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Are PTSD Responses Inherited or Acquired?
Neuroimaging studies have consistently reported reduced activation of the medial prefrontal cortex (mPFC) in patients with posttraumatic stress disorder (PTSD) while they recall and imagine stressful personal events. During script-driven imagery (SDI) sessions, patients with PTSD exhibit increased psychophysiologic (eg, heart rate, skin conductance, and facial electromyographic) responses to trauma-related memories. However, the origin of the responses remained unclear. Are they familial, acquired, or resulting from trauma exposure?
Researchers from Harvard University, University of California Los Angeles, and University of New England conducted a study of 26 male identical twin pairs to help find the answer. The participants were divided into 4 groups: combat-exposed with PTSD (ExP+), their combat-unexposed twins without PTSD, combat-exposed participants without PTSD, and their combat-unexposed twins without PTSD. They engaged in SDI during functional magnetic resonance (fMRI) imaging and concurrent skin conductance measurement.
The results of the fMRI tests showed diminished activation in the medial prefrontal cortex of the patients with PTSD compared with the other groups. The SC response scores did not correlate significantly with PTSD symptom severity.
Contrary to the researchers’ predictions, mPFC activation was not inversely correlated with PTSD symptom severity. However, they say their finding of reduced mPFC activation in the ExP+ group provides evidence that the abnormality is an acquired characteristic. If those findings are replicated, such objectively measured biologic characteristics could potentially aid in diagnosing PTSD or assessing treatment response.
Source:
Dahlgren MK, Laifer LM, VanElzakker MB, et al. Psychol Med. 2018;48(7):1128-1138.
doi: 10.1017/S003329171700263X.
Neuroimaging studies have consistently reported reduced activation of the medial prefrontal cortex (mPFC) in patients with posttraumatic stress disorder (PTSD) while they recall and imagine stressful personal events. During script-driven imagery (SDI) sessions, patients with PTSD exhibit increased psychophysiologic (eg, heart rate, skin conductance, and facial electromyographic) responses to trauma-related memories. However, the origin of the responses remained unclear. Are they familial, acquired, or resulting from trauma exposure?
Researchers from Harvard University, University of California Los Angeles, and University of New England conducted a study of 26 male identical twin pairs to help find the answer. The participants were divided into 4 groups: combat-exposed with PTSD (ExP+), their combat-unexposed twins without PTSD, combat-exposed participants without PTSD, and their combat-unexposed twins without PTSD. They engaged in SDI during functional magnetic resonance (fMRI) imaging and concurrent skin conductance measurement.
The results of the fMRI tests showed diminished activation in the medial prefrontal cortex of the patients with PTSD compared with the other groups. The SC response scores did not correlate significantly with PTSD symptom severity.
Contrary to the researchers’ predictions, mPFC activation was not inversely correlated with PTSD symptom severity. However, they say their finding of reduced mPFC activation in the ExP+ group provides evidence that the abnormality is an acquired characteristic. If those findings are replicated, such objectively measured biologic characteristics could potentially aid in diagnosing PTSD or assessing treatment response.
Source:
Dahlgren MK, Laifer LM, VanElzakker MB, et al. Psychol Med. 2018;48(7):1128-1138.
doi: 10.1017/S003329171700263X.
Neuroimaging studies have consistently reported reduced activation of the medial prefrontal cortex (mPFC) in patients with posttraumatic stress disorder (PTSD) while they recall and imagine stressful personal events. During script-driven imagery (SDI) sessions, patients with PTSD exhibit increased psychophysiologic (eg, heart rate, skin conductance, and facial electromyographic) responses to trauma-related memories. However, the origin of the responses remained unclear. Are they familial, acquired, or resulting from trauma exposure?
Researchers from Harvard University, University of California Los Angeles, and University of New England conducted a study of 26 male identical twin pairs to help find the answer. The participants were divided into 4 groups: combat-exposed with PTSD (ExP+), their combat-unexposed twins without PTSD, combat-exposed participants without PTSD, and their combat-unexposed twins without PTSD. They engaged in SDI during functional magnetic resonance (fMRI) imaging and concurrent skin conductance measurement.
The results of the fMRI tests showed diminished activation in the medial prefrontal cortex of the patients with PTSD compared with the other groups. The SC response scores did not correlate significantly with PTSD symptom severity.
Contrary to the researchers’ predictions, mPFC activation was not inversely correlated with PTSD symptom severity. However, they say their finding of reduced mPFC activation in the ExP+ group provides evidence that the abnormality is an acquired characteristic. If those findings are replicated, such objectively measured biologic characteristics could potentially aid in diagnosing PTSD or assessing treatment response.
Source:
Dahlgren MK, Laifer LM, VanElzakker MB, et al. Psychol Med. 2018;48(7):1128-1138.
doi: 10.1017/S003329171700263X.
Federal Health Data Trends:Vietnam Era Veterans (FULL)
According to the VA, 8,744,000 veterans served in the Armed Forces in the time between the Gulf of Tonkin incident and the signing of the Paris Peace Accords.1 Of those, 3,403,000 were deployed to Southeast Asia. Those who served during this period often were exposed to unique environmental hazards, such as commonly used pesticides and herbicides, as well as diseases attributed to the tropical environment, such as fungal infections, and there were more than 40,000 reported cases of malaria. Upon returning home, these veterans faced a tough readjustment that often magnified the stress associated with combat.
Today, the VA recognizes 8 conditions related to service in Vietnam for the purposes of establishing service-connection: soft tissue sarcoma, non-Hodgkin lymphoma, Hodgkin disease, chloracne, porphyria cutanea tarda, respiratory cancers, multiple myeloma, prostate cancer, acute peripheral neuropathy, and spina bifida in offspring. As the veterans of this conflict age into their retirement years, the VA now also faces the challenge of providing care to this growing senior population.
According to the VA, 8,744,000 veterans served in the Armed Forces in the time between the Gulf of Tonkin incident and the signing of the Paris Peace Accords.1 Of those, 3,403,000 were deployed to Southeast Asia. Those who served during this period often were exposed to unique environmental hazards, such as commonly used pesticides and herbicides, as well as diseases attributed to the tropical environment, such as fungal infections, and there were more than 40,000 reported cases of malaria. Upon returning home, these veterans faced a tough readjustment that often magnified the stress associated with combat.
Today, the VA recognizes 8 conditions related to service in Vietnam for the purposes of establishing service-connection: soft tissue sarcoma, non-Hodgkin lymphoma, Hodgkin disease, chloracne, porphyria cutanea tarda, respiratory cancers, multiple myeloma, prostate cancer, acute peripheral neuropathy, and spina bifida in offspring. As the veterans of this conflict age into their retirement years, the VA now also faces the challenge of providing care to this growing senior population.
According to the VA, 8,744,000 veterans served in the Armed Forces in the time between the Gulf of Tonkin incident and the signing of the Paris Peace Accords.1 Of those, 3,403,000 were deployed to Southeast Asia. Those who served during this period often were exposed to unique environmental hazards, such as commonly used pesticides and herbicides, as well as diseases attributed to the tropical environment, such as fungal infections, and there were more than 40,000 reported cases of malaria. Upon returning home, these veterans faced a tough readjustment that often magnified the stress associated with combat.
Today, the VA recognizes 8 conditions related to service in Vietnam for the purposes of establishing service-connection: soft tissue sarcoma, non-Hodgkin lymphoma, Hodgkin disease, chloracne, porphyria cutanea tarda, respiratory cancers, multiple myeloma, prostate cancer, acute peripheral neuropathy, and spina bifida in offspring. As the veterans of this conflict age into their retirement years, the VA now also faces the challenge of providing care to this growing senior population.
