Andrew D. Bowser

Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.

Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.

The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).

Among nine patients who experienced a second neurotoxic event, all were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.

“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.

Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).

Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.

That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.

It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.

The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.

The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.

SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.

Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.

Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.

The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).

Among nine patients who experienced a second neurotoxic event, all were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.

“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.

Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).

Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.

That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.

It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.

The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.

The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.

SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.

Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.

Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.

The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).

Among nine patients who experienced a second neurotoxic event, all were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.

“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.

Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).

Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.

That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.

It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.

The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.

The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.

SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.

A new classification system that incorporates clinical and serologic data may be useful in the classification of idiopathic inflammatory myopathies, results of a recent analysis suggest.

By analyzing the patterns of relationships between 47 variables in this observational, retrospective cohort study, investigators identified 4 clusters of patients that corresponded to known idiopathic inflammatory myopathy subtypes.

Myositis-specific antibodies played a key role in predicting whether a patient belonged in a cluster, according to investigators, who noted that myositis-specific antibodies known to be associated with certain subgroups fell into the corresponding clusters they identified.

“This emphasizes that muscle biopsy may no longer be necessary for diagnosis of idiopathic inflammatory myopathies in patients with [myositis-specific antibodies] and corresponding phenotypes,” said the investigators, led by Kubéraka Mariampillai, PhD, of the Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.

The study, described in JAMA Neurology, was based on data for 260 patients in the database of the French Myositis Network. The mean age of the patients was 62 years, and 63% were women.

Investigators conducted a multiple correspondence analysis based on 47 selected variables, including age, race, historical and recent diagnoses, dermatologic changes, creatine kinase levels, myositis-specific antibodies, and pathologic characteristics, among others.

Based on that analysis, they identified four subgroups corresponding to known entities: Dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome.

Using decisional algorithm trees, investigators found that myositis-specific antibodies “played a key role in estimating connection to a cluster,” while by contrast, the pathologic data were “dispensable,” Dr. Mariampillai and her associates said.

The best tree omitted variables related to muscle biopsy and had a 78% correct estimation looking just at antisynthetase antibodies, dermatomyositis rash, and finger flexor scores of 3 or less, investigators said.

“The classification quality of the tree was appreciated on the basis of all classification criteria, with an overall sensitivity of 77.0% and a specificity of 92.0%,” the investigators said.

Patients with polymyositis were present in the study data, but fell mainly in the clusters corresponding to immune-mediated necrotizing myopathy and antisynthetase syndrome.

“This finding indicates that patients with polymyositis do not represent a subgroup of patients, and use of this term should probably be discontinued,” Dr. Mariampillai and coinvestigators said.

The study was supported by Association Française contre les Myopathies, and by CSL Behring, which partly funded the development of electronic case report forms. Dr. Mariampillai and colleagues reported no conflicts of interest related to this work.

SOURCE: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.

A new classification system that incorporates clinical and serologic data may be useful in the classification of idiopathic inflammatory myopathies, results of a recent analysis suggest.

By analyzing the patterns of relationships between 47 variables in this observational, retrospective cohort study, investigators identified 4 clusters of patients that corresponded to known idiopathic inflammatory myopathy subtypes.

Myositis-specific antibodies played a key role in predicting whether a patient belonged in a cluster, according to investigators, who noted that myositis-specific antibodies known to be associated with certain subgroups fell into the corresponding clusters they identified.

“This emphasizes that muscle biopsy may no longer be necessary for diagnosis of idiopathic inflammatory myopathies in patients with [myositis-specific antibodies] and corresponding phenotypes,” said the investigators, led by Kubéraka Mariampillai, PhD, of the Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.

The study, described in JAMA Neurology, was based on data for 260 patients in the database of the French Myositis Network. The mean age of the patients was 62 years, and 63% were women.

Investigators conducted a multiple correspondence analysis based on 47 selected variables, including age, race, historical and recent diagnoses, dermatologic changes, creatine kinase levels, myositis-specific antibodies, and pathologic characteristics, among others.

Based on that analysis, they identified four subgroups corresponding to known entities: Dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome.

Using decisional algorithm trees, investigators found that myositis-specific antibodies “played a key role in estimating connection to a cluster,” while by contrast, the pathologic data were “dispensable,” Dr. Mariampillai and her associates said.

The best tree omitted variables related to muscle biopsy and had a 78% correct estimation looking just at antisynthetase antibodies, dermatomyositis rash, and finger flexor scores of 3 or less, investigators said.

“The classification quality of the tree was appreciated on the basis of all classification criteria, with an overall sensitivity of 77.0% and a specificity of 92.0%,” the investigators said.

Patients with polymyositis were present in the study data, but fell mainly in the clusters corresponding to immune-mediated necrotizing myopathy and antisynthetase syndrome.

“This finding indicates that patients with polymyositis do not represent a subgroup of patients, and use of this term should probably be discontinued,” Dr. Mariampillai and coinvestigators said.

The study was supported by Association Française contre les Myopathies, and by CSL Behring, which partly funded the development of electronic case report forms. Dr. Mariampillai and colleagues reported no conflicts of interest related to this work.

SOURCE: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.

A new classification system that incorporates clinical and serologic data may be useful in the classification of idiopathic inflammatory myopathies, results of a recent analysis suggest.

By analyzing the patterns of relationships between 47 variables in this observational, retrospective cohort study, investigators identified 4 clusters of patients that corresponded to known idiopathic inflammatory myopathy subtypes.

Myositis-specific antibodies played a key role in predicting whether a patient belonged in a cluster, according to investigators, who noted that myositis-specific antibodies known to be associated with certain subgroups fell into the corresponding clusters they identified.

“This emphasizes that muscle biopsy may no longer be necessary for diagnosis of idiopathic inflammatory myopathies in patients with [myositis-specific antibodies] and corresponding phenotypes,” said the investigators, led by Kubéraka Mariampillai, PhD, of the Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.

