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Risankizumab in Crohn’s Disease: Clinical, Endoscopic Outcomes Remain Stable for up to 3 Years
STOCKHOLM — , according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”
Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents.
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”
Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents.
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”
Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents.
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
A version of this article appeared on Medscape.com.
FROM ECCO 2024
Capsule Endoscopy–Guided Treatment Reduces Flares in Crohn’s Disease Compared With Standard Care
STOCKHOLM — , a new study showed.
Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification.
The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.
Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus.
He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse.
The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months.
A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic.
The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care.
Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months.
A Nearly Threefold Difference
Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20).
By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported.
The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).
In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy.
“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.”
It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained.
The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out.
“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”
Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes.
She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”
“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted.
Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm.
Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.
A version of this article appeared on Medscape.com.
STOCKHOLM — , a new study showed.
Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification.
The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.
Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus.
He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse.
The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months.
A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic.
The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care.
Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months.
A Nearly Threefold Difference
Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20).
By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported.
The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).
In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy.
“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.”
It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained.
The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out.
“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”
Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes.
She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”
“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted.
Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm.
Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.
A version of this article appeared on Medscape.com.
STOCKHOLM — , a new study showed.
Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification.
The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.
Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus.
He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse.
The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months.
A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic.
The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care.
Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months.
A Nearly Threefold Difference
Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20).
By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported.
The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).
In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy.
“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.”
It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained.
The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out.
“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”
Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes.
She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”
“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted.
Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm.
Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.
A version of this article appeared on Medscape.com.
FROM ECCO 2024
Conservative management results in no greater morbidity than other alternatives after placenta accreta
NATIONAL HARBOR, MARYLAND — Rates of maternal morbidity in individuals with placenta accreta were similar with alternative strategies to cesarean hysterectomy regardless of the severity of the condition, based on data from 60 individuals.
Currently, the recommended management strategy for placenta accreta spectrum (PAS) is a cesarean hysterectomy, but data are lacking on alternative strategies, especially for individuals wishing to keep their uterus and potentially preserve fertility, Farah H. Amro, MD, of the University of Texas Health Science Center at Houston McGovern Medical School said in a presentation at the Pregnancy Meeting (abstract 70).
Alternative options are being studied worldwide, including delayed hysterectomy (typically performed at 4-6 weeks postpartum), Dr. Amro said at the meeting, which was sponsored by the Society for Maternal-Fetal Medicine.
At UT Houston, delayed hysterectomy is performed for more aggressive PAS that involves parametrial invasion, and the placenta left in situ until resorption/passage for those wishing to keep their uterus, Dr. Amro said in an interview.
In a cohort study at UT Houston, a level IV academic center, Dr. Amro and colleagues evaluated outcomes in 60 individuals with suspected PAS who were given three management options after extensive counseling. Of these, 29 opted for a cesarean hysterectomy (CH); 16 opted for delayed interval hysterectomy (IH) performed 4-6 weeks after delivery; and 15 individuals with a preference for uterine preservation were assigned to conservative management.
The study occurred between January 2020 and July 2023. The primary outcome was composite maternal morbidity, which was further divided into composite acute morbidity (within 24 hours from cesarean delivery or hysterectomy) and composite delayed morbidity (24 hours or more postoperatively). Secondary outcomes included total estimated blood loss, need for blood transfusion, unplanned hospital readmission, and pathology diagnosis.
Overall maternal morbidity rates were 55%, 56%, and 53% in the CH, IH, and CM groups, respectively, although those who were planned for IH and CM had more severe PAS.
The planned procedure was performed in 90% of the CH patients. Approximately 20% of patients in the IH and CM groups underwent unplanned procedures. No cases of sepsis or maternal death occurred, and uterine infection rates were 0%, 6%, and 13% in the CH, IH, and CM groups, respectively.
Patients in the CM and IH groups were significantly less likely to require blood transfusions than those in the CH group. In addition, composite delayed morbidity (24 hours or more after surgery) was similar among the groups, with rates of 31%, 38%, and 33% for CH, IH, and CM, respectively (P = .94). These results are important, given the concerns regarding leaving a placenta in situ after cesarean delivery, said Dr. Amro.
The findings were limited by several factors including the use of data from a single site, the lack of randomization, patient compliance, and cost effectiveness. However, the results were strengthened by the diverse population and comparison of novel approaches that aren’t frequently utilized In the United States, as well as the large volume of PAS cases treated in a relatively short time frame, Dr. Amro said.
