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High-intensity interval training cuts cardiometabolic risks in women with PCOS
High-intensity interval training (HIIT) was better than moderate-intensity continuous training (MICT) for improving several measures of cardiometabolic health in women with polycystic ovary syndrome (PCOS) in a prospective, randomized, single-center study with 27 women.
After 12 weeks on a supervised exercise regimen, the women with PCOS who followed the HIIT program had significantly better improvements in aerobic capacity, insulin sensitivity, and level of sex hormone–binding globulin, Rhiannon K. Patten, MSc, said at the annual meeting of the Endocrine Society.
“HIIT can offer superior improvements in health outcomes, and should be considered as an effective tool to reduce cardiometabolic risk in women with PCOS,” concluded Ms. Patten, a researcher in the Institute for Health and Sport at Victoria University in Melbourne in her presentation (Abstract OR10-1).
“The changes we see [after 12 weeks on the HIIT regimen] seem to occur despite no change in body mass index, so rather than focus on weight loss we encourage participants to focus on the health improvements that seem to be greater with HIIT. We actively encourage the HIIT protocol right now,” she said.
Both regimens use a stationary cycle ergometer. In the HIIT protocol patients twice weekly pedal through 12 1-minute intervals at a heart rate of 90%-100% maximum, interspersed with 1 minute rest intervals. On a third day per week, patients pedal to a heart rate of 90%-95% maximum for 6-8 intervals maintained for 2 minutes and interspersed with rest intervals of 2 minutes. The MICT regimen used as a comparator has participants pedal to 60%-70% of their maximum heart rate continuously for 50 minutes 3 days weekly.
HIIT saves time
“These findings are relevant to clinical practice, because they demonstrate that HIIT is effective in women with PCOS. Reducing the time devoted to exercise to achieve fitness goals is attractive to patients. The reduced time to achieve training benefits with HIIT should improve patient compliance,” commented Andrea Dunaif, MD, professor and chief of the division of endocrinology, diabetes, and bone disease of the Mount Sinai Health System in New York, who was not involved with the study.
The overall weekly exercise time on the MICT regimen, 150 minutes, halves down to 75 minutes a week in the HIIT program. Guideline recommendations released in 2018 by the International PCOS Network recommended these as acceptable alternative exercise strategies. Ms. Patten and her associates sought to determine whether one strategy surpassed the other, the first time this has been examined in women with PCOS, she said.
They randomized 27 sedentary women 18-45 years old with a body mass index (BMI) above 25 kg/m2 and diagnosed with PCOS by the Rotterdam criteria to a 12-week supervised exercise program on either the HIIT or MICT protocol. Their average BMI at entry was 36-37 kg/m2. The study excluded women who smoked, were pregnant, had an illness or injury that would prevent exercise, or were on an oral contraceptive or insulin-sensitizing medication.
At the end of 12 weeks, neither group had a significant change in average weight or BMI, and waist circumference dropped by an average of just over 2 cm in both treatment groups. Lean mass increased by a mean 1 kg in the HIIT group, a significant change, compared with a nonsignificant 0.3 kg average increase in the MICT group.
Increased aerobic capacity ‘partially explains’ improved insulin sensitivity
Aerobic capacity, measured as peak oxygen consumption (VO2peak), increased by an average 5.7 mL/kg per min among the HIIT patients, significantly more than the mean 3.2 mL/kg per min increase among those in the MICT program.
The insulin sensitivity index rose by a significant, relative 35% among the HIIT patients, but barely budged in the MICT group. Fasting glucose fell significantly and the glucose infusion rate increased significantly among the women who performed HIIT, but again showed little change among those doing MICT.
Analysis showed a significant link between the increase in VO2peak and the increase in insulin sensitivity among the women engaged in HIIT, Ms. Patten reported. The improvement in the insulin sensitivity index was “partially explained” by the increase in VO2peak, she said.
Assessment of hormone levels showed a significant increase in sex hormone–binding globulin in the HIIT patients while those in the MICT group showed a small decline in this level. The free androgen index fell by a relative 39% on average in the HIIT group, a significant drop, but decreased by a much smaller and not significant amount among the women who did MICT. The women who performed HIIT also showed a significant drop in their free testosterone level, a change not seen with MICT.
Women who performed the HIIT protocol also had a significant improvement in their menstrual cyclicity, and significant improvements in depression, stress, and anxiety, Ms Patten reported. She next plans to do longer follow-up on study participants, out to 6 and 12 months after the end of the exercise protocol.
“Overall, the findings suggest that HIIT is superior to MICT for improving fitness and insulin sensitivity in the short term. Results from a number of studies in individuals without PCOS suggest that HIIT is superior to MICT for improving fitness short term,” commented Dr. Dunaif. “This study makes an important contribution by directly investigating the impact of training intensity in women with PCOS. Larger studies will be needed before the superiority of HIIT is established for women with PCOS, and study durations of at least several months will be needed to assess the impact on reproductive outcomes such as ovulation,” she said in an interview. She also called for assessing the effects of HIIT in more diverse populations of women with PCOS.
Ms. Patten had no disclosures. Dr. Dunaif has been a consultant to Equator Therapeutics, Fractyl Laboratories, and Globe Life Sciences.
High-intensity interval training (HIIT) was better than moderate-intensity continuous training (MICT) for improving several measures of cardiometabolic health in women with polycystic ovary syndrome (PCOS) in a prospective, randomized, single-center study with 27 women.
After 12 weeks on a supervised exercise regimen, the women with PCOS who followed the HIIT program had significantly better improvements in aerobic capacity, insulin sensitivity, and level of sex hormone–binding globulin, Rhiannon K. Patten, MSc, said at the annual meeting of the Endocrine Society.
“HIIT can offer superior improvements in health outcomes, and should be considered as an effective tool to reduce cardiometabolic risk in women with PCOS,” concluded Ms. Patten, a researcher in the Institute for Health and Sport at Victoria University in Melbourne in her presentation (Abstract OR10-1).
“The changes we see [after 12 weeks on the HIIT regimen] seem to occur despite no change in body mass index, so rather than focus on weight loss we encourage participants to focus on the health improvements that seem to be greater with HIIT. We actively encourage the HIIT protocol right now,” she said.
Both regimens use a stationary cycle ergometer. In the HIIT protocol patients twice weekly pedal through 12 1-minute intervals at a heart rate of 90%-100% maximum, interspersed with 1 minute rest intervals. On a third day per week, patients pedal to a heart rate of 90%-95% maximum for 6-8 intervals maintained for 2 minutes and interspersed with rest intervals of 2 minutes. The MICT regimen used as a comparator has participants pedal to 60%-70% of their maximum heart rate continuously for 50 minutes 3 days weekly.
