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Study validates EULAR definition of arthralgia suspicious for progression to RA
Results of a longitudinal study have confirmed that the recently established EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis can help to distinguish patients who are at highest risk for progression from those who do not progress to RA.
Patients clinically suspected of arthralgia who met the definition for arthralgia suspicious for progression to RA displayed an increased risk for arthritis development, compared with patients who did not meet the EULAR definition (hazard ratio, 2.1; 95% confidence interval, 0.9-4.7). The approach had a sensitivity of 83% and positive predictive value of 30%, study head Annette van der Helm–van Mil, MD, reported at the European Congress of Rheumatology in Madrid.
The findings should help investigators looking at early arthritis progression to design better clinical trials by enabling more homogeneous populations of patients to be included, said Dr. van der Helm–van Mil, professor of rheumatology at Leiden University Medical Center and at Erasmus Medical Center in Rotterdam, both in the Netherlands.
“Previous data have shown that rheumatologists do recognize patients at risk for RA based on their clinical expertise and pattern recognition. So, they do recognize patients who have a combination of clinical characteristics that characterize the symptomatic prearthritis stage of RA. (This pattern is also called clinically suspect arthralgia,)” Dr. van der Helm–van Mil said in an interview.
However, the disadvantage of rheumatologists’ use of pattern recognition to identify patients at risk for RA is that it can be subjective, she said.
Several proof-of-concept trials are testing the hypothesis that the disease is more susceptible to disease-modifying treatment in the symptomatic prearthritis phase and that such early treatment might even prevent progression to chronic RA. But, selecting the “correct symptomatic patient” for early treatment with disease-modifying antirheumatic drugs is important, she said. Such a patient does not have clinical arthritis but is truly at risk for RA. Not all arthralgia patients are similar, and the type of arthralgia that is the hallmark for a heightened risk of progression to RA had not been defined formally prior to the EULAR definition.
A EULAR task force sought to provide some objective clarity by defining arthralgia at risk for RA (Ann Rheum Dis. 2017;76:491-6). The process relied on clinical expertise at all stages. However, until now, the definition had not been validated longitudinally. The current study used progression from arthralgia to clinical arthritis or RA as the outcome.
The definition of arthralgia at risk for RA hinges on seven parameters: symptom duration less than 1 year, symptoms in metacarpophalangeal joints, morning stiffness lasting an hour or more, symptoms that are worst in the morning, family history of RA, difficulty forming a fist, and positive squeeze test of metacarpophalangeal joints.
The researchers used those seven parameters to follow 241 Dutch patients considered likely to develop RA and 113 patients with recent-onset arthralgia in small joints who had not been evaluated by rheumatologists and who were referred to secondary care.
“The EULAR definition was developed for use in scientific studies and this definition is immediately applicable for this purpose,” Dr. van der Helm–van Mil said.
“With regards to application in daily practice, the clinical definition should be combined with results of additional investigations to accurately identify imminent RA in the phase of arthralgia. Which combination of markers yields the best accuracy is a subject for further studies,” Dr. van der Helm–van Mil said.
An important aspect of the task force’s definition is that rheumatologists should use it in patients in whom they consider imminent RA more likely than other diagnoses. The definition was not discriminative for RA when the investigators of the current study ignored this entry criterion, leading to a sensitivity of just 10% and positive predictive value of 3%.
“This suggests that the definition should be used in secondary care but may not be useful in primary care. However, more research is needed here,” Dr. van der Helm–van Mil said.
The authors reported no disclosures of interest.
Results of a longitudinal study have confirmed that the recently established EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis can help to distinguish patients who are at highest risk for progression from those who do not progress to RA.
Patients clinically suspected of arthralgia who met the definition for arthralgia suspicious for progression to RA displayed an increased risk for arthritis development, compared with patients who did not meet the EULAR definition (hazard ratio, 2.1; 95% confidence interval, 0.9-4.7). The approach had a sensitivity of 83% and positive predictive value of 30%, study head Annette van der Helm–van Mil, MD, reported at the European Congress of Rheumatology in Madrid.
The findings should help investigators looking at early arthritis progression to design better clinical trials by enabling more homogeneous populations of patients to be included, said Dr. van der Helm–van Mil, professor of rheumatology at Leiden University Medical Center and at Erasmus Medical Center in Rotterdam, both in the Netherlands.
“Previous data have shown that rheumatologists do recognize patients at risk for RA based on their clinical expertise and pattern recognition. So, they do recognize patients who have a combination of clinical characteristics that characterize the symptomatic prearthritis stage of RA. (This pattern is also called clinically suspect arthralgia,)” Dr. van der Helm–van Mil said in an interview.
However, the disadvantage of rheumatologists’ use of pattern recognition to identify patients at risk for RA is that it can be subjective, she said.
Several proof-of-concept trials are testing the hypothesis that the disease is more susceptible to disease-modifying treatment in the symptomatic prearthritis phase and that such early treatment might even prevent progression to chronic RA. But, selecting the “correct symptomatic patient” for early treatment with disease-modifying antirheumatic drugs is important, she said. Such a patient does not have clinical arthritis but is truly at risk for RA. Not all arthralgia patients are similar, and the type of arthralgia that is the hallmark for a heightened risk of progression to RA had not been defined formally prior to the EULAR definition.
A EULAR task force sought to provide some objective clarity by defining arthralgia at risk for RA (Ann Rheum Dis. 2017;76:491-6). The process relied on clinical expertise at all stages. However, until now, the definition had not been validated longitudinally. The current study used progression from arthralgia to clinical arthritis or RA as the outcome.
The definition of arthralgia at risk for RA hinges on seven parameters: symptom duration less than 1 year, symptoms in metacarpophalangeal joints, morning stiffness lasting an hour or more, symptoms that are worst in the morning, family history of RA, difficulty forming a fist, and positive squeeze test of metacarpophalangeal joints.
The researchers used those seven parameters to follow 241 Dutch patients considered likely to develop RA and 113 patients with recent-onset arthralgia in small joints who had not been evaluated by rheumatologists and who were referred to secondary care.
“The EULAR definition was developed for use in scientific studies and this definition is immediately applicable for this purpose,” Dr. van der Helm–van Mil said.
“With regards to application in daily practice, the clinical definition should be combined with results of additional investigations to accurately identify imminent RA in the phase of arthralgia. Which combination of markers yields the best accuracy is a subject for further studies,” Dr. van der Helm–van Mil said.
An important aspect of the task force’s definition is that rheumatologists should use it in patients in whom they consider imminent RA more likely than other diagnoses. The definition was not discriminative for RA when the investigators of the current study ignored this entry criterion, leading to a sensitivity of just 10% and positive predictive value of 3%.
“This suggests that the definition should be used in secondary care but may not be useful in primary care. However, more research is needed here,” Dr. van der Helm–van Mil said.
The authors reported no disclosures of interest.
Results of a longitudinal study have confirmed that the recently established EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis can help to distinguish patients who are at highest risk for progression from those who do not progress to RA.
Patients clinically suspected of arthralgia who met the definition for arthralgia suspicious for progression to RA displayed an increased risk for arthritis development, compared with patients who did not meet the EULAR definition (hazard ratio, 2.1; 95% confidence interval, 0.9-4.7). The approach had a sensitivity of 83% and positive predictive value of 30%, study head Annette van der Helm–van Mil, MD, reported at the European Congress of Rheumatology in Madrid.
The findings should help investigators looking at early arthritis progression to design better clinical trials by enabling more homogeneous populations of patients to be included, said Dr. van der Helm–van Mil, professor of rheumatology at Leiden University Medical Center and at Erasmus Medical Center in Rotterdam, both in the Netherlands.
“Previous data have shown that rheumatologists do recognize patients at risk for RA based on their clinical expertise and pattern recognition. So, they do recognize patients who have a combination of clinical characteristics that characterize the symptomatic prearthritis stage of RA. (This pattern is also called clinically suspect arthralgia,)” Dr. van der Helm–van Mil said in an interview.
However, the disadvantage of rheumatologists’ use of pattern recognition to identify patients at risk for RA is that it can be subjective, she said.
Several proof-of-concept trials are testing the hypothesis that the disease is more susceptible to disease-modifying treatment in the symptomatic prearthritis phase and that such early treatment might even prevent progression to chronic RA. But, selecting the “correct symptomatic patient” for early treatment with disease-modifying antirheumatic drugs is important, she said. Such a patient does not have clinical arthritis but is truly at risk for RA. Not all arthralgia patients are similar, and the type of arthralgia that is the hallmark for a heightened risk of progression to RA had not been defined formally prior to the EULAR definition.
A EULAR task force sought to provide some objective clarity by defining arthralgia at risk for RA (Ann Rheum Dis. 2017;76:491-6). The process relied on clinical expertise at all stages. However, until now, the definition had not been validated longitudinally. The current study used progression from arthralgia to clinical arthritis or RA as the outcome.
The definition of arthralgia at risk for RA hinges on seven parameters: symptom duration less than 1 year, symptoms in metacarpophalangeal joints, morning stiffness lasting an hour or more, symptoms that are worst in the morning, family history of RA, difficulty forming a fist, and positive squeeze test of metacarpophalangeal joints.
The researchers used those seven parameters to follow 241 Dutch patients considered likely to develop RA and 113 patients with recent-onset arthralgia in small joints who had not been evaluated by rheumatologists and who were referred to secondary care.
“The EULAR definition was developed for use in scientific studies and this definition is immediately applicable for this purpose,” Dr. van der Helm–van Mil said.
“With regards to application in daily practice, the clinical definition should be combined with results of additional investigations to accurately identify imminent RA in the phase of arthralgia. Which combination of markers yields the best accuracy is a subject for further studies,” Dr. van der Helm–van Mil said.
An important aspect of the task force’s definition is that rheumatologists should use it in patients in whom they consider imminent RA more likely than other diagnoses. The definition was not discriminative for RA when the investigators of the current study ignored this entry criterion, leading to a sensitivity of just 10% and positive predictive value of 3%.
“This suggests that the definition should be used in secondary care but may not be useful in primary care. However, more research is needed here,” Dr. van der Helm–van Mil said.
The authors reported no disclosures of interest.
FROM THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Patients clinically suspected of arthralgia who met the EULAR definition were twice as likely to develop RA at 2 years than were those who did not meet the definition (hazard ratio, 2.1; 95% confidence interval, 0.9–4.7).
Data source: Longitudinal study of 241 patients considered likely to develop RA and 113 patients with recent-onset arthralgia in small joints who had not been evaluated by rheumatologists and who were referred to secondary care.
Disclosures: The authors reported no disclosures of interest.
Dacomitinib boosts PFS in advanced NSCLC
CHICAGO – The clear advantage goes to the second-generation tyrosine kinase inhibitor in a new trial comparing dacomitinib to gefitinib for advanced non–small cell lung cancer.
In a randomized, open-label phase III trial designed as a head-to-head comparison of the two drugs for the first-line treatment of advanced non–small cell lung cancer (NSCLC), “the blinded, independent review showed that we have a median progression-free survival (PFS) of 14.7 months versus 9.2 months,” said first author Tony Mok, MD, professor and chair of the department of clinical oncology at the Chinese University of Hong Kong. This PFS rate, he said, “is among the highest of randomized phase III trials in the first-line setting.”
