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TLR9 agonist may overcome resistance to anti–PD-1 therapy in melanoma
NATIONAL HARBOR, MD. – A TLR9 agonist called CMP-001 can reverse resistance to anti–programmed death-1 (PD-1) therapy in patients with melanoma, a phase 1 trial suggests.
Combination CMP-001 and pembrolizumab produced durable responses in patients who had progressed on prior anti–PD-1 therapy, and the combination was considered well tolerated.
CMP-001 is a CpG-A TLR9 agonist packaged in a viruslike particle, John Kirkwood, MD, of University of Pittsburgh Medical Center, explained in a late-breaking abstract at the annual meeting of the Society for Immunotherapy of Cancer. CMP-001 activates tumor-associated plasmacytoid dendritic cells and induces systemic tumor-specific CD8+ T-cell responses.
Dr. Kirkwood and associates are investigating CMP-001, given alone or in combination with pembrolizumab, in a phase 1 trial (NCT02680184) of patients with metastatic or unresectable melanoma who are refractory to anti–PD-1 therapy.
Data were presented on 144 patients who received CMP-001 in combination with pembrolizumab. About 40% of patients (39.6%) had elevated lactate dehydrogenase at baseline, and 32.6% had BRAF mutations.
All patients had received prior anti–PD-1 therapy alone (75%) and/or in combination (50%). For most patients (93.1%), their last response to anti–PD-1 therapy was progression.
For this study, the patients received intratumoral CMP-001 injections at a range of doses (1 mg, 3 mg, 5 mg, 7.5 mg, and 10 mg). CMP-001 was given weekly for either 2 weeks or 7 weeks, then every 3 weeks until discontinuation. There were two different formulations of CMP-001 given – 0.01% polysorbate 20 (PS20; n = 83) and 0.00167% PS20 (n = 61).
Safety
“CMP-001 in combination with pembrolizumab is very well tolerated, with no apparent increase in autoimmune toxicities associated with anti–PD-1,” Dr. Kirkwood said.
The most common treatment-related adverse events were flulike symptoms, including chills (72%), pyrexia (56%), fatigue (51%), nausea (45%), vomiting (29%), and headache (28%). Another common event was injection-site pain (28%).
The most common grade 3 adverse events were hypotension (n = 9) and hypertension (n = 7). Grade 4 events included hypotension, aspartate aminotransferase increase, and alanine aminotransferase increase (n = 1 for all). There were no grade 5 events.
Six patients discontinued treatment because of adverse events.
Response
The overall response rate was 25% (21/83) among patients who received the 0.01% PS20 formulation of CMP-001 and 11.5% (7/61) among patients who received the 0.00167% PS20 formulation.
Responses were similar in injected and noninjected target lesions. The median duration of response has not been reached at a median follow-up of 16.9 months.
“Intratumoral CMP-001 reverses resistance to anti–PD-1 in patients who have progressed on prior anti–PD-1 therapy,” Dr. Kirkwood said, adding that these data support further clinical development of CMP-001.
The research is sponsored by Checkmate Pharmaceuticals. Dr. Kirkwood disclosed relationships with Amgen, BMS, Immunocore, Iovance, Novartis, Elsevier, Castle, Merck, and Checkmate.
SOURCE: Kirkwood J et al. SITC 2019, Abstract O85.
NATIONAL HARBOR, MD. – A TLR9 agonist called CMP-001 can reverse resistance to anti–programmed death-1 (PD-1) therapy in patients with melanoma, a phase 1 trial suggests.
Combination CMP-001 and pembrolizumab produced durable responses in patients who had progressed on prior anti–PD-1 therapy, and the combination was considered well tolerated.
CMP-001 is a CpG-A TLR9 agonist packaged in a viruslike particle, John Kirkwood, MD, of University of Pittsburgh Medical Center, explained in a late-breaking abstract at the annual meeting of the Society for Immunotherapy of Cancer. CMP-001 activates tumor-associated plasmacytoid dendritic cells and induces systemic tumor-specific CD8+ T-cell responses.
Dr. Kirkwood and associates are investigating CMP-001, given alone or in combination with pembrolizumab, in a phase 1 trial (NCT02680184) of patients with metastatic or unresectable melanoma who are refractory to anti–PD-1 therapy.
Data were presented on 144 patients who received CMP-001 in combination with pembrolizumab. About 40% of patients (39.6%) had elevated lactate dehydrogenase at baseline, and 32.6% had BRAF mutations.
All patients had received prior anti–PD-1 therapy alone (75%) and/or in combination (50%). For most patients (93.1%), their last response to anti–PD-1 therapy was progression.
For this study, the patients received intratumoral CMP-001 injections at a range of doses (1 mg, 3 mg, 5 mg, 7.5 mg, and 10 mg). CMP-001 was given weekly for either 2 weeks or 7 weeks, then every 3 weeks until discontinuation. There were two different formulations of CMP-001 given – 0.01% polysorbate 20 (PS20; n = 83) and 0.00167% PS20 (n = 61).
Safety
“CMP-001 in combination with pembrolizumab is very well tolerated, with no apparent increase in autoimmune toxicities associated with anti–PD-1,” Dr. Kirkwood said.
The most common treatment-related adverse events were flulike symptoms, including chills (72%), pyrexia (56%), fatigue (51%), nausea (45%), vomiting (29%), and headache (28%). Another common event was injection-site pain (28%).
The most common grade 3 adverse events were hypotension (n = 9) and hypertension (n = 7). Grade 4 events included hypotension, aspartate aminotransferase increase, and alanine aminotransferase increase (n = 1 for all). There were no grade 5 events.
Six patients discontinued treatment because of adverse events.
Response
The overall response rate was 25% (21/83) among patients who received the 0.01% PS20 formulation of CMP-001 and 11.5% (7/61) among patients who received the 0.00167% PS20 formulation.
Responses were similar in injected and noninjected target lesions. The median duration of response has not been reached at a median follow-up of 16.9 months.
“Intratumoral CMP-001 reverses resistance to anti–PD-1 in patients who have progressed on prior anti–PD-1 therapy,” Dr. Kirkwood said, adding that these data support further clinical development of CMP-001.
The research is sponsored by Checkmate Pharmaceuticals. Dr. Kirkwood disclosed relationships with Amgen, BMS, Immunocore, Iovance, Novartis, Elsevier, Castle, Merck, and Checkmate.
SOURCE: Kirkwood J et al. SITC 2019, Abstract O85.
NATIONAL HARBOR, MD. – A TLR9 agonist called CMP-001 can reverse resistance to anti–programmed death-1 (PD-1) therapy in patients with melanoma, a phase 1 trial suggests.
Combination CMP-001 and pembrolizumab produced durable responses in patients who had progressed on prior anti–PD-1 therapy, and the combination was considered well tolerated.
CMP-001 is a CpG-A TLR9 agonist packaged in a viruslike particle, John Kirkwood, MD, of University of Pittsburgh Medical Center, explained in a late-breaking abstract at the annual meeting of the Society for Immunotherapy of Cancer. CMP-001 activates tumor-associated plasmacytoid dendritic cells and induces systemic tumor-specific CD8+ T-cell responses.
Dr. Kirkwood and associates are investigating CMP-001, given alone or in combination with pembrolizumab, in a phase 1 trial (NCT02680184) of patients with metastatic or unresectable melanoma who are refractory to anti–PD-1 therapy.
Data were presented on 144 patients who received CMP-001 in combination with pembrolizumab. About 40% of patients (39.6%) had elevated lactate dehydrogenase at baseline, and 32.6% had BRAF mutations.
All patients had received prior anti–PD-1 therapy alone (75%) and/or in combination (50%). For most patients (93.1%), their last response to anti–PD-1 therapy was progression.
For this study, the patients received intratumoral CMP-001 injections at a range of doses (1 mg, 3 mg, 5 mg, 7.5 mg, and 10 mg). CMP-001 was given weekly for either 2 weeks or 7 weeks, then every 3 weeks until discontinuation. There were two different formulations of CMP-001 given – 0.01% polysorbate 20 (PS20; n = 83) and 0.00167% PS20 (n = 61).
Safety
“CMP-001 in combination with pembrolizumab is very well tolerated, with no apparent increase in autoimmune toxicities associated with anti–PD-1,” Dr. Kirkwood said.
The most common treatment-related adverse events were flulike symptoms, including chills (72%), pyrexia (56%), fatigue (51%), nausea (45%), vomiting (29%), and headache (28%). Another common event was injection-site pain (28%).
The most common grade 3 adverse events were hypotension (n = 9) and hypertension (n = 7). Grade 4 events included hypotension, aspartate aminotransferase increase, and alanine aminotransferase increase (n = 1 for all). There were no grade 5 events.
Six patients discontinued treatment because of adverse events.
Response
The overall response rate was 25% (21/83) among patients who received the 0.01% PS20 formulation of CMP-001 and 11.5% (7/61) among patients who received the 0.00167% PS20 formulation.
Responses were similar in injected and noninjected target lesions. The median duration of response has not been reached at a median follow-up of 16.9 months.
“Intratumoral CMP-001 reverses resistance to anti–PD-1 in patients who have progressed on prior anti–PD-1 therapy,” Dr. Kirkwood said, adding that these data support further clinical development of CMP-001.
The research is sponsored by Checkmate Pharmaceuticals. Dr. Kirkwood disclosed relationships with Amgen, BMS, Immunocore, Iovance, Novartis, Elsevier, Castle, Merck, and Checkmate.
SOURCE: Kirkwood J et al. SITC 2019, Abstract O85.
REPORTING FROM SITC 2019
Veterans at higher risk of sleep behavior disorders
Veterans may be at higher risk of idiopathic rapid eye movement sleep behavior disorders, particularly if they have traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) according to a paper published in Sleep.
In a prospective, cross-sectional study, researchers recruited 394 veterans – 94% of whom were male – who underwent in-lab video-polysomnography and questionnaires about REM sleep behavior disorder (RBD), as well as assessment of their trauma status and medical history.
Overall, 9% of subjects had RBD, a figure considerably higher than has been estimated in the general population (prevalence of 0.38%-1.0%). Seven percent had REM sleep without atonia, 31% had other parasomnias such as a history of dream enactment behavior, and 53% were classified as normal.
The majority of subjects determined to have RBD (n = 34) had either PTSD or comorbid TBI+PTSD (n = 19, 56%). The combined overall crude prevalence of RBD in subjects with either PTSD alone or TBI+PTSD was 16.8% (n = 19 out of 113).
The individuals with PTSD had a 2.81-fold greater odds of RBD and 3.13-fold greater odds of other parasomnias compared with those without PTSD.
Those with both traumatic brain injury and PTSD had 3.43-fold greater odds of RBD and 3.22-fold greater odds of other parasomnias compared with individuals without.