HIIT saves time
“These findings are relevant to clinical practice, because they demonstrate that HIIT is effective in women with PCOS. Reducing the time devoted to exercise to achieve fitness goals is attractive to patients. The reduced time to achieve training benefits with HIIT should improve patient compliance,” commented Andrea Dunaif, MD, professor and chief of the division of endocrinology, diabetes, and bone disease of the Mount Sinai Health System in New York, who was not involved with the study.
The overall weekly exercise time on the MICT regimen, 150 minutes, halves down to 75 minutes a week in the HIIT program. Guideline recommendations released in 2018 by the International PCOS Network recommended these as acceptable alternative exercise strategies. Ms. Patten and her associates sought to determine whether one strategy surpassed the other, the first time this has been examined in women with PCOS, she said.
They randomized 27 sedentary women 18-45 years old with a body mass index (BMI) above 25 kg/m2 and diagnosed with PCOS by the Rotterdam criteria to a 12-week supervised exercise program on either the HIIT or MICT protocol. Their average BMI at entry was 36-37 kg/m2. The study excluded women who smoked, were pregnant, had an illness or injury that would prevent exercise, or were on an oral contraceptive or insulin-sensitizing medication.
At the end of 12 weeks, neither group had a significant change in average weight or BMI, and waist circumference dropped by an average of just over 2 cm in both treatment groups. Lean mass increased by a mean 1 kg in the HIIT group, a significant change, compared with a nonsignificant 0.3 kg average increase in the MICT group.
Increased aerobic capacity ‘partially explains’ improved insulin sensitivity
Aerobic capacity, measured as peak oxygen consumption (VO2peak), increased by an average 5.7 mL/kg per min among the HIIT patients, significantly more than the mean 3.2 mL/kg per min increase among those in the MICT program.
The insulin sensitivity index rose by a significant, relative 35% among the HIIT patients, but barely budged in the MICT group. Fasting glucose fell significantly and the glucose infusion rate increased significantly among the women who performed HIIT, but again showed little change among those doing MICT.
Analysis showed a significant link between the increase in VO2peak and the increase in insulin sensitivity among the women engaged in HIIT, Ms. Patten reported. The improvement in the insulin sensitivity index was “partially explained” by the increase in VO2peak, she said.
Assessment of hormone levels showed a significant increase in sex hormone–binding globulin in the HIIT patients while those in the MICT group showed a small decline in this level. The free androgen index fell by a relative 39% on average in the HIIT group, a significant drop, but decreased by a much smaller and not significant amount among the women who did MICT. The women who performed HIIT also showed a significant drop in their free testosterone level, a change not seen with MICT.
Women who performed the HIIT protocol also had a significant improvement in their menstrual cyclicity, and significant improvements in depression, stress, and anxiety, Ms Patten reported. She next plans to do longer follow-up on study participants, out to 6 and 12 months after the end of the exercise protocol.
“Overall, the findings suggest that HIIT is superior to MICT for improving fitness and insulin sensitivity in the short term. Results from a number of studies in individuals without PCOS suggest that HIIT is superior to MICT for improving fitness short term,” commented Dr. Dunaif. “This study makes an important contribution by directly investigating the impact of training intensity in women with PCOS. Larger studies will be needed before the superiority of HIIT is established for women with PCOS, and study durations of at least several months will be needed to assess the impact on reproductive outcomes such as ovulation,” she said in an interview. She also called for assessing the effects of HIIT in more diverse populations of women with PCOS.
Ms. Patten had no disclosures. Dr. Dunaif has been a consultant to Equator Therapeutics, Fractyl Laboratories, and Globe Life Sciences.
High-intensity interval training (HIIT) was better than moderate-intensity continuous training (MICT) for improving several measures of cardiometabolic health in women with polycystic ovary syndrome (PCOS) in a prospective, randomized, single-center study with 27 women.
After 12 weeks on a supervised exercise regimen, the women with PCOS who followed the HIIT program had significantly better improvements in aerobic capacity, insulin sensitivity, and level of sex hormone–binding globulin, Rhiannon K. Patten, MSc, said at the annual meeting of the Endocrine Society.
“HIIT can offer superior improvements in health outcomes, and should be considered as an effective tool to reduce cardiometabolic risk in women with PCOS,” concluded Ms. Patten, a researcher in the Institute for Health and Sport at Victoria University in Melbourne in her presentation (Abstract OR10-1).
“The changes we see [after 12 weeks on the HIIT regimen] seem to occur despite no change in body mass index, so rather than focus on weight loss we encourage participants to focus on the health improvements that seem to be greater with HIIT. We actively encourage the HIIT protocol right now,” she said.
Both regimens use a stationary cycle ergometer. In the HIIT protocol patients twice weekly pedal through 12 1-minute intervals at a heart rate of 90%-100% maximum, interspersed with 1 minute rest intervals. On a third day per week, patients pedal to a heart rate of 90%-95% maximum for 6-8 intervals maintained for 2 minutes and interspersed with rest intervals of 2 minutes. The MICT regimen used as a comparator has participants pedal to 60%-70% of their maximum heart rate continuously for 50 minutes 3 days weekly.
HIIT saves time
“These findings are relevant to clinical practice, because they demonstrate that HIIT is effective in women with PCOS. Reducing the time devoted to exercise to achieve fitness goals is attractive to patients. The reduced time to achieve training benefits with HIIT should improve patient compliance,” commented Andrea Dunaif, MD, professor and chief of the division of endocrinology, diabetes, and bone disease of the Mount Sinai Health System in New York, who was not involved with the study.
The overall weekly exercise time on the MICT regimen, 150 minutes, halves down to 75 minutes a week in the HIIT program. Guideline recommendations released in 2018 by the International PCOS Network recommended these as acceptable alternative exercise strategies. Ms. Patten and her associates sought to determine whether one strategy surpassed the other, the first time this has been examined in women with PCOS, she said.
They randomized 27 sedentary women 18-45 years old with a body mass index (BMI) above 25 kg/m2 and diagnosed with PCOS by the Rotterdam criteria to a 12-week supervised exercise program on either the HIIT or MICT protocol. Their average BMI at entry was 36-37 kg/m2. The study excluded women who smoked, were pregnant, had an illness or injury that would prevent exercise, or were on an oral contraceptive or insulin-sensitizing medication.
