PHILADELPHIA – Horace DeLisser, MD, and Elisabeth Poorman, MD, described some of the work they have done to provide health care in communities challenged by the social determinants of health, during a panel discussion moderated by Sarah Candler, MD, an internist in Houston.

Dr. Candler, former chair, Council of Resident and Fellow Members, Board of Regents, American College of Physicians, began the discussion by asking Dr. DeLisser, to describe his role in teaching medical students about the social determinants of health, at the annual Internal Medicine meeting of the ACP.

Dr. DeLisser, associate dean for professionalism and humanism at the University of Pennsylvania, Philadelphia, said he focuses on a number of issues, including social medicine, cultural competency, and cultural humility.

“We look at health care disparities and try to do a lot of innovation around service learning that will bring our students into the community, one to learn about these determinants but more importantly to be able to see how these issues can be addressed both on a provider level but also on a more structural systemic level,” he noted.

Dr. Poorman, an internist at the University of Washington, later discussed the importance of practicing cultural humility as it related to her experience providing care to migrant workers while she was a medical school student.

Dr. Candler, an internist in Houston, concluded the discussion by describing some of the ACP’s newest resources designed to address the social determinants of health for specific groups of patients.

The full panel discussion was recorded as a video.
 

[email protected]

PHILADELPHIA – Horace DeLisser, MD, and Elisabeth Poorman, MD, described some of the work they have done to provide health care in communities challenged by the social determinants of health, during a panel discussion moderated by Sarah Candler, MD, an internist in Houston.

Dr. Candler, former chair, Council of Resident and Fellow Members, Board of Regents, American College of Physicians, began the discussion by asking Dr. DeLisser, to describe his role in teaching medical students about the social determinants of health, at the annual Internal Medicine meeting of the ACP.

Dr. DeLisser, associate dean for professionalism and humanism at the University of Pennsylvania, Philadelphia, said he focuses on a number of issues, including social medicine, cultural competency, and cultural humility.

“We look at health care disparities and try to do a lot of innovation around service learning that will bring our students into the community, one to learn about these determinants but more importantly to be able to see how these issues can be addressed both on a provider level but also on a more structural systemic level,” he noted.

Dr. Poorman, an internist at the University of Washington, later discussed the importance of practicing cultural humility as it related to her experience providing care to migrant workers while she was a medical school student.

Dr. Candler, an internist in Houston, concluded the discussion by describing some of the ACP’s newest resources designed to address the social determinants of health for specific groups of patients.

The full panel discussion was recorded as a video.
 

[email protected]

PHILADELPHIA – Horace DeLisser, MD, and Elisabeth Poorman, MD, described some of the work they have done to provide health care in communities challenged by the social determinants of health, during a panel discussion moderated by Sarah Candler, MD, an internist in Houston.

Dr. Candler, former chair, Council of Resident and Fellow Members, Board of Regents, American College of Physicians, began the discussion by asking Dr. DeLisser, to describe his role in teaching medical students about the social determinants of health, at the annual Internal Medicine meeting of the ACP.

Dr. DeLisser, associate dean for professionalism and humanism at the University of Pennsylvania, Philadelphia, said he focuses on a number of issues, including social medicine, cultural competency, and cultural humility.

“We look at health care disparities and try to do a lot of innovation around service learning that will bring our students into the community, one to learn about these determinants but more importantly to be able to see how these issues can be addressed both on a provider level but also on a more structural systemic level,” he noted.

Dr. Poorman, an internist at the University of Washington, later discussed the importance of practicing cultural humility as it related to her experience providing care to migrant workers while she was a medical school student.

Dr. Candler, an internist in Houston, concluded the discussion by describing some of the ACP’s newest resources designed to address the social determinants of health for specific groups of patients.

The full panel discussion was recorded as a video.
 

[email protected]

ATLANTA – Combined therapy with the class I selective histone deacetylase (HDAC) inhibitor entinostat and the programmed cell death 1 (PD-1) inhibitor pembrolizumab has significant clinical activity and acceptable safety in melanoma patients who progressed on prior PD-1 blockade, according to findings from the open-label ENCORE-601 trial.

Of 53 patients with recurrent or metastatic melanoma who were treated with 5 mg of oral entinostat weekly plus 200 mg of intravenous pembrolizumab every 3 weeks, 1 had a complete response, and 9 had a partial response, for an objective response rate of 19%, Ryan J. Sullivan, MD, reported at the annual meeting of the American Association for Cancer Research.

The median duration of response at the January 2018 data cut-off was 13 months, and four responders had ongoing responses. An additional nine patients had stable disease for at least 6 months at that time, for a clinical benefit rate of 36%, said Dr. Sullivan of Massachusetts General Hospital, Boston.

“At 1 year, 10 patients remained on therapy or in response,” he said, noting that, although one patient had received only a very short course of therapy before developing “significant hepatitis” and coming off therapy, but this patient still had a response at 1 year. Five others also went off therapy and continue to have a response, and four patients remain on active therapy and are being followed, he said.

Study participants are adults with Eastern Cooperative Oncology Group Performance Status of less than 2 who were previously treated with a PD-1–blocking antibody and experienced progression on or after therapy. The 23% of patients with a BRAF V600 mutation were required to have received BRAF/MEK therapy, and 70% of patients had received both a prior PD-1 inhibitor and ipilimumab, either in combination or in sequence.

The response rate to prior anti–PD-1 therapy was 13%, which was “much lower than you would imagine in all-comers,” Dr Sullivan said.

Inhibitors of PD-1 and its ligand (PD-L1) have improved outcomes in patients with advanced melanoma, but despite the progress, most patients develop resistance and most will still die from metastatic melanoma, he said.

“I think its always important to define what the unmet need is, and here it’s quite clear: Most patients are not receiving ultimate benefit, and as a result we need a better therapeutic approach,” he said, adding that “the front-line treatment setting is a critical place to be in terms of clinical trials ... but the most relevant and most unmet need now is what do we do in patients who have received anti–PD-1 therapy and need something else.”


