BARCELONA – Final overall survival (OS) did not differ significantly among patients with stage IV squamous non–small cell lung carcinoma who were treated with either first-line atezolizumab + chemotherapy or chemotherapy alone in the phase 3 IMpower131 trial.

Sharon Worcester/MDedge News

Median OS in the intent-to-treat population was 14.2 months vs. 13.5 months with vs. without the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab, respectively (hazard ratio, 0.88), Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna, Italy, reported at the World Conference on Lung Cancer.

However, patients with high PD-L1 expression (14% and 13% of patients in the groups, respectively), experienced a clinically meaningful improvement in OS with atezolizumab + chemotherapy vs. chemotherapy alone (median of 23.4 vs. 10.2 months; HR, 0.48), Dr. Cappuzzo said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“This means we had a reduction in the risk of death that was more than 50%,” he said, adding that no new or unexpected safety signals were reported.

IMpower131 randomized 1,021 patients with a median age of 65 years 1:1:1 to receive either atezolizumab (1,200 mg) + carboplatin (area under the curve 6) + paclitaxel (200 mg/m2) every 3 weeks, or atezolizumab + carboplatin + nab-paclitaxel (100 mg/m² every week), or carboplatin + nab-paclitaxel for four or six cycles. Patients in the first two arms (A and B) received atezolizumab maintenance therapy until loss of clinical benefit or progressive disease occurred, and those in latter arm (C) received best supportive care after completing the treatment cycles.

SOURCE: Cappuzzo F et al. WCLC 2019, Abstract OS14.02 .

BARCELONA – Final overall survival (OS) did not differ significantly among patients with stage IV squamous non–small cell lung carcinoma who were treated with either first-line atezolizumab + chemotherapy or chemotherapy alone in the phase 3 IMpower131 trial.

Sharon Worcester/MDedge News

Median OS in the intent-to-treat population was 14.2 months vs. 13.5 months with vs. without the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab, respectively (hazard ratio, 0.88), Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna, Italy, reported at the World Conference on Lung Cancer.

However, patients with high PD-L1 expression (14% and 13% of patients in the groups, respectively), experienced a clinically meaningful improvement in OS with atezolizumab + chemotherapy vs. chemotherapy alone (median of 23.4 vs. 10.2 months; HR, 0.48), Dr. Cappuzzo said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“This means we had a reduction in the risk of death that was more than 50%,” he said, adding that no new or unexpected safety signals were reported.

IMpower131 randomized 1,021 patients with a median age of 65 years 1:1:1 to receive either atezolizumab (1,200 mg) + carboplatin (area under the curve 6) + paclitaxel (200 mg/m2) every 3 weeks, or atezolizumab + carboplatin + nab-paclitaxel (100 mg/m² every week), or carboplatin + nab-paclitaxel for four or six cycles. Patients in the first two arms (A and B) received atezolizumab maintenance therapy until loss of clinical benefit or progressive disease occurred, and those in latter arm (C) received best supportive care after completing the treatment cycles.

SOURCE: Cappuzzo F et al. WCLC 2019, Abstract OS14.02 .

BARCELONA – Final overall survival (OS) did not differ significantly among patients with stage IV squamous non–small cell lung carcinoma who were treated with either first-line atezolizumab + chemotherapy or chemotherapy alone in the phase 3 IMpower131 trial.

Sharon Worcester/MDedge News

Median OS in the intent-to-treat population was 14.2 months vs. 13.5 months with vs. without the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab, respectively (hazard ratio, 0.88), Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna, Italy, reported at the World Conference on Lung Cancer.

However, patients with high PD-L1 expression (14% and 13% of patients in the groups, respectively), experienced a clinically meaningful improvement in OS with atezolizumab + chemotherapy vs. chemotherapy alone (median of 23.4 vs. 10.2 months; HR, 0.48), Dr. Cappuzzo said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“This means we had a reduction in the risk of death that was more than 50%,” he said, adding that no new or unexpected safety signals were reported.

IMpower131 randomized 1,021 patients with a median age of 65 years 1:1:1 to receive either atezolizumab (1,200 mg) + carboplatin (area under the curve 6) + paclitaxel (200 mg/m2) every 3 weeks, or atezolizumab + carboplatin + nab-paclitaxel (100 mg/m² every week), or carboplatin + nab-paclitaxel for four or six cycles. Patients in the first two arms (A and B) received atezolizumab maintenance therapy until loss of clinical benefit or progressive disease occurred, and those in latter arm (C) received best supportive care after completing the treatment cycles.

SOURCE: Cappuzzo F et al. WCLC 2019, Abstract OS14.02 .

Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.

©photoaged/FOTOLIA

Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.

The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.

Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. High school athletes have lower rates of anxiety and depression than those of their peers. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,¹ possibly because of the social connections to peers and adults that grow out of them.

While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.

Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.

Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.²

Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.

2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.

Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.

©photoaged/FOTOLIA

Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.

The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.

Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. High school athletes have lower rates of anxiety and depression than those of their peers. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,¹ possibly because of the social connections to peers and adults that grow out of them.

While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.

Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.

Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.²

Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.

2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.

Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.

©photoaged/FOTOLIA

Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.

The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.

Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. High school athletes have lower rates of anxiety and depression than those of their peers. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,¹ possibly because of the social connections to peers and adults that grow out of them.

While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.

Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.

Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.²

Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.

2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.

Loss-of-function mutations in the PBRM1 gene are more common among patients with metastatic clear cell renal cell carcinoma (ccRCC) who have clinical responses to immune checkpoint inhibitors (ICIs), but the mutations fall a little short of serving as clinical biomarkers, investigators say.

Among patients with metastatic ccRCC enrolled in a randomized, phase 3 clinical trial comparing nivolumab (Opdivo) with everolimus (Afinitor) in patients who had previously received antiangiogenic therapy, patients with responses to nivolumab were more than twice as likely as nonresponders to have a truncating loss-of-function mutation in PBRM1, reported Toni K. Choueiri, MD, and colleagues from the Dana-Farber Cancer Institute in Boston.

Patients with PBRM1 mutations were also more likely to have a clinical benefit (complete/partial response, or stable disease with tumor shrinkage and progression-free survival [PFS] of at least 6 months) as well as better PFS and overall survival than patients without mutations.

“The association of PBRM1 truncating mutations with response to anti–[programmed death-1] therapy was confirmed in an independent ccRCC cohort. However, key limitations restrict use of PBRM1 mutations as a clinical biomarker,” they wrote in a research letter to JAMA Oncology.

Those limitations include an only modest effect of mutations on response and survival, a lack of evidence for a PBRM1 mutation effect in the first-line setting, and a possible association between mutations and benefit from prior antiangiogenic therapies, they acknowledged.

Dr. Choueiri was a coauthor of a previous study of genomic correlates of response to ICIs in ccRCC, which found that PBRM1 loss may influence response to checkpoint inhibitors by altering global tumor-cell expression.

In the current study, he and his colleagues looked at archival tumor tissue from an independent cohort of 382 patients who were part of a larger phase 3 trial. Of this group, 189 were treated with nivolumab, and 193 were treated with everolimus. PBRM1 mutations were identified in 55 of the nivolumab-treated patients (29%) and in 45 of the everolimus-treated patients (23%).

When they looked at clinical responses, they found that 15 of 38 patients with response to nivolumab (39%) had truncating PBRM1 mutations, compared with 16 of 74 nonresponding patients (22%), which translated into an odds ratio for response of 2.34 (P = .04).

Similarly, PBRM1 mutations among nivolumab-treated patients were significantly associated with clinical benefit (OR, 2.14; P = .0497), PFS (hazard ratio for progression, 0.67; P = .03), and overall survival (HR, 0.65; P = .03).

In contrast, there were no significant associations in everolimus-treated patients between PBRM1 mutations and either response, PFS, or overall survival.

“The concomitant presence of other cellular or molecular features may further influence the findings described herein. Nonetheless, this validated association between PBRM1 alterations and ICI response in a large randomized study represents a further step toward the development of genomic predictors for immunotherapies in advanced RCC,” the investigators concluded.

The study was supported by Department of Defense Congressionally Directed Medical Research Programs and Bristol-Myers Squibb. Dr. Choueiri disclosed personal fees from Bristol-Myers Squibb and fees and grants from other companies. One coauthor is a Bristol-Myers Squibb employee and shareholder.

SOURCE: Choueiri TK et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.3158.

Loss-of-function mutations in the PBRM1 gene are more common among patients with metastatic clear cell renal cell carcinoma (ccRCC) who have clinical responses to immune checkpoint inhibitors (ICIs), but the mutations fall a little short of serving as clinical biomarkers, investigators say.

Among patients with metastatic ccRCC enrolled in a randomized, phase 3 clinical trial comparing nivolumab (Opdivo) with everolimus (Afinitor) in patients who had previously received antiangiogenic therapy, patients with responses to nivolumab were more than twice as likely as nonresponders to have a truncating loss-of-function mutation in PBRM1, reported Toni K. Choueiri, MD, and colleagues from the Dana-Farber Cancer Institute in Boston.

Patients with PBRM1 mutations were also more likely to have a clinical benefit (complete/partial response, or stable disease with tumor shrinkage and progression-free survival [PFS] of at least 6 months) as well as better PFS and overall survival than patients without mutations.

“The association of PBRM1 truncating mutations with response to anti–[programmed death-1] therapy was confirmed in an independent ccRCC cohort. However, key limitations restrict use of PBRM1 mutations as a clinical biomarker,” they wrote in a research letter to JAMA Oncology.

Those limitations include an only modest effect of mutations on response and survival, a lack of evidence for a PBRM1 mutation effect in the first-line setting, and a possible association between mutations and benefit from prior antiangiogenic therapies, they acknowledged.

Dr. Choueiri was a coauthor of a previous study of genomic correlates of response to ICIs in ccRCC, which found that PBRM1 loss may influence response to checkpoint inhibitors by altering global tumor-cell expression.

In the current study, he and his colleagues looked at archival tumor tissue from an independent cohort of 382 patients who were part of a larger phase 3 trial. Of this group, 189 were treated with nivolumab, and 193 were treated with everolimus. PBRM1 mutations were identified in 55 of the nivolumab-treated patients (29%) and in 45 of the everolimus-treated patients (23%).

When they looked at clinical responses, they found that 15 of 38 patients with response to nivolumab (39%) had truncating PBRM1 mutations, compared with 16 of 74 nonresponding patients (22%), which translated into an odds ratio for response of 2.34 (P = .04).

Similarly, PBRM1 mutations among nivolumab-treated patients were significantly associated with clinical benefit (OR, 2.14; P = .0497), PFS (hazard ratio for progression, 0.67; P = .03), and overall survival (HR, 0.65; P = .03).

In contrast, there were no significant associations in everolimus-treated patients between PBRM1 mutations and either response, PFS, or overall survival.

“The concomitant presence of other cellular or molecular features may further influence the findings described herein. Nonetheless, this validated association between PBRM1 alterations and ICI response in a large randomized study represents a further step toward the development of genomic predictors for immunotherapies in advanced RCC,” the investigators concluded.

The study was supported by Department of Defense Congressionally Directed Medical Research Programs and Bristol-Myers Squibb. Dr. Choueiri disclosed personal fees from Bristol-Myers Squibb and fees and grants from other companies. One coauthor is a Bristol-Myers Squibb employee and shareholder.

SOURCE: Choueiri TK et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.3158.

Loss-of-function mutations in the PBRM1 gene are more common among patients with metastatic clear cell renal cell carcinoma (ccRCC) who have clinical responses to immune checkpoint inhibitors (ICIs), but the mutations fall a little short of serving as clinical biomarkers, investigators say.

Among patients with metastatic ccRCC enrolled in a randomized, phase 3 clinical trial comparing nivolumab (Opdivo) with everolimus (Afinitor) in patients who had previously received antiangiogenic therapy, patients with responses to nivolumab were more than twice as likely as nonresponders to have a truncating loss-of-function mutation in PBRM1, reported Toni K. Choueiri, MD, and colleagues from the Dana-Farber Cancer Institute in Boston.

Patients with PBRM1 mutations were also more likely to have a clinical benefit (complete/partial response, or stable disease with tumor shrinkage and progression-free survival [PFS] of at least 6 months) as well as better PFS and overall survival than patients without mutations.

“The association of PBRM1 truncating mutations with response to anti–[programmed death-1] therapy was confirmed in an independent ccRCC cohort. However, key limitations restrict use of PBRM1 mutations as a clinical biomarker,” they wrote in a research letter to JAMA Oncology.

Those limitations include an only modest effect of mutations on response and survival, a lack of evidence for a PBRM1 mutation effect in the first-line setting, and a possible association between mutations and benefit from prior antiangiogenic therapies, they acknowledged.

Dr. Choueiri was a coauthor of a previous study of genomic correlates of response to ICIs in ccRCC, which found that PBRM1 loss may influence response to checkpoint inhibitors by altering global tumor-cell expression.