At the end of 12 weeks, neither group had a significant change in average weight or BMI, and waist circumference dropped by an average of just over 2 cm in both treatment groups. Lean mass increased by a mean 1 kg in the HIIT group, a significant change, compared with a nonsignificant 0.3 kg average increase in the MICT group.
Increased aerobic capacity ‘partially explains’ improved insulin sensitivity
Aerobic capacity, measured as peak oxygen consumption (VO2peak), increased by an average 5.7 mL/kg per min among the HIIT patients, significantly more than the mean 3.2 mL/kg per min increase among those in the MICT program.
The insulin sensitivity index rose by a significant, relative 35% among the HIIT patients, but barely budged in the MICT group. Fasting glucose fell significantly and the glucose infusion rate increased significantly among the women who performed HIIT, but again showed little change among those doing MICT.
Analysis showed a significant link between the increase in VO2peak and the increase in insulin sensitivity among the women engaged in HIIT, Ms. Patten reported. The improvement in the insulin sensitivity index was “partially explained” by the increase in VO2peak, she said.
Assessment of hormone levels showed a significant increase in sex hormone–binding globulin in the HIIT patients while those in the MICT group showed a small decline in this level. The free androgen index fell by a relative 39% on average in the HIIT group, a significant drop, but decreased by a much smaller and not significant amount among the women who did MICT. The women who performed HIIT also showed a significant drop in their free testosterone level, a change not seen with MICT.
Women who performed the HIIT protocol also had a significant improvement in their menstrual cyclicity, and significant improvements in depression, stress, and anxiety, Ms Patten reported. She next plans to do longer follow-up on study participants, out to 6 and 12 months after the end of the exercise protocol.
“Overall, the findings suggest that HIIT is superior to MICT for improving fitness and insulin sensitivity in the short term. Results from a number of studies in individuals without PCOS suggest that HIIT is superior to MICT for improving fitness short term,” commented Dr. Dunaif. “This study makes an important contribution by directly investigating the impact of training intensity in women with PCOS. Larger studies will be needed before the superiority of HIIT is established for women with PCOS, and study durations of at least several months will be needed to assess the impact on reproductive outcomes such as ovulation,” she said in an interview. She also called for assessing the effects of HIIT in more diverse populations of women with PCOS.
Ms. Patten had no disclosures. Dr. Dunaif has been a consultant to Equator Therapeutics, Fractyl Laboratories, and Globe Life Sciences.
FROM ENDO 2021
Ruxolitinib cream for atopic dermatitis is in regulatory home stretch
, demonstrated a dual mechanism of action in two pivotal phase 3 trials: antipruritic and anti-inflammatory, Kim A. Papp, MD, PhD, said at Innovations in Dermatology: Virtual Spring Conference 2021. He presented a pooled analysis of the TRuE-AD1 and TRuE-AD2 trials, in which 1,249 patients with AD affecting 3%-20% of the body surface area were randomized 2:2:1 double-blind to ruxolitinib cream 0.75%, 1.5%, or vehicle twice daily for 8 weeks.
Striking evidence of the drug’s antipruritic effect comes from the finding that patient-reported itch scores separated significantly from the vehicle controls within just 12 hours after the first application. The margin of difference grew over time such that at 4 weeks, 48.5% of patients on ruxolitinib 1.5% experienced a clinically meaningful reduction in itch – defined by at least a 4-point improvement on the itch numeric rating scale – as did 30.1% of those on ruxolitinib 0.75% and 6.1% of controls. By week 8, these figures had further improved to 51.5%, 41.5%, and 15.8%, respectively, noted Dr. Papp, a dermatologist and president of Probity Medical Research in Waterloo, Ont.
Ruxolitinib’s anti-inflammatory mechanism of action was on display in the primary study endpoint, which was the proportion of patients achieving an Investigator Global Assessment score of 0 or 1 with at least a 2-grade improvement from baseline at week 8. The rates were 52.6% with ruxolitinib 1.5% and 44.7% at the lower dose, both significantly better than the 11.5% rate with vehicle.
For the secondary endpoint of at least a 75% improvement in Eczema Area and Severity Index score at week 8, the rates were 62% with ruxolitinib 1.5% and 53.8% at the 0.75% concentration, compared with 19.7% with vehicle.
The topical JAK inhibitor also showed superior efficacy in terms of improvement on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Score, with a clinically meaningful 6-point or greater improvement in 23.9% and 20.9% of patients in the high- and low-dose ruxolitinib groups, versus 14.2% in controls.
Plasma drug levels remained consistently low and near-flat throughout the study.
Session comoderator Lawrence F. Eichenfield, MD, was struck by what he termed the “incredibly low” rates of irritancy, burning, and stinging in the ruxolitinib-treated patients: 7 cases of application-site burning in 999 treated patients, compared with 11 cases in 250 vehicle-treated patients, and 4 cases of application-site pruritus in nearly 1,000 patients on ruxolitinib, versus 6 cases in one-fourth as many controls.
“If that’s really true in clinical practice, it would be tremendous to have a nonsteroid that doesn’t have stinging and burning and may have that efficacy,” said Dr. Eichenfield, professor of dermatology and pediatrics and vice-chair of dermatology at the University of California, San Diego.
“I think the fast action is an exciting aspect of this,” said comoderator Jonathan I. Silverberg, MD, PhD, MBA, director of clinical research and contact dermatitis in the department of dermatology at George Washington University in Washington.
He noted that in an earlier phase 2 study, ruxolitinib cream was at least as efficacious as 0.1% triamcinolone cream, providing dermatologists with a rough yardstick as to where the topical JAK inhibitor lies on the potency spectrum for AD treatment.
The FDA is expected to issue a decision on the application for approval of ruxolitinib cream in June. Dr. Eichenfield expects the drug to easily win approval. The big unanswered question is whether the regulatory agency will require boxed safety warnings, as it does for the oral JAK inhibitors approved for various indications, even though safety issues haven’t arisen with the topical agent in the clinical trials.
Dr. Papp reported receiving research grants from and serving as a consultant to Incyte Corp., which funded the ruxolitinib studies, as well as numerous other pharmaceutical companies. MedscapeLive and this news organization are owned by the same parent company.
, demonstrated a dual mechanism of action in two pivotal phase 3 trials: antipruritic and anti-inflammatory, Kim A. Papp, MD, PhD, said at Innovations in Dermatology: Virtual Spring Conference 2021. He presented a pooled analysis of the TRuE-AD1 and TRuE-AD2 trials, in which 1,249 patients with AD affecting 3%-20% of the body surface area were randomized 2:2:1 double-blind to ruxolitinib cream 0.75%, 1.5%, or vehicle twice daily for 8 weeks.
