, those rates were 89.2% vs. 32.0%, and for stage IV disease, they were 72.7% vs. 28.3%.
At a median follow-up of 11.4 months, the 6- and 12-month DFS was 96.5% and 92.7% for all patients who were ctDNA negative at 4 weeks post-op. Outcomes for patients who were ctDNA positive were significantly poorer, at 62.8% and 47.5% (hazard ratio, 10.9; P <.001; sensitivity for recurrence, 63.6%).
Of the 188 patients who were MRD positive at 4 weeks post-op with available MRD status at 12 weeks, 95 received adjuvant therapy. The ctDNA clearance rate at 12 weeks was significantly higher in the adjuvant therapy group vs. no adjuvant therapy; 57% vs. 8% in stage I-IV (P < .001), and 58% vs. 11% (4/37) in stage II–III (P < .001).
Additionally, the ctDNA clearance rate at 24 weeks was also significantly higher in adjuvant vs. no adjuvant therapy arms; 26% vs. 0% in patients with stage I-IV disease (P = .003), and 33% vs. 0% in patients with stage II-III disease (P = .03).
Cumulative clearance of ctDNA at 6 months post-op was significantly higher in the adjuvant vs. no adjuvant therapy arms (67% vs. 7% by 24 weeks; cumulative HR, 17.1; P < .001). For patients MRD positive at 4 weeks, the 6-month DFS was also significantly higher in adjuvant vs. no adjuvant therapy arms; 84% vs 34% (HR, 0.15; P < .001), which was observed across all stages.
Upon multivariate analysis, the highest risk of recurrence for patients with stage II-III cancer correlated with ctDNA-positive vs. ctDNA-negative status (HR, 15.3; P <. 001), mutant vs. wild-type RAS (HR, 1.8; P = .04), or mutant vs. wild-type BRAF (HR, 5.2; P < .001).
The group is continuing with its research into a ctDNA-guided adjuvant strategy. More data will be available soon from the ongoing randomized VEGA and ALTAIR studies and will be presented at future conference, Dr. Kotaka commented.
CIRCULATE‐Japan receives financial supports from the Japan Agency for Medical Research and Development and from Taiho Pharmaceutical, through Alpha‐A. Dr. Kotaka reported relationships with Chugai, Lilly Japan, Taiho, Takeda, and Yakult Honsha. Dr. Yaeger reported relationships with Array BioPharma, Boehringer Ingelheim, Mirati Therapeutics, Natera, and Pfizer.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO — A
The team used a personalized tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay) to measure molecular residual disease (MRD) 4 weeks after surgery.
Among patients who were ctDNA positive at 4 weeks post-op, those who received adjuvant chemotherapy had significantly longer disease-free survival (DFS) at 6 months, compared with patients who didn’t receive it.
The adjuvant chemotherapy was able to clear ctDNA in 68% of that subgroup by 24 weeks, noted study author Masahito Kotaka, MD, PhD, from the gastrointestinal cancer center, Sano Hospital, Hyogo, Japan
“Even with an extended follow-up time, ctDNA positivity at 4 weeks post-op was significantly associated with inferior disease-free survival,” he said.
“Two out of three post-op patients who were positive at 4 weeks recurred, even in stage I or low-risk stage II.”
However, he noted that “patients who were 4 weeks post-op and ctDNA negative did not derive significant benefit from adjuvant chemotherapy in high- risk stage II and III.”
Overall, the study shows that stratifying postsurgical treatment decisions using the assay can identify patients likely to benefit from adjuvant chemotherapy across all stages of the disease, explained Dr. Kotaka.
Dr. Kotaka presented the new results at the Gastrointestinal Cancers Symposium.
“ctDNA dynamics from 4-week post-op positivity to 12 weeks afterwards could become new surrogate endpoints beyond disease-free survival,” he suggested.
However, the discussant for this abstract, Rona Yaeger, MD, from Memorial Sloan Kettering Cancer Center in New York, cautioned that this is not yet ready for clinical use.
“There was a clear prognostic effect,” she said. “This was a very large sample size and validates some of the earlier studies showing that ctDNA is a very important prognostic marker.” This study “gives us a tighter confidence interval due to the large size.”
However, there are limitations, one being that it was not a randomized study so it is unknown who received adjuvant therapy, she pointed out. “Since it is not randomized, the groups are not equal.”
Summarizing, she said that ctDNA is a strong prognostic marker that identifies MRD. “But it is expensive and currently doesn’t guide our adjuvant decisions,” she said. “It is not ready yet for standard evaluation of early-stage colorectal cancer patients, and we don’t know yet if additional therapy after adjuvant therapy in ctDNA-positive patients will change outcomes.”
Study details
The new results come from the GALAXY study, which is part of a large platform in Japan, called CIRCULATE, that is evaluating the clinical utility of ctDNA in patients with resectable colorectal cancer. Aside from GALAXY, which is a prospective observational trial, CIRCULATE also includes two phase 3 randomized trials: VEGA and ALTAIR.
For their study, Dr. Kotaka and colleagues monitored ctDNA status in patients with clinical stage l to IV colorectal cancer who underwent complete surgical resection and then evaluated the association of ctDNA dynamics with a short-term clinical outcome and adjuvant therapy efficacy.