In the current study, he and his colleagues looked at archival tumor tissue from an independent cohort of 382 patients who were part of a larger phase 3 trial. Of this group, 189 were treated with nivolumab, and 193 were treated with everolimus. PBRM1 mutations were identified in 55 of the nivolumab-treated patients (29%) and in 45 of the everolimus-treated patients (23%).

When they looked at clinical responses, they found that 15 of 38 patients with response to nivolumab (39%) had truncating PBRM1 mutations, compared with 16 of 74 nonresponding patients (22%), which translated into an odds ratio for response of 2.34 (P = .04).

Similarly, PBRM1 mutations among nivolumab-treated patients were significantly associated with clinical benefit (OR, 2.14; P = .0497), PFS (hazard ratio for progression, 0.67; P = .03), and overall survival (HR, 0.65; P = .03).

In contrast, there were no significant associations in everolimus-treated patients between PBRM1 mutations and either response, PFS, or overall survival.

“The concomitant presence of other cellular or molecular features may further influence the findings described herein. Nonetheless, this validated association between PBRM1 alterations and ICI response in a large randomized study represents a further step toward the development of genomic predictors for immunotherapies in advanced RCC,” the investigators concluded.

The study was supported by Department of Defense Congressionally Directed Medical Research Programs and Bristol-Myers Squibb. Dr. Choueiri disclosed personal fees from Bristol-Myers Squibb and fees and grants from other companies. One coauthor is a Bristol-Myers Squibb employee and shareholder.

SOURCE: Choueiri TK et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.3158.

Skin inflammation, infections, mouth ulcers, and wound healing are among the indications for the use of the traditional Polynesian medicinal plant Morinda citrifolia, also known as Noni, which has been in use on the islands for two millennia.^1-4 The plant, found abundantly in Southeast Asia, Australia, the Pacific Basin, and the Caribbean, is called Great Morinda or cheese fruit in Australia, Nono in Tahiti, Indian Mulberry in India, and Ba ji tian in China.^4-6 It is also deployed for a wide range of health purposes in Brazil.⁷

CampPhoto/iStock/Getty Images

Noni has been credited with conferring various salutary benefits against arthritis, diabetes, fever, gingivitis, headaches, infections, inflammation, respiratory illnesses, and tuberculosis.^3,8 In alternative medicine, the fruit juice, which has been found to be safe, is used for multiple indications, with a slew of studies presenting evidence for anti-inflammatory, antioxidant, and apoptosis-inducing benefits against cancer.^5,6 All parts of M. citrifolia – leaves, fruits, roots, bark, flowers, and seeds – have been used in traditional medical practices.⁸ This column will focus on recent research into the broad array of biologic activities attributed to the plant and possible dermatologic uses.
 

Diverse biologic properties

In 2007, Nayak et al. showed that the juice of M. citrifolia fruit significantly lowered sugar levels in diabetic rats and facilitated their wound healing.¹

Three years later, Thani et al. determined that the leaves of M. citrifolia exert antiproliferative and antioxidative activities, with chemopreventive benefits seen against epidermoid and cervical cancers.⁹

In 2011, Serafini et al. confirmed the antibacterial, anti-inflammatory, antioxidant, and antinociceptive qualities of the aqueous extract from M. citrifolia leaves, with the extract shown to significantly lower leukocyte migration in doses of 200 and 400 mg/kg. Mild antibacterial properties were seen as was an antinociceptive effect at the higher dose in the acetic-acid-induced writhing test.³

A comprehensive literature review in 2017 by Torres et al. identified a varied and extensive list of biological activities of M. citrifolia, including immunostimulatory, antitumor, antidiabetic, antiobesity, antibacterial and antiseptic, antifungal, antiviral, anti-inflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, photoprotective, and antiwrinkle among several others. Despite its use in disease prevention and treatment around the world, the researchers call for more in vitro and in vivo models in addition to clinical trials to further examine the health benefits of Noni.⁷

Early in 2019, De La Cruz-Sánchez et al. determined that the methanolic extract of M. citrifolia displayed marked activity against methicillin-resistant Staphylococcus aureus (MRSA), thus supporting its continuing applications in traditional medical practice.²

Photoprotection and antiaging potential

Based on their prior work demonstrating that M. citrifolia fruit upregulates the production of type I collagen and glycosaminoglycans in primary cultures of normal human fibroblasts, Kim et al. isolated anthraquinone from the fruit and showed that it dose-dependently decreased the expression of collagenase matrix metalloproteinase-1 in human dermal fibroblasts. The investigators also found that an anthraquinone-containing nano-emulsion raised type I procollagen in nude mouse skin. They concluded, in this 2005 study, that Noni extract warrants consideration as an antiwrinkle agent given its proclivity to induce the production of collagen.¹⁰

In 2009, West et al. assessed a carbomer gel base containing the ethanol extract and juice pressed from Noni leaves for possible allergenic activity in a repeat-insult patch test in 49 volunteers. They also used a UVB-induced erythema model in 25 subjects to test the topical photoprotective potential of the ethanol extract and leaf juice. The investigators reported no allergic potential evinced by the patch tests, and in a histamine H-1 receptor antagonism assay, the leaves hindered receptor binding by 57%, suggesting anti-inflammatory activity. In the UVB test, the dose necessary to engender erythema was nearly 3.5 times higher than in untreated skin. The team concluded that M. citrifolia leaves are safe for topical application and show promise in lessening UVB-induced skin damage.¹¹

A 2014 study on mice by Serafini et al. showed that the dorsal skin of mice treated for 7 days with topical M. citrifolia was protected from damage by exposure to UVA-UVB radiation as measured by skin thickness, transepidermal water loss, erythema, and histological changes.¹²
 

Conclusion

Morinda citrifolia has been used in traditional medicine for at least 2,000 years. Its reported list of uses covers an impressive gamut of indications.

Modern medicine is beginning to catch up with new research conducted on this copious and beloved plant. That said, much more data, particularly from human clinical trials, are necessary to elucidate the most appropriate dermatologic roles for M. citrifolia. I just started growing a Noni tree in my yard because some patients have reported using it on their skin. I will report back and let you know how it goes. It is flowering now!

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Nayak BS et al. J Wound Care. 2007 Feb;16(2):83-6.

2. De La Cruz-Sánchez NG et al. Microb Pathog. 2019 Mar;128:347-53.

3. Serafini MR et al. J Med Food. 2011 Oct;14(10):1159-66.

4. Wang MY, Su C. Ann N Y Acad Sci. 2001 Dec;952:161-8.

5. Gupta RK, Patel AK. Asian Pac J Cancer Prev. 2013;14(8):4495-9.

6. Brown AC. Phytother Res. 2012 Oct;26(10):1427-40.

7. Torres MAO et al. Phytother Res. 2017 Jul;31(7):971-9.

8. Potterat O, Hamburger M. Planta Med. 2007 Mar;73(3):191-9.

9. Thani W et al. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):482-9.
 

10. Kim SW et al. J Med Food. 2005 Winter;8(4):552-5.

11. West BJ et al. J Nat Med. 2009 Jul;63(3):351-4.

12. Serafini MR et al. Biomed Res Int. 2014;2014:587819. doi: 10.1155/2014/587819.

Skin inflammation, infections, mouth ulcers, and wound healing are among the indications for the use of the traditional Polynesian medicinal plant Morinda citrifolia, also known as Noni, which has been in use on the islands for two millennia.^1-4 The plant, found abundantly in Southeast Asia, Australia, the Pacific Basin, and the Caribbean, is called Great Morinda or cheese fruit in Australia, Nono in Tahiti, Indian Mulberry in India, and Ba ji tian in China.^4-6 It is also deployed for a wide range of health purposes in Brazil.⁷

CampPhoto/iStock/Getty Images

Noni has been credited with conferring various salutary benefits against arthritis, diabetes, fever, gingivitis, headaches, infections, inflammation, respiratory illnesses, and tuberculosis.^3,8 In alternative medicine, the fruit juice, which has been found to be safe, is used for multiple indications, with a slew of studies presenting evidence for anti-inflammatory, antioxidant, and apoptosis-inducing benefits against cancer.^5,6 All parts of M. citrifolia – leaves, fruits, roots, bark, flowers, and seeds – have been used in traditional medical practices.⁸ This column will focus on recent research into the broad array of biologic activities attributed to the plant and possible dermatologic uses.
 

Diverse biologic properties

In 2007, Nayak et al. showed that the juice of M. citrifolia fruit significantly lowered sugar levels in diabetic rats and facilitated their wound healing.¹

Three years later, Thani et al. determined that the leaves of M. citrifolia exert antiproliferative and antioxidative activities, with chemopreventive benefits seen against epidermoid and cervical cancers.⁹

In 2011, Serafini et al. confirmed the antibacterial, anti-inflammatory, antioxidant, and antinociceptive qualities of the aqueous extract from M. citrifolia leaves, with the extract shown to significantly lower leukocyte migration in doses of 200 and 400 mg/kg. Mild antibacterial properties were seen as was an antinociceptive effect at the higher dose in the acetic-acid-induced writhing test.³

A comprehensive literature review in 2017 by Torres et al. identified a varied and extensive list of biological activities of M. citrifolia, including immunostimulatory, antitumor, antidiabetic, antiobesity, antibacterial and antiseptic, antifungal, antiviral, anti-inflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, photoprotective, and antiwrinkle among several others. Despite its use in disease prevention and treatment around the world, the researchers call for more in vitro and in vivo models in addition to clinical trials to further examine the health benefits of Noni.⁷

Early in 2019, De La Cruz-Sánchez et al. determined that the methanolic extract of M. citrifolia displayed marked activity against methicillin-resistant Staphylococcus aureus (MRSA), thus supporting its continuing applications in traditional medical practice.²

Photoprotection and antiaging potential

Based on their prior work demonstrating that M. citrifolia fruit upregulates the production of type I collagen and glycosaminoglycans in primary cultures of normal human fibroblasts, Kim et al. isolated anthraquinone from the fruit and showed that it dose-dependently decreased the expression of collagenase matrix metalloproteinase-1 in human dermal fibroblasts. The investigators also found that an anthraquinone-containing nano-emulsion raised type I procollagen in nude mouse skin. They concluded, in this 2005 study, that Noni extract warrants consideration as an antiwrinkle agent given its proclivity to induce the production of collagen.¹⁰

In 2009, West et al. assessed a carbomer gel base containing the ethanol extract and juice pressed from Noni leaves for possible allergenic activity in a repeat-insult patch test in 49 volunteers. They also used a UVB-induced erythema model in 25 subjects to test the topical photoprotective potential of the ethanol extract and leaf juice. The investigators reported no allergic potential evinced by the patch tests, and in a histamine H-1 receptor antagonism assay, the leaves hindered receptor binding by 57%, suggesting anti-inflammatory activity. In the UVB test, the dose necessary to engender erythema was nearly 3.5 times higher than in untreated skin. The team concluded that M. citrifolia leaves are safe for topical application and show promise in lessening UVB-induced skin damage.¹¹

A 2014 study on mice by Serafini et al. showed that the dorsal skin of mice treated for 7 days with topical M. citrifolia was protected from damage by exposure to UVA-UVB radiation as measured by skin thickness, transepidermal water loss, erythema, and histological changes.¹²
 

Conclusion

Morinda citrifolia has been used in traditional medicine for at least 2,000 years. Its reported list of uses covers an impressive gamut of indications.

Modern medicine is beginning to catch up with new research conducted on this copious and beloved plant. That said, much more data, particularly from human clinical trials, are necessary to elucidate the most appropriate dermatologic roles for M. citrifolia. I just started growing a Noni tree in my yard because some patients have reported using it on their skin. I will report back and let you know how it goes. It is flowering now!

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Nayak BS et al. J Wound Care. 2007 Feb;16(2):83-6.

2. De La Cruz-Sánchez NG et al. Microb Pathog. 2019 Mar;128:347-53.

3. Serafini MR et al. J Med Food. 2011 Oct;14(10):1159-66.

4. Wang MY, Su C. Ann N Y Acad Sci. 2001 Dec;952:161-8.

5. Gupta RK, Patel AK. Asian Pac J Cancer Prev. 2013;14(8):4495-9.

6. Brown AC. Phytother Res. 2012 Oct;26(10):1427-40.

7. Torres MAO et al. Phytother Res. 2017 Jul;31(7):971-9.

8. Potterat O, Hamburger M. Planta Med. 2007 Mar;73(3):191-9.

9. Thani W et al. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):482-9.
 

10. Kim SW et al. J Med Food. 2005 Winter;8(4):552-5.

11. West BJ et al. J Nat Med. 2009 Jul;63(3):351-4.

12. Serafini MR et al. Biomed Res Int. 2014;2014:587819. doi: 10.1155/2014/587819.

Skin inflammation, infections, mouth ulcers, and wound healing are among the indications for the use of the traditional Polynesian medicinal plant Morinda citrifolia, also known as Noni, which has been in use on the islands for two millennia.^1-4 The plant, found abundantly in Southeast Asia, Australia, the Pacific Basin, and the Caribbean, is called Great Morinda or cheese fruit in Australia, Nono in Tahiti, Indian Mulberry in India, and Ba ji tian in China.^4-6 It is also deployed for a wide range of health purposes in Brazil.⁷

CampPhoto/iStock/Getty Images

Noni has been credited with conferring various salutary benefits against arthritis, diabetes, fever, gingivitis, headaches, infections, inflammation, respiratory illnesses, and tuberculosis.^3,8 In alternative medicine, the fruit juice, which has been found to be safe, is used for multiple indications, with a slew of studies presenting evidence for anti-inflammatory, antioxidant, and apoptosis-inducing benefits against cancer.^5,6 All parts of M. citrifolia – leaves, fruits, roots, bark, flowers, and seeds – have been used in traditional medical practices.⁸ This column will focus on recent research into the broad array of biologic activities attributed to the plant and possible dermatologic uses.
 

