User login
Uric Acid Levels, Gout Symptoms Improved With Plant-Based Diet in Pilot Trial
A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found.
There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet.
Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands.
Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy.
The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).
Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).
At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said.
She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said.
The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.
During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.
She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.
Kretova reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found.
There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet.
Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands.
Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy.
The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).
Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).
At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said.
She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said.
The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.
During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.
She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.
Kretova reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found.
There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet.
Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands.
Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy.
The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).
Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).
At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said.
She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said.
The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.
During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.
She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.
Kretova reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM G-CAN 2024
New Gout Remission Criteria Approved
In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas.
The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:
- Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
- No gout flares over 12 months
- No tophi
- Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
- Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.
Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.
Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”
“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.
Simplified Version Created With Only Three Criteria
In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.
To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).
Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.
Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah.
Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.
Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.
During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked.
Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said.
During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.
Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said.
Tabi-Amponsah and Dalbeth did not disclose any financial relationships.
A version of this article appeared on Medscape.com.
In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas.
The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:
- Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
- No gout flares over 12 months
- No tophi
- Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
- Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.
Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.
Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”
“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.
Simplified Version Created With Only Three Criteria
In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.
To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).
Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.
Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah.
Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.
Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.
During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked.
Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said.
During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.
Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said.
Tabi-Amponsah and Dalbeth did not disclose any financial relationships.
A version of this article appeared on Medscape.com.
In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas.
The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:
- Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
- No gout flares over 12 months
- No tophi
- Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
- Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.
Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.
Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”
“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.
Simplified Version Created With Only Three Criteria
In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.
To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).
Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.
Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah.
Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.
Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.
During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked.
Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said.
During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.
Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said.
Tabi-Amponsah and Dalbeth did not disclose any financial relationships.
A version of this article appeared on Medscape.com.
FROM G-CAN 2024
Could Probiotics Tuned to Reduce Intestinal Urate Counter Gout?
Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.
Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.
Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.
Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.
There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.
Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways.
Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine.
Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said.
During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.
Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.
Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.
Dodd disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.
Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.
Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.
Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.
There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.
Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways.
Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine.
Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said.
During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.
Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.
Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.
Dodd disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.
Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.
Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.
Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.
There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.
Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways.
Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine.
Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said.
During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.
Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.
Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.
Dodd disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM G-CAN 2024
Social Adversity Increases Mortality Risk in Patients With Pulmonary Hypertension
BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population.
A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.
“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.
“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.
Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.
The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).
Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028).
The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.
Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.
The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.
That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.
Dr. Biavati and Dr. Jain reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population.
A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.
“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.
“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.
Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.
The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).
Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028).
The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.
Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.
The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.
That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.
Dr. Biavati and Dr. Jain reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population.
A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.
“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.
“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.
Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.
The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).
Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028).
The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.
Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.
The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.
That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.
Dr. Biavati and Dr. Jain reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CHEST 2024
Digital Twin Model Predicts Sepsis Mortality
A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis.
The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.
The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.
The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.
The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.
At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.
The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.
She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.
Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.
Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis.
The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.
The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.
The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.
The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.
At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.
The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.
She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.
Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.
Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis.
The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.
The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.
The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.
The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.
At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.
The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.
She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.
Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.
Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CHEST 2024
ILD Linked to Poorer Outcomes in Pulmonary Embolism
BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.
Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.
The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.
The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).
Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).
In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.
“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.
He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.
Yuan and Rali disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.
Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.
The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.
The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).
Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).
In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.
“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.
He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.
Yuan and Rali disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.
Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.
The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.
The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).
Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).
In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.
“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.
He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.
Yuan and Rali disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
CHEST 2024
Use of SGLT2 Inhibitors Associated With Better Survival in PAH
BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.
“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).
At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).
The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.
Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.
Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.
Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.
The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.
“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).
At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).
The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.
Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.
Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.
Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.
The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.
“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).
At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).
The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.
Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.
Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.
Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.
The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CHEST 2024
Hospitalized Patients With COPD and GERD Have Better Short-Term Outcomes
BOSTON — Gastroesophageal reflux disease (GERD) is associated with better in-hospital outcomes for patients hospitalized with chronic obstructive pulmonary disease (COPD).
