SAN ANTONIO – Active shooter events and other episodes of workplace violence can be better managed with proper planning and training by hospitals and staff, Lewis J. Kaplan, MD, said in a late-breaking session at the Critical Care Congress.

“Workplace violence is not just active shooter – it’s ubiquitous, and we only know a little bit about it,” noted Dr. Kaplan, section chief, surgical critical care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia. “The facility and everyone in the health care team have a role in being an active participant, rather than a passive one.”

By Andrew D. Bowser/Frontline Medical News

To actively prepare for premeditated events, Dr. Kaplan recommended that clinicians develop partnerships with local law enforcement officials and initiate active training that involves anyone who could come into contact with an active shooter.

There are many steps that can be taken to protect the facility, including visitor screening and management, security that extends to the perimeter of the facility, building design that limits access to specific places in the facility, and deployment of firearm detection canines, Dr. Kaplan said, during the session at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.

In all, Dr. Kaplan listed 19 steps that facilities could take to avert a planned attack, drawing in part on recommendations from the FBI publication, Workplace violence: Issues in response.

“This is a lot, and you don’t need to do all of it,” Dr. Kaplan said. “But you need to have an internally consistent plan for how you will do this at your facility, and it must involve everyone. They all need to be able to be part of your team.”

Recent data on workplace violence

The latest data show that the great majority of workplace violence is perpetrated by individuals outside the organization. According to the IAHSS Foundation 2017 Healthcare Crime Survey, 89% of events involved a customer or patient of the workplace or employees.

In-hospital violence is prevalent, according to 2016 data from Occupational Safety and Health Administration that identified 24,000 workplace assaults in a 3-year span covering 2013-2015, including 33 homicides, 30 assaults, and 74 rapes.

Many in-hospital incidents are marked by failures in communication, patient observation, noncompliance with workplace violence policies or lack of such policies, and perhaps most importantly, an inadequate assessment for the violent potential of the perpetrator, according to Dr. Kaplan.

In a 2017 survey of 150 trauma nurses, 67% said they had been the victim of physical violence at work, though many did not report the incidents, Dr. Kaplan noted. Some reasons nurses gave for not reporting violence included the feeling that it was “just part of the job” in 27% of cases, and concerns about patient satisfaction scores in 10% of the cases.

Active shooter events in the workplace are of particular concern, though they are relatively rare; one recent report identified 160 events that occurred during 2000-2013 in which 1,043 individuals were injured, according to Dr. Kaplan.

Other presentations in the late-breaking session covered issues related to disaster preparedness and the Charlie Gard case.

“We picked these three topics to be in a late-breaker session not only because of the recent events that had happened, but because they have a common thread – it’s not a matter of if it will happen, but when will it happen, and are you ready and how do we prepare,” said session chair Gloria M. Rodriguez Vega, MD.

“One of the things I learned as a fellow was that part of the success in critical care was attention to detail and layers of safety,” said Dr. Rodriguez Vega, an intensivist in Bayamon, Puerto Rico. “I think you can apply that to all these situations.”

Dr. Kaplan had no industry disclosures related to his presentation.

SAN ANTONIO – Active shooter events and other episodes of workplace violence can be better managed with proper planning and training by hospitals and staff, Lewis J. Kaplan, MD, said in a late-breaking session at the Critical Care Congress.

“Workplace violence is not just active shooter – it’s ubiquitous, and we only know a little bit about it,” noted Dr. Kaplan, section chief, surgical critical care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia. “The facility and everyone in the health care team have a role in being an active participant, rather than a passive one.”

By Andrew D. Bowser/Frontline Medical News

To actively prepare for premeditated events, Dr. Kaplan recommended that clinicians develop partnerships with local law enforcement officials and initiate active training that involves anyone who could come into contact with an active shooter.

There are many steps that can be taken to protect the facility, including visitor screening and management, security that extends to the perimeter of the facility, building design that limits access to specific places in the facility, and deployment of firearm detection canines, Dr. Kaplan said, during the session at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.

In all, Dr. Kaplan listed 19 steps that facilities could take to avert a planned attack, drawing in part on recommendations from the FBI publication, Workplace violence: Issues in response.

“This is a lot, and you don’t need to do all of it,” Dr. Kaplan said. “But you need to have an internally consistent plan for how you will do this at your facility, and it must involve everyone. They all need to be able to be part of your team.”

Recent data on workplace violence

The latest data show that the great majority of workplace violence is perpetrated by individuals outside the organization. According to the IAHSS Foundation 2017 Healthcare Crime Survey, 89% of events involved a customer or patient of the workplace or employees.

In-hospital violence is prevalent, according to 2016 data from Occupational Safety and Health Administration that identified 24,000 workplace assaults in a 3-year span covering 2013-2015, including 33 homicides, 30 assaults, and 74 rapes.

Many in-hospital incidents are marked by failures in communication, patient observation, noncompliance with workplace violence policies or lack of such policies, and perhaps most importantly, an inadequate assessment for the violent potential of the perpetrator, according to Dr. Kaplan.

In a 2017 survey of 150 trauma nurses, 67% said they had been the victim of physical violence at work, though many did not report the incidents, Dr. Kaplan noted. Some reasons nurses gave for not reporting violence included the feeling that it was “just part of the job” in 27% of cases, and concerns about patient satisfaction scores in 10% of the cases.

Active shooter events in the workplace are of particular concern, though they are relatively rare; one recent report identified 160 events that occurred during 2000-2013 in which 1,043 individuals were injured, according to Dr. Kaplan.

Other presentations in the late-breaking session covered issues related to disaster preparedness and the Charlie Gard case.

“We picked these three topics to be in a late-breaker session not only because of the recent events that had happened, but because they have a common thread – it’s not a matter of if it will happen, but when will it happen, and are you ready and how do we prepare,” said session chair Gloria M. Rodriguez Vega, MD.

“One of the things I learned as a fellow was that part of the success in critical care was attention to detail and layers of safety,” said Dr. Rodriguez Vega, an intensivist in Bayamon, Puerto Rico. “I think you can apply that to all these situations.”

Dr. Kaplan had no industry disclosures related to his presentation.

SAN ANTONIO – Active shooter events and other episodes of workplace violence can be better managed with proper planning and training by hospitals and staff, Lewis J. Kaplan, MD, said in a late-breaking session at the Critical Care Congress.

“Workplace violence is not just active shooter – it’s ubiquitous, and we only know a little bit about it,” noted Dr. Kaplan, section chief, surgical critical care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia. “The facility and everyone in the health care team have a role in being an active participant, rather than a passive one.”

By Andrew D. Bowser/Frontline Medical News

To actively prepare for premeditated events, Dr. Kaplan recommended that clinicians develop partnerships with local law enforcement officials and initiate active training that involves anyone who could come into contact with an active shooter.

There are many steps that can be taken to protect the facility, including visitor screening and management, security that extends to the perimeter of the facility, building design that limits access to specific places in the facility, and deployment of firearm detection canines, Dr. Kaplan said, during the session at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.

In all, Dr. Kaplan listed 19 steps that facilities could take to avert a planned attack, drawing in part on recommendations from the FBI publication, Workplace violence: Issues in response.

“This is a lot, and you don’t need to do all of it,” Dr. Kaplan said. “But you need to have an internally consistent plan for how you will do this at your facility, and it must involve everyone. They all need to be able to be part of your team.”

Recent data on workplace violence

The latest data show that the great majority of workplace violence is perpetrated by individuals outside the organization. According to the IAHSS Foundation 2017 Healthcare Crime Survey, 89% of events involved a customer or patient of the workplace or employees.