Addressing the unmet need requires an improved understanding of the mechanisms of resistance and the development of more effective therapies, he said.

Dr. Sullivan and his colleagues previously reported preliminary data from the current cohort showing promising activity with entinostat in combination with pembrolizumab, which was found to alter the immunosuppressive tumor microenvironment. The rationale for using entinostat in this setting relates to its down-regulation of immunosuppressive cell types in the tumor microenvironment and its “quite robust” synergy with PD-1 inhibition as demonstrated in preclinical models, he explained.

Following those initial dose and safety findings, four phase 2 expansion cohorts were opened, including two non–small cell lung cancer cohorts, one mismatched-repair proficient colorectal cancer cohort, and the melanoma cohort. The current report, which focused on the latter, showed that the treatment-related adverse events (AEs) occurring in at least 15% of patients included nausea, fatigue, diarrhea, and myelosuppression.

“Six patients discontinued due to related AEs, and importantly, there were only five grade 3 or 4 immune-related AEs,” Dr. Sullivan said, adding that these included one case each of immune-related hepatitis, pneumonitis, and colitis and two cases of significant dermatitis.

The findings show that in this group of patients with limited treatment options, entinostat with pembrolizumab is “clearly safe and tolerable,” he said.

Additionally, “very preliminary biomarker analyses” in a small number of patients demonstrated findings consistent with the mechanism of action of entinostat, including a reduction in circulating myeloid-derived suppressor cells, he said.

Dr. Sullivan reported consulting or serving on an advisory board for Novartis, Amgen, Merck, Array, Syndax, Replimmune, and Bristol-Myers Squibb and receiving research sponsorship from Amgen and Merck & Co.

[email protected]

SOURCE: Sullivan R et al. AACR 2019, Abstract CT-072.

ATLANTA – Combined therapy with the class I selective histone deacetylase (HDAC) inhibitor entinostat and the programmed cell death 1 (PD-1) inhibitor pembrolizumab has significant clinical activity and acceptable safety in melanoma patients who progressed on prior PD-1 blockade, according to findings from the open-label ENCORE-601 trial.

Of 53 patients with recurrent or metastatic melanoma who were treated with 5 mg of oral entinostat weekly plus 200 mg of intravenous pembrolizumab every 3 weeks, 1 had a complete response, and 9 had a partial response, for an objective response rate of 19%, Ryan J. Sullivan, MD, reported at the annual meeting of the American Association for Cancer Research.

The median duration of response at the January 2018 data cut-off was 13 months, and four responders had ongoing responses. An additional nine patients had stable disease for at least 6 months at that time, for a clinical benefit rate of 36%, said Dr. Sullivan of Massachusetts General Hospital, Boston.

“At 1 year, 10 patients remained on therapy or in response,” he said, noting that, although one patient had received only a very short course of therapy before developing “significant hepatitis” and coming off therapy, but this patient still had a response at 1 year. Five others also went off therapy and continue to have a response, and four patients remain on active therapy and are being followed, he said.

Study participants are adults with Eastern Cooperative Oncology Group Performance Status of less than 2 who were previously treated with a PD-1–blocking antibody and experienced progression on or after therapy. The 23% of patients with a BRAF V600 mutation were required to have received BRAF/MEK therapy, and 70% of patients had received both a prior PD-1 inhibitor and ipilimumab, either in combination or in sequence.

The response rate to prior anti–PD-1 therapy was 13%, which was “much lower than you would imagine in all-comers,” Dr Sullivan said.

Inhibitors of PD-1 and its ligand (PD-L1) have improved outcomes in patients with advanced melanoma, but despite the progress, most patients develop resistance and most will still die from metastatic melanoma, he said.

“I think its always important to define what the unmet need is, and here it’s quite clear: Most patients are not receiving ultimate benefit, and as a result we need a better therapeutic approach,” he said, adding that “the front-line treatment setting is a critical place to be in terms of clinical trials ... but the most relevant and most unmet need now is what do we do in patients who have received anti–PD-1 therapy and need something else.”


Addressing the unmet need requires an improved understanding of the mechanisms of resistance and the development of more effective therapies, he said.

Dr. Sullivan and his colleagues previously reported preliminary data from the current cohort showing promising activity with entinostat in combination with pembrolizumab, which was found to alter the immunosuppressive tumor microenvironment. The rationale for using entinostat in this setting relates to its down-regulation of immunosuppressive cell types in the tumor microenvironment and its “quite robust” synergy with PD-1 inhibition as demonstrated in preclinical models, he explained.

Following those initial dose and safety findings, four phase 2 expansion cohorts were opened, including two non–small cell lung cancer cohorts, one mismatched-repair proficient colorectal cancer cohort, and the melanoma cohort. The current report, which focused on the latter, showed that the treatment-related adverse events (AEs) occurring in at least 15% of patients included nausea, fatigue, diarrhea, and myelosuppression.

“Six patients discontinued due to related AEs, and importantly, there were only five grade 3 or 4 immune-related AEs,” Dr. Sullivan said, adding that these included one case each of immune-related hepatitis, pneumonitis, and colitis and two cases of significant dermatitis.

The findings show that in this group of patients with limited treatment options, entinostat with pembrolizumab is “clearly safe and tolerable,” he said.

Additionally, “very preliminary biomarker analyses” in a small number of patients demonstrated findings consistent with the mechanism of action of entinostat, including a reduction in circulating myeloid-derived suppressor cells, he said.

Dr. Sullivan reported consulting or serving on an advisory board for Novartis, Amgen, Merck, Array, Syndax, Replimmune, and Bristol-Myers Squibb and receiving research sponsorship from Amgen and Merck & Co.

[email protected]

SOURCE: Sullivan R et al. AACR 2019, Abstract CT-072.

ATLANTA – Combined therapy with the class I selective histone deacetylase (HDAC) inhibitor entinostat and the programmed cell death 1 (PD-1) inhibitor pembrolizumab has significant clinical activity and acceptable safety in melanoma patients who progressed on prior PD-1 blockade, according to findings from the open-label ENCORE-601 trial.