Two years into the study, those taking dacomitinib had triple the PFS rate of those on gefitinib (30.6% versus 9.6%). The overall hazard ratio (HR) for PFS with dacomitinib compared to gefitinib was 0.59 (95% confidence interval [CI], 0.47-0.74, P less than .0001).
A previous single-arm phase II trial of the drug, ARCHER 2017, showed a response rate of 75.6% and a median PFS of 18.2 months for patients with NSCLC and an EGFR-activating mutation.
“Based on these data, we thought it was likely that we could have a hypothesis for dacomitinib to be superior to gefitinib, a first-generation TKI [tyrosine kinase inhibitor], in terms of progression-free survival,” Dr. Mok said in a press conference at the annual meeting of the American Society of Clinical Oncology. Dacomitinib is a second-generation TKI.
Patients in the new study, ARCHER 1050, had advanced NSCLC with EGFR-activating mutations and no prior systemic treatment for their advanced disease. In addition, patients had good performance status, could not have had prior TKI exposure, and could not have CNS metastases. This last exclusion, explained Dr. Mok, was because investigators were uncertain about dacomitinib’s CNS penetration at the time of study design, and because gefitinib may also not be the best therapeutic choice for CNS metastases.
Patients were randomized 1:1 to receive either dacomitinib 45 mg orally daily (n = 227), or gefitinib 250 mg orally daily (n = 225). Patients were stratified by whether or not they were ethnically Asian, and by whether they had EGFR mutation of exon 19 or exon 21. Patients were balanced in terms of age, gender, ethnicity, smoking, and performance status between arms. About 75% of the patients were Asian, and 65% were nonsmokers.
The international study enrolled patients from 71 centers in Asia and Europe. At the time of the data cutoff, investigators saw PFS events totaling 59.9% in the dacomitinib arm and 79.6% in the gefitinib arm. Patients were followed for PFS for a median of 22.1 months. “We have relatively mature data,” said Dr. Mok, except for overall survival, with only 36.9% of events occurring at the time of the data cutoff.
The primary endpoint in the open-label trial was PFS in the intention-to-treat population, as assessed by an independent, blinded reviewer. Dr. Mok said that the study was powered to see at least 256 PFS events, and to see an improvement in PFS for dacomitinib that equated to an HR of no more than 0.667. This would translate to median PFS for dacomitinib of 14.3 months versus 9.5 months for gefitinib, values Dr. Mok said were “reasonable.” And, he pointed out, the study results fell almost exactly in line with these predictions, though the actual HR was a bit lower than predicted.
An analysis of PFS by subgroup, also conducted by independent review, found that dacomitinib was favored for all subgroups except for non-Asian patients, for whom the HR was 0.89 but did not reach statistical significance. Since these patients made up about one-fourth of the study population, said Dr. Mok, small sample size was a potential issue. “But we have to ask ourselves the question, do they really perform worse than the Asians, if they have a response?”
To attempt to answer this question, the investigators performed an exploratory analysis of the 72 non-Asian patients who had responded to therapy. Among this group, they saw data similar to that of the overall group, with an HR of 0.547 (95% CI, 0.321-0.933, P less than .0123).
Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate, duration of response, quality of life, and safety assessments.
Objective response rates were similar between arms, at 74.9% for dacomitinib and 71.6% for gefitinib (P = .3883). However, the median duration of response was significantly longer for those on dacomitinib (14.8 versus 8.3 months, P less than .0001).
“This may be best explained by looking into the depth of the response,” said Dr. Mok. Patient-level data showed that dacomitinib patients had a larger reduction in target lesion size; “this may reflect a more potent inhibition of EGFR,” he said.
With the more potent inhibition, however, came more frequent grade 3 adverse events involving diarrhea, dermatitis, stomatitis, and paronychia for those on dacomitinib; however, noted Dr. Mok, serious transaminase elevations were more common in the gefitinib group. “There is no new signal” for concerning toxicity, he said. Dose reductions were more common in dacomitinib than in gefitinib (66.1% versus 18%), but there are two tiers of dose reductions permissible with dacomitinib, giving some flexibility.
Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which sponsored the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – The clear advantage goes to the second-generation tyrosine kinase inhibitor in a new trial comparing dacomitinib to gefitinib for advanced non–small cell lung cancer.
In a randomized, open-label phase III trial designed as a head-to-head comparison of the two drugs for the first-line treatment of advanced non–small cell lung cancer (NSCLC), “the blinded, independent review showed that we have a median progression-free survival (PFS) of 14.7 months versus 9.2 months,” said first author Tony Mok, MD, professor and chair of the department of clinical oncology at the Chinese University of Hong Kong. This PFS rate, he said, “is among the highest of randomized phase III trials in the first-line setting.”
Two years into the study, those taking dacomitinib had triple the PFS rate of those on gefitinib (30.6% versus 9.6%). The overall hazard ratio (HR) for PFS with dacomitinib compared to gefitinib was 0.59 (95% confidence interval [CI], 0.47-0.74, P less than .0001).
A previous single-arm phase II trial of the drug, ARCHER 2017, showed a response rate of 75.6% and a median PFS of 18.2 months for patients with NSCLC and an EGFR-activating mutation.
“Based on these data, we thought it was likely that we could have a hypothesis for dacomitinib to be superior to gefitinib, a first-generation TKI [tyrosine kinase inhibitor], in terms of progression-free survival,” Dr. Mok said in a press conference at the annual meeting of the American Society of Clinical Oncology. Dacomitinib is a second-generation TKI.
Patients in the new study, ARCHER 1050, had advanced NSCLC with EGFR-activating mutations and no prior systemic treatment for their advanced disease. In addition, patients had good performance status, could not have had prior TKI exposure, and could not have CNS metastases. This last exclusion, explained Dr. Mok, was because investigators were uncertain about dacomitinib’s CNS penetration at the time of study design, and because gefitinib may also not be the best therapeutic choice for CNS metastases.
Patients were randomized 1:1 to receive either dacomitinib 45 mg orally daily (n = 227), or gefitinib 250 mg orally daily (n = 225). Patients were stratified by whether or not they were ethnically Asian, and by whether they had EGFR mutation of exon 19 or exon 21. Patients were balanced in terms of age, gender, ethnicity, smoking, and performance status between arms. About 75% of the patients were Asian, and 65% were nonsmokers.
The international study enrolled patients from 71 centers in Asia and Europe. At the time of the data cutoff, investigators saw PFS events totaling 59.9% in the dacomitinib arm and 79.6% in the gefitinib arm. Patients were followed for PFS for a median of 22.1 months. “We have relatively mature data,” said Dr. Mok, except for overall survival, with only 36.9% of events occurring at the time of the data cutoff.
The primary endpoint in the open-label trial was PFS in the intention-to-treat population, as assessed by an independent, blinded reviewer. Dr. Mok said that the study was powered to see at least 256 PFS events, and to see an improvement in PFS for dacomitinib that equated to an HR of no more than 0.667. This would translate to median PFS for dacomitinib of 14.3 months versus 9.5 months for gefitinib, values Dr. Mok said were “reasonable.” And, he pointed out, the study results fell almost exactly in line with these predictions, though the actual HR was a bit lower than predicted.
An analysis of PFS by subgroup, also conducted by independent review, found that dacomitinib was favored for all subgroups except for non-Asian patients, for whom the HR was 0.89 but did not reach statistical significance. Since these patients made up about one-fourth of the study population, said Dr. Mok, small sample size was a potential issue. “But we have to ask ourselves the question, do they really perform worse than the Asians, if they have a response?”
To attempt to answer this question, the investigators performed an exploratory analysis of the 72 non-Asian patients who had responded to therapy. Among this group, they saw data similar to that of the overall group, with an HR of 0.547 (95% CI, 0.321-0.933, P less than .0123).
Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate, duration of response, quality of life, and safety assessments.
Objective response rates were similar between arms, at 74.9% for dacomitinib and 71.6% for gefitinib (P = .3883). However, the median duration of response was significantly longer for those on dacomitinib (14.8 versus 8.3 months, P less than .0001).
“This may be best explained by looking into the depth of the response,” said Dr. Mok. Patient-level data showed that dacomitinib patients had a larger reduction in target lesion size; “this may reflect a more potent inhibition of EGFR,” he said.
With the more potent inhibition, however, came more frequent grade 3 adverse events involving diarrhea, dermatitis, stomatitis, and paronychia for those on dacomitinib; however, noted Dr. Mok, serious transaminase elevations were more common in the gefitinib group. “There is no new signal” for concerning toxicity, he said. Dose reductions were more common in dacomitinib than in gefitinib (66.1% versus 18%), but there are two tiers of dose reductions permissible with dacomitinib, giving some flexibility.
Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which sponsored the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – The clear advantage goes to the second-generation tyrosine kinase inhibitor in a new trial comparing dacomitinib to gefitinib for advanced non–small cell lung cancer.
In a randomized, open-label phase III trial designed as a head-to-head comparison of the two drugs for the first-line treatment of advanced non–small cell lung cancer (NSCLC), “the blinded, independent review showed that we have a median progression-free survival (PFS) of 14.7 months versus 9.2 months,” said first author Tony Mok, MD, professor and chair of the department of clinical oncology at the Chinese University of Hong Kong. This PFS rate, he said, “is among the highest of randomized phase III trials in the first-line setting.”
Two years into the study, those taking dacomitinib had triple the PFS rate of those on gefitinib (30.6% versus 9.6%). The overall hazard ratio (HR) for PFS with dacomitinib compared to gefitinib was 0.59 (95% confidence interval [CI], 0.47-0.74, P less than .0001).
A previous single-arm phase II trial of the drug, ARCHER 2017, showed a response rate of 75.6% and a median PFS of 18.2 months for patients with NSCLC and an EGFR-activating mutation.
“Based on these data, we thought it was likely that we could have a hypothesis for dacomitinib to be superior to gefitinib, a first-generation TKI [tyrosine kinase inhibitor], in terms of progression-free survival,” Dr. Mok said in a press conference at the annual meeting of the American Society of Clinical Oncology. Dacomitinib is a second-generation TKI.
Patients in the new study, ARCHER 1050, had advanced NSCLC with EGFR-activating mutations and no prior systemic treatment for their advanced disease. In addition, patients had good performance status, could not have had prior TKI exposure, and could not have CNS metastases. This last exclusion, explained Dr. Mok, was because investigators were uncertain about dacomitinib’s CNS penetration at the time of study design, and because gefitinib may also not be the best therapeutic choice for CNS metastases.
Patients were randomized 1:1 to receive either dacomitinib 45 mg orally daily (n = 227), or gefitinib 250 mg orally daily (n = 225). Patients were stratified by whether or not they were ethnically Asian, and by whether they had EGFR mutation of exon 19 or exon 21. Patients were balanced in terms of age, gender, ethnicity, smoking, and performance status between arms. About 75% of the patients were Asian, and 65% were nonsmokers.
The international study enrolled patients from 71 centers in Asia and Europe. At the time of the data cutoff, investigators saw PFS events totaling 59.9% in the dacomitinib arm and 79.6% in the gefitinib arm. Patients were followed for PFS for a median of 22.1 months. “We have relatively mature data,” said Dr. Mok, except for overall survival, with only 36.9% of events occurring at the time of the data cutoff.
