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Adolescents, young adults endorse marijuana for IBD
according to study findings.
In a cross-sectional study of 99 patients with IBD aged 13-22 years, 32% of participants reported ever having used marijuana or endorsing use in the past 6 months. Additionally, 42% of patients perceived little to no risk of harm with regular use, reported Edward J. Hoffenberg, MD, of the departments of pediatrics and psychiatry at the University of Colorado, Aurora, and his associates.
Overall, 62 patients had a diagnosis of Crohn’s disease, 27 had ulcerative colitis, and 10 had indeterminate/unknown colitis. Patients in the ever-use group were older (mean, 17 years) than those in the never-use group (mean, 15.9 years). Serum cannabinoids were detected in 50% of patients in the ever-use group. “The detection of serum cannabinoids only in the ever-users is consistent with truthful reporting,” the researchers said.
Additionally, 80% of ever-users and 25% of never users perceived low to no risk of harm with regular use. After adjustment for age, ever-users were 10.7 times more likely to perceive low to no risk of harm (odds ratio, 10.7; P less than .001), the authors reported.
Weekly and daily marijuana use was reported by 52% and 31% of ever-users, respectively; 9% reported daily or almost daily use. Medical reasons for use was endorsed by 57%, and 53% reported physical pain relief as a reason. Nonmedical recreational or psychological reasons for use were reported by 87%. Problems with use were reported by 37% of users, including cravings or strong desire to use (20%), needing to use more to achieve the same effect (17%), and using a larger amount for longer than intended (17%).
“There is a need for further understanding of the potential medical benefits of marijuana use in IBD,” Dr. Hoffenberg and his associates wrote. “Theoretically, a different study design, such as a randomized controlled trial of marijuana use or placebo, could better evaluate the safety and benefit of frequent marijuana use for induction or maintenance of remission.”
Limitations of the study include difficulty determining differences in disease activity between groups because of the large number of patients with inactive or mild disease, as well as the need to group patients with Crohn’s disease and ulcerative colitis together because of the small total number of participants who endorse marijuana use.
The study was funded by the Colorado Department of Public Health and Environment. No conflicts of interest were reported.
SOURCE: Hoffenberg EJ et al. 2018. doi: 10.1016/j.jpeds.2018.03.041.
according to study findings.
In a cross-sectional study of 99 patients with IBD aged 13-22 years, 32% of participants reported ever having used marijuana or endorsing use in the past 6 months. Additionally, 42% of patients perceived little to no risk of harm with regular use, reported Edward J. Hoffenberg, MD, of the departments of pediatrics and psychiatry at the University of Colorado, Aurora, and his associates.
Overall, 62 patients had a diagnosis of Crohn’s disease, 27 had ulcerative colitis, and 10 had indeterminate/unknown colitis. Patients in the ever-use group were older (mean, 17 years) than those in the never-use group (mean, 15.9 years). Serum cannabinoids were detected in 50% of patients in the ever-use group. “The detection of serum cannabinoids only in the ever-users is consistent with truthful reporting,” the researchers said.
Additionally, 80% of ever-users and 25% of never users perceived low to no risk of harm with regular use. After adjustment for age, ever-users were 10.7 times more likely to perceive low to no risk of harm (odds ratio, 10.7; P less than .001), the authors reported.
Weekly and daily marijuana use was reported by 52% and 31% of ever-users, respectively; 9% reported daily or almost daily use. Medical reasons for use was endorsed by 57%, and 53% reported physical pain relief as a reason. Nonmedical recreational or psychological reasons for use were reported by 87%. Problems with use were reported by 37% of users, including cravings or strong desire to use (20%), needing to use more to achieve the same effect (17%), and using a larger amount for longer than intended (17%).
“There is a need for further understanding of the potential medical benefits of marijuana use in IBD,” Dr. Hoffenberg and his associates wrote. “Theoretically, a different study design, such as a randomized controlled trial of marijuana use or placebo, could better evaluate the safety and benefit of frequent marijuana use for induction or maintenance of remission.”
Limitations of the study include difficulty determining differences in disease activity between groups because of the large number of patients with inactive or mild disease, as well as the need to group patients with Crohn’s disease and ulcerative colitis together because of the small total number of participants who endorse marijuana use.
The study was funded by the Colorado Department of Public Health and Environment. No conflicts of interest were reported.
SOURCE: Hoffenberg EJ et al. 2018. doi: 10.1016/j.jpeds.2018.03.041.
according to study findings.
In a cross-sectional study of 99 patients with IBD aged 13-22 years, 32% of participants reported ever having used marijuana or endorsing use in the past 6 months. Additionally, 42% of patients perceived little to no risk of harm with regular use, reported Edward J. Hoffenberg, MD, of the departments of pediatrics and psychiatry at the University of Colorado, Aurora, and his associates.
Overall, 62 patients had a diagnosis of Crohn’s disease, 27 had ulcerative colitis, and 10 had indeterminate/unknown colitis. Patients in the ever-use group were older (mean, 17 years) than those in the never-use group (mean, 15.9 years). Serum cannabinoids were detected in 50% of patients in the ever-use group. “The detection of serum cannabinoids only in the ever-users is consistent with truthful reporting,” the researchers said.
Additionally, 80% of ever-users and 25% of never users perceived low to no risk of harm with regular use. After adjustment for age, ever-users were 10.7 times more likely to perceive low to no risk of harm (odds ratio, 10.7; P less than .001), the authors reported.
Weekly and daily marijuana use was reported by 52% and 31% of ever-users, respectively; 9% reported daily or almost daily use. Medical reasons for use was endorsed by 57%, and 53% reported physical pain relief as a reason. Nonmedical recreational or psychological reasons for use were reported by 87%. Problems with use were reported by 37% of users, including cravings or strong desire to use (20%), needing to use more to achieve the same effect (17%), and using a larger amount for longer than intended (17%).
“There is a need for further understanding of the potential medical benefits of marijuana use in IBD,” Dr. Hoffenberg and his associates wrote. “Theoretically, a different study design, such as a randomized controlled trial of marijuana use or placebo, could better evaluate the safety and benefit of frequent marijuana use for induction or maintenance of remission.”
Limitations of the study include difficulty determining differences in disease activity between groups because of the large number of patients with inactive or mild disease, as well as the need to group patients with Crohn’s disease and ulcerative colitis together because of the small total number of participants who endorse marijuana use.
The study was funded by the Colorado Department of Public Health and Environment. No conflicts of interest were reported.
SOURCE: Hoffenberg EJ et al. 2018. doi: 10.1016/j.jpeds.2018.03.041.
FROM THE JOURNAL OF PEDIATRICS
Key clinical point: Many adolescents and young adults with IBD use marijuana and perceive little to no harm from regular use.
Major finding: Of the participants in the study, 32% reported ever having used marijuana or endorsing use in the past 6 months, and 42% perceived little to no risk of harm with regular use.
Study details: A cross-sectional study of 99 IBD patients aged 13-22 years at Children’s Hospital Colorado.
Disclosures: The study was funded by the Colorado Department of Public Health and Environment. No conflicts of interest were reported.
Source: Hoffenberg EJ et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.041.
Early results favorable for combo TLR9 agonist + pembro in advanced melanoma
CHICAGO – The intratumoral Toll-Like Receptor 9 (TLR-9) agonist, CMP-001, in combination with pembrolizumab in advanced melanoma patients, was well tolerated with a durable systemic clinical response, according to early results from an ongoing phase 1 trial.
Objective response rates on weekly (n = 56) and every 3 weeks schedules (n = 13) were 23% (13%-36%) and 15% (2%-45%) respectively, reported Mohammed M. Milhem, MBBS, of the University of Iowa, Iowa City.
For those dosed weekly at low dose (less than 5 mL) and high dose (5 mL or more), the ORR was 19% (n = 43, 95% confidence interval, 8%-33%) and 27% (n = 26, 95% CI, 12%-48%), respectively. Activity was demonstrated in subjects regardless of tumor burden, Dr. Milhem said at the annual meeting of the American Association for Cancer Research.
In this phase 1b study with a 3+3 design of dose escalation and expansion, the researchers enrolled patients with advanced melanoma who did not respond or had progressed resistant on prior anti-PD-1 monotherapy or in combination. CMP-001 was injected intratumorally in combination with pembrolizumab as per label intravenously.
The study drug CMP-001 has two components, a 30-mer CpG-A DNA oligonucleotide and a nonvirulent virus-like particle (VLP). The CpG-A DNA is packaged within the VLP that protects it from degradation and also allows TLR9 receptor uptake. CpG-A DNA acts as a TLR9 agonist by binding to it, thereby activating plasmacytoid dendritic cells (pDCs) within the tumor microenvironment. The activation results in secretion of large amounts of type 1 interferon and Th1 chemokines, changing the microenvironment from a “cold/desert-like” immune suppressed state to a “hot” antitumor inflamed state, Dr. Milhem said.
“The T cells thus generated can mediate tumor rejection both in the injected and noninjected tumor,” he said. Two CMP-001 schedules were evaluated, weekly for 7 weeks or weekly for 2 weeks, followed thereafter by every 3 weeks until discontinuation (due to progression, toxicity, investigator decision, or withdrawal of consent). Scans were done every 12 weeks and tumor response was assessed by RECIST v1.1.