In-hospital violence is prevalent, according to 2016 data from Occupational Safety and Health Administration that identified 24,000 workplace assaults in a 3-year span covering 2013-2015, including 33 homicides, 30 assaults, and 74 rapes.

Many in-hospital incidents are marked by failures in communication, patient observation, noncompliance with workplace violence policies or lack of such policies, and perhaps most importantly, an inadequate assessment for the violent potential of the perpetrator, according to Dr. Kaplan.

In a 2017 survey of 150 trauma nurses, 67% said they had been the victim of physical violence at work, though many did not report the incidents, Dr. Kaplan noted. Some reasons nurses gave for not reporting violence included the feeling that it was “just part of the job” in 27% of cases, and concerns about patient satisfaction scores in 10% of the cases.

Active shooter events in the workplace are of particular concern, though they are relatively rare; one recent report identified 160 events that occurred during 2000-2013 in which 1,043 individuals were injured, according to Dr. Kaplan.

Other presentations in the late-breaking session covered issues related to disaster preparedness and the Charlie Gard case.

“We picked these three topics to be in a late-breaker session not only because of the recent events that had happened, but because they have a common thread – it’s not a matter of if it will happen, but when will it happen, and are you ready and how do we prepare,” said session chair Gloria M. Rodriguez Vega, MD.

“One of the things I learned as a fellow was that part of the success in critical care was attention to detail and layers of safety,” said Dr. Rodriguez Vega, an intensivist in Bayamon, Puerto Rico. “I think you can apply that to all these situations.”

Dr. Kaplan had no industry disclosures related to his presentation.

SAN FRANCISCO – Two new therapies that target vascular endothelial growth factor signaling are efficacious and may expand the treatment armamentarium for intermediate and advanced hepatocellular carcinoma, data from a pair of randomized trials suggest.

In the phase 2 TACTICS (Transcatheter Arterial Chemoembolization Therapy in Combination With Sorafenib) trial, median progression-free survival, using a new, more narrow definition of progression, was almost a year longer when the oral tyrosine kinase inhibitor sorafenib (Nexavar) was added to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), translating to a 41% reduction in risk of events. This benefit came at the price of higher rates of certain grade 3 adverse events, but the combination was overall feasible and safe.

Susan London/Frontline Medical News

As welcome as such new therapeutic options are, they will likely increase the complexity of the treatment landscape for HCC and could muddy the ability of future trials to establish survival benefit, Jordi Bruix, MD, PhD, cautioned in an invited discussion. In addition, patients who cannot receive anti–vascular endothelial growth factor (VEGF) therapy because of comorbidities still represent an unmet need, underscoring the importance of continued research on other fronts.

TACTICS trial

“Because TACE has been shown to lead to a spike in the intratumoral concentration of VEGF, blockade of VEGF receptors may prevent the effects of a surge in proangiogenic factors,” said TACTICS lead investigator Masatoshi Kudo, MD, professor and chairman of the department of gastroenterology and hepatology at Kindai University, Osaka, Japan. “Since TACE and sorafenib have been shown to prolong survival in patients with unresectable HCC, their combination may improve clinical outcomes.”

The 156 patients enrolled in the TACTICS trial, sponsored by the Japan Liver Oncology Group, had unresectable HCC, a Child-Pugh score of 7 or lower, and no vascular invasion or extrahepatic spread.

They were randomly assigned to as-needed TACE alone or TACE plus sorafenib, which inhibits VEGF receptors, platelet-derived growth factor receptors, and Raf kinases, reducing growth signaling and angiogenesis. Sorafenib therapy was interrupted only for several days before and after each TACE session.

Susan London/Frontline Medical News

The trial’s positive results contrast with those of the earlier randomized Post-TACE trial, SPACE trial, and TACE 2 trial, noted Dr. Kudo. This may be due to both the new, narrower definition of progression and the longer duration of sorafenib therapy in TACTICS (median 38.7 weeks) as compared with those trials (17.0-21.0 weeks).

“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” he concluded.

CELESTIAL trial

The 707 patients in the phase 3 CELESTIAL trial, sponsored by Exelixis, had advanced HCC with Child-Pugh class A and had previously received sorafenib. About 70% had received only one prior systemic regimen for their advanced disease, according to lead investigator Ghassan K. Abou-Alfa, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York.

Susan London/Frontline Medical News

Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (HR, 0.76; P = .0049). Median progression-free survival was 5.2 months and 1.9 months, respectively (HR, 0.44; P less than .0001). For both outcomes, benefit was similar across most patient subgroups and among patients whose only prior therapy was sorafenib.

The objective response rate was 4% with cabozantinib (all partial responses) and 0.4% with placebo. Median time to subsequent systemic anticancer therapy – most commonly cytotoxic chemotherapy – was 6.6 months with the drug and 3.3 months with placebo.

Median duration of treatment was 3.8 months and 2.0 months, respectively. The rate of discontinuation from treatment-related adverse events was 16% and 3%.

Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group (mainly hand-foot syndrome, hypertension, and gastrointestinal events) and 36% in the placebo group. Six patients in the former group and one in the latter group had grade 5 treatment-related adverse events, most due to worsening of hepatic function.

New treatments increase options, complexity

The new endpoint of unTACEable progression used in TACTICS “is an interesting potential surrogate endpoint for survival. It probably needs to be refined. I would not follow exactly the Japanese methodology,” said Dr. Bruix, the invited discussant.

“More importantly, it needs to be validated,” he added. “The survival data need to be there to see what is the value of the surrogate intermediate endpoint.”

The pattern of overall survival thus far suggests that an early advantage from adding sorafenib to TACE is lost over time. “Potentially, what we have here is the treatment maintained a bit beyond what would be recommended in the Western guidelines,” proposed Dr. Bruix, professor of medicine at the University of Barcelona and director of the Barcelona Clinic Liver Cancer Group. “The longer duration of sorafenib obviously may be related to the specific management in Japan, but also to the fact that progression recognition is delayed. If you delay recognition, you delay the definition of treatment interruption.”

Results of TACTICS probably will not lead to incorporation of sorafenib in clinical practice at this time, he concluded. “This will take a while. There is lots of noise in the chemoembolization trials, there are lots of discussions about what should be done.” In addition, “this should be studied in the West and in a large sample size.”

In the CELESTIAL trial, it would have been helpful to see biomarker data (given that tumor MET status may influence benefit from cabozantinib) and patient stratification according to reason for stopping prior sorafenib (intolerance versus progression), according to Dr. Bruix.

Furthermore, pattern of progression was not reported. “What drives a poorer outcome [in HCC] is the extrahepatic dissemination, meaning vascular invasion or extrahepatic spread. The trials, at least as a post hoc analysis, should have nowadays this kind of analysis that I think is not going to be available in the cabozantinib trial,” he said.

The fact that time to progression with cabozantinib was longer than time on the drug hints at possible safety and tolerability issues, according to Dr. Bruix. “This makes me suspect that some patients had something prior to progression that primed treatment interruption. This is something that I would like to see better explored … to understand to what extent the drug is safe, can be managed, or whether there are too many treatment interruptions that can lead to this discrepancy.”

All of the emerging systemic therapies for first- and second-line therapy in HCC, now also including immune checkpoint inhibitors, are likely to complicate the treatment landscape in the next few years, he cautioned. “The positioning of agents and the sequencing of treatments is different across the world. So there may be confusion in the field and that will affect all the trials that are going to be run by different companies, because if we do not maintain the discipline, patients will jump from one trial to the other and the follow-up after progression will be contaminated.” Ultimately, this could lead to noninformative trials.