The primary endpoint in the open-label trial was PFS in the intention-to-treat population, as assessed by an independent, blinded reviewer. Dr. Mok said that the study was powered to see at least 256 PFS events, and to see an improvement in PFS for dacomitinib that equated to an HR of no more than 0.667. This would translate to median PFS for dacomitinib of 14.3 months versus 9.5 months for gefitinib, values Dr. Mok said were “reasonable.” And, he pointed out, the study results fell almost exactly in line with these predictions, though the actual HR was a bit lower than predicted.
An analysis of PFS by subgroup, also conducted by independent review, found that dacomitinib was favored for all subgroups except for non-Asian patients, for whom the HR was 0.89 but did not reach statistical significance. Since these patients made up about one-fourth of the study population, said Dr. Mok, small sample size was a potential issue. “But we have to ask ourselves the question, do they really perform worse than the Asians, if they have a response?”
To attempt to answer this question, the investigators performed an exploratory analysis of the 72 non-Asian patients who had responded to therapy. Among this group, they saw data similar to that of the overall group, with an HR of 0.547 (95% CI, 0.321-0.933, P less than .0123).
Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate, duration of response, quality of life, and safety assessments.
Objective response rates were similar between arms, at 74.9% for dacomitinib and 71.6% for gefitinib (P = .3883). However, the median duration of response was significantly longer for those on dacomitinib (14.8 versus 8.3 months, P less than .0001).
“This may be best explained by looking into the depth of the response,” said Dr. Mok. Patient-level data showed that dacomitinib patients had a larger reduction in target lesion size; “this may reflect a more potent inhibition of EGFR,” he said.
With the more potent inhibition, however, came more frequent grade 3 adverse events involving diarrhea, dermatitis, stomatitis, and paronychia for those on dacomitinib; however, noted Dr. Mok, serious transaminase elevations were more common in the gefitinib group. “There is no new signal” for concerning toxicity, he said. Dose reductions were more common in dacomitinib than in gefitinib (66.1% versus 18%), but there are two tiers of dose reductions permissible with dacomitinib, giving some flexibility.
Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which sponsored the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
AT ASCO 2017
Key clinical point:
Major finding: At 2 years, the dacomitinib arm had triple the PFS rate of the gefitinib arm (30.6% versus 9.6%).
Data source: Randomized, open-label phase III clinical trial of 452 patients who received dacomitinib or gefitinib for first-line therapy for advanced non–small cell lung cancer.
Disclosures: Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which funded the study.
Add-on tofacitinib as good as adalimumab for active RA
MADRID – When it comes to patients with rheumatoid arthritis who are responding inadequately to methotrexate therapy, results of the Oral Rheumatoid Arthritis triaL (ORAL) Strategy study suggest that adding the Janus kinase inhibitor tofacitinib is just as effective as adding the tumor necrosis factor inhibitor adalimumab.
At 6 months’ follow-up, 46% of patients randomized to tofacitinib (Xeljanz) plus methotrexate met the trial’s primary endpoint of an American College of Rheumatology response of at least 50% (ACR50), compared with 44% of those who were given adalimumab (Humira) plus methotrexate. This result met the trial’s prespecified criteria for noninferiority. An ACR50 response means that there was at least 50% improvement in tender or swollen joint counts as well as a 50% improvement in at least three of the other five criteria (acute phase reactant, such as erythrocyte sedimentation rate; patient assessment; physician assessment; pain scale; and disability/functional questionnaire).
Nevertheless, “in circumstances where methotrexate is precluded, tofacitinib monotherapy is a clinically viable option,” lead study author Roy Fleischmann, MD, said at the European Congress of Rheumatology.
“This actually substantiates what I’ve done in clinical practice since [tofacitinib] was approved,” said Dr. Fleischmann, a rheumatologist in group practice in Dallas. “If I have patients on methotrexate and they show an incomplete response, I add tofacitinib; I don’t switch, I add. Then if the patient has a good response – a really good response – then I discontinue [methotrexate].”
Dr. Fleischmann said he does the same when adding a tumor necrosis factor inhibitor to methotrexate and that there are some patients who just do better with combination treatment.
ORAL Strategy was a phase IIIB/IV study that randomized 1,152 adults with active RA, despite treatment for more than 4 months with 15-25 mg/kg of methotrexate per week. Patients had to have four or more painful or tender joints and four or more swollen joints at baseline, and a high-sensitivity C-reactive protein level of 3 mg/L or more.
Patients were randomized to one of the study’s three treatment arms: tofacitinib 5 mg twice daily as monotherapy (n = 384), the same regimen of tofacitinib added to methotrexate (n = 376), or adalimumab 40 mg every 2 weeks added to methotrexate (n = 386). (Two patients in each group did not receive their assigned treatment.) Treatment was for 1 year, and concomitant treatment with nonsteroidal anti-inflammatory drugs, oral glucocorticoids, or both was allowed so long as their doses remained stable and no dose adjustments were necessary.
ACR20 responses were also recorded and were achieved by 65% with tofacitinib monotherapy, 73% with tofacitinib plus methotrexate, and 71% with adalimumab plus methotrexate, and ACR70 responses were 18%, 25%, and 21%, respectively. Comparable improvements from baseline to the end of the study were also seen for Simple Disease Activity Index, Clinical Disease Activity Index, Disease Activity Score in 28 joints using erythrocyte sedimentation rate, and Health Assessment Questionnaire scores in patients given the combination treatments.
The study’s findings were published online (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31618-5) to coincide with their presentation in a late-breaking abstract at the meeting.
“The ORAL Strategy trial highlights three benefits from the combination of tofacitinib and methotrexate in active rheumatoid arthritis,” independent commentators David Scott, MD, and Matt D. Stevenson, PhD, wrote in an editorial (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31659-8).
“First, this combination’s efficacy and toxicity are similar to injectable biologics such as adalimumab,” said Dr. Scott of King’s College London and Dr. Stevenson of the University of Sheffield (England). Indeed, no new side effects were seen, and side effects were consistent with those seen in previous studies.
“Second,” they wrote, “the onset of action of these drugs seems equally rapid. Third, most patients are able to remain on tofacitinib therapy for 12 months.”
Dr. Scott and Dr. Stevenson suggested these findings are “extremely encouraging” as “they show the ongoing benefits of innovation in drug treatment.”
The findings support the previous RA-BEAM trial (N Engl J Med. 2017;376:652-62) with another Janus kinase inhibitor, baricitinib, Dr. Fleischmann said during his presentation, which had also shown combination therapy with methotrexate was perhaps more beneficial than adding adalimumab.
In the Lancet editorial, Dr. Scott and Dr. Stevenson wrote: “Although a combination of [Janus kinase] inhibitors with methotrexate is likely to be the way they are used in clinical practice, monotherapy results in clinical and functional responses, as shown in the ORAL Strategy trial, and thus might be appropriate in some patients.”
The study was funded by Pfizer. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi-Genzyme, and UCB. Dr. Scott has advised Eli Lilly, Roche Products, Napp Pharmaceuticals, Baxalta, and Novartis. Dr. Stevenson did not have any industry disclosures.
MADRID – When it comes to patients with rheumatoid arthritis who are responding inadequately to methotrexate therapy, results of the Oral Rheumatoid Arthritis triaL (ORAL) Strategy study suggest that adding the Janus kinase inhibitor tofacitinib is just as effective as adding the tumor necrosis factor inhibitor adalimumab.
At 6 months’ follow-up, 46% of patients randomized to tofacitinib (Xeljanz) plus methotrexate met the trial’s primary endpoint of an American College of Rheumatology response of at least 50% (ACR50), compared with 44% of those who were given adalimumab (Humira) plus methotrexate. This result met the trial’s prespecified criteria for noninferiority. An ACR50 response means that there was at least 50% improvement in tender or swollen joint counts as well as a 50% improvement in at least three of the other five criteria (acute phase reactant, such as erythrocyte sedimentation rate; patient assessment; physician assessment; pain scale; and disability/functional questionnaire).
Nevertheless, “in circumstances where methotrexate is precluded, tofacitinib monotherapy is a clinically viable option,” lead study author Roy Fleischmann, MD, said at the European Congress of Rheumatology.
“This actually substantiates what I’ve done in clinical practice since [tofacitinib] was approved,” said Dr. Fleischmann, a rheumatologist in group practice in Dallas. “If I have patients on methotrexate and they show an incomplete response, I add tofacitinib; I don’t switch, I add. Then if the patient has a good response – a really good response – then I discontinue [methotrexate].”
Dr. Fleischmann said he does the same when adding a tumor necrosis factor inhibitor to methotrexate and that there are some patients who just do better with combination treatment.
ORAL Strategy was a phase IIIB/IV study that randomized 1,152 adults with active RA, despite treatment for more than 4 months with 15-25 mg/kg of methotrexate per week. Patients had to have four or more painful or tender joints and four or more swollen joints at baseline, and a high-sensitivity C-reactive protein level of 3 mg/L or more.
Patients were randomized to one of the study’s three treatment arms: tofacitinib 5 mg twice daily as monotherapy (n = 384), the same regimen of tofacitinib added to methotrexate (n = 376), or adalimumab 40 mg every 2 weeks added to methotrexate (n = 386). (Two patients in each group did not receive their assigned treatment.) Treatment was for 1 year, and concomitant treatment with nonsteroidal anti-inflammatory drugs, oral glucocorticoids, or both was allowed so long as their doses remained stable and no dose adjustments were necessary.
ACR20 responses were also recorded and were achieved by 65% with tofacitinib monotherapy, 73% with tofacitinib plus methotrexate, and 71% with adalimumab plus methotrexate, and ACR70 responses were 18%, 25%, and 21%, respectively. Comparable improvements from baseline to the end of the study were also seen for Simple Disease Activity Index, Clinical Disease Activity Index, Disease Activity Score in 28 joints using erythrocyte sedimentation rate, and Health Assessment Questionnaire scores in patients given the combination treatments.
The study’s findings were published online (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31618-5) to coincide with their presentation in a late-breaking abstract at the meeting.
“The ORAL Strategy trial highlights three benefits from the combination of tofacitinib and methotrexate in active rheumatoid arthritis,” independent commentators David Scott, MD, and Matt D. Stevenson, PhD, wrote in an editorial (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31659-8).
“First, this combination’s efficacy and toxicity are similar to injectable biologics such as adalimumab,” said Dr. Scott of King’s College London and Dr. Stevenson of the University of Sheffield (England). Indeed, no new side effects were seen, and side effects were consistent with those seen in previous studies.
“Second,” they wrote, “the onset of action of these drugs seems equally rapid. Third, most patients are able to remain on tofacitinib therapy for 12 months.”
Dr. Scott and Dr. Stevenson suggested these findings are “extremely encouraging” as “they show the ongoing benefits of innovation in drug treatment.”
The findings support the previous RA-BEAM trial (N Engl J Med. 2017;376:652-62) with another Janus kinase inhibitor, baricitinib, Dr. Fleischmann said during his presentation, which had also shown combination therapy with methotrexate was perhaps more beneficial than adding adalimumab.
In the Lancet editorial, Dr. Scott and Dr. Stevenson wrote: “Although a combination of [Janus kinase] inhibitors with methotrexate is likely to be the way they are used in clinical practice, monotherapy results in clinical and functional responses, as shown in the ORAL Strategy trial, and thus might be appropriate in some patients.”
The study was funded by Pfizer. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi-Genzyme, and UCB. Dr. Scott has advised Eli Lilly, Roche Products, Napp Pharmaceuticals, Baxalta, and Novartis. Dr. Stevenson did not have any industry disclosures.