“It was a very surprising result. We double-checked the analysis once we got it the first time because the whole expectation was that the outcomes will be worse. But because it’s a retrospective study and it’s based on a national database, there are some limitations,” said ABM Nasibul Alam, MD, who presented the study at the annual meeting of the American College of Chest Physicians (CHEST) . Alam is an internal medicine resident at Northwestern Medicine McHenry Hospital, McHenry, Illinois.
One possible conclusion is that acid reflux therapies received in hospital may be benefitting COPD. The retrospective nature of the study precludes establishing a causal relationship, but there are possible mechanisms that could account for a benefit, according to Alam.
“They might prevent micro-aspirations or silent aspirations in COPD patients. Sometimes you may not have a clinical diagnosis of GERD, but the patient might have silent micro-aspirations, so it might contribute to decreasing that,” said Alam.
The study was conducted to fill a gap in the literature. “Some studies have shown that the lung function in COPD patients gets moderately decreased if they have coexisting GERD, but there aren’t any studies that have looked into how it impacts COPD patients when they’re hospitalized, and especially acute complications,” said Alam.
The researchers retrospectively analyzed data from the Nationwide Readmissions Database from 2017 to 2020, utilizing ICD-10 codes to identify 3,798,952 hospitalized adults with a primary diagnosis of COPD, of which 26.97% also had GERD. Individuals without GERD were more likely to be male (47.72% vs 39.88%).
After multivariate adjustment, the presence of GERD was associated with a lower mortality rate (adjusted odds ratio [aOR], 0.717; P < .001) and reduced risks for acute respiratory failure (aOR, 0.915; P < .001), need for noninvasive mechanical ventilation (aOR, 0.907; P < .001), need for invasive ventilation for 24 hours or more (aOR, 0.727; P < .001), acute kidney injury (aOR, 0.877; P < .001), septic shock (aOR, 0.731; P < .001), and acute heart failure (aOR, 0.762; P < .001).
Despite these improved in-hospital outcomes, the researchers found that patients with GERD were at a higher risk for 30-day readmission (aOR, 1.08; P < .001). They also had slightly longer lengths of stay (+0.09 day; P < .001) and lower total charges (−$2824.5996; P < .001).
There have also been studies suggesting that GERD can directly lead to worse lung function among patients with COPD. “So it will be interesting to see if these medications have some kind of impact on the lung function as well. We need more robust studies [to determine that],” said Alam.
It is also important to keep in mind the long-term risk of proton pump inhibitors, especially in older patients. “We have to have good data before we start recommending this,” said Alam.
He suggested that physicians should begin to think more holistically about COPD management and consider the comorbidities. Alam has studied vitamin B12 deficiency in patients with COPD and found an association with cardiovascular comorbidities. “There are so many comorbidities with COPD. COPD itself puts patients at risk of cardiovascular comorbidity, for example. So when we have patients with COPD, we have to think about all those comorbidities and have to manage the patients comprehensively rather than just focusing on the specific targeted interventions,” said Alam.
The study should encourage further research, according to Kunal Deokar, MD, who moderated the session where the study was presented. “It does give us a signal that probably we should have more studies to look into whether patients hospitalized for COPD with GERD really have lower mortality rates, and what will be the effect of treatment on these patients,” said Deokar, who is an assistant professor of pulmonary medicine at the All India Institute of Medical Sciences, Delhi, India.
Alam and Deokar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON — Gastroesophageal reflux disease (GERD) is associated with better in-hospital outcomes for patients hospitalized with chronic obstructive pulmonary disease (COPD).
“It was a very surprising result. We double-checked the analysis once we got it the first time because the whole expectation was that the outcomes will be worse. But because it’s a retrospective study and it’s based on a national database, there are some limitations,” said ABM Nasibul Alam, MD, who presented the study at the annual meeting of the American College of Chest Physicians (CHEST) . Alam is an internal medicine resident at Northwestern Medicine McHenry Hospital, McHenry, Illinois.