Finally, “something that needs to be stated is that all the agents that are positive act on the VEGF pathway. This leaves a proportion of patients that cannot benefit from these agents because of comorbidity that are still in need of something that improves survival,” Dr. Bruix concluded. “We all should focus beyond VEGF and try to develop new strategies.”

SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.

SAN FRANCISCO – Two new therapies that target vascular endothelial growth factor signaling are efficacious and may expand the treatment armamentarium for intermediate and advanced hepatocellular carcinoma, data from a pair of randomized trials suggest.

In the phase 2 TACTICS (Transcatheter Arterial Chemoembolization Therapy in Combination With Sorafenib) trial, median progression-free survival, using a new, more narrow definition of progression, was almost a year longer when the oral tyrosine kinase inhibitor sorafenib (Nexavar) was added to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), translating to a 41% reduction in risk of events. This benefit came at the price of higher rates of certain grade 3 adverse events, but the combination was overall feasible and safe.

Susan London/Frontline Medical News

As welcome as such new therapeutic options are, they will likely increase the complexity of the treatment landscape for HCC and could muddy the ability of future trials to establish survival benefit, Jordi Bruix, MD, PhD, cautioned in an invited discussion. In addition, patients who cannot receive anti–vascular endothelial growth factor (VEGF) therapy because of comorbidities still represent an unmet need, underscoring the importance of continued research on other fronts.

TACTICS trial

“Because TACE has been shown to lead to a spike in the intratumoral concentration of VEGF, blockade of VEGF receptors may prevent the effects of a surge in proangiogenic factors,” said TACTICS lead investigator Masatoshi Kudo, MD, professor and chairman of the department of gastroenterology and hepatology at Kindai University, Osaka, Japan. “Since TACE and sorafenib have been shown to prolong survival in patients with unresectable HCC, their combination may improve clinical outcomes.”

The 156 patients enrolled in the TACTICS trial, sponsored by the Japan Liver Oncology Group, had unresectable HCC, a Child-Pugh score of 7 or lower, and no vascular invasion or extrahepatic spread.

They were randomly assigned to as-needed TACE alone or TACE plus sorafenib, which inhibits VEGF receptors, platelet-derived growth factor receptors, and Raf kinases, reducing growth signaling and angiogenesis. Sorafenib therapy was interrupted only for several days before and after each TACE session.

Susan London/Frontline Medical News

The trial’s positive results contrast with those of the earlier randomized Post-TACE trial, SPACE trial, and TACE 2 trial, noted Dr. Kudo. This may be due to both the new, narrower definition of progression and the longer duration of sorafenib therapy in TACTICS (median 38.7 weeks) as compared with those trials (17.0-21.0 weeks).

“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” he concluded.

CELESTIAL trial

The 707 patients in the phase 3 CELESTIAL trial, sponsored by Exelixis, had advanced HCC with Child-Pugh class A and had previously received sorafenib. About 70% had received only one prior systemic regimen for their advanced disease, according to lead investigator Ghassan K. Abou-Alfa, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York.

Susan London/Frontline Medical News

Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (HR, 0.76; P = .0049). Median progression-free survival was 5.2 months and 1.9 months, respectively (HR, 0.44; P less than .0001). For both outcomes, benefit was similar across most patient subgroups and among patients whose only prior therapy was sorafenib.

The objective response rate was 4% with cabozantinib (all partial responses) and 0.4% with placebo. Median time to subsequent systemic anticancer therapy – most commonly cytotoxic chemotherapy – was 6.6 months with the drug and 3.3 months with placebo.

Median duration of treatment was 3.8 months and 2.0 months, respectively. The rate of discontinuation from treatment-related adverse events was 16% and 3%.

Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group (mainly hand-foot syndrome, hypertension, and gastrointestinal events) and 36% in the placebo group. Six patients in the former group and one in the latter group had grade 5 treatment-related adverse events, most due to worsening of hepatic function.

New treatments increase options, complexity

The new endpoint of unTACEable progression used in TACTICS “is an interesting potential surrogate endpoint for survival. It probably needs to be refined. I would not follow exactly the Japanese methodology,” said Dr. Bruix, the invited discussant.

“More importantly, it needs to be validated,” he added. “The survival data need to be there to see what is the value of the surrogate intermediate endpoint.”

The pattern of overall survival thus far suggests that an early advantage from adding sorafenib to TACE is lost over time. “Potentially, what we have here is the treatment maintained a bit beyond what would be recommended in the Western guidelines,” proposed Dr. Bruix, professor of medicine at the University of Barcelona and director of the Barcelona Clinic Liver Cancer Group. “The longer duration of sorafenib obviously may be related to the specific management in Japan, but also to the fact that progression recognition is delayed. If you delay recognition, you delay the definition of treatment interruption.”

Results of TACTICS probably will not lead to incorporation of sorafenib in clinical practice at this time, he concluded. “This will take a while. There is lots of noise in the chemoembolization trials, there are lots of discussions about what should be done.” In addition, “this should be studied in the West and in a large sample size.”

In the CELESTIAL trial, it would have been helpful to see biomarker data (given that tumor MET status may influence benefit from cabozantinib) and patient stratification according to reason for stopping prior sorafenib (intolerance versus progression), according to Dr. Bruix.

Furthermore, pattern of progression was not reported. “What drives a poorer outcome [in HCC] is the extrahepatic dissemination, meaning vascular invasion or extrahepatic spread. The trials, at least as a post hoc analysis, should have nowadays this kind of analysis that I think is not going to be available in the cabozantinib trial,” he said.

The fact that time to progression with cabozantinib was longer than time on the drug hints at possible safety and tolerability issues, according to Dr. Bruix. “This makes me suspect that some patients had something prior to progression that primed treatment interruption. This is something that I would like to see better explored … to understand to what extent the drug is safe, can be managed, or whether there are too many treatment interruptions that can lead to this discrepancy.”

All of the emerging systemic therapies for first- and second-line therapy in HCC, now also including immune checkpoint inhibitors, are likely to complicate the treatment landscape in the next few years, he cautioned. “The positioning of agents and the sequencing of treatments is different across the world. So there may be confusion in the field and that will affect all the trials that are going to be run by different companies, because if we do not maintain the discipline, patients will jump from one trial to the other and the follow-up after progression will be contaminated.” Ultimately, this could lead to noninformative trials.

Finally, “something that needs to be stated is that all the agents that are positive act on the VEGF pathway. This leaves a proportion of patients that cannot benefit from these agents because of comorbidity that are still in need of something that improves survival,” Dr. Bruix concluded. “We all should focus beyond VEGF and try to develop new strategies.”

SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.

SAN FRANCISCO – Two new therapies that target vascular endothelial growth factor signaling are efficacious and may expand the treatment armamentarium for intermediate and advanced hepatocellular carcinoma, data from a pair of randomized trials suggest.

In the phase 2 TACTICS (Transcatheter Arterial Chemoembolization Therapy in Combination With Sorafenib) trial, median progression-free survival, using a new, more narrow definition of progression, was almost a year longer when the oral tyrosine kinase inhibitor sorafenib (Nexavar) was added to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), translating to a 41% reduction in risk of events. This benefit came at the price of higher rates of certain grade 3 adverse events, but the combination was overall feasible and safe.