MADRID – When it comes to patients with rheumatoid arthritis who are responding inadequately to methotrexate therapy, results of the Oral Rheumatoid Arthritis triaL (ORAL) Strategy study suggest that adding the Janus kinase inhibitor tofacitinib is just as effective as adding the tumor necrosis factor inhibitor adalimumab.
At 6 months’ follow-up, 46% of patients randomized to tofacitinib (Xeljanz) plus methotrexate met the trial’s primary endpoint of an American College of Rheumatology response of at least 50% (ACR50), compared with 44% of those who were given adalimumab (Humira) plus methotrexate. This result met the trial’s prespecified criteria for noninferiority. An ACR50 response means that there was at least 50% improvement in tender or swollen joint counts as well as a 50% improvement in at least three of the other five criteria (acute phase reactant, such as erythrocyte sedimentation rate; patient assessment; physician assessment; pain scale; and disability/functional questionnaire).
Nevertheless, “in circumstances where methotrexate is precluded, tofacitinib monotherapy is a clinically viable option,” lead study author Roy Fleischmann, MD, said at the European Congress of Rheumatology.
“This actually substantiates what I’ve done in clinical practice since [tofacitinib] was approved,” said Dr. Fleischmann, a rheumatologist in group practice in Dallas. “If I have patients on methotrexate and they show an incomplete response, I add tofacitinib; I don’t switch, I add. Then if the patient has a good response – a really good response – then I discontinue [methotrexate].”
Dr. Fleischmann said he does the same when adding a tumor necrosis factor inhibitor to methotrexate and that there are some patients who just do better with combination treatment.
ORAL Strategy was a phase IIIB/IV study that randomized 1,152 adults with active RA, despite treatment for more than 4 months with 15-25 mg/kg of methotrexate per week. Patients had to have four or more painful or tender joints and four or more swollen joints at baseline, and a high-sensitivity C-reactive protein level of 3 mg/L or more.
Patients were randomized to one of the study’s three treatment arms: tofacitinib 5 mg twice daily as monotherapy (n = 384), the same regimen of tofacitinib added to methotrexate (n = 376), or adalimumab 40 mg every 2 weeks added to methotrexate (n = 386). (Two patients in each group did not receive their assigned treatment.) Treatment was for 1 year, and concomitant treatment with nonsteroidal anti-inflammatory drugs, oral glucocorticoids, or both was allowed so long as their doses remained stable and no dose adjustments were necessary.
ACR20 responses were also recorded and were achieved by 65% with tofacitinib monotherapy, 73% with tofacitinib plus methotrexate, and 71% with adalimumab plus methotrexate, and ACR70 responses were 18%, 25%, and 21%, respectively. Comparable improvements from baseline to the end of the study were also seen for Simple Disease Activity Index, Clinical Disease Activity Index, Disease Activity Score in 28 joints using erythrocyte sedimentation rate, and Health Assessment Questionnaire scores in patients given the combination treatments.
The study’s findings were published online (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31618-5) to coincide with their presentation in a late-breaking abstract at the meeting.
“The ORAL Strategy trial highlights three benefits from the combination of tofacitinib and methotrexate in active rheumatoid arthritis,” independent commentators David Scott, MD, and Matt D. Stevenson, PhD, wrote in an editorial (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31659-8).
“First, this combination’s efficacy and toxicity are similar to injectable biologics such as adalimumab,” said Dr. Scott of King’s College London and Dr. Stevenson of the University of Sheffield (England). Indeed, no new side effects were seen, and side effects were consistent with those seen in previous studies.
“Second,” they wrote, “the onset of action of these drugs seems equally rapid. Third, most patients are able to remain on tofacitinib therapy for 12 months.”
Dr. Scott and Dr. Stevenson suggested these findings are “extremely encouraging” as “they show the ongoing benefits of innovation in drug treatment.”
The findings support the previous RA-BEAM trial (N Engl J Med. 2017;376:652-62) with another Janus kinase inhibitor, baricitinib, Dr. Fleischmann said during his presentation, which had also shown combination therapy with methotrexate was perhaps more beneficial than adding adalimumab.
In the Lancet editorial, Dr. Scott and Dr. Stevenson wrote: “Although a combination of [Janus kinase] inhibitors with methotrexate is likely to be the way they are used in clinical practice, monotherapy results in clinical and functional responses, as shown in the ORAL Strategy trial, and thus might be appropriate in some patients.”
The study was funded by Pfizer. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi-Genzyme, and UCB. Dr. Scott has advised Eli Lilly, Roche Products, Napp Pharmaceuticals, Baxalta, and Novartis. Dr. Stevenson did not have any industry disclosures.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The primary endpoint of an ACR50 was met by 46% of patients randomized to tofacitinib plus methotrexate vs. 44% of those who were given adalimumab plus methotrexate. This result met the trial’s prespecified criteria for noninferiority.
Data source: ORAL Strategy: A phase IIIB/IV, double-blind, head-to-head, noninferiority, randomized, controlled trial of tofacitinib with or without methotrexate, and adalimumab with methotrexate, in 1,152 RA patients inadequately responding to methotrexate.
Disclosures: The study was funded by Pfizer. The study presenter has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi-Genzyme, and UCB. One independent commentator has advised Eli Lilly, Roche Products, Napp Pharmaceuticals, Baxalta, and Novartis, while the other did not have any industry disclosures.
Adoptions increasingly involve special needs, prenatal drug exposures
SAN FRANCISCO – International adoptions today almost exclusively involve children with special needs, and domestic adoptions are far more likely to involve children exposed prenatally to marijuana, opiates, or another drug, Lisa Prock, MD, MPH, found in a study.
“Pediatric health care providers reviewing referrals for adoption should be knowledgeable about the changing demographics of this population and the long-term implications of prenatal substance exposure, given increasing opiate and marijuana use nationally,” said Dr. Prock of Boston Children’s Hospital.
During the initial flood of international adoptions in the 1990s, families sought preadoption consultations, often centering on infectious disease, at an increasing number of adoption clinics. Even with the decline of international adoptions, however, prospective parents still frequently seek information from pediatric providers about children they are considering adopting, whether internationally or domestically.
Prospective parents can receive medical record reviews of children they are considering adopting, provided by adoption agencies or attorneys. Dr. Prock retrospectively reviewed all the preadoptive charts submitted to one adoption clinic during 2 years a decade apart: 63 charts in 2006 and 91 charts in 2016.
Domestic records for both years usually included information about family history, prenatal history, maternal substance abuse history, lab results, and, for newborns, a physical exam. International records, however, generally included only lab results and a physical exam, sometimes with limited information on substance abuse as well, at both time points.
The records reveal just how dramatically referrals have flipped from an international focus to a domestic one in the past decade. International adoption referrals dropped from 84% in 2006 to 29% in 2016 as domestic ones increased from 16% to 71%.
Children with special needs also account for a larger proportion of all adoption referrals today. Just a quarter of international adoption referrals in 2006 involved children with special needs, including cleft lip and/or palate and congenital heart disease, but nearly all international referrals (96%) involved special needs in 2016.
Similarly, domestic adoption referrals in which the child is known to have prenatal exposure to alcohol or drugs doubled from 30% in 2006 to 66% in 2016, driven predominantly by maternal use of marijuana and opiates, Dr. Prock found. It’s important both for providers and for prospective parents to be aware of the higher likelihood that an internationally adopted child will have significant medical and/or developmental needs and that domestically adopted children are more likely to have experienced prenatal drug or alcohol exposures.
“Prospective adoptive parents may benefit from increased understanding of the long-term impact of prenatal substance exposure to marijuana, opiates and other substances,” Dr. Prock said. She also noted the need for prospective parents to be aware of the mental health concerns that can co-occur with substance use even though they may not be reported in preadoptive medical records.
No external funding was used for the research. Dr. Prock had no relevant financial disclosures.
SAN FRANCISCO – International adoptions today almost exclusively involve children with special needs, and domestic adoptions are far more likely to involve children exposed prenatally to marijuana, opiates, or another drug, Lisa Prock, MD, MPH, found in a study.
“Pediatric health care providers reviewing referrals for adoption should be knowledgeable about the changing demographics of this population and the long-term implications of prenatal substance exposure, given increasing opiate and marijuana use nationally,” said Dr. Prock of Boston Children’s Hospital.
During the initial flood of international adoptions in the 1990s, families sought preadoption consultations, often centering on infectious disease, at an increasing number of adoption clinics. Even with the decline of international adoptions, however, prospective parents still frequently seek information from pediatric providers about children they are considering adopting, whether internationally or domestically.
Prospective parents can receive medical record reviews of children they are considering adopting, provided by adoption agencies or attorneys. Dr. Prock retrospectively reviewed all the preadoptive charts submitted to one adoption clinic during 2 years a decade apart: 63 charts in 2006 and 91 charts in 2016.
Domestic records for both years usually included information about family history, prenatal history, maternal substance abuse history, lab results, and, for newborns, a physical exam. International records, however, generally included only lab results and a physical exam, sometimes with limited information on substance abuse as well, at both time points.
The records reveal just how dramatically referrals have flipped from an international focus to a domestic one in the past decade. International adoption referrals dropped from 84% in 2006 to 29% in 2016 as domestic ones increased from 16% to 71%.
Children with special needs also account for a larger proportion of all adoption referrals today. Just a quarter of international adoption referrals in 2006 involved children with special needs, including cleft lip and/or palate and congenital heart disease, but nearly all international referrals (96%) involved special needs in 2016.
Similarly, domestic adoption referrals in which the child is known to have prenatal exposure to alcohol or drugs doubled from 30% in 2006 to 66% in 2016, driven predominantly by maternal use of marijuana and opiates, Dr. Prock found. It’s important both for providers and for prospective parents to be aware of the higher likelihood that an internationally adopted child will have significant medical and/or developmental needs and that domestically adopted children are more likely to have experienced prenatal drug or alcohol exposures.
“Prospective adoptive parents may benefit from increased understanding of the long-term impact of prenatal substance exposure to marijuana, opiates and other substances,” Dr. Prock said. She also noted the need for prospective parents to be aware of the mental health concerns that can co-occur with substance use even though they may not be reported in preadoptive medical records.
No external funding was used for the research. Dr. Prock had no relevant financial disclosures.
SAN FRANCISCO – International adoptions today almost exclusively involve children with special needs, and domestic adoptions are far more likely to involve children exposed prenatally to marijuana, opiates, or another drug, Lisa Prock, MD, MPH, found in a study.
“Pediatric health care providers reviewing referrals for adoption should be knowledgeable about the changing demographics of this population and the long-term implications of prenatal substance exposure, given increasing opiate and marijuana use nationally,” said Dr. Prock of Boston Children’s Hospital.
During the initial flood of international adoptions in the 1990s, families sought preadoption consultations, often centering on infectious disease, at an increasing number of adoption clinics. Even with the decline of international adoptions, however, prospective parents still frequently seek information from pediatric providers about children they are considering adopting, whether internationally or domestically.
Prospective parents can receive medical record reviews of children they are considering adopting, provided by adoption agencies or attorneys. Dr. Prock retrospectively reviewed all the preadoptive charts submitted to one adoption clinic during 2 years a decade apart: 63 charts in 2006 and 91 charts in 2016.