Of 53 patients with recurrent or metastatic melanoma who were treated with 5 mg of oral entinostat weekly plus 200 mg of intravenous pembrolizumab every 3 weeks, 1 had a complete response, and 9 had a partial response, for an objective response rate of 19%, Ryan J. Sullivan, MD, reported at the annual meeting of the American Association for Cancer Research.

The median duration of response at the January 2018 data cut-off was 13 months, and four responders had ongoing responses. An additional nine patients had stable disease for at least 6 months at that time, for a clinical benefit rate of 36%, said Dr. Sullivan of Massachusetts General Hospital, Boston.

“At 1 year, 10 patients remained on therapy or in response,” he said, noting that, although one patient had received only a very short course of therapy before developing “significant hepatitis” and coming off therapy, but this patient still had a response at 1 year. Five others also went off therapy and continue to have a response, and four patients remain on active therapy and are being followed, he said.

Study participants are adults with Eastern Cooperative Oncology Group Performance Status of less than 2 who were previously treated with a PD-1–blocking antibody and experienced progression on or after therapy. The 23% of patients with a BRAF V600 mutation were required to have received BRAF/MEK therapy, and 70% of patients had received both a prior PD-1 inhibitor and ipilimumab, either in combination or in sequence.

The response rate to prior anti–PD-1 therapy was 13%, which was “much lower than you would imagine in all-comers,” Dr Sullivan said.

Inhibitors of PD-1 and its ligand (PD-L1) have improved outcomes in patients with advanced melanoma, but despite the progress, most patients develop resistance and most will still die from metastatic melanoma, he said.

“I think its always important to define what the unmet need is, and here it’s quite clear: Most patients are not receiving ultimate benefit, and as a result we need a better therapeutic approach,” he said, adding that “the front-line treatment setting is a critical place to be in terms of clinical trials ... but the most relevant and most unmet need now is what do we do in patients who have received anti–PD-1 therapy and need something else.”


Addressing the unmet need requires an improved understanding of the mechanisms of resistance and the development of more effective therapies, he said.

Dr. Sullivan and his colleagues previously reported preliminary data from the current cohort showing promising activity with entinostat in combination with pembrolizumab, which was found to alter the immunosuppressive tumor microenvironment. The rationale for using entinostat in this setting relates to its down-regulation of immunosuppressive cell types in the tumor microenvironment and its “quite robust” synergy with PD-1 inhibition as demonstrated in preclinical models, he explained.

Following those initial dose and safety findings, four phase 2 expansion cohorts were opened, including two non–small cell lung cancer cohorts, one mismatched-repair proficient colorectal cancer cohort, and the melanoma cohort. The current report, which focused on the latter, showed that the treatment-related adverse events (AEs) occurring in at least 15% of patients included nausea, fatigue, diarrhea, and myelosuppression.

“Six patients discontinued due to related AEs, and importantly, there were only five grade 3 or 4 immune-related AEs,” Dr. Sullivan said, adding that these included one case each of immune-related hepatitis, pneumonitis, and colitis and two cases of significant dermatitis.

The findings show that in this group of patients with limited treatment options, entinostat with pembrolizumab is “clearly safe and tolerable,” he said.

Additionally, “very preliminary biomarker analyses” in a small number of patients demonstrated findings consistent with the mechanism of action of entinostat, including a reduction in circulating myeloid-derived suppressor cells, he said.

Dr. Sullivan reported consulting or serving on an advisory board for Novartis, Amgen, Merck, Array, Syndax, Replimmune, and Bristol-Myers Squibb and receiving research sponsorship from Amgen and Merck & Co.

[email protected]

SOURCE: Sullivan R et al. AACR 2019, Abstract CT-072.

PHILADELPHIA – Americans need more access to medication assisted therapy (MAT) as a way to address opioid use disorder.

Gregory Twachtman/MDedge News

That was the key takeaway from a presentation given by Charles Reznikoff, MD, at the annual meeting of the American College of Physicians.

“There is fairly robust evidence on medication assisted therapy for OUD [opioid use disorder],” said Dr. Reznikoff of the University of Minnesota, Minneapolis. “MAT lowers mortality 70% in people with OUD all-cause mortality.”

He mentioned some examples in Europe, where access to medication assisted therapy has had a dramatic effect on opioid overdoses and deaths.

For example, any doctor in France since 1995 can prescribe drugs to help with OUD treatment and most buprenorphine prescriptions are written by primary care physicians. As a result, there has been a tenfold increase in the number of patients suffering from OUD receiving medication assisted treatment. In addition, there has been an 80% drop in the overdose death rate.

But Dr. Reznikoff’s recommendation on the need for more MAT was more about methadone and Suboxone, which contains a combination of buprenorphine and naloxone, than the current drive to expand the distribution of naloxone alone. He noted that naloxone is good but it really serves as a short-term fix that slows the rate of overdose deaths and provides time to implement other long-term fixes. Many states are providing naloxone to first responders to help treat patients who are overdosing on opioids, but little is being done to expand access to other medication assisted treatments, he said.

“I am bringing it up to try to illustrate what is happening in American policy making that we are reaching for naloxone first and we are not reaching for MAT first,” Dr. Reznikoff said, noting that you can give naloxone to patients without changing the underlying system of care.

He also stressed the need to get more medication assisted treatment into the penal system.

“If you have opioid use disorder [and] you are incarcerated, almost nowhere in America can you get medication assisted therapy while incarcerated,” Dr. Reznikoff said. “You lose your tolerance, but you still have addiction. You are released from incarceration and your rate of death is 20-fold the average OUD rate of death in the first 2 weeks after release.”

As a counter example, he noted that Portugal in 2001 switched its approach to OUD from criminal to a public health issue and stopped incarcerating people with opioid addiction. This led to a decrease by 75% in active heroin users, and the country now boasts the lowest rate of drug-related death in Western Europe, 1/50th of the rate in America.