The study, described in JAMA Neurology, was based on data for 260 patients in the database of the French Myositis Network. The mean age of the patients was 62 years, and 63% were women.

Investigators conducted a multiple correspondence analysis based on 47 selected variables, including age, race, historical and recent diagnoses, dermatologic changes, creatine kinase levels, myositis-specific antibodies, and pathologic characteristics, among others.

Based on that analysis, they identified four subgroups corresponding to known entities: Dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome.

Using decisional algorithm trees, investigators found that myositis-specific antibodies “played a key role in estimating connection to a cluster,” while by contrast, the pathologic data were “dispensable,” Dr. Mariampillai and her associates said.

The best tree omitted variables related to muscle biopsy and had a 78% correct estimation looking just at antisynthetase antibodies, dermatomyositis rash, and finger flexor scores of 3 or less, investigators said.

“The classification quality of the tree was appreciated on the basis of all classification criteria, with an overall sensitivity of 77.0% and a specificity of 92.0%,” the investigators said.

Patients with polymyositis were present in the study data, but fell mainly in the clusters corresponding to immune-mediated necrotizing myopathy and antisynthetase syndrome.

“This finding indicates that patients with polymyositis do not represent a subgroup of patients, and use of this term should probably be discontinued,” Dr. Mariampillai and coinvestigators said.

The study was supported by Association Française contre les Myopathies, and by CSL Behring, which partly funded the development of electronic case report forms. Dr. Mariampillai and colleagues reported no conflicts of interest related to this work.

SOURCE: Mariampillai K, et al. JAMA Neurol. 2018 Sep 10. doi: 10.1001/jamaneurol.2018.2598.

Youths with opioid use disorder (OUD) are more likely to remain in care if they receive medications to treat the condition, but very few are receiving them, results of a retrospective cohort study suggest.

Hailshadow/iStock/Getty Images

Prescribing buprenorphine, naltrexone, or methadone soon after an OUD diagnosis in this study was associated with increased retention in care for adolescents and young adults.

However, medications were provided to just 1 in 4 youths overall in the study, and only 1 in 21 adolescents, according to Scott E. Hadland, MD, MPH, MS, of Grayken Center for Addiction and Department of Pediatrics, Boston Medical Center, and coinvestigators.

These findings highlight a crucial need to improve care of youths with opioid use disorder (OUD) and enhance retention in treatment, Dr. Hadland and coauthors said in JAMA Pediatrics.

“As deaths from overdose increase among U.S. youths, it is vital that clinicians, researchers, and policy makers ensure that access to evidence-based OUD medications for young people remains a national priority,” they said. Their study, based on Medicaid enrollment and claims data from 11 states, included 4,837 youths aged 13-22 years with a diagnosis of OUD. The median age at diagnosis was 20 years, and 2,752 of the youths were female.

Timely buprenorphine, naltrexone, or methadone were received by just 34 out of 728 adolescents (4.7%) and 1,105 out of 4,109 young adults (27%). Most received buprenorphine (82%), while 12% got naltrexone and 6% got methadone. Treatment was considered timely if received within 3 months, and most patients received this treatment within 1 month.

Youths who received timely OUD medications were more likely to be retained in addiction treatment, the investigators found. Median retention in care was 67 days for youths who received behavioral health services only, compared with 123 days for those who received buprenorphine, 150 days for naltrexone, and 324 days for methadone.

Youths receiving buprenorphine were 42% less likely to discontinue addiction treatment, compared with those receiving behavioral services only, while those receiving naltrexone were 46% less likely to discontinue, and those receiving methadone were 68% less likely to discontinue.

Similarly, median duration of behavioral health services was longer for youths who received OUD medications versus those who did not, they added.

Retention in care is critical to successful addiction treatment, according to Dr. Hadland and coauthors.“Even when patients do not reduce their substance use, individuals engaged and retained in care can receive harm-reduction services and treatment of comorbid medical and psychiatric conditions.”

The benefit of that approach is affirmed by results of a recent meta-analysis in adults showing that staying in treatment was associated with reduced all-cause mortality and mortality from overdose, they said.

Dr. Hadland and coauthors reported no conflicts of interest related to the study. Researchers were supported by grants from the National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA), a grant from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Thrasher Research Fund Early Career Award, and the Academic Pediatric Association Young Investigator Award.
 

SOURCE: Hadland SE, et al. JAMA Pediatr. 2018 Sep 10. doi:10.1001/jamapediatrics.2018.2143.

Youths with opioid use disorder (OUD) are more likely to remain in care if they receive medications to treat the condition, but very few are receiving them, results of a retrospective cohort study suggest.

Hailshadow/iStock/Getty Images

Prescribing buprenorphine, naltrexone, or methadone soon after an OUD diagnosis in this study was associated with increased retention in care for adolescents and young adults.

However, medications were provided to just 1 in 4 youths overall in the study, and only 1 in 21 adolescents, according to Scott E. Hadland, MD, MPH, MS, of Grayken Center for Addiction and Department of Pediatrics, Boston Medical Center, and coinvestigators.

These findings highlight a crucial need to improve care of youths with opioid use disorder (OUD) and enhance retention in treatment, Dr. Hadland and coauthors said in JAMA Pediatrics.

“As deaths from overdose increase among U.S. youths, it is vital that clinicians, researchers, and policy makers ensure that access to evidence-based OUD medications for young people remains a national priority,” they said. Their study, based on Medicaid enrollment and claims data from 11 states, included 4,837 youths aged 13-22 years with a diagnosis of OUD. The median age at diagnosis was 20 years, and 2,752 of the youths were female.