The CMP-001 dose escalation scheme ranged from 1 mg to 10 mg. The maximum tolerated dose was not reached and the dose of 5 mg/weekly plus pembrolizumab was used for the dose expansion phase. It was up to the investigator to increase the dose to 10 mg since maximum tolerated dose was not reached. The key inclusion criteria were metastatic or unresectable melanoma; in the dose escalation phase prior best response to anti-PD1-based therapy was disease progression or stable disease. In the dose expansion phase, patients who had progressed on anti-PD1 based therapy were allowed regardless of best response. There was no restriction on the number of prior lines of therapy.
A total of 69 subjects were treated, 44 subjects from dose escalation and 25 in the expansion phase (ongoing). Two subjects discontinued because of treatment-related adverse events. The rest of the patients had a manageable toxicity profile consisting predominantly of fever, nausea/vomiting, hypotension and rigors. Severe grade 3/4 treatment-related adverse events were reported in more than 1 subject, with hypotension (n = 9, 13%) being the most prominent AE, followed by anemia (n = 2, 3%), chills (n = 2, 3%), and hypertension (n = 2, 3%). Hypotension was manageable by responsive fluid resuscitation and in some patients required stress dose steroids. Most of these side effects occurred 1-4 hours after the CMP-001 injection.
Of the 18 responders, 1 progressed, 2 withdrew consent, and 13 remain on study with 2 subjects maintaining their response though week 72. The median duration of response was not reached. Regression of noninjected tumors occurred in cutaneous, nodal, hepatic, and splenic metastases.
“CMP-001 plus pembrolizumab induced systemic antitumor activity, and not just local efficacy since both injected and noninjected target lesions changed from baseline per RECIST,” Dr. Milhem said. Not only did the responders show a rapid reduction in target lesions from baseline, but also a durable tumor regression as usually seen with other immunotherapeutics.
Immunohistochemical analysis of tumor biopsies demonstrated increase in CD8 (greater than fivefold) and PD-L1 expression, 5 weeks after therapy in a subset of patients with pre- and posttreatment biopsies. Transcriptional analysis by RNA-seq revealed induction of T cell inflamed gene signature, notably significant upregulation of TLR, and IFN-responsive genes.
It would be interesting to further investigate how this combination therapy compares with other strategies in a similar clinical scenario, such as oncolytic virus, other TLR ligands or means of APC activation, discussant Jedd Wolchok, MD, PhD, pointed out. Understanding resistance mechanisms at an individual patient level and optimal patient selection for this combination therapy remains a challenge, he said.
Dr. Milhem had no financial relationships to disclose.
SOURCE: Milhem MD et al. AACR Annual Meeting Abstract CT144.
CHICAGO – The intratumoral Toll-Like Receptor 9 (TLR-9) agonist, CMP-001, in combination with pembrolizumab in advanced melanoma patients, was well tolerated with a durable systemic clinical response, according to early results from an ongoing phase 1 trial.
Objective response rates on weekly (n = 56) and every 3 weeks schedules (n = 13) were 23% (13%-36%) and 15% (2%-45%) respectively, reported Mohammed M. Milhem, MBBS, of the University of Iowa, Iowa City.
For those dosed weekly at low dose (less than 5 mL) and high dose (5 mL or more), the ORR was 19% (n = 43, 95% confidence interval, 8%-33%) and 27% (n = 26, 95% CI, 12%-48%), respectively. Activity was demonstrated in subjects regardless of tumor burden, Dr. Milhem said at the annual meeting of the American Association for Cancer Research.
In this phase 1b study with a 3+3 design of dose escalation and expansion, the researchers enrolled patients with advanced melanoma who did not respond or had progressed resistant on prior anti-PD-1 monotherapy or in combination. CMP-001 was injected intratumorally in combination with pembrolizumab as per label intravenously.
The study drug CMP-001 has two components, a 30-mer CpG-A DNA oligonucleotide and a nonvirulent virus-like particle (VLP). The CpG-A DNA is packaged within the VLP that protects it from degradation and also allows TLR9 receptor uptake. CpG-A DNA acts as a TLR9 agonist by binding to it, thereby activating plasmacytoid dendritic cells (pDCs) within the tumor microenvironment. The activation results in secretion of large amounts of type 1 interferon and Th1 chemokines, changing the microenvironment from a “cold/desert-like” immune suppressed state to a “hot” antitumor inflamed state, Dr. Milhem said.
“The T cells thus generated can mediate tumor rejection both in the injected and noninjected tumor,” he said. Two CMP-001 schedules were evaluated, weekly for 7 weeks or weekly for 2 weeks, followed thereafter by every 3 weeks until discontinuation (due to progression, toxicity, investigator decision, or withdrawal of consent). Scans were done every 12 weeks and tumor response was assessed by RECIST v1.1.
The CMP-001 dose escalation scheme ranged from 1 mg to 10 mg. The maximum tolerated dose was not reached and the dose of 5 mg/weekly plus pembrolizumab was used for the dose expansion phase. It was up to the investigator to increase the dose to 10 mg since maximum tolerated dose was not reached. The key inclusion criteria were metastatic or unresectable melanoma; in the dose escalation phase prior best response to anti-PD1-based therapy was disease progression or stable disease. In the dose expansion phase, patients who had progressed on anti-PD1 based therapy were allowed regardless of best response. There was no restriction on the number of prior lines of therapy.
A total of 69 subjects were treated, 44 subjects from dose escalation and 25 in the expansion phase (ongoing). Two subjects discontinued because of treatment-related adverse events. The rest of the patients had a manageable toxicity profile consisting predominantly of fever, nausea/vomiting, hypotension and rigors. Severe grade 3/4 treatment-related adverse events were reported in more than 1 subject, with hypotension (n = 9, 13%) being the most prominent AE, followed by anemia (n = 2, 3%), chills (n = 2, 3%), and hypertension (n = 2, 3%). Hypotension was manageable by responsive fluid resuscitation and in some patients required stress dose steroids. Most of these side effects occurred 1-4 hours after the CMP-001 injection.
Of the 18 responders, 1 progressed, 2 withdrew consent, and 13 remain on study with 2 subjects maintaining their response though week 72. The median duration of response was not reached. Regression of noninjected tumors occurred in cutaneous, nodal, hepatic, and splenic metastases.
“CMP-001 plus pembrolizumab induced systemic antitumor activity, and not just local efficacy since both injected and noninjected target lesions changed from baseline per RECIST,” Dr. Milhem said. Not only did the responders show a rapid reduction in target lesions from baseline, but also a durable tumor regression as usually seen with other immunotherapeutics.
Immunohistochemical analysis of tumor biopsies demonstrated increase in CD8 (greater than fivefold) and PD-L1 expression, 5 weeks after therapy in a subset of patients with pre- and posttreatment biopsies. Transcriptional analysis by RNA-seq revealed induction of T cell inflamed gene signature, notably significant upregulation of TLR, and IFN-responsive genes.
It would be interesting to further investigate how this combination therapy compares with other strategies in a similar clinical scenario, such as oncolytic virus, other TLR ligands or means of APC activation, discussant Jedd Wolchok, MD, PhD, pointed out. Understanding resistance mechanisms at an individual patient level and optimal patient selection for this combination therapy remains a challenge, he said.
Dr. Milhem had no financial relationships to disclose.
SOURCE: Milhem MD et al. AACR Annual Meeting Abstract CT144.
CHICAGO – The intratumoral Toll-Like Receptor 9 (TLR-9) agonist, CMP-001, in combination with pembrolizumab in advanced melanoma patients, was well tolerated with a durable systemic clinical response, according to early results from an ongoing phase 1 trial.
Objective response rates on weekly (n = 56) and every 3 weeks schedules (n = 13) were 23% (13%-36%) and 15% (2%-45%) respectively, reported Mohammed M. Milhem, MBBS, of the University of Iowa, Iowa City.
For those dosed weekly at low dose (less than 5 mL) and high dose (5 mL or more), the ORR was 19% (n = 43, 95% confidence interval, 8%-33%) and 27% (n = 26, 95% CI, 12%-48%), respectively. Activity was demonstrated in subjects regardless of tumor burden, Dr. Milhem said at the annual meeting of the American Association for Cancer Research.
In this phase 1b study with a 3+3 design of dose escalation and expansion, the researchers enrolled patients with advanced melanoma who did not respond or had progressed resistant on prior anti-PD-1 monotherapy or in combination. CMP-001 was injected intratumorally in combination with pembrolizumab as per label intravenously.
The study drug CMP-001 has two components, a 30-mer CpG-A DNA oligonucleotide and a nonvirulent virus-like particle (VLP). The CpG-A DNA is packaged within the VLP that protects it from degradation and also allows TLR9 receptor uptake. CpG-A DNA acts as a TLR9 agonist by binding to it, thereby activating plasmacytoid dendritic cells (pDCs) within the tumor microenvironment. The activation results in secretion of large amounts of type 1 interferon and Th1 chemokines, changing the microenvironment from a “cold/desert-like” immune suppressed state to a “hot” antitumor inflamed state, Dr. Milhem said.