“We pretty strongly believe that if they were given medication while incarcerated or just not incarcerated, they would not have that 20-fold risk of death after release,” he said. “Incarceration is actually an accelerant in the opioid epidemic and we are not going to get out of this without addressing that tough issue.”

Another effective policy option that should be expanded further is the use of prescription drug monitoring programs, which can be effective in controlling the amount of prescriptions written, said Rebecca Haffajee, PhD, assistant professor, health management and policy, University of Michigan School of Public Health, Ann Arbor.

“We do have good evidence on the prescribing outcomes and particularly attributable to a few key features, [such as] use mandates, registration mandates, delegate access, all of those features have been shown across different types of patient populations – Medicaid, Medicare, commercially insured – to reduce overall opioid prescribing and some high risk measures, polypharmacy, doctor shopping, pharmacy shopping, those sorts of things,” noted Dr. Haffajee.

Twenty percent of state laws enacted to address the opioid crisis have involved prescription drug monitoring programs, she added.

There is not enough evidence to determine whether other laws, such as those that limit quantity and dosage levels, are effective in the fight against opioid use disorder, added Dr. Reznikoff.

The speakers did not report any conflicts.

[email protected]

PHILADELPHIA – Americans need more access to medication assisted therapy (MAT) as a way to address opioid use disorder.

Gregory Twachtman/MDedge News

That was the key takeaway from a presentation given by Charles Reznikoff, MD, at the annual meeting of the American College of Physicians.

“There is fairly robust evidence on medication assisted therapy for OUD [opioid use disorder],” said Dr. Reznikoff of the University of Minnesota, Minneapolis. “MAT lowers mortality 70% in people with OUD all-cause mortality.”

He mentioned some examples in Europe, where access to medication assisted therapy has had a dramatic effect on opioid overdoses and deaths.

For example, any doctor in France since 1995 can prescribe drugs to help with OUD treatment and most buprenorphine prescriptions are written by primary care physicians. As a result, there has been a tenfold increase in the number of patients suffering from OUD receiving medication assisted treatment. In addition, there has been an 80% drop in the overdose death rate.

But Dr. Reznikoff’s recommendation on the need for more MAT was more about methadone and Suboxone, which contains a combination of buprenorphine and naloxone, than the current drive to expand the distribution of naloxone alone. He noted that naloxone is good but it really serves as a short-term fix that slows the rate of overdose deaths and provides time to implement other long-term fixes. Many states are providing naloxone to first responders to help treat patients who are overdosing on opioids, but little is being done to expand access to other medication assisted treatments, he said.

“I am bringing it up to try to illustrate what is happening in American policy making that we are reaching for naloxone first and we are not reaching for MAT first,” Dr. Reznikoff said, noting that you can give naloxone to patients without changing the underlying system of care.

He also stressed the need to get more medication assisted treatment into the penal system.

“If you have opioid use disorder [and] you are incarcerated, almost nowhere in America can you get medication assisted therapy while incarcerated,” Dr. Reznikoff said. “You lose your tolerance, but you still have addiction. You are released from incarceration and your rate of death is 20-fold the average OUD rate of death in the first 2 weeks after release.”

As a counter example, he noted that Portugal in 2001 switched its approach to OUD from criminal to a public health issue and stopped incarcerating people with opioid addiction. This led to a decrease by 75% in active heroin users, and the country now boasts the lowest rate of drug-related death in Western Europe, 1/50th of the rate in America.

“We pretty strongly believe that if they were given medication while incarcerated or just not incarcerated, they would not have that 20-fold risk of death after release,” he said. “Incarceration is actually an accelerant in the opioid epidemic and we are not going to get out of this without addressing that tough issue.”

Another effective policy option that should be expanded further is the use of prescription drug monitoring programs, which can be effective in controlling the amount of prescriptions written, said Rebecca Haffajee, PhD, assistant professor, health management and policy, University of Michigan School of Public Health, Ann Arbor.

“We do have good evidence on the prescribing outcomes and particularly attributable to a few key features, [such as] use mandates, registration mandates, delegate access, all of those features have been shown across different types of patient populations – Medicaid, Medicare, commercially insured – to reduce overall opioid prescribing and some high risk measures, polypharmacy, doctor shopping, pharmacy shopping, those sorts of things,” noted Dr. Haffajee.

Twenty percent of state laws enacted to address the opioid crisis have involved prescription drug monitoring programs, she added.

There is not enough evidence to determine whether other laws, such as those that limit quantity and dosage levels, are effective in the fight against opioid use disorder, added Dr. Reznikoff.

The speakers did not report any conflicts.

[email protected]

PHILADELPHIA – Americans need more access to medication assisted therapy (MAT) as a way to address opioid use disorder.

Gregory Twachtman/MDedge News

That was the key takeaway from a presentation given by Charles Reznikoff, MD, at the annual meeting of the American College of Physicians.

“There is fairly robust evidence on medication assisted therapy for OUD [opioid use disorder],” said Dr. Reznikoff of the University of Minnesota, Minneapolis. “MAT lowers mortality 70% in people with OUD all-cause mortality.”

He mentioned some examples in Europe, where access to medication assisted therapy has had a dramatic effect on opioid overdoses and deaths.

For example, any doctor in France since 1995 can prescribe drugs to help with OUD treatment and most buprenorphine prescriptions are written by primary care physicians. As a result, there has been a tenfold increase in the number of patients suffering from OUD receiving medication assisted treatment. In addition, there has been an 80% drop in the overdose death rate.

But Dr. Reznikoff’s recommendation on the need for more MAT was more about methadone and Suboxone, which contains a combination of buprenorphine and naloxone, than the current drive to expand the distribution of naloxone alone. He noted that naloxone is good but it really serves as a short-term fix that slows the rate of overdose deaths and provides time to implement other long-term fixes. Many states are providing naloxone to first responders to help treat patients who are overdosing on opioids, but little is being done to expand access to other medication assisted treatments, he said.