One possible conclusion is that acid reflux therapies received in hospital may be benefitting COPD. The retrospective nature of the study precludes establishing a causal relationship, but there are possible mechanisms that could account for a benefit, according to Alam.
“They might prevent micro-aspirations or silent aspirations in COPD patients. Sometimes you may not have a clinical diagnosis of GERD, but the patient might have silent micro-aspirations, so it might contribute to decreasing that,” said Alam.
The study was conducted to fill a gap in the literature. “Some studies have shown that the lung function in COPD patients gets moderately decreased if they have coexisting GERD, but there aren’t any studies that have looked into how it impacts COPD patients when they’re hospitalized, and especially acute complications,” said Alam.
The researchers retrospectively analyzed data from the Nationwide Readmissions Database from 2017 to 2020, utilizing ICD-10 codes to identify 3,798,952 hospitalized adults with a primary diagnosis of COPD, of which 26.97% also had GERD. Individuals without GERD were more likely to be male (47.72% vs 39.88%).
After multivariate adjustment, the presence of GERD was associated with a lower mortality rate (adjusted odds ratio [aOR], 0.717; P < .001) and reduced risks for acute respiratory failure (aOR, 0.915; P < .001), need for noninvasive mechanical ventilation (aOR, 0.907; P < .001), need for invasive ventilation for 24 hours or more (aOR, 0.727; P < .001), acute kidney injury (aOR, 0.877; P < .001), septic shock (aOR, 0.731; P < .001), and acute heart failure (aOR, 0.762; P < .001).
Despite these improved in-hospital outcomes, the researchers found that patients with GERD were at a higher risk for 30-day readmission (aOR, 1.08; P < .001). They also had slightly longer lengths of stay (+0.09 day; P < .001) and lower total charges (−$2824.5996; P < .001).
There have also been studies suggesting that GERD can directly lead to worse lung function among patients with COPD. “So it will be interesting to see if these medications have some kind of impact on the lung function as well. We need more robust studies [to determine that],” said Alam.
It is also important to keep in mind the long-term risk of proton pump inhibitors, especially in older patients. “We have to have good data before we start recommending this,” said Alam.
He suggested that physicians should begin to think more holistically about COPD management and consider the comorbidities. Alam has studied vitamin B12 deficiency in patients with COPD and found an association with cardiovascular comorbidities. “There are so many comorbidities with COPD. COPD itself puts patients at risk of cardiovascular comorbidity, for example. So when we have patients with COPD, we have to think about all those comorbidities and have to manage the patients comprehensively rather than just focusing on the specific targeted interventions,” said Alam.
The study should encourage further research, according to Kunal Deokar, MD, who moderated the session where the study was presented. “It does give us a signal that probably we should have more studies to look into whether patients hospitalized for COPD with GERD really have lower mortality rates, and what will be the effect of treatment on these patients,” said Deokar, who is an assistant professor of pulmonary medicine at the All India Institute of Medical Sciences, Delhi, India.
Alam and Deokar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON — Gastroesophageal reflux disease (GERD) is associated with better in-hospital outcomes for patients hospitalized with chronic obstructive pulmonary disease (COPD).
“It was a very surprising result. We double-checked the analysis once we got it the first time because the whole expectation was that the outcomes will be worse. But because it’s a retrospective study and it’s based on a national database, there are some limitations,” said ABM Nasibul Alam, MD, who presented the study at the annual meeting of the American College of Chest Physicians (CHEST) . Alam is an internal medicine resident at Northwestern Medicine McHenry Hospital, McHenry, Illinois.
One possible conclusion is that acid reflux therapies received in hospital may be benefitting COPD. The retrospective nature of the study precludes establishing a causal relationship, but there are possible mechanisms that could account for a benefit, according to Alam.
“They might prevent micro-aspirations or silent aspirations in COPD patients. Sometimes you may not have a clinical diagnosis of GERD, but the patient might have silent micro-aspirations, so it might contribute to decreasing that,” said Alam.