“The T cells thus generated can mediate tumor rejection both in the injected and noninjected tumor,” he said. Two CMP-001 schedules were evaluated, weekly for 7 weeks or weekly for 2 weeks, followed thereafter by every 3 weeks until discontinuation (due to progression, toxicity, investigator decision, or withdrawal of consent). Scans were done every 12 weeks and tumor response was assessed by RECIST v1.1.
The CMP-001 dose escalation scheme ranged from 1 mg to 10 mg. The maximum tolerated dose was not reached and the dose of 5 mg/weekly plus pembrolizumab was used for the dose expansion phase. It was up to the investigator to increase the dose to 10 mg since maximum tolerated dose was not reached. The key inclusion criteria were metastatic or unresectable melanoma; in the dose escalation phase prior best response to anti-PD1-based therapy was disease progression or stable disease. In the dose expansion phase, patients who had progressed on anti-PD1 based therapy were allowed regardless of best response. There was no restriction on the number of prior lines of therapy.
A total of 69 subjects were treated, 44 subjects from dose escalation and 25 in the expansion phase (ongoing). Two subjects discontinued because of treatment-related adverse events. The rest of the patients had a manageable toxicity profile consisting predominantly of fever, nausea/vomiting, hypotension and rigors. Severe grade 3/4 treatment-related adverse events were reported in more than 1 subject, with hypotension (n = 9, 13%) being the most prominent AE, followed by anemia (n = 2, 3%), chills (n = 2, 3%), and hypertension (n = 2, 3%). Hypotension was manageable by responsive fluid resuscitation and in some patients required stress dose steroids. Most of these side effects occurred 1-4 hours after the CMP-001 injection.
Of the 18 responders, 1 progressed, 2 withdrew consent, and 13 remain on study with 2 subjects maintaining their response though week 72. The median duration of response was not reached. Regression of noninjected tumors occurred in cutaneous, nodal, hepatic, and splenic metastases.
“CMP-001 plus pembrolizumab induced systemic antitumor activity, and not just local efficacy since both injected and noninjected target lesions changed from baseline per RECIST,” Dr. Milhem said. Not only did the responders show a rapid reduction in target lesions from baseline, but also a durable tumor regression as usually seen with other immunotherapeutics.
Immunohistochemical analysis of tumor biopsies demonstrated increase in CD8 (greater than fivefold) and PD-L1 expression, 5 weeks after therapy in a subset of patients with pre- and posttreatment biopsies. Transcriptional analysis by RNA-seq revealed induction of T cell inflamed gene signature, notably significant upregulation of TLR, and IFN-responsive genes.
It would be interesting to further investigate how this combination therapy compares with other strategies in a similar clinical scenario, such as oncolytic virus, other TLR ligands or means of APC activation, discussant Jedd Wolchok, MD, PhD, pointed out. Understanding resistance mechanisms at an individual patient level and optimal patient selection for this combination therapy remains a challenge, he said.
Dr. Milhem had no financial relationships to disclose.
SOURCE: Milhem MD et al. AACR Annual Meeting Abstract CT144.
REPORTING FROM THE AACR ANNUAL MEETING
Key clinical point: The combination demonstrated a manageable toxicity profile with ORR of 22%.
Major finding: Objective response rates on weekly (n = 56) and every 3 weeks schedules (n = 13) were 23% (13%-36%) and 15% (2%-45%) respectively.
Study details: This phase 1b study comprised 69 patients (44 in escalation and 25 in expansion).
Disclosures: Dr. Milhem had no financial relationships to disclose.
Source: Milhem MD et al. AACR Annual Meeting. Abstract CT144.
Adjunct treatments assist with persistent asthma
Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.
Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.
Overall, patients who took a LAMA had a lower risk of asthma exacerbation requiring systemic corticosteroids and improved spirometry measures than did the patients who took a placebo or used another controller as an adjunct therapy.
In trials that compared LAMAs with placebo as an add-on to inhaled corticosteroids, LAMA patients experienced a significantly reduced risk of exacerbation requiring systemic corticosteroids (–1.8) and a significantly reduced risk of asthma worsening (–4.8). Another benefit seen in the patients who used a LAMA rather than those who used a placebo was improved spirometry measures, but the differences between these two patient groups’ numbers did not reach statistical significance.
The analysis also included studies that compared “triple therapy” – defined as use of a LAMA as add-on therapy to inhaled corticosteroids and LABAs – to LABA plus use of inhaled corticosteroids.
Triple therapy was significantly associated with a lower risk of asthma worsening, compared with inhaled corticosteroids and LABAs, but not with a reduced risk of exacerbation. In addition, no significant differences appeared in Asthma Control Questionnaire-7 scores or overall Asthma Quality of Life Questionnaire scores between the two patient groups.
“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.
The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.
In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.
Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.
In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.
In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV1) and a reduction in the need for rescue medication.
The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.
No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV1, forced vital capacity, or the percentage of predicted FEV1, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.
The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.
However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.
The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
Asthma remains a major public health problem in the United States, but 11 years have passed since the last update to treatment guidelines, and an update to the current guidelines for asthma treatment is needed, wrote Jerry A. Krishnan, MD, and David H. Au, MD, in an accompanying editorial (JAMA. 2018;319[14]:1441-3). “It is time to connect the efforts of the FDA, the evidence presented by Sobieraj et al., and the support from the National Education and Prevention Program to update the 2007 [Expert Panel Report 3] guidelines on asthma.”
Both reviews showed effectiveness for the treatments being assessed, compared with placebo, but each had limitations, the editorialists noted.
The study findings in the report on the efficacy of inhaled long-acting muscarinic antagonists (LAMAs) in adolescents and adults with uncontrolled asthma were limited by several factors including a focus primarily on tiotropium, absence of data on potential harms and relative costs of treatment, and a lack of data on children younger than 12 years, they noted. The findings in the analysis of the strategy known as Single Maintenance and Reliever Therapy (SMART) containing formoterol, a long-acting beta2-agonist, were similarly limited by a lack of assessment of potential harm and a data on children within the same age group, they said.
However, the effectiveness of the treatments seen in both reviews suggest that the forthcoming revision of the Expert Panel Report 3 guidelines on asthma from the National Asthma Education and Prevention Program should include the option for inhaled tiotropium, a LAMA, and for the formoterol-based SMART protocol, the editorialists wrote.
“For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control while using inhaled corticosteroids alone,” they said. The new guidelines should include evidence for the SMART therapy as well, but “studies assessing the efficacy of SMART using combination formoterol and budesonide via a metered-dose inhaler are needed,” they concluded.
Dr. Krishnan is affiliated with the division of pulmonary, critical care, sleep, and allergy at the University of Illinois, Chicago, and disclosed having received compensation from Sanofi for participation on an independent data-monitoring committee. Dr. Au is affiliated with the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and disclosed having received compensation from Novartis for participation on a data-monitoring committee and for serving as a consultant to Gilead Sciences.
Asthma remains a major public health problem in the United States, but 11 years have passed since the last update to treatment guidelines, and an update to the current guidelines for asthma treatment is needed, wrote Jerry A. Krishnan, MD, and David H. Au, MD, in an accompanying editorial (JAMA. 2018;319[14]:1441-3). “It is time to connect the efforts of the FDA, the evidence presented by Sobieraj et al., and the support from the National Education and Prevention Program to update the 2007 [Expert Panel Report 3] guidelines on asthma.”
Both reviews showed effectiveness for the treatments being assessed, compared with placebo, but each had limitations, the editorialists noted.
The study findings in the report on the efficacy of inhaled long-acting muscarinic antagonists (LAMAs) in adolescents and adults with uncontrolled asthma were limited by several factors including a focus primarily on tiotropium, absence of data on potential harms and relative costs of treatment, and a lack of data on children younger than 12 years, they noted. The findings in the analysis of the strategy known as Single Maintenance and Reliever Therapy (SMART) containing formoterol, a long-acting beta2-agonist, were similarly limited by a lack of assessment of potential harm and a data on children within the same age group, they said.
However, the effectiveness of the treatments seen in both reviews suggest that the forthcoming revision of the Expert Panel Report 3 guidelines on asthma from the National Asthma Education and Prevention Program should include the option for inhaled tiotropium, a LAMA, and for the formoterol-based SMART protocol, the editorialists wrote.
“For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control while using inhaled corticosteroids alone,” they said. The new guidelines should include evidence for the SMART therapy as well, but “studies assessing the efficacy of SMART using combination formoterol and budesonide via a metered-dose inhaler are needed,” they concluded.
Dr. Krishnan is affiliated with the division of pulmonary, critical care, sleep, and allergy at the University of Illinois, Chicago, and disclosed having received compensation from Sanofi for participation on an independent data-monitoring committee. Dr. Au is affiliated with the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and disclosed having received compensation from Novartis for participation on a data-monitoring committee and for serving as a consultant to Gilead Sciences.
Asthma remains a major public health problem in the United States, but 11 years have passed since the last update to treatment guidelines, and an update to the current guidelines for asthma treatment is needed, wrote Jerry A. Krishnan, MD, and David H. Au, MD, in an accompanying editorial (JAMA. 2018;319[14]:1441-3). “It is time to connect the efforts of the FDA, the evidence presented by Sobieraj et al., and the support from the National Education and Prevention Program to update the 2007 [Expert Panel Report 3] guidelines on asthma.”