“I am bringing it up to try to illustrate what is happening in American policy making that we are reaching for naloxone first and we are not reaching for MAT first,” Dr. Reznikoff said, noting that you can give naloxone to patients without changing the underlying system of care.

He also stressed the need to get more medication assisted treatment into the penal system.

“If you have opioid use disorder [and] you are incarcerated, almost nowhere in America can you get medication assisted therapy while incarcerated,” Dr. Reznikoff said. “You lose your tolerance, but you still have addiction. You are released from incarceration and your rate of death is 20-fold the average OUD rate of death in the first 2 weeks after release.”

As a counter example, he noted that Portugal in 2001 switched its approach to OUD from criminal to a public health issue and stopped incarcerating people with opioid addiction. This led to a decrease by 75% in active heroin users, and the country now boasts the lowest rate of drug-related death in Western Europe, 1/50th of the rate in America.

“We pretty strongly believe that if they were given medication while incarcerated or just not incarcerated, they would not have that 20-fold risk of death after release,” he said. “Incarceration is actually an accelerant in the opioid epidemic and we are not going to get out of this without addressing that tough issue.”

Another effective policy option that should be expanded further is the use of prescription drug monitoring programs, which can be effective in controlling the amount of prescriptions written, said Rebecca Haffajee, PhD, assistant professor, health management and policy, University of Michigan School of Public Health, Ann Arbor.

“We do have good evidence on the prescribing outcomes and particularly attributable to a few key features, [such as] use mandates, registration mandates, delegate access, all of those features have been shown across different types of patient populations – Medicaid, Medicare, commercially insured – to reduce overall opioid prescribing and some high risk measures, polypharmacy, doctor shopping, pharmacy shopping, those sorts of things,” noted Dr. Haffajee.

Twenty percent of state laws enacted to address the opioid crisis have involved prescription drug monitoring programs, she added.

There is not enough evidence to determine whether other laws, such as those that limit quantity and dosage levels, are effective in the fight against opioid use disorder, added Dr. Reznikoff.

The speakers did not report any conflicts.

[email protected]

GLASGOW – APL-2, a complement factor 3 (C3) inhibitor, may be a future treatment option for paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia (AIHA), according to investigators from two separate studies.

Will Pass/MDedge News

Early results from the phase 1b PADDOCK trial for PNH and the phase 2 PLAUDIT trial for AIHA showed that APL-2 significantly increased hemoglobin levels, with additional improvements reported in lactate dehydrogenase (LDH), absolute reticulocyte count, and bilirubin. The findings were presented at the annual meeting of the British Society for Haematology.

By blocking C3, APL-2 acts further upstream than approved C5 inhibitors eculizumab and ravulizumab, thereby controlling extravascular hemolysis in addition to intravascular hemolysis. This broader level of control is needed for some patients, the investigators said, such as those with PNH who have inadequate responses to C5 inhibition.

PNH

“Even in PNH patients treated with eculizumab, up to 70% may have suboptimal hemoglobin responses and about 30% may still require blood transfusions,” said lead author of the PADDOCK trial, Raymond Wong, MD, of the Prince of Wales Hospital in Hong Kong.

PNH patients included in the open-label, dose-escalation PADDOCK study had greater than 10% white blood cell clones, LDH that was at least twice the upper limit of normal, at least one transfusion within the past year, a platelet count below 30,000/mm³, and an absolute neutrophil count greater than 500 x 10⁹/L.

Dr. Wong described experiences with a cohort of 20 patients who received 270 mg APL-2 subcutaneously daily for at least 28 days, with the option to continue treatment for up to 2 years thereafter, if desired.

From these 20 patients, 2 patients completed the initial 28-day period but did not elect to continue and 2 patients withdrew because of adverse events (ovarian cancer and severe aplastic anemia), leaving 16 patients in the present analysis. Before treatment, these individuals were transfusion dependent, with an average transfusion rate of 8.7 transfusions per year.

Results showed that mean hemoglobin increased from 8.0 g/dL at baseline to 10.8 g/dL at day 29 and 12.2 g/dL at day 85. LDH dropped 900%, from 2,416 U/L (9 times the upper limit of normal) to 271 U/L (0.9 times the upper limit of normal). Absolute reticulocyte count and bilirubin also normalized.

Overall, these improvements led to a meaningful clinical impact, Dr. Wong said, with fatigue scores improving and most patients becoming transfusion independent on maintenance therapy, with the exception of one patient who developed severe aplastic anemia after 1 year. No significant infections or thromboses occurred.

When asked where APL-2 might fit in with current treatment paradigm, Dr. Wong said that multiple applications for PNH are being investigated, including first-line therapy and after failure of eculizumab.

AIHA

Results from the phase 2 PLAUDIT trial, presented by Bruno Fattizzo, MD, of the University of Milan, offered a glimpse at APL-2 in a different setting: AIHA.

Will Pass/MDedge News

Eligibility required hemoglobin levels of less than 11 g/dL, signs of hemolysis, and positive direct antiglobulin test for IgG and/or complement C3.

Dr. Fattizzo discussed results from five patients with cold agglutinin disease and five patients with C3-positive warm AIHA who had received 56 days of therapy.

Among the five patients with cold agglutinin disease, mean hemoglobin increased from 8.7 g/dL to 12.1 g/dL, while patients with warm C3-positive AIHA had a mean increase from 9.3 g/dL to 11.3 g/dL. As with the PNH study, absolute reticulocyte count, LDH, and indirect bilirubin normalized across all 10 patients.

“Some of the patients included in the trial have already reached more than 48 weeks, something like 64 weeks in the study, and they are still doing well,” Dr. Fattizzo said. “So it really seems that those who are do respond really keep the response with ongoing treatment.”

Nine out of 12 patients with cold agglutinin disease (75%) and 8 out of 9 patients (89%) with warm AIHA experienced adverse events, although these were mostly grade 1 or 2 and deemed unrelated to APL-2 by the investigators.