Domestic records for both years usually included information about family history, prenatal history, maternal substance abuse history, lab results, and, for newborns, a physical exam. International records, however, generally included only lab results and a physical exam, sometimes with limited information on substance abuse as well, at both time points.
The records reveal just how dramatically referrals have flipped from an international focus to a domestic one in the past decade. International adoption referrals dropped from 84% in 2006 to 29% in 2016 as domestic ones increased from 16% to 71%.
Children with special needs also account for a larger proportion of all adoption referrals today. Just a quarter of international adoption referrals in 2006 involved children with special needs, including cleft lip and/or palate and congenital heart disease, but nearly all international referrals (96%) involved special needs in 2016.
Similarly, domestic adoption referrals in which the child is known to have prenatal exposure to alcohol or drugs doubled from 30% in 2006 to 66% in 2016, driven predominantly by maternal use of marijuana and opiates, Dr. Prock found. It’s important both for providers and for prospective parents to be aware of the higher likelihood that an internationally adopted child will have significant medical and/or developmental needs and that domestically adopted children are more likely to have experienced prenatal drug or alcohol exposures.
“Prospective adoptive parents may benefit from increased understanding of the long-term impact of prenatal substance exposure to marijuana, opiates and other substances,” Dr. Prock said. She also noted the need for prospective parents to be aware of the mental health concerns that can co-occur with substance use even though they may not be reported in preadoptive medical records.
No external funding was used for the research. Dr. Prock had no relevant financial disclosures.
AT PAS 17
Key clinical point:
Major finding: International adoption referrals with special needs increased from 25% to 96% from 2006 to 2016; domestic referrals with prenatal substance exposure increased from 30% to 66% over the same time period.
Data source: A retrospective review of all preadoptive medical records at a single adoption clinic in 2006 and 2016.
Disclosures: The researchers did not receive external funding. Dr. Prock had no relevant financial disclosures.
Sneak Peek: The Hospital Leader blog - July 2017
“We Are Not Done Changing”
Recently, the online version of JAMA published an original investigation titled, “Patient Mortality During Unannounced Accreditation Surveys at US Hospitals.” The purpose of this investigation was to determine the effect of heightened vigilance during unannounced accreditation surveys on safety and quality of inpatient care.
The authors found that there was a significant reduction in mortality in patients admitted during the week of surveys by The Joint Commission. The change was more significant in major teaching hospitals, where mortality fell from 6.41% to 5.93% during survey weeks, a 5.9% relative decrease. The positive effects of being monitored have been well documented in all kinds of arenas, such as hand washing and antibiotic stewardship. But mortality?
Overall, I feel like I’m a reasonable person, but the clear lack of interest – or willingness to consider that this might not be a good idea on the part of the hospitalist in charge – incited a certain amount of anger and disbelief in me. She also received an antibiotic that she had a documented allergy to – a clear medical error. I instructed my sis-in-law to refuse access to the line; it was removed, and she ultimately recovered to discharge.
This brings me back to the JAMA study. It’s easy to perceive unannounced inspections as merely an inconvenience, where things are locked up that normally aren’t, or where that coveted cup of coffee you normally bring on rounds to get you through your day is summarily yanked out of your hand.
Read the full text of this blog post at hospitalleader.org.
Also on The Hospital Leader…
• How Often Do You Ask This (Ineffective) Question? by Brad Flansbaum, DO, MPH, MHM• Building a Practice that People Want to Be a Part Of by Leslie Flores, MHA• A Need for Medicare Appeals Process Reform in Hospital Observation Care by Anne Sheehy, MD, MS, FHM
“We Are Not Done Changing”
Recently, the online version of JAMA published an original investigation titled, “Patient Mortality During Unannounced Accreditation Surveys at US Hospitals.” The purpose of this investigation was to determine the effect of heightened vigilance during unannounced accreditation surveys on safety and quality of inpatient care.
The authors found that there was a significant reduction in mortality in patients admitted during the week of surveys by The Joint Commission. The change was more significant in major teaching hospitals, where mortality fell from 6.41% to 5.93% during survey weeks, a 5.9% relative decrease. The positive effects of being monitored have been well documented in all kinds of arenas, such as hand washing and antibiotic stewardship. But mortality?
Overall, I feel like I’m a reasonable person, but the clear lack of interest – or willingness to consider that this might not be a good idea on the part of the hospitalist in charge – incited a certain amount of anger and disbelief in me. She also received an antibiotic that she had a documented allergy to – a clear medical error. I instructed my sis-in-law to refuse access to the line; it was removed, and she ultimately recovered to discharge.
This brings me back to the JAMA study. It’s easy to perceive unannounced inspections as merely an inconvenience, where things are locked up that normally aren’t, or where that coveted cup of coffee you normally bring on rounds to get you through your day is summarily yanked out of your hand.
Read the full text of this blog post at hospitalleader.org.
Also on The Hospital Leader…
• How Often Do You Ask This (Ineffective) Question? by Brad Flansbaum, DO, MPH, MHM• Building a Practice that People Want to Be a Part Of by Leslie Flores, MHA• A Need for Medicare Appeals Process Reform in Hospital Observation Care by Anne Sheehy, MD, MS, FHM
“We Are Not Done Changing”
Recently, the online version of JAMA published an original investigation titled, “Patient Mortality During Unannounced Accreditation Surveys at US Hospitals.” The purpose of this investigation was to determine the effect of heightened vigilance during unannounced accreditation surveys on safety and quality of inpatient care.
The authors found that there was a significant reduction in mortality in patients admitted during the week of surveys by The Joint Commission. The change was more significant in major teaching hospitals, where mortality fell from 6.41% to 5.93% during survey weeks, a 5.9% relative decrease. The positive effects of being monitored have been well documented in all kinds of arenas, such as hand washing and antibiotic stewardship. But mortality?
Overall, I feel like I’m a reasonable person, but the clear lack of interest – or willingness to consider that this might not be a good idea on the part of the hospitalist in charge – incited a certain amount of anger and disbelief in me. She also received an antibiotic that she had a documented allergy to – a clear medical error. I instructed my sis-in-law to refuse access to the line; it was removed, and she ultimately recovered to discharge.
This brings me back to the JAMA study. It’s easy to perceive unannounced inspections as merely an inconvenience, where things are locked up that normally aren’t, or where that coveted cup of coffee you normally bring on rounds to get you through your day is summarily yanked out of your hand.
Read the full text of this blog post at hospitalleader.org.
Also on The Hospital Leader…
• How Often Do You Ask This (Ineffective) Question? by Brad Flansbaum, DO, MPH, MHM• Building a Practice that People Want to Be a Part Of by Leslie Flores, MHA• A Need for Medicare Appeals Process Reform in Hospital Observation Care by Anne Sheehy, MD, MS, FHM
Health IT: Cybercrime risks are real
Aging equipment, valuable data, and an improperly trained workforce make health care IT extraordinarily vulnerable to external malfeasance, as demonstrated by the WannaCry virus episode that occurred this spring in the United Kingdom.
Computer hackers used a weakness in the operating system employed by the U.K. National Health Service, allowing the WannaCry virus to spread quickly across connected systems. The ransomware attack locked clinicians out of patient records and diagnostic machines that were connected, bringing patient care to a near standstill.
The attack lasted 3 days until Marcus Hutchins, a 22-year-old security researcher, stumbled onto a way to slow the spread of the virus enough to manage it, but not before nearly 60 million attacks had been conducted, Salim Neino, CEO of Kryptos Logic, testified June 15 at a joint hearing of two subcommittees of the House Science, Space & Technology Committee. Mr. Hutchins is employed by Kryptos Logic.
U.S. officials are keenly aware that a similar attack could happen here. In June, the federally sponsored Health Care Industry Cybersecurity Task Force issued a report on their year-long look at the state of the health care IT in this country. The task force was mandated by the Cybersecurity Act of 2015and formed in March 2016.
Specifically, the task force recommended:
• Defining and streamlining leadership, governance, and expectations for health care industry cybersecurity.
• Increasing the security and resilience of medical devices and health IT.
• Developing the health care workforce capacity necessary to prioritize and ensure cybersecurity awareness and technical capabilities.
• Increasing health care industry readiness through improved cybersecurity awareness and education.
• Identifying mechanisms to protect research and development efforts and intellectual property from attacks or exposure.
• Improving information sharing of industry threats, weaknesses, and mitigations.
Health care cybercrime is a significant problem in the United States. In 2016, 328 U.S. health care firms reported data breaches, up from 268 in 2015, with a total of 16.6 million Americans affected, according to a report conducted by Bitglass (registration required), a security software company. In February 2016, a hospital in California was forced to pay about $17,000 in Bitcoin, an electronic currency that is known to be favored by cybercriminals, to access electronic health records (EHRs) that were held in a similar manner to last month’s attack on the NHS.
For physicians, this may seem like someone else’s problem; however, unsafe day-to-day interactions with connected devices and patient EHRs were among the task force’s primary concerns.
For many, creating a safe password or not giving out critical information may seem like common sense, but many physicians are not able or willing to take the time to make sure they are interacting with systems safely, or they are overconfident in their security system, according to task force member Mark Jarrett, MD, senior vice president and chief quality officer at Northwell Health in New York.
“Most physicians now will try to access medical records of their patients who have been in the hospital because that’s good care,” Dr. Jarrett said in an interview. But they have to recognize that “they cannot give these passwords to other people and they need to make these passwords complex.”
“Phishing” is another concern. In a phishing scam, cybercriminals will pose as a fraudulent institution or individual in order to trick a target into downloading a virus, sending additional valuable information, or even paying money directly to the criminals.
“Physicians checking their emails need to be aware of possible phishing episodes, because they could be infected, and then there is the possibility that infection could be introduced into the system, Dr. Jarrett said. “I think the disconnect is [that physicians] are not used to [cybersecurity]. It’s not part of their daily life and they also, up until recently, thought ‘it’s never going to happen to me.’ ”
While hospitals are not completely incapable of protecting themselves, experts are concerned about an overinflated sense of confidence among health care professionals.
“Health care workers often assume that the IT network and the devices they support function efficiently and that their level of cybersecurity vulnerability is low,” according to the task force report.
This can be a costly assumption, financially, as well for safety; the price per stolen EHR averaged at $380 in 2016-2017, according to the Ponemon Institute’s 2017 Cost of Data Breach Study, released in June. That is nearly triple the average cost of all breaches – $141– and higher than the price of $241 for information stolen from financial industries because, unlike a credit card number, patients’ data are unique and cannot be replaced.
Aging equipment is another concern. Legacy software and machine systems used in medical practices and hospitals are not equipped with the necessary security services needed to handle the growing risks of connectivity, despite being included in the network.
“Every CT machine, every x-ray machine today is connected online, on one consolidated Internet” cybersecurity expert Idan Udi Edry of Trustifi said in an interview. “The more comfortable we are with the digital edge coming into our lives, the more vulnerable we become and the more security we need to implement to protect ourselves.”
Some solutions already have been suggested to help health care professionals replace their outdated equipment, especially private practice physicians or smaller hospitals without much financial wiggle room,
The cybersecurity task force report recommended creating health IT version of Cash for Clunkers, an Obama administration program that offered rebates to consumers who traded in older, less fuel efficient cars when purchasing a new car.
While experts agree that the growing focus on connected health care will continue to create cybersecurity risks, with all members of the health care industry working together, it is possible to keep hospitals and patients safe from would-be criminals.