Susan London/Frontline Medical News

As welcome as such new therapeutic options are, they will likely increase the complexity of the treatment landscape for HCC and could muddy the ability of future trials to establish survival benefit, Jordi Bruix, MD, PhD, cautioned in an invited discussion. In addition, patients who cannot receive anti–vascular endothelial growth factor (VEGF) therapy because of comorbidities still represent an unmet need, underscoring the importance of continued research on other fronts.

TACTICS trial

“Because TACE has been shown to lead to a spike in the intratumoral concentration of VEGF, blockade of VEGF receptors may prevent the effects of a surge in proangiogenic factors,” said TACTICS lead investigator Masatoshi Kudo, MD, professor and chairman of the department of gastroenterology and hepatology at Kindai University, Osaka, Japan. “Since TACE and sorafenib have been shown to prolong survival in patients with unresectable HCC, their combination may improve clinical outcomes.”

The 156 patients enrolled in the TACTICS trial, sponsored by the Japan Liver Oncology Group, had unresectable HCC, a Child-Pugh score of 7 or lower, and no vascular invasion or extrahepatic spread.

They were randomly assigned to as-needed TACE alone or TACE plus sorafenib, which inhibits VEGF receptors, platelet-derived growth factor receptors, and Raf kinases, reducing growth signaling and angiogenesis. Sorafenib therapy was interrupted only for several days before and after each TACE session.

Susan London/Frontline Medical News

The trial’s positive results contrast with those of the earlier randomized Post-TACE trial, SPACE trial, and TACE 2 trial, noted Dr. Kudo. This may be due to both the new, narrower definition of progression and the longer duration of sorafenib therapy in TACTICS (median 38.7 weeks) as compared with those trials (17.0-21.0 weeks).

“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” he concluded.

CELESTIAL trial

The 707 patients in the phase 3 CELESTIAL trial, sponsored by Exelixis, had advanced HCC with Child-Pugh class A and had previously received sorafenib. About 70% had received only one prior systemic regimen for their advanced disease, according to lead investigator Ghassan K. Abou-Alfa, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York.

Susan London/Frontline Medical News

Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (HR, 0.76; P = .0049). Median progression-free survival was 5.2 months and 1.9 months, respectively (HR, 0.44; P less than .0001). For both outcomes, benefit was similar across most patient subgroups and among patients whose only prior therapy was sorafenib.

The objective response rate was 4% with cabozantinib (all partial responses) and 0.4% with placebo. Median time to subsequent systemic anticancer therapy – most commonly cytotoxic chemotherapy – was 6.6 months with the drug and 3.3 months with placebo.

Median duration of treatment was 3.8 months and 2.0 months, respectively. The rate of discontinuation from treatment-related adverse events was 16% and 3%.

Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group (mainly hand-foot syndrome, hypertension, and gastrointestinal events) and 36% in the placebo group. Six patients in the former group and one in the latter group had grade 5 treatment-related adverse events, most due to worsening of hepatic function.

New treatments increase options, complexity

The new endpoint of unTACEable progression used in TACTICS “is an interesting potential surrogate endpoint for survival. It probably needs to be refined. I would not follow exactly the Japanese methodology,” said Dr. Bruix, the invited discussant.

“More importantly, it needs to be validated,” he added. “The survival data need to be there to see what is the value of the surrogate intermediate endpoint.”

The pattern of overall survival thus far suggests that an early advantage from adding sorafenib to TACE is lost over time. “Potentially, what we have here is the treatment maintained a bit beyond what would be recommended in the Western guidelines,” proposed Dr. Bruix, professor of medicine at the University of Barcelona and director of the Barcelona Clinic Liver Cancer Group. “The longer duration of sorafenib obviously may be related to the specific management in Japan, but also to the fact that progression recognition is delayed. If you delay recognition, you delay the definition of treatment interruption.”

Results of TACTICS probably will not lead to incorporation of sorafenib in clinical practice at this time, he concluded. “This will take a while. There is lots of noise in the chemoembolization trials, there are lots of discussions about what should be done.” In addition, “this should be studied in the West and in a large sample size.”

In the CELESTIAL trial, it would have been helpful to see biomarker data (given that tumor MET status may influence benefit from cabozantinib) and patient stratification according to reason for stopping prior sorafenib (intolerance versus progression), according to Dr. Bruix.

Furthermore, pattern of progression was not reported. “What drives a poorer outcome [in HCC] is the extrahepatic dissemination, meaning vascular invasion or extrahepatic spread. The trials, at least as a post hoc analysis, should have nowadays this kind of analysis that I think is not going to be available in the cabozantinib trial,” he said.

The fact that time to progression with cabozantinib was longer than time on the drug hints at possible safety and tolerability issues, according to Dr. Bruix. “This makes me suspect that some patients had something prior to progression that primed treatment interruption. This is something that I would like to see better explored … to understand to what extent the drug is safe, can be managed, or whether there are too many treatment interruptions that can lead to this discrepancy.”

All of the emerging systemic therapies for first- and second-line therapy in HCC, now also including immune checkpoint inhibitors, are likely to complicate the treatment landscape in the next few years, he cautioned. “The positioning of agents and the sequencing of treatments is different across the world. So there may be confusion in the field and that will affect all the trials that are going to be run by different companies, because if we do not maintain the discipline, patients will jump from one trial to the other and the follow-up after progression will be contaminated.” Ultimately, this could lead to noninformative trials.

Finally, “something that needs to be stated is that all the agents that are positive act on the VEGF pathway. This leaves a proportion of patients that cannot benefit from these agents because of comorbidity that are still in need of something that improves survival,” Dr. Bruix concluded. “We all should focus beyond VEGF and try to develop new strategies.”

SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.

Transmasculine youths distressed by breast development who undergo chest reconstruction reported low levels of distress and almost none said they regretted the surgery, according to study results.

This study is one of the first to document the ongoing impact of chest dysphoria in transgender youths, defined as individuals assigned female at birth who have a masculine gender identity.

“Given these findings, professional guidelines and clinical practice should consider patients for chest surgery based on individual need rather than chronologic age,” said Johanna Olson-Kennedy, MD, of the division of adolescent medicine at Children’s Hospital Los Angeles, and her coauthors.

National guidelines on transgender health care are unclear as to whether minors should be referred for chest surgery because of a lack of data documenting effects of chest surgery in individuals younger than 18 years of age, Dr. Olson-Kennedy and her colleagues wrote in the study, published in JAMA Pediatrics.

To evaluate the discomfort and subsequent consequences of chest dysphoria, the researchers developed a 10-minute, 21-item survey based on Dr. Olson-Kennedy’s 11 years of experience providing care for transgender youth. It was reviewed by a small number of transmasculine youth and adults to determine whether the questions contained the elements of chest dysphoria effectively, used appropriate language, and was otherwise acceptable. From the survey, the researchers derived a chest dysphoria composite score of 0-51, with higher scores indicating increased distress.

Some of the items on the chest dysphoria survey included avoiding exercise, not seeking medical care, and not swimming because of “my chest,” and that taking a shower is difficult as is dating and physical intimacy.

The study included surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of transmasculine individuals aged 13-25 years.

The chest dysphoria composite score was significantly higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (29.6 vs. 3.3; P less than .001), the investigators reported.

Among transmasculine youths who had not undergone surgery, 94% perceived the procedure as very important, Dr. Olson-Kennedy and her coauthors noted.

[email protected]

SOURCE: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.

Transmasculine youths distressed by breast development who undergo chest reconstruction reported low levels of distress and almost none said they regretted the surgery, according to study results.