Diverse biologic properties

In 2007, Nayak et al. showed that the juice of M. citrifolia fruit significantly lowered sugar levels in diabetic rats and facilitated their wound healing.¹

Three years later, Thani et al. determined that the leaves of M. citrifolia exert antiproliferative and antioxidative activities, with chemopreventive benefits seen against epidermoid and cervical cancers.⁹

In 2011, Serafini et al. confirmed the antibacterial, anti-inflammatory, antioxidant, and antinociceptive qualities of the aqueous extract from M. citrifolia leaves, with the extract shown to significantly lower leukocyte migration in doses of 200 and 400 mg/kg. Mild antibacterial properties were seen as was an antinociceptive effect at the higher dose in the acetic-acid-induced writhing test.³

A comprehensive literature review in 2017 by Torres et al. identified a varied and extensive list of biological activities of M. citrifolia, including immunostimulatory, antitumor, antidiabetic, antiobesity, antibacterial and antiseptic, antifungal, antiviral, anti-inflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, photoprotective, and antiwrinkle among several others. Despite its use in disease prevention and treatment around the world, the researchers call for more in vitro and in vivo models in addition to clinical trials to further examine the health benefits of Noni.⁷

Early in 2019, De La Cruz-Sánchez et al. determined that the methanolic extract of M. citrifolia displayed marked activity against methicillin-resistant Staphylococcus aureus (MRSA), thus supporting its continuing applications in traditional medical practice.²

Photoprotection and antiaging potential

Based on their prior work demonstrating that M. citrifolia fruit upregulates the production of type I collagen and glycosaminoglycans in primary cultures of normal human fibroblasts, Kim et al. isolated anthraquinone from the fruit and showed that it dose-dependently decreased the expression of collagenase matrix metalloproteinase-1 in human dermal fibroblasts. The investigators also found that an anthraquinone-containing nano-emulsion raised type I procollagen in nude mouse skin. They concluded, in this 2005 study, that Noni extract warrants consideration as an antiwrinkle agent given its proclivity to induce the production of collagen.¹⁰

In 2009, West et al. assessed a carbomer gel base containing the ethanol extract and juice pressed from Noni leaves for possible allergenic activity in a repeat-insult patch test in 49 volunteers. They also used a UVB-induced erythema model in 25 subjects to test the topical photoprotective potential of the ethanol extract and leaf juice. The investigators reported no allergic potential evinced by the patch tests, and in a histamine H-1 receptor antagonism assay, the leaves hindered receptor binding by 57%, suggesting anti-inflammatory activity. In the UVB test, the dose necessary to engender erythema was nearly 3.5 times higher than in untreated skin. The team concluded that M. citrifolia leaves are safe for topical application and show promise in lessening UVB-induced skin damage.¹¹

A 2014 study on mice by Serafini et al. showed that the dorsal skin of mice treated for 7 days with topical M. citrifolia was protected from damage by exposure to UVA-UVB radiation as measured by skin thickness, transepidermal water loss, erythema, and histological changes.¹²
 

Conclusion

Morinda citrifolia has been used in traditional medicine for at least 2,000 years. Its reported list of uses covers an impressive gamut of indications.

Modern medicine is beginning to catch up with new research conducted on this copious and beloved plant. That said, much more data, particularly from human clinical trials, are necessary to elucidate the most appropriate dermatologic roles for M. citrifolia. I just started growing a Noni tree in my yard because some patients have reported using it on their skin. I will report back and let you know how it goes. It is flowering now!

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Nayak BS et al. J Wound Care. 2007 Feb;16(2):83-6.

2. De La Cruz-Sánchez NG et al. Microb Pathog. 2019 Mar;128:347-53.

3. Serafini MR et al. J Med Food. 2011 Oct;14(10):1159-66.

4. Wang MY, Su C. Ann N Y Acad Sci. 2001 Dec;952:161-8.

5. Gupta RK, Patel AK. Asian Pac J Cancer Prev. 2013;14(8):4495-9.

6. Brown AC. Phytother Res. 2012 Oct;26(10):1427-40.

7. Torres MAO et al. Phytother Res. 2017 Jul;31(7):971-9.

8. Potterat O, Hamburger M. Planta Med. 2007 Mar;73(3):191-9.

9. Thani W et al. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):482-9.
 

10. Kim SW et al. J Med Food. 2005 Winter;8(4):552-5.

11. West BJ et al. J Nat Med. 2009 Jul;63(3):351-4.

12. Serafini MR et al. Biomed Res Int. 2014;2014:587819. doi: 10.1155/2014/587819.

Interleukin-6, IL-1 receptor antagonist (IL-1RA), and tumor necrosis factor–alpha (TNF-alpha) activity was associated with inflammation and neurodegeneration in patients with chronic bipolar disorder, according to Sercan Karabulut, MD, of Kepez State Hospital in Antalya, Turkey, and associates.

In a study published in the Turkish Journal of Psychiatry, the investigators collected enzyme-linked immunosorbent assays from 30 patients with early-stage bipolar disorder, 77 with chronic disease, and 30 healthy controls. Early-stage disease patients were significantly younger than chronic patients (25.3 years vs. 37.8 years). TNF-alpha, IL-6, IL-1RA, neuron-specific enolase, and S100 calcium-binding protein B (S100B) were measured, reported Dr. Karabulut and associates.

Patients with chronic bipolar disorder had significantly increased levels of all measured markers, compared with those with early-stage disease and the healthy controls. IL-6 and IL-1RA levels correlated with neuron-specific enolase and S100B, biomarkers that are associated with glial alterations and neuronal damage. TNF-alpha correlated with scores on the Clinical Global Impressions Scale and other measures.

“The present findings support in part the hypothesis that inflammation starts at later stages of [bipolar disorder], presumably as an associated effect of gliosis and neuronal loss, which appear to be particularly associated with IL-1RA and IL-6 activity,” the investigators wrote. “TNF-alpha ... might be a useful prognostic marker in patients with [bipolar disorder].”

No conflicts of interest were reported.

[email protected]

SOURCE: Karabulut S et al. Turk Psikiyatri Derg. 2019 Winter;30(2):75-81.

Interleukin-6, IL-1 receptor antagonist (IL-1RA), and tumor necrosis factor–alpha (TNF-alpha) activity was associated with inflammation and neurodegeneration in patients with chronic bipolar disorder, according to Sercan Karabulut, MD, of Kepez State Hospital in Antalya, Turkey, and associates.

In a study published in the Turkish Journal of Psychiatry, the investigators collected enzyme-linked immunosorbent assays from 30 patients with early-stage bipolar disorder, 77 with chronic disease, and 30 healthy controls. Early-stage disease patients were significantly younger than chronic patients (25.3 years vs. 37.8 years). TNF-alpha, IL-6, IL-1RA, neuron-specific enolase, and S100 calcium-binding protein B (S100B) were measured, reported Dr. Karabulut and associates.

Patients with chronic bipolar disorder had significantly increased levels of all measured markers, compared with those with early-stage disease and the healthy controls. IL-6 and IL-1RA levels correlated with neuron-specific enolase and S100B, biomarkers that are associated with glial alterations and neuronal damage. TNF-alpha correlated with scores on the Clinical Global Impressions Scale and other measures.

“The present findings support in part the hypothesis that inflammation starts at later stages of [bipolar disorder], presumably as an associated effect of gliosis and neuronal loss, which appear to be particularly associated with IL-1RA and IL-6 activity,” the investigators wrote. “TNF-alpha ... might be a useful prognostic marker in patients with [bipolar disorder].”

No conflicts of interest were reported.

[email protected]

SOURCE: Karabulut S et al. Turk Psikiyatri Derg. 2019 Winter;30(2):75-81.

Interleukin-6, IL-1 receptor antagonist (IL-1RA), and tumor necrosis factor–alpha (TNF-alpha) activity was associated with inflammation and neurodegeneration in patients with chronic bipolar disorder, according to Sercan Karabulut, MD, of Kepez State Hospital in Antalya, Turkey, and associates.

In a study published in the Turkish Journal of Psychiatry, the investigators collected enzyme-linked immunosorbent assays from 30 patients with early-stage bipolar disorder, 77 with chronic disease, and 30 healthy controls. Early-stage disease patients were significantly younger than chronic patients (25.3 years vs. 37.8 years). TNF-alpha, IL-6, IL-1RA, neuron-specific enolase, and S100 calcium-binding protein B (S100B) were measured, reported Dr. Karabulut and associates.

Patients with chronic bipolar disorder had significantly increased levels of all measured markers, compared with those with early-stage disease and the healthy controls. IL-6 and IL-1RA levels correlated with neuron-specific enolase and S100B, biomarkers that are associated with glial alterations and neuronal damage. TNF-alpha correlated with scores on the Clinical Global Impressions Scale and other measures.

“The present findings support in part the hypothesis that inflammation starts at later stages of [bipolar disorder], presumably as an associated effect of gliosis and neuronal loss, which appear to be particularly associated with IL-1RA and IL-6 activity,” the investigators wrote. “TNF-alpha ... might be a useful prognostic marker in patients with [bipolar disorder].”

No conflicts of interest were reported.

[email protected]

SOURCE: Karabulut S et al. Turk Psikiyatri Derg. 2019 Winter;30(2):75-81.

STOCKHOLM – Among patients with multiple sclerosis (MS), average daily step count correlates with clinical measures of ambulation, cognitive function, brain atrophy on MRI, and quality of life, according to research presented at the annual congress of the European Committee for Treatment and Research in MS. Remote gait monitoring using a popular fitness tracker may offer a surrogate measure of MS disability in clinical trials, the researchers reported.

Many outcome measures in MS are evaluated in controlled contexts and do not indicate how patients are functioning outside of the clinical setting, said Valerie J. Block, PhD, from the Weill Institute for Neurosciences at the University of California, San Francisco. Patient-reported outcome measures are subject to recall bias and uneven perception of deficits. Remote ambulatory monitoring, on the other hand, could be a more objective measure that provides continuous information in the real-world setting, said Dr. Block. She and her colleagues have proposed remote ambulatory activity monitoring as an outcome measure for clinical trials.

The investigators chose this measure as an exploratory endpoint for SPI2, a phase 3 trial investigating the efficacy and safety of MD1003 (high-dose pharmaceutical-grade biotin) in patients with inactive primary progressive MS and secondary progressive MS. “To our knowledge, this is the first major clinical trial in progressive MS to include continuous remote step count monitoring as an exploratory endpoint,” said Dr. Block.

In the SPI2 study, patients received either MD1003 (300 mg/day) or placebo. To examine the relationship between ambulatory monitoring and clinical disability and MRI measures, the researchers remotely monitored participants’ ambulatory activity for 27 months using a fitness tracker. The investigators used the average daily step count from the first 30 days as the baseline activity measure. At first, they set a low daily step-count goal to minimize the influence of motivation on ambulatory activity. Participants later were taught how to change the goal independently.

Dr. Block and colleagues created LASSO subset selection regression models to correlate average daily step count with sex, age, disease duration, age at onset, disease course, and various MRI models (such as upper cervical cord area, gray matter volume, normalized brain volume, thalamic volume, and T1 and T2 lesion volumes). They performed least squares regression models on the subset selection results. Finally, the researchers calculated Spearman correlations between average daily step count and clinical disability, as measured by Expanded Disability Status Scale (EDSS) and timed 25-foot walk, and the Physical and Mental Health Composite measures of the MS Quality of Life scale (MSQoL-29).

As of April 23, 2019, the researchers had enrolled 492 patients (262 women) with full data at 90 centers (40 in the United States, 39 in Europe, 8 in Canada, and 3 in Australia). In all, 311 patients (63%) had secondary progressive MS, and 181 had primary progressive MS. Participants had moderate disability; the median EDSS score was 6.0. Median disease duration was 10.6 years. The mean daily step count during the first month was 3,699.

Greater step count was correlated with lower EDSS score, faster completion of the timed 25-foot walk, better Physical Health Composite score, better Symbol Digit Modalities Test score, and better Mental Health Composite score. Furthermore, greater mean daily step count also correlated with greater upper cervical cord area, greater normalized brain volume, greater gray matter volume, and lower T1 lesion volume. The correlations between step count and thalamic volume and T2 lesion volume were not significant. “These data support the study of steps as an exploratory outcome measure in clinical trials for progressive MS,” said Dr. Block.