Five grade 3 adverse events in six patients included oral squamous carcinoma, hemolytic flare, pneumonia, purpura, and acute kidney injury. Five grade 4 adverse events in two patients included high calcium, high creatinine, hypoxia, and hemolytic flare, causing these two patients to withdraw from the study. No grade 3 or 4 adverse events were considered related to APL-2.

“APL-2 appears to be well tolerated and safe,” Dr. Fattizzo said, adding that a phase 3 trial for cold agglutinin disease and C3-positive warm AIHA C3+ is planned.

Both studies are sponsored by Apellis Pharmaceuticals. Dr. Wong and his colleagues reported financial relationships with Alexion Pharmaceuticals, Apellis, Celgene, Janssen, and other companies. Dr. Fattizzo reported having no conflicts of interest.

GLASGOW – APL-2, a complement factor 3 (C3) inhibitor, may be a future treatment option for paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia (AIHA), according to investigators from two separate studies.

Will Pass/MDedge News

Early results from the phase 1b PADDOCK trial for PNH and the phase 2 PLAUDIT trial for AIHA showed that APL-2 significantly increased hemoglobin levels, with additional improvements reported in lactate dehydrogenase (LDH), absolute reticulocyte count, and bilirubin. The findings were presented at the annual meeting of the British Society for Haematology.

By blocking C3, APL-2 acts further upstream than approved C5 inhibitors eculizumab and ravulizumab, thereby controlling extravascular hemolysis in addition to intravascular hemolysis. This broader level of control is needed for some patients, the investigators said, such as those with PNH who have inadequate responses to C5 inhibition.

PNH

“Even in PNH patients treated with eculizumab, up to 70% may have suboptimal hemoglobin responses and about 30% may still require blood transfusions,” said lead author of the PADDOCK trial, Raymond Wong, MD, of the Prince of Wales Hospital in Hong Kong.

PNH patients included in the open-label, dose-escalation PADDOCK study had greater than 10% white blood cell clones, LDH that was at least twice the upper limit of normal, at least one transfusion within the past year, a platelet count below 30,000/mm³, and an absolute neutrophil count greater than 500 x 10⁹/L.

Dr. Wong described experiences with a cohort of 20 patients who received 270 mg APL-2 subcutaneously daily for at least 28 days, with the option to continue treatment for up to 2 years thereafter, if desired.

From these 20 patients, 2 patients completed the initial 28-day period but did not elect to continue and 2 patients withdrew because of adverse events (ovarian cancer and severe aplastic anemia), leaving 16 patients in the present analysis. Before treatment, these individuals were transfusion dependent, with an average transfusion rate of 8.7 transfusions per year.

Results showed that mean hemoglobin increased from 8.0 g/dL at baseline to 10.8 g/dL at day 29 and 12.2 g/dL at day 85. LDH dropped 900%, from 2,416 U/L (9 times the upper limit of normal) to 271 U/L (0.9 times the upper limit of normal). Absolute reticulocyte count and bilirubin also normalized.

Overall, these improvements led to a meaningful clinical impact, Dr. Wong said, with fatigue scores improving and most patients becoming transfusion independent on maintenance therapy, with the exception of one patient who developed severe aplastic anemia after 1 year. No significant infections or thromboses occurred.

When asked where APL-2 might fit in with current treatment paradigm, Dr. Wong said that multiple applications for PNH are being investigated, including first-line therapy and after failure of eculizumab.

AIHA

Results from the phase 2 PLAUDIT trial, presented by Bruno Fattizzo, MD, of the University of Milan, offered a glimpse at APL-2 in a different setting: AIHA.

Will Pass/MDedge News

Eligibility required hemoglobin levels of less than 11 g/dL, signs of hemolysis, and positive direct antiglobulin test for IgG and/or complement C3.

Dr. Fattizzo discussed results from five patients with cold agglutinin disease and five patients with C3-positive warm AIHA who had received 56 days of therapy.

Among the five patients with cold agglutinin disease, mean hemoglobin increased from 8.7 g/dL to 12.1 g/dL, while patients with warm C3-positive AIHA had a mean increase from 9.3 g/dL to 11.3 g/dL. As with the PNH study, absolute reticulocyte count, LDH, and indirect bilirubin normalized across all 10 patients.

“Some of the patients included in the trial have already reached more than 48 weeks, something like 64 weeks in the study, and they are still doing well,” Dr. Fattizzo said. “So it really seems that those who are do respond really keep the response with ongoing treatment.”

Nine out of 12 patients with cold agglutinin disease (75%) and 8 out of 9 patients (89%) with warm AIHA experienced adverse events, although these were mostly grade 1 or 2 and deemed unrelated to APL-2 by the investigators.

Five grade 3 adverse events in six patients included oral squamous carcinoma, hemolytic flare, pneumonia, purpura, and acute kidney injury. Five grade 4 adverse events in two patients included high calcium, high creatinine, hypoxia, and hemolytic flare, causing these two patients to withdraw from the study. No grade 3 or 4 adverse events were considered related to APL-2.

“APL-2 appears to be well tolerated and safe,” Dr. Fattizzo said, adding that a phase 3 trial for cold agglutinin disease and C3-positive warm AIHA C3+ is planned.

Both studies are sponsored by Apellis Pharmaceuticals. Dr. Wong and his colleagues reported financial relationships with Alexion Pharmaceuticals, Apellis, Celgene, Janssen, and other companies. Dr. Fattizzo reported having no conflicts of interest.

GLASGOW – APL-2, a complement factor 3 (C3) inhibitor, may be a future treatment option for paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia (AIHA), according to investigators from two separate studies.

Will Pass/MDedge News

Early results from the phase 1b PADDOCK trial for PNH and the phase 2 PLAUDIT trial for AIHA showed that APL-2 significantly increased hemoglobin levels, with additional improvements reported in lactate dehydrogenase (LDH), absolute reticulocyte count, and bilirubin. The findings were presented at the annual meeting of the British Society for Haematology.