Striking evidence of the drug’s antipruritic effect comes from the finding that patient-reported itch scores separated significantly from the vehicle controls within just 12 hours after the first application. The margin of difference grew over time such that at 4 weeks, 48.5% of patients on ruxolitinib 1.5% experienced a clinically meaningful reduction in itch – defined by at least a 4-point improvement on the itch numeric rating scale – as did 30.1% of those on ruxolitinib 0.75% and 6.1% of controls. By week 8, these figures had further improved to 51.5%, 41.5%, and 15.8%, respectively, noted Dr. Papp, a dermatologist and president of Probity Medical Research in Waterloo, Ont.
Ruxolitinib’s anti-inflammatory mechanism of action was on display in the primary study endpoint, which was the proportion of patients achieving an Investigator Global Assessment score of 0 or 1 with at least a 2-grade improvement from baseline at week 8. The rates were 52.6% with ruxolitinib 1.5% and 44.7% at the lower dose, both significantly better than the 11.5% rate with vehicle.
For the secondary endpoint of at least a 75% improvement in Eczema Area and Severity Index score at week 8, the rates were 62% with ruxolitinib 1.5% and 53.8% at the 0.75% concentration, compared with 19.7% with vehicle.
The topical JAK inhibitor also showed superior efficacy in terms of improvement on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Score, with a clinically meaningful 6-point or greater improvement in 23.9% and 20.9% of patients in the high- and low-dose ruxolitinib groups, versus 14.2% in controls.
Plasma drug levels remained consistently low and near-flat throughout the study.
Session comoderator Lawrence F. Eichenfield, MD, was struck by what he termed the “incredibly low” rates of irritancy, burning, and stinging in the ruxolitinib-treated patients: 7 cases of application-site burning in 999 treated patients, compared with 11 cases in 250 vehicle-treated patients, and 4 cases of application-site pruritus in nearly 1,000 patients on ruxolitinib, versus 6 cases in one-fourth as many controls.
“If that’s really true in clinical practice, it would be tremendous to have a nonsteroid that doesn’t have stinging and burning and may have that efficacy,” said Dr. Eichenfield, professor of dermatology and pediatrics and vice-chair of dermatology at the University of California, San Diego.
“I think the fast action is an exciting aspect of this,” said comoderator Jonathan I. Silverberg, MD, PhD, MBA, director of clinical research and contact dermatitis in the department of dermatology at George Washington University in Washington.
He noted that in an earlier phase 2 study, ruxolitinib cream was at least as efficacious as 0.1% triamcinolone cream, providing dermatologists with a rough yardstick as to where the topical JAK inhibitor lies on the potency spectrum for AD treatment.
The FDA is expected to issue a decision on the application for approval of ruxolitinib cream in June. Dr. Eichenfield expects the drug to easily win approval. The big unanswered question is whether the regulatory agency will require boxed safety warnings, as it does for the oral JAK inhibitors approved for various indications, even though safety issues haven’t arisen with the topical agent in the clinical trials.
Dr. Papp reported receiving research grants from and serving as a consultant to Incyte Corp., which funded the ruxolitinib studies, as well as numerous other pharmaceutical companies. MedscapeLive and this news organization are owned by the same parent company.
, demonstrated a dual mechanism of action in two pivotal phase 3 trials: antipruritic and anti-inflammatory, Kim A. Papp, MD, PhD, said at Innovations in Dermatology: Virtual Spring Conference 2021. He presented a pooled analysis of the TRuE-AD1 and TRuE-AD2 trials, in which 1,249 patients with AD affecting 3%-20% of the body surface area were randomized 2:2:1 double-blind to ruxolitinib cream 0.75%, 1.5%, or vehicle twice daily for 8 weeks.
Striking evidence of the drug’s antipruritic effect comes from the finding that patient-reported itch scores separated significantly from the vehicle controls within just 12 hours after the first application. The margin of difference grew over time such that at 4 weeks, 48.5% of patients on ruxolitinib 1.5% experienced a clinically meaningful reduction in itch – defined by at least a 4-point improvement on the itch numeric rating scale – as did 30.1% of those on ruxolitinib 0.75% and 6.1% of controls. By week 8, these figures had further improved to 51.5%, 41.5%, and 15.8%, respectively, noted Dr. Papp, a dermatologist and president of Probity Medical Research in Waterloo, Ont.
Ruxolitinib’s anti-inflammatory mechanism of action was on display in the primary study endpoint, which was the proportion of patients achieving an Investigator Global Assessment score of 0 or 1 with at least a 2-grade improvement from baseline at week 8. The rates were 52.6% with ruxolitinib 1.5% and 44.7% at the lower dose, both significantly better than the 11.5% rate with vehicle.
For the secondary endpoint of at least a 75% improvement in Eczema Area and Severity Index score at week 8, the rates were 62% with ruxolitinib 1.5% and 53.8% at the 0.75% concentration, compared with 19.7% with vehicle.
The topical JAK inhibitor also showed superior efficacy in terms of improvement on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Score, with a clinically meaningful 6-point or greater improvement in 23.9% and 20.9% of patients in the high- and low-dose ruxolitinib groups, versus 14.2% in controls.
Plasma drug levels remained consistently low and near-flat throughout the study.
Session comoderator Lawrence F. Eichenfield, MD, was struck by what he termed the “incredibly low” rates of irritancy, burning, and stinging in the ruxolitinib-treated patients: 7 cases of application-site burning in 999 treated patients, compared with 11 cases in 250 vehicle-treated patients, and 4 cases of application-site pruritus in nearly 1,000 patients on ruxolitinib, versus 6 cases in one-fourth as many controls.
“If that’s really true in clinical practice, it would be tremendous to have a nonsteroid that doesn’t have stinging and burning and may have that efficacy,” said Dr. Eichenfield, professor of dermatology and pediatrics and vice-chair of dermatology at the University of California, San Diego.
“I think the fast action is an exciting aspect of this,” said comoderator Jonathan I. Silverberg, MD, PhD, MBA, director of clinical research and contact dermatitis in the department of dermatology at George Washington University in Washington.
He noted that in an earlier phase 2 study, ruxolitinib cream was at least as efficacious as 0.1% triamcinolone cream, providing dermatologists with a rough yardstick as to where the topical JAK inhibitor lies on the potency spectrum for AD treatment.
The FDA is expected to issue a decision on the application for approval of ruxolitinib cream in June. Dr. Eichenfield expects the drug to easily win approval. The big unanswered question is whether the regulatory agency will require boxed safety warnings, as it does for the oral JAK inhibitors approved for various indications, even though safety issues haven’t arisen with the topical agent in the clinical trials.