This study is one of the first to document the ongoing impact of chest dysphoria in transgender youths, defined as individuals assigned female at birth who have a masculine gender identity.

“Given these findings, professional guidelines and clinical practice should consider patients for chest surgery based on individual need rather than chronologic age,” said Johanna Olson-Kennedy, MD, of the division of adolescent medicine at Children’s Hospital Los Angeles, and her coauthors.

National guidelines on transgender health care are unclear as to whether minors should be referred for chest surgery because of a lack of data documenting effects of chest surgery in individuals younger than 18 years of age, Dr. Olson-Kennedy and her colleagues wrote in the study, published in JAMA Pediatrics.

To evaluate the discomfort and subsequent consequences of chest dysphoria, the researchers developed a 10-minute, 21-item survey based on Dr. Olson-Kennedy’s 11 years of experience providing care for transgender youth. It was reviewed by a small number of transmasculine youth and adults to determine whether the questions contained the elements of chest dysphoria effectively, used appropriate language, and was otherwise acceptable. From the survey, the researchers derived a chest dysphoria composite score of 0-51, with higher scores indicating increased distress.

Some of the items on the chest dysphoria survey included avoiding exercise, not seeking medical care, and not swimming because of “my chest,” and that taking a shower is difficult as is dating and physical intimacy.

The study included surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of transmasculine individuals aged 13-25 years.

The chest dysphoria composite score was significantly higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (29.6 vs. 3.3; P less than .001), the investigators reported.

Among transmasculine youths who had not undergone surgery, 94% perceived the procedure as very important, Dr. Olson-Kennedy and her coauthors noted.

[email protected]

SOURCE: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.

Transmasculine youths distressed by breast development who undergo chest reconstruction reported low levels of distress and almost none said they regretted the surgery, according to study results.

This study is one of the first to document the ongoing impact of chest dysphoria in transgender youths, defined as individuals assigned female at birth who have a masculine gender identity.

“Given these findings, professional guidelines and clinical practice should consider patients for chest surgery based on individual need rather than chronologic age,” said Johanna Olson-Kennedy, MD, of the division of adolescent medicine at Children’s Hospital Los Angeles, and her coauthors.

National guidelines on transgender health care are unclear as to whether minors should be referred for chest surgery because of a lack of data documenting effects of chest surgery in individuals younger than 18 years of age, Dr. Olson-Kennedy and her colleagues wrote in the study, published in JAMA Pediatrics.

To evaluate the discomfort and subsequent consequences of chest dysphoria, the researchers developed a 10-minute, 21-item survey based on Dr. Olson-Kennedy’s 11 years of experience providing care for transgender youth. It was reviewed by a small number of transmasculine youth and adults to determine whether the questions contained the elements of chest dysphoria effectively, used appropriate language, and was otherwise acceptable. From the survey, the researchers derived a chest dysphoria composite score of 0-51, with higher scores indicating increased distress.

Some of the items on the chest dysphoria survey included avoiding exercise, not seeking medical care, and not swimming because of “my chest,” and that taking a shower is difficult as is dating and physical intimacy.

The study included surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of transmasculine individuals aged 13-25 years.

The chest dysphoria composite score was significantly higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (29.6 vs. 3.3; P less than .001), the investigators reported.

Among transmasculine youths who had not undergone surgery, 94% perceived the procedure as very important, Dr. Olson-Kennedy and her coauthors noted.

[email protected]

SOURCE: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.

When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.

At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.

The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.

However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.

“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.

The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).

In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.

“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.

SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087

When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.

At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.

The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.

However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.

“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.

The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).

In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.

“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.

SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087

When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.

At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.

The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.

However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.

“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.

The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).

In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.

“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.

SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087

The Trump administration on March 5 approved Arkansas’ request for a Medicaid work requirement but deferred a decision on the state’s request to roll back its Medicaid expansion that has added 300,000 adults to the program.

Arkansas had sought to reduce the number of people eligible for Medicaid by allowing only those with incomes below the federal poverty level, or about $12,140 for an individual, to qualify. For the past 4 years, Arkansas Medicaid covered everyone with incomes under 138% of the poverty level, or about $16,750. The new policy would have cut the number of people eligible for Medicaid in the state by about 60,000 people.

Seema Verma, administrator of the Centers for Medicare & Medicaid Services, who announced the decision, has said her goal as head of the program was to grant states more flexibility in running their Medicaid programs than they’ve had before.

Arkansas follows Indiana and Kentucky this year in winning CMS’ approval for the work requirement. Arkansas plans to start the new requirement affecting adults under age 50 years by June, making it the first to do so.

Ms. Verma recused herself on CMS’ decisions involving Indiana and Kentucky because she used to consult with those state Medicaid agencies before joining the Trump administration in 2017. As a health care consultant, she also worked with Arkansas. But Ms. Verma decided to personally approve the Arkansas waiver on Monday and flew to Little Rock, Ark., to make the announcement with Gov. Asa Hutchinson (R).

CMS officials did not respond to questions about why she did not recuse herself again.

But a top Senate Democrat lambasted Ms. Verma’s decision.

“She pledged during her confirmation to recuse herself from working on many states’ Medicaid waivers to avoid conflicts of interest, including Arkansas, Sen. Ron Wyden (D-Ore.) said in a statement. “The Trump administration has simply made a mockery of the HHS ethics process.”

It is unclear why she deferred deciding on Arkansas’ request to scale back its Medicaid decision. Deferring a decision on rolling back expansion could be a way of rejecting the application but in a less politically harsh way. Arkansas was one of the few Southern states to expand Medicaid under the ACA, a decision that brought hundreds of millions of federal dollars into the state.

Nine other states have requests pending with CMS to enact a Medicaid work requirement.

In Arkansas, enrollees who don’t work or volunteer at least 80 hours a month could lose coverage as early as September. The work requirement exempts many people, such as those with opioid addiction and parents with dependent children.

Ms. Verma said the work requirement “is about helping people rise out of poverty to achieve the American dream.”

But advocates for the poor blasted the move, noting most Medicaid enrollees already work, go to school, or are taking care of sick relatives.

“The Trump administration’s approval of Arkansas’ harsh work requirement in Medicaid will likely set back the state’s considerable progress under the Affordable Care Act in increasing coverage and improving access to care, health and financial stability for low-income Arkansans,” said Judith Solomon, vice president for health policy at the left-leaning Center on Budget and Policy Priorities.

Arkansas officials said they need the work requirement because without it many enrollees won’t seek out work or job training. Since January 2017, fewer than 5% of Medicaid enrollees who were referred to the state Department of Workforce Services to help with job training followed through and accessed services.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The Trump administration on March 5 approved Arkansas’ request for a Medicaid work requirement but deferred a decision on the state’s request to roll back its Medicaid expansion that has added 300,000 adults to the program.

Arkansas had sought to reduce the number of people eligible for Medicaid by allowing only those with incomes below the federal poverty level, or about $12,140 for an individual, to qualify. For the past 4 years, Arkansas Medicaid covered everyone with incomes under 138% of the poverty level, or about $16,750. The new policy would have cut the number of people eligible for Medicaid in the state by about 60,000 people.

Seema Verma, administrator of the Centers for Medicare & Medicaid Services, who announced the decision, has said her goal as head of the program was to grant states more flexibility in running their Medicaid programs than they’ve had before.

Arkansas follows Indiana and Kentucky this year in winning CMS’ approval for the work requirement. Arkansas plans to start the new requirement affecting adults under age 50 years by June, making it the first to do so.