Dr. Block received reimbursement for travel expenses related to this study from MedDay Pharmaceuticals. Coinvestigators received research support and compensation from companies such as Abbvie, Alexion, Biogen, Genentech, MedDay Pharmaceuticals, Novartis, and Sanofi Genzyme. One investigator is an employee of MedDay Pharmaceuticals.

[email protected]

SOURCE: Block V et al. ECTRIMS 2019, Abstract 217.

STOCKHOLM – Among patients with multiple sclerosis (MS), average daily step count correlates with clinical measures of ambulation, cognitive function, brain atrophy on MRI, and quality of life, according to research presented at the annual congress of the European Committee for Treatment and Research in MS. Remote gait monitoring using a popular fitness tracker may offer a surrogate measure of MS disability in clinical trials, the researchers reported.

Many outcome measures in MS are evaluated in controlled contexts and do not indicate how patients are functioning outside of the clinical setting, said Valerie J. Block, PhD, from the Weill Institute for Neurosciences at the University of California, San Francisco. Patient-reported outcome measures are subject to recall bias and uneven perception of deficits. Remote ambulatory monitoring, on the other hand, could be a more objective measure that provides continuous information in the real-world setting, said Dr. Block. She and her colleagues have proposed remote ambulatory activity monitoring as an outcome measure for clinical trials.

The investigators chose this measure as an exploratory endpoint for SPI2, a phase 3 trial investigating the efficacy and safety of MD1003 (high-dose pharmaceutical-grade biotin) in patients with inactive primary progressive MS and secondary progressive MS. “To our knowledge, this is the first major clinical trial in progressive MS to include continuous remote step count monitoring as an exploratory endpoint,” said Dr. Block.

In the SPI2 study, patients received either MD1003 (300 mg/day) or placebo. To examine the relationship between ambulatory monitoring and clinical disability and MRI measures, the researchers remotely monitored participants’ ambulatory activity for 27 months using a fitness tracker. The investigators used the average daily step count from the first 30 days as the baseline activity measure. At first, they set a low daily step-count goal to minimize the influence of motivation on ambulatory activity. Participants later were taught how to change the goal independently.

Dr. Block and colleagues created LASSO subset selection regression models to correlate average daily step count with sex, age, disease duration, age at onset, disease course, and various MRI models (such as upper cervical cord area, gray matter volume, normalized brain volume, thalamic volume, and T1 and T2 lesion volumes). They performed least squares regression models on the subset selection results. Finally, the researchers calculated Spearman correlations between average daily step count and clinical disability, as measured by Expanded Disability Status Scale (EDSS) and timed 25-foot walk, and the Physical and Mental Health Composite measures of the MS Quality of Life scale (MSQoL-29).

As of April 23, 2019, the researchers had enrolled 492 patients (262 women) with full data at 90 centers (40 in the United States, 39 in Europe, 8 in Canada, and 3 in Australia). In all, 311 patients (63%) had secondary progressive MS, and 181 had primary progressive MS. Participants had moderate disability; the median EDSS score was 6.0. Median disease duration was 10.6 years. The mean daily step count during the first month was 3,699.

Greater step count was correlated with lower EDSS score, faster completion of the timed 25-foot walk, better Physical Health Composite score, better Symbol Digit Modalities Test score, and better Mental Health Composite score. Furthermore, greater mean daily step count also correlated with greater upper cervical cord area, greater normalized brain volume, greater gray matter volume, and lower T1 lesion volume. The correlations between step count and thalamic volume and T2 lesion volume were not significant. “These data support the study of steps as an exploratory outcome measure in clinical trials for progressive MS,” said Dr. Block.

Dr. Block received reimbursement for travel expenses related to this study from MedDay Pharmaceuticals. Coinvestigators received research support and compensation from companies such as Abbvie, Alexion, Biogen, Genentech, MedDay Pharmaceuticals, Novartis, and Sanofi Genzyme. One investigator is an employee of MedDay Pharmaceuticals.

[email protected]

SOURCE: Block V et al. ECTRIMS 2019, Abstract 217.

STOCKHOLM – Among patients with multiple sclerosis (MS), average daily step count correlates with clinical measures of ambulation, cognitive function, brain atrophy on MRI, and quality of life, according to research presented at the annual congress of the European Committee for Treatment and Research in MS. Remote gait monitoring using a popular fitness tracker may offer a surrogate measure of MS disability in clinical trials, the researchers reported.

Many outcome measures in MS are evaluated in controlled contexts and do not indicate how patients are functioning outside of the clinical setting, said Valerie J. Block, PhD, from the Weill Institute for Neurosciences at the University of California, San Francisco. Patient-reported outcome measures are subject to recall bias and uneven perception of deficits. Remote ambulatory monitoring, on the other hand, could be a more objective measure that provides continuous information in the real-world setting, said Dr. Block. She and her colleagues have proposed remote ambulatory activity monitoring as an outcome measure for clinical trials.

The investigators chose this measure as an exploratory endpoint for SPI2, a phase 3 trial investigating the efficacy and safety of MD1003 (high-dose pharmaceutical-grade biotin) in patients with inactive primary progressive MS and secondary progressive MS. “To our knowledge, this is the first major clinical trial in progressive MS to include continuous remote step count monitoring as an exploratory endpoint,” said Dr. Block.

In the SPI2 study, patients received either MD1003 (300 mg/day) or placebo. To examine the relationship between ambulatory monitoring and clinical disability and MRI measures, the researchers remotely monitored participants’ ambulatory activity for 27 months using a fitness tracker. The investigators used the average daily step count from the first 30 days as the baseline activity measure. At first, they set a low daily step-count goal to minimize the influence of motivation on ambulatory activity. Participants later were taught how to change the goal independently.

Dr. Block and colleagues created LASSO subset selection regression models to correlate average daily step count with sex, age, disease duration, age at onset, disease course, and various MRI models (such as upper cervical cord area, gray matter volume, normalized brain volume, thalamic volume, and T1 and T2 lesion volumes). They performed least squares regression models on the subset selection results. Finally, the researchers calculated Spearman correlations between average daily step count and clinical disability, as measured by Expanded Disability Status Scale (EDSS) and timed 25-foot walk, and the Physical and Mental Health Composite measures of the MS Quality of Life scale (MSQoL-29).

As of April 23, 2019, the researchers had enrolled 492 patients (262 women) with full data at 90 centers (40 in the United States, 39 in Europe, 8 in Canada, and 3 in Australia). In all, 311 patients (63%) had secondary progressive MS, and 181 had primary progressive MS. Participants had moderate disability; the median EDSS score was 6.0. Median disease duration was 10.6 years. The mean daily step count during the first month was 3,699.

Greater step count was correlated with lower EDSS score, faster completion of the timed 25-foot walk, better Physical Health Composite score, better Symbol Digit Modalities Test score, and better Mental Health Composite score. Furthermore, greater mean daily step count also correlated with greater upper cervical cord area, greater normalized brain volume, greater gray matter volume, and lower T1 lesion volume. The correlations between step count and thalamic volume and T2 lesion volume were not significant. “These data support the study of steps as an exploratory outcome measure in clinical trials for progressive MS,” said Dr. Block.

Dr. Block received reimbursement for travel expenses related to this study from MedDay Pharmaceuticals. Coinvestigators received research support and compensation from companies such as Abbvie, Alexion, Biogen, Genentech, MedDay Pharmaceuticals, Novartis, and Sanofi Genzyme. One investigator is an employee of MedDay Pharmaceuticals.

[email protected]

SOURCE: Block V et al. ECTRIMS 2019, Abstract 217.

STOCKHOLM – Among a cohort of patients with highly active multiple sclerosis (MS), MRI without gadolinium contrast still detected most lesions. Further, lesions missed by skipping gadolinium would have changed treatment course for just 1 of the 84 patients in the study, said Lucia Gentili, MD, a neurologist in the department of medicine, section of neurology, at the University of Perugia (Italy), in an interview at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.

“Postcontrast MRI might not be mandatory to detect signs of disease activity in patients with active MS,” she observed.

The question of the long-term effects of gadolinium deposition from serial scans in patients with MS is a hot topic among both patients and those caring for people with MS, said Dr. Gentili, so she and her associates decided to see how avoiding gadolinium exposure would affect lesion detection and patient management among their patient population.

For the retrospective study, the investigators looked at the records of 84 patients with relapsing remitting MS at two Italian MS centers over a 5-year time span. This was a cohort enriched for patients with highly active disease, said Dr. Gentili. A total of 45 patients, or over half of the cohort, had experienced at least one relapse in the preceding year.

The study included patients who were being screened for a second-line treatment and had evidence of brain or spinal cord contrast-enhancing lesions on MRI, if they also had a previous MRI of the brain and spinal cord performed on the same scanner.

The uniform protocol used for all MRIs included axial T2-weighted, fluid attenuated inversion recovery (FLAIR), and pre- and postcontrast T1-weighted sequences.

In all, the reference MRI scans picked up 164 contrast-enhancing lesions; of these, 151 (92.1%) were also seen on the T2/FLAIR sequences, showing up as new or enlarging lesions. Thirteen lesions were not visible on T2/FLAIR sequences when compared with the previous MRI, said Dr. Gentili.

Almost all patients in the cohort – a group with highly active disease, Dr. Gentili emphasized – also had new or enlarging lesions visible in T2 sequences. “Only two patients with MRI evidence of contrast-enhancing lesions showed no new or enlarged lesions in T2/FLAIR images,” she added. “Therefore, without gadolinium administration, only two patients in our cohort would have been incorrectly classified as radiologically stable.”

In reality, though, one of the two subjects whose disease activity was missed without gadolinium contrast had a relapse in the preceding 12 months, so clinical evidence of disease activity prompted attention to this individual. “Thus, only one subject in the entire cohort would have been incorrectly classified as stable,” Dr. Gentili and coauthors reported.

The results of this small study do not represent a case for abandoning gadolinium, Dr. Gentili stressed. “In our study, active lesions detected only by gadolinium enhancement, that is, without any evidence of new or enlarged lesions on T2/FLAIR, occurred in a limited but significant portion of contrast-enhancing lesions,” occurring in about 8% of the total lesions.

Rather, this study and other ongoing work represents a basis for shared decision making between persons with MS and those caring for them. Particularly for patients with highly active MS who can anticipate receiving a high burden of contrast to track disease activity, physicians can consider presenting them with the option to omit gadolinium contrast, she said.

Dr. Gentili reported receiving a travel grant from the ECTRIMS scientific program committee, and several coauthors reported relationships with multiple pharmaceutical companies. One coauthor received research funding from the Italian Multiple Sclerosis Society, the Italian Ministry of health, and the Italian Ministry of Education.

[email protected]

SOURCE: Gentili L et al. ECTRIMS 2019, Abstract P901.

STOCKHOLM – Among a cohort of patients with highly active multiple sclerosis (MS), MRI without gadolinium contrast still detected most lesions. Further, lesions missed by skipping gadolinium would have changed treatment course for just 1 of the 84 patients in the study, said Lucia Gentili, MD, a neurologist in the department of medicine, section of neurology, at the University of Perugia (Italy), in an interview at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.

“Postcontrast MRI might not be mandatory to detect signs of disease activity in patients with active MS,” she observed.

The question of the long-term effects of gadolinium deposition from serial scans in patients with MS is a hot topic among both patients and those caring for people with MS, said Dr. Gentili, so she and her associates decided to see how avoiding gadolinium exposure would affect lesion detection and patient management among their patient population.

For the retrospective study, the investigators looked at the records of 84 patients with relapsing remitting MS at two Italian MS centers over a 5-year time span. This was a cohort enriched for patients with highly active disease, said Dr. Gentili. A total of 45 patients, or over half of the cohort, had experienced at least one relapse in the preceding year.

The study included patients who were being screened for a second-line treatment and had evidence of brain or spinal cord contrast-enhancing lesions on MRI, if they also had a previous MRI of the brain and spinal cord performed on the same scanner.

The uniform protocol used for all MRIs included axial T2-weighted, fluid attenuated inversion recovery (FLAIR), and pre- and postcontrast T1-weighted sequences.

In all, the reference MRI scans picked up 164 contrast-enhancing lesions; of these, 151 (92.1%) were also seen on the T2/FLAIR sequences, showing up as new or enlarging lesions. Thirteen lesions were not visible on T2/FLAIR sequences when compared with the previous MRI, said Dr. Gentili.

Almost all patients in the cohort – a group with highly active disease, Dr. Gentili emphasized – also had new or enlarging lesions visible in T2 sequences. “Only two patients with MRI evidence of contrast-enhancing lesions showed no new or enlarged lesions in T2/FLAIR images,” she added. “Therefore, without gadolinium administration, only two patients in our cohort would have been incorrectly classified as radiologically stable.”

In reality, though, one of the two subjects whose disease activity was missed without gadolinium contrast had a relapse in the preceding 12 months, so clinical evidence of disease activity prompted attention to this individual. “Thus, only one subject in the entire cohort would have been incorrectly classified as stable,” Dr. Gentili and coauthors reported.