More Options Empower Mothers
Overall, the results support the use of delayed hysterectomy and conservative management as safe alternatives to cesarean hysterectomy, especially in those with severe PAS (opting for IH Instead of CH) and those seeking to preserve the uterus (CM), Dr. Amro said. However, these alternative options can be offered only to patients who can engage in frequent postpartum follow-up and live close to the hospital; with the CM group, resorption/passage of the placenta may take as long as 6 months in some cases, she explained.
The greatest concerns with leaving the placenta in place in PAS patients are the risk of infection or subsequent hemorrhage, Dr. Amro said in an interview. However, the current study showed that the infection rate was not as high as anticipated, and the frequency of unplanned procedures occurred in only 20%, which should alleviate some of these concerns, she said.
“We have completed 28 cases of conservative management since 2015, four have gone on to successful pregnancy with no cases of PAS in the subsequent pregnancies,” Dr. Amro said. Conservative management gives mothers another option, she added. “Moms feel empowered by being given a choice, especially for those that want to keep their uterus for fertility or religious/cultural considerations, and many opt for CM.”
The next step is to take the conservative management strategy to larger groups at other centers to replicate the results in other locations, said Dr. Amro. “Also, we are looking at the utility of other interventions such as uterine artery embolization and performing delayed dilation and curettage to help with passage of the placenta in those opting for CM.”
Study Supports Safety of Conservative Management
“There are patients that may want to preserve their reproductive organs in the face of an accreta (such as for religious, cultural, and personal reasons), and this study helps address some of the safety considerations with conservative approaches,” Corrina M. Oxford-Horrey, MD, a maternal-fetal medicine specialist at Weill Cornell Medicine, New York, said in an interview.
“I was surprised that there was not a lot of infectious morbidity (such as sepsis) in the cohorts; that was helpful to see,” said Dr. Oxford-Horrey, who served as a moderator for the session in which the study was presented.
Based on the study findings, “nontraditional approaches to placenta accreta spectrum management may be reasonable, given similar overall postoperative composite morbidity between the groups,” she said.
As for additional research, replicating the study in a multicenter fashion would add to the generalizability of the findings, Dr. Oxford-Horrey said.
The study received no outside funding. The researchers and Dr. Oxford-Horrey had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — Rates of maternal morbidity in individuals with placenta accreta were similar with alternative strategies to cesarean hysterectomy regardless of the severity of the condition, based on data from 60 individuals.
Currently, the recommended management strategy for placenta accreta spectrum (PAS) is a cesarean hysterectomy, but data are lacking on alternative strategies, especially for individuals wishing to keep their uterus and potentially preserve fertility, Farah H. Amro, MD, of the University of Texas Health Science Center at Houston McGovern Medical School said in a presentation at the Pregnancy Meeting (abstract 70).
Alternative options are being studied worldwide, including delayed hysterectomy (typically performed at 4-6 weeks postpartum), Dr. Amro said at the meeting, which was sponsored by the Society for Maternal-Fetal Medicine.
At UT Houston, delayed hysterectomy is performed for more aggressive PAS that involves parametrial invasion, and the placenta left in situ until resorption/passage for those wishing to keep their uterus, Dr. Amro said in an interview.
In a cohort study at UT Houston, a level IV academic center, Dr. Amro and colleagues evaluated outcomes in 60 individuals with suspected PAS who were given three management options after extensive counseling. Of these, 29 opted for a cesarean hysterectomy (CH); 16 opted for delayed interval hysterectomy (IH) performed 4-6 weeks after delivery; and 15 individuals with a preference for uterine preservation were assigned to conservative management.
The study occurred between January 2020 and July 2023. The primary outcome was composite maternal morbidity, which was further divided into composite acute morbidity (within 24 hours from cesarean delivery or hysterectomy) and composite delayed morbidity (24 hours or more postoperatively). Secondary outcomes included total estimated blood loss, need for blood transfusion, unplanned hospital readmission, and pathology diagnosis.
Overall maternal morbidity rates were 55%, 56%, and 53% in the CH, IH, and CM groups, respectively, although those who were planned for IH and CM had more severe PAS.
The planned procedure was performed in 90% of the CH patients. Approximately 20% of patients in the IH and CM groups underwent unplanned procedures. No cases of sepsis or maternal death occurred, and uterine infection rates were 0%, 6%, and 13% in the CH, IH, and CM groups, respectively.
Patients in the CM and IH groups were significantly less likely to require blood transfusions than those in the CH group. In addition, composite delayed morbidity (24 hours or more after surgery) was similar among the groups, with rates of 31%, 38%, and 33% for CH, IH, and CM, respectively (P = .94). These results are important, given the concerns regarding leaving a placenta in situ after cesarean delivery, said Dr. Amro.