“Interestingly, the neuropathology underpinning PTSD shares common features with RBD, raising the question as to whether or not PTSD has a causal role in the development of RBD, or if a single pathophysiologic process generates two clinical entities,” wrote Jonathan E. Elliott, PhD, of the VA Portland Health Care System, and coauthors.
The researchers also looked for evidence of trauma-associated sleep disorder (TASD), a recently proposed phenomenological sleep disorder whose diagnostic criteria overlaps with REM sleep behavior disorder but includes subjects reporting having an inciting traumatic experience and a history of dreaming related to this experience as well as evidence of autonomic hyperarousal.
The researchers found 22 of the subjects with REM behavior disorder had a traumatic brain injury and/or PTSD, and 9 of these subjects reported evidence of altered dream mentation related to that prior traumatic experience. However, none showed evidence of autonomic nervous system hyperarousal that coincided with abnormal REM sleep activity.
The investigators noted that although the sample of 394 subjects with in-lab video-polysomnography is large, the study is underpowered to draw broader conclusions about prevalence of RBD among veterans. In addition, the study did not establish whether or not trauma exposure preceded, and contributed to, the development of parasomnias and this question should be pursued in further studies.
“Given the purported relationships between TBI, PTSD, RBD, and neurodegeneration, we sought to determine the crude prevalence and related associations of RBD following TBI and PTSD among veterans. Our data show that the prevalence of RBD and related parasomnias is significantly higher in veterans with PTSD and TBI+PTSD compared to veterans without a history of neuropsychiatric trauma,” the authors wrote.
No funding or conflicts of interest were declared.
SOURCE: Elliott JE et al. Sleep 2019 Oct 7. doi: 10.1093/sleep/zsz237.
Veterans may be at higher risk of idiopathic rapid eye movement sleep behavior disorders, particularly if they have traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) according to a paper published in Sleep.
In a prospective, cross-sectional study, researchers recruited 394 veterans – 94% of whom were male – who underwent in-lab video-polysomnography and questionnaires about REM sleep behavior disorder (RBD), as well as assessment of their trauma status and medical history.
Overall, 9% of subjects had RBD, a figure considerably higher than has been estimated in the general population (prevalence of 0.38%-1.0%). Seven percent had REM sleep without atonia, 31% had other parasomnias such as a history of dream enactment behavior, and 53% were classified as normal.
The majority of subjects determined to have RBD (n = 34) had either PTSD or comorbid TBI+PTSD (n = 19, 56%). The combined overall crude prevalence of RBD in subjects with either PTSD alone or TBI+PTSD was 16.8% (n = 19 out of 113).
The individuals with PTSD had a 2.81-fold greater odds of RBD and 3.13-fold greater odds of other parasomnias compared with those without PTSD.
Those with both traumatic brain injury and PTSD had 3.43-fold greater odds of RBD and 3.22-fold greater odds of other parasomnias compared with individuals without.
“Interestingly, the neuropathology underpinning PTSD shares common features with RBD, raising the question as to whether or not PTSD has a causal role in the development of RBD, or if a single pathophysiologic process generates two clinical entities,” wrote Jonathan E. Elliott, PhD, of the VA Portland Health Care System, and coauthors.
The researchers also looked for evidence of trauma-associated sleep disorder (TASD), a recently proposed phenomenological sleep disorder whose diagnostic criteria overlaps with REM sleep behavior disorder but includes subjects reporting having an inciting traumatic experience and a history of dreaming related to this experience as well as evidence of autonomic hyperarousal.
The researchers found 22 of the subjects with REM behavior disorder had a traumatic brain injury and/or PTSD, and 9 of these subjects reported evidence of altered dream mentation related to that prior traumatic experience. However, none showed evidence of autonomic nervous system hyperarousal that coincided with abnormal REM sleep activity.
The investigators noted that although the sample of 394 subjects with in-lab video-polysomnography is large, the study is underpowered to draw broader conclusions about prevalence of RBD among veterans. In addition, the study did not establish whether or not trauma exposure preceded, and contributed to, the development of parasomnias and this question should be pursued in further studies.
“Given the purported relationships between TBI, PTSD, RBD, and neurodegeneration, we sought to determine the crude prevalence and related associations of RBD following TBI and PTSD among veterans. Our data show that the prevalence of RBD and related parasomnias is significantly higher in veterans with PTSD and TBI+PTSD compared to veterans without a history of neuropsychiatric trauma,” the authors wrote.
No funding or conflicts of interest were declared.
SOURCE: Elliott JE et al. Sleep 2019 Oct 7. doi: 10.1093/sleep/zsz237.
Veterans may be at higher risk of idiopathic rapid eye movement sleep behavior disorders, particularly if they have traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) according to a paper published in Sleep.
In a prospective, cross-sectional study, researchers recruited 394 veterans – 94% of whom were male – who underwent in-lab video-polysomnography and questionnaires about REM sleep behavior disorder (RBD), as well as assessment of their trauma status and medical history.
Overall, 9% of subjects had RBD, a figure considerably higher than has been estimated in the general population (prevalence of 0.38%-1.0%). Seven percent had REM sleep without atonia, 31% had other parasomnias such as a history of dream enactment behavior, and 53% were classified as normal.
The majority of subjects determined to have RBD (n = 34) had either PTSD or comorbid TBI+PTSD (n = 19, 56%). The combined overall crude prevalence of RBD in subjects with either PTSD alone or TBI+PTSD was 16.8% (n = 19 out of 113).
The individuals with PTSD had a 2.81-fold greater odds of RBD and 3.13-fold greater odds of other parasomnias compared with those without PTSD.
Those with both traumatic brain injury and PTSD had 3.43-fold greater odds of RBD and 3.22-fold greater odds of other parasomnias compared with individuals without.
“Interestingly, the neuropathology underpinning PTSD shares common features with RBD, raising the question as to whether or not PTSD has a causal role in the development of RBD, or if a single pathophysiologic process generates two clinical entities,” wrote Jonathan E. Elliott, PhD, of the VA Portland Health Care System, and coauthors.
The researchers also looked for evidence of trauma-associated sleep disorder (TASD), a recently proposed phenomenological sleep disorder whose diagnostic criteria overlaps with REM sleep behavior disorder but includes subjects reporting having an inciting traumatic experience and a history of dreaming related to this experience as well as evidence of autonomic hyperarousal.
The researchers found 22 of the subjects with REM behavior disorder had a traumatic brain injury and/or PTSD, and 9 of these subjects reported evidence of altered dream mentation related to that prior traumatic experience. However, none showed evidence of autonomic nervous system hyperarousal that coincided with abnormal REM sleep activity.
The investigators noted that although the sample of 394 subjects with in-lab video-polysomnography is large, the study is underpowered to draw broader conclusions about prevalence of RBD among veterans. In addition, the study did not establish whether or not trauma exposure preceded, and contributed to, the development of parasomnias and this question should be pursued in further studies.
“Given the purported relationships between TBI, PTSD, RBD, and neurodegeneration, we sought to determine the crude prevalence and related associations of RBD following TBI and PTSD among veterans. Our data show that the prevalence of RBD and related parasomnias is significantly higher in veterans with PTSD and TBI+PTSD compared to veterans without a history of neuropsychiatric trauma,” the authors wrote.
No funding or conflicts of interest were declared.
SOURCE: Elliott JE et al. Sleep 2019 Oct 7. doi: 10.1093/sleep/zsz237.
FROM SLEEP
Resting-state cerebral blood flow tied to apathy in schizophrenia
Regional resting-state cerebral blood flow (rCBF) in the ventral and dorsal striatum is associated with apathy in patients with schizophrenia – but not with diminished expression, results of a small study suggest.
“This distinction is of high relevance when investigating striatal rCBF,” wrote Karoline Schneider, MD, and colleagues. “The paucity of reported associations beween striatal rCBF and negative symptoms could result from the fact that until now apathy and diminished expression have not been addressed separately.” The study was published in the Journal of Psychiatry & Neuroscience.
Dr. Schneider and colleagues used arterial spin labeling MRI to measure rCBF in 29 patients with schizophrenia from outpatient and inpatient units affiliated with the University of Zürich and in 20 controls without schizophrenia. Negative symptoms were assessed via the Brief Negative Symptom Scale and were divided into those of apathy or those of diminished expression.
, and between severity and higher rCBF in the left and right dorsal striatum (r = 0.48; P = .008). However, the correlations were nonsignificant for symptoms of diminished expression, reported Dr. Schneider, of the university’s department of psychiatry, psychotherapy, and psychosomatics.
“The association between increased striatal rCBF and the negative symptom dimension of apathy, but not diminished expression, provides further evidence for the assumption of different underlying neural bases,” Dr. Schneider and colleagues concluded. “These dimensions should be considered separately in future research on negative symptoms.”
Limitations of the study include its sample size. Another limitation is that all patients with schizophrenia in the study were taking second-generation antipsychotics, which in some research appears to influence striatal rCBF.
Grants from the Swiss National Science Foundation funded the study. Dr. Schneider reported no conflicts of interest. Two authors disclosed receiving grant support or honoraria from pharmaceutical companies but said those activities were unrelated to this study.
SOURCE: Schneider K et al. J Psychiatry Neurosci. 2019;44(2):102-10.
Regional resting-state cerebral blood flow (rCBF) in the ventral and dorsal striatum is associated with apathy in patients with schizophrenia – but not with diminished expression, results of a small study suggest.
“This distinction is of high relevance when investigating striatal rCBF,” wrote Karoline Schneider, MD, and colleagues. “The paucity of reported associations beween striatal rCBF and negative symptoms could result from the fact that until now apathy and diminished expression have not been addressed separately.” The study was published in the Journal of Psychiatry & Neuroscience.
Dr. Schneider and colleagues used arterial spin labeling MRI to measure rCBF in 29 patients with schizophrenia from outpatient and inpatient units affiliated with the University of Zürich and in 20 controls without schizophrenia. Negative symptoms were assessed via the Brief Negative Symptom Scale and were divided into those of apathy or those of diminished expression.
, and between severity and higher rCBF in the left and right dorsal striatum (r = 0.48; P = .008). However, the correlations were nonsignificant for symptoms of diminished expression, reported Dr. Schneider, of the university’s department of psychiatry, psychotherapy, and psychosomatics.
“The association between increased striatal rCBF and the negative symptom dimension of apathy, but not diminished expression, provides further evidence for the assumption of different underlying neural bases,” Dr. Schneider and colleagues concluded. “These dimensions should be considered separately in future research on negative symptoms.”
Limitations of the study include its sample size. Another limitation is that all patients with schizophrenia in the study were taking second-generation antipsychotics, which in some research appears to influence striatal rCBF.
Grants from the Swiss National Science Foundation funded the study. Dr. Schneider reported no conflicts of interest. Two authors disclosed receiving grant support or honoraria from pharmaceutical companies but said those activities were unrelated to this study.