Dr. Papp reported receiving research grants from and serving as a consultant to Incyte Corp., which funded the ruxolitinib studies, as well as numerous other pharmaceutical companies. MedscapeLive and this news organization are owned by the same parent company.
FROM INNOVATIONS IN DERMATOLOGY
Direct transfer to angiography improves outcome in large-vessel stroke
in a new study.
Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.
The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.
In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.
If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
Bypassing the emergency department
Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.
If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.
Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.
After CT scanning, patients received thrombolysis as recommended in the guidelines.
The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.
Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).
The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).
There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)
Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.
“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”
Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”
A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.
He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
The cost of speed
Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.
He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.
“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”
The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.
Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”
Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”
The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in a new study.
Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.
The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.
In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.
If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
Bypassing the emergency department
Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.
If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.
Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.
After CT scanning, patients received thrombolysis as recommended in the guidelines.
The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.
Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).
The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).
There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)
Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.
“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”
Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”
A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.
He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
The cost of speed
Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.
He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.
“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”
The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.
Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”
Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”
The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in a new study.
Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.
The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.
In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.
If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
Bypassing the emergency department
Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.
If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.
Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.
After CT scanning, patients received thrombolysis as recommended in the guidelines.
The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.
Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).
The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).
There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)
Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.
“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”
Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”
A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.
He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
The cost of speed
Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.
He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.
“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”
The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.
Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”
Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”
The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2021
Cumulative inflammatory burden predicts cancer risk in ulcerative colitis
The cumulative burden of histologic inflammation is a strong predictor of colorectal neoplasia risk in ulcerative colitis, according to a recent case-control study.
David T. Rubin, MD, was the senior author of the study, which provided independent validation of a metric for cumulative burden of inflammation as a risk stratification tool in ulcerative colitis and presented these findings at the Gastroenterology Updates, IBD, Liver Disease Conference. The metric was developed at St. Mark’s Hospital, London, which he called “a leader in the field.”
“The implication of demonstrating this is that, if you control inflammation and keep it controlled over time, it would imply that you can reduce the overall risk for cancer and dysplasia,” explained Dr. Rubin, professor of medicine and chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago.
The original retrospective St. Mark’s study included 987 patients with extensive ulcerative colitis followed with colonoscopic surveillance for a median of 13 years. Each colonoscopy was scored for severity of microscopic inflammation on a 0-3 scale. The investigators calculated a patient’s cumulative inflammatory burden by adding each histologic inflammatory activity score and multiplying that figure by the surveillance interval in years.
In a multivariate analysis, the London investigators demonstrated that the risk of colorectal neoplasia jumped by 2.1-fold for each 10-unit increase in cumulative inflammatory burden, defined as the equivalent of either 10 years of continuous mild active histologic inflammation, 5 years of continuous moderate inflammation, or 3.3 years of continuous severe inflammation.
The University of Chicago retrospective external validation study included 26 ulcerative colitis patients with colorectal neoplasia and 36 others without cancer. The mean cumulative histologic inflammatory activity score in the group with colorectal neoplasia was 12.63, compared with 7.98 in controls. For each 1-unit increase in cumulative inflammatory burden the risk of developing colorectal neoplasia increased by 8%, consistent with the magnitude of the hazard previously reported at St. Mark’s.
“The way you could take this back to your practice is by thinking carefully about what is the degree of inflammation each time you’ve done a colonoscopy and considering whether the patient who is in deep remission and doing well might deserve a longer interval between their next exam and the one you just completed,” according to the gastroenterologist.
“The most interval I give a patient is 3 years – for somebody in deep remission with no inflammation on the last exam. And when they’ve had prior inflammation but are now doing well, I keep in mind what that prior inflammation was. We’re now working on using that cumulative histologic inflammation score to guide intervals, but we don’t have prospective data to validate this approach. So when you’re not sure, the conservative approach is surveillance colonoscopy every 1-2 years after you’ve had 10 years of disease. That’s probably overutilization of our resources, but we don’t have a better way to do it yet,” Dr. Rubin said.
The novel metric for calculating cumulative histologic inflammation burden as a means of predicting colorectal cancer in ulcerative colitis dovetails with the current emphasis upon individualized risk assessment as recommended in the latest American College of Gastroenterology practice guidelines, for which Dr. Rubin was first author.
“Like we individualize our treatments, we should individualize our colorectal cancer screening and prevention strategies,” he emphasized.
Risk factors for colorectal cancer and dysplasia in patients with ulcerative colitis can be grouped as either potentially modifiable or immutable. Potentially modifiable risk factors include backwash ileitis, pseudopolyps, prior dysplasia, and mass or stricture, as well as the degree of histologic inflammation. Immutable risk factors include younger age at diagnosis, male gender, duration and extent of disease, family history of colorectal cancer, and primary sclerosing cholangitis, Dr. Rubin noted.
He reported receiving grant support from and/or serving as a consultant to more than two dozen medical companies.
The cumulative burden of histologic inflammation is a strong predictor of colorectal neoplasia risk in ulcerative colitis, according to a recent case-control study.
David T. Rubin, MD, was the senior author of the study, which provided independent validation of a metric for cumulative burden of inflammation as a risk stratification tool in ulcerative colitis and presented these findings at the Gastroenterology Updates, IBD, Liver Disease Conference. The metric was developed at St. Mark’s Hospital, London, which he called “a leader in the field.”
“The implication of demonstrating this is that, if you control inflammation and keep it controlled over time, it would imply that you can reduce the overall risk for cancer and dysplasia,” explained Dr. Rubin, professor of medicine and chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago.
The original retrospective St. Mark’s study included 987 patients with extensive ulcerative colitis followed with colonoscopic surveillance for a median of 13 years. Each colonoscopy was scored for severity of microscopic inflammation on a 0-3 scale. The investigators calculated a patient’s cumulative inflammatory burden by adding each histologic inflammatory activity score and multiplying that figure by the surveillance interval in years.
In a multivariate analysis, the London investigators demonstrated that the risk of colorectal neoplasia jumped by 2.1-fold for each 10-unit increase in cumulative inflammatory burden, defined as the equivalent of either 10 years of continuous mild active histologic inflammation, 5 years of continuous moderate inflammation, or 3.3 years of continuous severe inflammation.
The University of Chicago retrospective external validation study included 26 ulcerative colitis patients with colorectal neoplasia and 36 others without cancer. The mean cumulative histologic inflammatory activity score in the group with colorectal neoplasia was 12.63, compared with 7.98 in controls. For each 1-unit increase in cumulative inflammatory burden the risk of developing colorectal neoplasia increased by 8%, consistent with the magnitude of the hazard previously reported at St. Mark’s.