The study was conducted to fill a gap in the literature. “Some studies have shown that the lung function in COPD patients gets moderately decreased if they have coexisting GERD, but there aren’t any studies that have looked into how it impacts COPD patients when they’re hospitalized, and especially acute complications,” said Alam.
The researchers retrospectively analyzed data from the Nationwide Readmissions Database from 2017 to 2020, utilizing ICD-10 codes to identify 3,798,952 hospitalized adults with a primary diagnosis of COPD, of which 26.97% also had GERD. Individuals without GERD were more likely to be male (47.72% vs 39.88%).
After multivariate adjustment, the presence of GERD was associated with a lower mortality rate (adjusted odds ratio [aOR], 0.717; P < .001) and reduced risks for acute respiratory failure (aOR, 0.915; P < .001), need for noninvasive mechanical ventilation (aOR, 0.907; P < .001), need for invasive ventilation for 24 hours or more (aOR, 0.727; P < .001), acute kidney injury (aOR, 0.877; P < .001), septic shock (aOR, 0.731; P < .001), and acute heart failure (aOR, 0.762; P < .001).
Despite these improved in-hospital outcomes, the researchers found that patients with GERD were at a higher risk for 30-day readmission (aOR, 1.08; P < .001). They also had slightly longer lengths of stay (+0.09 day; P < .001) and lower total charges (−$2824.5996; P < .001).
There have also been studies suggesting that GERD can directly lead to worse lung function among patients with COPD. “So it will be interesting to see if these medications have some kind of impact on the lung function as well. We need more robust studies [to determine that],” said Alam.
It is also important to keep in mind the long-term risk of proton pump inhibitors, especially in older patients. “We have to have good data before we start recommending this,” said Alam.
He suggested that physicians should begin to think more holistically about COPD management and consider the comorbidities. Alam has studied vitamin B12 deficiency in patients with COPD and found an association with cardiovascular comorbidities. “There are so many comorbidities with COPD. COPD itself puts patients at risk of cardiovascular comorbidity, for example. So when we have patients with COPD, we have to think about all those comorbidities and have to manage the patients comprehensively rather than just focusing on the specific targeted interventions,” said Alam.
The study should encourage further research, according to Kunal Deokar, MD, who moderated the session where the study was presented. “It does give us a signal that probably we should have more studies to look into whether patients hospitalized for COPD with GERD really have lower mortality rates, and what will be the effect of treatment on these patients,” said Deokar, who is an assistant professor of pulmonary medicine at the All India Institute of Medical Sciences, Delhi, India.
Alam and Deokar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CHEST 2024
In Crohn’s Disease, Early Anti-TNF Levels May be Crucial
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
Nasal Staph Aureus Carriage Linked to Surgical Infections
published in the August issue of Open Forum Infectious Diseases.
“This was a pan-European study with many hospitals, many different clinical settings, and as far as I’m aware, it hasn’t been done before. [The new study] covers a lot of European countries and a lot of surgical specialties,” said lead author Jan Kluytmans, MD. The study also captures the current state of preventive strategies in surgery, such as changes in air flow, dress, and skin preparation, he added.
The study included 5004 patients from 33 hospitals in ten European countries, of whom 67.3% were found to be SA carriers. The median age was 65 years, and 49.8% of patients were male. Open cardiac, and knee and hip prosthesis surgeries made up the largest fraction, but there were 12 types of surgery included in the study.
There were 100 SA surgical site or blood infections. The researchers found an association between surgical site or blood infection and SA carriage at any site (adjusted hazard ratio [aHR], 4.6; 95% CI, 2.1-10.0) and nasal SA carriage (aHR, 4.2; 95% CI, 2.0-8.6). Extranasal SA carriage was not associated with an increased infection risk.
Each 1-unit increase in nasal bacteria was associated with an increase in infection risk (aHR, 1.23; 95% CI, 1.05-1.43).