The results of this small study do not represent a case for abandoning gadolinium, Dr. Gentili stressed. “In our study, active lesions detected only by gadolinium enhancement, that is, without any evidence of new or enlarged lesions on T2/FLAIR, occurred in a limited but significant portion of contrast-enhancing lesions,” occurring in about 8% of the total lesions.

Rather, this study and other ongoing work represents a basis for shared decision making between persons with MS and those caring for them. Particularly for patients with highly active MS who can anticipate receiving a high burden of contrast to track disease activity, physicians can consider presenting them with the option to omit gadolinium contrast, she said.

Dr. Gentili reported receiving a travel grant from the ECTRIMS scientific program committee, and several coauthors reported relationships with multiple pharmaceutical companies. One coauthor received research funding from the Italian Multiple Sclerosis Society, the Italian Ministry of health, and the Italian Ministry of Education.

[email protected]

SOURCE: Gentili L et al. ECTRIMS 2019, Abstract P901.

STOCKHOLM – Among a cohort of patients with highly active multiple sclerosis (MS), MRI without gadolinium contrast still detected most lesions. Further, lesions missed by skipping gadolinium would have changed treatment course for just 1 of the 84 patients in the study, said Lucia Gentili, MD, a neurologist in the department of medicine, section of neurology, at the University of Perugia (Italy), in an interview at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.

“Postcontrast MRI might not be mandatory to detect signs of disease activity in patients with active MS,” she observed.

The question of the long-term effects of gadolinium deposition from serial scans in patients with MS is a hot topic among both patients and those caring for people with MS, said Dr. Gentili, so she and her associates decided to see how avoiding gadolinium exposure would affect lesion detection and patient management among their patient population.

For the retrospective study, the investigators looked at the records of 84 patients with relapsing remitting MS at two Italian MS centers over a 5-year time span. This was a cohort enriched for patients with highly active disease, said Dr. Gentili. A total of 45 patients, or over half of the cohort, had experienced at least one relapse in the preceding year.

The study included patients who were being screened for a second-line treatment and had evidence of brain or spinal cord contrast-enhancing lesions on MRI, if they also had a previous MRI of the brain and spinal cord performed on the same scanner.

The uniform protocol used for all MRIs included axial T2-weighted, fluid attenuated inversion recovery (FLAIR), and pre- and postcontrast T1-weighted sequences.

In all, the reference MRI scans picked up 164 contrast-enhancing lesions; of these, 151 (92.1%) were also seen on the T2/FLAIR sequences, showing up as new or enlarging lesions. Thirteen lesions were not visible on T2/FLAIR sequences when compared with the previous MRI, said Dr. Gentili.

Almost all patients in the cohort – a group with highly active disease, Dr. Gentili emphasized – also had new or enlarging lesions visible in T2 sequences. “Only two patients with MRI evidence of contrast-enhancing lesions showed no new or enlarged lesions in T2/FLAIR images,” she added. “Therefore, without gadolinium administration, only two patients in our cohort would have been incorrectly classified as radiologically stable.”

In reality, though, one of the two subjects whose disease activity was missed without gadolinium contrast had a relapse in the preceding 12 months, so clinical evidence of disease activity prompted attention to this individual. “Thus, only one subject in the entire cohort would have been incorrectly classified as stable,” Dr. Gentili and coauthors reported.

The results of this small study do not represent a case for abandoning gadolinium, Dr. Gentili stressed. “In our study, active lesions detected only by gadolinium enhancement, that is, without any evidence of new or enlarged lesions on T2/FLAIR, occurred in a limited but significant portion of contrast-enhancing lesions,” occurring in about 8% of the total lesions.

Rather, this study and other ongoing work represents a basis for shared decision making between persons with MS and those caring for them. Particularly for patients with highly active MS who can anticipate receiving a high burden of contrast to track disease activity, physicians can consider presenting them with the option to omit gadolinium contrast, she said.

Dr. Gentili reported receiving a travel grant from the ECTRIMS scientific program committee, and several coauthors reported relationships with multiple pharmaceutical companies. One coauthor received research funding from the Italian Multiple Sclerosis Society, the Italian Ministry of health, and the Italian Ministry of Education.

[email protected]

SOURCE: Gentili L et al. ECTRIMS 2019, Abstract P901.

STOCKHOLM – Radiologically isolated syndrome (RIS) converted to multiple sclerosis (MS) within 10 years of an initial abnormal MRI in 51% of patients in a large international cohort, Christine Lebrun-Frenay, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

She and her coinvestigators in the Radiologically Isolated Syndrome Consortium identified four significant risk factors for conversion. The likelihood of developing MS rose stepwise with the number of risk factors present at baseline such that patients possessing all four risk factors had an 87% conversion rate by 10 years.

The four significant risk factors that emerged from multivariate analysis were being age 37 years or younger at the time of the initial abnormal MRI, having spinal cord lesions on MRI, being cerebrospinal fluid positive for oligoclonal immunoglobulin bands and/or an elevated IgG index, and having infratentorial brain lesions on MRI.

Patients with none or one of the risk factors at baseline had a 29% conversion rate at 10 years. That risk climbed to 54% with two risk factors and 68% with any three, according to Dr. Lebrun-Frenay, head of the inflammatory neurologic disorders clinical research unit and MS Center at the University of Nice (France).

The new 10-year results expand upon the previously reported outcomes involving 5 years of prospective follow-up in the initial cohort of 451 RIS patients at participating MS centers in the United States, three European countries, and Turkey. At 5 years, 34% of subjects had converted to MS as defined by a first acute symptomatic clinical event involving CNS demyelination or 12 months of a progressive neurologic deficit (PLoS One. 2014 Mar 5;9[3]:e90509).

Of note, 17% of patients were treated off label with MS disease-modifying therapies, including natalizumab, injectables, or fingolimod, while they still had RIS, she noted.

RIS was defined on the basis of an incidentally identified CNS white-matter lesion meeting the 2009 Okuda criteria (Neurology. 2009 Mar 3;72[9]:800-5), which remain the only validated criteria for RIS.

Fourteen patients converted from RIS to primary progressive MS, indicating the existence of a previously unrecognized presymptomatic phase for this form of the disease.

The mounting conversions from RIS to MS over time suggest that RIS is part of the MS spectrum. In light of the RIS Consortium’s 10-year findings, Dr. Lebrun-Frenay and colleagues strongly recommended yearly monitoring of patients with RIS via a clinical visit including a neurologic examination and possibly a cognitive evaluation, as well as brain and spinal cord MRI scans.

Based on the observed conversion trajectory between 5 and 10 years, Dr. Lebrun-Frenay speculated that with further prospective follow-up eventually all of the RIS patients will develop MS. Despite this, she did not recommend prescribing disease-modifying therapies for these asymptomatic RIS patients. Dr. Lebrun-Frenay noted that there are two ongoing major randomized, phase 3, placebo-controlled clinical trials addressing this very question: the ARISE study of dimethyl fumarate in the United States, and the TERIS study of teriflunomide in Europe.

“It hasn’t been demonstrated yet that to give an active drug at this early stage is useful, so we have to wait a little bit for the results of these ongoing trials. I think we have to believe in evidence-based medicine. After all, 5 or 6 years ago we didn’t have any diagnostic criteria for RIS. We didn’t have any knowledge of this syndrome. Now we have to wait for maybe 2 years. It’s not too long to wait for the answer,” she said.

Dr. Lebrun-Frenay serves as a consultant to more than a half-dozen pharmaceutical companies but reported having no financial conflicts regarding the RIS Consortium study, which is being conducted without commercial support.
 

[email protected]

SOURCE: Lebrun-Frenay C et al. ECTRIMS 2019, Abstract 97.

STOCKHOLM – Radiologically isolated syndrome (RIS) converted to multiple sclerosis (MS) within 10 years of an initial abnormal MRI in 51% of patients in a large international cohort, Christine Lebrun-Frenay, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

She and her coinvestigators in the Radiologically Isolated Syndrome Consortium identified four significant risk factors for conversion. The likelihood of developing MS rose stepwise with the number of risk factors present at baseline such that patients possessing all four risk factors had an 87% conversion rate by 10 years.

The four significant risk factors that emerged from multivariate analysis were being age 37 years or younger at the time of the initial abnormal MRI, having spinal cord lesions on MRI, being cerebrospinal fluid positive for oligoclonal immunoglobulin bands and/or an elevated IgG index, and having infratentorial brain lesions on MRI.

Patients with none or one of the risk factors at baseline had a 29% conversion rate at 10 years. That risk climbed to 54% with two risk factors and 68% with any three, according to Dr. Lebrun-Frenay, head of the inflammatory neurologic disorders clinical research unit and MS Center at the University of Nice (France).

The new 10-year results expand upon the previously reported outcomes involving 5 years of prospective follow-up in the initial cohort of 451 RIS patients at participating MS centers in the United States, three European countries, and Turkey. At 5 years, 34% of subjects had converted to MS as defined by a first acute symptomatic clinical event involving CNS demyelination or 12 months of a progressive neurologic deficit (PLoS One. 2014 Mar 5;9[3]:e90509).

Of note, 17% of patients were treated off label with MS disease-modifying therapies, including natalizumab, injectables, or fingolimod, while they still had RIS, she noted.

RIS was defined on the basis of an incidentally identified CNS white-matter lesion meeting the 2009 Okuda criteria (Neurology. 2009 Mar 3;72[9]:800-5), which remain the only validated criteria for RIS.

Fourteen patients converted from RIS to primary progressive MS, indicating the existence of a previously unrecognized presymptomatic phase for this form of the disease.

The mounting conversions from RIS to MS over time suggest that RIS is part of the MS spectrum. In light of the RIS Consortium’s 10-year findings, Dr. Lebrun-Frenay and colleagues strongly recommended yearly monitoring of patients with RIS via a clinical visit including a neurologic examination and possibly a cognitive evaluation, as well as brain and spinal cord MRI scans.

Based on the observed conversion trajectory between 5 and 10 years, Dr. Lebrun-Frenay speculated that with further prospective follow-up eventually all of the RIS patients will develop MS. Despite this, she did not recommend prescribing disease-modifying therapies for these asymptomatic RIS patients. Dr. Lebrun-Frenay noted that there are two ongoing major randomized, phase 3, placebo-controlled clinical trials addressing this very question: the ARISE study of dimethyl fumarate in the United States, and the TERIS study of teriflunomide in Europe.

“It hasn’t been demonstrated yet that to give an active drug at this early stage is useful, so we have to wait a little bit for the results of these ongoing trials. I think we have to believe in evidence-based medicine. After all, 5 or 6 years ago we didn’t have any diagnostic criteria for RIS. We didn’t have any knowledge of this syndrome. Now we have to wait for maybe 2 years. It’s not too long to wait for the answer,” she said.

Dr. Lebrun-Frenay serves as a consultant to more than a half-dozen pharmaceutical companies but reported having no financial conflicts regarding the RIS Consortium study, which is being conducted without commercial support.
 

[email protected]

SOURCE: Lebrun-Frenay C et al. ECTRIMS 2019, Abstract 97.

STOCKHOLM – Radiologically isolated syndrome (RIS) converted to multiple sclerosis (MS) within 10 years of an initial abnormal MRI in 51% of patients in a large international cohort, Christine Lebrun-Frenay, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

She and her coinvestigators in the Radiologically Isolated Syndrome Consortium identified four significant risk factors for conversion. The likelihood of developing MS rose stepwise with the number of risk factors present at baseline such that patients possessing all four risk factors had an 87% conversion rate by 10 years.

The four significant risk factors that emerged from multivariate analysis were being age 37 years or younger at the time of the initial abnormal MRI, having spinal cord lesions on MRI, being cerebrospinal fluid positive for oligoclonal immunoglobulin bands and/or an elevated IgG index, and having infratentorial brain lesions on MRI.

Patients with none or one of the risk factors at baseline had a 29% conversion rate at 10 years. That risk climbed to 54% with two risk factors and 68% with any three, according to Dr. Lebrun-Frenay, head of the inflammatory neurologic disorders clinical research unit and MS Center at the University of Nice (France).

The new 10-year results expand upon the previously reported outcomes involving 5 years of prospective follow-up in the initial cohort of 451 RIS patients at participating MS centers in the United States, three European countries, and Turkey. At 5 years, 34% of subjects had converted to MS as defined by a first acute symptomatic clinical event involving CNS demyelination or 12 months of a progressive neurologic deficit (PLoS One. 2014 Mar 5;9[3]:e90509).

Of note, 17% of patients were treated off label with MS disease-modifying therapies, including natalizumab, injectables, or fingolimod, while they still had RIS, she noted.

RIS was defined on the basis of an incidentally identified CNS white-matter lesion meeting the 2009 Okuda criteria (Neurology. 2009 Mar 3;72[9]:800-5), which remain the only validated criteria for RIS.

Fourteen patients converted from RIS to primary progressive MS, indicating the existence of a previously unrecognized presymptomatic phase for this form of the disease.