Both reviews showed effectiveness for the treatments being assessed, compared with placebo, but each had limitations, the editorialists noted.
The study findings in the report on the efficacy of inhaled long-acting muscarinic antagonists (LAMAs) in adolescents and adults with uncontrolled asthma were limited by several factors including a focus primarily on tiotropium, absence of data on potential harms and relative costs of treatment, and a lack of data on children younger than 12 years, they noted. The findings in the analysis of the strategy known as Single Maintenance and Reliever Therapy (SMART) containing formoterol, a long-acting beta2-agonist, were similarly limited by a lack of assessment of potential harm and a data on children within the same age group, they said.
However, the effectiveness of the treatments seen in both reviews suggest that the forthcoming revision of the Expert Panel Report 3 guidelines on asthma from the National Asthma Education and Prevention Program should include the option for inhaled tiotropium, a LAMA, and for the formoterol-based SMART protocol, the editorialists wrote.
“For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control while using inhaled corticosteroids alone,” they said. The new guidelines should include evidence for the SMART therapy as well, but “studies assessing the efficacy of SMART using combination formoterol and budesonide via a metered-dose inhaler are needed,” they concluded.
Dr. Krishnan is affiliated with the division of pulmonary, critical care, sleep, and allergy at the University of Illinois, Chicago, and disclosed having received compensation from Sanofi for participation on an independent data-monitoring committee. Dr. Au is affiliated with the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and disclosed having received compensation from Novartis for participation on a data-monitoring committee and for serving as a consultant to Gilead Sciences.
Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.
Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.
Overall, patients who took a LAMA had a lower risk of asthma exacerbation requiring systemic corticosteroids and improved spirometry measures than did the patients who took a placebo or used another controller as an adjunct therapy.
In trials that compared LAMAs with placebo as an add-on to inhaled corticosteroids, LAMA patients experienced a significantly reduced risk of exacerbation requiring systemic corticosteroids (–1.8) and a significantly reduced risk of asthma worsening (–4.8). Another benefit seen in the patients who used a LAMA rather than those who used a placebo was improved spirometry measures, but the differences between these two patient groups’ numbers did not reach statistical significance.
The analysis also included studies that compared “triple therapy” – defined as use of a LAMA as add-on therapy to inhaled corticosteroids and LABAs – to LABA plus use of inhaled corticosteroids.
Triple therapy was significantly associated with a lower risk of asthma worsening, compared with inhaled corticosteroids and LABAs, but not with a reduced risk of exacerbation. In addition, no significant differences appeared in Asthma Control Questionnaire-7 scores or overall Asthma Quality of Life Questionnaire scores between the two patient groups.
“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.
The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.
In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.
Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.
In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.
In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV1) and a reduction in the need for rescue medication.
The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.
No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV1, forced vital capacity, or the percentage of predicted FEV1, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.
The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.
However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.
The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.
Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.
Overall, patients who took a LAMA had a lower risk of asthma exacerbation requiring systemic corticosteroids and improved spirometry measures than did the patients who took a placebo or used another controller as an adjunct therapy.
In trials that compared LAMAs with placebo as an add-on to inhaled corticosteroids, LAMA patients experienced a significantly reduced risk of exacerbation requiring systemic corticosteroids (–1.8) and a significantly reduced risk of asthma worsening (–4.8). Another benefit seen in the patients who used a LAMA rather than those who used a placebo was improved spirometry measures, but the differences between these two patient groups’ numbers did not reach statistical significance.
The analysis also included studies that compared “triple therapy” – defined as use of a LAMA as add-on therapy to inhaled corticosteroids and LABAs – to LABA plus use of inhaled corticosteroids.
Triple therapy was significantly associated with a lower risk of asthma worsening, compared with inhaled corticosteroids and LABAs, but not with a reduced risk of exacerbation. In addition, no significant differences appeared in Asthma Control Questionnaire-7 scores or overall Asthma Quality of Life Questionnaire scores between the two patient groups.
“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.
The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.
In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.
Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.
In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.
In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV1) and a reduction in the need for rescue medication.
The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.
No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV1, forced vital capacity, or the percentage of predicted FEV1, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.
The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.
However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.
The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
FROM JAMA
Key clinical point:
Major finding: LAMA patients had a risk difference of –1.8 for asthma exacerbations, compared with placebo users, while patients using the SMART protocol had an absolute risk difference of –2.8%, compared with those taking a higher dose of inhaled corticosteroids plus LABAs as a controller.
Study details: The data came from two reviews of randomized clinical trials; the first included 7,122 patients and the second included 22,524 patients.
Disclosures: The reviews were supported in part by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
Source: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
Anti-TNF drugs appear to lessen PD risk in IBD patients
Patients with inflammatory bowel disease had about a 28% higher risk of Parkinson’s disease (PD) than that of matched controls in a large retrospective analysis of administrative health care claims.
But tumor necrosis factor (TNF) inhibitor therapy appeared to attenuate this risk, wrote Inga Peter, PhD, of Icahn School of Medicine at Mount Sinai, New York, and her associates. Patients with inflammatory bowel disease (IBD) who received TNF inhibitors were 78% less likely to develop PD than were those who did not (P = .03). “Reducing systemic inflammation in at-risk individuals may decrease the incidence of PD [Parkinson disease],” the researchers wrote. The study was published online April 23 in JAMA Neurology.
The researchers queried the Truven Health MarketScan database and the Medicare Supplemental Database for patients with IBD from 2000 through 2016. The databases included more than 170 million patients, of whom 144,018 had at least two IBD-related claims, at least 6 months of follow-up, and no baseline PD diagnosis. These patients were matched by age, sex, and treatment year with 720,090 individuals without IBD from the same databases.
A total of 1,796 patients had at least two recorded PD diagnoses and had filled at least one associated prescription, said the researchers. Based on this PD definition, patients with IBD developed PD at a 28% higher rate than that of matched controls (adjusted IRR, 1.28; 95% CI, 1.14 to 1.44; P less than .001).
Among the IBD patients, those receiving anti-TNF therapy developed about 0.08 cases of PD for every 1,000 person-years, versus 0.76 PD cases per 1,000 person-years in the group not receiving anti-TNF therapy. After adjustment for age, sex, and time at risk, anti-TNF therapy was associated with a 78% reduction in the incidence of PD among IBD patients (adjusted incidence rate ratio, 0.22; 95% confidence interval, 0.05-0.88; P = .03).
“In summary, we showed a potential clinical link between IBD and PD, supporting shared mechanisms involved in the pathogenesis of these diseases,” the researchers wrote. “Moreover, our data suggest that early exposure to anti-TNF therapy may reduce the risk of PD among patients with IBD, potentially owing to a reduction in systemic inflammation. These findings should be further assessed and confirmed by other studies.”
Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.
SOURCE: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.
The research provides “a glimpse of the promise and beauty of big data for Parkinson’s disease (PD) and for neurology in general,” experts wrote in an editorial accompanying the study.
“Every physician knows how much can be learned by listening to a patient,” wrote Abby L. Olsen, MD, PhD, Trond Riise, PhD, and Clemens R. Scherzer, MD. “Imagine how much might be learned by scaling this singular experience to torrents of digital health data from millions of patients.”
If inflammatory bowel disease and PD share a common inflammatory etiology, anti–tumor necrosis factor therapy might well help prevent PD, they wrote. But a clinical trial testing that hypothesis would be “incredibly difficult and expensive” because PD has a fairly low incidence, even among people at increased risk.
To surmount this obstacle, the researchers created a “virtual” trial that repurposed old drugs for new potential benefit, the experts continued. Although the study fell short on follow-up time and certain clinical data (such as smoking status), it offered “exciting evidence” in support of this concept.
The editorialists are with Precision Neurology Program, Brigham and Women’s Hospital, Boston. These comments paraphrase their editorial (JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0345 ).
The research provides “a glimpse of the promise and beauty of big data for Parkinson’s disease (PD) and for neurology in general,” experts wrote in an editorial accompanying the study.
“Every physician knows how much can be learned by listening to a patient,” wrote Abby L. Olsen, MD, PhD, Trond Riise, PhD, and Clemens R. Scherzer, MD. “Imagine how much might be learned by scaling this singular experience to torrents of digital health data from millions of patients.”
If inflammatory bowel disease and PD share a common inflammatory etiology, anti–tumor necrosis factor therapy might well help prevent PD, they wrote. But a clinical trial testing that hypothesis would be “incredibly difficult and expensive” because PD has a fairly low incidence, even among people at increased risk.
To surmount this obstacle, the researchers created a “virtual” trial that repurposed old drugs for new potential benefit, the experts continued. Although the study fell short on follow-up time and certain clinical data (such as smoking status), it offered “exciting evidence” in support of this concept.
The editorialists are with Precision Neurology Program, Brigham and Women’s Hospital, Boston. These comments paraphrase their editorial (JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0345 ).
The research provides “a glimpse of the promise and beauty of big data for Parkinson’s disease (PD) and for neurology in general,” experts wrote in an editorial accompanying the study.
“Every physician knows how much can be learned by listening to a patient,” wrote Abby L. Olsen, MD, PhD, Trond Riise, PhD, and Clemens R. Scherzer, MD. “Imagine how much might be learned by scaling this singular experience to torrents of digital health data from millions of patients.”