A total of 1,040 patients were included in the current analysis. They were stratified into subgroups that were either ctDNA positive (n = 183) or ctDNA negative (n = 531) 4 weeks post surgery. The cohort included 116 patients with stage I disease, 478 with stage II, 503 with stage III, and 268 patients with oligomet resectable stage IV (of whom 16% received neoadjuvant chemotherapy).
Blood samples were collected before surgery and at 4, 12, 24, 36, 48, 72, and 96 weeks following resection.
The team looked at 6-month disease-free survival rates. Among patients with high-risk stage II disease and with a positive ctDNA assay at 4 weeks post-op, those who received adjuvant chemotherapy had a 6-month DFS rate of 100% vs. 53.8% who did not receive adjuvant chemotherapy.
For stage III disease, those rates were 89.2% vs. 32.0%, and for stage IV disease, they were 72.7% vs. 28.3%.
At a median follow-up of 11.4 months, the 6- and 12-month DFS was 96.5% and 92.7% for all patients who were ctDNA negative at 4 weeks post-op. Outcomes for patients who were ctDNA positive were significantly poorer, at 62.8% and 47.5% (hazard ratio, 10.9; P <.001; sensitivity for recurrence, 63.6%).
Of the 188 patients who were MRD positive at 4 weeks post-op with available MRD status at 12 weeks, 95 received adjuvant therapy. The ctDNA clearance rate at 12 weeks was significantly higher in the adjuvant therapy group vs. no adjuvant therapy; 57% vs. 8% in stage I-IV (P < .001), and 58% vs. 11% (4/37) in stage II–III (P < .001).
Additionally, the ctDNA clearance rate at 24 weeks was also significantly higher in adjuvant vs. no adjuvant therapy arms; 26% vs. 0% in patients with stage I-IV disease (P = .003), and 33% vs. 0% in patients with stage II-III disease (P = .03).
Cumulative clearance of ctDNA at 6 months post-op was significantly higher in the adjuvant vs. no adjuvant therapy arms (67% vs. 7% by 24 weeks; cumulative HR, 17.1; P < .001). For patients MRD positive at 4 weeks, the 6-month DFS was also significantly higher in adjuvant vs. no adjuvant therapy arms; 84% vs 34% (HR, 0.15; P < .001), which was observed across all stages.
Upon multivariate analysis, the highest risk of recurrence for patients with stage II-III cancer correlated with ctDNA-positive vs. ctDNA-negative status (HR, 15.3; P <. 001), mutant vs. wild-type RAS (HR, 1.8; P = .04), or mutant vs. wild-type BRAF (HR, 5.2; P < .001).
The group is continuing with its research into a ctDNA-guided adjuvant strategy. More data will be available soon from the ongoing randomized VEGA and ALTAIR studies and will be presented at future conference, Dr. Kotaka commented.
CIRCULATE‐Japan receives financial supports from the Japan Agency for Medical Research and Development and from Taiho Pharmaceutical, through Alpha‐A. Dr. Kotaka reported relationships with Chugai, Lilly Japan, Taiho, Takeda, and Yakult Honsha. Dr. Yaeger reported relationships with Array BioPharma, Boehringer Ingelheim, Mirati Therapeutics, Natera, and Pfizer.
A version of this article first appeared on Medscape.com.
FROM GI CANCERS SYMPOSIUM 2022
Dual immunotherapy promising new option for liver cancer
The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).
Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.
At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.
This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”
He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.
“But there are some limitations to the study and topics that will require further additional investigation,” he added.
Liver cancer increasing
Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.
Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.
“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.
Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.
Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.
The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).
Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.
At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.
Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.
The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.
Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.
Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.
New option for first-line treatment
In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.
Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.
Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.
“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.
STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.
Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.
Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.
“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”
For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.
“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”
HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”
This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.
A version of this article first appeared on Medscape.com.
The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).
Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.
At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.
This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”
He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.
“But there are some limitations to the study and topics that will require further additional investigation,” he added.
Liver cancer increasing
Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.
Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.
“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.
Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.
Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.
The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).
Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.
At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.
Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.
The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.
Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.
Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.
New option for first-line treatment
In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.
Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.
Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.
“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.
STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.
Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.
Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.
“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”
For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.
“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”
HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”
This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.
A version of this article first appeared on Medscape.com.
The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).
Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.
At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.
This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”
He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.
“But there are some limitations to the study and topics that will require further additional investigation,” he added.
Liver cancer increasing
Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.
Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.
“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.
Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.
Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.
The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).
Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.
At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.
Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.
The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.
Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.
Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.
New option for first-line treatment
In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.
Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.
Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.
“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.
STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.
Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.
Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.
“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”
For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.
“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”
HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”
This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM GI CANCERS SYMPOSIUM 2022
Adding TACE to lenvatinib improves survival in liver cancer
The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.
Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).
The study results were presented at the Gastrointestinal Cancers Symposium.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.
“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.
“However, it does not change the standard of care in the U.S.,” he cautioned.
“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.
Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.
Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”
Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.
He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
Improved outcomes with combination therapy
The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).
TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.
The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).
At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).
The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.
Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.
“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
Study limitations
In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”
This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.
Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).
The study results were presented at the Gastrointestinal Cancers Symposium.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.
“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.
“However, it does not change the standard of care in the U.S.,” he cautioned.