Health Canada expands approval of obinutuzumab
Health Canada has expanded the approved use of obinutuzumab (Gazyva®).
The anti-CD20 monoclonal antibody is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV).
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
Health Canada previously approved obinutuzumab for the following indications:
- In combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia
- First in combination with bendamustine, then as monotherapy, in FL patients who relapsed after or are refractory to a rituximab-containing regimen.
Phase 3 results
Health Canada’s latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were published in NEJM in October 2017. The following are updated data from the product monograph.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had previously untreated, advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CVP (cyclophosphamide, vincristine, and prednisone), and bendamustine.
At a median observation time of 41.1 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
The estimated 3-year progression-free survival was 78.9% in the rituximab arm and 83.4% in the obinutuzumab arm.
Safety was evaluated based on all 1385 patients in the study, 86% of whom had FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
During the monotherapy period, the most common AEs (≥ 5%) in patients treated with obinutuzumab were cough (21%), neutropenia (19%), upper respiratory tract infection (15%), viral upper respiratory tract infection (15%), diarrhea (13%), arthralgia (10%), fatigue (9%), sinusitis (9%), infusion reactions (8%), pneumonia (8%), herpes zoster (8%), lower respiratory tract infection (7%), pyrexia (7%), back pain (6%), headache (6%), urinary tract infection (6%), nausea (6%), bronchitis (5%), and vomiting (5%).
Grade 3-4 AEs (≥1%) in patients treated with obinutuzumab included neutropenia (17%), pneumonia (3%), and febrile neutropenia (2%). There were 2 deaths due to pneumonia in the obinutuzumab arm.
Health Canada has expanded the approved use of obinutuzumab (Gazyva®).
The anti-CD20 monoclonal antibody is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV).
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
Health Canada previously approved obinutuzumab for the following indications:
- In combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia
- First in combination with bendamustine, then as monotherapy, in FL patients who relapsed after or are refractory to a rituximab-containing regimen.
Phase 3 results
Health Canada’s latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were published in NEJM in October 2017. The following are updated data from the product monograph.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had previously untreated, advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CVP (cyclophosphamide, vincristine, and prednisone), and bendamustine.
At a median observation time of 41.1 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
The estimated 3-year progression-free survival was 78.9% in the rituximab arm and 83.4% in the obinutuzumab arm.
Safety was evaluated based on all 1385 patients in the study, 86% of whom had FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
During the monotherapy period, the most common AEs (≥ 5%) in patients treated with obinutuzumab were cough (21%), neutropenia (19%), upper respiratory tract infection (15%), viral upper respiratory tract infection (15%), diarrhea (13%), arthralgia (10%), fatigue (9%), sinusitis (9%), infusion reactions (8%), pneumonia (8%), herpes zoster (8%), lower respiratory tract infection (7%), pyrexia (7%), back pain (6%), headache (6%), urinary tract infection (6%), nausea (6%), bronchitis (5%), and vomiting (5%).
Grade 3-4 AEs (≥1%) in patients treated with obinutuzumab included neutropenia (17%), pneumonia (3%), and febrile neutropenia (2%). There were 2 deaths due to pneumonia in the obinutuzumab arm.
Health Canada has expanded the approved use of obinutuzumab (Gazyva®).
The anti-CD20 monoclonal antibody is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV).
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
Health Canada previously approved obinutuzumab for the following indications:
- In combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia
- First in combination with bendamustine, then as monotherapy, in FL patients who relapsed after or are refractory to a rituximab-containing regimen.
Phase 3 results
Health Canada’s latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were published in NEJM in October 2017. The following are updated data from the product monograph.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had previously untreated, advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CVP (cyclophosphamide, vincristine, and prednisone), and bendamustine.
At a median observation time of 41.1 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
The estimated 3-year progression-free survival was 78.9% in the rituximab arm and 83.4% in the obinutuzumab arm.
Safety was evaluated based on all 1385 patients in the study, 86% of whom had FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
During the monotherapy period, the most common AEs (≥ 5%) in patients treated with obinutuzumab were cough (21%), neutropenia (19%), upper respiratory tract infection (15%), viral upper respiratory tract infection (15%), diarrhea (13%), arthralgia (10%), fatigue (9%), sinusitis (9%), infusion reactions (8%), pneumonia (8%), herpes zoster (8%), lower respiratory tract infection (7%), pyrexia (7%), back pain (6%), headache (6%), urinary tract infection (6%), nausea (6%), bronchitis (5%), and vomiting (5%).
Grade 3-4 AEs (≥1%) in patients treated with obinutuzumab included neutropenia (17%), pneumonia (3%), and febrile neutropenia (2%). There were 2 deaths due to pneumonia in the obinutuzumab arm.
A new use for ibrutinib?
Preclinical research suggests ibrutinib could treat G-CSFR-mutant myeloid disorders.
“Mutations in G-CSFR have a harmful effect on the production of neutrophils and are reported in patients with several blood disorders, including severe congenital neutropenia, chronic neutrophilic leukemia, and acute myeloid leukemia,” said Ken Greis, PhD, of the University of Cincinnati in Ohio.
“Unfortunately, despite years of research, the malignant signaling of the mutated G-CSFRs is not well understood.”
With this in mind, Dr Greis and his colleagues created a comprehensive signaling network of normal and mutated G-CSFR. Their goal was to understand how abnormal cellular signaling from the mutant receptors results in disease development.
The researchers described this work in Leukemia.
“We are able to look at . . . phosphorylation that results in phosphate groups being attached to the amino acid tyrosine (Tyr) in proteins,” Dr Greis explained. “These phosphorylation events (pTyr) can act as switches to activate or inactivate proteins and/or specific cellular processes.”
“By evaluating pTyr activity in the normal versus mutant receptor cells, we can produce a network similar to a wiring diagram of cellular regulation. Observed disruptions at any of the nodes in the network for the mutated receptors can then be investigated further to understand and perhaps target the abnormal signaling corresponding to the disease.”
This analysis of pTyr activity revealed that G-CSFR mutants had aberrant activation of BTK, as well as abnormal kinetics of canonical STAT3, STAT5, and MAPK phosphorylation.
“When we first got these results, one of the most exciting things was that BTK was already the target of an FDA-approved drug, ibrutinib . . .,” said study author H. Leighton Grimes, PhD, of the University of Cincinnati.
The researchers tested ibrutinib in cells with mutant and wild-type G-CSFR and found the drug killed the mutant cells but not the wild-type cells. This was the case in myeloid progenitor 32D cell lines and primary human CD34+ umbilical cord blood cells.
“Progenitor cells expressing mutated G-CSFR in animal models and in human blood cells also showed enhanced sensitivity to ibrutinib compared to the normal G-CSFR, thus confirming that the mutated cells could likely be eliminated by treatment with ibrutinib and may represent an effective therapy for these patients,” Dr Grimes said.
Ibrutinib also demonstrated synergy with the JAK1/2 inhibitor ruxolitinib. G-CSFR-mutant CD34+ cells were sensitive to each drug alone, but combining them “dramatically enhanced” the sensitivity, according to the researchers.
“These data demonstrate the strength of global proteomics approaches, like the pTyr profiling used here, in dissecting cancer-forming pathways and points to the possibility that ibrutinib could be an effective therapy for myeloid leukemias with G-CSFR mutations,” Dr Greis said.
“Further studies are needed to determine if these findings will be applicable in patient samples, but the hope is that clinical trials are just around the corner, since we’re investigating a drug that has already been found to be safe by the FDA.”
Preclinical research suggests ibrutinib could treat G-CSFR-mutant myeloid disorders.