If inflammatory bowel disease and PD share a common inflammatory etiology, anti–tumor necrosis factor therapy might well help prevent PD, they wrote. But a clinical trial testing that hypothesis would be “incredibly difficult and expensive” because PD has a fairly low incidence, even among people at increased risk.
To surmount this obstacle, the researchers created a “virtual” trial that repurposed old drugs for new potential benefit, the experts continued. Although the study fell short on follow-up time and certain clinical data (such as smoking status), it offered “exciting evidence” in support of this concept.
The editorialists are with Precision Neurology Program, Brigham and Women’s Hospital, Boston. These comments paraphrase their editorial (JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0345 ).
Patients with inflammatory bowel disease had about a 28% higher risk of Parkinson’s disease (PD) than that of matched controls in a large retrospective analysis of administrative health care claims.
But tumor necrosis factor (TNF) inhibitor therapy appeared to attenuate this risk, wrote Inga Peter, PhD, of Icahn School of Medicine at Mount Sinai, New York, and her associates. Patients with inflammatory bowel disease (IBD) who received TNF inhibitors were 78% less likely to develop PD than were those who did not (P = .03). “Reducing systemic inflammation in at-risk individuals may decrease the incidence of PD [Parkinson disease],” the researchers wrote. The study was published online April 23 in JAMA Neurology.
The researchers queried the Truven Health MarketScan database and the Medicare Supplemental Database for patients with IBD from 2000 through 2016. The databases included more than 170 million patients, of whom 144,018 had at least two IBD-related claims, at least 6 months of follow-up, and no baseline PD diagnosis. These patients were matched by age, sex, and treatment year with 720,090 individuals without IBD from the same databases.
A total of 1,796 patients had at least two recorded PD diagnoses and had filled at least one associated prescription, said the researchers. Based on this PD definition, patients with IBD developed PD at a 28% higher rate than that of matched controls (adjusted IRR, 1.28; 95% CI, 1.14 to 1.44; P less than .001).
Among the IBD patients, those receiving anti-TNF therapy developed about 0.08 cases of PD for every 1,000 person-years, versus 0.76 PD cases per 1,000 person-years in the group not receiving anti-TNF therapy. After adjustment for age, sex, and time at risk, anti-TNF therapy was associated with a 78% reduction in the incidence of PD among IBD patients (adjusted incidence rate ratio, 0.22; 95% confidence interval, 0.05-0.88; P = .03).
“In summary, we showed a potential clinical link between IBD and PD, supporting shared mechanisms involved in the pathogenesis of these diseases,” the researchers wrote. “Moreover, our data suggest that early exposure to anti-TNF therapy may reduce the risk of PD among patients with IBD, potentially owing to a reduction in systemic inflammation. These findings should be further assessed and confirmed by other studies.”
Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.
SOURCE: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.
Patients with inflammatory bowel disease had about a 28% higher risk of Parkinson’s disease (PD) than that of matched controls in a large retrospective analysis of administrative health care claims.
But tumor necrosis factor (TNF) inhibitor therapy appeared to attenuate this risk, wrote Inga Peter, PhD, of Icahn School of Medicine at Mount Sinai, New York, and her associates. Patients with inflammatory bowel disease (IBD) who received TNF inhibitors were 78% less likely to develop PD than were those who did not (P = .03). “Reducing systemic inflammation in at-risk individuals may decrease the incidence of PD [Parkinson disease],” the researchers wrote. The study was published online April 23 in JAMA Neurology.
The researchers queried the Truven Health MarketScan database and the Medicare Supplemental Database for patients with IBD from 2000 through 2016. The databases included more than 170 million patients, of whom 144,018 had at least two IBD-related claims, at least 6 months of follow-up, and no baseline PD diagnosis. These patients were matched by age, sex, and treatment year with 720,090 individuals without IBD from the same databases.
A total of 1,796 patients had at least two recorded PD diagnoses and had filled at least one associated prescription, said the researchers. Based on this PD definition, patients with IBD developed PD at a 28% higher rate than that of matched controls (adjusted IRR, 1.28; 95% CI, 1.14 to 1.44; P less than .001).
Among the IBD patients, those receiving anti-TNF therapy developed about 0.08 cases of PD for every 1,000 person-years, versus 0.76 PD cases per 1,000 person-years in the group not receiving anti-TNF therapy. After adjustment for age, sex, and time at risk, anti-TNF therapy was associated with a 78% reduction in the incidence of PD among IBD patients (adjusted incidence rate ratio, 0.22; 95% confidence interval, 0.05-0.88; P = .03).
“In summary, we showed a potential clinical link between IBD and PD, supporting shared mechanisms involved in the pathogenesis of these diseases,” the researchers wrote. “Moreover, our data suggest that early exposure to anti-TNF therapy may reduce the risk of PD among patients with IBD, potentially owing to a reduction in systemic inflammation. These findings should be further assessed and confirmed by other studies.”
Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.
SOURCE: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.
FROM JAMA NEUROLOGY
Key clinical point: Inflammatory bowel disease was associated with a significantly increased risk of Parkinson’s disease. Anti–tumor necrosis factor therapy appeared to lessen this risk.
Major finding: Patients with IBD had a 28% higher PD incidence than that of matched controls (adjusted IRR, 1.28; P less than .001). Patients with IBD who received anti-TNF therapy had a 78% lower incidence of PD compared with those who did not (adjusted IRR, 0.22; P = .03).
Study details: Administrative data claims analysis of 144,018 patients with IBD and 720,090 patients without IBD.
Disclosures: Dr. Peter received support from the Leona M. and Harry B. Helmsley Charitable Trust. AbbVie employed three coinvestigators. Two coinvestigators had other ties to Abbvie and Amgen.
Source: Peter I et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0605.
Meta-analysis finds no link between stroke and sickle cell trait
Those findings contrast with an earlier longitudinal study that found a 1.4-fold risk of ischemic stroke in SCT carriers, the authors noted.
In their study, neither crude stroke incidence rates nor regression analysis indicated a link between SCT and stroke, said first author Hyacinth I. Hyacinth, MD, PhD, MPH, of the Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, and his coauthors.
“The absence of an association between SCT and risk of ischemic stroke was consistent among the cohorts, and suggests that SCT is not an independent genetic risk factor for ischemic stroke among African Americans,” Dr. Hyacinth and his coauthors wrote.
The results may have implications for patient care. In particular, a more thorough evaluation of stroke in a patient with SCT may be warranted, instead of assuming that the SCT is an underlying cause of the stroke, they said.
The meta-analysis included a total of 19,464 subjects from four large, prospective, population-based studies with African American cohorts.
Results of the meta-analysis show that crude incidence of stroke was similar for individuals with SCT, at 2.9 per 1,000 person-years (95% confidence interval, 2.2-4.0), and for those with no SCT, at 3.2 per 1,000 person-years (95% CI, 2.7-3.8).
After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = 0.82), results further show.
It’s unclear why this study found no association between SCT and stroke when the earlier population-based study suggested a link between the two. Dr. Hyacinth and his coauthors suggested differences in study methods or proportion of individuals at risk for stroke may account for the divergent findings. They also controlled for left ventricular hypertrophy, while the previous study did not.
“However, in our analysis, adjusting for left ventricular hypertrophy did not change the direction of estimate effects,” they said in the report.
Further study is needed to determine whether or not SCT may be linked to a particular type of stroke. “We were unable to test the association of SCT with ischemic stroke subtypes,” the authors noted.
Dr. Hyacinth and his coauthors reported no conflicts of interest related to the study.
SOURCE: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi:10.1001/jamaneurol.2018.0571
Those findings contrast with an earlier longitudinal study that found a 1.4-fold risk of ischemic stroke in SCT carriers, the authors noted.
In their study, neither crude stroke incidence rates nor regression analysis indicated a link between SCT and stroke, said first author Hyacinth I. Hyacinth, MD, PhD, MPH, of the Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, and his coauthors.
“The absence of an association between SCT and risk of ischemic stroke was consistent among the cohorts, and suggests that SCT is not an independent genetic risk factor for ischemic stroke among African Americans,” Dr. Hyacinth and his coauthors wrote.
The results may have implications for patient care. In particular, a more thorough evaluation of stroke in a patient with SCT may be warranted, instead of assuming that the SCT is an underlying cause of the stroke, they said.
The meta-analysis included a total of 19,464 subjects from four large, prospective, population-based studies with African American cohorts.
Results of the meta-analysis show that crude incidence of stroke was similar for individuals with SCT, at 2.9 per 1,000 person-years (95% confidence interval, 2.2-4.0), and for those with no SCT, at 3.2 per 1,000 person-years (95% CI, 2.7-3.8).
After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = 0.82), results further show.
It’s unclear why this study found no association between SCT and stroke when the earlier population-based study suggested a link between the two. Dr. Hyacinth and his coauthors suggested differences in study methods or proportion of individuals at risk for stroke may account for the divergent findings. They also controlled for left ventricular hypertrophy, while the previous study did not.
“However, in our analysis, adjusting for left ventricular hypertrophy did not change the direction of estimate effects,” they said in the report.