The findings were limited by several factors including the use of data from a single site, the lack of randomization, patient compliance, and cost effectiveness. However, the results were strengthened by the diverse population and comparison of novel approaches that aren’t frequently utilized In the United States, as well as the large volume of PAS cases treated in a relatively short time frame, Dr. Amro said.
More Options Empower Mothers
Overall, the results support the use of delayed hysterectomy and conservative management as safe alternatives to cesarean hysterectomy, especially in those with severe PAS (opting for IH Instead of CH) and those seeking to preserve the uterus (CM), Dr. Amro said. However, these alternative options can be offered only to patients who can engage in frequent postpartum follow-up and live close to the hospital; with the CM group, resorption/passage of the placenta may take as long as 6 months in some cases, she explained.
The greatest concerns with leaving the placenta in place in PAS patients are the risk of infection or subsequent hemorrhage, Dr. Amro said in an interview. However, the current study showed that the infection rate was not as high as anticipated, and the frequency of unplanned procedures occurred in only 20%, which should alleviate some of these concerns, she said.
“We have completed 28 cases of conservative management since 2015, four have gone on to successful pregnancy with no cases of PAS in the subsequent pregnancies,” Dr. Amro said. Conservative management gives mothers another option, she added. “Moms feel empowered by being given a choice, especially for those that want to keep their uterus for fertility or religious/cultural considerations, and many opt for CM.”
The next step is to take the conservative management strategy to larger groups at other centers to replicate the results in other locations, said Dr. Amro. “Also, we are looking at the utility of other interventions such as uterine artery embolization and performing delayed dilation and curettage to help with passage of the placenta in those opting for CM.”
Study Supports Safety of Conservative Management
“There are patients that may want to preserve their reproductive organs in the face of an accreta (such as for religious, cultural, and personal reasons), and this study helps address some of the safety considerations with conservative approaches,” Corrina M. Oxford-Horrey, MD, a maternal-fetal medicine specialist at Weill Cornell Medicine, New York, said in an interview.
“I was surprised that there was not a lot of infectious morbidity (such as sepsis) in the cohorts; that was helpful to see,” said Dr. Oxford-Horrey, who served as a moderator for the session in which the study was presented.
Based on the study findings, “nontraditional approaches to placenta accreta spectrum management may be reasonable, given similar overall postoperative composite morbidity between the groups,” she said.
As for additional research, replicating the study in a multicenter fashion would add to the generalizability of the findings, Dr. Oxford-Horrey said.
The study received no outside funding. The researchers and Dr. Oxford-Horrey had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — Rates of maternal morbidity in individuals with placenta accreta were similar with alternative strategies to cesarean hysterectomy regardless of the severity of the condition, based on data from 60 individuals.
Currently, the recommended management strategy for placenta accreta spectrum (PAS) is a cesarean hysterectomy, but data are lacking on alternative strategies, especially for individuals wishing to keep their uterus and potentially preserve fertility, Farah H. Amro, MD, of the University of Texas Health Science Center at Houston McGovern Medical School said in a presentation at the Pregnancy Meeting (abstract 70).
Alternative options are being studied worldwide, including delayed hysterectomy (typically performed at 4-6 weeks postpartum), Dr. Amro said at the meeting, which was sponsored by the Society for Maternal-Fetal Medicine.
At UT Houston, delayed hysterectomy is performed for more aggressive PAS that involves parametrial invasion, and the placenta left in situ until resorption/passage for those wishing to keep their uterus, Dr. Amro said in an interview.
In a cohort study at UT Houston, a level IV academic center, Dr. Amro and colleagues evaluated outcomes in 60 individuals with suspected PAS who were given three management options after extensive counseling. Of these, 29 opted for a cesarean hysterectomy (CH); 16 opted for delayed interval hysterectomy (IH) performed 4-6 weeks after delivery; and 15 individuals with a preference for uterine preservation were assigned to conservative management.
The study occurred between January 2020 and July 2023. The primary outcome was composite maternal morbidity, which was further divided into composite acute morbidity (within 24 hours from cesarean delivery or hysterectomy) and composite delayed morbidity (24 hours or more postoperatively). Secondary outcomes included total estimated blood loss, need for blood transfusion, unplanned hospital readmission, and pathology diagnosis.
Overall maternal morbidity rates were 55%, 56%, and 53% in the CH, IH, and CM groups, respectively, although those who were planned for IH and CM had more severe PAS.