A strength of the study is that it is the largest prospective study yet conducted on SA carriage in surgical patients, but the researchers were unable to do a subgroup of methicillin-resistant SA (MRSA) due to small numbers of infections.
The study confirms the value of the decolonization strategy, which the World Health Organization has endorsed with the highest level of scientific evidence that is available in preventive strategies in surgery. WHO strongly recommends decolonization for cardiothoracic and orthopedic surgery using intranasal applications of mupirocin 2% ointment with or without a combination of chlorhexidine gluconate body wash. It has a conditional recommendation for a similar procedure before other types of surgery.
However, “It is not widely practiced, and although that was not a surprise to me, I think it’s really disappointing to see that proven effective strategies are not being practiced,” said Dr. Kluytmans, professor of medical microbiology at University Medical Center Utrecht, Utrecht University, the Netherlands. “If I would come into surgery being a carrier, and not be decolonized, I would really be quite angry because it puts you at risk, which is preventable. I think that’s something we owe to our patients,” he said.
He said that some may have concerns about the potential for decolonization to contribute to antibiotic resistance, but the short-term prophylaxis — typically a few days — should not foster resistance, according to Dr. Kluytmans. “If you use it short term, just before surgery, it has been shown in many studies that resistance isn’t a big problem and it can be monitored.”
The link specifically to SA nasal carriage is a mystery, according to Dr. Kluytmans. “It puzzles me still how it gets from the nares to the wound during surgery. So that’s my million-dollar question that I would like to resolve. We would like to study it, but we haven’t quite a bright idea how to do that,” he said.
The results are compelling, according to Heather Evans, MD, who was asked for comment. “On the face of it, this looks like a no-brainer. We should be decolonizing all patients that go to the operating room, and it’s not a terribly unpleasant thing for a patient to undergo to have decolonization done. Particularly for patients who are at higher risk for having a severe complication, like someone that has an operation that’s involving an implant, for example, I think it really makes a lot of sense to do this low-cost intervention for those patients,” said Dr. Evans, professor of medicine at The Medical University of South Carolina as well as the president of the Surgical Infection Society.
She noted that many facilities test for methicillin-resistant SA, but usual not SA more broadly. “This is a very interesting and compelling study that makes us rethink that, and maybe it isn’t even worth testing to see if you have staph aureus, maybe we should just be putting Betadine in everyone’s nostrils when they come to the operating room. It just seems like it would be a pretty low-cost intervention and something that could potentially have a big impact,” said Dr. Evans.
Although she was impressed by the study, Dr. Evans noted that the researchers tested for carriage at sites unrelated to the surgical site. “It really made me wonder if it would have added even more credibility to the study if there had been a sample taken after surgical prep was done to demonstrate that there is actually no staph aureus present on the skin at the time that the wound was made,” she said.
The question ties into the recent “Trojan horse” hypothesis, which suggests that endemic carriage of bacteria is responsible for most surgical site infections, rather than the long-held belief that operating room contamination is to blame. “That would sort of fly with this study, that the patient is walking around with Staph aureus and not necessarily on their skin or at their surgical site, but it’s endemic in their body,” said Dr. Evans.
Dr. Kluytmans and Dr. Evans have no relevant financial disclosures.
published in the August issue of Open Forum Infectious Diseases.
“This was a pan-European study with many hospitals, many different clinical settings, and as far as I’m aware, it hasn’t been done before. [The new study] covers a lot of European countries and a lot of surgical specialties,” said lead author Jan Kluytmans, MD. The study also captures the current state of preventive strategies in surgery, such as changes in air flow, dress, and skin preparation, he added.
The study included 5004 patients from 33 hospitals in ten European countries, of whom 67.3% were found to be SA carriers. The median age was 65 years, and 49.8% of patients were male. Open cardiac, and knee and hip prosthesis surgeries made up the largest fraction, but there were 12 types of surgery included in the study.