Further study is needed to determine whether or not SCT may be linked to a particular type of stroke. “We were unable to test the association of SCT with ischemic stroke subtypes,” the authors noted.
Dr. Hyacinth and his coauthors reported no conflicts of interest related to the study.
SOURCE: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi:10.1001/jamaneurol.2018.0571
Those findings contrast with an earlier longitudinal study that found a 1.4-fold risk of ischemic stroke in SCT carriers, the authors noted.
In their study, neither crude stroke incidence rates nor regression analysis indicated a link between SCT and stroke, said first author Hyacinth I. Hyacinth, MD, PhD, MPH, of the Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, and his coauthors.
“The absence of an association between SCT and risk of ischemic stroke was consistent among the cohorts, and suggests that SCT is not an independent genetic risk factor for ischemic stroke among African Americans,” Dr. Hyacinth and his coauthors wrote.
The results may have implications for patient care. In particular, a more thorough evaluation of stroke in a patient with SCT may be warranted, instead of assuming that the SCT is an underlying cause of the stroke, they said.
The meta-analysis included a total of 19,464 subjects from four large, prospective, population-based studies with African American cohorts.
Results of the meta-analysis show that crude incidence of stroke was similar for individuals with SCT, at 2.9 per 1,000 person-years (95% confidence interval, 2.2-4.0), and for those with no SCT, at 3.2 per 1,000 person-years (95% CI, 2.7-3.8).
After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = 0.82), results further show.
It’s unclear why this study found no association between SCT and stroke when the earlier population-based study suggested a link between the two. Dr. Hyacinth and his coauthors suggested differences in study methods or proportion of individuals at risk for stroke may account for the divergent findings. They also controlled for left ventricular hypertrophy, while the previous study did not.
“However, in our analysis, adjusting for left ventricular hypertrophy did not change the direction of estimate effects,” they said in the report.
Further study is needed to determine whether or not SCT may be linked to a particular type of stroke. “We were unable to test the association of SCT with ischemic stroke subtypes,” the authors noted.
Dr. Hyacinth and his coauthors reported no conflicts of interest related to the study.
SOURCE: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi:10.1001/jamaneurol.2018.0571
FROM JAMA NEUROLOGY
Key clinical point: In contrast to results of a previous study, a meta-analysis has found no evidence linking sickle cell trait (SCT) and risk of incident ischemic stroke in African Americans.
Major finding: Crude stroke incidence was not different for SCT versus no SCT. After adjusting for stroke risk factors, the hazard ratio of stroke independently associated with SCT was 0.80 (95% CI, 0.47-1.35; P = .82).
Study details: A meta-analysis of the association between SCT and risk of incident ischemic stroke in four large prospective, population-based studies with African American cohorts (19,464 total subjects).
Disclosures: Authors reported no conflicts of interest related to the study.
Source: Hyacinth HI et al. JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0571.
Long-Term Perampanel Treatment Is Safe and Effective for Adolescents
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
Company discontinues phase 3 ADAPT for mRCC
A second interim analysis of
In ADAPT, 462 patients with previously untreated advanced or metastatic renal cell carcinoma (mRCC) were randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib versus sunitinib monotherapy, after undergoing cytoreductive nephrectomy.
In February 2017, the trial’s Independent Data Monitoring Committee had reviewed the data and concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended halting the trial. However, the principal investigators and the company, Argos Therapeutics, considered the data too immature to observe the delayed effects associated with immunotherapy and decided to continue the trial. They submitted a protocol amendment to the Food and Drug Administration adding additional co-primary endpoints, and in April of last year, met with the Food and Drug Administration, which accepted the amendment and agreed to continuation of the trial, according to a company press release issued in November.
In the latest interim analysis, which was conducted following an additional 51 deaths, median overall survival for the intent-to-treat patient population was 28.2 months for the combination arm (95% confidence interval, 23.4, 35.2) compared with 31.2 months (95% CI, 23.0, 44.5) for the control arm; this was one of four new co-primary endpoints. The hazard ratio was 1.10 (95% CI, 0.85, 1.42).
Other co-primary endpoints that were evaluated, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, did not demonstrate a favorable result, Argos Therapeutics said in a recent press release.
Rocapuldencel-T “consists of autologous dendritic cells programmed with amplified RNA from a patient’s primary tumor” and is “designed to overcome immunosuppression and induce broadly reactive, long-lasting anti-tumor memory T cells” according to the early interim analysis presented at the European Society for Medical Oncology (ESMO) 2017. The drug is also being evaluated in non–small cell lung cancer and bladder cancer.
A second interim analysis of
In ADAPT, 462 patients with previously untreated advanced or metastatic renal cell carcinoma (mRCC) were randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib versus sunitinib monotherapy, after undergoing cytoreductive nephrectomy.
In February 2017, the trial’s Independent Data Monitoring Committee had reviewed the data and concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended halting the trial. However, the principal investigators and the company, Argos Therapeutics, considered the data too immature to observe the delayed effects associated with immunotherapy and decided to continue the trial. They submitted a protocol amendment to the Food and Drug Administration adding additional co-primary endpoints, and in April of last year, met with the Food and Drug Administration, which accepted the amendment and agreed to continuation of the trial, according to a company press release issued in November.
In the latest interim analysis, which was conducted following an additional 51 deaths, median overall survival for the intent-to-treat patient population was 28.2 months for the combination arm (95% confidence interval, 23.4, 35.2) compared with 31.2 months (95% CI, 23.0, 44.5) for the control arm; this was one of four new co-primary endpoints. The hazard ratio was 1.10 (95% CI, 0.85, 1.42).
Other co-primary endpoints that were evaluated, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, did not demonstrate a favorable result, Argos Therapeutics said in a recent press release.
Rocapuldencel-T “consists of autologous dendritic cells programmed with amplified RNA from a patient’s primary tumor” and is “designed to overcome immunosuppression and induce broadly reactive, long-lasting anti-tumor memory T cells” according to the early interim analysis presented at the European Society for Medical Oncology (ESMO) 2017. The drug is also being evaluated in non–small cell lung cancer and bladder cancer.
A second interim analysis of
In ADAPT, 462 patients with previously untreated advanced or metastatic renal cell carcinoma (mRCC) were randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib versus sunitinib monotherapy, after undergoing cytoreductive nephrectomy.
In February 2017, the trial’s Independent Data Monitoring Committee had reviewed the data and concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended halting the trial. However, the principal investigators and the company, Argos Therapeutics, considered the data too immature to observe the delayed effects associated with immunotherapy and decided to continue the trial. They submitted a protocol amendment to the Food and Drug Administration adding additional co-primary endpoints, and in April of last year, met with the Food and Drug Administration, which accepted the amendment and agreed to continuation of the trial, according to a company press release issued in November.
In the latest interim analysis, which was conducted following an additional 51 deaths, median overall survival for the intent-to-treat patient population was 28.2 months for the combination arm (95% confidence interval, 23.4, 35.2) compared with 31.2 months (95% CI, 23.0, 44.5) for the control arm; this was one of four new co-primary endpoints. The hazard ratio was 1.10 (95% CI, 0.85, 1.42).
Other co-primary endpoints that were evaluated, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, did not demonstrate a favorable result, Argos Therapeutics said in a recent press release.
Rocapuldencel-T “consists of autologous dendritic cells programmed with amplified RNA from a patient’s primary tumor” and is “designed to overcome immunosuppression and induce broadly reactive, long-lasting anti-tumor memory T cells” according to the early interim analysis presented at the European Society for Medical Oncology (ESMO) 2017. The drug is also being evaluated in non–small cell lung cancer and bladder cancer.
Patient perspective improves dry eye syndrome research
WASHINGTON –
With dry eye found in over 85% of Sjogren’s patients, pinpointing important outcomes accurately can help researchers and physicians focus their efforts and be more cost effective when developing clinical trials, systematic reviews , practice guidelines, and evidence-based health care, according to presenter Ian J. Saldanha, MBBS, MPH, PhD, of the department of epidemiology at Johns Hopkins, Baltimore.
“When designing clinical trials, if you are trying to incorporate the views of patients, this can help more accurately depict what you should be measuring and in what time frame,“ Dr. Saldanha said to attendees. This can be important as agencies such as the Food and Drug Administration have absolved to be more committed to bringing the patient perspective to drug development, according to Dr. Saldanha.
Investigators surveyed 420 subscribers to KeratoScoop, a news source that specifically reports on dry eye, using a two-round survey process with participants ranking outcomes from 0 to 10, 0 being the least important and 10 being the most.
The majority of the patients were white American women, aged 50 years and older.
To start, Dr. Saldanha and his fellow investigators identified 109 outcomes commonly found in existing research. Of these, 28 were identified as important to survey takers.
The investigators noted that 39% of the outcomes identified were symptoms, compared with 25% for clinical testing, 14% related to quality of life, and the remainder split evenly between lab measures, safety, and others.
When ranked, the top 10 outcomes chosen were ocular burning, ocular discomfort, ocular pain, ocular dryness, visual acuity, overall assessment of surface symptoms, ocular foreign body sensation, tear film stability, artificial tear use, and adverse events.
Of the 28 outcomes deemed “important” by the surveyed population, 10 were found to be uncommon in current research.
When asked when patients would like these outcomes to be measured if they were to participate in a clinical trial, over 75% preferred a 3-month period for ocular burning, discomfort, pain, and foreign body sensations, as well as impact of dry eye in daily life, tear film stability, and costs of treatment. In comparison, a majority of patients agreed that outcomes such as satisfaction of treatment, ocular fatigue, and vision-related quality of life should be measured between 3 and 6 months.
With these data, according to Dr. Saldanha, researchers can maximize consistency across trials as well as contribute to better evidence-based medicine.
“This is useful for the next step, which would be to develop core outcome sets, which are an agreed upon minimum set of outcomes that should be examined in a given disease area,” Dr. Saldanha explained.
Dr. Saldanha reported no relevant financial disclosures. The meeting was sponsored by Johns Hopkins University and the National Institutes of Health.
SOURCE: Saldanha I et al. International Symposium on Sjogren’s Syndrome.
WASHINGTON –
With dry eye found in over 85% of Sjogren’s patients, pinpointing important outcomes accurately can help researchers and physicians focus their efforts and be more cost effective when developing clinical trials, systematic reviews , practice guidelines, and evidence-based health care, according to presenter Ian J. Saldanha, MBBS, MPH, PhD, of the department of epidemiology at Johns Hopkins, Baltimore.
“When designing clinical trials, if you are trying to incorporate the views of patients, this can help more accurately depict what you should be measuring and in what time frame,“ Dr. Saldanha said to attendees. This can be important as agencies such as the Food and Drug Administration have absolved to be more committed to bringing the patient perspective to drug development, according to Dr. Saldanha.
Investigators surveyed 420 subscribers to KeratoScoop, a news source that specifically reports on dry eye, using a two-round survey process with participants ranking outcomes from 0 to 10, 0 being the least important and 10 being the most.
The majority of the patients were white American women, aged 50 years and older.
To start, Dr. Saldanha and his fellow investigators identified 109 outcomes commonly found in existing research. Of these, 28 were identified as important to survey takers.
The investigators noted that 39% of the outcomes identified were symptoms, compared with 25% for clinical testing, 14% related to quality of life, and the remainder split evenly between lab measures, safety, and others.
When ranked, the top 10 outcomes chosen were ocular burning, ocular discomfort, ocular pain, ocular dryness, visual acuity, overall assessment of surface symptoms, ocular foreign body sensation, tear film stability, artificial tear use, and adverse events.
Of the 28 outcomes deemed “important” by the surveyed population, 10 were found to be uncommon in current research.
When asked when patients would like these outcomes to be measured if they were to participate in a clinical trial, over 75% preferred a 3-month period for ocular burning, discomfort, pain, and foreign body sensations, as well as impact of dry eye in daily life, tear film stability, and costs of treatment. In comparison, a majority of patients agreed that outcomes such as satisfaction of treatment, ocular fatigue, and vision-related quality of life should be measured between 3 and 6 months.
With these data, according to Dr. Saldanha, researchers can maximize consistency across trials as well as contribute to better evidence-based medicine.
“This is useful for the next step, which would be to develop core outcome sets, which are an agreed upon minimum set of outcomes that should be examined in a given disease area,” Dr. Saldanha explained.
Dr. Saldanha reported no relevant financial disclosures. The meeting was sponsored by Johns Hopkins University and the National Institutes of Health.
SOURCE: Saldanha I et al. International Symposium on Sjogren’s Syndrome.
WASHINGTON –
With dry eye found in over 85% of Sjogren’s patients, pinpointing important outcomes accurately can help researchers and physicians focus their efforts and be more cost effective when developing clinical trials, systematic reviews , practice guidelines, and evidence-based health care, according to presenter Ian J. Saldanha, MBBS, MPH, PhD, of the department of epidemiology at Johns Hopkins, Baltimore.
“When designing clinical trials, if you are trying to incorporate the views of patients, this can help more accurately depict what you should be measuring and in what time frame,“ Dr. Saldanha said to attendees. This can be important as agencies such as the Food and Drug Administration have absolved to be more committed to bringing the patient perspective to drug development, according to Dr. Saldanha.
Investigators surveyed 420 subscribers to KeratoScoop, a news source that specifically reports on dry eye, using a two-round survey process with participants ranking outcomes from 0 to 10, 0 being the least important and 10 being the most.
The majority of the patients were white American women, aged 50 years and older.
To start, Dr. Saldanha and his fellow investigators identified 109 outcomes commonly found in existing research. Of these, 28 were identified as important to survey takers.
The investigators noted that 39% of the outcomes identified were symptoms, compared with 25% for clinical testing, 14% related to quality of life, and the remainder split evenly between lab measures, safety, and others.
When ranked, the top 10 outcomes chosen were ocular burning, ocular discomfort, ocular pain, ocular dryness, visual acuity, overall assessment of surface symptoms, ocular foreign body sensation, tear film stability, artificial tear use, and adverse events.
Of the 28 outcomes deemed “important” by the surveyed population, 10 were found to be uncommon in current research.
When asked when patients would like these outcomes to be measured if they were to participate in a clinical trial, over 75% preferred a 3-month period for ocular burning, discomfort, pain, and foreign body sensations, as well as impact of dry eye in daily life, tear film stability, and costs of treatment. In comparison, a majority of patients agreed that outcomes such as satisfaction of treatment, ocular fatigue, and vision-related quality of life should be measured between 3 and 6 months.
With these data, according to Dr. Saldanha, researchers can maximize consistency across trials as well as contribute to better evidence-based medicine.
“This is useful for the next step, which would be to develop core outcome sets, which are an agreed upon minimum set of outcomes that should be examined in a given disease area,” Dr. Saldanha explained.
Dr. Saldanha reported no relevant financial disclosures. The meeting was sponsored by Johns Hopkins University and the National Institutes of Health.
SOURCE: Saldanha I et al. International Symposium on Sjogren’s Syndrome.
REPORTING FROM ISSS
Key clinical point: Investigators have identified core outcomes important to Sjogren’s patients with dry eye.
Major finding: Out of 28 outcomes identified, 39% were symptoms and 36% have not been commonly included in existing research.
Study details: An anonymous, two-round Delphi survey of 420 subscribers to KeratoScoop between November and December, 2017.
Disclosures: The presenter reported no relevant financial disclosures.
Source: Saldanha I et al. International Symposium on Sjogren’s Syndrome.
Calendar
For more information about upcoming events and award deadlines, please visit http://www.gastro.org/education and http://www.gastro.org/research-funding.
June 2-5, 2018
DIGESTIVE DISEASE WEEK® (DDW) 2018 – WASHINGTON, DC
DDW® is the premier meeting for the GI professional. Every year, it attracts approximately 15,000 physicians, researchers, and academics from around the world who desire to stay up to date in the field.
AGA Trainee and Early-Career GI Sessions
Join your colleagues at special sessions to meet the unique needs of physicians who are new to the field. Participants will learn about all aspects of starting a career in clinical practice or research, have the opportunity to network with mentors and peers, and review board material.
- June 2, 8:15 a.m.–5:30 p.m.; June 3, 8:30 a.m.–12:35 p.m.
AGA Postgraduate Course: From Abstract to Reality
Attend this multi-topic course to get practical, useful information to push your practice to the next level. The 2018 course will provide a comprehensive look at the latest medical, surgical, and technological advances over the past 12 months that aim to keep you up to date in a field that is rapidly changing. Each presenter will turn abstract ideas into concrete action items that you can immediately implement in your practice. AGA member trainees and early-career GIs receive discounted pricing for this course. - June 3, 4–5:30 p.m.
Difficult Conversations: Navigating People, Negotiations, Promotions, and Complications
During this session, attendees will obtain effective negotiation techniques and learn how to navigate difficult situations in clinical and research environments. - June 3, 6-7 p.m.
AGA Early Career Networking Hour
This event is open to all DDW trainee and early career GI attendees and provides a casual atmosphere to bond with your peers. Complimentary food and drinks will be available. - June 4, 4–5:30 p.m.
Advancing Clinical Practice: Gastroenterology Fellow–Directed Quality-Improvement Projects
This trainee-focused session will showcase selected abstracts from GI fellows based on quality improvement with a state-of-the-art lecture. Attendees will be provided with information that defines practical approaches to quality improvement from start to finish. A limited supply of coffee and tea will be provided during the session. - June 5, 1:30–5:30 p.m.
Board Review Course
This session, designed using content from DDSEP® 8, serves as a primer for third-year fellows preparing for the board exam as well as a review course for others wanting to test their knowledge. Session attendees will receive a $50 coupon to use at the AGA Store at DDW to purchase DDSEP 8.
UPCOMING EVENTS
June 4-8, 2018
Exosomes/Microvesicles: Heterogeneity, Biogenesis, Function, and Therapeutic Developments (E2)
Deepen your understanding of the structural and functional complexity of extracellular vesicles, their biogenesis and function in health and disease, cargo enrichment, potential as ideal biomarkers, and breakthroughs in their use as therapeutic targets/agents.
Breckenridge, CO
June 13-14; Aug. 15-16; Sept. 19-20; Oct. 10-11, 2018
Two-Day, In-Depth Coding and Billing Seminar
Become a certified GI coder with a two-day, in-depth training course provided by McVey Associates, Inc.
Nashville, TN (6/13-6/14); Baltimore, MD (8/15-8/16); Atlanta, GA (9/19-9/20); Las Vegas, NV (10/10-10/11)
Aug. 10–12, 2018
Principles of GI for the NP and PA
Hear from the experts as they provide you with critical updates on treating and managing patients with a variety of GI disorders.
Chicago, IL
Aug. 18-19, 2018
James W. Freston Conference: Obesity and Metabolic Disease – Integrating New Paradigms in Pathophysiology to Advance Treatment
Collaborate with researchers and clinicians to help advance obesity treatment and enhance the continuum of obesity care.
Arlington, VA
Feb. 7-9, 2019
Crohn’s & Colitis Congress™ (A Partnership of the Crohn’s & Colitis Foundation and American Gastroenterological Association)
Expand your knowledge, network with IBD leaders, spark innovative research and get inspired to improve patient care.
Las Vegas, NV
For more information about upcoming events and award deadlines, please visit http://www.gastro.org/education and http://www.gastro.org/research-funding.
June 2-5, 2018
DIGESTIVE DISEASE WEEK® (DDW) 2018 – WASHINGTON, DC
DDW® is the premier meeting for the GI professional. Every year, it attracts approximately 15,000 physicians, researchers, and academics from around the world who desire to stay up to date in the field.
AGA Trainee and Early-Career GI Sessions
Join your colleagues at special sessions to meet the unique needs of physicians who are new to the field. Participants will learn about all aspects of starting a career in clinical practice or research, have the opportunity to network with mentors and peers, and review board material.
- June 2, 8:15 a.m.–5:30 p.m.; June 3, 8:30 a.m.–12:35 p.m.
AGA Postgraduate Course: From Abstract to Reality
Attend this multi-topic course to get practical, useful information to push your practice to the next level. The 2018 course will provide a comprehensive look at the latest medical, surgical, and technological advances over the past 12 months that aim to keep you up to date in a field that is rapidly changing. Each presenter will turn abstract ideas into concrete action items that you can immediately implement in your practice. AGA member trainees and early-career GIs receive discounted pricing for this course. - June 3, 4–5:30 p.m.
Difficult Conversations: Navigating People, Negotiations, Promotions, and Complications
During this session, attendees will obtain effective negotiation techniques and learn how to navigate difficult situations in clinical and research environments. - June 3, 6-7 p.m.
AGA Early Career Networking Hour
This event is open to all DDW trainee and early career GI attendees and provides a casual atmosphere to bond with your peers. Complimentary food and drinks will be available. - June 4, 4–5:30 p.m.
Advancing Clinical Practice: Gastroenterology Fellow–Directed Quality-Improvement Projects
This trainee-focused session will showcase selected abstracts from GI fellows based on quality improvement with a state-of-the-art lecture. Attendees will be provided with information that defines practical approaches to quality improvement from start to finish. A limited supply of coffee and tea will be provided during the session. - June 5, 1:30–5:30 p.m.
Board Review Course
This session, designed using content from DDSEP® 8, serves as a primer for third-year fellows preparing for the board exam as well as a review course for others wanting to test their knowledge. Session attendees will receive a $50 coupon to use at the AGA Store at DDW to purchase DDSEP 8.
UPCOMING EVENTS
June 4-8, 2018
Exosomes/Microvesicles: Heterogeneity, Biogenesis, Function, and Therapeutic Developments (E2)
Deepen your understanding of the structural and functional complexity of extracellular vesicles, their biogenesis and function in health and disease, cargo enrichment, potential as ideal biomarkers, and breakthroughs in their use as therapeutic targets/agents.
Breckenridge, CO
June 13-14; Aug. 15-16; Sept. 19-20; Oct. 10-11, 2018
Two-Day, In-Depth Coding and Billing Seminar
Become a certified GI coder with a two-day, in-depth training course provided by McVey Associates, Inc.
Nashville, TN (6/13-6/14); Baltimore, MD (8/15-8/16); Atlanta, GA (9/19-9/20); Las Vegas, NV (10/10-10/11)
Aug. 10–12, 2018
Principles of GI for the NP and PA
Hear from the experts as they provide you with critical updates on treating and managing patients with a variety of GI disorders.
Chicago, IL
Aug. 18-19, 2018
James W. Freston Conference: Obesity and Metabolic Disease – Integrating New Paradigms in Pathophysiology to Advance Treatment
Collaborate with researchers and clinicians to help advance obesity treatment and enhance the continuum of obesity care.
Arlington, VA
Feb. 7-9, 2019
Crohn’s & Colitis Congress™ (A Partnership of the Crohn’s & Colitis Foundation and American Gastroenterological Association)
Expand your knowledge, network with IBD leaders, spark innovative research and get inspired to improve patient care.
Las Vegas, NV
For more information about upcoming events and award deadlines, please visit http://www.gastro.org/education and http://www.gastro.org/research-funding.
June 2-5, 2018
DIGESTIVE DISEASE WEEK® (DDW) 2018 – WASHINGTON, DC
DDW® is the premier meeting for the GI professional. Every year, it attracts approximately 15,000 physicians, researchers, and academics from around the world who desire to stay up to date in the field.
AGA Trainee and Early-Career GI Sessions
Join your colleagues at special sessions to meet the unique needs of physicians who are new to the field. Participants will learn about all aspects of starting a career in clinical practice or research, have the opportunity to network with mentors and peers, and review board material.
- June 2, 8:15 a.m.–5:30 p.m.; June 3, 8:30 a.m.–12:35 p.m.
AGA Postgraduate Course: From Abstract to Reality
Attend this multi-topic course to get practical, useful information to push your practice to the next level. The 2018 course will provide a comprehensive look at the latest medical, surgical, and technological advances over the past 12 months that aim to keep you up to date in a field that is rapidly changing. Each presenter will turn abstract ideas into concrete action items that you can immediately implement in your practice. AGA member trainees and early-career GIs receive discounted pricing for this course. - June 3, 4–5:30 p.m.
Difficult Conversations: Navigating People, Negotiations, Promotions, and Complications
During this session, attendees will obtain effective negotiation techniques and learn how to navigate difficult situations in clinical and research environments. - June 3, 6-7 p.m.
AGA Early Career Networking Hour
This event is open to all DDW trainee and early career GI attendees and provides a casual atmosphere to bond with your peers. Complimentary food and drinks will be available. - June 4, 4–5:30 p.m.
Advancing Clinical Practice: Gastroenterology Fellow–Directed Quality-Improvement Projects
This trainee-focused session will showcase selected abstracts from GI fellows based on quality improvement with a state-of-the-art lecture. Attendees will be provided with information that defines practical approaches to quality improvement from start to finish. A limited supply of coffee and tea will be provided during the session. - June 5, 1:30–5:30 p.m.
Board Review Course
This session, designed using content from DDSEP® 8, serves as a primer for third-year fellows preparing for the board exam as well as a review course for others wanting to test their knowledge. Session attendees will receive a $50 coupon to use at the AGA Store at DDW to purchase DDSEP 8.
UPCOMING EVENTS
June 4-8, 2018
Exosomes/Microvesicles: Heterogeneity, Biogenesis, Function, and Therapeutic Developments (E2)
Deepen your understanding of the structural and functional complexity of extracellular vesicles, their biogenesis and function in health and disease, cargo enrichment, potential as ideal biomarkers, and breakthroughs in their use as therapeutic targets/agents.
Breckenridge, CO
June 13-14; Aug. 15-16; Sept. 19-20; Oct. 10-11, 2018
Two-Day, In-Depth Coding and Billing Seminar
Become a certified GI coder with a two-day, in-depth training course provided by McVey Associates, Inc.
Nashville, TN (6/13-6/14); Baltimore, MD (8/15-8/16); Atlanta, GA (9/19-9/20); Las Vegas, NV (10/10-10/11)
Aug. 10–12, 2018
Principles of GI for the NP and PA
Hear from the experts as they provide you with critical updates on treating and managing patients with a variety of GI disorders.
Chicago, IL
Aug. 18-19, 2018
James W. Freston Conference: Obesity and Metabolic Disease – Integrating New Paradigms in Pathophysiology to Advance Treatment
Collaborate with researchers and clinicians to help advance obesity treatment and enhance the continuum of obesity care.
Arlington, VA
Feb. 7-9, 2019
Crohn’s & Colitis Congress™ (A Partnership of the Crohn’s & Colitis Foundation and American Gastroenterological Association)
Expand your knowledge, network with IBD leaders, spark innovative research and get inspired to improve patient care.
Las Vegas, NV
MDedge Daily News: Bridging medicine’s gender gap
Reshaping medicine’s mindset about gender roles, when to rechallenge for statin-associated muscle symptoms, how zip code (not gene code) influences health, and surgeries are driving hospital costs.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Reshaping medicine’s mindset about gender roles, when to rechallenge for statin-associated muscle symptoms, how zip code (not gene code) influences health, and surgeries are driving hospital costs.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Reshaping medicine’s mindset about gender roles, when to rechallenge for statin-associated muscle symptoms, how zip code (not gene code) influences health, and surgeries are driving hospital costs.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