The planned procedure was performed in 90% of the CH patients. Approximately 20% of patients in the IH and CM groups underwent unplanned procedures. No cases of sepsis or maternal death occurred, and uterine infection rates were 0%, 6%, and 13% in the CH, IH, and CM groups, respectively.
Patients in the CM and IH groups were significantly less likely to require blood transfusions than those in the CH group. In addition, composite delayed morbidity (24 hours or more after surgery) was similar among the groups, with rates of 31%, 38%, and 33% for CH, IH, and CM, respectively (P = .94). These results are important, given the concerns regarding leaving a placenta in situ after cesarean delivery, said Dr. Amro.
The findings were limited by several factors including the use of data from a single site, the lack of randomization, patient compliance, and cost effectiveness. However, the results were strengthened by the diverse population and comparison of novel approaches that aren’t frequently utilized In the United States, as well as the large volume of PAS cases treated in a relatively short time frame, Dr. Amro said.
More Options Empower Mothers
Overall, the results support the use of delayed hysterectomy and conservative management as safe alternatives to cesarean hysterectomy, especially in those with severe PAS (opting for IH Instead of CH) and those seeking to preserve the uterus (CM), Dr. Amro said. However, these alternative options can be offered only to patients who can engage in frequent postpartum follow-up and live close to the hospital; with the CM group, resorption/passage of the placenta may take as long as 6 months in some cases, she explained.
The greatest concerns with leaving the placenta in place in PAS patients are the risk of infection or subsequent hemorrhage, Dr. Amro said in an interview. However, the current study showed that the infection rate was not as high as anticipated, and the frequency of unplanned procedures occurred in only 20%, which should alleviate some of these concerns, she said.
“We have completed 28 cases of conservative management since 2015, four have gone on to successful pregnancy with no cases of PAS in the subsequent pregnancies,” Dr. Amro said. Conservative management gives mothers another option, she added. “Moms feel empowered by being given a choice, especially for those that want to keep their uterus for fertility or religious/cultural considerations, and many opt for CM.”
The next step is to take the conservative management strategy to larger groups at other centers to replicate the results in other locations, said Dr. Amro. “Also, we are looking at the utility of other interventions such as uterine artery embolization and performing delayed dilation and curettage to help with passage of the placenta in those opting for CM.”
Study Supports Safety of Conservative Management
“There are patients that may want to preserve their reproductive organs in the face of an accreta (such as for religious, cultural, and personal reasons), and this study helps address some of the safety considerations with conservative approaches,” Corrina M. Oxford-Horrey, MD, a maternal-fetal medicine specialist at Weill Cornell Medicine, New York, said in an interview.
“I was surprised that there was not a lot of infectious morbidity (such as sepsis) in the cohorts; that was helpful to see,” said Dr. Oxford-Horrey, who served as a moderator for the session in which the study was presented.
Based on the study findings, “nontraditional approaches to placenta accreta spectrum management may be reasonable, given similar overall postoperative composite morbidity between the groups,” she said.
As for additional research, replicating the study in a multicenter fashion would add to the generalizability of the findings, Dr. Oxford-Horrey said.
The study received no outside funding. The researchers and Dr. Oxford-Horrey had no financial conflicts to disclose.
AT THE PREGNANCY MEETING
Adding Antithrombotic to tPA Does Not Improve Stroke Outcome
PHOENIX — , results of new research show.
“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri.
The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said.
The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.
The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.”
Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective.
Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto.
The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.
All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).
Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
Two Different Mechanisms
The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.
Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.
The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.
The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial.
Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study.
The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.
The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial.
In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto.
No Increased ICH Risk
The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.
The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug.
Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase.
Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.”
But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence.
“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.”
Down the Rabbit Hole
Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful.
“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.”
He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.”
Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
PHOENIX — , results of new research show.
“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri.
The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said.
The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.
The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.”
Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective.
Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto.
The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.
All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).
Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
Two Different Mechanisms
The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.
Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.
The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.
The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial.
Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study.
The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.
The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial.
In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto.
No Increased ICH Risk
The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.
The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug.
Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase.
Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.”
But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence.
“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.”
Down the Rabbit Hole
Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful.
“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.”
He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.”
Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
PHOENIX — , results of new research show.
“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri.
The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said.
The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.
The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.”
Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective.
Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto.
The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.
All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).
Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
Two Different Mechanisms
The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.
Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.
The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.
The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial.
Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study.
The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.
The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial.
In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto.
No Increased ICH Risk
The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.
The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug.
Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase.
Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.”
But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence.
“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.”
Down the Rabbit Hole
Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful.
“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.”
He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.”
Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM ISC 2024
Expanded Window of Stroke Thrombectomy With Simpler Imaging
PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.