“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.
Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.
Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”
Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.
He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
Improved outcomes with combination therapy
The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).
TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.
The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).
At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).
The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.
Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.
“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
Study limitations
In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”
This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.
Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).
The study results were presented at the Gastrointestinal Cancers Symposium.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.
“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.
“However, it does not change the standard of care in the U.S.,” he cautioned.
“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.
Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.
Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”
Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.
He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
Improved outcomes with combination therapy
The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).
TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.
The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).
At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).
The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.
Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.
“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
Study limitations
In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”
This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
FROM GI CANCERS SYMPOSIUM 2022
LGBTQ parents fare worse giving birth
Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.
“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”
Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”
Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.
“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”
It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.
The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.
The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.
SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m2, compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.
In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).
“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”
Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.
Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.
“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”
Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.
“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.
Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.
“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”
One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.
It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.
”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”
The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.
Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.
“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”
Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”
Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.
“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”
It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.
The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.
The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.
SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m2, compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.
In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).
“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”
Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.
Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.
“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”
Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.
“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.
Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.
“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”
One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.
It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.
”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”
The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.
Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.
“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”
Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”
Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.
“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”
It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.
The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.
The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.
SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m2, compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.
In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).
“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”
Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.
Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.
“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”
Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.
“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.
Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.
“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”
One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.
It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.
”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”
The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.
FROM THE PREGNANCY MEETING
Real-world data reinforce stem cell transplant for progressive systemic sclerosis
Current selection criteria for autologous hematopoietic stem cell transplant (AHSCT) in patients with rapidly progressing systemic sclerosis were validated in a study presented at the annual meeting of the Canadian Rheumatology Association.
The study, which associated AHSCT with improvement in overall survival and an acceptable risk of adverse events, “provides valuable real-world, long-term data pertaining to key clinical outcomes to support the use of AHSCT in patients with rapidly progressing systemic sclerosis,” reported Nancy Maltez, MD, a rheumatologist and clinical investigator who is on the faculty of the University of Ottawa.
The prospective study enrolled 85 patients in Canada and 41 patients in France with rapidly progressing systemic sclerosis. The patients in both countries were enrolled with the same eligibility criteria for AHSCT, but patients in France underwent AHSCT while the patients in Canada were treated with conventional therapies, such as cyclophosphamide.
On the primary outcome of overall survival, the Kaplan-Meier curve split almost immediately in favor of AHSCT. At 4 years, more than 25% of patients in the conventional therapy group had died versus less than 5% of those who underwent AHSCT. Although the mortality curve did slope downwards in the AHSCT group over the subsequent 6 years of follow-up, it largely paralleled and remained superior to convention therapy.
About 50% survival advantage seen for AHSCT
In this nonrandomized study, the statistical survival advantage of AHSCT was not provided, but the survival graph showed about 75% survival at 8 years of follow-up in the AHSCT group, compared with about 50% survival in the conventional-therapy group.
Many of the secondary outcomes, including those evaluating skin involvement, preservation of lung function, and absence of renal complications also favored AHSCT, according to Dr. Maltez.
On the modified Rodnan skin score, a significant difference (P < .001) observed at 12 months was sustained at 36 months, when the score was 4.48 points lower among patients treated with AHSCT. The difference in forced vital capacity (FVC) was about 10% higher (P < .0001) in the AHSCT group.
Over long-term follow-up, the incidence of scleroderma renal crisis per 100 person-years was 6.02 cases in the conventional therapy group versus 0.58 cases (P < .001) in the AHSCT group. There was no significant difference in the proportion of patients in the two groups receiving a pacemaker over the course of follow-up, but the rate of new malignancies per 100 person-years was 3.71 in the conventional care group versus 0.58 (P < .001) in the AHSCT group.
Significant complications attributed to AHSCT were uncommon. This is important, because AHSCT was not uniformly well tolerated in the initial trials. The first of three randomized trials with AHSCT in progressive systemic sclerosis was published more than 10 years ago after a series of promising early phase trials. Each associated AHSCT with benefit, but patient selection appeared to be important.
In the ASSIST trial of 2011, AHSCT was associated with significant reductions in skin involvement and improvements in pulmonary function relative to cyclophosphamide, but enrollment was stopped after only 19 patients, and follow-up extended to only 2 years.
Substantial AHSCT-related mortality in ASTIS
In the second trial, called ASTIS, AHSCT was associated with a higher rate of mortality than cyclophosphamide after 1 year of follow-up, although there was a significantly greater long-term event-free survival for AHSCT when patients were followed out to 4 years. This study reinforced the need for cardiac screening because of because of concern that severe cardiac compromise contributed to the increased risk of AHSCT-related mortality.
The SCOT trial employed a high-intensity myeloablative conditioning regimen and total body irradiation prior to AHSCT. It is not clear that these contributed to improved survival, particularly because of the risk for irradiation to exacerbate complications in the lung and kidney, but AHSCT-related mortality was only 3% at 54 months. Patient enrollment criteria in this trial were also suspected of having played a role in the favorable results.
In the Canadian-French collaborative study, patients were considered eligible for AHSCT if they met the enrollment criteria used in the ASTIS trial, according to Dr. Maltez. She attributed the low rates of early mortality and relative absence of transplant-related death to the lessons learned in the published trials.