The mounting conversions from RIS to MS over time suggest that RIS is part of the MS spectrum. In light of the RIS Consortium’s 10-year findings, Dr. Lebrun-Frenay and colleagues strongly recommended yearly monitoring of patients with RIS via a clinical visit including a neurologic examination and possibly a cognitive evaluation, as well as brain and spinal cord MRI scans.

Based on the observed conversion trajectory between 5 and 10 years, Dr. Lebrun-Frenay speculated that with further prospective follow-up eventually all of the RIS patients will develop MS. Despite this, she did not recommend prescribing disease-modifying therapies for these asymptomatic RIS patients. Dr. Lebrun-Frenay noted that there are two ongoing major randomized, phase 3, placebo-controlled clinical trials addressing this very question: the ARISE study of dimethyl fumarate in the United States, and the TERIS study of teriflunomide in Europe.

“It hasn’t been demonstrated yet that to give an active drug at this early stage is useful, so we have to wait a little bit for the results of these ongoing trials. I think we have to believe in evidence-based medicine. After all, 5 or 6 years ago we didn’t have any diagnostic criteria for RIS. We didn’t have any knowledge of this syndrome. Now we have to wait for maybe 2 years. It’s not too long to wait for the answer,” she said.

Dr. Lebrun-Frenay serves as a consultant to more than a half-dozen pharmaceutical companies but reported having no financial conflicts regarding the RIS Consortium study, which is being conducted without commercial support.
 

[email protected]

SOURCE: Lebrun-Frenay C et al. ECTRIMS 2019, Abstract 97.

Physician groups are praising a new option by the American Board of Internal Medicine (ABIM) that will offer doctors a self-paced pathway for maintenance of certification (MOC) in place of the traditional long-form assessment route.

The new longitudinal assessment option, announced in late August, would enable physicians to acquire and demonstrate ongoing knowledge through shorter evaluations of specific content. The option, currently under development, also would provide doctors with immediate feedback about their answers and share links to educational material to address knowledge gaps, according to an announcement. While details are still being fleshed out, a summary of the longitudinal assessment concept by the American Board of Medical Specialties explains that the approach draws on the principles of adult learning and modern technology “to promote learning, retention, and transfer of information.”

Developing a longitudinal assessment option is part of ABIM’s ongoing evolution, Marianne M. Green, MD, chair for ABIM’s board of directors and ABIM President Richard J. Baron, MD, wrote in a joint letter to internists posted on ABIM’s blog.

“We recognize that some physicians may prefer a more continuous process that easily integrates into their lives and allows them to engage seamlessly at their preferred pace, while being able to access the resources they use in practice,” the doctors wrote.

“Until recently, AGA [American Gastroenterological Association], along with AASLD [American Association for the Study of Liver Diseases], ACG [American College of Gastroenterology], and ASGE [American Society for Gastrointestinal Endoscopy], had been working on a new recertification pathway for GI. That effort has been temporarily suspended as ABIM pursues a pathway that will be available to all internal medicine specialties,” said Hashem El Serag, MD, MPH, AGAF, AGA president. “AGA appreciates that ABIM’s new longitudinal pathway appears to conform to the principles that the GI societies have espoused. We will monitor the development of the pathway as it moves toward implementation continuing to advocate for the needs of gastroenterologists.”

These GI societies are guided by these core principles in their campaign to reform MOC:

• MOC needs to be simpler, less intrusive, and less expensive.

• We continue to support alternatives to the high-stakes, every-10-year recertification exam.

• We do not support single-source or time-limited assessments, as they do not represent the current realities of medicine in the digital age.

• We support the concept that, for the many diplomates who specialize within certain areas of gastroenterology and hepatology, MOC should not include high-stakes assessments of areas in which the diplomate may not practice.

• We support the principles of lifelong learning, as evidenced by ongoing CME activities, rather than lifelong testing.

Douglas DeLong, MD, chair of the American College of Physician’s (ACP) board of regents said the option is a positive, first step that will support lifelong learning. He noted the new option is in line with recommendations released in 2019 by the American Board of Medical Specialties’ Continuing Board Certification: Vision for the Future Commission, which included ACP concerns.

“It’s pretty clear that some of the principles of adult learning – frequent information with quick feedback, repetition of material, and identifying gaps in knowledge – is really how people most effectively learn,” Dr. DeLong said in an interview. “Just cramming for an examination every decade hasn’t ever really been shown to affect long-term retention of knowledge or even patient care outcomes.”

Alan Lichtin, MD, chair of the MOC working group for the American Society of Hematology (ASH), said the self-paced pathway is a much-needed option, particularly the immediate feedback on test questions.

“For years, ASH has been advocating that ABIM move from the traditional sit-down testing to an alternative form of ‘formative’ assessment that has been adapted by other specialty boards,” Dr. Lichtin said in an interview. Anesthesiology and pediatrics have novel testing methods that fit into physicians’ schedules without being so disruptive and anxiety provoking. There is instantaneous feedback about whether the answers are correct or not. It is not useful to study hard for a time-intensive, comprehensive test only to get a summary of what was missed a long time after the test. By that point, the exam material is no longer fresh in one’s mind and therefore the feedback is no longer useful.”

The new pathway is still under development, and ABIM has not said when the option might be launched. In the meantime, the current MOC program and its traditional exam will remain in effect. The ABIM is requesting feedback and comments from physicians about the option. Dr. Baron wrote that more information about the change will be forthcoming in the months ahead.

The ABIM announcement comes on the heels of several ongoing legal challenges levied at the board by a group of internists over its MOC process.

A lawsuit, filed Dec. 6, 2018, in Pennsylvania district court and later amended in 2019, claims that ABIM is charging inflated monopoly prices for maintaining certification, that the organization is forcing physicians to purchase MOC, and that ABIM is inducing employers and others to require ABIM certification. The four plaintiff-physicians are asking a judge to find ABIM in violation of federal antitrust law and to bar the board from continuing its MOC process. The suit is filed as a class action on behalf of all internists and subspecialists required by ABIM to purchase MOC to maintain their ABIM certifications. 

On Sept. 26, U.S. District Court Judge for the Eastern District of Pennsylvania Robert F. Kelly Sr. said the plaintiffs failed to demonstrate sufficient evidence for their antitrust and unjust enrichment claims against ABIM. The judge ruled that the doctors also did not establish any showing of anticompetitive conduct by ABIM to support a monopolization claim. 

Physicians in three other lawsuits are also suing medical boards over their respective MOC processes. In February 2019, a radiologist issued a legal challenge against the American Board of Radiology over its MOC regulations. Also in February, two emergency physicians and an anesthesiologist filed a lawsuit against the American Board of Medical Specialties, the American Board of Emergency Medicine, and the American Board of Anesthesiology over MOC requirements. A month later, two psychiatrists issued a legal challenge against the American Board of Psychiatry and Neurology over its MOC process.

Attorneys for all three boards in the ABIM, American Board of Psychiatry and Neurology, and American Board of Radiology cases are seeking to dismiss the complaints. Judges have not yet ruled on the motions. In addition, a motion to consolidate all the cases was denied by the court.

A GoFundMe campaign launched by the Practicing Physicians of America to pay for plaintiffs’ costs associated with the class-action lawsuits has now garnered more than $300,000.

This story was updated on October 1, 2019.

[email protected]

Physician groups are praising a new option by the American Board of Internal Medicine (ABIM) that will offer doctors a self-paced pathway for maintenance of certification (MOC) in place of the traditional long-form assessment route.

The new longitudinal assessment option, announced in late August, would enable physicians to acquire and demonstrate ongoing knowledge through shorter evaluations of specific content. The option, currently under development, also would provide doctors with immediate feedback about their answers and share links to educational material to address knowledge gaps, according to an announcement. While details are still being fleshed out, a summary of the longitudinal assessment concept by the American Board of Medical Specialties explains that the approach draws on the principles of adult learning and modern technology “to promote learning, retention, and transfer of information.”

Developing a longitudinal assessment option is part of ABIM’s ongoing evolution, Marianne M. Green, MD, chair for ABIM’s board of directors and ABIM President Richard J. Baron, MD, wrote in a joint letter to internists posted on ABIM’s blog.

“We recognize that some physicians may prefer a more continuous process that easily integrates into their lives and allows them to engage seamlessly at their preferred pace, while being able to access the resources they use in practice,” the doctors wrote.

“Until recently, AGA [American Gastroenterological Association], along with AASLD [American Association for the Study of Liver Diseases], ACG [American College of Gastroenterology], and ASGE [American Society for Gastrointestinal Endoscopy], had been working on a new recertification pathway for GI. That effort has been temporarily suspended as ABIM pursues a pathway that will be available to all internal medicine specialties,” said Hashem El Serag, MD, MPH, AGAF, AGA president. “AGA appreciates that ABIM’s new longitudinal pathway appears to conform to the principles that the GI societies have espoused. We will monitor the development of the pathway as it moves toward implementation continuing to advocate for the needs of gastroenterologists.”

These GI societies are guided by these core principles in their campaign to reform MOC:

• MOC needs to be simpler, less intrusive, and less expensive.

• We continue to support alternatives to the high-stakes, every-10-year recertification exam.

• We do not support single-source or time-limited assessments, as they do not represent the current realities of medicine in the digital age.

• We support the concept that, for the many diplomates who specialize within certain areas of gastroenterology and hepatology, MOC should not include high-stakes assessments of areas in which the diplomate may not practice.

• We support the principles of lifelong learning, as evidenced by ongoing CME activities, rather than lifelong testing.

Douglas DeLong, MD, chair of the American College of Physician’s (ACP) board of regents said the option is a positive, first step that will support lifelong learning. He noted the new option is in line with recommendations released in 2019 by the American Board of Medical Specialties’ Continuing Board Certification: Vision for the Future Commission, which included ACP concerns.

“It’s pretty clear that some of the principles of adult learning – frequent information with quick feedback, repetition of material, and identifying gaps in knowledge – is really how people most effectively learn,” Dr. DeLong said in an interview. “Just cramming for an examination every decade hasn’t ever really been shown to affect long-term retention of knowledge or even patient care outcomes.”

Alan Lichtin, MD, chair of the MOC working group for the American Society of Hematology (ASH), said the self-paced pathway is a much-needed option, particularly the immediate feedback on test questions.

“For years, ASH has been advocating that ABIM move from the traditional sit-down testing to an alternative form of ‘formative’ assessment that has been adapted by other specialty boards,” Dr. Lichtin said in an interview. Anesthesiology and pediatrics have novel testing methods that fit into physicians’ schedules without being so disruptive and anxiety provoking. There is instantaneous feedback about whether the answers are correct or not. It is not useful to study hard for a time-intensive, comprehensive test only to get a summary of what was missed a long time after the test. By that point, the exam material is no longer fresh in one’s mind and therefore the feedback is no longer useful.”

The new pathway is still under development, and ABIM has not said when the option might be launched. In the meantime, the current MOC program and its traditional exam will remain in effect. The ABIM is requesting feedback and comments from physicians about the option. Dr. Baron wrote that more information about the change will be forthcoming in the months ahead.

The ABIM announcement comes on the heels of several ongoing legal challenges levied at the board by a group of internists over its MOC process.

A lawsuit, filed Dec. 6, 2018, in Pennsylvania district court and later amended in 2019, claims that ABIM is charging inflated monopoly prices for maintaining certification, that the organization is forcing physicians to purchase MOC, and that ABIM is inducing employers and others to require ABIM certification. The four plaintiff-physicians are asking a judge to find ABIM in violation of federal antitrust law and to bar the board from continuing its MOC process. The suit is filed as a class action on behalf of all internists and subspecialists required by ABIM to purchase MOC to maintain their ABIM certifications. 

On Sept. 26, U.S. District Court Judge for the Eastern District of Pennsylvania Robert F. Kelly Sr. said the plaintiffs failed to demonstrate sufficient evidence for their antitrust and unjust enrichment claims against ABIM. The judge ruled that the doctors also did not establish any showing of anticompetitive conduct by ABIM to support a monopolization claim. 

Physicians in three other lawsuits are also suing medical boards over their respective MOC processes. In February 2019, a radiologist issued a legal challenge against the American Board of Radiology over its MOC regulations. Also in February, two emergency physicians and an anesthesiologist filed a lawsuit against the American Board of Medical Specialties, the American Board of Emergency Medicine, and the American Board of Anesthesiology over MOC requirements. A month later, two psychiatrists issued a legal challenge against the American Board of Psychiatry and Neurology over its MOC process.

Attorneys for all three boards in the ABIM, American Board of Psychiatry and Neurology, and American Board of Radiology cases are seeking to dismiss the complaints. Judges have not yet ruled on the motions. In addition, a motion to consolidate all the cases was denied by the court.

A GoFundMe campaign launched by the Practicing Physicians of America to pay for plaintiffs’ costs associated with the class-action lawsuits has now garnered more than $300,000.

This story was updated on October 1, 2019.