By blocking C3, APL-2 acts further upstream than approved C5 inhibitors eculizumab and ravulizumab, thereby controlling extravascular hemolysis in addition to intravascular hemolysis. This broader level of control is needed for some patients, the investigators said, such as those with PNH who have inadequate responses to C5 inhibition.

PNH

“Even in PNH patients treated with eculizumab, up to 70% may have suboptimal hemoglobin responses and about 30% may still require blood transfusions,” said lead author of the PADDOCK trial, Raymond Wong, MD, of the Prince of Wales Hospital in Hong Kong.

PNH patients included in the open-label, dose-escalation PADDOCK study had greater than 10% white blood cell clones, LDH that was at least twice the upper limit of normal, at least one transfusion within the past year, a platelet count below 30,000/mm³, and an absolute neutrophil count greater than 500 x 10⁹/L.

Dr. Wong described experiences with a cohort of 20 patients who received 270 mg APL-2 subcutaneously daily for at least 28 days, with the option to continue treatment for up to 2 years thereafter, if desired.

From these 20 patients, 2 patients completed the initial 28-day period but did not elect to continue and 2 patients withdrew because of adverse events (ovarian cancer and severe aplastic anemia), leaving 16 patients in the present analysis. Before treatment, these individuals were transfusion dependent, with an average transfusion rate of 8.7 transfusions per year.

Results showed that mean hemoglobin increased from 8.0 g/dL at baseline to 10.8 g/dL at day 29 and 12.2 g/dL at day 85. LDH dropped 900%, from 2,416 U/L (9 times the upper limit of normal) to 271 U/L (0.9 times the upper limit of normal). Absolute reticulocyte count and bilirubin also normalized.

Overall, these improvements led to a meaningful clinical impact, Dr. Wong said, with fatigue scores improving and most patients becoming transfusion independent on maintenance therapy, with the exception of one patient who developed severe aplastic anemia after 1 year. No significant infections or thromboses occurred.

When asked where APL-2 might fit in with current treatment paradigm, Dr. Wong said that multiple applications for PNH are being investigated, including first-line therapy and after failure of eculizumab.

AIHA

Results from the phase 2 PLAUDIT trial, presented by Bruno Fattizzo, MD, of the University of Milan, offered a glimpse at APL-2 in a different setting: AIHA.

Will Pass/MDedge News

Eligibility required hemoglobin levels of less than 11 g/dL, signs of hemolysis, and positive direct antiglobulin test for IgG and/or complement C3.

Dr. Fattizzo discussed results from five patients with cold agglutinin disease and five patients with C3-positive warm AIHA who had received 56 days of therapy.

Among the five patients with cold agglutinin disease, mean hemoglobin increased from 8.7 g/dL to 12.1 g/dL, while patients with warm C3-positive AIHA had a mean increase from 9.3 g/dL to 11.3 g/dL. As with the PNH study, absolute reticulocyte count, LDH, and indirect bilirubin normalized across all 10 patients.

“Some of the patients included in the trial have already reached more than 48 weeks, something like 64 weeks in the study, and they are still doing well,” Dr. Fattizzo said. “So it really seems that those who are do respond really keep the response with ongoing treatment.”

Nine out of 12 patients with cold agglutinin disease (75%) and 8 out of 9 patients (89%) with warm AIHA experienced adverse events, although these were mostly grade 1 or 2 and deemed unrelated to APL-2 by the investigators.

Five grade 3 adverse events in six patients included oral squamous carcinoma, hemolytic flare, pneumonia, purpura, and acute kidney injury. Five grade 4 adverse events in two patients included high calcium, high creatinine, hypoxia, and hemolytic flare, causing these two patients to withdraw from the study. No grade 3 or 4 adverse events were considered related to APL-2.

“APL-2 appears to be well tolerated and safe,” Dr. Fattizzo said, adding that a phase 3 trial for cold agglutinin disease and C3-positive warm AIHA C3+ is planned.

Both studies are sponsored by Apellis Pharmaceuticals. Dr. Wong and his colleagues reported financial relationships with Alexion Pharmaceuticals, Apellis, Celgene, Janssen, and other companies. Dr. Fattizzo reported having no conflicts of interest.

ORLANDO – Profiling metabolites found in the plasma could be a way to get an earlier handle on how a person’s mental illness will progress, researchers said the annual congress of the Schizophrenia International Research Society.

Thomas R. Collins/MDedge News

Investigators at the University of São Paulo found that certain substances – such as phospholipids and sphingolipids – were found in differing levels at the time of a first episode of psychosis, allowing them to accurately identify bipolar disorder or schizophrenia or healthy controls 87% of the time.

The findings suggest a way to help get patients more targeted treatment earlier in their disease course, said Helena Joaquim, MD, PhD, a postdoctoral fellow in the university’s psychiatry department.

“The levels of these metabolites can be a biomarker for psychosis, as well as a diagnostic marker for schizophrenia and bipolar disorder, aiding clinical practice,” the researchers wrote in a poster presentation.

At the time of a first episode of psychosis, the actual diagnosis can be difficult to pinpoint, making the illness more difficult to treat. Since lipid metabolism is altered in neuropsychiatric diseases, the researchers turned to the metabolite levels of patients to pin down a specific diagnosis sooner.

They collected plasma from 28 schizophrenia patients, 27 bipolar patients, and 30 healthy controls. They looked specifically at acylcarnitines, phospholipids, lysophospholipids and sphingolipids. They found that phospholipids were elevated in schizophrenia patients, compared with controls, and even more elevated in patients with bipolar disorder. A similar pattern was seen with lysophospholipids. Sphingolipids were found at lower levels in schizophrenia and elevated in bipolar disorder, compared with controls.

Levels of those three metabolites allowed researchers 87.1% of the time to correctly identify patients as a healthy control or as having schizophrenia or bipolar disorder. Acylcarnitines were not found to be differentiated between schizophrenia and bipolar disorder, the researchers found.