There were 100 SA surgical site or blood infections. The researchers found an association between surgical site or blood infection and SA carriage at any site (adjusted hazard ratio [aHR], 4.6; 95% CI, 2.1-10.0) and nasal SA carriage (aHR, 4.2; 95% CI, 2.0-8.6). Extranasal SA carriage was not associated with an increased infection risk.
Each 1-unit increase in nasal bacteria was associated with an increase in infection risk (aHR, 1.23; 95% CI, 1.05-1.43).
A strength of the study is that it is the largest prospective study yet conducted on SA carriage in surgical patients, but the researchers were unable to do a subgroup of methicillin-resistant SA (MRSA) due to small numbers of infections.
The study confirms the value of the decolonization strategy, which the World Health Organization has endorsed with the highest level of scientific evidence that is available in preventive strategies in surgery. WHO strongly recommends decolonization for cardiothoracic and orthopedic surgery using intranasal applications of mupirocin 2% ointment with or without a combination of chlorhexidine gluconate body wash. It has a conditional recommendation for a similar procedure before other types of surgery.
However, “It is not widely practiced, and although that was not a surprise to me, I think it’s really disappointing to see that proven effective strategies are not being practiced,” said Dr. Kluytmans, professor of medical microbiology at University Medical Center Utrecht, Utrecht University, the Netherlands. “If I would come into surgery being a carrier, and not be decolonized, I would really be quite angry because it puts you at risk, which is preventable. I think that’s something we owe to our patients,” he said.
He said that some may have concerns about the potential for decolonization to contribute to antibiotic resistance, but the short-term prophylaxis — typically a few days — should not foster resistance, according to Dr. Kluytmans. “If you use it short term, just before surgery, it has been shown in many studies that resistance isn’t a big problem and it can be monitored.”
The link specifically to SA nasal carriage is a mystery, according to Dr. Kluytmans. “It puzzles me still how it gets from the nares to the wound during surgery. So that’s my million-dollar question that I would like to resolve. We would like to study it, but we haven’t quite a bright idea how to do that,” he said.
The results are compelling, according to Heather Evans, MD, who was asked for comment. “On the face of it, this looks like a no-brainer. We should be decolonizing all patients that go to the operating room, and it’s not a terribly unpleasant thing for a patient to undergo to have decolonization done. Particularly for patients who are at higher risk for having a severe complication, like someone that has an operation that’s involving an implant, for example, I think it really makes a lot of sense to do this low-cost intervention for those patients,” said Dr. Evans, professor of medicine at The Medical University of South Carolina as well as the president of the Surgical Infection Society.
She noted that many facilities test for methicillin-resistant SA, but usual not SA more broadly. “This is a very interesting and compelling study that makes us rethink that, and maybe it isn’t even worth testing to see if you have staph aureus, maybe we should just be putting Betadine in everyone’s nostrils when they come to the operating room. It just seems like it would be a pretty low-cost intervention and something that could potentially have a big impact,” said Dr. Evans.
Although she was impressed by the study, Dr. Evans noted that the researchers tested for carriage at sites unrelated to the surgical site. “It really made me wonder if it would have added even more credibility to the study if there had been a sample taken after surgical prep was done to demonstrate that there is actually no staph aureus present on the skin at the time that the wound was made,” she said.
The question ties into the recent “Trojan horse” hypothesis, which suggests that endemic carriage of bacteria is responsible for most surgical site infections, rather than the long-held belief that operating room contamination is to blame. “That would sort of fly with this study, that the patient is walking around with Staph aureus and not necessarily on their skin or at their surgical site, but it’s endemic in their body,” said Dr. Evans.
Dr. Kluytmans and Dr. Evans have no relevant financial disclosures.
published in the August issue of Open Forum Infectious Diseases.
“This was a pan-European study with many hospitals, many different clinical settings, and as far as I’m aware, it hasn’t been done before. [The new study] covers a lot of European countries and a lot of surgical specialties,” said lead author Jan Kluytmans, MD. The study also captures the current state of preventive strategies in surgery, such as changes in air flow, dress, and skin preparation, he added.