Overall, the data support the routine but selective use of AHSCT in rapidly progressing systemic sclerosis, Dr. Maltez concluded.
Maria Carolina Oliveira, MD, of the department of internal medicine at the University of São Paulo, generally agreed. A coauthor of a recent review of AHSCT for systemic sclerosis, Dr. Oliveira emphasized that patient selection is critical.
“AHSCT for systemic sclerosis has very specific inclusion criteria. Indeed, it is indicated for patients with severe and progressive disease but under two specific conditions: severe and progressive diffuse skin involvement and/or progressive interstitial lung disease,” she said in an interview.
Because of the thin line between benefit and risk according to disease subtypes and comorbidities, she said that it is important to be aware of relative contraindications and to recognize the risks of AHSCT.
At this time, and in the absence of better biomarkers to identify those most likely to benefit, “patients with other forms of severe scleroderma, such as those with pulmonary hypertension, scleroderma renal crisis, or severe cardiac involvement, for example, are not eligible,” she said.
Dr. Maltez and Dr. Oliveira reported having no potential conflicts of interest.
Current selection criteria for autologous hematopoietic stem cell transplant (AHSCT) in patients with rapidly progressing systemic sclerosis were validated in a study presented at the annual meeting of the Canadian Rheumatology Association.
The study, which associated AHSCT with improvement in overall survival and an acceptable risk of adverse events, “provides valuable real-world, long-term data pertaining to key clinical outcomes to support the use of AHSCT in patients with rapidly progressing systemic sclerosis,” reported Nancy Maltez, MD, a rheumatologist and clinical investigator who is on the faculty of the University of Ottawa.
The prospective study enrolled 85 patients in Canada and 41 patients in France with rapidly progressing systemic sclerosis. The patients in both countries were enrolled with the same eligibility criteria for AHSCT, but patients in France underwent AHSCT while the patients in Canada were treated with conventional therapies, such as cyclophosphamide.
On the primary outcome of overall survival, the Kaplan-Meier curve split almost immediately in favor of AHSCT. At 4 years, more than 25% of patients in the conventional therapy group had died versus less than 5% of those who underwent AHSCT. Although the mortality curve did slope downwards in the AHSCT group over the subsequent 6 years of follow-up, it largely paralleled and remained superior to convention therapy.
About 50% survival advantage seen for AHSCT
In this nonrandomized study, the statistical survival advantage of AHSCT was not provided, but the survival graph showed about 75% survival at 8 years of follow-up in the AHSCT group, compared with about 50% survival in the conventional-therapy group.
Many of the secondary outcomes, including those evaluating skin involvement, preservation of lung function, and absence of renal complications also favored AHSCT, according to Dr. Maltez.
On the modified Rodnan skin score, a significant difference (P < .001) observed at 12 months was sustained at 36 months, when the score was 4.48 points lower among patients treated with AHSCT. The difference in forced vital capacity (FVC) was about 10% higher (P < .0001) in the AHSCT group.
Over long-term follow-up, the incidence of scleroderma renal crisis per 100 person-years was 6.02 cases in the conventional therapy group versus 0.58 cases (P < .001) in the AHSCT group. There was no significant difference in the proportion of patients in the two groups receiving a pacemaker over the course of follow-up, but the rate of new malignancies per 100 person-years was 3.71 in the conventional care group versus 0.58 (P < .001) in the AHSCT group.
Significant complications attributed to AHSCT were uncommon. This is important, because AHSCT was not uniformly well tolerated in the initial trials. The first of three randomized trials with AHSCT in progressive systemic sclerosis was published more than 10 years ago after a series of promising early phase trials. Each associated AHSCT with benefit, but patient selection appeared to be important.
In the ASSIST trial of 2011, AHSCT was associated with significant reductions in skin involvement and improvements in pulmonary function relative to cyclophosphamide, but enrollment was stopped after only 19 patients, and follow-up extended to only 2 years.
Substantial AHSCT-related mortality in ASTIS
In the second trial, called ASTIS, AHSCT was associated with a higher rate of mortality than cyclophosphamide after 1 year of follow-up, although there was a significantly greater long-term event-free survival for AHSCT when patients were followed out to 4 years. This study reinforced the need for cardiac screening because of because of concern that severe cardiac compromise contributed to the increased risk of AHSCT-related mortality.
The SCOT trial employed a high-intensity myeloablative conditioning regimen and total body irradiation prior to AHSCT. It is not clear that these contributed to improved survival, particularly because of the risk for irradiation to exacerbate complications in the lung and kidney, but AHSCT-related mortality was only 3% at 54 months. Patient enrollment criteria in this trial were also suspected of having played a role in the favorable results.
In the Canadian-French collaborative study, patients were considered eligible for AHSCT if they met the enrollment criteria used in the ASTIS trial, according to Dr. Maltez. She attributed the low rates of early mortality and relative absence of transplant-related death to the lessons learned in the published trials.
Overall, the data support the routine but selective use of AHSCT in rapidly progressing systemic sclerosis, Dr. Maltez concluded.
Maria Carolina Oliveira, MD, of the department of internal medicine at the University of São Paulo, generally agreed. A coauthor of a recent review of AHSCT for systemic sclerosis, Dr. Oliveira emphasized that patient selection is critical.