[email protected]

Physician groups are praising a new option by the American Board of Internal Medicine (ABIM) that will offer doctors a self-paced pathway for maintenance of certification (MOC) in place of the traditional long-form assessment route.

The new longitudinal assessment option, announced in late August, would enable physicians to acquire and demonstrate ongoing knowledge through shorter evaluations of specific content. The option, currently under development, also would provide doctors with immediate feedback about their answers and share links to educational material to address knowledge gaps, according to an announcement. While details are still being fleshed out, a summary of the longitudinal assessment concept by the American Board of Medical Specialties explains that the approach draws on the principles of adult learning and modern technology “to promote learning, retention, and transfer of information.”

Developing a longitudinal assessment option is part of ABIM’s ongoing evolution, Marianne M. Green, MD, chair for ABIM’s board of directors and ABIM President Richard J. Baron, MD, wrote in a joint letter to internists posted on ABIM’s blog.

“We recognize that some physicians may prefer a more continuous process that easily integrates into their lives and allows them to engage seamlessly at their preferred pace, while being able to access the resources they use in practice,” the doctors wrote.

“Until recently, AGA [American Gastroenterological Association], along with AASLD [American Association for the Study of Liver Diseases], ACG [American College of Gastroenterology], and ASGE [American Society for Gastrointestinal Endoscopy], had been working on a new recertification pathway for GI. That effort has been temporarily suspended as ABIM pursues a pathway that will be available to all internal medicine specialties,” said Hashem El Serag, MD, MPH, AGAF, AGA president. “AGA appreciates that ABIM’s new longitudinal pathway appears to conform to the principles that the GI societies have espoused. We will monitor the development of the pathway as it moves toward implementation continuing to advocate for the needs of gastroenterologists.”

These GI societies are guided by these core principles in their campaign to reform MOC:

• MOC needs to be simpler, less intrusive, and less expensive.

• We continue to support alternatives to the high-stakes, every-10-year recertification exam.

• We do not support single-source or time-limited assessments, as they do not represent the current realities of medicine in the digital age.

• We support the concept that, for the many diplomates who specialize within certain areas of gastroenterology and hepatology, MOC should not include high-stakes assessments of areas in which the diplomate may not practice.

• We support the principles of lifelong learning, as evidenced by ongoing CME activities, rather than lifelong testing.

Douglas DeLong, MD, chair of the American College of Physician’s (ACP) board of regents said the option is a positive, first step that will support lifelong learning. He noted the new option is in line with recommendations released in 2019 by the American Board of Medical Specialties’ Continuing Board Certification: Vision for the Future Commission, which included ACP concerns.

“It’s pretty clear that some of the principles of adult learning – frequent information with quick feedback, repetition of material, and identifying gaps in knowledge – is really how people most effectively learn,” Dr. DeLong said in an interview. “Just cramming for an examination every decade hasn’t ever really been shown to affect long-term retention of knowledge or even patient care outcomes.”

Alan Lichtin, MD, chair of the MOC working group for the American Society of Hematology (ASH), said the self-paced pathway is a much-needed option, particularly the immediate feedback on test questions.

“For years, ASH has been advocating that ABIM move from the traditional sit-down testing to an alternative form of ‘formative’ assessment that has been adapted by other specialty boards,” Dr. Lichtin said in an interview. Anesthesiology and pediatrics have novel testing methods that fit into physicians’ schedules without being so disruptive and anxiety provoking. There is instantaneous feedback about whether the answers are correct or not. It is not useful to study hard for a time-intensive, comprehensive test only to get a summary of what was missed a long time after the test. By that point, the exam material is no longer fresh in one’s mind and therefore the feedback is no longer useful.”

The new pathway is still under development, and ABIM has not said when the option might be launched. In the meantime, the current MOC program and its traditional exam will remain in effect. The ABIM is requesting feedback and comments from physicians about the option. Dr. Baron wrote that more information about the change will be forthcoming in the months ahead.

The ABIM announcement comes on the heels of several ongoing legal challenges levied at the board by a group of internists over its MOC process.

A lawsuit, filed Dec. 6, 2018, in Pennsylvania district court and later amended in 2019, claims that ABIM is charging inflated monopoly prices for maintaining certification, that the organization is forcing physicians to purchase MOC, and that ABIM is inducing employers and others to require ABIM certification. The four plaintiff-physicians are asking a judge to find ABIM in violation of federal antitrust law and to bar the board from continuing its MOC process. The suit is filed as a class action on behalf of all internists and subspecialists required by ABIM to purchase MOC to maintain their ABIM certifications. 

On Sept. 26, U.S. District Court Judge for the Eastern District of Pennsylvania Robert F. Kelly Sr. said the plaintiffs failed to demonstrate sufficient evidence for their antitrust and unjust enrichment claims against ABIM. The judge ruled that the doctors also did not establish any showing of anticompetitive conduct by ABIM to support a monopolization claim. 

Physicians in three other lawsuits are also suing medical boards over their respective MOC processes. In February 2019, a radiologist issued a legal challenge against the American Board of Radiology over its MOC regulations. Also in February, two emergency physicians and an anesthesiologist filed a lawsuit against the American Board of Medical Specialties, the American Board of Emergency Medicine, and the American Board of Anesthesiology over MOC requirements. A month later, two psychiatrists issued a legal challenge against the American Board of Psychiatry and Neurology over its MOC process.

Attorneys for all three boards in the ABIM, American Board of Psychiatry and Neurology, and American Board of Radiology cases are seeking to dismiss the complaints. Judges have not yet ruled on the motions. In addition, a motion to consolidate all the cases was denied by the court.

A GoFundMe campaign launched by the Practicing Physicians of America to pay for plaintiffs’ costs associated with the class-action lawsuits has now garnered more than $300,000.

This story was updated on October 1, 2019.

[email protected]

Social determinants of health – access to nutritious food, safe housing, prescription drugs and transportation to medical appointments – affect a patient’s ability to adhere to a medical treatment plan. Initiatives are underway to capture and chart these data in order to connect patients with the services they need and to measure the results of those efforts.

Courtesy Boston Medical Center

But how can these tasks be accomplished by physicians with too little patient time and too many administrative responsibilities?

In a series of interviews, those developing and evaluating screening tools and proposed codes for social determinants of health said that physicians are unlikely to see direct financial rewards for documenting social determinants of health.

The ability to capture social factors through coding could, however, become more relevant under value-based care and population health payment models, which reward physicians and other providers for improved outcomes. They could also be used for risk adjustments to the physician’s caseload and for automatically steering community resources more precisely, such as through the EHR, by triggering referrals for social programs, said Sue Bowman, MJ, RHIA, CCS, FAHIMA, senior director for Coding Policy and Compliance at the American Health Information Management Association (AHIMA).

According to several sources interviewed for this article, documenting social determinants of health will become increasingly important for Federally Qualified Health Centers, accountable care organizations, large health systems, Medicare Advantage plans, and Centers for Medicare & Medicaid Services and Medicaid managed care pilots.

An initiative for new codes that would better document and standardize how social determinants of health data are collected, processed and integrated was unveiled earlier this year at a meeting of the U.S. ICD-10 Coordination and Maintenance Committee of the National Center for Health Statistics. The proposal came from UnitedHealthcare and has been endorsed by the American Medical Association. It includes 23 new codes that would be incorporated into the ICD-10-CM. By combining traditional medical data and social determinants of health data, the codes would trigger referrals to local and national resources in patients’ communities. A ruling on adopting the proposal is not expected until next year, with possible implementation of the codes in October 2021.

In the interim, there are 11 existing ICD-10-CM codes that can be used today to capture some of the social, nonmedical patient needs that might affect outcomes of care. These 11 “Z” codes (Z55-Z65) identify social problems related to education and literacy, employment, housing and economic circumstances, and psychosocial circumstances, but they don’t incorporate the data into a person’s overall care plan.
 

Mobilizing the EHR

Pablo Buitron de la Vega, MD, MSc, an internist at Boston Medical Center (BMC), has spearheaded the THRIVE social determinants initiative at BMC. THRIVE (Tool for Health and Resilience in Vulnerable Environments) is an EHR-based intervention that facilitates an automatic printout of referrals for resources in the community and in the hospital to address identified social factors.

THRIVE has been used to screen 60,000 patients at the medical center since 2017.

The patient completes the screening tool and a medical assistant enters the information into the medical record, which takes an average of one minute, he said. If patients answer that they are homeless or need help obtaining food, the EHR automatically generates a printed resource guide and a medical navigator is called. Data indicates that 85% of eligible patients at BMC have been screened, and of those who ask for help, 80%-90% are offered resources.

The THRIVE screening tool also automatically generates a code on the bill, and an accountable care organization of MassHealth, the state’s Medicaid authority which contracts with BMC’s HealthNet managed care plan, has begun recognizing the physician’s role in assessing problems like homelessness. Social factors that can be captured with ICD-10 codes, primarily homelessness, are now being included in the bill. And MassHealth is increasing its physician payment accordingly to take into account the physician’s role in addressing the issue.

More than half of the THRIVE caseload is covered under the Medicaid Accountable Care Organization (ACO). Other health plans have been slower to catch on. “Our patients have many different coverage models, and it gets very complicated,” he said. “That’s why ACOs and value-based payment models are so important to recognizing the business case that, if you address patients’ social needs, you are helping to better manage the ACO’s covered population,” he said.

Dr. Buitron de la Vega added that except for homelessness and food insecurity, existing ICD-10 codes aren’t that helpful in identifying social needs, so he looks forward to adoption of new codes such as those proposed by UnitedHealthcare. “At this time, the evidence that universal screening for [social determinants of health] will decrease cost and improve health outcomes is not there. Meanwhile, healthcare institutions need to make massive investments to help community organizations to grow and help all those patients that we are referring to them for social needs.”

Codes that spark actions

Sheila Shapiro, senior vice president of National Strategic Partnerships for UnitedHealthcare, said that “for populations covered by our plans, UnitedHealthcare has also created alternate coding methodologies, for example for transportation, as placeholder codes in lieu of an ICD-10 code, allowing us to bring this information forward.”

If identified patient needs are reported on the claim, UnitedHealthcare case managers use the information to assist members directly with referrals to social and governmental services, and then share those names and numbers with the medical providers, Ms. Shapiro said. A total of 600,000 UnitedHealthcare members have been assisted with over 760,000 such referrals.

If adopted, the new coding proposal could capture more data and trigger more referrals to service programs. The hope would be a savings in health expenditures and an improvement in patient outcomes.

Through its Integrated Health Model Initiative (IHMI), the AMA is collaborating with UnitedHealthcare on processes for incorporating social determinants of health into routine medical care, said Tom Giannulli, MD, chief medical information officer for IHMI. It’s hard to assess patients’ risks and outcomes without a rich data set to allow comparisons across populations, he added.

The proposed codes “will also help us do more research, with the idea that once we understand the risk, we can see how to mitigate it,” he said. “How do we take adjacent social resources and pull them into the medical space and create benefits – which could make the doctor’s life easier?”
 

Measuring efficacy

“Today we really don’t know enough about how social determinants of health are driving utilization and costs, or how to design mechanisms that will allow us eventually to change our payment systems in response,” says Bruce Chernof, MD, president and CEO of the SCAN Foundation, an independent California-based foundation devoted to transforming the health care of older adults.

The new codes proposed by UnitedHealthcare could provide powerful layers of information to make something that’s invisible more visible. “You can’t really improve what you can’t measure, but it’s not enough to just identify social factors in health. If you identify and don’t refer, or if you refer and programs are not available to respond, then what have you really accomplished?” asked Dr. Chernof, an internist,

“We were trained as internists to discuss the patient’s social history. But what has become clearer, as the population ages and we learn more about the challenges internists face today, social determinants of health are not an area where we have received enough training. And doctors already feel like they are up to their eyeballs in codes,” he said. “If we are going to start collecting this data, it is incumbent that the data actually be used to improve outcomes.”

AHIMA is advising a cautious approach. In its comments on the 23 proposed new ICD-10 codes, AHIMA recommended delaying implementation until more information is available from initiatives such as the Gravity Project of the Social Interventions Research and Evaluation Network at the University of California, San Francisco. The Gravity Project is a national collaborative to advance interoperable social risk documentation.

“There may be other, better ways to capture social factors. ... I’m not sure ICD-10-CM codes are the best way to do this because these issues are somewhat outside the scope of what ICD-10 is designed to capture,” Ms. Bowman said. There are also privacy concerns, and some of the social factors change frequently in the lives of patients.
 

Social determinants of health – access to nutritious food, safe housing, prescription drugs and transportation to medical appointments – affect a patient’s ability to adhere to a medical treatment plan. Initiatives are underway to capture and chart these data in order to connect patients with the services they need and to measure the results of those efforts.

Courtesy Boston Medical Center

But how can these tasks be accomplished by physicians with too little patient time and too many administrative responsibilities?

In a series of interviews, those developing and evaluating screening tools and proposed codes for social determinants of health said that physicians are unlikely to see direct financial rewards for documenting social determinants of health.