“Mutations in G-CSFR have a harmful effect on the production of neutrophils and are reported in patients with several blood disorders, including severe congenital neutropenia, chronic neutrophilic leukemia, and acute myeloid leukemia,” said Ken Greis, PhD, of the University of Cincinnati in Ohio.
“Unfortunately, despite years of research, the malignant signaling of the mutated G-CSFRs is not well understood.”
With this in mind, Dr Greis and his colleagues created a comprehensive signaling network of normal and mutated G-CSFR. Their goal was to understand how abnormal cellular signaling from the mutant receptors results in disease development.
The researchers described this work in Leukemia.
“We are able to look at . . . phosphorylation that results in phosphate groups being attached to the amino acid tyrosine (Tyr) in proteins,” Dr Greis explained. “These phosphorylation events (pTyr) can act as switches to activate or inactivate proteins and/or specific cellular processes.”
“By evaluating pTyr activity in the normal versus mutant receptor cells, we can produce a network similar to a wiring diagram of cellular regulation. Observed disruptions at any of the nodes in the network for the mutated receptors can then be investigated further to understand and perhaps target the abnormal signaling corresponding to the disease.”
This analysis of pTyr activity revealed that G-CSFR mutants had aberrant activation of BTK, as well as abnormal kinetics of canonical STAT3, STAT5, and MAPK phosphorylation.
“When we first got these results, one of the most exciting things was that BTK was already the target of an FDA-approved drug, ibrutinib . . .,” said study author H. Leighton Grimes, PhD, of the University of Cincinnati.
The researchers tested ibrutinib in cells with mutant and wild-type G-CSFR and found the drug killed the mutant cells but not the wild-type cells. This was the case in myeloid progenitor 32D cell lines and primary human CD34+ umbilical cord blood cells.
“Progenitor cells expressing mutated G-CSFR in animal models and in human blood cells also showed enhanced sensitivity to ibrutinib compared to the normal G-CSFR, thus confirming that the mutated cells could likely be eliminated by treatment with ibrutinib and may represent an effective therapy for these patients,” Dr Grimes said.
Ibrutinib also demonstrated synergy with the JAK1/2 inhibitor ruxolitinib. G-CSFR-mutant CD34+ cells were sensitive to each drug alone, but combining them “dramatically enhanced” the sensitivity, according to the researchers.
“These data demonstrate the strength of global proteomics approaches, like the pTyr profiling used here, in dissecting cancer-forming pathways and points to the possibility that ibrutinib could be an effective therapy for myeloid leukemias with G-CSFR mutations,” Dr Greis said.
“Further studies are needed to determine if these findings will be applicable in patient samples, but the hope is that clinical trials are just around the corner, since we’re investigating a drug that has already been found to be safe by the FDA.”
Preclinical research suggests ibrutinib could treat G-CSFR-mutant myeloid disorders.
“Mutations in G-CSFR have a harmful effect on the production of neutrophils and are reported in patients with several blood disorders, including severe congenital neutropenia, chronic neutrophilic leukemia, and acute myeloid leukemia,” said Ken Greis, PhD, of the University of Cincinnati in Ohio.
“Unfortunately, despite years of research, the malignant signaling of the mutated G-CSFRs is not well understood.”
With this in mind, Dr Greis and his colleagues created a comprehensive signaling network of normal and mutated G-CSFR. Their goal was to understand how abnormal cellular signaling from the mutant receptors results in disease development.
The researchers described this work in Leukemia.
“We are able to look at . . . phosphorylation that results in phosphate groups being attached to the amino acid tyrosine (Tyr) in proteins,” Dr Greis explained. “These phosphorylation events (pTyr) can act as switches to activate or inactivate proteins and/or specific cellular processes.”
“By evaluating pTyr activity in the normal versus mutant receptor cells, we can produce a network similar to a wiring diagram of cellular regulation. Observed disruptions at any of the nodes in the network for the mutated receptors can then be investigated further to understand and perhaps target the abnormal signaling corresponding to the disease.”
This analysis of pTyr activity revealed that G-CSFR mutants had aberrant activation of BTK, as well as abnormal kinetics of canonical STAT3, STAT5, and MAPK phosphorylation.
“When we first got these results, one of the most exciting things was that BTK was already the target of an FDA-approved drug, ibrutinib . . .,” said study author H. Leighton Grimes, PhD, of the University of Cincinnati.
The researchers tested ibrutinib in cells with mutant and wild-type G-CSFR and found the drug killed the mutant cells but not the wild-type cells. This was the case in myeloid progenitor 32D cell lines and primary human CD34+ umbilical cord blood cells.
“Progenitor cells expressing mutated G-CSFR in animal models and in human blood cells also showed enhanced sensitivity to ibrutinib compared to the normal G-CSFR, thus confirming that the mutated cells could likely be eliminated by treatment with ibrutinib and may represent an effective therapy for these patients,” Dr Grimes said.
Ibrutinib also demonstrated synergy with the JAK1/2 inhibitor ruxolitinib. G-CSFR-mutant CD34+ cells were sensitive to each drug alone, but combining them “dramatically enhanced” the sensitivity, according to the researchers.
“These data demonstrate the strength of global proteomics approaches, like the pTyr profiling used here, in dissecting cancer-forming pathways and points to the possibility that ibrutinib could be an effective therapy for myeloid leukemias with G-CSFR mutations,” Dr Greis said.
“Further studies are needed to determine if these findings will be applicable in patient samples, but the hope is that clinical trials are just around the corner, since we’re investigating a drug that has already been found to be safe by the FDA.”
Conflicts of interest among FDA advisers
An investigative report has unearthed potential conflicts of interest among physicians who serve on advisory panels for the US Food and Drug Administration (FDA).
The investigation revealed that some FDA advisers are receiving significant post-hoc payments from the makers of drugs they reviewed.
The investigation also uncovered relationships between advisers and drug companies that predate drug reviews.
Journalist Charles Piller and his colleagues conducted this investigation and detailed the results in Science.
The report includes data—from the federal Open Payments website—on 107 physicians who voted on FDA advisory committees between 2013 and 2016.
Forty of these advisers received more than $10,000 in post-hoc earnings or research support from the makers of drugs they reviewed or from competing drug companies.
Twenty-six advisers received more than $100,000, and 7 advisers received more than $1 million.
The 17 top earners received more than $300,000 each. For these advisers, 94% of their earnings came from the makers of drugs they previously reviewed or from those companies’ competitors.
The data also show that some advisers received funds from drug companies concurrent with or in the year before their advisory service.
Of the 17 top-earning advisers, 11 received financial support from competing companies on one or more of the drugs they reviewed. Five advisers also received support from the makers of one or more of the drugs reviewed.
The FDA did not disclose this information to the public or issue waivers for these potential conflicts. The FDA can issue a waiver to allow the participation of an adviser with an active conflict or one that ended in the year before a vote, as long as the adviser in question can provide expertise that cannot be provided by someone else.
It is possible that the FDA dismissed the aforementioned financial ties that predated drug reviews, deciding these relationships were not conflicts and did not require a waiver. However, it is also possible that the FDA did not know about these potential conflicts.
Piller and his colleagues were unable to determine what the FDA knew, as the agency refused to release disclosure documents, discuss individual advisers, or explain what steps, if any, the FDA takes to validate advisers’ disclosures.
An investigative report has unearthed potential conflicts of interest among physicians who serve on advisory panels for the US Food and Drug Administration (FDA).
The investigation revealed that some FDA advisers are receiving significant post-hoc payments from the makers of drugs they reviewed.
The investigation also uncovered relationships between advisers and drug companies that predate drug reviews.