The study included 5004 patients from 33 hospitals in ten European countries, of whom 67.3% were found to be SA carriers. The median age was 65 years, and 49.8% of patients were male. Open cardiac, and knee and hip prosthesis surgeries made up the largest fraction, but there were 12 types of surgery included in the study.
There were 100 SA surgical site or blood infections. The researchers found an association between surgical site or blood infection and SA carriage at any site (adjusted hazard ratio [aHR], 4.6; 95% CI, 2.1-10.0) and nasal SA carriage (aHR, 4.2; 95% CI, 2.0-8.6). Extranasal SA carriage was not associated with an increased infection risk.
Each 1-unit increase in nasal bacteria was associated with an increase in infection risk (aHR, 1.23; 95% CI, 1.05-1.43).
A strength of the study is that it is the largest prospective study yet conducted on SA carriage in surgical patients, but the researchers were unable to do a subgroup of methicillin-resistant SA (MRSA) due to small numbers of infections.
The study confirms the value of the decolonization strategy, which the World Health Organization has endorsed with the highest level of scientific evidence that is available in preventive strategies in surgery. WHO strongly recommends decolonization for cardiothoracic and orthopedic surgery using intranasal applications of mupirocin 2% ointment with or without a combination of chlorhexidine gluconate body wash. It has a conditional recommendation for a similar procedure before other types of surgery.
However, “It is not widely practiced, and although that was not a surprise to me, I think it’s really disappointing to see that proven effective strategies are not being practiced,” said Dr. Kluytmans, professor of medical microbiology at University Medical Center Utrecht, Utrecht University, the Netherlands. “If I would come into surgery being a carrier, and not be decolonized, I would really be quite angry because it puts you at risk, which is preventable. I think that’s something we owe to our patients,” he said.
He said that some may have concerns about the potential for decolonization to contribute to antibiotic resistance, but the short-term prophylaxis — typically a few days — should not foster resistance, according to Dr. Kluytmans. “If you use it short term, just before surgery, it has been shown in many studies that resistance isn’t a big problem and it can be monitored.”
The link specifically to SA nasal carriage is a mystery, according to Dr. Kluytmans. “It puzzles me still how it gets from the nares to the wound during surgery. So that’s my million-dollar question that I would like to resolve. We would like to study it, but we haven’t quite a bright idea how to do that,” he said.
The results are compelling, according to Heather Evans, MD, who was asked for comment. “On the face of it, this looks like a no-brainer. We should be decolonizing all patients that go to the operating room, and it’s not a terribly unpleasant thing for a patient to undergo to have decolonization done. Particularly for patients who are at higher risk for having a severe complication, like someone that has an operation that’s involving an implant, for example, I think it really makes a lot of sense to do this low-cost intervention for those patients,” said Dr. Evans, professor of medicine at The Medical University of South Carolina as well as the president of the Surgical Infection Society.
She noted that many facilities test for methicillin-resistant SA, but usual not SA more broadly. “This is a very interesting and compelling study that makes us rethink that, and maybe it isn’t even worth testing to see if you have staph aureus, maybe we should just be putting Betadine in everyone’s nostrils when they come to the operating room. It just seems like it would be a pretty low-cost intervention and something that could potentially have a big impact,” said Dr. Evans.
Although she was impressed by the study, Dr. Evans noted that the researchers tested for carriage at sites unrelated to the surgical site. “It really made me wonder if it would have added even more credibility to the study if there had been a sample taken after surgical prep was done to demonstrate that there is actually no staph aureus present on the skin at the time that the wound was made,” she said.
The question ties into the recent “Trojan horse” hypothesis, which suggests that endemic carriage of bacteria is responsible for most surgical site infections, rather than the long-held belief that operating room contamination is to blame. “That would sort of fly with this study, that the patient is walking around with Staph aureus and not necessarily on their skin or at their surgical site, but it’s endemic in their body,” said Dr. Evans.
Dr. Kluytmans and Dr. Evans have no relevant financial disclosures.