Timely buprenorphine, naltrexone, or methadone were received by just 34 out of 728 adolescents (4.7%) and 1,105 out of 4,109 young adults (27%). Most received buprenorphine (82%), while 12% got naltrexone and 6% got methadone. Treatment was considered timely if received within 3 months, and most patients received this treatment within 1 month.

Youths who received timely OUD medications were more likely to be retained in addiction treatment, the investigators found. Median retention in care was 67 days for youths who received behavioral health services only, compared with 123 days for those who received buprenorphine, 150 days for naltrexone, and 324 days for methadone.

Youths receiving buprenorphine were 42% less likely to discontinue addiction treatment, compared with those receiving behavioral services only, while those receiving naltrexone were 46% less likely to discontinue, and those receiving methadone were 68% less likely to discontinue.

Similarly, median duration of behavioral health services was longer for youths who received OUD medications versus those who did not, they added.

Retention in care is critical to successful addiction treatment, according to Dr. Hadland and coauthors.“Even when patients do not reduce their substance use, individuals engaged and retained in care can receive harm-reduction services and treatment of comorbid medical and psychiatric conditions.”

The benefit of that approach is affirmed by results of a recent meta-analysis in adults showing that staying in treatment was associated with reduced all-cause mortality and mortality from overdose, they said.

Dr. Hadland and coauthors reported no conflicts of interest related to the study. Researchers were supported by grants from the National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA), a grant from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Thrasher Research Fund Early Career Award, and the Academic Pediatric Association Young Investigator Award.
 

SOURCE: Hadland SE, et al. JAMA Pediatr. 2018 Sep 10. doi:10.1001/jamapediatrics.2018.2143.

Youths with opioid use disorder (OUD) are more likely to remain in care if they receive medications to treat the condition, but very few are receiving them, results of a retrospective cohort study suggest.

Hailshadow/iStock/Getty Images

Prescribing buprenorphine, naltrexone, or methadone soon after an OUD diagnosis in this study was associated with increased retention in care for adolescents and young adults.

However, medications were provided to just 1 in 4 youths overall in the study, and only 1 in 21 adolescents, according to Scott E. Hadland, MD, MPH, MS, of Grayken Center for Addiction and Department of Pediatrics, Boston Medical Center, and coinvestigators.

These findings highlight a crucial need to improve care of youths with opioid use disorder (OUD) and enhance retention in treatment, Dr. Hadland and coauthors said in JAMA Pediatrics.

“As deaths from overdose increase among U.S. youths, it is vital that clinicians, researchers, and policy makers ensure that access to evidence-based OUD medications for young people remains a national priority,” they said. Their study, based on Medicaid enrollment and claims data from 11 states, included 4,837 youths aged 13-22 years with a diagnosis of OUD. The median age at diagnosis was 20 years, and 2,752 of the youths were female.

Timely buprenorphine, naltrexone, or methadone were received by just 34 out of 728 adolescents (4.7%) and 1,105 out of 4,109 young adults (27%). Most received buprenorphine (82%), while 12% got naltrexone and 6% got methadone. Treatment was considered timely if received within 3 months, and most patients received this treatment within 1 month.

Youths who received timely OUD medications were more likely to be retained in addiction treatment, the investigators found. Median retention in care was 67 days for youths who received behavioral health services only, compared with 123 days for those who received buprenorphine, 150 days for naltrexone, and 324 days for methadone.

Youths receiving buprenorphine were 42% less likely to discontinue addiction treatment, compared with those receiving behavioral services only, while those receiving naltrexone were 46% less likely to discontinue, and those receiving methadone were 68% less likely to discontinue.

Similarly, median duration of behavioral health services was longer for youths who received OUD medications versus those who did not, they added.

Retention in care is critical to successful addiction treatment, according to Dr. Hadland and coauthors.“Even when patients do not reduce their substance use, individuals engaged and retained in care can receive harm-reduction services and treatment of comorbid medical and psychiatric conditions.”

The benefit of that approach is affirmed by results of a recent meta-analysis in adults showing that staying in treatment was associated with reduced all-cause mortality and mortality from overdose, they said.

Dr. Hadland and coauthors reported no conflicts of interest related to the study. Researchers were supported by grants from the National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA), a grant from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Thrasher Research Fund Early Career Award, and the Academic Pediatric Association Young Investigator Award.
 

SOURCE: Hadland SE, et al. JAMA Pediatr. 2018 Sep 10. doi:10.1001/jamapediatrics.2018.2143.

Photo by Rhoda Baer

Experts have published updated guidelines on antimicrobial prophylaxis for adults with cancer-related immunosuppression.

The guidelines include antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions, such as hand hygiene, that may reduce infection risk.

The guidelines were developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA) and published in the Journal of Clinical Oncology.

For the most part, the expert panel that created these guidelines endorsed the previous ASCO recommendations, published in 2013.

However, the panel considered six new studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Recommendations

The ASCO/IDSA guidelines say health care providers should systematically assess the risk of febrile neutropenia, taking into account patient-, cancer-, and treatment-related factors.

Fluoroquinolone prophylaxis is recommended for patients at high risk of febrile neutropenia or profound, protracted neutropenia. This includes most patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and patients undergoing hematopoietic stem cell transplant (HSCT) who are treated with myeloablative conditioning regimens.

Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk of profound, protracted neutropenia, which includes HSCT recipients and most patients with AML/MDS.

However, neither antifungal nor antibiotic prophylaxis are routinely recommended for patients with solid tumors.

Prophylaxis with a nucleoside analog, such as acyclovir, is recommended in patients who are herpes simplex virus–seropositive and are undergoing allogeneic HSCT or leukemia induction.

Pneumocystis jirovecii prophylaxis, such as trimethoprim-sulfamethoxazole, is recommended for patients receiving chemotherapy regimens associated with a greater than 3.5% risk for pneumonia from P jirovecii.