The next key step is creating regulations that would encourage a cohesive structure of cybersecurity guidelines. According to the task force report, “a priority for regulatory agencies should be to ensure consistency among various federal and state cybersecurity regulations so that health care providers can focus on deploying their resources appropriately between securing patient information and the quality, safety, and accessibility of patient care” rather than having to focus on statutory and regulatory inconsistencies.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
When computer hackers took control of the United Kingdom’s National Health Service using a virus known as “WannaCry,” doctors and nurses were left helpless, blocked from the files they would need to treat their patients until they paid to get them those files back.
Doctors were forced to revert to older methods, slowing everything to a snail’s pace.
The media coverage of the event was dramatic, but there is no doubt the effects made it justifiably so.
NHS hospitals had not achieved their goal of being paperless; had they been, the service would have been completely unable to stop the attack.
It was not just software that was affected but medical devices as well. Physicians were unable to perform x-rays, and some hospitals found that the refrigerators used to store blood products were shut down.
While the NHS was particularly vulnerable to the WannaCry because of budget cuts, this cybercrime could have happened to any hospital, and its lessons are applicable far all.
Doctors do understand the value of patients records, but they seem to be unaware of the physical harm that could befall patients from a cyberattack.
This attack needs to serve as a wake-up call for health care professionals who are not invested in their facilities’ cybersecurity practices.
Underfunding left NHS hospitals terribly exposed and, if physicians continue to be complacent with how to handle this issue, the results are sure to be more severe.
Rachel Clarke, MD, is at Oxford (England) University Hospitals NHS Foundation Trust, and Taryn Youngstein, MD, is at Imperial College Healthcare NHS Trust, London. They reported having no relevant financial conflicts of interest. Their remarks were make in a perspective published in the New England Journal of Medicine (doi: 10.1056/NEJMp1706754).
When computer hackers took control of the United Kingdom’s National Health Service using a virus known as “WannaCry,” doctors and nurses were left helpless, blocked from the files they would need to treat their patients until they paid to get them those files back.
Doctors were forced to revert to older methods, slowing everything to a snail’s pace.
The media coverage of the event was dramatic, but there is no doubt the effects made it justifiably so.
NHS hospitals had not achieved their goal of being paperless; had they been, the service would have been completely unable to stop the attack.
It was not just software that was affected but medical devices as well. Physicians were unable to perform x-rays, and some hospitals found that the refrigerators used to store blood products were shut down.
While the NHS was particularly vulnerable to the WannaCry because of budget cuts, this cybercrime could have happened to any hospital, and its lessons are applicable far all.
Doctors do understand the value of patients records, but they seem to be unaware of the physical harm that could befall patients from a cyberattack.
This attack needs to serve as a wake-up call for health care professionals who are not invested in their facilities’ cybersecurity practices.
Underfunding left NHS hospitals terribly exposed and, if physicians continue to be complacent with how to handle this issue, the results are sure to be more severe.
Rachel Clarke, MD, is at Oxford (England) University Hospitals NHS Foundation Trust, and Taryn Youngstein, MD, is at Imperial College Healthcare NHS Trust, London. They reported having no relevant financial conflicts of interest. Their remarks were make in a perspective published in the New England Journal of Medicine (doi: 10.1056/NEJMp1706754).
When computer hackers took control of the United Kingdom’s National Health Service using a virus known as “WannaCry,” doctors and nurses were left helpless, blocked from the files they would need to treat their patients until they paid to get them those files back.
Doctors were forced to revert to older methods, slowing everything to a snail’s pace.
The media coverage of the event was dramatic, but there is no doubt the effects made it justifiably so.
NHS hospitals had not achieved their goal of being paperless; had they been, the service would have been completely unable to stop the attack.
It was not just software that was affected but medical devices as well. Physicians were unable to perform x-rays, and some hospitals found that the refrigerators used to store blood products were shut down.
While the NHS was particularly vulnerable to the WannaCry because of budget cuts, this cybercrime could have happened to any hospital, and its lessons are applicable far all.
Doctors do understand the value of patients records, but they seem to be unaware of the physical harm that could befall patients from a cyberattack.
This attack needs to serve as a wake-up call for health care professionals who are not invested in their facilities’ cybersecurity practices.
Underfunding left NHS hospitals terribly exposed and, if physicians continue to be complacent with how to handle this issue, the results are sure to be more severe.
Rachel Clarke, MD, is at Oxford (England) University Hospitals NHS Foundation Trust, and Taryn Youngstein, MD, is at Imperial College Healthcare NHS Trust, London. They reported having no relevant financial conflicts of interest. Their remarks were make in a perspective published in the New England Journal of Medicine (doi: 10.1056/NEJMp1706754).
Aging equipment, valuable data, and an improperly trained workforce make health care IT extraordinarily vulnerable to external malfeasance, as demonstrated by the WannaCry virus episode that occurred this spring in the United Kingdom.
Computer hackers used a weakness in the operating system employed by the U.K. National Health Service, allowing the WannaCry virus to spread quickly across connected systems. The ransomware attack locked clinicians out of patient records and diagnostic machines that were connected, bringing patient care to a near standstill.
The attack lasted 3 days until Marcus Hutchins, a 22-year-old security researcher, stumbled onto a way to slow the spread of the virus enough to manage it, but not before nearly 60 million attacks had been conducted, Salim Neino, CEO of Kryptos Logic, testified June 15 at a joint hearing of two subcommittees of the House Science, Space & Technology Committee. Mr. Hutchins is employed by Kryptos Logic.
U.S. officials are keenly aware that a similar attack could happen here. In June, the federally sponsored Health Care Industry Cybersecurity Task Force issued a report on their year-long look at the state of the health care IT in this country. The task force was mandated by the Cybersecurity Act of 2015and formed in March 2016.
Specifically, the task force recommended:
• Defining and streamlining leadership, governance, and expectations for health care industry cybersecurity.
• Increasing the security and resilience of medical devices and health IT.
• Developing the health care workforce capacity necessary to prioritize and ensure cybersecurity awareness and technical capabilities.
• Increasing health care industry readiness through improved cybersecurity awareness and education.
• Identifying mechanisms to protect research and development efforts and intellectual property from attacks or exposure.
• Improving information sharing of industry threats, weaknesses, and mitigations.
Health care cybercrime is a significant problem in the United States. In 2016, 328 U.S. health care firms reported data breaches, up from 268 in 2015, with a total of 16.6 million Americans affected, according to a report conducted by Bitglass (registration required), a security software company. In February 2016, a hospital in California was forced to pay about $17,000 in Bitcoin, an electronic currency that is known to be favored by cybercriminals, to access electronic health records (EHRs) that were held in a similar manner to last month’s attack on the NHS.
For physicians, this may seem like someone else’s problem; however, unsafe day-to-day interactions with connected devices and patient EHRs were among the task force’s primary concerns.
For many, creating a safe password or not giving out critical information may seem like common sense, but many physicians are not able or willing to take the time to make sure they are interacting with systems safely, or they are overconfident in their security system, according to task force member Mark Jarrett, MD, senior vice president and chief quality officer at Northwell Health in New York.
“Most physicians now will try to access medical records of their patients who have been in the hospital because that’s good care,” Dr. Jarrett said in an interview. But they have to recognize that “they cannot give these passwords to other people and they need to make these passwords complex.”
“Phishing” is another concern. In a phishing scam, cybercriminals will pose as a fraudulent institution or individual in order to trick a target into downloading a virus, sending additional valuable information, or even paying money directly to the criminals.
“Physicians checking their emails need to be aware of possible phishing episodes, because they could be infected, and then there is the possibility that infection could be introduced into the system, Dr. Jarrett said. “I think the disconnect is [that physicians] are not used to [cybersecurity]. It’s not part of their daily life and they also, up until recently, thought ‘it’s never going to happen to me.’ ”
While hospitals are not completely incapable of protecting themselves, experts are concerned about an overinflated sense of confidence among health care professionals.
“Health care workers often assume that the IT network and the devices they support function efficiently and that their level of cybersecurity vulnerability is low,” according to the task force report.
This can be a costly assumption, financially, as well for safety; the price per stolen EHR averaged at $380 in 2016-2017, according to the Ponemon Institute’s 2017 Cost of Data Breach Study, released in June. That is nearly triple the average cost of all breaches – $141– and higher than the price of $241 for information stolen from financial industries because, unlike a credit card number, patients’ data are unique and cannot be replaced.
Aging equipment is another concern. Legacy software and machine systems used in medical practices and hospitals are not equipped with the necessary security services needed to handle the growing risks of connectivity, despite being included in the network.
“Every CT machine, every x-ray machine today is connected online, on one consolidated Internet” cybersecurity expert Idan Udi Edry of Trustifi said in an interview. “The more comfortable we are with the digital edge coming into our lives, the more vulnerable we become and the more security we need to implement to protect ourselves.”
Some solutions already have been suggested to help health care professionals replace their outdated equipment, especially private practice physicians or smaller hospitals without much financial wiggle room,
The cybersecurity task force report recommended creating health IT version of Cash for Clunkers, an Obama administration program that offered rebates to consumers who traded in older, less fuel efficient cars when purchasing a new car.
While experts agree that the growing focus on connected health care will continue to create cybersecurity risks, with all members of the health care industry working together, it is possible to keep hospitals and patients safe from would-be criminals.
The next key step is creating regulations that would encourage a cohesive structure of cybersecurity guidelines. According to the task force report, “a priority for regulatory agencies should be to ensure consistency among various federal and state cybersecurity regulations so that health care providers can focus on deploying their resources appropriately between securing patient information and the quality, safety, and accessibility of patient care” rather than having to focus on statutory and regulatory inconsistencies.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
Aging equipment, valuable data, and an improperly trained workforce make health care IT extraordinarily vulnerable to external malfeasance, as demonstrated by the WannaCry virus episode that occurred this spring in the United Kingdom.
Computer hackers used a weakness in the operating system employed by the U.K. National Health Service, allowing the WannaCry virus to spread quickly across connected systems. The ransomware attack locked clinicians out of patient records and diagnostic machines that were connected, bringing patient care to a near standstill.
The attack lasted 3 days until Marcus Hutchins, a 22-year-old security researcher, stumbled onto a way to slow the spread of the virus enough to manage it, but not before nearly 60 million attacks had been conducted, Salim Neino, CEO of Kryptos Logic, testified June 15 at a joint hearing of two subcommittees of the House Science, Space & Technology Committee. Mr. Hutchins is employed by Kryptos Logic.
U.S. officials are keenly aware that a similar attack could happen here. In June, the federally sponsored Health Care Industry Cybersecurity Task Force issued a report on their year-long look at the state of the health care IT in this country. The task force was mandated by the Cybersecurity Act of 2015and formed in March 2016.
Specifically, the task force recommended:
• Defining and streamlining leadership, governance, and expectations for health care industry cybersecurity.
• Increasing the security and resilience of medical devices and health IT.
• Developing the health care workforce capacity necessary to prioritize and ensure cybersecurity awareness and technical capabilities.
• Increasing health care industry readiness through improved cybersecurity awareness and education.
• Identifying mechanisms to protect research and development efforts and intellectual property from attacks or exposure.
• Improving information sharing of industry threats, weaknesses, and mitigations.