The most interesting part of their efforts so far, Dr. Joaquim said, was a shotgun analysis, an untargeted approach in which about 186 metabolites were measured and plotted on a graph. The compounds have not yet all been identified, but researchers found that levels of these substances were clustered in conspicuous ways.

“It seems like the negative schizophrenia patients are more like the depressive bipolar, and the positive symptoms are more like manic bipolar,” Dr. Joaquim said.

Once refined, these metabolite levels could be a way not only to differentiate schizophrenia patients and bipolar patients, but also to predict severity and directionality of their disorders. For example, looking at metabolite levels might help determine whether schizophrenia patients are more likely to be troubled by positive symptoms, such as hallucinations.

“We have to look back,” Dr. Joaquim said, “and try to identify those metabolites that are the most different between the groups.”

Dr. Joaquim reported no relevant disclosures.

ORLANDO – Profiling metabolites found in the plasma could be a way to get an earlier handle on how a person’s mental illness will progress, researchers said the annual congress of the Schizophrenia International Research Society.

Thomas R. Collins/MDedge News

Investigators at the University of São Paulo found that certain substances – such as phospholipids and sphingolipids – were found in differing levels at the time of a first episode of psychosis, allowing them to accurately identify bipolar disorder or schizophrenia or healthy controls 87% of the time.

The findings suggest a way to help get patients more targeted treatment earlier in their disease course, said Helena Joaquim, MD, PhD, a postdoctoral fellow in the university’s psychiatry department.

“The levels of these metabolites can be a biomarker for psychosis, as well as a diagnostic marker for schizophrenia and bipolar disorder, aiding clinical practice,” the researchers wrote in a poster presentation.

At the time of a first episode of psychosis, the actual diagnosis can be difficult to pinpoint, making the illness more difficult to treat. Since lipid metabolism is altered in neuropsychiatric diseases, the researchers turned to the metabolite levels of patients to pin down a specific diagnosis sooner.

They collected plasma from 28 schizophrenia patients, 27 bipolar patients, and 30 healthy controls. They looked specifically at acylcarnitines, phospholipids, lysophospholipids and sphingolipids. They found that phospholipids were elevated in schizophrenia patients, compared with controls, and even more elevated in patients with bipolar disorder. A similar pattern was seen with lysophospholipids. Sphingolipids were found at lower levels in schizophrenia and elevated in bipolar disorder, compared with controls.

Levels of those three metabolites allowed researchers 87.1% of the time to correctly identify patients as a healthy control or as having schizophrenia or bipolar disorder. Acylcarnitines were not found to be differentiated between schizophrenia and bipolar disorder, the researchers found.

The most interesting part of their efforts so far, Dr. Joaquim said, was a shotgun analysis, an untargeted approach in which about 186 metabolites were measured and plotted on a graph. The compounds have not yet all been identified, but researchers found that levels of these substances were clustered in conspicuous ways.

“It seems like the negative schizophrenia patients are more like the depressive bipolar, and the positive symptoms are more like manic bipolar,” Dr. Joaquim said.

Once refined, these metabolite levels could be a way not only to differentiate schizophrenia patients and bipolar patients, but also to predict severity and directionality of their disorders. For example, looking at metabolite levels might help determine whether schizophrenia patients are more likely to be troubled by positive symptoms, such as hallucinations.

“We have to look back,” Dr. Joaquim said, “and try to identify those metabolites that are the most different between the groups.”

Dr. Joaquim reported no relevant disclosures.

ORLANDO – Profiling metabolites found in the plasma could be a way to get an earlier handle on how a person’s mental illness will progress, researchers said the annual congress of the Schizophrenia International Research Society.

Thomas R. Collins/MDedge News

Investigators at the University of São Paulo found that certain substances – such as phospholipids and sphingolipids – were found in differing levels at the time of a first episode of psychosis, allowing them to accurately identify bipolar disorder or schizophrenia or healthy controls 87% of the time.

The findings suggest a way to help get patients more targeted treatment earlier in their disease course, said Helena Joaquim, MD, PhD, a postdoctoral fellow in the university’s psychiatry department.

“The levels of these metabolites can be a biomarker for psychosis, as well as a diagnostic marker for schizophrenia and bipolar disorder, aiding clinical practice,” the researchers wrote in a poster presentation.

At the time of a first episode of psychosis, the actual diagnosis can be difficult to pinpoint, making the illness more difficult to treat. Since lipid metabolism is altered in neuropsychiatric diseases, the researchers turned to the metabolite levels of patients to pin down a specific diagnosis sooner.

They collected plasma from 28 schizophrenia patients, 27 bipolar patients, and 30 healthy controls. They looked specifically at acylcarnitines, phospholipids, lysophospholipids and sphingolipids. They found that phospholipids were elevated in schizophrenia patients, compared with controls, and even more elevated in patients with bipolar disorder. A similar pattern was seen with lysophospholipids. Sphingolipids were found at lower levels in schizophrenia and elevated in bipolar disorder, compared with controls.

Levels of those three metabolites allowed researchers 87.1% of the time to correctly identify patients as a healthy control or as having schizophrenia or bipolar disorder. Acylcarnitines were not found to be differentiated between schizophrenia and bipolar disorder, the researchers found.

The most interesting part of their efforts so far, Dr. Joaquim said, was a shotgun analysis, an untargeted approach in which about 186 metabolites were measured and plotted on a graph. The compounds have not yet all been identified, but researchers found that levels of these substances were clustered in conspicuous ways.

“It seems like the negative schizophrenia patients are more like the depressive bipolar, and the positive symptoms are more like manic bipolar,” Dr. Joaquim said.

Once refined, these metabolite levels could be a way not only to differentiate schizophrenia patients and bipolar patients, but also to predict severity and directionality of their disorders. For example, looking at metabolite levels might help determine whether schizophrenia patients are more likely to be troubled by positive symptoms, such as hallucinations.

“We have to look back,” Dr. Joaquim said, “and try to identify those metabolites that are the most different between the groups.”

Dr. Joaquim reported no relevant disclosures.