“AHSCT for systemic sclerosis has very specific inclusion criteria. Indeed, it is indicated for patients with severe and progressive disease but under two specific conditions: severe and progressive diffuse skin involvement and/or progressive interstitial lung disease,” she said in an interview.
Because of the thin line between benefit and risk according to disease subtypes and comorbidities, she said that it is important to be aware of relative contraindications and to recognize the risks of AHSCT.
At this time, and in the absence of better biomarkers to identify those most likely to benefit, “patients with other forms of severe scleroderma, such as those with pulmonary hypertension, scleroderma renal crisis, or severe cardiac involvement, for example, are not eligible,” she said.
Dr. Maltez and Dr. Oliveira reported having no potential conflicts of interest.
Current selection criteria for autologous hematopoietic stem cell transplant (AHSCT) in patients with rapidly progressing systemic sclerosis were validated in a study presented at the annual meeting of the Canadian Rheumatology Association.
The study, which associated AHSCT with improvement in overall survival and an acceptable risk of adverse events, “provides valuable real-world, long-term data pertaining to key clinical outcomes to support the use of AHSCT in patients with rapidly progressing systemic sclerosis,” reported Nancy Maltez, MD, a rheumatologist and clinical investigator who is on the faculty of the University of Ottawa.
The prospective study enrolled 85 patients in Canada and 41 patients in France with rapidly progressing systemic sclerosis. The patients in both countries were enrolled with the same eligibility criteria for AHSCT, but patients in France underwent AHSCT while the patients in Canada were treated with conventional therapies, such as cyclophosphamide.
On the primary outcome of overall survival, the Kaplan-Meier curve split almost immediately in favor of AHSCT. At 4 years, more than 25% of patients in the conventional therapy group had died versus less than 5% of those who underwent AHSCT. Although the mortality curve did slope downwards in the AHSCT group over the subsequent 6 years of follow-up, it largely paralleled and remained superior to convention therapy.
About 50% survival advantage seen for AHSCT
In this nonrandomized study, the statistical survival advantage of AHSCT was not provided, but the survival graph showed about 75% survival at 8 years of follow-up in the AHSCT group, compared with about 50% survival in the conventional-therapy group.
Many of the secondary outcomes, including those evaluating skin involvement, preservation of lung function, and absence of renal complications also favored AHSCT, according to Dr. Maltez.
On the modified Rodnan skin score, a significant difference (P < .001) observed at 12 months was sustained at 36 months, when the score was 4.48 points lower among patients treated with AHSCT. The difference in forced vital capacity (FVC) was about 10% higher (P < .0001) in the AHSCT group.
Over long-term follow-up, the incidence of scleroderma renal crisis per 100 person-years was 6.02 cases in the conventional therapy group versus 0.58 cases (P < .001) in the AHSCT group. There was no significant difference in the proportion of patients in the two groups receiving a pacemaker over the course of follow-up, but the rate of new malignancies per 100 person-years was 3.71 in the conventional care group versus 0.58 (P < .001) in the AHSCT group.
Significant complications attributed to AHSCT were uncommon. This is important, because AHSCT was not uniformly well tolerated in the initial trials. The first of three randomized trials with AHSCT in progressive systemic sclerosis was published more than 10 years ago after a series of promising early phase trials. Each associated AHSCT with benefit, but patient selection appeared to be important.
In the ASSIST trial of 2011, AHSCT was associated with significant reductions in skin involvement and improvements in pulmonary function relative to cyclophosphamide, but enrollment was stopped after only 19 patients, and follow-up extended to only 2 years.
Substantial AHSCT-related mortality in ASTIS
In the second trial, called ASTIS, AHSCT was associated with a higher rate of mortality than cyclophosphamide after 1 year of follow-up, although there was a significantly greater long-term event-free survival for AHSCT when patients were followed out to 4 years. This study reinforced the need for cardiac screening because of because of concern that severe cardiac compromise contributed to the increased risk of AHSCT-related mortality.
The SCOT trial employed a high-intensity myeloablative conditioning regimen and total body irradiation prior to AHSCT. It is not clear that these contributed to improved survival, particularly because of the risk for irradiation to exacerbate complications in the lung and kidney, but AHSCT-related mortality was only 3% at 54 months. Patient enrollment criteria in this trial were also suspected of having played a role in the favorable results.
In the Canadian-French collaborative study, patients were considered eligible for AHSCT if they met the enrollment criteria used in the ASTIS trial, according to Dr. Maltez. She attributed the low rates of early mortality and relative absence of transplant-related death to the lessons learned in the published trials.
Overall, the data support the routine but selective use of AHSCT in rapidly progressing systemic sclerosis, Dr. Maltez concluded.
Maria Carolina Oliveira, MD, of the department of internal medicine at the University of São Paulo, generally agreed. A coauthor of a recent review of AHSCT for systemic sclerosis, Dr. Oliveira emphasized that patient selection is critical.
“AHSCT for systemic sclerosis has very specific inclusion criteria. Indeed, it is indicated for patients with severe and progressive disease but under two specific conditions: severe and progressive diffuse skin involvement and/or progressive interstitial lung disease,” she said in an interview.