“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD.
“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.
However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.
Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.
“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”
The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.
“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.
The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.
They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.
These patients were identified exclusively using non-contrast CT and CT angiography imaging.
The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.
The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.
The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
Conflicting Results on Shift Analysis
The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.
This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).
“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.
The researchers therefore used the secondary outcomes as the main results of the study.
These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).
The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.
But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).
The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.
Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.
“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.
A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.
“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
Frailty: A Ceiling Effect?
Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.
“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.
“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”
Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.
“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
Interpreting the Findings
Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.
“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”
Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.
Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”
He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.
The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
A version of this article appeared on Medscape.com.
PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.
“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD.
“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.
However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.
Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.
“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”
The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.
“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.
The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.
They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.
These patients were identified exclusively using non-contrast CT and CT angiography imaging.
The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.
The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.
The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
Conflicting Results on Shift Analysis
The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.
This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).
“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.
The researchers therefore used the secondary outcomes as the main results of the study.
These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).
The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.
But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).
The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.
Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.
“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.
A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.
“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
Frailty: A Ceiling Effect?
Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.
“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.
“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”
Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.
“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
Interpreting the Findings
Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.
“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”
Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.
Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”
He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.
The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
A version of this article appeared on Medscape.com.
PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.
“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD.
“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.
However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.
Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.
“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”
The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.
“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.
The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.
They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.
These patients were identified exclusively using non-contrast CT and CT angiography imaging.
The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.
The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.
The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
Conflicting Results on Shift Analysis
The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.
This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).
“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.
The researchers therefore used the secondary outcomes as the main results of the study.
These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).
The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.
But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).
The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.
Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.
“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.
A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.
“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
Frailty: A Ceiling Effect?
Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.
“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.
“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”
Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.
“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
Interpreting the Findings
Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.
“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”
Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.
Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”
He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.
The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
A version of this article appeared on Medscape.com.
From ISC 2004
Hypertension Before Age 35 Tied to Triple Stroke Risk in Midlife
PHOENIX — , new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.
“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”
Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.
“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
A Large Study Cohort
The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.
Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.
At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.
Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.
The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).
“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”
He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.
“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.
“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
The Role of Psychosocial Stressors
Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.
She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.
This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.
“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.
“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.
The authors reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHOENIX — , new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.
“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”
Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.
“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
A Large Study Cohort
The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.
Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.
At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.
Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.
The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).
“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”
He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.
“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.
“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
The Role of Psychosocial Stressors
Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.
She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.
This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.
“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.
“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.
The authors reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHOENIX — , new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.
“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”
Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.
“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
A Large Study Cohort
The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.
Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.
At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.
Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.
The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).
“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”
He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.
“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.
“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
The Role of Psychosocial Stressors
Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.
She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.
This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.
“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.
“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.
The authors reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ISC 2024
Obesity’s Effect on Neonatal Outcomes Is Dose Dependent
TOPLINE:
Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.
METHODOLOGY:
- Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
- They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
- 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.
TAKEAWAY:
- Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
- Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
- Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
- With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
- Obesity also was associated with increased risk for grade III-IV (RR), 4.58 for class III obesity) and (RR, 3.76).
IN PRACTICE:
“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported.
SOURCE:
Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland.
DISCLOSURES:
The researchers had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.
METHODOLOGY:
- Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
- They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
- 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.
TAKEAWAY:
- Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
- Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
- Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
- With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
- Obesity also was associated with increased risk for grade III-IV (RR), 4.58 for class III obesity) and (RR, 3.76).
IN PRACTICE:
“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported.
SOURCE:
Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland.
DISCLOSURES:
The researchers had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.
METHODOLOGY:
- Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
- They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
- 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.
TAKEAWAY:
- Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
- Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
- Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
- With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
- Obesity also was associated with increased risk for grade III-IV (RR), 4.58 for class III obesity) and (RR, 3.76).
IN PRACTICE:
“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported.
SOURCE:
Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland.
DISCLOSURES:
The researchers had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
Lying-in No Longer: Staying Active Key to Healthy Pregnancy
A trio of studies (abstracts 1101, 1079, and 944) presented on February 14 at the meeting sponsored by the Society for Maternal-Fetal Medicine point to the power of staying physically active during pregnancy. The work highlights the beneficial effects of exercise on a variety of outcomes, including depression, anxiety, and reducing the rate of cesarean deliveries.
“Twenty-plus years ago, there were so many recommendations for bed rest in pregnancy,” said Danielle Panelli, MD, a maternal-fetal medicine physician and research scholar at Stanford University in Stanford, California. “We’ve really come full circle on that.” The American College of Obstetricians and Gynecologists recommends pregnant people get at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week.