“The way you could take this back to your practice is by thinking carefully about what is the degree of inflammation each time you’ve done a colonoscopy and considering whether the patient who is in deep remission and doing well might deserve a longer interval between their next exam and the one you just completed,” according to the gastroenterologist.
“The most interval I give a patient is 3 years – for somebody in deep remission with no inflammation on the last exam. And when they’ve had prior inflammation but are now doing well, I keep in mind what that prior inflammation was. We’re now working on using that cumulative histologic inflammation score to guide intervals, but we don’t have prospective data to validate this approach. So when you’re not sure, the conservative approach is surveillance colonoscopy every 1-2 years after you’ve had 10 years of disease. That’s probably overutilization of our resources, but we don’t have a better way to do it yet,” Dr. Rubin said.
The novel metric for calculating cumulative histologic inflammation burden as a means of predicting colorectal cancer in ulcerative colitis dovetails with the current emphasis upon individualized risk assessment as recommended in the latest American College of Gastroenterology practice guidelines, for which Dr. Rubin was first author.
“Like we individualize our treatments, we should individualize our colorectal cancer screening and prevention strategies,” he emphasized.
Risk factors for colorectal cancer and dysplasia in patients with ulcerative colitis can be grouped as either potentially modifiable or immutable. Potentially modifiable risk factors include backwash ileitis, pseudopolyps, prior dysplasia, and mass or stricture, as well as the degree of histologic inflammation. Immutable risk factors include younger age at diagnosis, male gender, duration and extent of disease, family history of colorectal cancer, and primary sclerosing cholangitis, Dr. Rubin noted.
He reported receiving grant support from and/or serving as a consultant to more than two dozen medical companies.
The cumulative burden of histologic inflammation is a strong predictor of colorectal neoplasia risk in ulcerative colitis, according to a recent case-control study.
David T. Rubin, MD, was the senior author of the study, which provided independent validation of a metric for cumulative burden of inflammation as a risk stratification tool in ulcerative colitis and presented these findings at the Gastroenterology Updates, IBD, Liver Disease Conference. The metric was developed at St. Mark’s Hospital, London, which he called “a leader in the field.”
“The implication of demonstrating this is that, if you control inflammation and keep it controlled over time, it would imply that you can reduce the overall risk for cancer and dysplasia,” explained Dr. Rubin, professor of medicine and chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago.
The original retrospective St. Mark’s study included 987 patients with extensive ulcerative colitis followed with colonoscopic surveillance for a median of 13 years. Each colonoscopy was scored for severity of microscopic inflammation on a 0-3 scale. The investigators calculated a patient’s cumulative inflammatory burden by adding each histologic inflammatory activity score and multiplying that figure by the surveillance interval in years.
In a multivariate analysis, the London investigators demonstrated that the risk of colorectal neoplasia jumped by 2.1-fold for each 10-unit increase in cumulative inflammatory burden, defined as the equivalent of either 10 years of continuous mild active histologic inflammation, 5 years of continuous moderate inflammation, or 3.3 years of continuous severe inflammation.
The University of Chicago retrospective external validation study included 26 ulcerative colitis patients with colorectal neoplasia and 36 others without cancer. The mean cumulative histologic inflammatory activity score in the group with colorectal neoplasia was 12.63, compared with 7.98 in controls. For each 1-unit increase in cumulative inflammatory burden the risk of developing colorectal neoplasia increased by 8%, consistent with the magnitude of the hazard previously reported at St. Mark’s.
“The way you could take this back to your practice is by thinking carefully about what is the degree of inflammation each time you’ve done a colonoscopy and considering whether the patient who is in deep remission and doing well might deserve a longer interval between their next exam and the one you just completed,” according to the gastroenterologist.
“The most interval I give a patient is 3 years – for somebody in deep remission with no inflammation on the last exam. And when they’ve had prior inflammation but are now doing well, I keep in mind what that prior inflammation was. We’re now working on using that cumulative histologic inflammation score to guide intervals, but we don’t have prospective data to validate this approach. So when you’re not sure, the conservative approach is surveillance colonoscopy every 1-2 years after you’ve had 10 years of disease. That’s probably overutilization of our resources, but we don’t have a better way to do it yet,” Dr. Rubin said.
The novel metric for calculating cumulative histologic inflammation burden as a means of predicting colorectal cancer in ulcerative colitis dovetails with the current emphasis upon individualized risk assessment as recommended in the latest American College of Gastroenterology practice guidelines, for which Dr. Rubin was first author.
“Like we individualize our treatments, we should individualize our colorectal cancer screening and prevention strategies,” he emphasized.
Risk factors for colorectal cancer and dysplasia in patients with ulcerative colitis can be grouped as either potentially modifiable or immutable. Potentially modifiable risk factors include backwash ileitis, pseudopolyps, prior dysplasia, and mass or stricture, as well as the degree of histologic inflammation. Immutable risk factors include younger age at diagnosis, male gender, duration and extent of disease, family history of colorectal cancer, and primary sclerosing cholangitis, Dr. Rubin noted.
He reported receiving grant support from and/or serving as a consultant to more than two dozen medical companies.
FROM GUILD 2021
Study: Gynecologic cancer therapy does not increase COVID-19 risks
Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.
The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.
Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.
Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.
With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.
Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
Study results
Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.
Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.
Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).
An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.
Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
More research needed
The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”
The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.
“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”
The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.
However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.
Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.
This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.
Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.
The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.
Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.
Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.
With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.
Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
Study results
Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.
Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.
Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).
An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.
Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
More research needed
The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”
The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.
“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”
The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.
However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.
Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.
This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.
Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.
The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.
Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.
Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.
With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.
Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
Study results
Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.
Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.
Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).
An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.
Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
More research needed
The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”
The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.
“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”
The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.
However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.
Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.
This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.
FROM SGO 2021
Omidubicel improves on umbilical cord blood transplants
Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.
The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.
“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.
“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.
Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”
Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.
Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
Expanding possibilities
Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.
Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.
“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.
In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
Details of phase 3 trial results
The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.
Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).
At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).
In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).
Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.
The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).
In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.
The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.
The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.
Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.
In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).
The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.
The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.
“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.
“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.
Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”
Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.
Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
Expanding possibilities
Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.
Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.
“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.
In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
Details of phase 3 trial results
The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.
Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).
At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).
In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).
Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.
The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).
In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.
The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.
The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.
Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.
In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).
The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.
The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.
“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.
“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.
Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”
Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.
Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
Expanding possibilities
Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.
Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.
“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.
In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
Details of phase 3 trial results
The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.
Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).
At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).
In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).
Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.
The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).
In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.
The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.
The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.
Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.
In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).
The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Intervention reduced racial disparities among patients in cancer trials
, according to researchers.
The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.
The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.
Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
Rationale: Building trust, providing equitable care
Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.
“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.
In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.
The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.
“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
A ‘multifaceted’ intervention
“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.
His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.
Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.
Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
Results: Improved PFS
To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.
After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.
Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).
In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.
The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
Doing better, starting small
Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”
Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.
For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.
She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.
“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”
The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.
Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.
She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.
“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”
Dr. Jones and Dr. Doll both reported having no disclosures.
, according to researchers.
The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.
The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.
Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
Rationale: Building trust, providing equitable care
Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.
“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.
In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.
The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.
“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
A ‘multifaceted’ intervention
“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.
His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.
Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.
Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
Results: Improved PFS
To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.
After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.
Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).
In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.
The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
Doing better, starting small
Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”
Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.
For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.
She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.
“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”
The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.
Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.
She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.
“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”
Dr. Jones and Dr. Doll both reported having no disclosures.
, according to researchers.
The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.
The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.
Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
Rationale: Building trust, providing equitable care
Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.
“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.
In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.
The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.
“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
A ‘multifaceted’ intervention
“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.
His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.
Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.
Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
Results: Improved PFS
To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.
After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.
Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).
In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.
The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
Doing better, starting small
Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”
Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.
For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.
She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.
“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”
The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.
Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.
She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.
“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”
Dr. Jones and Dr. Doll both reported having no disclosures.
FROM SGO 2021
1 in 3 on levothyroxine take meds that interfere with thyroid tests
, potentially compromising treatment decisions, new research shows.
“We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways,” senior author Maria Papaleontiou, MD, told Medscape Medical News.
“However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored,” added Dr. Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.
The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society’s annual meeting.
Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Md., said: “It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests.”
“If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences,” he told Medscape Medical News.
32% of patients taking meds that could interfere with tests
In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).
Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests.
Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).
Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR, 2.47 vs score of 0).
Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).
The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.
“Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities,” Dr. Papaleontiou said.
Nature of interference possibilities varies
Medications or supplements can interfere with thyroid function tests in a variety of ways, she explained. “Some medications could lead to a decrease in the absorption of levothyroxine, others may affect how well the pill dissolves.”
In addition, certain medications can affect the circulation of thyroid hormone in the blood and how it binds with proteins, or they can lead to decreasing thyroid hormone levels due to a variety of interactions.
And in contrast, “What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don’t actually affect thyroid function and may lead to dose adjustments unnecessarily,” Dr. Papaleontiou noted.
Recommendations to counter interference
Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.
If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.
“The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions,” Dr. Papaleontiou said.
“Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference.”
The authors have reported no relevant financial relationships. Dr. Hoang has reported being a speaker for Acella Pharmaceuticals.
A version of this article first appeared on Medscape.com.
, potentially compromising treatment decisions, new research shows.
“We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways,” senior author Maria Papaleontiou, MD, told Medscape Medical News.
“However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored,” added Dr. Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.
The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society’s annual meeting.
Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Md., said: “It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests.”
“If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences,” he told Medscape Medical News.
32% of patients taking meds that could interfere with tests
In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).
Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests.
Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).
Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR, 2.47 vs score of 0).
Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).
The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.
“Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities,” Dr. Papaleontiou said.
Nature of interference possibilities varies
Medications or supplements can interfere with thyroid function tests in a variety of ways, she explained. “Some medications could lead to a decrease in the absorption of levothyroxine, others may affect how well the pill dissolves.”
In addition, certain medications can affect the circulation of thyroid hormone in the blood and how it binds with proteins, or they can lead to decreasing thyroid hormone levels due to a variety of interactions.
And in contrast, “What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don’t actually affect thyroid function and may lead to dose adjustments unnecessarily,” Dr. Papaleontiou noted.
Recommendations to counter interference
Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.
If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.
“The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions,” Dr. Papaleontiou said.
“Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference.”
The authors have reported no relevant financial relationships. Dr. Hoang has reported being a speaker for Acella Pharmaceuticals.
A version of this article first appeared on Medscape.com.
, potentially compromising treatment decisions, new research shows.
“We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways,” senior author Maria Papaleontiou, MD, told Medscape Medical News.
“However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored,” added Dr. Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.
The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society’s annual meeting.
Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Md., said: “It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests.”
“If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences,” he told Medscape Medical News.
32% of patients taking meds that could interfere with tests
In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).
Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests.
Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).
Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR, 2.47 vs score of 0).
Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).
The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.
“Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities,” Dr. Papaleontiou said.
Nature of interference possibilities varies
Medications or supplements can interfere with thyroid function tests in a variety of ways, she explained. “Some medications could lead to a decrease in the absorption of levothyroxine, others may affect how well the pill dissolves.”
In addition, certain medications can affect the circulation of thyroid hormone in the blood and how it binds with proteins, or they can lead to decreasing thyroid hormone levels due to a variety of interactions.
And in contrast, “What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don’t actually affect thyroid function and may lead to dose adjustments unnecessarily,” Dr. Papaleontiou noted.
Recommendations to counter interference
Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.
If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.
“The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions,” Dr. Papaleontiou said.
“Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference.”
The authors have reported no relevant financial relationships. Dr. Hoang has reported being a speaker for Acella Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Success in achondroplasia spurs testing vosoritide in more growth disorders
On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.
After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.
Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.
Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.
The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.
Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
After crossover, placebo patients catch up
In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).
“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.
Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.
“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.
Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.
“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
Injection site reactions most common adverse event
In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).
Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.
Based on the benefits observed in achondroplasia, other applications are now being explored.
“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.
As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.
Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.
On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.
After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.
Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.
Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.
The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.
Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
After crossover, placebo patients catch up
In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).
“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.
Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.
“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.
Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.
“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
Injection site reactions most common adverse event
In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).
Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.
Based on the benefits observed in achondroplasia, other applications are now being explored.
“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.
As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.
Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.
On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.
After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.
Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.
Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.
The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.
Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
After crossover, placebo patients catch up
In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).
“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.
Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.
“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.
Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.
“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
Injection site reactions most common adverse event
In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).
Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.
Based on the benefits observed in achondroplasia, other applications are now being explored.
“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.
As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.
Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.
FROM ENDO 2021
Imaging alternative to AVS could boost detection of primary aldosteronism
A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.
This noninvasive alternative, which also does not require the substantial technical expertise that AVS demands, should make assessment of adenoma laterality in patients with primary aldosteronism (PA) much more widely available and accessible, predicted Dr. Wu, a researcher at Queen Mary University of London.