Journalist Charles Piller and his colleagues conducted this investigation and detailed the results in Science.
The report includes data—from the federal Open Payments website—on 107 physicians who voted on FDA advisory committees between 2013 and 2016.
Forty of these advisers received more than $10,000 in post-hoc earnings or research support from the makers of drugs they reviewed or from competing drug companies.
Twenty-six advisers received more than $100,000, and 7 advisers received more than $1 million.
The 17 top earners received more than $300,000 each. For these advisers, 94% of their earnings came from the makers of drugs they previously reviewed or from those companies’ competitors.
The data also show that some advisers received funds from drug companies concurrent with or in the year before their advisory service.
Of the 17 top-earning advisers, 11 received financial support from competing companies on one or more of the drugs they reviewed. Five advisers also received support from the makers of one or more of the drugs reviewed.
The FDA did not disclose this information to the public or issue waivers for these potential conflicts. The FDA can issue a waiver to allow the participation of an adviser with an active conflict or one that ended in the year before a vote, as long as the adviser in question can provide expertise that cannot be provided by someone else.
It is possible that the FDA dismissed the aforementioned financial ties that predated drug reviews, deciding these relationships were not conflicts and did not require a waiver. However, it is also possible that the FDA did not know about these potential conflicts.
Piller and his colleagues were unable to determine what the FDA knew, as the agency refused to release disclosure documents, discuss individual advisers, or explain what steps, if any, the FDA takes to validate advisers’ disclosures.
An investigative report has unearthed potential conflicts of interest among physicians who serve on advisory panels for the US Food and Drug Administration (FDA).
The investigation revealed that some FDA advisers are receiving significant post-hoc payments from the makers of drugs they reviewed.
The investigation also uncovered relationships between advisers and drug companies that predate drug reviews.
Journalist Charles Piller and his colleagues conducted this investigation and detailed the results in Science.
The report includes data—from the federal Open Payments website—on 107 physicians who voted on FDA advisory committees between 2013 and 2016.
Forty of these advisers received more than $10,000 in post-hoc earnings or research support from the makers of drugs they reviewed or from competing drug companies.
Twenty-six advisers received more than $100,000, and 7 advisers received more than $1 million.
The 17 top earners received more than $300,000 each. For these advisers, 94% of their earnings came from the makers of drugs they previously reviewed or from those companies’ competitors.
The data also show that some advisers received funds from drug companies concurrent with or in the year before their advisory service.
Of the 17 top-earning advisers, 11 received financial support from competing companies on one or more of the drugs they reviewed. Five advisers also received support from the makers of one or more of the drugs reviewed.
The FDA did not disclose this information to the public or issue waivers for these potential conflicts. The FDA can issue a waiver to allow the participation of an adviser with an active conflict or one that ended in the year before a vote, as long as the adviser in question can provide expertise that cannot be provided by someone else.
It is possible that the FDA dismissed the aforementioned financial ties that predated drug reviews, deciding these relationships were not conflicts and did not require a waiver. However, it is also possible that the FDA did not know about these potential conflicts.
Piller and his colleagues were unable to determine what the FDA knew, as the agency refused to release disclosure documents, discuss individual advisers, or explain what steps, if any, the FDA takes to validate advisers’ disclosures.
Long-term follow-up of monoclonal gammopathy of undetermined significance
Clinical question: What is the expected clinical progression of patients with monoclonal gammopathy of undetermined significance (MGUS)?
Study design: Prospective, observational cohort study.
Setting: Single institution in Minnesota.
Synopsis: Investigators identified 1,395 patients with MGUS during 1960-1994, with a median follow-up of 34 years. Progression to multiple myeloma, plasma cell disorders, or lymphoid disorders was noted in 147 patients (11%), which represents a 6.5-times higher risk for these disorders, compared with the age/sex–adjusted control population.
Two risk factors were associated with progression of disease: elevated serum M protein (greater than 1.5 g/dL) and an abnormal serum free light chain ratio. Risk of progression at 20 years in patients with both of these risk factors was 55% in patients with IgM subtypes and 30% in patients with non-IgM subtypes. With a single risk factor, risk of progression at 20 years was 41% and 20%, respectively. With no risk factors the risk of progression at 20 years was 19% and 7%. Overall expected survival was shorter in patients with MGUS versus that in the age/sex–matched control population.
Bottom line: Patients with MGUS have a shorter life expectancy than the general population, and the IgM subtype is associated with a greater risk of progression at 20 years, compared with the non-IgM subtype.
Citation: Kyle RA et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Eng J Med. 2018 Jan 18;378(3):241-9.
Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.
Clinical question: What is the expected clinical progression of patients with monoclonal gammopathy of undetermined significance (MGUS)?
Study design: Prospective, observational cohort study.
Setting: Single institution in Minnesota.
Synopsis: Investigators identified 1,395 patients with MGUS during 1960-1994, with a median follow-up of 34 years. Progression to multiple myeloma, plasma cell disorders, or lymphoid disorders was noted in 147 patients (11%), which represents a 6.5-times higher risk for these disorders, compared with the age/sex–adjusted control population.
Two risk factors were associated with progression of disease: elevated serum M protein (greater than 1.5 g/dL) and an abnormal serum free light chain ratio. Risk of progression at 20 years in patients with both of these risk factors was 55% in patients with IgM subtypes and 30% in patients with non-IgM subtypes. With a single risk factor, risk of progression at 20 years was 41% and 20%, respectively. With no risk factors the risk of progression at 20 years was 19% and 7%. Overall expected survival was shorter in patients with MGUS versus that in the age/sex–matched control population.
Bottom line: Patients with MGUS have a shorter life expectancy than the general population, and the IgM subtype is associated with a greater risk of progression at 20 years, compared with the non-IgM subtype.
Citation: Kyle RA et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Eng J Med. 2018 Jan 18;378(3):241-9.
Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.
Clinical question: What is the expected clinical progression of patients with monoclonal gammopathy of undetermined significance (MGUS)?
Study design: Prospective, observational cohort study.
Setting: Single institution in Minnesota.
Synopsis: Investigators identified 1,395 patients with MGUS during 1960-1994, with a median follow-up of 34 years. Progression to multiple myeloma, plasma cell disorders, or lymphoid disorders was noted in 147 patients (11%), which represents a 6.5-times higher risk for these disorders, compared with the age/sex–adjusted control population.
Two risk factors were associated with progression of disease: elevated serum M protein (greater than 1.5 g/dL) and an abnormal serum free light chain ratio. Risk of progression at 20 years in patients with both of these risk factors was 55% in patients with IgM subtypes and 30% in patients with non-IgM subtypes. With a single risk factor, risk of progression at 20 years was 41% and 20%, respectively. With no risk factors the risk of progression at 20 years was 19% and 7%. Overall expected survival was shorter in patients with MGUS versus that in the age/sex–matched control population.
Bottom line: Patients with MGUS have a shorter life expectancy than the general population, and the IgM subtype is associated with a greater risk of progression at 20 years, compared with the non-IgM subtype.
Citation: Kyle RA et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Eng J Med. 2018 Jan 18;378(3):241-9.
Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.
More than 16% of ED sepsis patients not admitted to hospital
SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.
“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”
To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.
Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).
“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”
The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”
Researchers emphasized that they do not recommend routine outpatient management for individual sepsis patients. “Almost certainly, some of the discharged patients should have been admitted to the hospital.” Dr. Peltan said. “I think there’s still a lot of opportunity to understand who these patients are, understand why there is so much physician variation, and to develop tools to further optimize triage decisions.”
The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.
SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.
“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”
To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.
Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).