SOURCE: Schneider K et al. J Psychiatry Neurosci. 2019;44(2):102-10.
Regional resting-state cerebral blood flow (rCBF) in the ventral and dorsal striatum is associated with apathy in patients with schizophrenia – but not with diminished expression, results of a small study suggest.
“This distinction is of high relevance when investigating striatal rCBF,” wrote Karoline Schneider, MD, and colleagues. “The paucity of reported associations beween striatal rCBF and negative symptoms could result from the fact that until now apathy and diminished expression have not been addressed separately.” The study was published in the Journal of Psychiatry & Neuroscience.
Dr. Schneider and colleagues used arterial spin labeling MRI to measure rCBF in 29 patients with schizophrenia from outpatient and inpatient units affiliated with the University of Zürich and in 20 controls without schizophrenia. Negative symptoms were assessed via the Brief Negative Symptom Scale and were divided into those of apathy or those of diminished expression.
, and between severity and higher rCBF in the left and right dorsal striatum (r = 0.48; P = .008). However, the correlations were nonsignificant for symptoms of diminished expression, reported Dr. Schneider, of the university’s department of psychiatry, psychotherapy, and psychosomatics.
“The association between increased striatal rCBF and the negative symptom dimension of apathy, but not diminished expression, provides further evidence for the assumption of different underlying neural bases,” Dr. Schneider and colleagues concluded. “These dimensions should be considered separately in future research on negative symptoms.”
Limitations of the study include its sample size. Another limitation is that all patients with schizophrenia in the study were taking second-generation antipsychotics, which in some research appears to influence striatal rCBF.
Grants from the Swiss National Science Foundation funded the study. Dr. Schneider reported no conflicts of interest. Two authors disclosed receiving grant support or honoraria from pharmaceutical companies but said those activities were unrelated to this study.
SOURCE: Schneider K et al. J Psychiatry Neurosci. 2019;44(2):102-10.
FROM THE JOURNAL OF PSYCHIATRY & NEUROSCIENCE
B-cell-poor RA responds better to tocilizumab than to rituximab
ATLANTA – Tocilizumab proved more effective than rituximab in B-cell-poor but not in B-cell-rich patients with RA who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibition in the randomized, open-label, 48-week, phase 4 R4-RA trial.
If validated, the findings of the trial – the first randomized, controlled, biopsy-driven trial in RA – could have “massive implications” for treatment selection and improved outcomes, Constantino Pitzalis, MD, reported during a press conference at the annual meeting of the American College of Rheumatology.
Of 164 RA patients who were failing or intolerant to conventional synthetic (cs) DMARD therapy and at least one tumor necrosis factor inhibitor (TNFi), 83 were randomized to receive rituximab and 81 received tocilizumab. Of those patients, 49.1% were considered B-cell poor (BCP) based on synovial tissue biopsies obtained at trial entry.
The BCP patients treated with tocilizumab were numerically more likely than those treated with rituximab to achieve the coprimary endpoint of Clinical Disease Activity Index (CDAI) improvement of at least 50% from baseline at 16 weeks (56.1% vs. 44.7%), and they were significantly more likely – twice as likely, in fact – to achieve the coprimary endpoint of CDAI improvement of at least 50% from baseline at 16 weeks as well as CDAI score less than 10, indicating a major treatment response (46.3% vs. 23.7%), said Dr. Pitzalis, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London.
BCP patients receiving tocilizumab also were significantly more likely to achieve a number of secondary endpoints, he noted.
In the B-cell-rich (BCR) population, no significant differences were seen in the majority of endpoints with tocilizumab versus rituximab, he said.
Study participants had a mean age of 55-56 years and were intolerant of or refractory to csDMARDs and at least one TNFi. They were recruited from 19 centers in Europe, were randomized and treated with standard doses of rituximab or tocilizumab, and were stratified based on histologic classification (BCP vs. BCR). Baseline characteristics were comparable among the treatment groups, Dr. Pitzalis said.
Adverse events occurred in 62 and 68 patients in the rituximab and tocilizumab groups, respectively, and serious adverse events occurred in 8 and 12 patients, respectively, thus 40% of all serious adverse events occurred in the rituximab group and 60% in the tocilizumab group. Infections and serious infections each occurred in three patients in each group, and two patients in each group discontinued treatment because of adverse events.
B cells are pivotal to RA pathogenesis, as demonstrated by the efficacy of the B-cell-depleting agent, rituximab. However, rituximab, which is licensed for use following failure of csDMARDs and TNFi therapy, is only effective for achieving a 50% improvement in ACR response criteria at 6 months in about 30% of such patients, Dr. Pitzalis noted. In a recent early RA cohort, he and his colleagues found synovial heterogeneity, with more than half of patients showing low or no synovial B-cell infiltration.
“So why would you give them rituximab?” he asked, explaining the rationale for the R4-RA trial: The hypothesis was that alternative biologic agents targeting alternative pathways may be more effective in BCP patients.
“The results showed quite clearly that rituximab was inferior to tocilizumab in this patient group,” he said. “We demonstrated that tocilizumab is more effective than rituximab in achieving low disease activity in patients who had, on synovial biopsy, low levels of B-cell infiltration.
“The study really highlights the importance of integrating molecular pathology into the clinical algorithms, because making the diagnosis is not sufficient. We really need to know what the pathology of the patient is so we can give the right drug to the right patients.”
Donald Thomas, MD, a rheumatologist in private practice in Silver Spring, Md., called the study “fascinating,” and noted during a question-and-answer period during the press conference that, during his lifetime, he “has probably wasted tens of thousands to hundreds of thousands of dollars,” using the trial-and-error approach to treatment.
“We can only treat by trial and error ... so being able to pinpoint therapy is just phenomenal,” he added, further noting in an interview after the press conference that finding the right treatment can be “such a struggle.”
“I literally have patients who have gone through 10 medicines and wasted thousands of dollars,” he said.
In response to a question from Dr. Thomas about the potential for rheumatologists to do their own synovial biopsies to help guide treatment in the event the findings are validated, Dr. Pitzalis said that is both feasible and an important goal.
“All the biopsies [in the study] were carried out by rheumatologists,” he noted. “We have trained over 150 rheumatologists worldwide, including at 15 centers in the United States. ... We want to empower the rheumatologists to do it.”
He added that “this is early data ... and will require validation in larger trials,” but said the point is that “we can’t continue to just give these drugs and see if the patient responds.”
R4-RA is funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program. Dr. Pitzalis and some of the other study authors reported financial relationships with Roche/Genentech, which markets tocilizumab and rituximab, and other pharmaceutical companies.
SOURCE: Pitzalis C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2911.
ATLANTA – Tocilizumab proved more effective than rituximab in B-cell-poor but not in B-cell-rich patients with RA who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibition in the randomized, open-label, 48-week, phase 4 R4-RA trial.
If validated, the findings of the trial – the first randomized, controlled, biopsy-driven trial in RA – could have “massive implications” for treatment selection and improved outcomes, Constantino Pitzalis, MD, reported during a press conference at the annual meeting of the American College of Rheumatology.
Of 164 RA patients who were failing or intolerant to conventional synthetic (cs) DMARD therapy and at least one tumor necrosis factor inhibitor (TNFi), 83 were randomized to receive rituximab and 81 received tocilizumab. Of those patients, 49.1% were considered B-cell poor (BCP) based on synovial tissue biopsies obtained at trial entry.
The BCP patients treated with tocilizumab were numerically more likely than those treated with rituximab to achieve the coprimary endpoint of Clinical Disease Activity Index (CDAI) improvement of at least 50% from baseline at 16 weeks (56.1% vs. 44.7%), and they were significantly more likely – twice as likely, in fact – to achieve the coprimary endpoint of CDAI improvement of at least 50% from baseline at 16 weeks as well as CDAI score less than 10, indicating a major treatment response (46.3% vs. 23.7%), said Dr. Pitzalis, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London.
BCP patients receiving tocilizumab also were significantly more likely to achieve a number of secondary endpoints, he noted.
In the B-cell-rich (BCR) population, no significant differences were seen in the majority of endpoints with tocilizumab versus rituximab, he said.
Study participants had a mean age of 55-56 years and were intolerant of or refractory to csDMARDs and at least one TNFi. They were recruited from 19 centers in Europe, were randomized and treated with standard doses of rituximab or tocilizumab, and were stratified based on histologic classification (BCP vs. BCR). Baseline characteristics were comparable among the treatment groups, Dr. Pitzalis said.
Adverse events occurred in 62 and 68 patients in the rituximab and tocilizumab groups, respectively, and serious adverse events occurred in 8 and 12 patients, respectively, thus 40% of all serious adverse events occurred in the rituximab group and 60% in the tocilizumab group. Infections and serious infections each occurred in three patients in each group, and two patients in each group discontinued treatment because of adverse events.
B cells are pivotal to RA pathogenesis, as demonstrated by the efficacy of the B-cell-depleting agent, rituximab. However, rituximab, which is licensed for use following failure of csDMARDs and TNFi therapy, is only effective for achieving a 50% improvement in ACR response criteria at 6 months in about 30% of such patients, Dr. Pitzalis noted. In a recent early RA cohort, he and his colleagues found synovial heterogeneity, with more than half of patients showing low or no synovial B-cell infiltration.
“So why would you give them rituximab?” he asked, explaining the rationale for the R4-RA trial: The hypothesis was that alternative biologic agents targeting alternative pathways may be more effective in BCP patients.
“The results showed quite clearly that rituximab was inferior to tocilizumab in this patient group,” he said. “We demonstrated that tocilizumab is more effective than rituximab in achieving low disease activity in patients who had, on synovial biopsy, low levels of B-cell infiltration.
“The study really highlights the importance of integrating molecular pathology into the clinical algorithms, because making the diagnosis is not sufficient. We really need to know what the pathology of the patient is so we can give the right drug to the right patients.”
Donald Thomas, MD, a rheumatologist in private practice in Silver Spring, Md., called the study “fascinating,” and noted during a question-and-answer period during the press conference that, during his lifetime, he “has probably wasted tens of thousands to hundreds of thousands of dollars,” using the trial-and-error approach to treatment.
“We can only treat by trial and error ... so being able to pinpoint therapy is just phenomenal,” he added, further noting in an interview after the press conference that finding the right treatment can be “such a struggle.”
“I literally have patients who have gone through 10 medicines and wasted thousands of dollars,” he said.
In response to a question from Dr. Thomas about the potential for rheumatologists to do their own synovial biopsies to help guide treatment in the event the findings are validated, Dr. Pitzalis said that is both feasible and an important goal.
“All the biopsies [in the study] were carried out by rheumatologists,” he noted. “We have trained over 150 rheumatologists worldwide, including at 15 centers in the United States. ... We want to empower the rheumatologists to do it.”