Dr. Panelli and colleagues looked at the association of physical activity and anxiety among three groups of pregnant people: 20 outpatients from low-risk obstetric clinics, 20 outpatients from high-risk obstetric clinics, and 19 inpatients. Participants wore accelerometer watches for up to seven days to measure physical activity. The primary outcome was mean daily step count, with secondary outcomes including metabolic equivalent tasks (METs), moderate to vigorous physical activity (MVPA), and anxiety as measured using the State-Trait Anxiety Inventory.
Low-risk outpatients had an average daily step count of 9090 compared with high-risk outpatients at 8898 and inpatients at 6493. Compared with outpatients, inpatients also had significantly lower METs (adjusted beta, -0.20; 95% CI -0.26 to -0.13; P < .001), and MVPAs (adjusted beta, -43.6; 95% CI, -61.2 to -25.9; P < .001). Over the course of a week, steps progressively decreased for inpatients but not for women in either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30; P = .02).
“These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people,” Dr. Panelli said. That could be something as simple as asking patients to walk three laps around the unit per day, she suggested.
A second study investigated the effect of physical activity during pregnancy on peripartum depression. Researchers at the University of Alabama at Birmingham reviewed data from participants in nuMoM2b, a large cohort study of pregnant women who would be delivering for the first time and had at least one medical comorbidity, such as chronic hypertension, asthma, or cardiac disease. The investigators looked at activity logs maintained by study participants and turned in at three study visits: 6-13.6 weeks, 14-21.6 weeks, and 22-29.6 weeks.
Being physically active was associated with 15% lower odds of having an Edinburgh Postnatal Depression Score (EPDS) > 10 (adjusted odds ratio, 0.85; 95% CI, 0.72-0.99). Nine percent of people in the active group and 12% of people in the nonactive group had an EPDS > 10, which is suggestive of depression. However, a change in EPDS from visit one to three and treatment for perinatal depression did not differ by physical activity.
“One of the interesting findings are that we didn’t see any safety signals [from exercise], so there wasn’t an increase in suspected fetal growth restriction or low fluid or preterm birth, or actual birthweight being low in the people who were active,” said Charlotte McCarley, MD, a maternal-fetal medicine fellow at the University of Alabama at Birmingham, who led the research. “A lot of studies have been done that have looked at prospective exercise in pregnancy, but they exclude the cohort that we looked at for concern that there may be a safety issue.”
In a third study, researchers at the Rambam Health Care Campus in Haifa, Israel, looked at the effect of physical activity on mode of delivery. The prospective observational analysis included 401 women with singleton pregnancies attempting vaginal deliveries.
The researchers tracked the number of daily steps taken during gestation using validated phone apps. They adjusted their findings for age, parity, body mass index, and medical and obstetric history.
The investigators observed a gradual decrease in physical activity as pregnancy progressed (mean of 3184 steps in the first trimester, 2700 steps in mid-pregnancy, and 2152 steps in the third trimester). The overall incidence of cesarean delivery was 10.5%. However, women who were more active during pregnancy had a significantly lower incidence of cesarean delivery.
Area under the ROC curve, with a cut-off of 2093.5 daily steps, was 0.694 (95% CI, 0.615-0.773), resulting in a significant risk reduction in a 78% reduction in the rate of cesarean surgery (odds ratio, 0.22; 95% CI, 0.104-0.465).
More active patients also had a reduced composite outcome of gestational diabetes, gestational hypertension, and preeclampsia; less use of epidural analgesia during labor; and less postpartum hemorrhage. Preterm birth, labor induction, neonatal weight, and admission to the neonatal intensive care unit were not significantly affected, the researchers reported.
“Maintaining an active lifestyle during pregnancy should be strongly encouraged,” they wrote.
The investigators disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
A trio of studies (abstracts 1101, 1079, and 944) presented on February 14 at the meeting sponsored by the Society for Maternal-Fetal Medicine point to the power of staying physically active during pregnancy. The work highlights the beneficial effects of exercise on a variety of outcomes, including depression, anxiety, and reducing the rate of cesarean deliveries.
“Twenty-plus years ago, there were so many recommendations for bed rest in pregnancy,” said Danielle Panelli, MD, a maternal-fetal medicine physician and research scholar at Stanford University in Stanford, California. “We’ve really come full circle on that.” The American College of Obstetricians and Gynecologists recommends pregnant people get at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week.