“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”
The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”
Researchers emphasized that they do not recommend routine outpatient management for individual sepsis patients. “Almost certainly, some of the discharged patients should have been admitted to the hospital.” Dr. Peltan said. “I think there’s still a lot of opportunity to understand who these patients are, understand why there is so much physician variation, and to develop tools to further optimize triage decisions.”
The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.
SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.
“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”
To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.
Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).
“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”
The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”
Researchers emphasized that they do not recommend routine outpatient management for individual sepsis patients. “Almost certainly, some of the discharged patients should have been admitted to the hospital.” Dr. Peltan said. “I think there’s still a lot of opportunity to understand who these patients are, understand why there is so much physician variation, and to develop tools to further optimize triage decisions.”
The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.
AT ATS 2018
Key clinical point: More research is needed to optimize triage decisions for ED sepsis patients and to understand possible disparities in ED disposition.
Major finding: Among adult patients who met clinical criteria for sepsis in the emergency department, 16.4% were not admitted to the hospital.
Study details: A retrospective study of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah.
Disclosures: The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
Source: Peltan ID et al. Abstract 5994/702, ATS 2018.
Biosimilar switch accepted by most rheumatic disease patients
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
REPORTING FROM BSR 2018
DOACs’ safety affirmed in real-world setting
Direct oral anticoagulants were associated with decreased bleeding risk versus warfarin in a recent retrospective analysis of primary care databases.
Apixaban (Eliquis) was associated with decreased risk of major bleeding events versus warfarin both in patients with atrial fibrillation (AF) and those prescribed anticoagulants for other causes, according to study results.
Rivaroxaban (Xarelto) was associated with a decrease in risk of intracranial bleeding, compared with warfarin in patients without AF, as was dabigatran (Pradaxa), reported Yana Vinogradova, a research statistician in the division of primary care at the University of Nottingham, England, and her coauthors.
An increased risk of all-cause mortality was seen with both rivaroxaban and low-dose apixaban, possibly because more patients died of age-related causes while on these direct oral anticoagulants (DOACs), they reported.
“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” Ms. Vinogradova and her colleagues said in the BMJ.
Evidence establishing the noninferiority of DOACs to warfarin comes mostly from controlled trials in AF leaving “residual concerns” about the safety of these newer agents in real world settings, where a broader range of patients may receive them, they added.
Accordingly, they conducted an analysis based on patient data from two U.K. primary care databases that were representative of the national population, according to the researchers.
A total of 196,061 patients were represented in the study, including 103,270 (53%) with AF and 92,791 (47%) who received anticoagulants for other reasons.
A total of 67% of patients received warfarin, though its use declined from 98% in 2011, the beginning of the study period, to 23% in 2016, the end of the study period. Over that same time period, use of rivaroxaban rose from 1% to 42%, and use of apixaban rose from 0% to 31%, while dabigatran use peaked in 2013 at 10%, dropping to 3% by 2016.
Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015, investigators said.
For patients with AF, apixaban was linked to a lower major bleeding risk, both versus warfarin (adjusted hazard ratio, 0.66; 95% confidence interval, 0.54-0.79) and versus rivaroxaban, the published data show. Apixaban was associated with a lower risk of intracranial bleed versus warfarin in patients with AF (aHR, 0.40; 95% CI, 0.25-0.64) as was dabigatran (aHR, 0.45; 95% CI, 0.26-0.77).
For patients without AF, apixaban was again associated with a lower risk of major bleeding versus warfarin and versus rivaroxaban, while rivaroxaban was associated with lower intracranial bleeding risk versus warfarin, and apixaban with lower risks for gastrointestinal bleeds.
Compared with apixaban, rivaroxaban and dabigatran were associated with higher risks of certain bleeding events, further analyses show.
Rivaroxaban and lower-dose apixaban were both associated with increased all-cause mortality risk versus warfarin, both in the atrial fibrillation and non-AF groups, Ms. Vinogradova and her coinvestigators noted.
“A greater proportion of the older patients on apixaban and rivaroxaban may have died while still taking anticoagulants but from age-related causes other than ischemic stroke or venous thromboembolism,” they wrote.
Compared with patients on higher doses of DOACs, patients receiving lower doses were older and had more comorbidities and more previous events, they added.
Between DOACs, results of this particular analysis were most favorable for apixaban, according to investigators.
“Our study has shown that the risk of major bleeding is lower in patients taking apixaban regardless of the reason for prescribing,” they wrote. “This was most pronounced for intracranial bleeding in patients with atrial fibrillation and for gastrointestinal bleeding in patients without atrial fibrillation, appearing, in general, to show apixaban to be the safest drug.”
The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
SOURCE: Vinogradova Y et al. BMJ 2018; 362:K2505.
Direct oral anticoagulants were associated with decreased bleeding risk versus warfarin in a recent retrospective analysis of primary care databases.
Apixaban (Eliquis) was associated with decreased risk of major bleeding events versus warfarin both in patients with atrial fibrillation (AF) and those prescribed anticoagulants for other causes, according to study results.
Rivaroxaban (Xarelto) was associated with a decrease in risk of intracranial bleeding, compared with warfarin in patients without AF, as was dabigatran (Pradaxa), reported Yana Vinogradova, a research statistician in the division of primary care at the University of Nottingham, England, and her coauthors.
An increased risk of all-cause mortality was seen with both rivaroxaban and low-dose apixaban, possibly because more patients died of age-related causes while on these direct oral anticoagulants (DOACs), they reported.
“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” Ms. Vinogradova and her colleagues said in the BMJ.
Evidence establishing the noninferiority of DOACs to warfarin comes mostly from controlled trials in AF leaving “residual concerns” about the safety of these newer agents in real world settings, where a broader range of patients may receive them, they added.
Accordingly, they conducted an analysis based on patient data from two U.K. primary care databases that were representative of the national population, according to the researchers.
A total of 196,061 patients were represented in the study, including 103,270 (53%) with AF and 92,791 (47%) who received anticoagulants for other reasons.
A total of 67% of patients received warfarin, though its use declined from 98% in 2011, the beginning of the study period, to 23% in 2016, the end of the study period. Over that same time period, use of rivaroxaban rose from 1% to 42%, and use of apixaban rose from 0% to 31%, while dabigatran use peaked in 2013 at 10%, dropping to 3% by 2016.
Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015, investigators said.
For patients with AF, apixaban was linked to a lower major bleeding risk, both versus warfarin (adjusted hazard ratio, 0.66; 95% confidence interval, 0.54-0.79) and versus rivaroxaban, the published data show. Apixaban was associated with a lower risk of intracranial bleed versus warfarin in patients with AF (aHR, 0.40; 95% CI, 0.25-0.64) as was dabigatran (aHR, 0.45; 95% CI, 0.26-0.77).
For patients without AF, apixaban was again associated with a lower risk of major bleeding versus warfarin and versus rivaroxaban, while rivaroxaban was associated with lower intracranial bleeding risk versus warfarin, and apixaban with lower risks for gastrointestinal bleeds.
Compared with apixaban, rivaroxaban and dabigatran were associated with higher risks of certain bleeding events, further analyses show.
Rivaroxaban and lower-dose apixaban were both associated with increased all-cause mortality risk versus warfarin, both in the atrial fibrillation and non-AF groups, Ms. Vinogradova and her coinvestigators noted.
“A greater proportion of the older patients on apixaban and rivaroxaban may have died while still taking anticoagulants but from age-related causes other than ischemic stroke or venous thromboembolism,” they wrote.
Compared with patients on higher doses of DOACs, patients receiving lower doses were older and had more comorbidities and more previous events, they added.
Between DOACs, results of this particular analysis were most favorable for apixaban, according to investigators.