He added that “this is early data ... and will require validation in larger trials,” but said the point is that “we can’t continue to just give these drugs and see if the patient responds.”
R4-RA is funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program. Dr. Pitzalis and some of the other study authors reported financial relationships with Roche/Genentech, which markets tocilizumab and rituximab, and other pharmaceutical companies.
SOURCE: Pitzalis C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2911.
ATLANTA – Tocilizumab proved more effective than rituximab in B-cell-poor but not in B-cell-rich patients with RA who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibition in the randomized, open-label, 48-week, phase 4 R4-RA trial.
If validated, the findings of the trial – the first randomized, controlled, biopsy-driven trial in RA – could have “massive implications” for treatment selection and improved outcomes, Constantino Pitzalis, MD, reported during a press conference at the annual meeting of the American College of Rheumatology.
Of 164 RA patients who were failing or intolerant to conventional synthetic (cs) DMARD therapy and at least one tumor necrosis factor inhibitor (TNFi), 83 were randomized to receive rituximab and 81 received tocilizumab. Of those patients, 49.1% were considered B-cell poor (BCP) based on synovial tissue biopsies obtained at trial entry.
The BCP patients treated with tocilizumab were numerically more likely than those treated with rituximab to achieve the coprimary endpoint of Clinical Disease Activity Index (CDAI) improvement of at least 50% from baseline at 16 weeks (56.1% vs. 44.7%), and they were significantly more likely – twice as likely, in fact – to achieve the coprimary endpoint of CDAI improvement of at least 50% from baseline at 16 weeks as well as CDAI score less than 10, indicating a major treatment response (46.3% vs. 23.7%), said Dr. Pitzalis, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London.
BCP patients receiving tocilizumab also were significantly more likely to achieve a number of secondary endpoints, he noted.
In the B-cell-rich (BCR) population, no significant differences were seen in the majority of endpoints with tocilizumab versus rituximab, he said.
Study participants had a mean age of 55-56 years and were intolerant of or refractory to csDMARDs and at least one TNFi. They were recruited from 19 centers in Europe, were randomized and treated with standard doses of rituximab or tocilizumab, and were stratified based on histologic classification (BCP vs. BCR). Baseline characteristics were comparable among the treatment groups, Dr. Pitzalis said.
Adverse events occurred in 62 and 68 patients in the rituximab and tocilizumab groups, respectively, and serious adverse events occurred in 8 and 12 patients, respectively, thus 40% of all serious adverse events occurred in the rituximab group and 60% in the tocilizumab group. Infections and serious infections each occurred in three patients in each group, and two patients in each group discontinued treatment because of adverse events.
B cells are pivotal to RA pathogenesis, as demonstrated by the efficacy of the B-cell-depleting agent, rituximab. However, rituximab, which is licensed for use following failure of csDMARDs and TNFi therapy, is only effective for achieving a 50% improvement in ACR response criteria at 6 months in about 30% of such patients, Dr. Pitzalis noted. In a recent early RA cohort, he and his colleagues found synovial heterogeneity, with more than half of patients showing low or no synovial B-cell infiltration.
“So why would you give them rituximab?” he asked, explaining the rationale for the R4-RA trial: The hypothesis was that alternative biologic agents targeting alternative pathways may be more effective in BCP patients.
“The results showed quite clearly that rituximab was inferior to tocilizumab in this patient group,” he said. “We demonstrated that tocilizumab is more effective than rituximab in achieving low disease activity in patients who had, on synovial biopsy, low levels of B-cell infiltration.
“The study really highlights the importance of integrating molecular pathology into the clinical algorithms, because making the diagnosis is not sufficient. We really need to know what the pathology of the patient is so we can give the right drug to the right patients.”
Donald Thomas, MD, a rheumatologist in private practice in Silver Spring, Md., called the study “fascinating,” and noted during a question-and-answer period during the press conference that, during his lifetime, he “has probably wasted tens of thousands to hundreds of thousands of dollars,” using the trial-and-error approach to treatment.
“We can only treat by trial and error ... so being able to pinpoint therapy is just phenomenal,” he added, further noting in an interview after the press conference that finding the right treatment can be “such a struggle.”
“I literally have patients who have gone through 10 medicines and wasted thousands of dollars,” he said.
In response to a question from Dr. Thomas about the potential for rheumatologists to do their own synovial biopsies to help guide treatment in the event the findings are validated, Dr. Pitzalis said that is both feasible and an important goal.
“All the biopsies [in the study] were carried out by rheumatologists,” he noted. “We have trained over 150 rheumatologists worldwide, including at 15 centers in the United States. ... We want to empower the rheumatologists to do it.”
He added that “this is early data ... and will require validation in larger trials,” but said the point is that “we can’t continue to just give these drugs and see if the patient responds.”
R4-RA is funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program. Dr. Pitzalis and some of the other study authors reported financial relationships with Roche/Genentech, which markets tocilizumab and rituximab, and other pharmaceutical companies.
SOURCE: Pitzalis C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2911.
REPORTING FROM ACR 2019
Worse air quality linked to premature deaths
, according to a working paper issued by the National Bureau of Economic Research.
The increase in air pollution, defined as the amount of fine particulate matter (PM2.5) in the air, was associated with an additional 9,700 premature deaths from 2016 to 2018, representing damages totaling $89 billion, wrote Karen Clay and Nicholas C. Miller of Carnegie Mellon University, Pittsburgh. The increase may reflect in part the impact of the a major wildfire that occurred in the fall of 2018.
“These increases are worrisome, because previous studies have shown that PM2.5 increases premature mortality risk,” the researchers wrote. To assess the changes in air quality, they reviewed data from the Air Quality System (AQS) database including total PM2.5 and three PM2.5 species: ammonium nitrate, sulfate, and elemental carbon.
To examine the impact of pollution on public health, the researchers used data from the damage function approach used in the Environmental Protection Agency’s Benefit-Cost Analysis of the Clean Air Act, the Regulatory Impact Analysis for PM2.5, and multiple academic studies.
The number of premature deaths linked to PM2.5 increased by approximately 4,900 between 2016 and 2017 and by 9,700 from 2016 to 2018 in U.S. counties with monitors.
Elderly individuals are especially vulnerable to particulate matter exposure and experience approximately 80% of the burden of disease related to pollution, the researchers said.
“While some deaths among the elderly are shifted by days or weeks, recent research suggests that the burden is ‘concentrated among the elderly with 5-10 years of remaining life expectancy, followed by those with 2-5 years remaining, because these groups represent a large fraction of the Medicare population and are also vulnerable to acute particulate matter exposure,’” they said.
Overall, pollution levels across the United States stopped declining in 2016. When broken down by four Census regions, no change in PM2.5 levels occurred in the Northeast and South between 2016 and 2018; the Midwest and West showed increases in PM2.5 of 9.3% and 11.5%, respectively.
The researchers suggested three possible factors affecting the increase in pollution: economic activity, wildfires, and air quality enforcement. They noted that increases in PM2.5 were especially high in California, and that California accounted for 43% of the increase in pollution-related premature deaths nationwide between 2016 and 2018. When the researchers examined PM2.5 month by month, “November 2018 had an outsized effect on our mortality calculations,” largely because the devastating Camp Fire occurred in California at that time, they said.
With regard to the impact of economic activity on pollution, the researchers reviewed data from the National Highway Administration and Energy Information Administration that showed increased use of natural gas and increased vehicle travel as contributing to higher levels of nitrate and elemental carbon in the air.
Finally, the researchers reported that enforcement of the Clean Air Act appeared to have declined since 2013, and this decline, although it might reflect increased compliance in some areas “is concerning in light of the increases in air pollution in both attainment and nonattainment counties after 2016,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Clay K, Miller NZ. NBER 2019. Working Paper 26381. doi: 10.3386/w26381.
, according to a working paper issued by the National Bureau of Economic Research.
The increase in air pollution, defined as the amount of fine particulate matter (PM2.5) in the air, was associated with an additional 9,700 premature deaths from 2016 to 2018, representing damages totaling $89 billion, wrote Karen Clay and Nicholas C. Miller of Carnegie Mellon University, Pittsburgh. The increase may reflect in part the impact of the a major wildfire that occurred in the fall of 2018.
“These increases are worrisome, because previous studies have shown that PM2.5 increases premature mortality risk,” the researchers wrote. To assess the changes in air quality, they reviewed data from the Air Quality System (AQS) database including total PM2.5 and three PM2.5 species: ammonium nitrate, sulfate, and elemental carbon.
To examine the impact of pollution on public health, the researchers used data from the damage function approach used in the Environmental Protection Agency’s Benefit-Cost Analysis of the Clean Air Act, the Regulatory Impact Analysis for PM2.5, and multiple academic studies.
The number of premature deaths linked to PM2.5 increased by approximately 4,900 between 2016 and 2017 and by 9,700 from 2016 to 2018 in U.S. counties with monitors.
Elderly individuals are especially vulnerable to particulate matter exposure and experience approximately 80% of the burden of disease related to pollution, the researchers said.
“While some deaths among the elderly are shifted by days or weeks, recent research suggests that the burden is ‘concentrated among the elderly with 5-10 years of remaining life expectancy, followed by those with 2-5 years remaining, because these groups represent a large fraction of the Medicare population and are also vulnerable to acute particulate matter exposure,’” they said.
Overall, pollution levels across the United States stopped declining in 2016. When broken down by four Census regions, no change in PM2.5 levels occurred in the Northeast and South between 2016 and 2018; the Midwest and West showed increases in PM2.5 of 9.3% and 11.5%, respectively.
The researchers suggested three possible factors affecting the increase in pollution: economic activity, wildfires, and air quality enforcement. They noted that increases in PM2.5 were especially high in California, and that California accounted for 43% of the increase in pollution-related premature deaths nationwide between 2016 and 2018. When the researchers examined PM2.5 month by month, “November 2018 had an outsized effect on our mortality calculations,” largely because the devastating Camp Fire occurred in California at that time, they said.
With regard to the impact of economic activity on pollution, the researchers reviewed data from the National Highway Administration and Energy Information Administration that showed increased use of natural gas and increased vehicle travel as contributing to higher levels of nitrate and elemental carbon in the air.
Finally, the researchers reported that enforcement of the Clean Air Act appeared to have declined since 2013, and this decline, although it might reflect increased compliance in some areas “is concerning in light of the increases in air pollution in both attainment and nonattainment counties after 2016,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Clay K, Miller NZ. NBER 2019. Working Paper 26381. doi: 10.3386/w26381.
, according to a working paper issued by the National Bureau of Economic Research.
The increase in air pollution, defined as the amount of fine particulate matter (PM2.5) in the air, was associated with an additional 9,700 premature deaths from 2016 to 2018, representing damages totaling $89 billion, wrote Karen Clay and Nicholas C. Miller of Carnegie Mellon University, Pittsburgh. The increase may reflect in part the impact of the a major wildfire that occurred in the fall of 2018.
“These increases are worrisome, because previous studies have shown that PM2.5 increases premature mortality risk,” the researchers wrote. To assess the changes in air quality, they reviewed data from the Air Quality System (AQS) database including total PM2.5 and three PM2.5 species: ammonium nitrate, sulfate, and elemental carbon.
To examine the impact of pollution on public health, the researchers used data from the damage function approach used in the Environmental Protection Agency’s Benefit-Cost Analysis of the Clean Air Act, the Regulatory Impact Analysis for PM2.5, and multiple academic studies.
The number of premature deaths linked to PM2.5 increased by approximately 4,900 between 2016 and 2017 and by 9,700 from 2016 to 2018 in U.S. counties with monitors.
Elderly individuals are especially vulnerable to particulate matter exposure and experience approximately 80% of the burden of disease related to pollution, the researchers said.
“While some deaths among the elderly are shifted by days or weeks, recent research suggests that the burden is ‘concentrated among the elderly with 5-10 years of remaining life expectancy, followed by those with 2-5 years remaining, because these groups represent a large fraction of the Medicare population and are also vulnerable to acute particulate matter exposure,’” they said.
Overall, pollution levels across the United States stopped declining in 2016. When broken down by four Census regions, no change in PM2.5 levels occurred in the Northeast and South between 2016 and 2018; the Midwest and West showed increases in PM2.5 of 9.3% and 11.5%, respectively.
The researchers suggested three possible factors affecting the increase in pollution: economic activity, wildfires, and air quality enforcement. They noted that increases in PM2.5 were especially high in California, and that California accounted for 43% of the increase in pollution-related premature deaths nationwide between 2016 and 2018. When the researchers examined PM2.5 month by month, “November 2018 had an outsized effect on our mortality calculations,” largely because the devastating Camp Fire occurred in California at that time, they said.
With regard to the impact of economic activity on pollution, the researchers reviewed data from the National Highway Administration and Energy Information Administration that showed increased use of natural gas and increased vehicle travel as contributing to higher levels of nitrate and elemental carbon in the air.
Finally, the researchers reported that enforcement of the Clean Air Act appeared to have declined since 2013, and this decline, although it might reflect increased compliance in some areas “is concerning in light of the increases in air pollution in both attainment and nonattainment counties after 2016,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Clay K, Miller NZ. NBER 2019. Working Paper 26381. doi: 10.3386/w26381.
FROM AN NBER AIR QUALITY STUDY
Don’t leave dermatomyositis to the rheumatologists
LAS VEGAS – When she brings up dermatomyositis in the context of dermatology, Alisa Femia, MD, often hears from trainees and medical students who assume that this is a condition for rheumatologists to diagnose and treat. That’s not true: Dermatologists need to watch for this potentially fatal connective tissue disorder because they may see it first, she said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
“A fifth are clinically amyopathic,” and they may not initially see a rheumatologist, said Dr. Femia, director of inpatient dermatology at the department of dermatology, New York University. “They have normal muscle enzymes and no muscle weakness. It really puts them in our care as dermatologists.”
The challenge is that patient presentations can be subtle, but the stakes may be high, she added. “If we catch them early and treat some of these patients aggressively, we can save their lives.”
During the presentation, :
- Don’t rely on tests like biopsies to absolutely tell you what’s going on. “Clinical examination is the most important test to establish the diagnosis,” she said. “If you’re suspecting dermatomyositis ... get the patient in a gown [for a full-body exam] and look for all the signs that might not be as prominent as they are in our textbooks.”
- Look for the “butterfly” rash on the midface that is unique because it spares the nasolabial folds. “It looks like someone took an eraser and wiped out those areas,” Dr. Femia said. “This is important to help us nail down the diagnosis.”
- Other telltale signs, she said, include erythema on the extensor surfaces of digits, severe itching in the scalp, and a rash on the eyelids.
- Be aware of pulmonary involvement, including interstitial lung disease. In some cases, patients and their physicians wrongly believe that patients with dermatomyositis have asthma or pneumonia. “Pulmonologists are not necessarily aware of lung disease associated with dermatomyositis,” she said.
It’s wise to refer patients with dermatomyositis for malignancy and lung disease screening even if they don’t show signs of muscular involvement. “There’s no significant difference in rates of malignancy or lung disease in classic versus amyopathic dermatomyositis.”
Keep the MDA5 form of dermatomyositis in mind, Dr. Femia said. Anti–melanoma differentiation–associated gene 5 dermatomyositis is linked to rapidly progressive interstitial lung disease, alopecia, arthritis and oral lacerations. “Initially, it can have features of lupus, and the patient can be on immunosuppressive therapy, which mitigates diagnostic findings.”
Dr. Femia disclosed serving as principal investigator for a clinical trial in cutaneous dermatomyositis therapy.
SDEF and this news organization are owned by the same parent company.
LAS VEGAS – When she brings up dermatomyositis in the context of dermatology, Alisa Femia, MD, often hears from trainees and medical students who assume that this is a condition for rheumatologists to diagnose and treat. That’s not true: Dermatologists need to watch for this potentially fatal connective tissue disorder because they may see it first, she said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
“A fifth are clinically amyopathic,” and they may not initially see a rheumatologist, said Dr. Femia, director of inpatient dermatology at the department of dermatology, New York University. “They have normal muscle enzymes and no muscle weakness. It really puts them in our care as dermatologists.”
The challenge is that patient presentations can be subtle, but the stakes may be high, she added. “If we catch them early and treat some of these patients aggressively, we can save their lives.”
During the presentation, :
- Don’t rely on tests like biopsies to absolutely tell you what’s going on. “Clinical examination is the most important test to establish the diagnosis,” she said. “If you’re suspecting dermatomyositis ... get the patient in a gown [for a full-body exam] and look for all the signs that might not be as prominent as they are in our textbooks.”
- Look for the “butterfly” rash on the midface that is unique because it spares the nasolabial folds. “It looks like someone took an eraser and wiped out those areas,” Dr. Femia said. “This is important to help us nail down the diagnosis.”
- Other telltale signs, she said, include erythema on the extensor surfaces of digits, severe itching in the scalp, and a rash on the eyelids.
- Be aware of pulmonary involvement, including interstitial lung disease. In some cases, patients and their physicians wrongly believe that patients with dermatomyositis have asthma or pneumonia. “Pulmonologists are not necessarily aware of lung disease associated with dermatomyositis,” she said.
It’s wise to refer patients with dermatomyositis for malignancy and lung disease screening even if they don’t show signs of muscular involvement. “There’s no significant difference in rates of malignancy or lung disease in classic versus amyopathic dermatomyositis.”
Keep the MDA5 form of dermatomyositis in mind, Dr. Femia said. Anti–melanoma differentiation–associated gene 5 dermatomyositis is linked to rapidly progressive interstitial lung disease, alopecia, arthritis and oral lacerations. “Initially, it can have features of lupus, and the patient can be on immunosuppressive therapy, which mitigates diagnostic findings.”
Dr. Femia disclosed serving as principal investigator for a clinical trial in cutaneous dermatomyositis therapy.
SDEF and this news organization are owned by the same parent company.
LAS VEGAS – When she brings up dermatomyositis in the context of dermatology, Alisa Femia, MD, often hears from trainees and medical students who assume that this is a condition for rheumatologists to diagnose and treat. That’s not true: Dermatologists need to watch for this potentially fatal connective tissue disorder because they may see it first, she said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
“A fifth are clinically amyopathic,” and they may not initially see a rheumatologist, said Dr. Femia, director of inpatient dermatology at the department of dermatology, New York University. “They have normal muscle enzymes and no muscle weakness. It really puts them in our care as dermatologists.”
The challenge is that patient presentations can be subtle, but the stakes may be high, she added. “If we catch them early and treat some of these patients aggressively, we can save their lives.”
During the presentation, :
- Don’t rely on tests like biopsies to absolutely tell you what’s going on. “Clinical examination is the most important test to establish the diagnosis,” she said. “If you’re suspecting dermatomyositis ... get the patient in a gown [for a full-body exam] and look for all the signs that might not be as prominent as they are in our textbooks.”
- Look for the “butterfly” rash on the midface that is unique because it spares the nasolabial folds. “It looks like someone took an eraser and wiped out those areas,” Dr. Femia said. “This is important to help us nail down the diagnosis.”
- Other telltale signs, she said, include erythema on the extensor surfaces of digits, severe itching in the scalp, and a rash on the eyelids.
- Be aware of pulmonary involvement, including interstitial lung disease. In some cases, patients and their physicians wrongly believe that patients with dermatomyositis have asthma or pneumonia. “Pulmonologists are not necessarily aware of lung disease associated with dermatomyositis,” she said.
It’s wise to refer patients with dermatomyositis for malignancy and lung disease screening even if they don’t show signs of muscular involvement. “There’s no significant difference in rates of malignancy or lung disease in classic versus amyopathic dermatomyositis.”
Keep the MDA5 form of dermatomyositis in mind, Dr. Femia said. Anti–melanoma differentiation–associated gene 5 dermatomyositis is linked to rapidly progressive interstitial lung disease, alopecia, arthritis and oral lacerations. “Initially, it can have features of lupus, and the patient can be on immunosuppressive therapy, which mitigates diagnostic findings.”
Dr. Femia disclosed serving as principal investigator for a clinical trial in cutaneous dermatomyositis therapy.
SDEF and this news organization are owned by the same parent company.
REPORTING FROM SDEF LAS VEGAS DERMATOLOGY SEMINAR
Conduct disorder in girls gets overdue research attention
COPENHAGEN – The physiological and emotion-processing abnormalities that underpin conduct disorder in teen girls are essentially the same as in teen boys, although the clinical presentation of conduct disorder in the two groups is often different, according to preliminary results from the large pan-European FemNAT-CD study, the first large study of conduct disorder in girls.
“The main finding of the study, I think, is that we found no major differences in physiology between male and female conduct disorder. There are some differences, mainly related to having less LPE [low prosocial emotions] and more internalizing comorbidity in the girls, but when you look at conduct disorder overall, then you see that the physiological systems are about the same,” Lucres Nauta-Jansen, PhD, commented in presenting some of the early FemNAT-CD findings at the annual congress of the European College of Neuropsychopharmacology.
LPE is a term included in the DSM-5 as a descriptor of individuals with conduct disorder (CD) who exhibit callous-unemotional traits. The LPE specifier was present in 37% of the 296 adolescent girls with CD in FemNAT-CD, significantly less than the 50% prevalence in the 187 adolescent boys with CD in the study. This analysis from the ongoing study, which is being conducted at 13 universities across Europe, also included 363 age-matched girls and 164 age-matched boys without CD as controls. Average participant age was 14 years.
FemNAT-CD is a multidisciplinary study aimed at exploring sex differences between boys and girls with and without CD in terms of brain structure and function, genetics, hormone levels, emotion recognition and regulation, and autonomic nervous system (ANS) activity. At Amsterdam University Medical Center, where Dr. Nauta-Jansen serves as deputy head of the department of child and adolescent psychiatry, she and her coinvestigators have focused on the autonomic activity and emotion-processing portions of FemNAT-CD.
CD is less common in girls than boys, although the prevalence in girls is growing. The importance of FemNAT-CD lies in the fact that virtually all prior studies of CD were conducted in boys. As a result, there is no specific treatment intervention available for girls with CD.
“We actually don’t know anything about girls. There are a few previous studies, but they have small samples and contradictory results. We need to know more about the mechanisms that are involved in this kind of behavior to develop more specific treatments in the future,” Dr. Nauta-Jansen said.
In FemNAT-CD, the girls with CD not only had a lower rate of LPE symptoms than the boys with CD, they also had a significantly higher prevalence of anxiety and other internalizing comorbidities, by a margin of 32% to 22%. These differences are manifested in different expressions of antisocial behavior as described in the model of the neurobiology of CD developed by R. James Blair, PhD, director of the Center for Neurobehavioral Research at the Boys Town National Research Hospital in Omaha, Neb (Nat Rev Neurosci. 2013 Nov;14[11]:786-99).
According to the model’s low psychophysiological arousal theory, boys with the callous-unemotional form of CD have low basal ANS activity and low amygdala responsiveness to stressful events, making them more prone to sensation-seeking behavior.
“This might make them want to do ice climbing or sky diving. Or, in a more negative environment or in a bad neighborhood, it can also lead to aggressive and delinquent behavior,” Dr. Nauta-Jansen said.
The other core impairment that is common in a subset of CD patients as described in the Blair model – again, based upon studies in boys – involves a tendency to engage in threat-based reactive aggression with an increased ANS response to stress and a related difficulty in processing emotions.
Dr. Nauta-Jansen and coinvestigators conducted a series of tests of FemNAT-CD participants which demonstrated, for the first time, that both the callous-unemotional and threat-based reactive aggression forms of CD are present in girls as well as boys, albeit in different proportions.
The investigators found no differences in baseline ANS activity between girls and boys with CD and the controls as measured by heart rate, heart rate variability, and cardiac preejection period. Nor were there any differences in baseline ANS activity between boys and girls with CD and LPE. However, girls with CD and anxiety or other internalizing comorbidity displayed significantly lower heart rate variability than those without internalizing comorbidity or female controls.
Next, the investigators subjected study participants to an emotion provocation task in which they viewed two sadness-inducing film clips, including a heart-rending scene from the 1979 movie, “The Champ,” in which an ex-boxer played by Jon Voight returns to the ring to raise money to support his young son, played by Ricky Shroder. The champ wins by a knockout after taking such a beating that he subsequently dies in his dressing room as his son watches.
Both the girls and boys with CD had an increased heart rate response to “The Champ,” compared with the controls. And those with CD who did not have the LPE specifier showed the biggest ANS response of all. They were highly sensitive to negative emotions.
On a countdown task involving exposure to a loud, startling noise, the girls with CD did not learn to anticipate the pending startle at the autonomic level, whereas the boys with CD reacted no differently from controls.
On the Trier Social Stress Test, which entails public speaking and performing mental math calculations in front of a camera and a live audience of two, both the boys and girls with CD demonstrated a similarly lower heart rate response to the tasks than controls. Those with the LPE specifier had the lowest heart rate response of all.
“The conduct disorder subjects were impaired in their anticipatory response to fear and stress, but their responses to sadness were increased,” Dr. Nauta-Jansen observed.
“I think the main thing with these kids is they are mostly disturbed in their anticipation of bad situations. What you see in the countdown task is they don’t anticipate that there will be a bad event. And you see this also in clinical practice, that they sometimes get overwhelmed by things because they don’t learn from their previous experiences, including bad events. I think they don’t anticipate and therefore are more overwhelmed by bad events – especially the girls,” she said.
The take-home message from this phase of the FemNAT-CD study, she added, is straightforward: “ although you have to be very aware that they show different symptomatology in terms of internalizing comorbidity.”
The FemNAT-CD investigators have developed a multifaceted therapeutic intervention for girls with CD that shows early promise in clinical settings. It includes aggression regulation training, medication in some cases, and emotion-processing training to teach patients how to deal with negative emotions without exploding into aggression.
FemNAT-CD is funded by the European Commission. Dr. Nauta-Jansen reported having no financial conflicts regarding the study.
COPENHAGEN – The physiological and emotion-processing abnormalities that underpin conduct disorder in teen girls are essentially the same as in teen boys, although the clinical presentation of conduct disorder in the two groups is often different, according to preliminary results from the large pan-European FemNAT-CD study, the first large study of conduct disorder in girls.
“The main finding of the study, I think, is that we found no major differences in physiology between male and female conduct disorder. There are some differences, mainly related to having less LPE [low prosocial emotions] and more internalizing comorbidity in the girls, but when you look at conduct disorder overall, then you see that the physiological systems are about the same,” Lucres Nauta-Jansen, PhD, commented in presenting some of the early FemNAT-CD findings at the annual congress of the European College of Neuropsychopharmacology.
LPE is a term included in the DSM-5 as a descriptor of individuals with conduct disorder (CD) who exhibit callous-unemotional traits. The LPE specifier was present in 37% of the 296 adolescent girls with CD in FemNAT-CD, significantly less than the 50% prevalence in the 187 adolescent boys with CD in the study. This analysis from the ongoing study, which is being conducted at 13 universities across Europe, also included 363 age-matched girls and 164 age-matched boys without CD as controls. Average participant age was 14 years.
FemNAT-CD is a multidisciplinary study aimed at exploring sex differences between boys and girls with and without CD in terms of brain structure and function, genetics, hormone levels, emotion recognition and regulation, and autonomic nervous system (ANS) activity. At Amsterdam University Medical Center, where Dr. Nauta-Jansen serves as deputy head of the department of child and adolescent psychiatry, she and her coinvestigators have focused on the autonomic activity and emotion-processing portions of FemNAT-CD.
CD is less common in girls than boys, although the prevalence in girls is growing. The importance of FemNAT-CD lies in the fact that virtually all prior studies of CD were conducted in boys. As a result, there is no specific treatment intervention available for girls with CD.
“We actually don’t know anything about girls. There are a few previous studies, but they have small samples and contradictory results. We need to know more about the mechanisms that are involved in this kind of behavior to develop more specific treatments in the future,” Dr. Nauta-Jansen said.
In FemNAT-CD, the girls with CD not only had a lower rate of LPE symptoms than the boys with CD, they also had a significantly higher prevalence of anxiety and other internalizing comorbidities, by a margin of 32% to 22%. These differences are manifested in different expressions of antisocial behavior as described in the model of the neurobiology of CD developed by R. James Blair, PhD, director of the Center for Neurobehavioral Research at the Boys Town National Research Hospital in Omaha, Neb (Nat Rev Neurosci. 2013 Nov;14[11]:786-99).
According to the model’s low psychophysiological arousal theory, boys with the callous-unemotional form of CD have low basal ANS activity and low amygdala responsiveness to stressful events, making them more prone to sensation-seeking behavior.
“This might make them want to do ice climbing or sky diving. Or, in a more negative environment or in a bad neighborhood, it can also lead to aggressive and delinquent behavior,” Dr. Nauta-Jansen said.
The other core impairment that is common in a subset of CD patients as described in the Blair model – again, based upon studies in boys – involves a tendency to engage in threat-based reactive aggression with an increased ANS response to stress and a related difficulty in processing emotions.
Dr. Nauta-Jansen and coinvestigators conducted a series of tests of FemNAT-CD participants which demonstrated, for the first time, that both the callous-unemotional and threat-based reactive aggression forms of CD are present in girls as well as boys, albeit in different proportions.
The investigators found no differences in baseline ANS activity between girls and boys with CD and the controls as measured by heart rate, heart rate variability, and cardiac preejection period. Nor were there any differences in baseline ANS activity between boys and girls with CD and LPE. However, girls with CD and anxiety or other internalizing comorbidity displayed significantly lower heart rate variability than those without internalizing comorbidity or female controls.
Next, the investigators subjected study participants to an emotion provocation task in which they viewed two sadness-inducing film clips, including a heart-rending scene from the 1979 movie, “The Champ,” in which an ex-boxer played by Jon Voight returns to the ring to raise money to support his young son, played by Ricky Shroder. The champ wins by a knockout after taking such a beating that he subsequently dies in his dressing room as his son watches.
Both the girls and boys with CD had an increased heart rate response to “The Champ,” compared with the controls. And those with CD who did not have the LPE specifier showed the biggest ANS response of all. They were highly sensitive to negative emotions.
On a countdown task involving exposure to a loud, startling noise, the girls with CD did not learn to anticipate the pending startle at the autonomic level, whereas the boys with CD reacted no differently from controls.
On the Trier Social Stress Test, which entails public speaking and performing mental math calculations in front of a camera and a live audience of two, both the boys and girls with CD demonstrated a similarly lower heart rate response to the tasks than controls. Those with the LPE specifier had the lowest heart rate response of all.
“The conduct disorder subjects were impaired in their anticipatory response to fear and stress, but their responses to sadness were increased,” Dr. Nauta-Jansen observed.
“I think the main thing with these kids is they are mostly disturbed in their anticipation of bad situations. What you see in the countdown task is they don’t anticipate that there will be a bad event. And you see this also in clinical practice, that they sometimes get overwhelmed by things because they don’t learn from their previous experiences, including bad events. I think they don’t anticipate and therefore are more overwhelmed by bad events – especially the girls,” she said.
The take-home message from this phase of the FemNAT-CD study, she added, is straightforward: “ although you have to be very aware that they show different symptomatology in terms of internalizing comorbidity.”
The FemNAT-CD investigators have developed a multifaceted therapeutic intervention for girls with CD that shows early promise in clinical settings. It includes aggression regulation training, medication in some cases, and emotion-processing training to teach patients how to deal with negative emotions without exploding into aggression.
FemNAT-CD is funded by the European Commission. Dr. Nauta-Jansen reported having no financial conflicts regarding the study.
COPENHAGEN – The physiological and emotion-processing abnormalities that underpin conduct disorder in teen girls are essentially the same as in teen boys, although the clinical presentation of conduct disorder in the two groups is often different, according to preliminary results from the large pan-European FemNAT-CD study, the first large study of conduct disorder in girls.
“The main finding of the study, I think, is that we found no major differences in physiology between male and female conduct disorder. There are some differences, mainly related to having less LPE [low prosocial emotions] and more internalizing comorbidity in the girls, but when you look at conduct disorder overall, then you see that the physiological systems are about the same,” Lucres Nauta-Jansen, PhD, commented in presenting some of the early FemNAT-CD findings at the annual congress of the European College of Neuropsychopharmacology.
LPE is a term included in the DSM-5 as a descriptor of individuals with conduct disorder (CD) who exhibit callous-unemotional traits. The LPE specifier was present in 37% of the 296 adolescent girls with CD in FemNAT-CD, significantly less than the 50% prevalence in the 187 adolescent boys with CD in the study. This analysis from the ongoing study, which is being conducted at 13 universities across Europe, also included 363 age-matched girls and 164 age-matched boys without CD as controls. Average participant age was 14 years.
FemNAT-CD is a multidisciplinary study aimed at exploring sex differences between boys and girls with and without CD in terms of brain structure and function, genetics, hormone levels, emotion recognition and regulation, and autonomic nervous system (ANS) activity. At Amsterdam University Medical Center, where Dr. Nauta-Jansen serves as deputy head of the department of child and adolescent psychiatry, she and her coinvestigators have focused on the autonomic activity and emotion-processing portions of FemNAT-CD.
CD is less common in girls than boys, although the prevalence in girls is growing. The importance of FemNAT-CD lies in the fact that virtually all prior studies of CD were conducted in boys. As a result, there is no specific treatment intervention available for girls with CD.
“We actually don’t know anything about girls. There are a few previous studies, but they have small samples and contradictory results. We need to know more about the mechanisms that are involved in this kind of behavior to develop more specific treatments in the future,” Dr. Nauta-Jansen said.
In FemNAT-CD, the girls with CD not only had a lower rate of LPE symptoms than the boys with CD, they also had a significantly higher prevalence of anxiety and other internalizing comorbidities, by a margin of 32% to 22%. These differences are manifested in different expressions of antisocial behavior as described in the model of the neurobiology of CD developed by R. James Blair, PhD, director of the Center for Neurobehavioral Research at the Boys Town National Research Hospital in Omaha, Neb (Nat Rev Neurosci. 2013 Nov;14[11]:786-99).
According to the model’s low psychophysiological arousal theory, boys with the callous-unemotional form of CD have low basal ANS activity and low amygdala responsiveness to stressful events, making them more prone to sensation-seeking behavior.
“This might make them want to do ice climbing or sky diving. Or, in a more negative environment or in a bad neighborhood, it can also lead to aggressive and delinquent behavior,” Dr. Nauta-Jansen said.
The other core impairment that is common in a subset of CD patients as described in the Blair model – again, based upon studies in boys – involves a tendency to engage in threat-based reactive aggression with an increased ANS response to stress and a related difficulty in processing emotions.
Dr. Nauta-Jansen and coinvestigators conducted a series of tests of FemNAT-CD participants which demonstrated, for the first time, that both the callous-unemotional and threat-based reactive aggression forms of CD are present in girls as well as boys, albeit in different proportions.
The investigators found no differences in baseline ANS activity between girls and boys with CD and the controls as measured by heart rate, heart rate variability, and cardiac preejection period. Nor were there any differences in baseline ANS activity between boys and girls with CD and LPE. However, girls with CD and anxiety or other internalizing comorbidity displayed significantly lower heart rate variability than those without internalizing comorbidity or female controls.
Next, the investigators subjected study participants to an emotion provocation task in which they viewed two sadness-inducing film clips, including a heart-rending scene from the 1979 movie, “The Champ,” in which an ex-boxer played by Jon Voight returns to the ring to raise money to support his young son, played by Ricky Shroder. The champ wins by a knockout after taking such a beating that he subsequently dies in his dressing room as his son watches.
Both the girls and boys with CD had an increased heart rate response to “The Champ,” compared with the controls. And those with CD who did not have the LPE specifier showed the biggest ANS response of all. They were highly sensitive to negative emotions.
On a countdown task involving exposure to a loud, startling noise, the girls with CD did not learn to anticipate the pending startle at the autonomic level, whereas the boys with CD reacted no differently from controls.
On the Trier Social Stress Test, which entails public speaking and performing mental math calculations in front of a camera and a live audience of two, both the boys and girls with CD demonstrated a similarly lower heart rate response to the tasks than controls. Those with the LPE specifier had the lowest heart rate response of all.
“The conduct disorder subjects were impaired in their anticipatory response to fear and stress, but their responses to sadness were increased,” Dr. Nauta-Jansen observed.
“I think the main thing with these kids is they are mostly disturbed in their anticipation of bad situations. What you see in the countdown task is they don’t anticipate that there will be a bad event. And you see this also in clinical practice, that they sometimes get overwhelmed by things because they don’t learn from their previous experiences, including bad events. I think they don’t anticipate and therefore are more overwhelmed by bad events – especially the girls,” she said.
The take-home message from this phase of the FemNAT-CD study, she added, is straightforward: “ although you have to be very aware that they show different symptomatology in terms of internalizing comorbidity.”
The FemNAT-CD investigators have developed a multifaceted therapeutic intervention for girls with CD that shows early promise in clinical settings. It includes aggression regulation training, medication in some cases, and emotion-processing training to teach patients how to deal with negative emotions without exploding into aggression.
FemNAT-CD is funded by the European Commission. Dr. Nauta-Jansen reported having no financial conflicts regarding the study.
REPORTING FROM ECNP 2019
Prescribing guide recommends fewer opioids after colorectal surgery
SAN FRANCISCO – Opioids may not always be necessary following elective colorectal surgery. That’s the message coming from a retrospective study of medical records at the University of Massachusetts Medical Center, Worcester, which found that over
“We found that over half of the patients took no opioid pills after discharge, and 60% of the prescribed pills were left over,” said David Meyer, MD, during a presentation of the study at the annual clinical congress of the American College of Surgeons. Dr. Meyer is a surgical resident at the University of Massachusetts.
The team also used the results of their analysis to develop a guideline for the amount of opioid to prescribe following major colorectal surgery, with specific amounts of pills recommended based on the amount of opioid use during the last 24 hours of hospitalization.
“It shows a real interest in tailoring our postoperative care in pain management. They’re trying to find a way to hit a sweet spot to get patients the right amount of pain control,” said Jonathan Mitchem, MD, in an interview. Dr. Mitchem is an assistant professor at University of Missouri–Columbia, and comoderated the session where the research was presented.
The researchers performed a retrospective analysis of major elective colorectal procedures at their institution, including colectomy, rectal resection, and ostomy reversal. The analysis included 100 patients (55 female), with a mean age of 59 years. A total of 71% were opioid naive, meaning there was no evidence of an opioid prescription in the year prior to surgery. A total of 74% underwent a laparoscopic procedure, and 75% had a partial colectomy. The postoperative stay averaged 4.5 days.
The researchers converted in-hospital opioid use categories (IOUC) to equianalgesic 5-mg oxycodone pills (EOPs). In the last 24 hours before release, 53% of patients had no opioids at all (no IOUC, 0 EOPs), 25% received low amounts of opioids (low IOUC, 0.1-3.0 EOPs), and 22% high amounts (high IOUC, more than 3.1 EOPs). Overall, prescribed EOP was 17.5, and just 38% was consumed. These numbers were lowest in the no-IOUC group (15.7, 16%), followed by the low-IOUC group (16.0, 32%), and the high group (23.7, 79%; P less than .01).
The researchers then looked at the 85th percentile of EOPs for each group, and used that to develop a guideline for opioid prescription. For the no-IOUC group, they recommend 3 EOPs, for the low-IOUC group they recommend 12 EOPs, and for the high-IOUC group they recommend 30 EOPs.
The researchers examined various factors that might have influenced opioid use, correcting for whether the patient was opioid naive, case type, postoperative length of stay, and new ostomy creation. The only factor with a significant association for excessive opioid use was inflammatory bowel disease, which was linked to a nearly 900% increased risk of using more than the guideline amounts (adjusted odds ratio, 8.3; P less than .01; area under the curve, 0.85).
The study is limited by the fact that it was conducted at a single center, and that patient opioid use was self-reported. The guidelines need to be validated prospectively.
No funding information was disclosed. Dr. Meyer and Dr. Mitchem had no relevant financial disclosures.
SOURCE: Meyer D et al. Clinical Congress 2019, Abstract.
SAN FRANCISCO – Opioids may not always be necessary following elective colorectal surgery. That’s the message coming from a retrospective study of medical records at the University of Massachusetts Medical Center, Worcester, which found that over
“We found that over half of the patients took no opioid pills after discharge, and 60% of the prescribed pills were left over,” said David Meyer, MD, during a presentation of the study at the annual clinical congress of the American College of Surgeons. Dr. Meyer is a surgical resident at the University of Massachusetts.
The team also used the results of their analysis to develop a guideline for the amount of opioid to prescribe following major colorectal surgery, with specific amounts of pills recommended based on the amount of opioid use during the last 24 hours of hospitalization.
“It shows a real interest in tailoring our postoperative care in pain management. They’re trying to find a way to hit a sweet spot to get patients the right amount of pain control,” said Jonathan Mitchem, MD, in an interview. Dr. Mitchem is an assistant professor at University of Missouri–Columbia, and comoderated the session where the research was presented.
The researchers performed a retrospective analysis of major elective colorectal procedures at their institution, including colectomy, rectal resection, and ostomy reversal. The analysis included 100 patients (55 female), with a mean age of 59 years. A total of 71% were opioid naive, meaning there was no evidence of an opioid prescription in the year prior to surgery. A total of 74% underwent a laparoscopic procedure, and 75% had a partial colectomy. The postoperative stay averaged 4.5 days.
The researchers converted in-hospital opioid use categories (IOUC) to equianalgesic 5-mg oxycodone pills (EOPs). In the last 24 hours before release, 53% of patients had no opioids at all (no IOUC, 0 EOPs), 25% received low amounts of opioids (low IOUC, 0.1-3.0 EOPs), and 22% high amounts (high IOUC, more than 3.1 EOPs). Overall, prescribed EOP was 17.5, and just 38% was consumed. These numbers were lowest in the no-IOUC group (15.7, 16%), followed by the low-IOUC group (16.0, 32%), and the high group (23.7, 79%; P less than .01).
The researchers then looked at the 85th percentile of EOPs for each group, and used that to develop a guideline for opioid prescription. For the no-IOUC group, they recommend 3 EOPs, for the low-IOUC group they recommend 12 EOPs, and for the high-IOUC group they recommend 30 EOPs.
The researchers examined various factors that might have influenced opioid use, correcting for whether the patient was opioid naive, case type, postoperative length of stay, and new ostomy creation. The only factor with a significant association for excessive opioid use was inflammatory bowel disease, which was linked to a nearly 900% increased risk of using more than the guideline amounts (adjusted odds ratio, 8.3; P less than .01; area under the curve, 0.85).