Health care cybercrime is a significant problem in the United States. In 2016, 328 U.S. health care firms reported data breaches, up from 268 in 2015, with a total of 16.6 million Americans affected, according to a report conducted by Bitglass (registration required), a security software company. In February 2016, a hospital in California was forced to pay about $17,000 in Bitcoin, an electronic currency that is known to be favored by cybercriminals, to access electronic health records (EHRs) that were held in a similar manner to last month’s attack on the NHS.
For physicians, this may seem like someone else’s problem; however, unsafe day-to-day interactions with connected devices and patient EHRs were among the task force’s primary concerns.
For many, creating a safe password or not giving out critical information may seem like common sense, but many physicians are not able or willing to take the time to make sure they are interacting with systems safely, or they are overconfident in their security system, according to task force member Mark Jarrett, MD, senior vice president and chief quality officer at Northwell Health in New York.
“Most physicians now will try to access medical records of their patients who have been in the hospital because that’s good care,” Dr. Jarrett said in an interview. But they have to recognize that “they cannot give these passwords to other people and they need to make these passwords complex.”
“Phishing” is another concern. In a phishing scam, cybercriminals will pose as a fraudulent institution or individual in order to trick a target into downloading a virus, sending additional valuable information, or even paying money directly to the criminals.
“Physicians checking their emails need to be aware of possible phishing episodes, because they could be infected, and then there is the possibility that infection could be introduced into the system, Dr. Jarrett said. “I think the disconnect is [that physicians] are not used to [cybersecurity]. It’s not part of their daily life and they also, up until recently, thought ‘it’s never going to happen to me.’ ”
While hospitals are not completely incapable of protecting themselves, experts are concerned about an overinflated sense of confidence among health care professionals.
“Health care workers often assume that the IT network and the devices they support function efficiently and that their level of cybersecurity vulnerability is low,” according to the task force report.
This can be a costly assumption, financially, as well for safety; the price per stolen EHR averaged at $380 in 2016-2017, according to the Ponemon Institute’s 2017 Cost of Data Breach Study, released in June. That is nearly triple the average cost of all breaches – $141– and higher than the price of $241 for information stolen from financial industries because, unlike a credit card number, patients’ data are unique and cannot be replaced.
Aging equipment is another concern. Legacy software and machine systems used in medical practices and hospitals are not equipped with the necessary security services needed to handle the growing risks of connectivity, despite being included in the network.
“Every CT machine, every x-ray machine today is connected online, on one consolidated Internet” cybersecurity expert Idan Udi Edry of Trustifi said in an interview. “The more comfortable we are with the digital edge coming into our lives, the more vulnerable we become and the more security we need to implement to protect ourselves.”
Some solutions already have been suggested to help health care professionals replace their outdated equipment, especially private practice physicians or smaller hospitals without much financial wiggle room,
The cybersecurity task force report recommended creating health IT version of Cash for Clunkers, an Obama administration program that offered rebates to consumers who traded in older, less fuel efficient cars when purchasing a new car.
While experts agree that the growing focus on connected health care will continue to create cybersecurity risks, with all members of the health care industry working together, it is possible to keep hospitals and patients safe from would-be criminals.
The next key step is creating regulations that would encourage a cohesive structure of cybersecurity guidelines. According to the task force report, “a priority for regulatory agencies should be to ensure consistency among various federal and state cybersecurity regulations so that health care providers can focus on deploying their resources appropriately between securing patient information and the quality, safety, and accessibility of patient care” rather than having to focus on statutory and regulatory inconsistencies.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
Malpractice reform: House passes bill to cap damages
The House of Representatives has passed a bill that would cap damages in medical malpractice cases and impose a tighter time frame for legal challenges against physicians.
The House passed the Protecting Access to Care Act (H.R. 1215) on June 28 by a 218-210 vote. The bill, modeled after California’s Medical Injury Compensation Reform Act (MICRA), would limit noneconomic damages in medical malpractice cases to $250,000, restrict contingency fees charged by attorneys, and enforce a 3-year statute of limitations for liability lawsuits from the date of alleged injury. The legislation also includes a fair share rule in which defendants are liable only for the damages in direct proportion to their percentage of responsibility.
The American College of Physicians (ACP) praised the House for passing the bill, saying the time is ripe to develop and pass common-sense liability reforms.
“The American College of Physicians applauds the House of Representatives for its passage of a multifaceted approach to medical-liability reform,” Jack Ende, MD, ACP president, said in a statement. “ACP believes that any solution to improve the medical liability system in the U.S. should include a multifaceted approach, because no single program or law by itself is likely to achieve the goals of improving patient safety, ensuring fair compensation to patients, strengthening rather than undermining the patient-physician relationship, and reducing the economic costs associated with the current system.”
The American Association for Justice, a lobbying organization for plaintiffs’ attorneys, sent a letter to the House prior to the bill’s passage urging legislators to oppose the bill. More than 75 organizations signed the letter.
“Even if H.R. 1215 applied only to doctors and hospitals, recent studies clearly establish that its provisions would lead to more deaths and injuries, and increased health care costs due to a ‘broad relaxation of care,’ ” the letter stated. “... The latest statistics show that medical errors, most of which are preventable, are the third leading cause of death in America. This intolerable situation is perhaps all the more shocking because we already know about how to fix much of this problem. Congress should focus on improving patient safety and reducing deaths and injuries, not insulating negligent providers from accountability, harming patients, and saddling taxpayers with the cost.”
The legislation would apply to any patient who receives medical care provided via a federal program, such as Medicare or Medicaid, or via a subsidy or tax benefit, such as coverage purchased under the Affordable Care Act or a replacement. Medical care paid for via employer health plans also would fall under the legislation’s umbrella since insurance premiums receive federal tax exemptions. The bill would not preempt state medical malpractice laws that impose damage caps, whether higher or lower than $250,000, nor would the legislation affect the availability of economic damages, according to bill language.
As part of the H.R. 1215, courts could limit how much attorneys receive from a patient’s ultimate award. Specifically, courts would have the power to restrict payments from a plaintiff’s damage recovery to an attorney who claims a financial stake in the outcome by virtue of a contingent fee.
PIAA, a trade association representing medical liability insurers, said the House passage of the bill is a major victory for tort reform advocates. The bill is the first comprehensive medical liability reform legislation to be passed by either chamber of Congress in more than 5 years, according to PIAA.
H.R. 1215 now moves on to the Senate.
agallegos@frontlinemedcom.com
On Twitter @legal_med
The House of Representatives has passed a bill that would cap damages in medical malpractice cases and impose a tighter time frame for legal challenges against physicians.
The House passed the Protecting Access to Care Act (H.R. 1215) on June 28 by a 218-210 vote. The bill, modeled after California’s Medical Injury Compensation Reform Act (MICRA), would limit noneconomic damages in medical malpractice cases to $250,000, restrict contingency fees charged by attorneys, and enforce a 3-year statute of limitations for liability lawsuits from the date of alleged injury. The legislation also includes a fair share rule in which defendants are liable only for the damages in direct proportion to their percentage of responsibility.
The American College of Physicians (ACP) praised the House for passing the bill, saying the time is ripe to develop and pass common-sense liability reforms.
“The American College of Physicians applauds the House of Representatives for its passage of a multifaceted approach to medical-liability reform,” Jack Ende, MD, ACP president, said in a statement. “ACP believes that any solution to improve the medical liability system in the U.S. should include a multifaceted approach, because no single program or law by itself is likely to achieve the goals of improving patient safety, ensuring fair compensation to patients, strengthening rather than undermining the patient-physician relationship, and reducing the economic costs associated with the current system.”
The American Association for Justice, a lobbying organization for plaintiffs’ attorneys, sent a letter to the House prior to the bill’s passage urging legislators to oppose the bill. More than 75 organizations signed the letter.
“Even if H.R. 1215 applied only to doctors and hospitals, recent studies clearly establish that its provisions would lead to more deaths and injuries, and increased health care costs due to a ‘broad relaxation of care,’ ” the letter stated. “... The latest statistics show that medical errors, most of which are preventable, are the third leading cause of death in America. This intolerable situation is perhaps all the more shocking because we already know about how to fix much of this problem. Congress should focus on improving patient safety and reducing deaths and injuries, not insulating negligent providers from accountability, harming patients, and saddling taxpayers with the cost.”
The legislation would apply to any patient who receives medical care provided via a federal program, such as Medicare or Medicaid, or via a subsidy or tax benefit, such as coverage purchased under the Affordable Care Act or a replacement. Medical care paid for via employer health plans also would fall under the legislation’s umbrella since insurance premiums receive federal tax exemptions. The bill would not preempt state medical malpractice laws that impose damage caps, whether higher or lower than $250,000, nor would the legislation affect the availability of economic damages, according to bill language.
As part of the H.R. 1215, courts could limit how much attorneys receive from a patient’s ultimate award. Specifically, courts would have the power to restrict payments from a plaintiff’s damage recovery to an attorney who claims a financial stake in the outcome by virtue of a contingent fee.
PIAA, a trade association representing medical liability insurers, said the House passage of the bill is a major victory for tort reform advocates. The bill is the first comprehensive medical liability reform legislation to be passed by either chamber of Congress in more than 5 years, according to PIAA.
H.R. 1215 now moves on to the Senate.
agallegos@frontlinemedcom.com
On Twitter @legal_med
The House of Representatives has passed a bill that would cap damages in medical malpractice cases and impose a tighter time frame for legal challenges against physicians.
The House passed the Protecting Access to Care Act (H.R. 1215) on June 28 by a 218-210 vote. The bill, modeled after California’s Medical Injury Compensation Reform Act (MICRA), would limit noneconomic damages in medical malpractice cases to $250,000, restrict contingency fees charged by attorneys, and enforce a 3-year statute of limitations for liability lawsuits from the date of alleged injury. The legislation also includes a fair share rule in which defendants are liable only for the damages in direct proportion to their percentage of responsibility.
The American College of Physicians (ACP) praised the House for passing the bill, saying the time is ripe to develop and pass common-sense liability reforms.
“The American College of Physicians applauds the House of Representatives for its passage of a multifaceted approach to medical-liability reform,” Jack Ende, MD, ACP president, said in a statement. “ACP believes that any solution to improve the medical liability system in the U.S. should include a multifaceted approach, because no single program or law by itself is likely to achieve the goals of improving patient safety, ensuring fair compensation to patients, strengthening rather than undermining the patient-physician relationship, and reducing the economic costs associated with the current system.”
The American Association for Justice, a lobbying organization for plaintiffs’ attorneys, sent a letter to the House prior to the bill’s passage urging legislators to oppose the bill. More than 75 organizations signed the letter.
“Even if H.R. 1215 applied only to doctors and hospitals, recent studies clearly establish that its provisions would lead to more deaths and injuries, and increased health care costs due to a ‘broad relaxation of care,’ ” the letter stated. “... The latest statistics show that medical errors, most of which are preventable, are the third leading cause of death in America. This intolerable situation is perhaps all the more shocking because we already know about how to fix much of this problem. Congress should focus on improving patient safety and reducing deaths and injuries, not insulating negligent providers from accountability, harming patients, and saddling taxpayers with the cost.”
The legislation would apply to any patient who receives medical care provided via a federal program, such as Medicare or Medicaid, or via a subsidy or tax benefit, such as coverage purchased under the Affordable Care Act or a replacement. Medical care paid for via employer health plans also would fall under the legislation’s umbrella since insurance premiums receive federal tax exemptions. The bill would not preempt state medical malpractice laws that impose damage caps, whether higher or lower than $250,000, nor would the legislation affect the availability of economic damages, according to bill language.