“Our study has shown that the risk of major bleeding is lower in patients taking apixaban regardless of the reason for prescribing,” they wrote. “This was most pronounced for intracranial bleeding in patients with atrial fibrillation and for gastrointestinal bleeding in patients without atrial fibrillation, appearing, in general, to show apixaban to be the safest drug.”
The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
SOURCE: Vinogradova Y et al. BMJ 2018; 362:K2505.
Direct oral anticoagulants were associated with decreased bleeding risk versus warfarin in a recent retrospective analysis of primary care databases.
Apixaban (Eliquis) was associated with decreased risk of major bleeding events versus warfarin both in patients with atrial fibrillation (AF) and those prescribed anticoagulants for other causes, according to study results.
Rivaroxaban (Xarelto) was associated with a decrease in risk of intracranial bleeding, compared with warfarin in patients without AF, as was dabigatran (Pradaxa), reported Yana Vinogradova, a research statistician in the division of primary care at the University of Nottingham, England, and her coauthors.
An increased risk of all-cause mortality was seen with both rivaroxaban and low-dose apixaban, possibly because more patients died of age-related causes while on these direct oral anticoagulants (DOACs), they reported.
“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” Ms. Vinogradova and her colleagues said in the BMJ.
Evidence establishing the noninferiority of DOACs to warfarin comes mostly from controlled trials in AF leaving “residual concerns” about the safety of these newer agents in real world settings, where a broader range of patients may receive them, they added.
Accordingly, they conducted an analysis based on patient data from two U.K. primary care databases that were representative of the national population, according to the researchers.
A total of 196,061 patients were represented in the study, including 103,270 (53%) with AF and 92,791 (47%) who received anticoagulants for other reasons.
A total of 67% of patients received warfarin, though its use declined from 98% in 2011, the beginning of the study period, to 23% in 2016, the end of the study period. Over that same time period, use of rivaroxaban rose from 1% to 42%, and use of apixaban rose from 0% to 31%, while dabigatran use peaked in 2013 at 10%, dropping to 3% by 2016.
Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015, investigators said.
For patients with AF, apixaban was linked to a lower major bleeding risk, both versus warfarin (adjusted hazard ratio, 0.66; 95% confidence interval, 0.54-0.79) and versus rivaroxaban, the published data show. Apixaban was associated with a lower risk of intracranial bleed versus warfarin in patients with AF (aHR, 0.40; 95% CI, 0.25-0.64) as was dabigatran (aHR, 0.45; 95% CI, 0.26-0.77).
For patients without AF, apixaban was again associated with a lower risk of major bleeding versus warfarin and versus rivaroxaban, while rivaroxaban was associated with lower intracranial bleeding risk versus warfarin, and apixaban with lower risks for gastrointestinal bleeds.
Compared with apixaban, rivaroxaban and dabigatran were associated with higher risks of certain bleeding events, further analyses show.
Rivaroxaban and lower-dose apixaban were both associated with increased all-cause mortality risk versus warfarin, both in the atrial fibrillation and non-AF groups, Ms. Vinogradova and her coinvestigators noted.
“A greater proportion of the older patients on apixaban and rivaroxaban may have died while still taking anticoagulants but from age-related causes other than ischemic stroke or venous thromboembolism,” they wrote.
Compared with patients on higher doses of DOACs, patients receiving lower doses were older and had more comorbidities and more previous events, they added.
Between DOACs, results of this particular analysis were most favorable for apixaban, according to investigators.
“Our study has shown that the risk of major bleeding is lower in patients taking apixaban regardless of the reason for prescribing,” they wrote. “This was most pronounced for intracranial bleeding in patients with atrial fibrillation and for gastrointestinal bleeding in patients without atrial fibrillation, appearing, in general, to show apixaban to be the safest drug.”
The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
SOURCE: Vinogradova Y et al. BMJ 2018; 362:K2505.
FROM THE BMJ
Key clinical point:
Major finding: Apixaban was linked with an adjusted 34% decreased risk of major bleeding in patients with AF and a 40% lower risk in those prescribed anticoagulants for other causes, compared with warfarin.
Study details: A retrospective cohort study representing 196,061 patients from two U.K. primary care databases.
Disclosures: The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
Source: Vinogradova Y et al. BMJ 2018;362:k2505.
Screening for Depression in Rosacea Patients
Rosacea is a chronic skin condition that can be classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Erythematotelangiectatic rosacea is characterized by redness of the face and excessive blushing. Papulopustular rosacea is a more severe form of disease that is characterized by papules and pustules of the central face. If left untreated, these subtypes may progress to phymatous rosacea, which is characterized by skin thickening, fibrosis, and cosmetic disfigurement. Ocular rosacea is characterized by redness and irritation of the eyes.1 Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.
The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This instrument could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.2 The PHQ-9 consists of 9 questions that assess for criteria used to define depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).3 The questionnaire is brief, easy to administer, and has 88% specificity and sensitivity.4
Other studies have evaluated the relationship between rosacea and psychiatric illness, but the PHQ-9 was not used as a screening tool.7,8 Rosacea patients are at increased risk for having psychiatrist-diagnosed depression.5 In one assessment, a positive correlation between rosacea and psychiatric illness was noted using the Dermatology Life Quality Index, the rejection scale of the Questionnaire on Experience with Skin Complaints, and the German version of the Hospital Anxiety and Depression Scale.6 Interpretation of Rosacea Quality of Life and Dermatology Life Quality Index scores indicated that rosacea has a negative impact on quality of life.7
The purpose of this study was to examine the relationship between self-assessed rosacea severity scores and level of depression using the validated rosacea self-assessment tool and the PHQ-9 questionnaire, respectively.
Methods
Study Population
Study participants were adult patients from the Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) dermatology clinic from January 2011 to December 2014 who had received a diagnosis of rosacea (International Classification of Diseases, Ninth Revision [ICD-9] code 695.3) from a Wake Forest dermatologist. Institutional review board approval was obtained prior to initiation of the study. Data collection occurred from October 2014 through February 2015. A total of 478 patients met criteria for participation in the study and were identified from the Wake Forest Baptist Hospital Transitional Data Warehouse and the electronic medical record. Because rosacea typically is not diagnosed in children and the data measures are not validated in children, this demographic group was excluded from participation.
Of 478 eligible patients who were invited to participate via mail or telephone, 46 completed the rosacea self-assessment tool and PHQ-9 survey in person. A total of 432 patients were mailed a presurvey recruitment letter notifying them that they would be receiving a survey in the mail unless they contacted the study team to decline participation. An email address and telephone number for the study team was provided. Twenty patients declined to participate in the study; surveys were then mailed to the remaining 412 patients. Sixteen of the mailed surveys were returned by the post office due to an incorrect address.
Self-assessments
Patients selected images to self-identify the severity of their rosacea symptoms, including erythema, papulopustular lesions, ocular symptoms, and nasal involvement by looking at photographs on the self-assessment tool, which showed various rosacea severity levels. Scores ranged from 2 (least severe) to 8 (most severe). The PHQ-9 survey was completed by participants to assess mental health and mood.
Statistical Analysis
Results were reported using descriptive statistics. Regression analysis was performed to identify independent outcome predictors. To study the relationship between age and demographic variables, the population was divided into 2 groups: patients aged 60 years and older and patients younger than 60 years. Correlation of variables with duration of disease also was studied by creating 2 groups: patients with a disease duration of 11 years or longer and patients with a disease duration of less than 11 years. Comparisons were completed between groups using χ2 tests for proportions and t tests or analysis of variance for continuous variables. Analysis of variance was applied among all patients classified according to the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe).