“It will allow more places to do this, and I think it will definitely allow more patients to be diagnosed” with PA from a unilateral source. AVS “is a real bottleneck,” she said. “We hope metomidate, or molecular imaging using other selective radiotracers, will enable many more patients to be diagnosed and appropriately managed.” Creating new diagnostic options for patients with PA and potentially increasing the number of these patients who are surgical candidates “is the aim of this study.”
Patients with PA develop a curable form of hypertension if their excess aldosterone can be neutralized with a mineralocorticoid receptor antagonist (MRA), or even more definitively by surgical removal of the adrenal aldosteronoma generating the hormonal excess as long as the adenoma is unilateral. Conventional imaging of the adrenals with CT or MRI has proven unreliable for identifying adrenal nodules noninvasively, which has made the invasive and technically challenging standard option of AVS the only game in town.
But some endocrinologists caution that the results from this one study do not suffice to make 11C-metomidate-based PET-CT imaging a widely used alternative.
‘This is a first step.’
“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.
But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.
“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.
Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.
MATCHing imaging against AVS
To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.
The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.
The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.
For each of the four metrics, 11C-metomidate PET-CT produced point estimates of diagnostic accuracy that consistently edged out AVS. While these advantages were not large enough to meet the prespecified threshold for proving superiority, they comfortably showed the noninferiority of this imaging method compared with AVS.
For example, the PET-CT method had 43.6% accuracy for predicting a clinical cure, compared with 39.7% accuracy for AVS. For complete biochemical cure, imaging had 68.8% accuracy, compared with 62.3% for AVS, Dr. Wu reported.
Another notable finding from the study was how strongly a robust blood pressure response to spironolactone predicted the clinical outcome from surgery. Patients whose systolic blood pressure fell below 135 mm Hg on MRA treatment had a nearly 18-fold higher rate of achieving a complete clinical cure following surgery compared with patients who did not have as dramatic a blood pressure response to MRA treatment.
Woefully low rates of PA assessment
But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.
Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.
“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.
The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.
This noninvasive alternative, which also does not require the substantial technical expertise that AVS demands, should make assessment of adenoma laterality in patients with primary aldosteronism (PA) much more widely available and accessible, predicted Dr. Wu, a researcher at Queen Mary University of London.
“It will allow more places to do this, and I think it will definitely allow more patients to be diagnosed” with PA from a unilateral source. AVS “is a real bottleneck,” she said. “We hope metomidate, or molecular imaging using other selective radiotracers, will enable many more patients to be diagnosed and appropriately managed.” Creating new diagnostic options for patients with PA and potentially increasing the number of these patients who are surgical candidates “is the aim of this study.”
Patients with PA develop a curable form of hypertension if their excess aldosterone can be neutralized with a mineralocorticoid receptor antagonist (MRA), or even more definitively by surgical removal of the adrenal aldosteronoma generating the hormonal excess as long as the adenoma is unilateral. Conventional imaging of the adrenals with CT or MRI has proven unreliable for identifying adrenal nodules noninvasively, which has made the invasive and technically challenging standard option of AVS the only game in town.
But some endocrinologists caution that the results from this one study do not suffice to make 11C-metomidate-based PET-CT imaging a widely used alternative.
‘This is a first step.’
“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.
But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.
“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.
Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.
MATCHing imaging against AVS
To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.
The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.
The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.
For each of the four metrics, 11C-metomidate PET-CT produced point estimates of diagnostic accuracy that consistently edged out AVS. While these advantages were not large enough to meet the prespecified threshold for proving superiority, they comfortably showed the noninferiority of this imaging method compared with AVS.
For example, the PET-CT method had 43.6% accuracy for predicting a clinical cure, compared with 39.7% accuracy for AVS. For complete biochemical cure, imaging had 68.8% accuracy, compared with 62.3% for AVS, Dr. Wu reported.
Another notable finding from the study was how strongly a robust blood pressure response to spironolactone predicted the clinical outcome from surgery. Patients whose systolic blood pressure fell below 135 mm Hg on MRA treatment had a nearly 18-fold higher rate of achieving a complete clinical cure following surgery compared with patients who did not have as dramatic a blood pressure response to MRA treatment.
Woefully low rates of PA assessment
But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.
Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.
“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.
The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.
This noninvasive alternative, which also does not require the substantial technical expertise that AVS demands, should make assessment of adenoma laterality in patients with primary aldosteronism (PA) much more widely available and accessible, predicted Dr. Wu, a researcher at Queen Mary University of London.
“It will allow more places to do this, and I think it will definitely allow more patients to be diagnosed” with PA from a unilateral source. AVS “is a real bottleneck,” she said. “We hope metomidate, or molecular imaging using other selective radiotracers, will enable many more patients to be diagnosed and appropriately managed.” Creating new diagnostic options for patients with PA and potentially increasing the number of these patients who are surgical candidates “is the aim of this study.”
Patients with PA develop a curable form of hypertension if their excess aldosterone can be neutralized with a mineralocorticoid receptor antagonist (MRA), or even more definitively by surgical removal of the adrenal aldosteronoma generating the hormonal excess as long as the adenoma is unilateral. Conventional imaging of the adrenals with CT or MRI has proven unreliable for identifying adrenal nodules noninvasively, which has made the invasive and technically challenging standard option of AVS the only game in town.
But some endocrinologists caution that the results from this one study do not suffice to make 11C-metomidate-based PET-CT imaging a widely used alternative.
‘This is a first step.’
“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.
But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.
“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.
Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.
MATCHing imaging against AVS
To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.
The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.
The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.
For each of the four metrics, 11C-metomidate PET-CT produced point estimates of diagnostic accuracy that consistently edged out AVS. While these advantages were not large enough to meet the prespecified threshold for proving superiority, they comfortably showed the noninferiority of this imaging method compared with AVS.
For example, the PET-CT method had 43.6% accuracy for predicting a clinical cure, compared with 39.7% accuracy for AVS. For complete biochemical cure, imaging had 68.8% accuracy, compared with 62.3% for AVS, Dr. Wu reported.
Another notable finding from the study was how strongly a robust blood pressure response to spironolactone predicted the clinical outcome from surgery. Patients whose systolic blood pressure fell below 135 mm Hg on MRA treatment had a nearly 18-fold higher rate of achieving a complete clinical cure following surgery compared with patients who did not have as dramatic a blood pressure response to MRA treatment.
Woefully low rates of PA assessment
But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.
Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.
“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.
The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
FROM ENDO 2021