As part of the H.R. 1215, courts could limit how much attorneys receive from a patient’s ultimate award. Specifically, courts would have the power to restrict payments from a plaintiff’s damage recovery to an attorney who claims a financial stake in the outcome by virtue of a contingent fee.
PIAA, a trade association representing medical liability insurers, said the House passage of the bill is a major victory for tort reform advocates. The bill is the first comprehensive medical liability reform legislation to be passed by either chamber of Congress in more than 5 years, according to PIAA.
H.R. 1215 now moves on to the Senate.
agallegos@frontlinemedcom.com
On Twitter @legal_med
Outcomes/costs similar for minimally invasive vs. sternotomy-based mitral surgery
NEW YORK – Minimally invasive mitral valve surgery provides outcomes that match those of conventional sternotomy without increasing use of resources, and lower costs after surgery offset potentially higher operation costs, according to a single-center, propensity-matched analysis of almost 500 patients presented at the meeting sponsored by the American Association for Thoracic Surgery.
“Minimally invasive mitral surgery has excellent outcomes with fewer transfusions and less time ventilated in this representative cohort,” said Robert Hawkins, MD, of the University of Virginia, Charlottesville, in reporting the results.
“While operative times were longer, surgical costs remained statistically similar, and minimally invasive mitral surgery was associated with similar total costs in more complex mitral cases.”
Dr. Hawkins said this study included higher risk patients to attempt to overcome shortcomings of previously published reports that skewed toward lower-risk, highly selective mitral repairs for degenerative mitral disease. “They’re not really representative of the current state of minimally invasive mitral valve surgery as it currently stands in the higher risk patient population,” he said of previous studies.
Major outcomes were similar in both groups. “The mitral valve repair rate was about 81% for both groups, and the tricuspid valve repair rate was 8.8%,” Dr. Hawkins said. “About 35% had atrial fibrillation surgery, including both ablation and left atrial appendage ligation.”
Dr. Hawkins characterized outcomes in both surgical groups as “excellent,” and added, “The operative mortality rate was 1.3% and the major morbidity rate was 11% and not different between groups.”
Some key operative characteristics differed between the two groups. “As expected the cross clamp times and bypass times for the minimally invasive approaches were longer,” Dr. Hawkins said. Also, those who had minimally invasive mitral surgery had a “dramatic decrease” in transfusion rates.
With regard to resource utilization, minimally invasive surgery had longer operative times – an average of 291 minutes vs. 222 minutes (P less than .0001) – but similar or improved use of postoperative resources. “We see that the minimally invasive approach leads to decreased treatment and ancillary costs without a statistically significant difference in surgical costs despite the longer operative times,” Dr. Hawkins said.
However, he noted the high variability of total hospital costs in higher-risk populations complicate any head-to-head comparisons of resource utilization between the conventional and minimally invasive approaches, so the researchers attempted to drill down to identify predictors of resource use. Using a regression model, they found that minimally invasive approach may actually save money, although this finding was not statistically significant (–$1,524; P = 0.83).
“We see that the major drivers of costs are complications,” Dr. Hawkins said. “Morbidity and mortality led to a $54,000 cost increase, and the addition of tricuspid repair also led to about $60,000 higher costs, which is more likely related to higher risk and thus complications. The costs of higher-acuity cases are driven by the complications and not the approach.”
Dr. Hawkins reported no financial relationships. Dr. Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
NEW YORK – Minimally invasive mitral valve surgery provides outcomes that match those of conventional sternotomy without increasing use of resources, and lower costs after surgery offset potentially higher operation costs, according to a single-center, propensity-matched analysis of almost 500 patients presented at the meeting sponsored by the American Association for Thoracic Surgery.
“Minimally invasive mitral surgery has excellent outcomes with fewer transfusions and less time ventilated in this representative cohort,” said Robert Hawkins, MD, of the University of Virginia, Charlottesville, in reporting the results.
“While operative times were longer, surgical costs remained statistically similar, and minimally invasive mitral surgery was associated with similar total costs in more complex mitral cases.”
Dr. Hawkins said this study included higher risk patients to attempt to overcome shortcomings of previously published reports that skewed toward lower-risk, highly selective mitral repairs for degenerative mitral disease. “They’re not really representative of the current state of minimally invasive mitral valve surgery as it currently stands in the higher risk patient population,” he said of previous studies.
Major outcomes were similar in both groups. “The mitral valve repair rate was about 81% for both groups, and the tricuspid valve repair rate was 8.8%,” Dr. Hawkins said. “About 35% had atrial fibrillation surgery, including both ablation and left atrial appendage ligation.”
Dr. Hawkins characterized outcomes in both surgical groups as “excellent,” and added, “The operative mortality rate was 1.3% and the major morbidity rate was 11% and not different between groups.”
Some key operative characteristics differed between the two groups. “As expected the cross clamp times and bypass times for the minimally invasive approaches were longer,” Dr. Hawkins said. Also, those who had minimally invasive mitral surgery had a “dramatic decrease” in transfusion rates.
With regard to resource utilization, minimally invasive surgery had longer operative times – an average of 291 minutes vs. 222 minutes (P less than .0001) – but similar or improved use of postoperative resources. “We see that the minimally invasive approach leads to decreased treatment and ancillary costs without a statistically significant difference in surgical costs despite the longer operative times,” Dr. Hawkins said.
However, he noted the high variability of total hospital costs in higher-risk populations complicate any head-to-head comparisons of resource utilization between the conventional and minimally invasive approaches, so the researchers attempted to drill down to identify predictors of resource use. Using a regression model, they found that minimally invasive approach may actually save money, although this finding was not statistically significant (–$1,524; P = 0.83).
“We see that the major drivers of costs are complications,” Dr. Hawkins said. “Morbidity and mortality led to a $54,000 cost increase, and the addition of tricuspid repair also led to about $60,000 higher costs, which is more likely related to higher risk and thus complications. The costs of higher-acuity cases are driven by the complications and not the approach.”
Dr. Hawkins reported no financial relationships. Dr. Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
NEW YORK – Minimally invasive mitral valve surgery provides outcomes that match those of conventional sternotomy without increasing use of resources, and lower costs after surgery offset potentially higher operation costs, according to a single-center, propensity-matched analysis of almost 500 patients presented at the meeting sponsored by the American Association for Thoracic Surgery.
“Minimally invasive mitral surgery has excellent outcomes with fewer transfusions and less time ventilated in this representative cohort,” said Robert Hawkins, MD, of the University of Virginia, Charlottesville, in reporting the results.
“While operative times were longer, surgical costs remained statistically similar, and minimally invasive mitral surgery was associated with similar total costs in more complex mitral cases.”
Dr. Hawkins said this study included higher risk patients to attempt to overcome shortcomings of previously published reports that skewed toward lower-risk, highly selective mitral repairs for degenerative mitral disease. “They’re not really representative of the current state of minimally invasive mitral valve surgery as it currently stands in the higher risk patient population,” he said of previous studies.
Major outcomes were similar in both groups. “The mitral valve repair rate was about 81% for both groups, and the tricuspid valve repair rate was 8.8%,” Dr. Hawkins said. “About 35% had atrial fibrillation surgery, including both ablation and left atrial appendage ligation.”
Dr. Hawkins characterized outcomes in both surgical groups as “excellent,” and added, “The operative mortality rate was 1.3% and the major morbidity rate was 11% and not different between groups.”
Some key operative characteristics differed between the two groups. “As expected the cross clamp times and bypass times for the minimally invasive approaches were longer,” Dr. Hawkins said. Also, those who had minimally invasive mitral surgery had a “dramatic decrease” in transfusion rates.
With regard to resource utilization, minimally invasive surgery had longer operative times – an average of 291 minutes vs. 222 minutes (P less than .0001) – but similar or improved use of postoperative resources. “We see that the minimally invasive approach leads to decreased treatment and ancillary costs without a statistically significant difference in surgical costs despite the longer operative times,” Dr. Hawkins said.
However, he noted the high variability of total hospital costs in higher-risk populations complicate any head-to-head comparisons of resource utilization between the conventional and minimally invasive approaches, so the researchers attempted to drill down to identify predictors of resource use. Using a regression model, they found that minimally invasive approach may actually save money, although this finding was not statistically significant (–$1,524; P = 0.83).
“We see that the major drivers of costs are complications,” Dr. Hawkins said. “Morbidity and mortality led to a $54,000 cost increase, and the addition of tricuspid repair also led to about $60,000 higher costs, which is more likely related to higher risk and thus complications. The costs of higher-acuity cases are driven by the complications and not the approach.”
Dr. Hawkins reported no financial relationships. Dr. Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
AT THE 2017 MITRAL VALVE CONCLAVE
Key clinical point: Outcomes and costs of minimally invasive mitral surgery are similar to that of conventional sternotomy for mitral valve surgery.
Major finding: Mortality rates of 1.3% and major morbidity rates of 11% were similar in both groups.
Data source: Propensity-matched analysis of 479 patients who had a primary mitral valve operation from January 2010 to June 2016 at the University of Virginia.
Disclosures: Dr. Hawkins reported no financial disclosures. Coauthor Dr. Gorav Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
CAR T-cell therapy shows early promise in DLBCL
LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.
In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.
At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.
“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.
He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.
Patients
Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.
The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.
Treatment
Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.
Thirty patients received a single dose of JCAR017 at 5 x 107 CAR cells (dose-level 1, single [DL1S]).
Six patients received 2 doses of 5 x 107 CAR cells (dose-level 1, double [DL1D]).
Nineteen patients received a single dose of 1 x 108 CAR cells (dose-level 2, single [DL2S]).
Safety
More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.
Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.
One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.
Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.
The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).
There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).
“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.
Response
Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Dr Abramson noted that there was a dose-response relationship.
Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.
At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.
Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.
At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy. 
LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.
In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.
At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.
“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.
He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.
Patients
Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.
The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.
Treatment
Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.
Thirty patients received a single dose of JCAR017 at 5 x 107 CAR cells (dose-level 1, single [DL1S]).
Six patients received 2 doses of 5 x 107 CAR cells (dose-level 1, double [DL1D]).
Nineteen patients received a single dose of 1 x 108 CAR cells (dose-level 2, single [DL2S]).
Safety
More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.
Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.
One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.
Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.
The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).
There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).
“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.
Response
Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Dr Abramson noted that there was a dose-response relationship.
Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.
At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.
Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.
At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.
LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.
In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.
At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.
“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.
He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.
Patients
Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.
The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.
Treatment
Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.
Thirty patients received a single dose of JCAR017 at 5 x 107 CAR cells (dose-level 1, single [DL1S]).
Six patients received 2 doses of 5 x 107 CAR cells (dose-level 1, double [DL1D]).
Nineteen patients received a single dose of 1 x 108 CAR cells (dose-level 2, single [DL2S]).
Safety
More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.
Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.
One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.
Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.
The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).
There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).
“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.
Response
Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Dr Abramson noted that there was a dose-response relationship.
Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.
At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.
Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.
At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.
SCD therapy granted access to PRIME program
The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).
GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
About PRIME
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
Phase 1/2 trial
The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.
Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).
GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
About PRIME
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
Phase 1/2 trial
The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.
Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).
GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
About PRIME
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
Phase 1/2 trial
The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.
Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).