Treatment with a nucleoside reverse transcription inhibitor, such as entecavir or tenofovir, is recommended for patients at high risk of hepatitis B virus reactivation.

Yearly influenza vaccination with an inactivated quadrivalent vaccine is recommended for all patients undergoing chemotherapy for malignancy as well as their family members, household contacts, and health care providers.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce the risk of pathogen transmission, according to the guidelines.

The guidelines also note that outpatients who develop neutropenia following cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores.

The guidelines do not recommend interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks. “Evidence of clinical benefit is lacking” for those interventions, the expert panel said.

Members of the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.

Photo by Rhoda Baer

Experts have published updated guidelines on antimicrobial prophylaxis for adults with cancer-related immunosuppression.

The guidelines include antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions, such as hand hygiene, that may reduce infection risk.

The guidelines were developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA) and published in the Journal of Clinical Oncology.

For the most part, the expert panel that created these guidelines endorsed the previous ASCO recommendations, published in 2013.

However, the panel considered six new studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Recommendations

The ASCO/IDSA guidelines say health care providers should systematically assess the risk of febrile neutropenia, taking into account patient-, cancer-, and treatment-related factors.

Fluoroquinolone prophylaxis is recommended for patients at high risk of febrile neutropenia or profound, protracted neutropenia. This includes most patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and patients undergoing hematopoietic stem cell transplant (HSCT) who are treated with myeloablative conditioning regimens.

Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk of profound, protracted neutropenia, which includes HSCT recipients and most patients with AML/MDS.

However, neither antifungal nor antibiotic prophylaxis are routinely recommended for patients with solid tumors.

Prophylaxis with a nucleoside analog, such as acyclovir, is recommended in patients who are herpes simplex virus–seropositive and are undergoing allogeneic HSCT or leukemia induction.

Pneumocystis jirovecii prophylaxis, such as trimethoprim-sulfamethoxazole, is recommended for patients receiving chemotherapy regimens associated with a greater than 3.5% risk for pneumonia from P jirovecii.

Treatment with a nucleoside reverse transcription inhibitor, such as entecavir or tenofovir, is recommended for patients at high risk of hepatitis B virus reactivation.

Yearly influenza vaccination with an inactivated quadrivalent vaccine is recommended for all patients undergoing chemotherapy for malignancy as well as their family members, household contacts, and health care providers.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce the risk of pathogen transmission, according to the guidelines.

The guidelines also note that outpatients who develop neutropenia following cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores.

The guidelines do not recommend interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks. “Evidence of clinical benefit is lacking” for those interventions, the expert panel said.

Members of the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.

Photo by Rhoda Baer

Experts have published updated guidelines on antimicrobial prophylaxis for adults with cancer-related immunosuppression.

The guidelines include antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions, such as hand hygiene, that may reduce infection risk.

The guidelines were developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA) and published in the Journal of Clinical Oncology.

For the most part, the expert panel that created these guidelines endorsed the previous ASCO recommendations, published in 2013.

However, the panel considered six new studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Recommendations

The ASCO/IDSA guidelines say health care providers should systematically assess the risk of febrile neutropenia, taking into account patient-, cancer-, and treatment-related factors.

Fluoroquinolone prophylaxis is recommended for patients at high risk of febrile neutropenia or profound, protracted neutropenia. This includes most patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and patients undergoing hematopoietic stem cell transplant (HSCT) who are treated with myeloablative conditioning regimens.

Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk of profound, protracted neutropenia, which includes HSCT recipients and most patients with AML/MDS.

However, neither antifungal nor antibiotic prophylaxis are routinely recommended for patients with solid tumors.

Prophylaxis with a nucleoside analog, such as acyclovir, is recommended in patients who are herpes simplex virus–seropositive and are undergoing allogeneic HSCT or leukemia induction.

Pneumocystis jirovecii prophylaxis, such as trimethoprim-sulfamethoxazole, is recommended for patients receiving chemotherapy regimens associated with a greater than 3.5% risk for pneumonia from P jirovecii.

Treatment with a nucleoside reverse transcription inhibitor, such as entecavir or tenofovir, is recommended for patients at high risk of hepatitis B virus reactivation.

Yearly influenza vaccination with an inactivated quadrivalent vaccine is recommended for all patients undergoing chemotherapy for malignancy as well as their family members, household contacts, and health care providers.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce the risk of pathogen transmission, according to the guidelines.

The guidelines also note that outpatients who develop neutropenia following cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores.

The guidelines do not recommend interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks. “Evidence of clinical benefit is lacking” for those interventions, the expert panel said.

Members of the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.

Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.

By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).

The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.

Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.

For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.

That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.

However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.

Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.

Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).

Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.

By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.

Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.

However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.

“Evidence of clinical benefit is lacking” for those interventions, they said.

Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
 

SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.

Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.

By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).

The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.

Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.

For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.

That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.

However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.

Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.

Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).

Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.

By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.

Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.

However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.

“Evidence of clinical benefit is lacking” for those interventions, they said.

Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
 

SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.

Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.

By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).

The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.

Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.

For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.

That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.

However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.

Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.

Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).

Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.

By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.

Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.

However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.

“Evidence of clinical benefit is lacking” for those interventions, they said.

Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
 

SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.

Micrograph showing CLL

Extended follow-up of the RESONATE-2 trial showed that first-line ibrutinib sustained efficacy in elderly patients with chronic lymphocytic leukemia (CLL).

Patients who received ibrutinib had a long-term progression-free survival benefit over those who received chlorambucil.

The depth of response to ibrutinib improved over time, which meant there was a substantial increase in the proportion of patients achieving complete response.

Additionally, rates of some serious adverse events associated with ibrutinib decreased over time.

Paul M. Barr, MD, of the University of Rochester in New York, and his colleagues reported these findings in Haematologica.