The ability to capture social factors through coding could, however, become more relevant under value-based care and population health payment models, which reward physicians and other providers for improved outcomes. They could also be used for risk adjustments to the physician’s caseload and for automatically steering community resources more precisely, such as through the EHR, by triggering referrals for social programs, said Sue Bowman, MJ, RHIA, CCS, FAHIMA, senior director for Coding Policy and Compliance at the American Health Information Management Association (AHIMA).

According to several sources interviewed for this article, documenting social determinants of health will become increasingly important for Federally Qualified Health Centers, accountable care organizations, large health systems, Medicare Advantage plans, and Centers for Medicare & Medicaid Services and Medicaid managed care pilots.

An initiative for new codes that would better document and standardize how social determinants of health data are collected, processed and integrated was unveiled earlier this year at a meeting of the U.S. ICD-10 Coordination and Maintenance Committee of the National Center for Health Statistics. The proposal came from UnitedHealthcare and has been endorsed by the American Medical Association. It includes 23 new codes that would be incorporated into the ICD-10-CM. By combining traditional medical data and social determinants of health data, the codes would trigger referrals to local and national resources in patients’ communities. A ruling on adopting the proposal is not expected until next year, with possible implementation of the codes in October 2021.

In the interim, there are 11 existing ICD-10-CM codes that can be used today to capture some of the social, nonmedical patient needs that might affect outcomes of care. These 11 “Z” codes (Z55-Z65) identify social problems related to education and literacy, employment, housing and economic circumstances, and psychosocial circumstances, but they don’t incorporate the data into a person’s overall care plan.
 

Mobilizing the EHR

Pablo Buitron de la Vega, MD, MSc, an internist at Boston Medical Center (BMC), has spearheaded the THRIVE social determinants initiative at BMC. THRIVE (Tool for Health and Resilience in Vulnerable Environments) is an EHR-based intervention that facilitates an automatic printout of referrals for resources in the community and in the hospital to address identified social factors.

THRIVE has been used to screen 60,000 patients at the medical center since 2017.

The patient completes the screening tool and a medical assistant enters the information into the medical record, which takes an average of one minute, he said. If patients answer that they are homeless or need help obtaining food, the EHR automatically generates a printed resource guide and a medical navigator is called. Data indicates that 85% of eligible patients at BMC have been screened, and of those who ask for help, 80%-90% are offered resources.

The THRIVE screening tool also automatically generates a code on the bill, and an accountable care organization of MassHealth, the state’s Medicaid authority which contracts with BMC’s HealthNet managed care plan, has begun recognizing the physician’s role in assessing problems like homelessness. Social factors that can be captured with ICD-10 codes, primarily homelessness, are now being included in the bill. And MassHealth is increasing its physician payment accordingly to take into account the physician’s role in addressing the issue.

More than half of the THRIVE caseload is covered under the Medicaid Accountable Care Organization (ACO). Other health plans have been slower to catch on. “Our patients have many different coverage models, and it gets very complicated,” he said. “That’s why ACOs and value-based payment models are so important to recognizing the business case that, if you address patients’ social needs, you are helping to better manage the ACO’s covered population,” he said.

Dr. Buitron de la Vega added that except for homelessness and food insecurity, existing ICD-10 codes aren’t that helpful in identifying social needs, so he looks forward to adoption of new codes such as those proposed by UnitedHealthcare. “At this time, the evidence that universal screening for [social determinants of health] will decrease cost and improve health outcomes is not there. Meanwhile, healthcare institutions need to make massive investments to help community organizations to grow and help all those patients that we are referring to them for social needs.”

Codes that spark actions

Sheila Shapiro, senior vice president of National Strategic Partnerships for UnitedHealthcare, said that “for populations covered by our plans, UnitedHealthcare has also created alternate coding methodologies, for example for transportation, as placeholder codes in lieu of an ICD-10 code, allowing us to bring this information forward.”

If identified patient needs are reported on the claim, UnitedHealthcare case managers use the information to assist members directly with referrals to social and governmental services, and then share those names and numbers with the medical providers, Ms. Shapiro said. A total of 600,000 UnitedHealthcare members have been assisted with over 760,000 such referrals.

If adopted, the new coding proposal could capture more data and trigger more referrals to service programs. The hope would be a savings in health expenditures and an improvement in patient outcomes.

Through its Integrated Health Model Initiative (IHMI), the AMA is collaborating with UnitedHealthcare on processes for incorporating social determinants of health into routine medical care, said Tom Giannulli, MD, chief medical information officer for IHMI. It’s hard to assess patients’ risks and outcomes without a rich data set to allow comparisons across populations, he added.

The proposed codes “will also help us do more research, with the idea that once we understand the risk, we can see how to mitigate it,” he said. “How do we take adjacent social resources and pull them into the medical space and create benefits – which could make the doctor’s life easier?”
 

Measuring efficacy

“Today we really don’t know enough about how social determinants of health are driving utilization and costs, or how to design mechanisms that will allow us eventually to change our payment systems in response,” says Bruce Chernof, MD, president and CEO of the SCAN Foundation, an independent California-based foundation devoted to transforming the health care of older adults.

The new codes proposed by UnitedHealthcare could provide powerful layers of information to make something that’s invisible more visible. “You can’t really improve what you can’t measure, but it’s not enough to just identify social factors in health. If you identify and don’t refer, or if you refer and programs are not available to respond, then what have you really accomplished?” asked Dr. Chernof, an internist,

“We were trained as internists to discuss the patient’s social history. But what has become clearer, as the population ages and we learn more about the challenges internists face today, social determinants of health are not an area where we have received enough training. And doctors already feel like they are up to their eyeballs in codes,” he said. “If we are going to start collecting this data, it is incumbent that the data actually be used to improve outcomes.”

AHIMA is advising a cautious approach. In its comments on the 23 proposed new ICD-10 codes, AHIMA recommended delaying implementation until more information is available from initiatives such as the Gravity Project of the Social Interventions Research and Evaluation Network at the University of California, San Francisco. The Gravity Project is a national collaborative to advance interoperable social risk documentation.

“There may be other, better ways to capture social factors. ... I’m not sure ICD-10-CM codes are the best way to do this because these issues are somewhat outside the scope of what ICD-10 is designed to capture,” Ms. Bowman said. There are also privacy concerns, and some of the social factors change frequently in the lives of patients.
 

Social determinants of health – access to nutritious food, safe housing, prescription drugs and transportation to medical appointments – affect a patient’s ability to adhere to a medical treatment plan. Initiatives are underway to capture and chart these data in order to connect patients with the services they need and to measure the results of those efforts.

Courtesy Boston Medical Center

But how can these tasks be accomplished by physicians with too little patient time and too many administrative responsibilities?

In a series of interviews, those developing and evaluating screening tools and proposed codes for social determinants of health said that physicians are unlikely to see direct financial rewards for documenting social determinants of health.

The ability to capture social factors through coding could, however, become more relevant under value-based care and population health payment models, which reward physicians and other providers for improved outcomes. They could also be used for risk adjustments to the physician’s caseload and for automatically steering community resources more precisely, such as through the EHR, by triggering referrals for social programs, said Sue Bowman, MJ, RHIA, CCS, FAHIMA, senior director for Coding Policy and Compliance at the American Health Information Management Association (AHIMA).

According to several sources interviewed for this article, documenting social determinants of health will become increasingly important for Federally Qualified Health Centers, accountable care organizations, large health systems, Medicare Advantage plans, and Centers for Medicare & Medicaid Services and Medicaid managed care pilots.

An initiative for new codes that would better document and standardize how social determinants of health data are collected, processed and integrated was unveiled earlier this year at a meeting of the U.S. ICD-10 Coordination and Maintenance Committee of the National Center for Health Statistics. The proposal came from UnitedHealthcare and has been endorsed by the American Medical Association. It includes 23 new codes that would be incorporated into the ICD-10-CM. By combining traditional medical data and social determinants of health data, the codes would trigger referrals to local and national resources in patients’ communities. A ruling on adopting the proposal is not expected until next year, with possible implementation of the codes in October 2021.

In the interim, there are 11 existing ICD-10-CM codes that can be used today to capture some of the social, nonmedical patient needs that might affect outcomes of care. These 11 “Z” codes (Z55-Z65) identify social problems related to education and literacy, employment, housing and economic circumstances, and psychosocial circumstances, but they don’t incorporate the data into a person’s overall care plan.
 

Mobilizing the EHR

Pablo Buitron de la Vega, MD, MSc, an internist at Boston Medical Center (BMC), has spearheaded the THRIVE social determinants initiative at BMC. THRIVE (Tool for Health and Resilience in Vulnerable Environments) is an EHR-based intervention that facilitates an automatic printout of referrals for resources in the community and in the hospital to address identified social factors.

THRIVE has been used to screen 60,000 patients at the medical center since 2017.

The patient completes the screening tool and a medical assistant enters the information into the medical record, which takes an average of one minute, he said. If patients answer that they are homeless or need help obtaining food, the EHR automatically generates a printed resource guide and a medical navigator is called. Data indicates that 85% of eligible patients at BMC have been screened, and of those who ask for help, 80%-90% are offered resources.

The THRIVE screening tool also automatically generates a code on the bill, and an accountable care organization of MassHealth, the state’s Medicaid authority which contracts with BMC’s HealthNet managed care plan, has begun recognizing the physician’s role in assessing problems like homelessness. Social factors that can be captured with ICD-10 codes, primarily homelessness, are now being included in the bill. And MassHealth is increasing its physician payment accordingly to take into account the physician’s role in addressing the issue.

More than half of the THRIVE caseload is covered under the Medicaid Accountable Care Organization (ACO). Other health plans have been slower to catch on. “Our patients have many different coverage models, and it gets very complicated,” he said. “That’s why ACOs and value-based payment models are so important to recognizing the business case that, if you address patients’ social needs, you are helping to better manage the ACO’s covered population,” he said.

Dr. Buitron de la Vega added that except for homelessness and food insecurity, existing ICD-10 codes aren’t that helpful in identifying social needs, so he looks forward to adoption of new codes such as those proposed by UnitedHealthcare. “At this time, the evidence that universal screening for [social determinants of health] will decrease cost and improve health outcomes is not there. Meanwhile, healthcare institutions need to make massive investments to help community organizations to grow and help all those patients that we are referring to them for social needs.”

Codes that spark actions

Sheila Shapiro, senior vice president of National Strategic Partnerships for UnitedHealthcare, said that “for populations covered by our plans, UnitedHealthcare has also created alternate coding methodologies, for example for transportation, as placeholder codes in lieu of an ICD-10 code, allowing us to bring this information forward.”

If identified patient needs are reported on the claim, UnitedHealthcare case managers use the information to assist members directly with referrals to social and governmental services, and then share those names and numbers with the medical providers, Ms. Shapiro said. A total of 600,000 UnitedHealthcare members have been assisted with over 760,000 such referrals.

If adopted, the new coding proposal could capture more data and trigger more referrals to service programs. The hope would be a savings in health expenditures and an improvement in patient outcomes.

Through its Integrated Health Model Initiative (IHMI), the AMA is collaborating with UnitedHealthcare on processes for incorporating social determinants of health into routine medical care, said Tom Giannulli, MD, chief medical information officer for IHMI. It’s hard to assess patients’ risks and outcomes without a rich data set to allow comparisons across populations, he added.

The proposed codes “will also help us do more research, with the idea that once we understand the risk, we can see how to mitigate it,” he said. “How do we take adjacent social resources and pull them into the medical space and create benefits – which could make the doctor’s life easier?”
 

Measuring efficacy

“Today we really don’t know enough about how social determinants of health are driving utilization and costs, or how to design mechanisms that will allow us eventually to change our payment systems in response,” says Bruce Chernof, MD, president and CEO of the SCAN Foundation, an independent California-based foundation devoted to transforming the health care of older adults.

The new codes proposed by UnitedHealthcare could provide powerful layers of information to make something that’s invisible more visible. “You can’t really improve what you can’t measure, but it’s not enough to just identify social factors in health. If you identify and don’t refer, or if you refer and programs are not available to respond, then what have you really accomplished?” asked Dr. Chernof, an internist,

“We were trained as internists to discuss the patient’s social history. But what has become clearer, as the population ages and we learn more about the challenges internists face today, social determinants of health are not an area where we have received enough training. And doctors already feel like they are up to their eyeballs in codes,” he said. “If we are going to start collecting this data, it is incumbent that the data actually be used to improve outcomes.”

AHIMA is advising a cautious approach. In its comments on the 23 proposed new ICD-10 codes, AHIMA recommended delaying implementation until more information is available from initiatives such as the Gravity Project of the Social Interventions Research and Evaluation Network at the University of California, San Francisco. The Gravity Project is a national collaborative to advance interoperable social risk documentation.

“There may be other, better ways to capture social factors. ... I’m not sure ICD-10-CM codes are the best way to do this because these issues are somewhat outside the scope of what ICD-10 is designed to capture,” Ms. Bowman said. There are also privacy concerns, and some of the social factors change frequently in the lives of patients.