Because of the thin line between benefit and risk according to disease subtypes and comorbidities, she said that it is important to be aware of relative contraindications and to recognize the risks of AHSCT.
At this time, and in the absence of better biomarkers to identify those most likely to benefit, “patients with other forms of severe scleroderma, such as those with pulmonary hypertension, scleroderma renal crisis, or severe cardiac involvement, for example, are not eligible,” she said.
Dr. Maltez and Dr. Oliveira reported having no potential conflicts of interest.
FROM THE ANNUAL MEETING OF THE CANADIAN RHEUMATOLOGY ASSOCIATION
How to advance equity, diversity, and inclusion in dermatology: Recommendations from an expert panel
– so he launched community outreach efforts with local businesses to attract patients from diverse backgrounds.
“For instance, I worked with U.S. Bank to give lectures on minorities in medicine and talked about outreach options and possible ways to include more ethnicities in medicine overall,” Dr. Qutub said during a panel discussion on equity, diversity, and inclusion (EDI) that took place at the ODAC Dermatology, Aesthetic & Surgical Conference. “I also did outreach with medical clinics in the area. Once patients are referred to you, they start to talk to people in their communities about you, and before you know it, you get people from their church and family members in your clinic.”
Dr. Qutub, who is ODAC’s director of Equity, Diversity, and Inclusion, kept EDI in mind when hiring staff for his practice, “to include candidates with varying experiences and backgrounds,” he said. “The idea was to make sure that when patients came into the clinic, they saw a varied group of individuals that were working together to help improve their health care outcomes. I found that made patients more comfortable in the clinic. It’s also important to have that representation daily in a larger setting like residency programs or multispecialty groups.”
Educational resources
Another panelist, Adam Friedman, MD, emphasized inclusivity of educational resources to ensure a dermatology workforce that can take care of all patients. “How can we expect the dermatology community to be able to treat anyone who comes through the door of their clinic if we don’t provide the resources that highlight and showcase the nuances and the diversity that skin disease has to offer?” asked Dr. Friedman, professor and chair of dermatology at George Washington University, Washington. “It comes down to educational tools and being purposeful when you’re putting together a talk or writing a paper, to be inclusive and have that on the top of your mind. It’s about saying right here, right now, we have to purposefully make a decision to be inclusive, to be welcoming to all so that we can practice at the highest level of our calling to treat everyone effectively and equitably.”
A unique feature of the atlas “is that we have taken multiple skin conditions, even common features such as erythema, and placed different skin tones side by side at the same angle to appreciate the full spectrum, and highlight those nuances,” Dr. Friedman said. “When you’re in clinic, when you see even common things like acne or seborrheic dermatitis,” he recommended taking photos to create a repository, “because you never know when that will be helpful when you want to show a medical student or a patient what something can look like on someone with a similar skin tone, or even to share with them how diverse skin conditions can appear across populations.”
Clinical research
Another way to help close racial gaps in dermatology is to improve access to mentorships and clinical research, according to panelist Chesahna Kindred, MD, of Kindred Hair & Skin Center in Columbia, Md. “We should be thoroughly embarrassed by the lack of diversity in our clinical trials,” she said.
In her role as chair of the dermatology section of the National Medical Association (NMA Derm), Dr. Kindred helped launch the NMA Derm research committee, which trains members to run clinical trials in their practices – an undertaking that was largely prompted by claims from pharmaceutical industry representatives that they struggle to find Black participants for clinical trials. “The truth of the matter is, if a Black patient doesn’t choose to go to Dr. Smith as a patient, they’re certainly not going to choose to go to Dr. Smith as a research participant,” Dr. Kindred said. “We have to meet those diverse populations where they are. By and large for Black patients, those are Black dermatologists.
In addition to meeting with primary investigators, she has been meeting with industry representatives, who she said are very interested in improving clinical trial diversity. “When a trial does not include a diverse population, we can call it out and say it is subpar,” she said.
In 2020, the Food and Drug Administration announced the availability of a guidance document, “Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs,” which includes recommendations for sponsors on how to increase enrollment of underrepresented populations in their clinical trials of medical products.
Dr. Kindred has created a clinical research unit in her own practice, in partnership with Howard University’s department of dermatology and NMA Dermatology.
Studies Dr. Kindred is involved with include those looking at the relationship between hair care products targeted to Black women and the development of central centrifugal cicatricial alopecia (CCCA). CCCA is getting worse with each generation, “and we think the cause might be environmental,” she said. “Studies show that there are almost zero percent carcinogens in hair care products that target Whites. But close to 100% of hair care products that target Blacks contain carcinogens and endocrine disrupting chemicals, the most common being phthalates, which are found in relaxers, chemicals that patients use to straighten their hair.”
Urinary phthalate concentrations have been found to be much higher in Black women than in White women, and one of the pilot studies she is involved with is checking the urinary phthalate levels in Black women with and without CCCA, to see if there is a correlation.
Mentorships
DiAnne S. Davis, MD, of North Dallas Dermatology Associates, rounded out the panel discussion by underscoring the importance of mentorships for underrepresented minority medical students, which includes providing guidance through the application process. “Mentorship is key to closing some of these gaps, particularly in our field of dermatology,” Dr. Davis said.
Through NMA Derm, Dr. Davis was tasked by one of her mentors, Dr. Kindred, to spearhead a mentorship program that pairs medical students with a mentor in the dermatology field, “so we can help guide them not only on their medical school process but help in coordinating research projects, and make them successful in matching to dermatology,” she said. “When students reach out to you, it’s important to take them under your wing or connect them to somebody you know so that we can increase the number of minority dermatologists.”
None of the panelists reported having disclosures relevant to their presentations.
– so he launched community outreach efforts with local businesses to attract patients from diverse backgrounds.
“For instance, I worked with U.S. Bank to give lectures on minorities in medicine and talked about outreach options and possible ways to include more ethnicities in medicine overall,” Dr. Qutub said during a panel discussion on equity, diversity, and inclusion (EDI) that took place at the ODAC Dermatology, Aesthetic & Surgical Conference. “I also did outreach with medical clinics in the area. Once patients are referred to you, they start to talk to people in their communities about you, and before you know it, you get people from their church and family members in your clinic.”
Dr. Qutub, who is ODAC’s director of Equity, Diversity, and Inclusion, kept EDI in mind when hiring staff for his practice, “to include candidates with varying experiences and backgrounds,” he said. “The idea was to make sure that when patients came into the clinic, they saw a varied group of individuals that were working together to help improve their health care outcomes. I found that made patients more comfortable in the clinic. It’s also important to have that representation daily in a larger setting like residency programs or multispecialty groups.”
Educational resources
Another panelist, Adam Friedman, MD, emphasized inclusivity of educational resources to ensure a dermatology workforce that can take care of all patients. “How can we expect the dermatology community to be able to treat anyone who comes through the door of their clinic if we don’t provide the resources that highlight and showcase the nuances and the diversity that skin disease has to offer?” asked Dr. Friedman, professor and chair of dermatology at George Washington University, Washington. “It comes down to educational tools and being purposeful when you’re putting together a talk or writing a paper, to be inclusive and have that on the top of your mind. It’s about saying right here, right now, we have to purposefully make a decision to be inclusive, to be welcoming to all so that we can practice at the highest level of our calling to treat everyone effectively and equitably.”
A unique feature of the atlas “is that we have taken multiple skin conditions, even common features such as erythema, and placed different skin tones side by side at the same angle to appreciate the full spectrum, and highlight those nuances,” Dr. Friedman said. “When you’re in clinic, when you see even common things like acne or seborrheic dermatitis,” he recommended taking photos to create a repository, “because you never know when that will be helpful when you want to show a medical student or a patient what something can look like on someone with a similar skin tone, or even to share with them how diverse skin conditions can appear across populations.”
Clinical research
Another way to help close racial gaps in dermatology is to improve access to mentorships and clinical research, according to panelist Chesahna Kindred, MD, of Kindred Hair & Skin Center in Columbia, Md. “We should be thoroughly embarrassed by the lack of diversity in our clinical trials,” she said.
In her role as chair of the dermatology section of the National Medical Association (NMA Derm), Dr. Kindred helped launch the NMA Derm research committee, which trains members to run clinical trials in their practices – an undertaking that was largely prompted by claims from pharmaceutical industry representatives that they struggle to find Black participants for clinical trials. “The truth of the matter is, if a Black patient doesn’t choose to go to Dr. Smith as a patient, they’re certainly not going to choose to go to Dr. Smith as a research participant,” Dr. Kindred said. “We have to meet those diverse populations where they are. By and large for Black patients, those are Black dermatologists.
In addition to meeting with primary investigators, she has been meeting with industry representatives, who she said are very interested in improving clinical trial diversity. “When a trial does not include a diverse population, we can call it out and say it is subpar,” she said.
In 2020, the Food and Drug Administration announced the availability of a guidance document, “Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs,” which includes recommendations for sponsors on how to increase enrollment of underrepresented populations in their clinical trials of medical products.
Dr. Kindred has created a clinical research unit in her own practice, in partnership with Howard University’s department of dermatology and NMA Dermatology.
Studies Dr. Kindred is involved with include those looking at the relationship between hair care products targeted to Black women and the development of central centrifugal cicatricial alopecia (CCCA). CCCA is getting worse with each generation, “and we think the cause might be environmental,” she said. “Studies show that there are almost zero percent carcinogens in hair care products that target Whites. But close to 100% of hair care products that target Blacks contain carcinogens and endocrine disrupting chemicals, the most common being phthalates, which are found in relaxers, chemicals that patients use to straighten their hair.”
Urinary phthalate concentrations have been found to be much higher in Black women than in White women, and one of the pilot studies she is involved with is checking the urinary phthalate levels in Black women with and without CCCA, to see if there is a correlation.
Mentorships
DiAnne S. Davis, MD, of North Dallas Dermatology Associates, rounded out the panel discussion by underscoring the importance of mentorships for underrepresented minority medical students, which includes providing guidance through the application process. “Mentorship is key to closing some of these gaps, particularly in our field of dermatology,” Dr. Davis said.
Through NMA Derm, Dr. Davis was tasked by one of her mentors, Dr. Kindred, to spearhead a mentorship program that pairs medical students with a mentor in the dermatology field, “so we can help guide them not only on their medical school process but help in coordinating research projects, and make them successful in matching to dermatology,” she said. “When students reach out to you, it’s important to take them under your wing or connect them to somebody you know so that we can increase the number of minority dermatologists.”
None of the panelists reported having disclosures relevant to their presentations.
– so he launched community outreach efforts with local businesses to attract patients from diverse backgrounds.
“For instance, I worked with U.S. Bank to give lectures on minorities in medicine and talked about outreach options and possible ways to include more ethnicities in medicine overall,” Dr. Qutub said during a panel discussion on equity, diversity, and inclusion (EDI) that took place at the ODAC Dermatology, Aesthetic & Surgical Conference. “I also did outreach with medical clinics in the area. Once patients are referred to you, they start to talk to people in their communities about you, and before you know it, you get people from their church and family members in your clinic.”
Dr. Qutub, who is ODAC’s director of Equity, Diversity, and Inclusion, kept EDI in mind when hiring staff for his practice, “to include candidates with varying experiences and backgrounds,” he said. “The idea was to make sure that when patients came into the clinic, they saw a varied group of individuals that were working together to help improve their health care outcomes. I found that made patients more comfortable in the clinic. It’s also important to have that representation daily in a larger setting like residency programs or multispecialty groups.”
Educational resources
Another panelist, Adam Friedman, MD, emphasized inclusivity of educational resources to ensure a dermatology workforce that can take care of all patients. “How can we expect the dermatology community to be able to treat anyone who comes through the door of their clinic if we don’t provide the resources that highlight and showcase the nuances and the diversity that skin disease has to offer?” asked Dr. Friedman, professor and chair of dermatology at George Washington University, Washington. “It comes down to educational tools and being purposeful when you’re putting together a talk or writing a paper, to be inclusive and have that on the top of your mind. It’s about saying right here, right now, we have to purposefully make a decision to be inclusive, to be welcoming to all so that we can practice at the highest level of our calling to treat everyone effectively and equitably.”
A unique feature of the atlas “is that we have taken multiple skin conditions, even common features such as erythema, and placed different skin tones side by side at the same angle to appreciate the full spectrum, and highlight those nuances,” Dr. Friedman said. “When you’re in clinic, when you see even common things like acne or seborrheic dermatitis,” he recommended taking photos to create a repository, “because you never know when that will be helpful when you want to show a medical student or a patient what something can look like on someone with a similar skin tone, or even to share with them how diverse skin conditions can appear across populations.”
Clinical research
Another way to help close racial gaps in dermatology is to improve access to mentorships and clinical research, according to panelist Chesahna Kindred, MD, of Kindred Hair & Skin Center in Columbia, Md. “We should be thoroughly embarrassed by the lack of diversity in our clinical trials,” she said.
In her role as chair of the dermatology section of the National Medical Association (NMA Derm), Dr. Kindred helped launch the NMA Derm research committee, which trains members to run clinical trials in their practices – an undertaking that was largely prompted by claims from pharmaceutical industry representatives that they struggle to find Black participants for clinical trials. “The truth of the matter is, if a Black patient doesn’t choose to go to Dr. Smith as a patient, they’re certainly not going to choose to go to Dr. Smith as a research participant,” Dr. Kindred said. “We have to meet those diverse populations where they are. By and large for Black patients, those are Black dermatologists.
In addition to meeting with primary investigators, she has been meeting with industry representatives, who she said are very interested in improving clinical trial diversity. “When a trial does not include a diverse population, we can call it out and say it is subpar,” she said.
In 2020, the Food and Drug Administration announced the availability of a guidance document, “Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs,” which includes recommendations for sponsors on how to increase enrollment of underrepresented populations in their clinical trials of medical products.
Dr. Kindred has created a clinical research unit in her own practice, in partnership with Howard University’s department of dermatology and NMA Dermatology.
Studies Dr. Kindred is involved with include those looking at the relationship between hair care products targeted to Black women and the development of central centrifugal cicatricial alopecia (CCCA). CCCA is getting worse with each generation, “and we think the cause might be environmental,” she said. “Studies show that there are almost zero percent carcinogens in hair care products that target Whites. But close to 100% of hair care products that target Blacks contain carcinogens and endocrine disrupting chemicals, the most common being phthalates, which are found in relaxers, chemicals that patients use to straighten their hair.”
Urinary phthalate concentrations have been found to be much higher in Black women than in White women, and one of the pilot studies she is involved with is checking the urinary phthalate levels in Black women with and without CCCA, to see if there is a correlation.
Mentorships
DiAnne S. Davis, MD, of North Dallas Dermatology Associates, rounded out the panel discussion by underscoring the importance of mentorships for underrepresented minority medical students, which includes providing guidance through the application process. “Mentorship is key to closing some of these gaps, particularly in our field of dermatology,” Dr. Davis said.
Through NMA Derm, Dr. Davis was tasked by one of her mentors, Dr. Kindred, to spearhead a mentorship program that pairs medical students with a mentor in the dermatology field, “so we can help guide them not only on their medical school process but help in coordinating research projects, and make them successful in matching to dermatology,” she said. “When students reach out to you, it’s important to take them under your wing or connect them to somebody you know so that we can increase the number of minority dermatologists.”
None of the panelists reported having disclosures relevant to their presentations.
FROM ODAC 2022