The study is limited by the fact that it was conducted at a single center, and that patient opioid use was self-reported. The guidelines need to be validated prospectively.
No funding information was disclosed. Dr. Meyer and Dr. Mitchem had no relevant financial disclosures.
SOURCE: Meyer D et al. Clinical Congress 2019, Abstract.
SAN FRANCISCO – Opioids may not always be necessary following elective colorectal surgery. That’s the message coming from a retrospective study of medical records at the University of Massachusetts Medical Center, Worcester, which found that over
“We found that over half of the patients took no opioid pills after discharge, and 60% of the prescribed pills were left over,” said David Meyer, MD, during a presentation of the study at the annual clinical congress of the American College of Surgeons. Dr. Meyer is a surgical resident at the University of Massachusetts.
The team also used the results of their analysis to develop a guideline for the amount of opioid to prescribe following major colorectal surgery, with specific amounts of pills recommended based on the amount of opioid use during the last 24 hours of hospitalization.
“It shows a real interest in tailoring our postoperative care in pain management. They’re trying to find a way to hit a sweet spot to get patients the right amount of pain control,” said Jonathan Mitchem, MD, in an interview. Dr. Mitchem is an assistant professor at University of Missouri–Columbia, and comoderated the session where the research was presented.
The researchers performed a retrospective analysis of major elective colorectal procedures at their institution, including colectomy, rectal resection, and ostomy reversal. The analysis included 100 patients (55 female), with a mean age of 59 years. A total of 71% were opioid naive, meaning there was no evidence of an opioid prescription in the year prior to surgery. A total of 74% underwent a laparoscopic procedure, and 75% had a partial colectomy. The postoperative stay averaged 4.5 days.
The researchers converted in-hospital opioid use categories (IOUC) to equianalgesic 5-mg oxycodone pills (EOPs). In the last 24 hours before release, 53% of patients had no opioids at all (no IOUC, 0 EOPs), 25% received low amounts of opioids (low IOUC, 0.1-3.0 EOPs), and 22% high amounts (high IOUC, more than 3.1 EOPs). Overall, prescribed EOP was 17.5, and just 38% was consumed. These numbers were lowest in the no-IOUC group (15.7, 16%), followed by the low-IOUC group (16.0, 32%), and the high group (23.7, 79%; P less than .01).
The researchers then looked at the 85th percentile of EOPs for each group, and used that to develop a guideline for opioid prescription. For the no-IOUC group, they recommend 3 EOPs, for the low-IOUC group they recommend 12 EOPs, and for the high-IOUC group they recommend 30 EOPs.
The researchers examined various factors that might have influenced opioid use, correcting for whether the patient was opioid naive, case type, postoperative length of stay, and new ostomy creation. The only factor with a significant association for excessive opioid use was inflammatory bowel disease, which was linked to a nearly 900% increased risk of using more than the guideline amounts (adjusted odds ratio, 8.3; P less than .01; area under the curve, 0.85).
The study is limited by the fact that it was conducted at a single center, and that patient opioid use was self-reported. The guidelines need to be validated prospectively.
No funding information was disclosed. Dr. Meyer and Dr. Mitchem had no relevant financial disclosures.
SOURCE: Meyer D et al. Clinical Congress 2019, Abstract.
REPORTING FROM CLINICAL CONGRESS 2019
Benefits of BGF triple fixed-dose therapy consistent in COPD patients without exacerbation history
NEW ORLEANS – When looking specifically at the subgroup patients with no recent exacerbations, in patients with moderate to very severe chronic obstructive pulmonary disorder (COPD), an analysis of the phase 3 KRONOS study shows.
For that subgroup of patients with no moderate to severe exacerbations in the past year, BGF MDI was associated with a nominally significant reduction in the rate of subsequent COPD exacerbations, compared with glycopyrrolate/formoterol fumarate (GFF) MDI, according to investigator Fernando J. Martinez MD, of Weill Cornell Medical College, New York.
Results for the COPD patients with no recent history of exacerbation were consistent with the overall results of KRONOS, suggesting that the benefits of BGF MDI shown in that study were not driven by patients with a recent exacerbation history, Dr. Martinez said at the annual meeting of the American College of Chest Physicians.
“It was clear that the effect of this particular triple did not really appear to be dramatically different by the prior history or not in the comparison of the triple versus dual bronchodilator,” he said in a late-breaking clinical trial session.
About three-quarters of the patients in KRONOS (1,411 out of 1,896) lacked a recent exacerbation history. These patients had a mean age of 65.5 years, 72.8% were male, and 69.9% used inhaled corticosteroids at screening, which are demographics were similar to the overall KRONOS patient population, Dr. Martinez said.
In this subset of patients with no recent exacerbation history, treatment with BGF MDI significantly reduced the rate of moderate or severe exacerbations, compared with GFF MDI, with a treatment incidence rate ratio of 0.52 (95% confidence interval, 0.37-0.72; P = .0001).
“The results were remarkably similar,” Dr. Martinez said. “I was surprised, to be honest with you, when I saw these results. I did not anticipate that would be the case.”
By contrast, BGF MDI did not significantly reduce the rate of moderate or severe exacerbations, compared with budesonide/formoterol fumarate (BFF) MDI or open-label budesonide/formoterol fumarate dihydrate dry-powder inhaler (BUD/FORM DPI) as studied in KRONOS, Dr. Martinez said.
The change from baseline in morning predose trough forced expiratory volume in 1 second (FEV1) at week 24 was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI, according to the investigator. Similarly, the FEV1 area under the curve from 0 to 4 hours was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI.
Dr. Martinez reported disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Sunovion, and Teva.
SOURCE: Martinez FJ et al. CHEST 2019, Abstract.
NEW ORLEANS – When looking specifically at the subgroup patients with no recent exacerbations, in patients with moderate to very severe chronic obstructive pulmonary disorder (COPD), an analysis of the phase 3 KRONOS study shows.
For that subgroup of patients with no moderate to severe exacerbations in the past year, BGF MDI was associated with a nominally significant reduction in the rate of subsequent COPD exacerbations, compared with glycopyrrolate/formoterol fumarate (GFF) MDI, according to investigator Fernando J. Martinez MD, of Weill Cornell Medical College, New York.
Results for the COPD patients with no recent history of exacerbation were consistent with the overall results of KRONOS, suggesting that the benefits of BGF MDI shown in that study were not driven by patients with a recent exacerbation history, Dr. Martinez said at the annual meeting of the American College of Chest Physicians.
“It was clear that the effect of this particular triple did not really appear to be dramatically different by the prior history or not in the comparison of the triple versus dual bronchodilator,” he said in a late-breaking clinical trial session.
About three-quarters of the patients in KRONOS (1,411 out of 1,896) lacked a recent exacerbation history. These patients had a mean age of 65.5 years, 72.8% were male, and 69.9% used inhaled corticosteroids at screening, which are demographics were similar to the overall KRONOS patient population, Dr. Martinez said.
In this subset of patients with no recent exacerbation history, treatment with BGF MDI significantly reduced the rate of moderate or severe exacerbations, compared with GFF MDI, with a treatment incidence rate ratio of 0.52 (95% confidence interval, 0.37-0.72; P = .0001).
“The results were remarkably similar,” Dr. Martinez said. “I was surprised, to be honest with you, when I saw these results. I did not anticipate that would be the case.”
By contrast, BGF MDI did not significantly reduce the rate of moderate or severe exacerbations, compared with budesonide/formoterol fumarate (BFF) MDI or open-label budesonide/formoterol fumarate dihydrate dry-powder inhaler (BUD/FORM DPI) as studied in KRONOS, Dr. Martinez said.
The change from baseline in morning predose trough forced expiratory volume in 1 second (FEV1) at week 24 was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI, according to the investigator. Similarly, the FEV1 area under the curve from 0 to 4 hours was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI.
Dr. Martinez reported disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Sunovion, and Teva.
SOURCE: Martinez FJ et al. CHEST 2019, Abstract.
NEW ORLEANS – When looking specifically at the subgroup patients with no recent exacerbations, in patients with moderate to very severe chronic obstructive pulmonary disorder (COPD), an analysis of the phase 3 KRONOS study shows.
For that subgroup of patients with no moderate to severe exacerbations in the past year, BGF MDI was associated with a nominally significant reduction in the rate of subsequent COPD exacerbations, compared with glycopyrrolate/formoterol fumarate (GFF) MDI, according to investigator Fernando J. Martinez MD, of Weill Cornell Medical College, New York.
Results for the COPD patients with no recent history of exacerbation were consistent with the overall results of KRONOS, suggesting that the benefits of BGF MDI shown in that study were not driven by patients with a recent exacerbation history, Dr. Martinez said at the annual meeting of the American College of Chest Physicians.
“It was clear that the effect of this particular triple did not really appear to be dramatically different by the prior history or not in the comparison of the triple versus dual bronchodilator,” he said in a late-breaking clinical trial session.
About three-quarters of the patients in KRONOS (1,411 out of 1,896) lacked a recent exacerbation history. These patients had a mean age of 65.5 years, 72.8% were male, and 69.9% used inhaled corticosteroids at screening, which are demographics were similar to the overall KRONOS patient population, Dr. Martinez said.
In this subset of patients with no recent exacerbation history, treatment with BGF MDI significantly reduced the rate of moderate or severe exacerbations, compared with GFF MDI, with a treatment incidence rate ratio of 0.52 (95% confidence interval, 0.37-0.72; P = .0001).
“The results were remarkably similar,” Dr. Martinez said. “I was surprised, to be honest with you, when I saw these results. I did not anticipate that would be the case.”
By contrast, BGF MDI did not significantly reduce the rate of moderate or severe exacerbations, compared with budesonide/formoterol fumarate (BFF) MDI or open-label budesonide/formoterol fumarate dihydrate dry-powder inhaler (BUD/FORM DPI) as studied in KRONOS, Dr. Martinez said.
The change from baseline in morning predose trough forced expiratory volume in 1 second (FEV1) at week 24 was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI, according to the investigator. Similarly, the FEV1 area under the curve from 0 to 4 hours was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI.
Dr. Martinez reported disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Sunovion, and Teva.
SOURCE: Martinez FJ et al. CHEST 2019, Abstract.
REPORTING FROM CHEST 2019
Even low-dose steroids increase DMARD infection risk
ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.
Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.
“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.
The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.
There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.
After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.
Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.
“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”
The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.
“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.
Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.
Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.
The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.
SOURCE: George M et al. ACR 2019, Abstract 848
ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.
Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.
“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.
The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.
There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.
After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.
Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.
“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”
The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.
“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.
Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.
Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.
The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.
SOURCE: George M et al. ACR 2019, Abstract 848
ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.
Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.
“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.
The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.
There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.
After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.
Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.
“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”
The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.
“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.
Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.
Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.
The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.
SOURCE: George M et al. ACR 2019, Abstract 848
REPORTING FROM ACR 2019