Results
There is a direct relationship between rosacea severity and depression when comparing across the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe)(P=.006; F=5.18; N=183)
Most patients reported they were nondepressed (68.9%). As measured by the PHQ-9, 31.1% of patients experienced some level of depression: 21.9% reported minimal depression symptoms, 7.1% reported minor depression, 1.1% reported major depression (moderate), and 1.1% reported major depression (severe)(Table).
Comment
There is a direct relationship between rosacea severity and level of depression. In our study, nearly one-third of patients reported some degree of depression. The reason for this correlation may be due to disease stigmatization and decreased quality of life due to the somatic symptoms of rosacea. Our study reinforced the results of other studies evaluating the psychosocial impact of rosacea.8,9 Depression is associated with poor treatment adherence and poor outcomes in rosacea patients; therefore, depression may serve as an important outcome measure.10 The psychosocial impact of rosacea can be severe, but with disease improvement, there often is an improvement in the patient’s psychosocial status.7
There are several limitations to our study. The study population consisted of patients at a university dermatology clinic who may not be representative of patients in the general population; however, our hospital system does not require referral and provides care to a large percentage of the surrounding community.
Clinical implementation of the validated rosacea self-assessment tool and PHQ-9 may have several benefits. Patient-assessed rosacea severity and psychosocial impact obtained via use of these tools would provide physicians with information to fine-tune rosacea treatment regimens. Patients with the greatest social impact may require a more aggressive treatment approach. Early detection of depression in the rosacea population is important in informing treatment strategy and improving outcomes. Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated. The correlation between rosacea and depression underscores the importance of treating this highly impactful disease; however, the low number of responders from the major depression (moderate) subgroup prevented us from making any strong conclusion about this specific subgroup.
- Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013;69(6, suppl 1):S15-S26.
- Kroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychol Ann. 2002;32:509-515.
- America Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000.
- Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613.
- Gupta MA, Gupta AK, Chen SJ, et al. Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey—outpatient department data collected by the US National Center for Health Statistics from 1995 to 2002. Br J Dermatol. 2005;153:1176-1181.
- Böhm D, Schwanitz P, Stock Gissendanner S, et al. Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med. 2014;19:586-591.
- Moustafa F, Lewallen RS, Feldman SR. The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol. 2014;71:973-980.
- Halioua B, Cribier B, Frey M, et al. Feelings of stigmatization in patients with rosacea [published online June 21, 2016]. J Eur Acad Dermatol Venereol. 2016;31:163-168.
- Bewley A, Fowler J, Schöfer H, et al. Erythema of rosacea impairs health-related quality of life: results of a meta-analysis [published online March 16, 2016]. Dermatol Ther (Heidelb). 2016;6:237-247.
- Korman AM, Hill D, Alikhan A, et al. Impact and management of depression in psoriasis patients [published online January 4, 2016]. Expert Opin Pharmacother. 2016;17:147-152.
Rosacea is a chronic skin condition that can be classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Erythematotelangiectatic rosacea is characterized by redness of the face and excessive blushing. Papulopustular rosacea is a more severe form of disease that is characterized by papules and pustules of the central face. If left untreated, these subtypes may progress to phymatous rosacea, which is characterized by skin thickening, fibrosis, and cosmetic disfigurement. Ocular rosacea is characterized by redness and irritation of the eyes.1 Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.
The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This instrument could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.2 The PHQ-9 consists of 9 questions that assess for criteria used to define depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).3 The questionnaire is brief, easy to administer, and has 88% specificity and sensitivity.4
Other studies have evaluated the relationship between rosacea and psychiatric illness, but the PHQ-9 was not used as a screening tool.7,8 Rosacea patients are at increased risk for having psychiatrist-diagnosed depression.5 In one assessment, a positive correlation between rosacea and psychiatric illness was noted using the Dermatology Life Quality Index, the rejection scale of the Questionnaire on Experience with Skin Complaints, and the German version of the Hospital Anxiety and Depression Scale.6 Interpretation of Rosacea Quality of Life and Dermatology Life Quality Index scores indicated that rosacea has a negative impact on quality of life.7
The purpose of this study was to examine the relationship between self-assessed rosacea severity scores and level of depression using the validated rosacea self-assessment tool and the PHQ-9 questionnaire, respectively.
Methods
Study Population
Study participants were adult patients from the Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) dermatology clinic from January 2011 to December 2014 who had received a diagnosis of rosacea (International Classification of Diseases, Ninth Revision [ICD-9] code 695.3) from a Wake Forest dermatologist. Institutional review board approval was obtained prior to initiation of the study. Data collection occurred from October 2014 through February 2015. A total of 478 patients met criteria for participation in the study and were identified from the Wake Forest Baptist Hospital Transitional Data Warehouse and the electronic medical record. Because rosacea typically is not diagnosed in children and the data measures are not validated in children, this demographic group was excluded from participation.
Of 478 eligible patients who were invited to participate via mail or telephone, 46 completed the rosacea self-assessment tool and PHQ-9 survey in person. A total of 432 patients were mailed a presurvey recruitment letter notifying them that they would be receiving a survey in the mail unless they contacted the study team to decline participation. An email address and telephone number for the study team was provided. Twenty patients declined to participate in the study; surveys were then mailed to the remaining 412 patients. Sixteen of the mailed surveys were returned by the post office due to an incorrect address.
Self-assessments
Patients selected images to self-identify the severity of their rosacea symptoms, including erythema, papulopustular lesions, ocular symptoms, and nasal involvement by looking at photographs on the self-assessment tool, which showed various rosacea severity levels. Scores ranged from 2 (least severe) to 8 (most severe). The PHQ-9 survey was completed by participants to assess mental health and mood.
Statistical Analysis
Results were reported using descriptive statistics. Regression analysis was performed to identify independent outcome predictors. To study the relationship between age and demographic variables, the population was divided into 2 groups: patients aged 60 years and older and patients younger than 60 years. Correlation of variables with duration of disease also was studied by creating 2 groups: patients with a disease duration of 11 years or longer and patients with a disease duration of less than 11 years. Comparisons were completed between groups using χ2 tests for proportions and t tests or analysis of variance for continuous variables. Analysis of variance was applied among all patients classified according to the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe).
Results
There is a direct relationship between rosacea severity and depression when comparing across the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe)(P=.006; F=5.18; N=183)
Most patients reported they were nondepressed (68.9%). As measured by the PHQ-9, 31.1% of patients experienced some level of depression: 21.9% reported minimal depression symptoms, 7.1% reported minor depression, 1.1% reported major depression (moderate), and 1.1% reported major depression (severe)(Table).
Comment
There is a direct relationship between rosacea severity and level of depression. In our study, nearly one-third of patients reported some degree of depression. The reason for this correlation may be due to disease stigmatization and decreased quality of life due to the somatic symptoms of rosacea. Our study reinforced the results of other studies evaluating the psychosocial impact of rosacea.8,9 Depression is associated with poor treatment adherence and poor outcomes in rosacea patients; therefore, depression may serve as an important outcome measure.10 The psychosocial impact of rosacea can be severe, but with disease improvement, there often is an improvement in the patient’s psychosocial status.7
There are several limitations to our study. The study population consisted of patients at a university dermatology clinic who may not be representative of patients in the general population; however, our hospital system does not require referral and provides care to a large percentage of the surrounding community.
Clinical implementation of the validated rosacea self-assessment tool and PHQ-9 may have several benefits. Patient-assessed rosacea severity and psychosocial impact obtained via use of these tools would provide physicians with information to fine-tune rosacea treatment regimens. Patients with the greatest social impact may require a more aggressive treatment approach. Early detection of depression in the rosacea population is important in informing treatment strategy and improving outcomes. Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated. The correlation between rosacea and depression underscores the importance of treating this highly impactful disease; however, the low number of responders from the major depression (moderate) subgroup prevented us from making any strong conclusion about this specific subgroup.