Ms. Verma recused herself on CMS’ decisions involving Indiana and Kentucky because she used to consult with those state Medicaid agencies before joining the Trump administration in 2017. As a health care consultant, she also worked with Arkansas. But Ms. Verma decided to personally approve the Arkansas waiver on Monday and flew to Little Rock, Ark., to make the announcement with Gov. Asa Hutchinson (R).

CMS officials did not respond to questions about why she did not recuse herself again.

But a top Senate Democrat lambasted Ms. Verma’s decision.

“She pledged during her confirmation to recuse herself from working on many states’ Medicaid waivers to avoid conflicts of interest, including Arkansas, Sen. Ron Wyden (D-Ore.) said in a statement. “The Trump administration has simply made a mockery of the HHS ethics process.”

It is unclear why she deferred deciding on Arkansas’ request to scale back its Medicaid decision. Deferring a decision on rolling back expansion could be a way of rejecting the application but in a less politically harsh way. Arkansas was one of the few Southern states to expand Medicaid under the ACA, a decision that brought hundreds of millions of federal dollars into the state.

Nine other states have requests pending with CMS to enact a Medicaid work requirement.

In Arkansas, enrollees who don’t work or volunteer at least 80 hours a month could lose coverage as early as September. The work requirement exempts many people, such as those with opioid addiction and parents with dependent children.

Ms. Verma said the work requirement “is about helping people rise out of poverty to achieve the American dream.”

But advocates for the poor blasted the move, noting most Medicaid enrollees already work, go to school, or are taking care of sick relatives.

“The Trump administration’s approval of Arkansas’ harsh work requirement in Medicaid will likely set back the state’s considerable progress under the Affordable Care Act in increasing coverage and improving access to care, health and financial stability for low-income Arkansans,” said Judith Solomon, vice president for health policy at the left-leaning Center on Budget and Policy Priorities.

Arkansas officials said they need the work requirement because without it many enrollees won’t seek out work or job training. Since January 2017, fewer than 5% of Medicaid enrollees who were referred to the state Department of Workforce Services to help with job training followed through and accessed services.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The Trump administration on March 5 approved Arkansas’ request for a Medicaid work requirement but deferred a decision on the state’s request to roll back its Medicaid expansion that has added 300,000 adults to the program.

Arkansas had sought to reduce the number of people eligible for Medicaid by allowing only those with incomes below the federal poverty level, or about $12,140 for an individual, to qualify. For the past 4 years, Arkansas Medicaid covered everyone with incomes under 138% of the poverty level, or about $16,750. The new policy would have cut the number of people eligible for Medicaid in the state by about 60,000 people.

Seema Verma, administrator of the Centers for Medicare & Medicaid Services, who announced the decision, has said her goal as head of the program was to grant states more flexibility in running their Medicaid programs than they’ve had before.

Arkansas follows Indiana and Kentucky this year in winning CMS’ approval for the work requirement. Arkansas plans to start the new requirement affecting adults under age 50 years by June, making it the first to do so.

Ms. Verma recused herself on CMS’ decisions involving Indiana and Kentucky because she used to consult with those state Medicaid agencies before joining the Trump administration in 2017. As a health care consultant, she also worked with Arkansas. But Ms. Verma decided to personally approve the Arkansas waiver on Monday and flew to Little Rock, Ark., to make the announcement with Gov. Asa Hutchinson (R).

CMS officials did not respond to questions about why she did not recuse herself again.

But a top Senate Democrat lambasted Ms. Verma’s decision.

“She pledged during her confirmation to recuse herself from working on many states’ Medicaid waivers to avoid conflicts of interest, including Arkansas, Sen. Ron Wyden (D-Ore.) said in a statement. “The Trump administration has simply made a mockery of the HHS ethics process.”

It is unclear why she deferred deciding on Arkansas’ request to scale back its Medicaid decision. Deferring a decision on rolling back expansion could be a way of rejecting the application but in a less politically harsh way. Arkansas was one of the few Southern states to expand Medicaid under the ACA, a decision that brought hundreds of millions of federal dollars into the state.

Nine other states have requests pending with CMS to enact a Medicaid work requirement.

In Arkansas, enrollees who don’t work or volunteer at least 80 hours a month could lose coverage as early as September. The work requirement exempts many people, such as those with opioid addiction and parents with dependent children.

Ms. Verma said the work requirement “is about helping people rise out of poverty to achieve the American dream.”

But advocates for the poor blasted the move, noting most Medicaid enrollees already work, go to school, or are taking care of sick relatives.

“The Trump administration’s approval of Arkansas’ harsh work requirement in Medicaid will likely set back the state’s considerable progress under the Affordable Care Act in increasing coverage and improving access to care, health and financial stability for low-income Arkansans,” said Judith Solomon, vice president for health policy at the left-leaning Center on Budget and Policy Priorities.

Arkansas officials said they need the work requirement because without it many enrollees won’t seek out work or job training. Since January 2017, fewer than 5% of Medicaid enrollees who were referred to the state Department of Workforce Services to help with job training followed through and accessed services.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The Food and Drug Administration has approved lurasidone HCI (Latuda) for treating bipolar I depression in children and adolescents, according to a March 6 statement from the drug’s manufacturer.

“We know that children who have been diagnosed with bipolar depression can be at risk for poor school performance and impairments in social functioning,” said Robert L. Findling, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, in the statement.

Patients who received lurasidone reportedly experienced improved bipolar depression symptoms, compared with placebo, based on “the primary efficacy endpoint of change from baseline to week 6 on the Children’s Depression Rating Scale–Revised total score (–21.0 vs. –15.3; effect size = 0.45; P less than .0001),” the statement said. Clinically relevant changes also were found among patients who took the medication on other measures, including the Clinical Global Impressions-Bipolar Scale.

The most common adverse effects were nausea (16% vs. 5.8%), weight gain (6.9% vs. 1.7%), and insomnia (5.1% vs. 2.3%).

Lurasidone also has been approved for treating schizophrenia and bipolar I depression in adults. Last year, the drug was approved for treating schizophrenia in adolescents.

[email protected]

The Food and Drug Administration has approved lurasidone HCI (Latuda) for treating bipolar I depression in children and adolescents, according to a March 6 statement from the drug’s manufacturer.

“We know that children who have been diagnosed with bipolar depression can be at risk for poor school performance and impairments in social functioning,” said Robert L. Findling, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, in the statement.

Patients who received lurasidone reportedly experienced improved bipolar depression symptoms, compared with placebo, based on “the primary efficacy endpoint of change from baseline to week 6 on the Children’s Depression Rating Scale–Revised total score (–21.0 vs. –15.3; effect size = 0.45; P less than .0001),” the statement said. Clinically relevant changes also were found among patients who took the medication on other measures, including the Clinical Global Impressions-Bipolar Scale.

The most common adverse effects were nausea (16% vs. 5.8%), weight gain (6.9% vs. 1.7%), and insomnia (5.1% vs. 2.3%).

Lurasidone also has been approved for treating schizophrenia and bipolar I depression in adults. Last year, the drug was approved for treating schizophrenia in adolescents.

[email protected]

The Food and Drug Administration has approved lurasidone HCI (Latuda) for treating bipolar I depression in children and adolescents, according to a March 6 statement from the drug’s manufacturer.

“We know that children who have been diagnosed with bipolar depression can be at risk for poor school performance and impairments in social functioning,” said Robert L. Findling, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, in the statement.

Patients who received lurasidone reportedly experienced improved bipolar depression symptoms, compared with placebo, based on “the primary efficacy endpoint of change from baseline to week 6 on the Children’s Depression Rating Scale–Revised total score (–21.0 vs. –15.3; effect size = 0.45; P less than .0001),” the statement said. Clinically relevant changes also were found among patients who took the medication on other measures, including the Clinical Global Impressions-Bipolar Scale.

The most common adverse effects were nausea (16% vs. 5.8%), weight gain (6.9% vs. 1.7%), and insomnia (5.1% vs. 2.3%).

Lurasidone also has been approved for treating schizophrenia and bipolar I depression in adults. Last year, the drug was approved for treating schizophrenia in adolescents.

[email protected]

BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.

Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.

Neil Osterweil, Frontline Medical News

Results from the study were simultaneously published online in JAMA.

Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.

In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.

Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.

To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.

After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.

In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.

In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.

The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).

Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).

The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.

Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.

SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.

BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.

Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.

Neil Osterweil, Frontline Medical News

Results from the study were simultaneously published online in JAMA.

Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.

In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.

Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.

To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.

After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.

In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.

In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.

The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).

Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).

The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.

Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.

SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.

BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.

Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.

Neil Osterweil, Frontline Medical News

Results from the study were simultaneously published online in JAMA.

Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.

In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.

Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.

To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.

After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.

In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.

In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.

The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).

Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).

The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.

Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.

SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.

A few years ago, Renea Molden’s doctors told her they wanted to take her off her opioid pills. It did not sound like good idea to her.

“I was mad, I’ll be honest. I was mad. I was frustrated,” said Molden, 40, of Kansas City, Mo. She struggles with fibromyalgia, bulging discs and degenerative disc disease. Her doctors were concerned about her potentially taking hydrocodone for the rest of her life, but to her, the three pills she took each day seemed to be the only way she could make it through work, go shopping or even fix dinner.

“It felt like they were taking a part of my life away from me,” she said.

For many people with chronic pain, opioids can seem like the difference between a full life or one lived in agony. Over the past few decades, they have become go-to drugs for acute pain, but Dr. Erin Krebs, with the Minneapolis Veterans Affairs Health Care System and the University of Minnesota, said research about the effectiveness of opioids for chronic pain was lacking. Even though millions of people take the drugs for long periods of time, there is little evidence to support that use.

“The studies that we had out there were short-term studies and mostly compared opioids to placebo medications,” Krebs said. “From those studies, we knew that opioids can improve pain a little bit more than a placebo, or sugar pill, in the short term, but that’s all we knew.”

But that’s changing. Krebs is the lead author of a new study that looks at the effectiveness of opioids for treating chronic pain over 12 months published Tuesday in the Journal of the American Medical Association.

The study involved 240 veterans with chronic back pain or osteoarthritis of the knee or hip who had pain that was ongoing and intense. Half were treated with opioids and half with non-opioid medications — either common over-the-counter drugs like acetaminophen or naproxen, or prescription drugs like topical lidocaine or meloxicam. Doctors and patients knew what group they were in, said Krebs, and that was deliberate because people’s expectations can influence how they feel.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she said.

But after as little as six months, the non-opioid group reported their pain was slightly less severe than the opioid group’s collective assessment. By the end of the year, Krebs said, “there was really no difference between the groups in terms of pain interference with activities. And over time, the non-opioid group had less pain intensity, and the opioid group had more side effects,” such as constipation, fatigue and nausea.

The study didn’t explore why, but Krebs has a theory: opioid tolerance.

“Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she said.

Opioids, of course, also carry the risk of dependence, addiction and overdose. Coming off of opioids gives patients who have developed a dependence flu-like symptoms that can last for days or weeks.

“This study adds the long-term evidence that shows that opioids really don’t have any advantages in terms of pain relief that might outweigh the known harms that they cause,” she said. “The bottom line for people who have chronic back pain or arthritis pain is just that you shouldn’t start opioids.”

But what about patients like Molden who had already been using opioids for a long time? Dr. Muhammed Farhan, medical director of the University of Missouri-Kansas City’s multidisciplinary pain management program, said diplomatic conversations with patients like Molden are part of his daily routine. Farhan also is the medical director of the University Health Pain Management Clinic at Truman Medical Centers, which doesn’t prescribe opioids.

He said he meets patients every day with problems like back pain who’ve reached the end of the line with the drugs.

“Most of the time what I see is that they are taking high doses of opioids and that they are in bed all the time or sleeping and still in pain,” he said.

Farhan said he starts by helping them adjust to the idea that they cannot eliminate pain entirely. He said this expectation can be especially dangerous for people who rely on increasing doses of opioids.

“Our idea of being completely pain-free can lead us to a place when they end up with more pain, no improvement in their quality of life after being on high doses of opioid medications, which can be harmful to the point that they may die,” Farhan said.

He said he tries to help his patients taper off opioids slowly and use alternative drugs and therapies.

Krebs agrees with this approach. “Medications have some role, but they really shouldn’t be the primary way we are treating chronic pain,” she said. “For osteoarthritis pain, the strongly recommended treatments are exercise treatments,” she said, and it’s important to maintain a healthy weight. “The same thing goes for back pain,” she said, where experts recommend exercise, rehabilitation treatments, yoga and cognitive therapies, among others.

Renea Molden said it’s been hard to leave hydrocodone behind, but she’s working at it.

“I know if I can just get through that day — there’s good days and there’s bad days, and you just kind of have to make it through the bad days,” she said.

But even on the worst days, Molden feels good that she’s facing her pain without opioids.

This story is part of a reporting partnership with NPR, KCUR and Kaiser Health News.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

A few years ago, Renea Molden’s doctors told her they wanted to take her off her opioid pills. It did not sound like good idea to her.

“I was mad, I’ll be honest. I was mad. I was frustrated,” said Molden, 40, of Kansas City, Mo. She struggles with fibromyalgia, bulging discs and degenerative disc disease. Her doctors were concerned about her potentially taking hydrocodone for the rest of her life, but to her, the three pills she took each day seemed to be the only way she could make it through work, go shopping or even fix dinner.

“It felt like they were taking a part of my life away from me,” she said.

For many people with chronic pain, opioids can seem like the difference between a full life or one lived in agony. Over the past few decades, they have become go-to drugs for acute pain, but Dr. Erin Krebs, with the Minneapolis Veterans Affairs Health Care System and the University of Minnesota, said research about the effectiveness of opioids for chronic pain was lacking. Even though millions of people take the drugs for long periods of time, there is little evidence to support that use.

“The studies that we had out there were short-term studies and mostly compared opioids to placebo medications,” Krebs said. “From those studies, we knew that opioids can improve pain a little bit more than a placebo, or sugar pill, in the short term, but that’s all we knew.”

But that’s changing. Krebs is the lead author of a new study that looks at the effectiveness of opioids for treating chronic pain over 12 months published Tuesday in the Journal of the American Medical Association.

The study involved 240 veterans with chronic back pain or osteoarthritis of the knee or hip who had pain that was ongoing and intense. Half were treated with opioids and half with non-opioid medications — either common over-the-counter drugs like acetaminophen or naproxen, or prescription drugs like topical lidocaine or meloxicam. Doctors and patients knew what group they were in, said Krebs, and that was deliberate because people’s expectations can influence how they feel.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she said.

But after as little as six months, the non-opioid group reported their pain was slightly less severe than the opioid group’s collective assessment. By the end of the year, Krebs said, “there was really no difference between the groups in terms of pain interference with activities. And over time, the non-opioid group had less pain intensity, and the opioid group had more side effects,” such as constipation, fatigue and nausea.

The study didn’t explore why, but Krebs has a theory: opioid tolerance.

“Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she said.

Opioids, of course, also carry the risk of dependence, addiction and overdose. Coming off of opioids gives patients who have developed a dependence flu-like symptoms that can last for days or weeks.

“This study adds the long-term evidence that shows that opioids really don’t have any advantages in terms of pain relief that might outweigh the known harms that they cause,” she said. “The bottom line for people who have chronic back pain or arthritis pain is just that you shouldn’t start opioids.”

But what about patients like Molden who had already been using opioids for a long time? Dr. Muhammed Farhan, medical director of the University of Missouri-Kansas City’s multidisciplinary pain management program, said diplomatic conversations with patients like Molden are part of his daily routine. Farhan also is the medical director of the University Health Pain Management Clinic at Truman Medical Centers, which doesn’t prescribe opioids.

He said he meets patients every day with problems like back pain who’ve reached the end of the line with the drugs.

“Most of the time what I see is that they are taking high doses of opioids and that they are in bed all the time or sleeping and still in pain,” he said.

Farhan said he starts by helping them adjust to the idea that they cannot eliminate pain entirely. He said this expectation can be especially dangerous for people who rely on increasing doses of opioids.

“Our idea of being completely pain-free can lead us to a place when they end up with more pain, no improvement in their quality of life after being on high doses of opioid medications, which can be harmful to the point that they may die,” Farhan said.

He said he tries to help his patients taper off opioids slowly and use alternative drugs and therapies.

Krebs agrees with this approach. “Medications have some role, but they really shouldn’t be the primary way we are treating chronic pain,” she said. “For osteoarthritis pain, the strongly recommended treatments are exercise treatments,” she said, and it’s important to maintain a healthy weight. “The same thing goes for back pain,” she said, where experts recommend exercise, rehabilitation treatments, yoga and cognitive therapies, among others.

Renea Molden said it’s been hard to leave hydrocodone behind, but she’s working at it.

“I know if I can just get through that day — there’s good days and there’s bad days, and you just kind of have to make it through the bad days,” she said.

But even on the worst days, Molden feels good that she’s facing her pain without opioids.

This story is part of a reporting partnership with NPR, KCUR and Kaiser Health News.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

A few years ago, Renea Molden’s doctors told her they wanted to take her off her opioid pills. It did not sound like good idea to her.

“I was mad, I’ll be honest. I was mad. I was frustrated,” said Molden, 40, of Kansas City, Mo. She struggles with fibromyalgia, bulging discs and degenerative disc disease. Her doctors were concerned about her potentially taking hydrocodone for the rest of her life, but to her, the three pills she took each day seemed to be the only way she could make it through work, go shopping or even fix dinner.

“It felt like they were taking a part of my life away from me,” she said.

For many people with chronic pain, opioids can seem like the difference between a full life or one lived in agony. Over the past few decades, they have become go-to drugs for acute pain, but Dr. Erin Krebs, with the Minneapolis Veterans Affairs Health Care System and the University of Minnesota, said research about the effectiveness of opioids for chronic pain was lacking. Even though millions of people take the drugs for long periods of time, there is little evidence to support that use.

“The studies that we had out there were short-term studies and mostly compared opioids to placebo medications,” Krebs said. “From those studies, we knew that opioids can improve pain a little bit more than a placebo, or sugar pill, in the short term, but that’s all we knew.”

But that’s changing. Krebs is the lead author of a new study that looks at the effectiveness of opioids for treating chronic pain over 12 months published Tuesday in the Journal of the American Medical Association.

The study involved 240 veterans with chronic back pain or osteoarthritis of the knee or hip who had pain that was ongoing and intense. Half were treated with opioids and half with non-opioid medications — either common over-the-counter drugs like acetaminophen or naproxen, or prescription drugs like topical lidocaine or meloxicam. Doctors and patients knew what group they were in, said Krebs, and that was deliberate because people’s expectations can influence how they feel.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she said.

But after as little as six months, the non-opioid group reported their pain was slightly less severe than the opioid group’s collective assessment. By the end of the year, Krebs said, “there was really no difference between the groups in terms of pain interference with activities. And over time, the non-opioid group had less pain intensity, and the opioid group had more side effects,” such as constipation, fatigue and nausea.

The study didn’t explore why, but Krebs has a theory: opioid tolerance.

“Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she said.

Opioids, of course, also carry the risk of dependence, addiction and overdose. Coming off of opioids gives patients who have developed a dependence flu-like symptoms that can last for days or weeks.

“This study adds the long-term evidence that shows that opioids really don’t have any advantages in terms of pain relief that might outweigh the known harms that they cause,” she said. “The bottom line for people who have chronic back pain or arthritis pain is just that you shouldn’t start opioids.”

But what about patients like Molden who had already been using opioids for a long time? Dr. Muhammed Farhan, medical director of the University of Missouri-Kansas City’s multidisciplinary pain management program, said diplomatic conversations with patients like Molden are part of his daily routine. Farhan also is the medical director of the University Health Pain Management Clinic at Truman Medical Centers, which doesn’t prescribe opioids.

He said he meets patients every day with problems like back pain who’ve reached the end of the line with the drugs.

“Most of the time what I see is that they are taking high doses of opioids and that they are in bed all the time or sleeping and still in pain,” he said.

Farhan said he starts by helping them adjust to the idea that they cannot eliminate pain entirely. He said this expectation can be especially dangerous for people who rely on increasing doses of opioids.

“Our idea of being completely pain-free can lead us to a place when they end up with more pain, no improvement in their quality of life after being on high doses of opioid medications, which can be harmful to the point that they may die,” Farhan said.

He said he tries to help his patients taper off opioids slowly and use alternative drugs and therapies.

Krebs agrees with this approach. “Medications have some role, but they really shouldn’t be the primary way we are treating chronic pain,” she said. “For osteoarthritis pain, the strongly recommended treatments are exercise treatments,” she said, and it’s important to maintain a healthy weight. “The same thing goes for back pain,” she said, where experts recommend exercise, rehabilitation treatments, yoga and cognitive therapies, among others.

Renea Molden said it’s been hard to leave hydrocodone behind, but she’s working at it.

“I know if I can just get through that day — there’s good days and there’s bad days, and you just kind of have to make it through the bad days,” she said.

But even on the worst days, Molden feels good that she’s facing her pain without opioids.

This story is part of a reporting partnership with NPR, KCUR and Kaiser Health News.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

Courtesy UAB Photo

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA_1c [hemoglobin A_1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

[email protected]

It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

Courtesy UAB Photo

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA_1c [hemoglobin A_1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

[email protected]

It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

Courtesy UAB Photo

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA_1c [hemoglobin A_1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

[email protected]

Mild cognitive impairment rises in heart patients with comorbidities. Allergies? There’s an app for that. Why nongastroenterologists should know SIBO. And tuberculosis prevention in HIV is about to speed up.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Mild cognitive impairment rises in heart patients with comorbidities. Allergies? There’s an app for that. Why nongastroenterologists should know SIBO. And tuberculosis prevention in HIV is about to speed up.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Mild cognitive impairment rises in heart patients with comorbidities. Allergies? There’s an app for that. Why nongastroenterologists should know SIBO. And tuberculosis prevention in HIV is about to speed up.

Listen to the MDedge Daily News podcast for all the details on today’s top news.