Previously reported results of the RESONATE-2 trial, which showed an 84% reduction in the risk of death for ibrutinib versus chlorambucil, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized to receive ibrutinib (n=136) or chlorambucil (n=133).

At a median follow-up of 29 months, 79% (107/136) of patients remained on ibrutinib.

There was an 88% reduction in the risk of progression or death for patients randomized to ibrutinib (P<0.0001).

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months to 15% at 24 months and 18% at 36 months (maximum follow-up).

The overall response rate (ORR) with ibrutinib was 92%, with comparable findings in high-risk subgroups. The ORR was 100% in patients with del(11q) and 95% in those with unmutated IGHV.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42%, compared to 7% of patients who received chlorambucil.

Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients and 52% in chlorambucil recipients, with complete resolution in 56% and 22%, respectively.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time.

The rate of grade 3 or higher neutropenia decreased from 8.1% in the first 12 months of treatment to 0% in the third year. The rate of grade 3 or higher anemia decreased from 5.9% to 1%. And the rate of grade 3 or higher thrombocytopenia decreased from 2.2% to 0%.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up. However, investigators said ibrutinib dose reductions and discontinuations because of this adverse event were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

This study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

Micrograph showing CLL

Extended follow-up of the RESONATE-2 trial showed that first-line ibrutinib sustained efficacy in elderly patients with chronic lymphocytic leukemia (CLL).

Patients who received ibrutinib had a long-term progression-free survival benefit over those who received chlorambucil.

The depth of response to ibrutinib improved over time, which meant there was a substantial increase in the proportion of patients achieving complete response.

Additionally, rates of some serious adverse events associated with ibrutinib decreased over time.

Paul M. Barr, MD, of the University of Rochester in New York, and his colleagues reported these findings in Haematologica.

Previously reported results of the RESONATE-2 trial, which showed an 84% reduction in the risk of death for ibrutinib versus chlorambucil, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized to receive ibrutinib (n=136) or chlorambucil (n=133).

At a median follow-up of 29 months, 79% (107/136) of patients remained on ibrutinib.

There was an 88% reduction in the risk of progression or death for patients randomized to ibrutinib (P<0.0001).

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months to 15% at 24 months and 18% at 36 months (maximum follow-up).

The overall response rate (ORR) with ibrutinib was 92%, with comparable findings in high-risk subgroups. The ORR was 100% in patients with del(11q) and 95% in those with unmutated IGHV.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42%, compared to 7% of patients who received chlorambucil.

Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients and 52% in chlorambucil recipients, with complete resolution in 56% and 22%, respectively.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time.

The rate of grade 3 or higher neutropenia decreased from 8.1% in the first 12 months of treatment to 0% in the third year. The rate of grade 3 or higher anemia decreased from 5.9% to 1%. And the rate of grade 3 or higher thrombocytopenia decreased from 2.2% to 0%.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up. However, investigators said ibrutinib dose reductions and discontinuations because of this adverse event were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

This study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

Micrograph showing CLL

Extended follow-up of the RESONATE-2 trial showed that first-line ibrutinib sustained efficacy in elderly patients with chronic lymphocytic leukemia (CLL).

Patients who received ibrutinib had a long-term progression-free survival benefit over those who received chlorambucil.

The depth of response to ibrutinib improved over time, which meant there was a substantial increase in the proportion of patients achieving complete response.

Additionally, rates of some serious adverse events associated with ibrutinib decreased over time.

Paul M. Barr, MD, of the University of Rochester in New York, and his colleagues reported these findings in Haematologica.

Previously reported results of the RESONATE-2 trial, which showed an 84% reduction in the risk of death for ibrutinib versus chlorambucil, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized to receive ibrutinib (n=136) or chlorambucil (n=133).

At a median follow-up of 29 months, 79% (107/136) of patients remained on ibrutinib.

There was an 88% reduction in the risk of progression or death for patients randomized to ibrutinib (P<0.0001).

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months to 15% at 24 months and 18% at 36 months (maximum follow-up).

The overall response rate (ORR) with ibrutinib was 92%, with comparable findings in high-risk subgroups. The ORR was 100% in patients with del(11q) and 95% in those with unmutated IGHV.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42%, compared to 7% of patients who received chlorambucil.

Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients and 52% in chlorambucil recipients, with complete resolution in 56% and 22%, respectively.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time.

The rate of grade 3 or higher neutropenia decreased from 8.1% in the first 12 months of treatment to 0% in the third year. The rate of grade 3 or higher anemia decreased from 5.9% to 1%. And the rate of grade 3 or higher thrombocytopenia decreased from 2.2% to 0%.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up. However, investigators said ibrutinib dose reductions and discontinuations because of this adverse event were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

This study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

Decreased quality of life attributed to eating disorder symptoms among college students may in fact be related to comorbid depression, results of a recent analysis suggest.

Depression scores and shape concerns both accounted for significant variance in quality of life scores in the analysis. However, depression scores accounted for nearly 10% of the variance, while shape concerns accounted for less than 1%, according to graduate student Paige J. Trojanowski and associate professor Sarah Fischer, PhD, both of the department of psychology at George Mason University, Fairfax, Va.

“Considering the low base rate of eating disorders, interventions to improve student quality of life that target depression may yield more widespread results than those focused on targeting weight or eating concerns,” Ms. Trojanowski and Dr. Fischer reported in Eating Behaviors. Targeting depression might unintentionally improve quality of life in students with disordered eating or body image concerns, they added, noting that depression and eating disorders often are comorbid.

Previous studies looking at relationships between exercise, disordered eating, and quality of life have not included depressive symptoms. Thus, the investigators analyzed the relative impact of depression, eating disorder symptoms, and exercise on Quality of Life Inventory (QOLI) scores in a sample of 851 college students (mean age, about 19 years), three-quarters of whom identified as white. Most of the participants were women (n = 676).

Nearly 90% of the students reported some level of physical activity in the past month, with a mean of 885 minutes. Scores on the Beck Depression Inventory-II (BDI-II) ranged from 0 to 57, with 13.5%, 7.4% and 3.4% falling in the mild, moderate, and severe depression ranges, respectively.

A regression model developed as part of the analysis explained 28.9% of the variance in QOLI scores, Ms. Trojanowski and Dr. Fischer wrote.

Shape concern was the only symptom on the Eating Disorder Examination Questionnaire that had a significant effect on quality of life (P = .005). In addition, BDI-II scores accounted for significant variance (P less than .001).

However, only 0.77% of the total variance in QOLI scores was accounted for by unique variance in shape concern, while 9.55% was accounted for by unique variance in depressive symptoms, their analysis showed.

“While clinical level eating disorders are present on college campuses and deserve specific attention to reduce their significant negative effect on QOL in those students, these results show that depressive symptoms may have a more significant impact on the quality of life of college students at large,” they wrote.

Exercise frequency was not related to quality of life, after accounting for the contribution of eating disorder symptoms. However, exercising for mood improvement or enjoyment was significantly associated with quality of life, Ms. Trojanowski and Dr. Fischer reported. In the final model, identifying as a woman was tied to a lower quality of life.

“Future studies should examine exercising for reasons of enjoyment as a protective factor against decreased QOL in college students,” they wrote.

Limitations cited include the study’s cross-sectional design and the investigators’ reliance on self-report questionnaires.

The authors reported no conflicts of interest or research funding.

SOURCE: Trojanowski PJ et al. Eat Behav. 2018 Aug 18. doi: 10.1016/j.eatbeh.2018.08.005.

Decreased quality of life attributed to eating disorder symptoms among college students may in fact be related to comorbid depression, results of a recent analysis suggest.

Depression scores and shape concerns both accounted for significant variance in quality of life scores in the analysis. However, depression scores accounted for nearly 10% of the variance, while shape concerns accounted for less than 1%, according to graduate student Paige J. Trojanowski and associate professor Sarah Fischer, PhD, both of the department of psychology at George Mason University, Fairfax, Va.

“Considering the low base rate of eating disorders, interventions to improve student quality of life that target depression may yield more widespread results than those focused on targeting weight or eating concerns,” Ms. Trojanowski and Dr. Fischer reported in Eating Behaviors. Targeting depression might unintentionally improve quality of life in students with disordered eating or body image concerns, they added, noting that depression and eating disorders often are comorbid.

Previous studies looking at relationships between exercise, disordered eating, and quality of life have not included depressive symptoms. Thus, the investigators analyzed the relative impact of depression, eating disorder symptoms, and exercise on Quality of Life Inventory (QOLI) scores in a sample of 851 college students (mean age, about 19 years), three-quarters of whom identified as white. Most of the participants were women (n = 676).

Nearly 90% of the students reported some level of physical activity in the past month, with a mean of 885 minutes. Scores on the Beck Depression Inventory-II (BDI-II) ranged from 0 to 57, with 13.5%, 7.4% and 3.4% falling in the mild, moderate, and severe depression ranges, respectively.

A regression model developed as part of the analysis explained 28.9% of the variance in QOLI scores, Ms. Trojanowski and Dr. Fischer wrote.

Shape concern was the only symptom on the Eating Disorder Examination Questionnaire that had a significant effect on quality of life (P = .005). In addition, BDI-II scores accounted for significant variance (P less than .001).

However, only 0.77% of the total variance in QOLI scores was accounted for by unique variance in shape concern, while 9.55% was accounted for by unique variance in depressive symptoms, their analysis showed.

“While clinical level eating disorders are present on college campuses and deserve specific attention to reduce their significant negative effect on QOL in those students, these results show that depressive symptoms may have a more significant impact on the quality of life of college students at large,” they wrote.

Exercise frequency was not related to quality of life, after accounting for the contribution of eating disorder symptoms. However, exercising for mood improvement or enjoyment was significantly associated with quality of life, Ms. Trojanowski and Dr. Fischer reported. In the final model, identifying as a woman was tied to a lower quality of life.

“Future studies should examine exercising for reasons of enjoyment as a protective factor against decreased QOL in college students,” they wrote.

Limitations cited include the study’s cross-sectional design and the investigators’ reliance on self-report questionnaires.

The authors reported no conflicts of interest or research funding.

SOURCE: Trojanowski PJ et al. Eat Behav. 2018 Aug 18. doi: 10.1016/j.eatbeh.2018.08.005.

Decreased quality of life attributed to eating disorder symptoms among college students may in fact be related to comorbid depression, results of a recent analysis suggest.

Depression scores and shape concerns both accounted for significant variance in quality of life scores in the analysis. However, depression scores accounted for nearly 10% of the variance, while shape concerns accounted for less than 1%, according to graduate student Paige J. Trojanowski and associate professor Sarah Fischer, PhD, both of the department of psychology at George Mason University, Fairfax, Va.

“Considering the low base rate of eating disorders, interventions to improve student quality of life that target depression may yield more widespread results than those focused on targeting weight or eating concerns,” Ms. Trojanowski and Dr. Fischer reported in Eating Behaviors. Targeting depression might unintentionally improve quality of life in students with disordered eating or body image concerns, they added, noting that depression and eating disorders often are comorbid.

Previous studies looking at relationships between exercise, disordered eating, and quality of life have not included depressive symptoms. Thus, the investigators analyzed the relative impact of depression, eating disorder symptoms, and exercise on Quality of Life Inventory (QOLI) scores in a sample of 851 college students (mean age, about 19 years), three-quarters of whom identified as white. Most of the participants were women (n = 676).

Nearly 90% of the students reported some level of physical activity in the past month, with a mean of 885 minutes. Scores on the Beck Depression Inventory-II (BDI-II) ranged from 0 to 57, with 13.5%, 7.4% and 3.4% falling in the mild, moderate, and severe depression ranges, respectively.

A regression model developed as part of the analysis explained 28.9% of the variance in QOLI scores, Ms. Trojanowski and Dr. Fischer wrote.

Shape concern was the only symptom on the Eating Disorder Examination Questionnaire that had a significant effect on quality of life (P = .005). In addition, BDI-II scores accounted for significant variance (P less than .001).

However, only 0.77% of the total variance in QOLI scores was accounted for by unique variance in shape concern, while 9.55% was accounted for by unique variance in depressive symptoms, their analysis showed.

“While clinical level eating disorders are present on college campuses and deserve specific attention to reduce their significant negative effect on QOL in those students, these results show that depressive symptoms may have a more significant impact on the quality of life of college students at large,” they wrote.

Exercise frequency was not related to quality of life, after accounting for the contribution of eating disorder symptoms. However, exercising for mood improvement or enjoyment was significantly associated with quality of life, Ms. Trojanowski and Dr. Fischer reported. In the final model, identifying as a woman was tied to a lower quality of life.

“Future studies should examine exercising for reasons of enjoyment as a protective factor against decreased QOL in college students,” they wrote.

Limitations cited include the study’s cross-sectional design and the investigators’ reliance on self-report questionnaires.

The authors reported no conflicts of interest or research funding.

SOURCE: Trojanowski PJ et al. Eat Behav. 2018 Aug 18. doi: 10.1016/j.eatbeh.2018.08.005.

The infliximab-dyyb biosimilar was only moderately less expensive than the originator infliximab product Remicade in the United States in 2017 under Medicare Part D, an analysis shows.

Thinkstock Photos

Infliximab-dyyb (Inflectra) cost 18% less than infliximab, with an annual cost exceeding $14,000 in an analysis published online Sept. 4 in JAMA by Jinoos Yazdany, MD, of the division of rheumatology at the University of California, San Francisco, and her coauthors.

However, “without biosimilar gap discounts in 2017, beneficiaries would have paid more than $5,100 for infliximab-dyyb, or nearly $1,700 more in projected out-of-pocket costs than infliximab,” Dr. Yazdany and her coauthors wrote.

Biologics represent only 2% of U.S. prescriptions but made up 38% of drug spending in 2015 and accounted for 70% of growth in drug spending from 2010 to 2015, according to Dr. Yazdany and her colleagues.

Biologics for rheumatoid arthritis (RA) cost more than $14,000 per year, and in 2015, 3 were among the top 15 drugs in terms of Medicare expenditures, they added.

While biosimilars are supposed to increase competition and lower prices, it’s an open question whether they actually reduce out-of-pocket expenditures for the 43 million individuals with drug benefits under Medicare Part D.

That uncertainty is due in part to the complex cost-sharing design of Part D, which includes an initial deductible, a coverage phase, a coverage gap, and catastrophic coverage.

In 2017, the plan included an initial $400 deductible, followed by the coverage phase, in which the patient paid 25% of drug costs. In the coverage gap, which started at $3,700 in total drug costs, the patient’s share of drug costs increased to 40% for biologics, and 51% for biosimilars. In the catastrophic coverage phase, triggered when out-of-pocket costs exceeded $4,950, the patient was responsible for 5% of drug costs.

“Currently, beneficiaries receive a 50% manufacturer discount during the gap for brand-name drugs and biologics, but not for biosimilars,” Dr. Yazdany and her coauthors said in the report.

To evaluate cost-sharing for infliximab-dyyb, which in 2016 became the first available RA biosimilar, the authors analyzed data for all Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.

Out of 2,547 plans, only 10% covered the biosimilar, while 96% covered infliximab, the authors found.

The mean total cost of infliximab-dyyb was “modestly lower,” they reported. Eight-week prescription costs were $2,185 for infliximab-dyyb versus $2,667 for infliximab, while annual costs were $14,202 for the biosimilar and $17,335 for infliximab.

However, all plans required coinsurance cost-sharing for the biosimilar, they said. The mean coinsurance rate was 26.6% of the total drug cost for the biosimilar and 28.4% for infliximab.

For beneficiaries, projected annual out-of-pocket costs without the gap discount were $5,118 for infliximab-dyyb and $3,432 for infliximab, the researchers said.

Biosimilar gap discounts are set to start in 2019, according to the authors. However, they said those discounts may not substantially reduce out-of-pocket costs for Part D beneficiaries because of the high price of infliximab-dyyb and a coinsurance cost-sharing rate similar to that of infliximab.

“Further policies are needed to address affordability and access to specialty drugs,” Dr. Yazdany and her coauthors concluded.

The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. Dr. Yazdany reported receiving an independent investigator award from Pfizer. Her coauthors reported no conflict of interest disclosures.

SOURCE: Yazdany J et al. JAMA. 2018;320(9):931-3.

The infliximab-dyyb biosimilar was only moderately less expensive than the originator infliximab product Remicade in the United States in 2017 under Medicare Part D, an analysis shows.

Thinkstock Photos

Infliximab-dyyb (Inflectra) cost 18% less than infliximab, with an annual cost exceeding $14,000 in an analysis published online Sept. 4 in JAMA by Jinoos Yazdany, MD, of the division of rheumatology at the University of California, San Francisco, and her coauthors.

However, “without biosimilar gap discounts in 2017, beneficiaries would have paid more than $5,100 for infliximab-dyyb, or nearly $1,700 more in projected out-of-pocket costs than infliximab,” Dr. Yazdany and her coauthors wrote.

Biologics represent only 2% of U.S. prescriptions but made up 38% of drug spending in 2015 and accounted for 70% of growth in drug spending from 2010 to 2015, according to Dr. Yazdany and her colleagues.

Biologics for rheumatoid arthritis (RA) cost more than $14,000 per year, and in 2015, 3 were among the top 15 drugs in terms of Medicare expenditures, they added.

While biosimilars are supposed to increase competition and lower prices, it’s an open question whether they actually reduce out-of-pocket expenditures for the 43 million individuals with drug benefits under Medicare Part D.

That uncertainty is due in part to the complex cost-sharing design of Part D, which includes an initial deductible, a coverage phase, a coverage gap, and catastrophic coverage.

In 2017, the plan included an initial $400 deductible, followed by the coverage phase, in which the patient paid 25% of drug costs. In the coverage gap, which started at $3,700 in total drug costs, the patient’s share of drug costs increased to 40% for biologics, and 51% for biosimilars. In the catastrophic coverage phase, triggered when out-of-pocket costs exceeded $4,950, the patient was responsible for 5% of drug costs.

“Currently, beneficiaries receive a 50% manufacturer discount during the gap for brand-name drugs and biologics, but not for biosimilars,” Dr. Yazdany and her coauthors said in the report.

To evaluate cost-sharing for infliximab-dyyb, which in 2016 became the first available RA biosimilar, the authors analyzed data for all Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.

Out of 2,547 plans, only 10% covered the biosimilar, while 96% covered infliximab, the authors found.

The mean total cost of infliximab-dyyb was “modestly lower,” they reported. Eight-week prescription costs were $2,185 for infliximab-dyyb versus $2,667 for infliximab, while annual costs were $14,202 for the biosimilar and $17,335 for infliximab.

However, all plans required coinsurance cost-sharing for the biosimilar, they said. The mean coinsurance rate was 26.6% of the total drug cost for the biosimilar and 28.4% for infliximab.

For beneficiaries, projected annual out-of-pocket costs without the gap discount were $5,118 for infliximab-dyyb and $3,432 for infliximab, the researchers said.

Biosimilar gap discounts are set to start in 2019, according to the authors. However, they said those discounts may not substantially reduce out-of-pocket costs for Part D beneficiaries because of the high price of infliximab-dyyb and a coinsurance cost-sharing rate similar to that of infliximab.

“Further policies are needed to address affordability and access to specialty drugs,” Dr. Yazdany and her coauthors concluded.

The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. Dr. Yazdany reported receiving an independent investigator award from Pfizer. Her coauthors reported no conflict of interest disclosures.

SOURCE: Yazdany J et al. JAMA. 2018;320(9):931-3.

The infliximab-dyyb biosimilar was only moderately less expensive than the originator infliximab product Remicade in the United States in 2017 under Medicare Part D, an analysis shows.

Thinkstock Photos

Infliximab-dyyb (Inflectra) cost 18% less than infliximab, with an annual cost exceeding $14,000 in an analysis published online Sept. 4 in JAMA by Jinoos Yazdany, MD, of the division of rheumatology at the University of California, San Francisco, and her coauthors.

However, “without biosimilar gap discounts in 2017, beneficiaries would have paid more than $5,100 for infliximab-dyyb, or nearly $1,700 more in projected out-of-pocket costs than infliximab,” Dr. Yazdany and her coauthors wrote.

Biologics represent only 2% of U.S. prescriptions but made up 38% of drug spending in 2015 and accounted for 70% of growth in drug spending from 2010 to 2015, according to Dr. Yazdany and her colleagues.

Biologics for rheumatoid arthritis (RA) cost more than $14,000 per year, and in 2015, 3 were among the top 15 drugs in terms of Medicare expenditures, they added.

While biosimilars are supposed to increase competition and lower prices, it’s an open question whether they actually reduce out-of-pocket expenditures for the 43 million individuals with drug benefits under Medicare Part D.

That uncertainty is due in part to the complex cost-sharing design of Part D, which includes an initial deductible, a coverage phase, a coverage gap, and catastrophic coverage.

In 2017, the plan included an initial $400 deductible, followed by the coverage phase, in which the patient paid 25% of drug costs. In the coverage gap, which started at $3,700 in total drug costs, the patient’s share of drug costs increased to 40% for biologics, and 51% for biosimilars. In the catastrophic coverage phase, triggered when out-of-pocket costs exceeded $4,950, the patient was responsible for 5% of drug costs.

“Currently, beneficiaries receive a 50% manufacturer discount during the gap for brand-name drugs and biologics, but not for biosimilars,” Dr. Yazdany and her coauthors said in the report.

To evaluate cost-sharing for infliximab-dyyb, which in 2016 became the first available RA biosimilar, the authors analyzed data for all Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.

Out of 2,547 plans, only 10% covered the biosimilar, while 96% covered infliximab, the authors found.

The mean total cost of infliximab-dyyb was “modestly lower,” they reported. Eight-week prescription costs were $2,185 for infliximab-dyyb versus $2,667 for infliximab, while annual costs were $14,202 for the biosimilar and $17,335 for infliximab.

However, all plans required coinsurance cost-sharing for the biosimilar, they said. The mean coinsurance rate was 26.6% of the total drug cost for the biosimilar and 28.4% for infliximab.

For beneficiaries, projected annual out-of-pocket costs without the gap discount were $5,118 for infliximab-dyyb and $3,432 for infliximab, the researchers said.

Biosimilar gap discounts are set to start in 2019, according to the authors. However, they said those discounts may not substantially reduce out-of-pocket costs for Part D beneficiaries because of the high price of infliximab-dyyb and a coinsurance cost-sharing rate similar to that of infliximab.

“Further policies are needed to address affordability and access to specialty drugs,” Dr. Yazdany and her coauthors concluded.

The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. Dr. Yazdany reported receiving an independent investigator award from Pfizer. Her coauthors reported no conflict of interest disclosures.

SOURCE: Yazdany J et al. JAMA. 2018;320(9):931-3.