Dr. Panelli and colleagues looked at the association of physical activity and anxiety among three groups of pregnant people: 20 outpatients from low-risk obstetric clinics, 20 outpatients from high-risk obstetric clinics, and 19 inpatients. Participants wore accelerometer watches for up to seven days to measure physical activity. The primary outcome was mean daily step count, with secondary outcomes including metabolic equivalent tasks (METs), moderate to vigorous physical activity (MVPA), and anxiety as measured using the State-Trait Anxiety Inventory.
Low-risk outpatients had an average daily step count of 9090 compared with high-risk outpatients at 8898 and inpatients at 6493. Compared with outpatients, inpatients also had significantly lower METs (adjusted beta, -0.20; 95% CI -0.26 to -0.13; P < .001), and MVPAs (adjusted beta, -43.6; 95% CI, -61.2 to -25.9; P < .001). Over the course of a week, steps progressively decreased for inpatients but not for women in either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30; P = .02).
“These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people,” Dr. Panelli said. That could be something as simple as asking patients to walk three laps around the unit per day, she suggested.
A second study investigated the effect of physical activity during pregnancy on peripartum depression. Researchers at the University of Alabama at Birmingham reviewed data from participants in nuMoM2b, a large cohort study of pregnant women who would be delivering for the first time and had at least one medical comorbidity, such as chronic hypertension, asthma, or cardiac disease. The investigators looked at activity logs maintained by study participants and turned in at three study visits: 6-13.6 weeks, 14-21.6 weeks, and 22-29.6 weeks.
Being physically active was associated with 15% lower odds of having an Edinburgh Postnatal Depression Score (EPDS) > 10 (adjusted odds ratio, 0.85; 95% CI, 0.72-0.99). Nine percent of people in the active group and 12% of people in the nonactive group had an EPDS > 10, which is suggestive of depression. However, a change in EPDS from visit one to three and treatment for perinatal depression did not differ by physical activity.
“One of the interesting findings are that we didn’t see any safety signals [from exercise], so there wasn’t an increase in suspected fetal growth restriction or low fluid or preterm birth, or actual birthweight being low in the people who were active,” said Charlotte McCarley, MD, a maternal-fetal medicine fellow at the University of Alabama at Birmingham, who led the research. “A lot of studies have been done that have looked at prospective exercise in pregnancy, but they exclude the cohort that we looked at for concern that there may be a safety issue.”
In a third study, researchers at the Rambam Health Care Campus in Haifa, Israel, looked at the effect of physical activity on mode of delivery. The prospective observational analysis included 401 women with singleton pregnancies attempting vaginal deliveries.
The researchers tracked the number of daily steps taken during gestation using validated phone apps. They adjusted their findings for age, parity, body mass index, and medical and obstetric history.
The investigators observed a gradual decrease in physical activity as pregnancy progressed (mean of 3184 steps in the first trimester, 2700 steps in mid-pregnancy, and 2152 steps in the third trimester). The overall incidence of cesarean delivery was 10.5%. However, women who were more active during pregnancy had a significantly lower incidence of cesarean delivery.
Area under the ROC curve, with a cut-off of 2093.5 daily steps, was 0.694 (95% CI, 0.615-0.773), resulting in a significant risk reduction in a 78% reduction in the rate of cesarean surgery (odds ratio, 0.22; 95% CI, 0.104-0.465).
More active patients also had a reduced composite outcome of gestational diabetes, gestational hypertension, and preeclampsia; less use of epidural analgesia during labor; and less postpartum hemorrhage. Preterm birth, labor induction, neonatal weight, and admission to the neonatal intensive care unit were not significantly affected, the researchers reported.
“Maintaining an active lifestyle during pregnancy should be strongly encouraged,” they wrote.
The investigators disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
A trio of studies (abstracts 1101, 1079, and 944) presented on February 14 at the meeting sponsored by the Society for Maternal-Fetal Medicine point to the power of staying physically active during pregnancy. The work highlights the beneficial effects of exercise on a variety of outcomes, including depression, anxiety, and reducing the rate of cesarean deliveries.
“Twenty-plus years ago, there were so many recommendations for bed rest in pregnancy,” said Danielle Panelli, MD, a maternal-fetal medicine physician and research scholar at Stanford University in Stanford, California. “We’ve really come full circle on that.” The American College of Obstetricians and Gynecologists recommends pregnant people get at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week.
Dr. Panelli and colleagues looked at the association of physical activity and anxiety among three groups of pregnant people: 20 outpatients from low-risk obstetric clinics, 20 outpatients from high-risk obstetric clinics, and 19 inpatients. Participants wore accelerometer watches for up to seven days to measure physical activity. The primary outcome was mean daily step count, with secondary outcomes including metabolic equivalent tasks (METs), moderate to vigorous physical activity (MVPA), and anxiety as measured using the State-Trait Anxiety Inventory.
Low-risk outpatients had an average daily step count of 9090 compared with high-risk outpatients at 8898 and inpatients at 6493. Compared with outpatients, inpatients also had significantly lower METs (adjusted beta, -0.20; 95% CI -0.26 to -0.13; P < .001), and MVPAs (adjusted beta, -43.6; 95% CI, -61.2 to -25.9; P < .001). Over the course of a week, steps progressively decreased for inpatients but not for women in either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30; P = .02).
“These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people,” Dr. Panelli said. That could be something as simple as asking patients to walk three laps around the unit per day, she suggested.
A second study investigated the effect of physical activity during pregnancy on peripartum depression. Researchers at the University of Alabama at Birmingham reviewed data from participants in nuMoM2b, a large cohort study of pregnant women who would be delivering for the first time and had at least one medical comorbidity, such as chronic hypertension, asthma, or cardiac disease. The investigators looked at activity logs maintained by study participants and turned in at three study visits: 6-13.6 weeks, 14-21.6 weeks, and 22-29.6 weeks.
Being physically active was associated with 15% lower odds of having an Edinburgh Postnatal Depression Score (EPDS) > 10 (adjusted odds ratio, 0.85; 95% CI, 0.72-0.99). Nine percent of people in the active group and 12% of people in the nonactive group had an EPDS > 10, which is suggestive of depression. However, a change in EPDS from visit one to three and treatment for perinatal depression did not differ by physical activity.
“One of the interesting findings are that we didn’t see any safety signals [from exercise], so there wasn’t an increase in suspected fetal growth restriction or low fluid or preterm birth, or actual birthweight being low in the people who were active,” said Charlotte McCarley, MD, a maternal-fetal medicine fellow at the University of Alabama at Birmingham, who led the research. “A lot of studies have been done that have looked at prospective exercise in pregnancy, but they exclude the cohort that we looked at for concern that there may be a safety issue.”
In a third study, researchers at the Rambam Health Care Campus in Haifa, Israel, looked at the effect of physical activity on mode of delivery. The prospective observational analysis included 401 women with singleton pregnancies attempting vaginal deliveries.
The researchers tracked the number of daily steps taken during gestation using validated phone apps. They adjusted their findings for age, parity, body mass index, and medical and obstetric history.
The investigators observed a gradual decrease in physical activity as pregnancy progressed (mean of 3184 steps in the first trimester, 2700 steps in mid-pregnancy, and 2152 steps in the third trimester). The overall incidence of cesarean delivery was 10.5%. However, women who were more active during pregnancy had a significantly lower incidence of cesarean delivery.
Area under the ROC curve, with a cut-off of 2093.5 daily steps, was 0.694 (95% CI, 0.615-0.773), resulting in a significant risk reduction in a 78% reduction in the rate of cesarean surgery (odds ratio, 0.22; 95% CI, 0.104-0.465).
More active patients also had a reduced composite outcome of gestational diabetes, gestational hypertension, and preeclampsia; less use of epidural analgesia during labor; and less postpartum hemorrhage. Preterm birth, labor induction, neonatal weight, and admission to the neonatal intensive care unit were not significantly affected, the researchers reported.
“Maintaining an active lifestyle during pregnancy should be strongly encouraged,” they wrote.
The investigators disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM THE PREGNANCY MEETING
Insulin and Oral Diabetes Drugs Are Similarly Effective for Gestational Diabetes
NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
Data Support Orals as Effective Gestational Diabetes Option
“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.
Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.
The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.
Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.
A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.
Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.
The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
Data Support Orals as Effective Gestational Diabetes Option
“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.
Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.
The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.
Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.
A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.
Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.
The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
Data Support Orals as Effective Gestational Diabetes Option
“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.
Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.
The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.
Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.
A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.
Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.
The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.
FROM THE PREGNANCY MEETING
Adverse pregnancy outcomes in first pregnancy are likely to recur
NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.
Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).
Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.
Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.
The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.
An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.
The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.
The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.
Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.
However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.
In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.
“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.
However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.
The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
Data May Inform Patient Guidance
“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.
“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.
“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.
The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.
Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).
Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.
Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.
The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.
An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.
The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.
The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.
Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.
However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.
In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.
“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.
However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.
The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
Data May Inform Patient Guidance
“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.
“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.
“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.
The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.
Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).
Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.
Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.
The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.
An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.
The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.
The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.
Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.
However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.
In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.
“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.
However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.
The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
Data May Inform Patient Guidance
“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.
“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.
“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.
The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.
FROM THE PREGNANCY MEETING