Rosacea is a chronic skin condition that can be classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Erythematotelangiectatic rosacea is characterized by redness of the face and excessive blushing. Papulopustular rosacea is a more severe form of disease that is characterized by papules and pustules of the central face. If left untreated, these subtypes may progress to phymatous rosacea, which is characterized by skin thickening, fibrosis, and cosmetic disfigurement. Ocular rosacea is characterized by redness and irritation of the eyes.1 Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.
The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This instrument could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.2 The PHQ-9 consists of 9 questions that assess for criteria used to define depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).3 The questionnaire is brief, easy to administer, and has 88% specificity and sensitivity.4
Other studies have evaluated the relationship between rosacea and psychiatric illness, but the PHQ-9 was not used as a screening tool.7,8 Rosacea patients are at increased risk for having psychiatrist-diagnosed depression.5 In one assessment, a positive correlation between rosacea and psychiatric illness was noted using the Dermatology Life Quality Index, the rejection scale of the Questionnaire on Experience with Skin Complaints, and the German version of the Hospital Anxiety and Depression Scale.6 Interpretation of Rosacea Quality of Life and Dermatology Life Quality Index scores indicated that rosacea has a negative impact on quality of life.7
The purpose of this study was to examine the relationship between self-assessed rosacea severity scores and level of depression using the validated rosacea self-assessment tool and the PHQ-9 questionnaire, respectively.
Methods
Study Population
Study participants were adult patients from the Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) dermatology clinic from January 2011 to December 2014 who had received a diagnosis of rosacea (International Classification of Diseases, Ninth Revision [ICD-9] code 695.3) from a Wake Forest dermatologist. Institutional review board approval was obtained prior to initiation of the study. Data collection occurred from October 2014 through February 2015. A total of 478 patients met criteria for participation in the study and were identified from the Wake Forest Baptist Hospital Transitional Data Warehouse and the electronic medical record. Because rosacea typically is not diagnosed in children and the data measures are not validated in children, this demographic group was excluded from participation.
Of 478 eligible patients who were invited to participate via mail or telephone, 46 completed the rosacea self-assessment tool and PHQ-9 survey in person. A total of 432 patients were mailed a presurvey recruitment letter notifying them that they would be receiving a survey in the mail unless they contacted the study team to decline participation. An email address and telephone number for the study team was provided. Twenty patients declined to participate in the study; surveys were then mailed to the remaining 412 patients. Sixteen of the mailed surveys were returned by the post office due to an incorrect address.
Self-assessments
Patients selected images to self-identify the severity of their rosacea symptoms, including erythema, papulopustular lesions, ocular symptoms, and nasal involvement by looking at photographs on the self-assessment tool, which showed various rosacea severity levels. Scores ranged from 2 (least severe) to 8 (most severe). The PHQ-9 survey was completed by participants to assess mental health and mood.
Statistical Analysis
Results were reported using descriptive statistics. Regression analysis was performed to identify independent outcome predictors. To study the relationship between age and demographic variables, the population was divided into 2 groups: patients aged 60 years and older and patients younger than 60 years. Correlation of variables with duration of disease also was studied by creating 2 groups: patients with a disease duration of 11 years or longer and patients with a disease duration of less than 11 years. Comparisons were completed between groups using χ2 tests for proportions and t tests or analysis of variance for continuous variables. Analysis of variance was applied among all patients classified according to the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe).
Results
There is a direct relationship between rosacea severity and depression when comparing across the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe)(P=.006; F=5.18; N=183)
Most patients reported they were nondepressed (68.9%). As measured by the PHQ-9, 31.1% of patients experienced some level of depression: 21.9% reported minimal depression symptoms, 7.1% reported minor depression, 1.1% reported major depression (moderate), and 1.1% reported major depression (severe)(Table).
Comment
There is a direct relationship between rosacea severity and level of depression. In our study, nearly one-third of patients reported some degree of depression. The reason for this correlation may be due to disease stigmatization and decreased quality of life due to the somatic symptoms of rosacea. Our study reinforced the results of other studies evaluating the psychosocial impact of rosacea.8,9 Depression is associated with poor treatment adherence and poor outcomes in rosacea patients; therefore, depression may serve as an important outcome measure.10 The psychosocial impact of rosacea can be severe, but with disease improvement, there often is an improvement in the patient’s psychosocial status.7
There are several limitations to our study. The study population consisted of patients at a university dermatology clinic who may not be representative of patients in the general population; however, our hospital system does not require referral and provides care to a large percentage of the surrounding community.
Clinical implementation of the validated rosacea self-assessment tool and PHQ-9 may have several benefits. Patient-assessed rosacea severity and psychosocial impact obtained via use of these tools would provide physicians with information to fine-tune rosacea treatment regimens. Patients with the greatest social impact may require a more aggressive treatment approach. Early detection of depression in the rosacea population is important in informing treatment strategy and improving outcomes. Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated. The correlation between rosacea and depression underscores the importance of treating this highly impactful disease; however, the low number of responders from the major depression (moderate) subgroup prevented us from making any strong conclusion about this specific subgroup.
- Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013;69(6, suppl 1):S15-S26.
- Kroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychol Ann. 2002;32:509-515.
- America Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000.
- Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613.
- Gupta MA, Gupta AK, Chen SJ, et al. Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey—outpatient department data collected by the US National Center for Health Statistics from 1995 to 2002. Br J Dermatol. 2005;153:1176-1181.
- Böhm D, Schwanitz P, Stock Gissendanner S, et al. Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med. 2014;19:586-591.
- Moustafa F, Lewallen RS, Feldman SR. The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol. 2014;71:973-980.
- Halioua B, Cribier B, Frey M, et al. Feelings of stigmatization in patients with rosacea [published online June 21, 2016]. J Eur Acad Dermatol Venereol. 2016;31:163-168.
- Bewley A, Fowler J, Schöfer H, et al. Erythema of rosacea impairs health-related quality of life: results of a meta-analysis [published online March 16, 2016]. Dermatol Ther (Heidelb). 2016;6:237-247.
- Korman AM, Hill D, Alikhan A, et al. Impact and management of depression in psoriasis patients [published online January 4, 2016]. Expert Opin Pharmacother. 2016;17:147-152.
- Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013;69(6, suppl 1):S15-S26.
- Kroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychol Ann. 2002;32:509-515.
- America Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000.
- Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613.
- Gupta MA, Gupta AK, Chen SJ, et al. Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey—outpatient department data collected by the US National Center for Health Statistics from 1995 to 2002. Br J Dermatol. 2005;153:1176-1181.
- Böhm D, Schwanitz P, Stock Gissendanner S, et al. Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med. 2014;19:586-591.
- Moustafa F, Lewallen RS, Feldman SR. The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol. 2014;71:973-980.
- Halioua B, Cribier B, Frey M, et al. Feelings of stigmatization in patients with rosacea [published online June 21, 2016]. J Eur Acad Dermatol Venereol. 2016;31:163-168.
- Bewley A, Fowler J, Schöfer H, et al. Erythema of rosacea impairs health-related quality of life: results of a meta-analysis [published online March 16, 2016]. Dermatol Ther (Heidelb). 2016;6:237-247.
- Korman AM, Hill D, Alikhan A, et al. Impact and management of depression in psoriasis patients [published online January 4, 2016]. Expert Opin Pharmacother. 2016;17:147-152.
Practice Points
- Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.
- There is a direct relationship between rosacea severity and degree of depression.
- Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated.