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‘Thank you, EMR!’
“Thank you, EMR!” Said no doctor. Ever.
At least up until now.
For years, we have had to put up with these machines in our exam rooms, distracting data entry devices that offer insignificant contributions to the work we do. That’s starting to change.
Recently, I led a workshop at the annual Kaiser Permanente internal medicine conference in Southern California. I gave one of my more popular sessions on the art of diagnosis and therapy (inspired and borrowed from Dr. Irwin M. Braverman’s marvelous lectures on learning dermatology through art).
What’s more, the listed steroids change automatically based on the current formulary. This ensures the lowest cost to the patient and minimizes rework of having to go back and pick another when the patient balks at unjustifiably high prices. The clinician has only to click and sign to place the order. Now a primary care physician – or even a dermatologist! – needs only to estimate the potency of the therapy, pick a vehicle (cream, ointment, gel, solution), and the EMR guides him or her to prescribe the right medication. It is easy to use, active at the point of care, and helpful to both clinician and patient.
This SRX program was developed by our local physicians in conjunction with pharmacists and the informatics team. It has enormous potential, providing more point of care clinical decision support based on best practice, formulary, and even personalized information automatically gleaned from that patient’s chart. As of now, we can customize our order entry such that if I want to order labs to look for connective tissue disease, I have to type only .CTD, and my personal picks for a lupus workup come up. It saves me time. Yes, I did just say that in reference to my EMR. And it helps ensure high-quality care. Whenever new diagnostics or new treatments become best practice, I can put them on my preference list, thereby making the best thing to do the easy thing to do.
The internal medicine physicians were appreciative for my lecture and loved learning through art. However, the big hit was the SRX DERM. “This will make it so much easier,” said one hospitalist, “thanks for doing this!”
I had nothing to do with it though. Thank you, EMR.
Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego. He is @Dermdoc on Twitter. Write to him at [email protected].
“Thank you, EMR!” Said no doctor. Ever.
At least up until now.
For years, we have had to put up with these machines in our exam rooms, distracting data entry devices that offer insignificant contributions to the work we do. That’s starting to change.
Recently, I led a workshop at the annual Kaiser Permanente internal medicine conference in Southern California. I gave one of my more popular sessions on the art of diagnosis and therapy (inspired and borrowed from Dr. Irwin M. Braverman’s marvelous lectures on learning dermatology through art).
What’s more, the listed steroids change automatically based on the current formulary. This ensures the lowest cost to the patient and minimizes rework of having to go back and pick another when the patient balks at unjustifiably high prices. The clinician has only to click and sign to place the order. Now a primary care physician – or even a dermatologist! – needs only to estimate the potency of the therapy, pick a vehicle (cream, ointment, gel, solution), and the EMR guides him or her to prescribe the right medication. It is easy to use, active at the point of care, and helpful to both clinician and patient.
This SRX program was developed by our local physicians in conjunction with pharmacists and the informatics team. It has enormous potential, providing more point of care clinical decision support based on best practice, formulary, and even personalized information automatically gleaned from that patient’s chart. As of now, we can customize our order entry such that if I want to order labs to look for connective tissue disease, I have to type only .CTD, and my personal picks for a lupus workup come up. It saves me time. Yes, I did just say that in reference to my EMR. And it helps ensure high-quality care. Whenever new diagnostics or new treatments become best practice, I can put them on my preference list, thereby making the best thing to do the easy thing to do.
The internal medicine physicians were appreciative for my lecture and loved learning through art. However, the big hit was the SRX DERM. “This will make it so much easier,” said one hospitalist, “thanks for doing this!”
I had nothing to do with it though. Thank you, EMR.
Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego. He is @Dermdoc on Twitter. Write to him at [email protected].
“Thank you, EMR!” Said no doctor. Ever.
At least up until now.
For years, we have had to put up with these machines in our exam rooms, distracting data entry devices that offer insignificant contributions to the work we do. That’s starting to change.
Recently, I led a workshop at the annual Kaiser Permanente internal medicine conference in Southern California. I gave one of my more popular sessions on the art of diagnosis and therapy (inspired and borrowed from Dr. Irwin M. Braverman’s marvelous lectures on learning dermatology through art).
What’s more, the listed steroids change automatically based on the current formulary. This ensures the lowest cost to the patient and minimizes rework of having to go back and pick another when the patient balks at unjustifiably high prices. The clinician has only to click and sign to place the order. Now a primary care physician – or even a dermatologist! – needs only to estimate the potency of the therapy, pick a vehicle (cream, ointment, gel, solution), and the EMR guides him or her to prescribe the right medication. It is easy to use, active at the point of care, and helpful to both clinician and patient.
This SRX program was developed by our local physicians in conjunction with pharmacists and the informatics team. It has enormous potential, providing more point of care clinical decision support based on best practice, formulary, and even personalized information automatically gleaned from that patient’s chart. As of now, we can customize our order entry such that if I want to order labs to look for connective tissue disease, I have to type only .CTD, and my personal picks for a lupus workup come up. It saves me time. Yes, I did just say that in reference to my EMR. And it helps ensure high-quality care. Whenever new diagnostics or new treatments become best practice, I can put them on my preference list, thereby making the best thing to do the easy thing to do.
The internal medicine physicians were appreciative for my lecture and loved learning through art. However, the big hit was the SRX DERM. “This will make it so much easier,” said one hospitalist, “thanks for doing this!”
I had nothing to do with it though. Thank you, EMR.
Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego. He is @Dermdoc on Twitter. Write to him at [email protected].
Ebola research update: September 2016
The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.
, according to a study of EVD patients treated in the United States.
An analysis of the 2014 Ebola virus disease outbreak in Nigeria found that early detection of cases, an efficacious incident management system, and rapid case management with on-site mobilization and training of local professionals were important to better outcomes, prompt containment, and no infection among EVD care-providers.
Viral genome sequence data uniquely reveals the 2013-2016 epidemic of Ebola virus disease in West Africa to be “a heterogeneous and spatially dissociated collection of transmission clusters of that were of varying size, duration, and connectivity,” according to a recent study.
A case study of Lassa fever involved the development of a mathematical framework which was applied to try to determine how much of disease transmission was from animal to human and how much was from human to human. This knowledge can be used to “infer human disease risk based on knowledge of infection patterns in the animal reservoir host and the contact mechanisms required for transmission to humans.”
A decontamination protocol that relies on the use of both peracetic acid and hydrogen peroxide fumigation was proposed for a biosafety level 3 field laboratory as a part of an Ebola treatment center in Guinea. Inoculated stainless steel disks of bioindicators containing spores of Geobacillus stearothermophilus were used to control the protocol.
A survey in New Zealand indicated that a future Ebola outbreak would have “large social and economic consequences” because judging from survey responses, a large percentage of the population would avoid social contact, such as going to work, school, and social events, to protect their health, according to a study in Disaster Medicine and Public Health Preparedness. Survey respondents also indicated a willingness to receive a vaccine.
Investigators identified contact tracing as an important determinant of the 2014-2015 Ebola epidemic’s behavior in Guinea. Also, early availability of Ebola treatment unit beds was key in limiting the number of Ebola cases.
The WHO Ebola Response Team said that empirical and modeling studies performed during the West African Ebola virus disease epidemic have demonstrated that large epidemics of EVD can be prevented, that “a rapid response can interrupt transmission and restrict the size of outbreaks, even in densely populated cities.”
In 2015, the first nationwide semen testing and counseling program for male Ebola survivors, the Men’s Health Screening Program, was established in Liberia, according to a report in MMWR. Researchers said involvement with the survivor community, communication, and flexibility were key to the program’s success.
A $13 million NIH grant to study how the Ebola virus replicates has been awarded to a team at Washington University, St. Louis.
A recent study found that vector delivery of two antibody components of the ZMapp product works in mice against systemic and airway challenge with a mouse-adapted strain of Ebola virus. The authors say this platform “provides a generic manufacturing solution and overcomes some of the delivery challenges associated with repeated administration of the protective protein.”
U.S. Army researchers based at Fort Detrick, Md., are developing relationships with Ebola survivors in Uganda, who the researchers believe may hold the key to a vaccine or treatment for the infection because many Ugandans have survived the epidemic.
A qualitative study in PLOS Current Outbreaks found that the preparedness of U.S. health care volunteers in the West Africa Ebola deployment was inadequate. The authors said effective policies and practices must be developed and implemented to properly protect the health and well-being of volunteers.
Investigators hypothesized that cannabidiol, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post-Ebola sequelae because it can reduce pain and inflammation.
[email protected]
On Twitter @richpizzi
The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.
, according to a study of EVD patients treated in the United States.
An analysis of the 2014 Ebola virus disease outbreak in Nigeria found that early detection of cases, an efficacious incident management system, and rapid case management with on-site mobilization and training of local professionals were important to better outcomes, prompt containment, and no infection among EVD care-providers.
Viral genome sequence data uniquely reveals the 2013-2016 epidemic of Ebola virus disease in West Africa to be “a heterogeneous and spatially dissociated collection of transmission clusters of that were of varying size, duration, and connectivity,” according to a recent study.
A case study of Lassa fever involved the development of a mathematical framework which was applied to try to determine how much of disease transmission was from animal to human and how much was from human to human. This knowledge can be used to “infer human disease risk based on knowledge of infection patterns in the animal reservoir host and the contact mechanisms required for transmission to humans.”
A decontamination protocol that relies on the use of both peracetic acid and hydrogen peroxide fumigation was proposed for a biosafety level 3 field laboratory as a part of an Ebola treatment center in Guinea. Inoculated stainless steel disks of bioindicators containing spores of Geobacillus stearothermophilus were used to control the protocol.
A survey in New Zealand indicated that a future Ebola outbreak would have “large social and economic consequences” because judging from survey responses, a large percentage of the population would avoid social contact, such as going to work, school, and social events, to protect their health, according to a study in Disaster Medicine and Public Health Preparedness. Survey respondents also indicated a willingness to receive a vaccine.
Investigators identified contact tracing as an important determinant of the 2014-2015 Ebola epidemic’s behavior in Guinea. Also, early availability of Ebola treatment unit beds was key in limiting the number of Ebola cases.
The WHO Ebola Response Team said that empirical and modeling studies performed during the West African Ebola virus disease epidemic have demonstrated that large epidemics of EVD can be prevented, that “a rapid response can interrupt transmission and restrict the size of outbreaks, even in densely populated cities.”
In 2015, the first nationwide semen testing and counseling program for male Ebola survivors, the Men’s Health Screening Program, was established in Liberia, according to a report in MMWR. Researchers said involvement with the survivor community, communication, and flexibility were key to the program’s success.
A $13 million NIH grant to study how the Ebola virus replicates has been awarded to a team at Washington University, St. Louis.
A recent study found that vector delivery of two antibody components of the ZMapp product works in mice against systemic and airway challenge with a mouse-adapted strain of Ebola virus. The authors say this platform “provides a generic manufacturing solution and overcomes some of the delivery challenges associated with repeated administration of the protective protein.”
U.S. Army researchers based at Fort Detrick, Md., are developing relationships with Ebola survivors in Uganda, who the researchers believe may hold the key to a vaccine or treatment for the infection because many Ugandans have survived the epidemic.
A qualitative study in PLOS Current Outbreaks found that the preparedness of U.S. health care volunteers in the West Africa Ebola deployment was inadequate. The authors said effective policies and practices must be developed and implemented to properly protect the health and well-being of volunteers.
Investigators hypothesized that cannabidiol, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post-Ebola sequelae because it can reduce pain and inflammation.
[email protected]
On Twitter @richpizzi
The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.
, according to a study of EVD patients treated in the United States.
An analysis of the 2014 Ebola virus disease outbreak in Nigeria found that early detection of cases, an efficacious incident management system, and rapid case management with on-site mobilization and training of local professionals were important to better outcomes, prompt containment, and no infection among EVD care-providers.
Viral genome sequence data uniquely reveals the 2013-2016 epidemic of Ebola virus disease in West Africa to be “a heterogeneous and spatially dissociated collection of transmission clusters of that were of varying size, duration, and connectivity,” according to a recent study.
A case study of Lassa fever involved the development of a mathematical framework which was applied to try to determine how much of disease transmission was from animal to human and how much was from human to human. This knowledge can be used to “infer human disease risk based on knowledge of infection patterns in the animal reservoir host and the contact mechanisms required for transmission to humans.”
A decontamination protocol that relies on the use of both peracetic acid and hydrogen peroxide fumigation was proposed for a biosafety level 3 field laboratory as a part of an Ebola treatment center in Guinea. Inoculated stainless steel disks of bioindicators containing spores of Geobacillus stearothermophilus were used to control the protocol.
A survey in New Zealand indicated that a future Ebola outbreak would have “large social and economic consequences” because judging from survey responses, a large percentage of the population would avoid social contact, such as going to work, school, and social events, to protect their health, according to a study in Disaster Medicine and Public Health Preparedness. Survey respondents also indicated a willingness to receive a vaccine.
Investigators identified contact tracing as an important determinant of the 2014-2015 Ebola epidemic’s behavior in Guinea. Also, early availability of Ebola treatment unit beds was key in limiting the number of Ebola cases.
The WHO Ebola Response Team said that empirical and modeling studies performed during the West African Ebola virus disease epidemic have demonstrated that large epidemics of EVD can be prevented, that “a rapid response can interrupt transmission and restrict the size of outbreaks, even in densely populated cities.”
In 2015, the first nationwide semen testing and counseling program for male Ebola survivors, the Men’s Health Screening Program, was established in Liberia, according to a report in MMWR. Researchers said involvement with the survivor community, communication, and flexibility were key to the program’s success.
A $13 million NIH grant to study how the Ebola virus replicates has been awarded to a team at Washington University, St. Louis.
A recent study found that vector delivery of two antibody components of the ZMapp product works in mice against systemic and airway challenge with a mouse-adapted strain of Ebola virus. The authors say this platform “provides a generic manufacturing solution and overcomes some of the delivery challenges associated with repeated administration of the protective protein.”
U.S. Army researchers based at Fort Detrick, Md., are developing relationships with Ebola survivors in Uganda, who the researchers believe may hold the key to a vaccine or treatment for the infection because many Ugandans have survived the epidemic.
A qualitative study in PLOS Current Outbreaks found that the preparedness of U.S. health care volunteers in the West Africa Ebola deployment was inadequate. The authors said effective policies and practices must be developed and implemented to properly protect the health and well-being of volunteers.
Investigators hypothesized that cannabidiol, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post-Ebola sequelae because it can reduce pain and inflammation.
[email protected]
On Twitter @richpizzi
PARP inhibitor prolongs PFS in ovarian cancer patients with and without BRCA mutations
COPENHAGEN – Women with platinum-sensitive, recurrent ovarian cancer treated with the PARP 1/2 inhibitor niraparib had significantly longer progression-free survival than did women who received a placebo, regardless of their BRCA mutational status, according to results of a phase III trial.
Median progression-free survival (PFS) among women with germline BRCA mutations who received niraparib was 21 months, compared with 5.5 months for women with germline BRCA mutations who received placebo (P less than .001).
For the overall population of women with no germline mutations, median PFS was 9.3 months for those who received niraparib, vs. 3.9 months for placebo-treated controls. Among women in this group whose tumors tested positive for homologous recombination deficiency (HRD), median PFS was 12.9 months, vs. 3.8 months without HRD.
Dr. Mirza reported results of the The NGOT-OV16/NOVA trial, the first phase III trial with a PARP inhibitor, at the European Society for Medical Oncology Congress. Results of the trial were simultaneously published online in The New England Journal of Medicine.
Niraparib is a selective, oral inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 that was previously shown to have efficacy against ovarian cancer in a phase I dose-escalation trial.
In the NGOT-OV16 NOVA trial, patients with platinum-sensitive high grade serous ovarian cancer first underwent chemotherapy with 4-6 cycles of a platinum-based regimen, and those who responded to platinum treatment were then stratified by the presence or absence of germline BRCA mutations, and then randomized on a 2:1 basis to either niraparib 300 mg once daily or placebo until disease progression.
A total of 203 patients with germline BRCA mutations and 350 with no mutations were enrolled in the trial.
As noted before, patients treated with niraparib in both trials arms had significantly longer PFS than did controls. The hazard ratio (HR) for niraparib in patients with germline BRCA mutations was 0.27. For the overall non–germline mutation population, the HR was 0.45, and for HRD-positive and HRD-negative subgroups, the HRs were 0.38 and 0.56, respectively (the latter is an exploratory endpoint, however; P less than .001 for the first three HRs shown).
Secondary efficacy endpoints, including chemotherapy-free interval and time to first subsequent treatment, also favored niraparib in patients with and without BRCA mutations.
Overall survival data for the trial are not sufficiently mature for reporting, however.
The safety profile of the drug was in line with that seen in other studies of PARP inhibitors, Dr. Mirza said. Grade 3/4 adverse events occurring in 5% or more of patients included thrombocytopenias in 33.8% of niraparib recipients vs. 0.6% of controls, anemia in 25.3% vs. 0%, neutropenia in 19.6% vs. 1.7%, fatigue in 8.2% vs. 0.6%, and hypertension in 8.2% vs. 2.2%.
Five of the 367 patients who received niraparib (1.4%) developed myelodysplasia or acute myeloid leukemia, compared with 2 of 179 patients (1.1%) treated with placebo.
Patient-reported outcomes measured via the Functional Assessment of Cancer Therapy – Ovarian Symptom Index and EQ (EuroQol) 5D-5L instrument showed high compliance rates and patient-reported symptom rates that were similar between niraparib and placebo groups.
The results also demonstrated that HRD testing can be used to identify patients without germline mutations in BRCA who may benefit from a PARP inhibitor, he said.
Tesaro funded the study. Dr. Mirza disclosed serving on the board of directors of the pharmaceutical companies, and consultant or advisory roles with multiple other companies. Dr. Pignata disclosed consulting, honoraria, and or research funding from several companies, but reported no relationship with Tesaro
COPENHAGEN – Women with platinum-sensitive, recurrent ovarian cancer treated with the PARP 1/2 inhibitor niraparib had significantly longer progression-free survival than did women who received a placebo, regardless of their BRCA mutational status, according to results of a phase III trial.
Median progression-free survival (PFS) among women with germline BRCA mutations who received niraparib was 21 months, compared with 5.5 months for women with germline BRCA mutations who received placebo (P less than .001).
For the overall population of women with no germline mutations, median PFS was 9.3 months for those who received niraparib, vs. 3.9 months for placebo-treated controls. Among women in this group whose tumors tested positive for homologous recombination deficiency (HRD), median PFS was 12.9 months, vs. 3.8 months without HRD.
Dr. Mirza reported results of the The NGOT-OV16/NOVA trial, the first phase III trial with a PARP inhibitor, at the European Society for Medical Oncology Congress. Results of the trial were simultaneously published online in The New England Journal of Medicine.
Niraparib is a selective, oral inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 that was previously shown to have efficacy against ovarian cancer in a phase I dose-escalation trial.
In the NGOT-OV16 NOVA trial, patients with platinum-sensitive high grade serous ovarian cancer first underwent chemotherapy with 4-6 cycles of a platinum-based regimen, and those who responded to platinum treatment were then stratified by the presence or absence of germline BRCA mutations, and then randomized on a 2:1 basis to either niraparib 300 mg once daily or placebo until disease progression.
A total of 203 patients with germline BRCA mutations and 350 with no mutations were enrolled in the trial.
As noted before, patients treated with niraparib in both trials arms had significantly longer PFS than did controls. The hazard ratio (HR) for niraparib in patients with germline BRCA mutations was 0.27. For the overall non–germline mutation population, the HR was 0.45, and for HRD-positive and HRD-negative subgroups, the HRs were 0.38 and 0.56, respectively (the latter is an exploratory endpoint, however; P less than .001 for the first three HRs shown).
Secondary efficacy endpoints, including chemotherapy-free interval and time to first subsequent treatment, also favored niraparib in patients with and without BRCA mutations.
Overall survival data for the trial are not sufficiently mature for reporting, however.
The safety profile of the drug was in line with that seen in other studies of PARP inhibitors, Dr. Mirza said. Grade 3/4 adverse events occurring in 5% or more of patients included thrombocytopenias in 33.8% of niraparib recipients vs. 0.6% of controls, anemia in 25.3% vs. 0%, neutropenia in 19.6% vs. 1.7%, fatigue in 8.2% vs. 0.6%, and hypertension in 8.2% vs. 2.2%.
Five of the 367 patients who received niraparib (1.4%) developed myelodysplasia or acute myeloid leukemia, compared with 2 of 179 patients (1.1%) treated with placebo.
Patient-reported outcomes measured via the Functional Assessment of Cancer Therapy – Ovarian Symptom Index and EQ (EuroQol) 5D-5L instrument showed high compliance rates and patient-reported symptom rates that were similar between niraparib and placebo groups.
The results also demonstrated that HRD testing can be used to identify patients without germline mutations in BRCA who may benefit from a PARP inhibitor, he said.
Tesaro funded the study. Dr. Mirza disclosed serving on the board of directors of the pharmaceutical companies, and consultant or advisory roles with multiple other companies. Dr. Pignata disclosed consulting, honoraria, and or research funding from several companies, but reported no relationship with Tesaro
COPENHAGEN – Women with platinum-sensitive, recurrent ovarian cancer treated with the PARP 1/2 inhibitor niraparib had significantly longer progression-free survival than did women who received a placebo, regardless of their BRCA mutational status, according to results of a phase III trial.
Median progression-free survival (PFS) among women with germline BRCA mutations who received niraparib was 21 months, compared with 5.5 months for women with germline BRCA mutations who received placebo (P less than .001).
For the overall population of women with no germline mutations, median PFS was 9.3 months for those who received niraparib, vs. 3.9 months for placebo-treated controls. Among women in this group whose tumors tested positive for homologous recombination deficiency (HRD), median PFS was 12.9 months, vs. 3.8 months without HRD.
Dr. Mirza reported results of the The NGOT-OV16/NOVA trial, the first phase III trial with a PARP inhibitor, at the European Society for Medical Oncology Congress. Results of the trial were simultaneously published online in The New England Journal of Medicine.
Niraparib is a selective, oral inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 that was previously shown to have efficacy against ovarian cancer in a phase I dose-escalation trial.
In the NGOT-OV16 NOVA trial, patients with platinum-sensitive high grade serous ovarian cancer first underwent chemotherapy with 4-6 cycles of a platinum-based regimen, and those who responded to platinum treatment were then stratified by the presence or absence of germline BRCA mutations, and then randomized on a 2:1 basis to either niraparib 300 mg once daily or placebo until disease progression.
A total of 203 patients with germline BRCA mutations and 350 with no mutations were enrolled in the trial.
As noted before, patients treated with niraparib in both trials arms had significantly longer PFS than did controls. The hazard ratio (HR) for niraparib in patients with germline BRCA mutations was 0.27. For the overall non–germline mutation population, the HR was 0.45, and for HRD-positive and HRD-negative subgroups, the HRs were 0.38 and 0.56, respectively (the latter is an exploratory endpoint, however; P less than .001 for the first three HRs shown).
Secondary efficacy endpoints, including chemotherapy-free interval and time to first subsequent treatment, also favored niraparib in patients with and without BRCA mutations.
Overall survival data for the trial are not sufficiently mature for reporting, however.
The safety profile of the drug was in line with that seen in other studies of PARP inhibitors, Dr. Mirza said. Grade 3/4 adverse events occurring in 5% or more of patients included thrombocytopenias in 33.8% of niraparib recipients vs. 0.6% of controls, anemia in 25.3% vs. 0%, neutropenia in 19.6% vs. 1.7%, fatigue in 8.2% vs. 0.6%, and hypertension in 8.2% vs. 2.2%.
Five of the 367 patients who received niraparib (1.4%) developed myelodysplasia or acute myeloid leukemia, compared with 2 of 179 patients (1.1%) treated with placebo.
Patient-reported outcomes measured via the Functional Assessment of Cancer Therapy – Ovarian Symptom Index and EQ (EuroQol) 5D-5L instrument showed high compliance rates and patient-reported symptom rates that were similar between niraparib and placebo groups.
The results also demonstrated that HRD testing can be used to identify patients without germline mutations in BRCA who may benefit from a PARP inhibitor, he said.
Tesaro funded the study. Dr. Mirza disclosed serving on the board of directors of the pharmaceutical companies, and consultant or advisory roles with multiple other companies. Dr. Pignata disclosed consulting, honoraria, and or research funding from several companies, but reported no relationship with Tesaro
Key clinical point: The poly ADP ribose polymerase (PARP) 1/2 inhibitor niraparib improved PFS in patients with ovarian cancer compared with those on placebo.
Major finding: Median PFS in women with germline BRCA mutations who received niraparib was 21 months, compared with 5.5 months for those on placebo.
Data source: Randomized double-blind phase III trial of 553 women with platinum-sensitive high grade serous ovarian cancer.
Disclosures: Tesaro funded the study. Dr. Mirza disclosed serving on the board of directors of the pharmaceutical companies, and consultant or advisory roles with multiple other companies. Dr. Pignata disclosed consulting, honoraria, and or research funding from several companies, but reported no relationship with Tesaro.
Cow’s milk allergy appears to affect more U.S. infants than thought
MONTREAL – The incidence of cow’s milk protein allergy during the first few months of life may be much more common than suggested by published studies, based on what was found is a prospective study with 700 infants seen regularly at a single, general pediatrics practice in suburban Massachusetts.
Among the 700 infants enrolled in this series, 105 (15%) were diagnosed with cow’s milk protein allergy (CMPA) when they were 5-163 days old, with a median age at diagnosis of 33 days, Victoria J. Martin, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. She and her associates confirmed that all these infants had true CMPA episodes of proctocolitis by requiring detection of blood in the stool of affected children.
The study results also suggested a protective effect against CMPA when infants received some amount of early breastfeeding, and a pilot substudy run in 47 of the enrolled infants also suggested a link between development of CMPA and abnormalities in the microbiome composition of affected infants, she reported.
While the 15% incidence rate was unexpectedly high, it “absolutely feels like what we see in routine clinical practice,” Dr. Martin said in an interview. She chalked up the much-lower figure cited in the pediatric literature as relying on strict follow-up confirmation by rechallenge of the child with cow’s milk, a step often not taken by busy clinicians. Deferring formal confirmation also often means delayed reintroduction of cow’s milk into the infant’s diet, with restriction often continuing for perhaps a year following the index episode of CMPA. Although such unnecessarily long delays in milk reintroduction have largely been considered benign, recent findings from the Learning Early About Peanut Allergy (LEAP) trial that withholding peanut exposure can increase development of peanut allergies suggests that children also might receive long-term benefit from quicker reintroduction of milk in terms of better development of the immune system and microbiome, she said.
“If we rechallenged all these infants after 1 month, I think we’d find a CMPA rate closer to 3%. Leaving infants on a mild restricted diet for 12 months is a mistake,” she added.
The Gastrointestinal Microbiome & Proctocolitis (GMAP) study enrolled 700 infants seen at a single general practice pediatric practice in suburban Massachusetts at the time of their first well-baby visit, at a median age of 8 days. During 2 years of follow-up, the researchers collected stool specimens from the enrolled children at each of up to five scheduled visits during the first 4 months. They also kept track of when children received a CMPA diagnosis confirmed by at least one bloody stool.
Analysis of CMPA correlates showed that, among infants who developed it, 17% had not received any breastfeeding soon after birth, while among infants who did not develop CMPA, 8% did not undergo early breastfeeding. The incidence of CMPA was roughly similar among infants who received an early combination of breast milk and formula and in those who received exclusively breast milk during the first days of life, showing that even partial breastfeeding is better than no breastfeeding, Dr. Martin noted.
Her analysis also includes initial results from microbial assessment of the collected serial stool specimens from a subgroup of 24 infants who developed CMPA and 23 who did not, with a total of 223 total specimens evaluated. These studies showed that the infants who developed CMPA significantly lagged in their colonization with Bifidobacteria, had significantly higher colonization levels with Enterobacteriaceae, and that in infants who did develop CMPA, their gut level of Clostridia significantly increased as their proctocolitis resolved.
Dr. Martin had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – The incidence of cow’s milk protein allergy during the first few months of life may be much more common than suggested by published studies, based on what was found is a prospective study with 700 infants seen regularly at a single, general pediatrics practice in suburban Massachusetts.
Among the 700 infants enrolled in this series, 105 (15%) were diagnosed with cow’s milk protein allergy (CMPA) when they were 5-163 days old, with a median age at diagnosis of 33 days, Victoria J. Martin, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. She and her associates confirmed that all these infants had true CMPA episodes of proctocolitis by requiring detection of blood in the stool of affected children.
The study results also suggested a protective effect against CMPA when infants received some amount of early breastfeeding, and a pilot substudy run in 47 of the enrolled infants also suggested a link between development of CMPA and abnormalities in the microbiome composition of affected infants, she reported.
While the 15% incidence rate was unexpectedly high, it “absolutely feels like what we see in routine clinical practice,” Dr. Martin said in an interview. She chalked up the much-lower figure cited in the pediatric literature as relying on strict follow-up confirmation by rechallenge of the child with cow’s milk, a step often not taken by busy clinicians. Deferring formal confirmation also often means delayed reintroduction of cow’s milk into the infant’s diet, with restriction often continuing for perhaps a year following the index episode of CMPA. Although such unnecessarily long delays in milk reintroduction have largely been considered benign, recent findings from the Learning Early About Peanut Allergy (LEAP) trial that withholding peanut exposure can increase development of peanut allergies suggests that children also might receive long-term benefit from quicker reintroduction of milk in terms of better development of the immune system and microbiome, she said.
“If we rechallenged all these infants after 1 month, I think we’d find a CMPA rate closer to 3%. Leaving infants on a mild restricted diet for 12 months is a mistake,” she added.
The Gastrointestinal Microbiome & Proctocolitis (GMAP) study enrolled 700 infants seen at a single general practice pediatric practice in suburban Massachusetts at the time of their first well-baby visit, at a median age of 8 days. During 2 years of follow-up, the researchers collected stool specimens from the enrolled children at each of up to five scheduled visits during the first 4 months. They also kept track of when children received a CMPA diagnosis confirmed by at least one bloody stool.
Analysis of CMPA correlates showed that, among infants who developed it, 17% had not received any breastfeeding soon after birth, while among infants who did not develop CMPA, 8% did not undergo early breastfeeding. The incidence of CMPA was roughly similar among infants who received an early combination of breast milk and formula and in those who received exclusively breast milk during the first days of life, showing that even partial breastfeeding is better than no breastfeeding, Dr. Martin noted.
Her analysis also includes initial results from microbial assessment of the collected serial stool specimens from a subgroup of 24 infants who developed CMPA and 23 who did not, with a total of 223 total specimens evaluated. These studies showed that the infants who developed CMPA significantly lagged in their colonization with Bifidobacteria, had significantly higher colonization levels with Enterobacteriaceae, and that in infants who did develop CMPA, their gut level of Clostridia significantly increased as their proctocolitis resolved.
Dr. Martin had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – The incidence of cow’s milk protein allergy during the first few months of life may be much more common than suggested by published studies, based on what was found is a prospective study with 700 infants seen regularly at a single, general pediatrics practice in suburban Massachusetts.
Among the 700 infants enrolled in this series, 105 (15%) were diagnosed with cow’s milk protein allergy (CMPA) when they were 5-163 days old, with a median age at diagnosis of 33 days, Victoria J. Martin, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. She and her associates confirmed that all these infants had true CMPA episodes of proctocolitis by requiring detection of blood in the stool of affected children.
The study results also suggested a protective effect against CMPA when infants received some amount of early breastfeeding, and a pilot substudy run in 47 of the enrolled infants also suggested a link between development of CMPA and abnormalities in the microbiome composition of affected infants, she reported.
While the 15% incidence rate was unexpectedly high, it “absolutely feels like what we see in routine clinical practice,” Dr. Martin said in an interview. She chalked up the much-lower figure cited in the pediatric literature as relying on strict follow-up confirmation by rechallenge of the child with cow’s milk, a step often not taken by busy clinicians. Deferring formal confirmation also often means delayed reintroduction of cow’s milk into the infant’s diet, with restriction often continuing for perhaps a year following the index episode of CMPA. Although such unnecessarily long delays in milk reintroduction have largely been considered benign, recent findings from the Learning Early About Peanut Allergy (LEAP) trial that withholding peanut exposure can increase development of peanut allergies suggests that children also might receive long-term benefit from quicker reintroduction of milk in terms of better development of the immune system and microbiome, she said.
“If we rechallenged all these infants after 1 month, I think we’d find a CMPA rate closer to 3%. Leaving infants on a mild restricted diet for 12 months is a mistake,” she added.
The Gastrointestinal Microbiome & Proctocolitis (GMAP) study enrolled 700 infants seen at a single general practice pediatric practice in suburban Massachusetts at the time of their first well-baby visit, at a median age of 8 days. During 2 years of follow-up, the researchers collected stool specimens from the enrolled children at each of up to five scheduled visits during the first 4 months. They also kept track of when children received a CMPA diagnosis confirmed by at least one bloody stool.
Analysis of CMPA correlates showed that, among infants who developed it, 17% had not received any breastfeeding soon after birth, while among infants who did not develop CMPA, 8% did not undergo early breastfeeding. The incidence of CMPA was roughly similar among infants who received an early combination of breast milk and formula and in those who received exclusively breast milk during the first days of life, showing that even partial breastfeeding is better than no breastfeeding, Dr. Martin noted.
Her analysis also includes initial results from microbial assessment of the collected serial stool specimens from a subgroup of 24 infants who developed CMPA and 23 who did not, with a total of 223 total specimens evaluated. These studies showed that the infants who developed CMPA significantly lagged in their colonization with Bifidobacteria, had significantly higher colonization levels with Enterobacteriaceae, and that in infants who did develop CMPA, their gut level of Clostridia significantly increased as their proctocolitis resolved.
Dr. Martin had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Among 700 enrolled well infants, aged 5-163 days, 105 (15%) developed proctocolitis linked with cow’s milk.
Data source: Prospective observational study of 700 healthy neonates seen at a single U.S. pediatric practice.
Disclosures: Dr. Martin had no relevant financial disclosures.
Vaccination rates up in U.S. kindergartners in 2015, steady in 19- to 35-month-olds
Vaccination coverage for MMR and DTaP increased for children in kindergarten during the 2015-2016 school year, but remained steady for children aged 19-35 months in 2015, according to reports from the Centers for Disease Control and Prevention.
The median MMR vaccination rate for kindergartners in 2015 was 94.6%, up significantly from 92.6% in 2014. DTaP coverage also increased, rising from 92.4% to 94.2%. A total of 32 states saw an increase in MMR coverage in 2015, with 22 states reporting greater than 95% coverage. Only 3 states and the District of Columbia reported less than 90% coverage, down from 7 states and D.C. in 2014.
While the median vaccination rates were increased in 2015, the median exemption rate also increased by nearly 11% to 1.9% overall. This was caused in part by the addition of reports from Texas and Wyoming, neither of which reported the number of exemptions in 2014, the CDC investigators remarked.
In a second CDC report from Dr. Holly Hill and her associates based on data collected from the National Immunization Survey, the vaccination rate for children aged 19-35 months in 2015 did not increase significantly from the previous year (MMWR. 2016 Oct 6. doi: 10.15585/mmwr.mm639a4). The rate of children who received four or more doses of DTaP and at least one dose of MMR increased by 0.4 percentage points each from 84.2% to 84.6% and from 91.5% to 91.9%, respectively. The largest increase was seen in hepatitis A vaccine, where the rate of vaccination increased from 57.5% to 59.6%.
Healthy People 2020 goals for greater than 90% coverage for children aged 19-35 months were met for four vaccines in 2015: three or more doses of poliovirus vaccine, one or more doses of MMR, three or more doses of hepatitis B vaccine, and one or more doses of varicella vaccine. Vaccine coverage was lower in almost all cases for children living below the poverty level. The largest discrepancies were seen in rotavirus and varicella vaccines. The combined seven-vaccine series rate for children at or above the poverty line was 74.7%, and was 68.7% for children below the poverty line.
“Continued surveillance is needed to monitor coverage, locate pockets of susceptibility, and evaluate the impact of interventions designed to ensure that all children remain adequately protected against vaccine-preventable diseases,” Dr. Hill and her associates noted.
The CDC investigators had no relevant financial disclosures to report.
Vaccination coverage for MMR and DTaP increased for children in kindergarten during the 2015-2016 school year, but remained steady for children aged 19-35 months in 2015, according to reports from the Centers for Disease Control and Prevention.
The median MMR vaccination rate for kindergartners in 2015 was 94.6%, up significantly from 92.6% in 2014. DTaP coverage also increased, rising from 92.4% to 94.2%. A total of 32 states saw an increase in MMR coverage in 2015, with 22 states reporting greater than 95% coverage. Only 3 states and the District of Columbia reported less than 90% coverage, down from 7 states and D.C. in 2014.
While the median vaccination rates were increased in 2015, the median exemption rate also increased by nearly 11% to 1.9% overall. This was caused in part by the addition of reports from Texas and Wyoming, neither of which reported the number of exemptions in 2014, the CDC investigators remarked.
In a second CDC report from Dr. Holly Hill and her associates based on data collected from the National Immunization Survey, the vaccination rate for children aged 19-35 months in 2015 did not increase significantly from the previous year (MMWR. 2016 Oct 6. doi: 10.15585/mmwr.mm639a4). The rate of children who received four or more doses of DTaP and at least one dose of MMR increased by 0.4 percentage points each from 84.2% to 84.6% and from 91.5% to 91.9%, respectively. The largest increase was seen in hepatitis A vaccine, where the rate of vaccination increased from 57.5% to 59.6%.
Healthy People 2020 goals for greater than 90% coverage for children aged 19-35 months were met for four vaccines in 2015: three or more doses of poliovirus vaccine, one or more doses of MMR, three or more doses of hepatitis B vaccine, and one or more doses of varicella vaccine. Vaccine coverage was lower in almost all cases for children living below the poverty level. The largest discrepancies were seen in rotavirus and varicella vaccines. The combined seven-vaccine series rate for children at or above the poverty line was 74.7%, and was 68.7% for children below the poverty line.
“Continued surveillance is needed to monitor coverage, locate pockets of susceptibility, and evaluate the impact of interventions designed to ensure that all children remain adequately protected against vaccine-preventable diseases,” Dr. Hill and her associates noted.
The CDC investigators had no relevant financial disclosures to report.
Vaccination coverage for MMR and DTaP increased for children in kindergarten during the 2015-2016 school year, but remained steady for children aged 19-35 months in 2015, according to reports from the Centers for Disease Control and Prevention.
The median MMR vaccination rate for kindergartners in 2015 was 94.6%, up significantly from 92.6% in 2014. DTaP coverage also increased, rising from 92.4% to 94.2%. A total of 32 states saw an increase in MMR coverage in 2015, with 22 states reporting greater than 95% coverage. Only 3 states and the District of Columbia reported less than 90% coverage, down from 7 states and D.C. in 2014.
While the median vaccination rates were increased in 2015, the median exemption rate also increased by nearly 11% to 1.9% overall. This was caused in part by the addition of reports from Texas and Wyoming, neither of which reported the number of exemptions in 2014, the CDC investigators remarked.
In a second CDC report from Dr. Holly Hill and her associates based on data collected from the National Immunization Survey, the vaccination rate for children aged 19-35 months in 2015 did not increase significantly from the previous year (MMWR. 2016 Oct 6. doi: 10.15585/mmwr.mm639a4). The rate of children who received four or more doses of DTaP and at least one dose of MMR increased by 0.4 percentage points each from 84.2% to 84.6% and from 91.5% to 91.9%, respectively. The largest increase was seen in hepatitis A vaccine, where the rate of vaccination increased from 57.5% to 59.6%.
Healthy People 2020 goals for greater than 90% coverage for children aged 19-35 months were met for four vaccines in 2015: three or more doses of poliovirus vaccine, one or more doses of MMR, three or more doses of hepatitis B vaccine, and one or more doses of varicella vaccine. Vaccine coverage was lower in almost all cases for children living below the poverty level. The largest discrepancies were seen in rotavirus and varicella vaccines. The combined seven-vaccine series rate for children at or above the poverty line was 74.7%, and was 68.7% for children below the poverty line.
“Continued surveillance is needed to monitor coverage, locate pockets of susceptibility, and evaluate the impact of interventions designed to ensure that all children remain adequately protected against vaccine-preventable diseases,” Dr. Hill and her associates noted.
The CDC investigators had no relevant financial disclosures to report.
Silicone joint arthroplasty for RA shows sustained improvements at 7 years
Rheumatoid arthritis patients who underwent silicone metacarpophalangeal joint replacement maintained significant improvement in ulnar drift and extensor lag after 7 years of follow-up in the prospective, multicenter Silicone Arthroplasty in Rheumatoid Arthritis (SARA) study.
The silicone metacarpophalangeal joint arthroplasty (SMPA) group also showed significantly better metacarpophalangeal (MCP) joint arc of motion, as well as function, aesthetics, and satisfaction scores than did patients in the cohort who chose nonsurgical management.
The practice of replacing deformed MCP joints with a hinged silicone implant has been around for almost half a century, the investigators noted, but despite widespread use, there is a lack of high-quality surgical outcomes data for the procedure. The authors suggested that the scarcity of data may create a barrier for surgical referrals from rheumatologists and could account for the declining rate of surgical intervention for RA joint deformities.
The significant improvement in ulnar drift that occurred in patients who underwent SMPA versus no surgery remained even after adjustment for baseline severity, age, sex, and use of biologics. The adjustment was especially important because the nonsurgical group had better function at baseline, with significantly stronger grip and pinch strength, better Michigan Hand Questionnaire (MHQ) scores, and significantly better ulnar drift, extensor lag, and arc of motion than in the surgical group (Arthritis Care Res. 2016 Oct 1. doi: 10.1002/acr.23105).
The nonsurgical group largely maintained its baseline functional state during the 7-year follow-up period except for a decline in pinch strength.
“When the SMPA cohort was compared with the non-SMPA cohort, the covariate-adjusted difference showed significant benefits associated with SMPA hand outcome as measured by the MHQ function, aesthetics, and satisfaction scores, with no measures showing significantly better outcomes for the non-SMPA group,” the researchers wrote. “Although the average treatment effect estimate (ATT estimate) showed a decline over time for the average benefit from SMPA in those treated, the function score benefit as shown by the ATT estimate remained significant at year 5.”
Patients in the nonsurgical group were also given the option to crossover and receive surgery after 1 year, which two did. Eleven patients in the surgical group also decided to undergo surgery on their other hand.
Researchers saw one mild and three moderate implant-related adverse events during the study, including one patient who experienced ulnar deviation and needed a new joint replacement, one who dislocated the implant of the little finger a few weeks after insertion, and one who experienced sepsis in the joints 6 years after insertion and needed replacements for two implants. The fracture incidence of about 10% fits into the mid-range of previously reported fracture rates with this implant.
The study experienced significant losses to follow-up, particularly in the surgical group in which 7-year data were only available for 43% of participants in this group. The authors suggested this could have been because the surgical patients achieved their goals and were less inclined to the follow-up visits.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No conflicts of interest were declared.
Rheumatoid arthritis patients who underwent silicone metacarpophalangeal joint replacement maintained significant improvement in ulnar drift and extensor lag after 7 years of follow-up in the prospective, multicenter Silicone Arthroplasty in Rheumatoid Arthritis (SARA) study.
The silicone metacarpophalangeal joint arthroplasty (SMPA) group also showed significantly better metacarpophalangeal (MCP) joint arc of motion, as well as function, aesthetics, and satisfaction scores than did patients in the cohort who chose nonsurgical management.
The practice of replacing deformed MCP joints with a hinged silicone implant has been around for almost half a century, the investigators noted, but despite widespread use, there is a lack of high-quality surgical outcomes data for the procedure. The authors suggested that the scarcity of data may create a barrier for surgical referrals from rheumatologists and could account for the declining rate of surgical intervention for RA joint deformities.
The significant improvement in ulnar drift that occurred in patients who underwent SMPA versus no surgery remained even after adjustment for baseline severity, age, sex, and use of biologics. The adjustment was especially important because the nonsurgical group had better function at baseline, with significantly stronger grip and pinch strength, better Michigan Hand Questionnaire (MHQ) scores, and significantly better ulnar drift, extensor lag, and arc of motion than in the surgical group (Arthritis Care Res. 2016 Oct 1. doi: 10.1002/acr.23105).
The nonsurgical group largely maintained its baseline functional state during the 7-year follow-up period except for a decline in pinch strength.
“When the SMPA cohort was compared with the non-SMPA cohort, the covariate-adjusted difference showed significant benefits associated with SMPA hand outcome as measured by the MHQ function, aesthetics, and satisfaction scores, with no measures showing significantly better outcomes for the non-SMPA group,” the researchers wrote. “Although the average treatment effect estimate (ATT estimate) showed a decline over time for the average benefit from SMPA in those treated, the function score benefit as shown by the ATT estimate remained significant at year 5.”
Patients in the nonsurgical group were also given the option to crossover and receive surgery after 1 year, which two did. Eleven patients in the surgical group also decided to undergo surgery on their other hand.
Researchers saw one mild and three moderate implant-related adverse events during the study, including one patient who experienced ulnar deviation and needed a new joint replacement, one who dislocated the implant of the little finger a few weeks after insertion, and one who experienced sepsis in the joints 6 years after insertion and needed replacements for two implants. The fracture incidence of about 10% fits into the mid-range of previously reported fracture rates with this implant.
The study experienced significant losses to follow-up, particularly in the surgical group in which 7-year data were only available for 43% of participants in this group. The authors suggested this could have been because the surgical patients achieved their goals and were less inclined to the follow-up visits.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No conflicts of interest were declared.
Rheumatoid arthritis patients who underwent silicone metacarpophalangeal joint replacement maintained significant improvement in ulnar drift and extensor lag after 7 years of follow-up in the prospective, multicenter Silicone Arthroplasty in Rheumatoid Arthritis (SARA) study.
The silicone metacarpophalangeal joint arthroplasty (SMPA) group also showed significantly better metacarpophalangeal (MCP) joint arc of motion, as well as function, aesthetics, and satisfaction scores than did patients in the cohort who chose nonsurgical management.
The practice of replacing deformed MCP joints with a hinged silicone implant has been around for almost half a century, the investigators noted, but despite widespread use, there is a lack of high-quality surgical outcomes data for the procedure. The authors suggested that the scarcity of data may create a barrier for surgical referrals from rheumatologists and could account for the declining rate of surgical intervention for RA joint deformities.
The significant improvement in ulnar drift that occurred in patients who underwent SMPA versus no surgery remained even after adjustment for baseline severity, age, sex, and use of biologics. The adjustment was especially important because the nonsurgical group had better function at baseline, with significantly stronger grip and pinch strength, better Michigan Hand Questionnaire (MHQ) scores, and significantly better ulnar drift, extensor lag, and arc of motion than in the surgical group (Arthritis Care Res. 2016 Oct 1. doi: 10.1002/acr.23105).
The nonsurgical group largely maintained its baseline functional state during the 7-year follow-up period except for a decline in pinch strength.
“When the SMPA cohort was compared with the non-SMPA cohort, the covariate-adjusted difference showed significant benefits associated with SMPA hand outcome as measured by the MHQ function, aesthetics, and satisfaction scores, with no measures showing significantly better outcomes for the non-SMPA group,” the researchers wrote. “Although the average treatment effect estimate (ATT estimate) showed a decline over time for the average benefit from SMPA in those treated, the function score benefit as shown by the ATT estimate remained significant at year 5.”
Patients in the nonsurgical group were also given the option to crossover and receive surgery after 1 year, which two did. Eleven patients in the surgical group also decided to undergo surgery on their other hand.
Researchers saw one mild and three moderate implant-related adverse events during the study, including one patient who experienced ulnar deviation and needed a new joint replacement, one who dislocated the implant of the little finger a few weeks after insertion, and one who experienced sepsis in the joints 6 years after insertion and needed replacements for two implants. The fracture incidence of about 10% fits into the mid-range of previously reported fracture rates with this implant.
The study experienced significant losses to follow-up, particularly in the surgical group in which 7-year data were only available for 43% of participants in this group. The authors suggested this could have been because the surgical patients achieved their goals and were less inclined to the follow-up visits.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No conflicts of interest were declared.
Key clinical point:
Major finding: Patients who elected to undergo silicone MCP joint replacement showed significant improvements in ulnar drift and extensor lag, as well as in function, aesthetics, and satisfaction scores at 7 years after the procedure.
Data source: Cohort study of 170 patients with rheumatoid arthritis–related severe deformity at the metacarpophalangeal joints.
Disclosures: The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No conflicts of interest were declared.
Study finds picosecond laser, with diffractive lens array, effective wrinkle treatment
An industry-funded study suggests that picosecond lasers, touted for their effectiveness at tattoo removal, can safely and effectively treat perioral and periocular wrinkles.
Six months after treatment with picosecond 755-nm alexandrite laser with a diffractive lens array, subjects reported high levels of satisfaction and blinded physicians rated the treated wrinkles as improved or much improved over the same time period (Lasers Surg Med. 2016 Sep 29. doi: 10.1002/lsm.22577).
The laser “is very useful for treating fine lines and other visible signs of premature photoaging,” said study coauthor David H. McDaniel, MD, a dermatologist in Virginia Beach, Va., and codirector of the Hampton University Skin of Color Research Institute. “These types of lasers have great potential benefit for patients and minimal risk of any significant adverse events.”
According to Dr. McDaniel, picosecond 755-nm alexandrite lasers are commonly used to treat wrinkles, acne scars, and pigment dyschromia, while picosecond 532- and 1,064-nm lasers are used to remove tattoos and treat some pigment dyschromia.
He and his coinvestigators sought to “better define the parameters that are uniquely contributing to wrinkle reduction and dermal matrix remodeling and also define the actual clinical benefits and treatment protocol,” Dr. McDaniel said in an interview.
At four 1-month intervals, they used a picosecond 755 nm alexandrite laser with diffractive lens array to treat the full faces of 40 women with wrinkles caused by photodamage. The subjects were all healthy white nonsmokers, whose average age was 58 years.
At 6 months following treatment, the average Fitzpatrick wrinkle score improved, dropping from 5.48 to 3.47 (P less than .05). Also at 6 months, blinded physician evaluators rated the average degree of improvement from baseline as “moderate” (for fine lines) “less than mild” (for erythema), “high moderate” (for dyschromia) and “mid moderate” (for global improvement).
The evaluators successfully identified posttreatment photos in 82% of cases. As for patients, 36.8% said they were extremely satisfied and 57.9% said they were satisfied at 6 months. Adverse effects were reported as mild: One patient reported 2 days of erythema, another reported 4 days of edema, and one experienced bruising. Serial punch biopsies obtained at 6 months after the last treatment in six patients revealed increases in dermal collagen and thicker, denser elastin fibers.
The picosecond 755- nm alexandrite laser produces “very little thermal effect, which reduces both treatment discomfort as well as the risk of adverse events,” Dr. McDaniel said in an interview. “It typically leads to shorter recovery time socially, as erythema is very mild and quite transient.”
He noted that the laser can be used in conjunction with other lasers. “Some of the other gold standard fractional lasers are still used in our practice, and they still deliver good results when properly indicated,” he said. “For example, we may use – or even combine with the picosecond laser – a fractional erbium laser to reach deeper into the dermis for severe acne scarring or for deep wrinkles. Or we may use a fractional thulium laser for people with early actinic keratosis or also combine it with the picosecond laser.
Cynosure, a maker of picosecond lasers, funded the study and provided a discounted price for the laser. Dr. McDaniel and another author report serving as consultants, researchers and speakers for Cynosure.
An industry-funded study suggests that picosecond lasers, touted for their effectiveness at tattoo removal, can safely and effectively treat perioral and periocular wrinkles.
Six months after treatment with picosecond 755-nm alexandrite laser with a diffractive lens array, subjects reported high levels of satisfaction and blinded physicians rated the treated wrinkles as improved or much improved over the same time period (Lasers Surg Med. 2016 Sep 29. doi: 10.1002/lsm.22577).
The laser “is very useful for treating fine lines and other visible signs of premature photoaging,” said study coauthor David H. McDaniel, MD, a dermatologist in Virginia Beach, Va., and codirector of the Hampton University Skin of Color Research Institute. “These types of lasers have great potential benefit for patients and minimal risk of any significant adverse events.”
According to Dr. McDaniel, picosecond 755-nm alexandrite lasers are commonly used to treat wrinkles, acne scars, and pigment dyschromia, while picosecond 532- and 1,064-nm lasers are used to remove tattoos and treat some pigment dyschromia.
He and his coinvestigators sought to “better define the parameters that are uniquely contributing to wrinkle reduction and dermal matrix remodeling and also define the actual clinical benefits and treatment protocol,” Dr. McDaniel said in an interview.
At four 1-month intervals, they used a picosecond 755 nm alexandrite laser with diffractive lens array to treat the full faces of 40 women with wrinkles caused by photodamage. The subjects were all healthy white nonsmokers, whose average age was 58 years.
At 6 months following treatment, the average Fitzpatrick wrinkle score improved, dropping from 5.48 to 3.47 (P less than .05). Also at 6 months, blinded physician evaluators rated the average degree of improvement from baseline as “moderate” (for fine lines) “less than mild” (for erythema), “high moderate” (for dyschromia) and “mid moderate” (for global improvement).
The evaluators successfully identified posttreatment photos in 82% of cases. As for patients, 36.8% said they were extremely satisfied and 57.9% said they were satisfied at 6 months. Adverse effects were reported as mild: One patient reported 2 days of erythema, another reported 4 days of edema, and one experienced bruising. Serial punch biopsies obtained at 6 months after the last treatment in six patients revealed increases in dermal collagen and thicker, denser elastin fibers.
The picosecond 755- nm alexandrite laser produces “very little thermal effect, which reduces both treatment discomfort as well as the risk of adverse events,” Dr. McDaniel said in an interview. “It typically leads to shorter recovery time socially, as erythema is very mild and quite transient.”
He noted that the laser can be used in conjunction with other lasers. “Some of the other gold standard fractional lasers are still used in our practice, and they still deliver good results when properly indicated,” he said. “For example, we may use – or even combine with the picosecond laser – a fractional erbium laser to reach deeper into the dermis for severe acne scarring or for deep wrinkles. Or we may use a fractional thulium laser for people with early actinic keratosis or also combine it with the picosecond laser.
Cynosure, a maker of picosecond lasers, funded the study and provided a discounted price for the laser. Dr. McDaniel and another author report serving as consultants, researchers and speakers for Cynosure.
An industry-funded study suggests that picosecond lasers, touted for their effectiveness at tattoo removal, can safely and effectively treat perioral and periocular wrinkles.
Six months after treatment with picosecond 755-nm alexandrite laser with a diffractive lens array, subjects reported high levels of satisfaction and blinded physicians rated the treated wrinkles as improved or much improved over the same time period (Lasers Surg Med. 2016 Sep 29. doi: 10.1002/lsm.22577).
The laser “is very useful for treating fine lines and other visible signs of premature photoaging,” said study coauthor David H. McDaniel, MD, a dermatologist in Virginia Beach, Va., and codirector of the Hampton University Skin of Color Research Institute. “These types of lasers have great potential benefit for patients and minimal risk of any significant adverse events.”
According to Dr. McDaniel, picosecond 755-nm alexandrite lasers are commonly used to treat wrinkles, acne scars, and pigment dyschromia, while picosecond 532- and 1,064-nm lasers are used to remove tattoos and treat some pigment dyschromia.
He and his coinvestigators sought to “better define the parameters that are uniquely contributing to wrinkle reduction and dermal matrix remodeling and also define the actual clinical benefits and treatment protocol,” Dr. McDaniel said in an interview.
At four 1-month intervals, they used a picosecond 755 nm alexandrite laser with diffractive lens array to treat the full faces of 40 women with wrinkles caused by photodamage. The subjects were all healthy white nonsmokers, whose average age was 58 years.
At 6 months following treatment, the average Fitzpatrick wrinkle score improved, dropping from 5.48 to 3.47 (P less than .05). Also at 6 months, blinded physician evaluators rated the average degree of improvement from baseline as “moderate” (for fine lines) “less than mild” (for erythema), “high moderate” (for dyschromia) and “mid moderate” (for global improvement).
The evaluators successfully identified posttreatment photos in 82% of cases. As for patients, 36.8% said they were extremely satisfied and 57.9% said they were satisfied at 6 months. Adverse effects were reported as mild: One patient reported 2 days of erythema, another reported 4 days of edema, and one experienced bruising. Serial punch biopsies obtained at 6 months after the last treatment in six patients revealed increases in dermal collagen and thicker, denser elastin fibers.
The picosecond 755- nm alexandrite laser produces “very little thermal effect, which reduces both treatment discomfort as well as the risk of adverse events,” Dr. McDaniel said in an interview. “It typically leads to shorter recovery time socially, as erythema is very mild and quite transient.”
He noted that the laser can be used in conjunction with other lasers. “Some of the other gold standard fractional lasers are still used in our practice, and they still deliver good results when properly indicated,” he said. “For example, we may use – or even combine with the picosecond laser – a fractional erbium laser to reach deeper into the dermis for severe acne scarring or for deep wrinkles. Or we may use a fractional thulium laser for people with early actinic keratosis or also combine it with the picosecond laser.
Cynosure, a maker of picosecond lasers, funded the study and provided a discounted price for the laser. Dr. McDaniel and another author report serving as consultants, researchers and speakers for Cynosure.
FROM LASERS IN SURGERY AND MEDICINE
Key clinical point: Wrinkle treatment via picosecond 755-nm alexandrite laser with a diffractive lens array appears to be safe and effective.
Major finding: Six months after the last treatment, 36.8% of patients were extremely satisfied and 57.9% were satisfied with the results, with minor, transient adverse effects. Blinded physician evaluators reported “mid moderate” global improvement.
Data source: A prospective, blinded study of 40 healthy white women, nonsmokers, average age 58 (range: 47-64), who underwent four full-face treatments via laser at 1-month intervals.
Disclosures: Cynosure, a maker of picosecond lasers, funded the study and provided a discounted price for the laser. Dr. McDaniel and another author report serving as consultants, researchers, and speakers for Cynosure.
More restrictive hemoglobin threshold recommended for transfusion
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
FROM JAMA
Key clinical point: A restrictive threshold for red blood cell transfusion, in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL, is now recommended for most patients.
Major finding: A more restrictive threshold for red blood cell transfusion is not associated with an increased risk of mortality or other adverse outcomes from transfusion.
Data source: Updated guidelines from the AABB (formerly known as the American Association of Blood Banks).
Disclosures: Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies including CSL and Fresenius Kabi, but no other conflicts of interest were declared.
Conservative oxygen therapy in the ICU reduces mortality
A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.
The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.
Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).
“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).
Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”
In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO2] between 94% and 98%) or conventional oxygen therapy (allowance of PaO2 values up to 150 mm Hg or SpO2 values between 97% and 100%) on an open-label basis.
The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.
Results of modified intent-to-treat analyses showed that daily time-weighted PaO2 averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO2, 102 vs. 87 mm Hg; P less than .001).
The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).
The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).
Lengths of ICU stay and hospital stay did not differ between the two groups.
One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.
The reduction in mortality seen with conservative oxygen therapy in the Oxygen-ICU trial was “striking,” according to editorialist Dr. Niall D. Ferguson. However, “it is likely that to some extent, this trial has overestimated the true treatment effect of conservative oxygen therapy,” he cautions, given baseline imbalances between groups, early stopping based in part on an unplanned interim analysis, and the small number of deaths. The editorialist noted that the study was underpowered and criticized its use of a modified intent-to-treat analysis.
The trial’s findings contrast with those of a pilot study conducted by the ANZICS clinical trials group that did not find better outcomes with use of lower oxygen targets, according to Dr. Ferguson. However, in that trial, both arms had lower target and actual PaO2 levels. Thus, the optimal clinical approach remains uncertain.
“Until the results of further trials addressing this issue are available, there appears to be little downside in the careful titration and monitoring of supplemental oxygen in the ICU to achieve physiologically normal levels of PaO2 while avoiding potentially dangerous hyperoxia,” he concludes.
Dr. Ferguson disclosed that he has no relevant conflicts of interest.
Niall D. Ferguson, MD, MSc, is with the Interdepartmental Division of Critical Care Medicine and Departments of Medicine and Physiology, University of Toronto; the Institute of Health Policy, Management, & Evaluation, University of Toronto; the Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital; and the Toronto General Research Institute.
The reduction in mortality seen with conservative oxygen therapy in the Oxygen-ICU trial was “striking,” according to editorialist Dr. Niall D. Ferguson. However, “it is likely that to some extent, this trial has overestimated the true treatment effect of conservative oxygen therapy,” he cautions, given baseline imbalances between groups, early stopping based in part on an unplanned interim analysis, and the small number of deaths. The editorialist noted that the study was underpowered and criticized its use of a modified intent-to-treat analysis.
The trial’s findings contrast with those of a pilot study conducted by the ANZICS clinical trials group that did not find better outcomes with use of lower oxygen targets, according to Dr. Ferguson. However, in that trial, both arms had lower target and actual PaO2 levels. Thus, the optimal clinical approach remains uncertain.
“Until the results of further trials addressing this issue are available, there appears to be little downside in the careful titration and monitoring of supplemental oxygen in the ICU to achieve physiologically normal levels of PaO2 while avoiding potentially dangerous hyperoxia,” he concludes.
Dr. Ferguson disclosed that he has no relevant conflicts of interest.
Niall D. Ferguson, MD, MSc, is with the Interdepartmental Division of Critical Care Medicine and Departments of Medicine and Physiology, University of Toronto; the Institute of Health Policy, Management, & Evaluation, University of Toronto; the Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital; and the Toronto General Research Institute.
The reduction in mortality seen with conservative oxygen therapy in the Oxygen-ICU trial was “striking,” according to editorialist Dr. Niall D. Ferguson. However, “it is likely that to some extent, this trial has overestimated the true treatment effect of conservative oxygen therapy,” he cautions, given baseline imbalances between groups, early stopping based in part on an unplanned interim analysis, and the small number of deaths. The editorialist noted that the study was underpowered and criticized its use of a modified intent-to-treat analysis.
The trial’s findings contrast with those of a pilot study conducted by the ANZICS clinical trials group that did not find better outcomes with use of lower oxygen targets, according to Dr. Ferguson. However, in that trial, both arms had lower target and actual PaO2 levels. Thus, the optimal clinical approach remains uncertain.
“Until the results of further trials addressing this issue are available, there appears to be little downside in the careful titration and monitoring of supplemental oxygen in the ICU to achieve physiologically normal levels of PaO2 while avoiding potentially dangerous hyperoxia,” he concludes.
Dr. Ferguson disclosed that he has no relevant conflicts of interest.
Niall D. Ferguson, MD, MSc, is with the Interdepartmental Division of Critical Care Medicine and Departments of Medicine and Physiology, University of Toronto; the Institute of Health Policy, Management, & Evaluation, University of Toronto; the Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital; and the Toronto General Research Institute.
A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.
The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.
Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).
“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).
Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”
In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO2] between 94% and 98%) or conventional oxygen therapy (allowance of PaO2 values up to 150 mm Hg or SpO2 values between 97% and 100%) on an open-label basis.
The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.
Results of modified intent-to-treat analyses showed that daily time-weighted PaO2 averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO2, 102 vs. 87 mm Hg; P less than .001).
The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).
The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).
Lengths of ICU stay and hospital stay did not differ between the two groups.
One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.
A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.
The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.
Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).
“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).
Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”
In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO2] between 94% and 98%) or conventional oxygen therapy (allowance of PaO2 values up to 150 mm Hg or SpO2 values between 97% and 100%) on an open-label basis.
The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.
Results of modified intent-to-treat analyses showed that daily time-weighted PaO2 averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO2, 102 vs. 87 mm Hg; P less than .001).
The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).
The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).
Lengths of ICU stay and hospital stay did not differ between the two groups.
One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.
FROM ESICM CONGRESS 2016
Key clinical point:
Major finding: Relative to conventional therapy, conservative therapy was associated with a lower ICU mortality (absolute risk reduction, 0.086; P = .01).
Data source: A randomized controlled trial among 434 patients admitted to a medical-surgical ICU and expected to stay at least 72 hours (Oxygen-ICU trial).
Disclosures: One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia. Dr. Ferguson disclosed that he has no relevant conflicts of interest.
Guselkumab achieves highest-ever response rates in psoriasis
VIENNA – The investigational interleukin-23 inhibitor guselkumab decisively outperformed adalimumab in a head-to-head comparison for treatment of moderate or severe plaque psoriasis in the pivotal VOYAGE 1 study, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
VOYAGE 1 was a 48-week, multicenter, international phase III trial in which 837 patients were randomized 2:2:1 to guselkumab, adalimumab (Humira), or placebo, with the placebo group switched to guselkumab at 16 weeks. Roughly three-quarters of patients had moderate psoriasis, the rest had severe disease. One in five had previously been treated with biologic agents; the only biologic disallowed was adalimumab.
The primary endpoints required by regulatory agencies involved efficacy comparisons between guselkumab and placebo at 16 weeks. Those results were a foregone conclusion. Far more arresting were the prespecified secondary endpoints comparing guselkumab to adalimumab at 24 and 48 weeks.
“These are very exciting results. We’re seeing efficacy in this trial that has not ever been seen before in a phase III study,” said Dr. Blauvelt, president of the Oregon Medical Research Center in Portland.
Take, for example, an efficacy yardstick dermatologists are quite familiar with: the PASI 75 response, defined as at least a 75% improvement from baseline in the Psoriasis Area Severity Index score, which averaged 22 at baseline in this trial. The PASI 75 rate in guselkumab-treated patients was 91.2% at 16 weeks, remained at 91.2% at 24 weeks, and was 87.8% at week 48.
“To my knowledge this is the highest PASI 75 response rate that’s been seen in a phase III study of any biologic in psoriasis,” the dermatologist said.
The PASI 75 rates with adalimumab, a tumor necrosis factor–alpha blocker widely prescribed for psoriasis, were markedly lower, although just a few years ago they would have been considered stratospheric: 73.1% at 16 weeks, 72.2% at 24 weeks, and 62.6% at 48 weeks.
The same pattern held for PASI 90, PASI 100, Investigator’s Global Assessment (IGA), and quality-of-life measures. 
“There is a clear early separation of guselkumab from adalimumab, sustained over time, curves staying flat, responses not dropping off,” Dr. Blauvelt said in summary.
Guselkumab was dosed at 100 mg subcutaneously at weeks 0 and 4, then every 8 weeks thereafter. Adalimumab was dosed subcutaneously at 80 mg at week 0, 40 mg at week 1, and then 40 mg every other week.
The two coprimary outcomes at week 16 in VOYAGE 1 were the guselkumab and placebo groups’ rates of clear or almost clear skin as defined by an IGA score of 0 or 1, and their PASI 90 response rates. An IGA of 0 or 1 was achieved by 85.1% of the guselkumab group compared with 6.9% on placebo. The week-16 PASI 90 rates – a “high bar” Dr. Blauvelt noted – were 73.3% and 2.9%, respectively.
“Clearly we’re now in an era where PASI 90 is the new PASI 75,” said session cochair Lajos Kemény, MD, professor and chairman of the department of dermatology and allergology at the University of Szeged, Hungary.
Guselkumab is a human monoclonal antibody directed at the p-19 subunit of interleukin-23, thereby preventing the inflammatory cytokine from binding to its receptor. In contrast, ustekinumab (Stelara) blocks both IL-23 and IL-12. Given that ustekinumab has established an excellent long-term safety record in PSOLAR, the Psoriasis Longitudinal Assessment and Registry, it stands to reason that guselkumab should have a favorable safety profile, too, since it targets only one of the two cytokines (J Drugs Dermatol. 2015 Jul;14[7]:706-14). And this indeed proved to be the case through 48 weeks in VOYAGE 1, according to Dr. Blauvelt.
Infections treated with antibiotics occurred in 6.1% of the guselkumab group, 7.2% of patients on adalimumab, and 7.5% on placebo. Mild to moderate injection site reactions occurred in 2.4% of patients on guselkumab and 7.5% on adalimumab. One patient on each of the biologics experienced an acute MI. Two malignancies occurred, both in the guselkumab group. One was prostate cancer, the other was a case of male breast cancer in a patient with a breast mass present at enrollment.
Results of two additional pivotal phase III trials, VOYAGE 2 and NAVIGATE, will be presented at future meetings. NAVIGATE is looking specifically at guselkumab’s performance in psoriasis patients with an inadequate response to ustekinumab.
“Those results look promising. It appears that patients who didn’t clear adequately on ustekinumab do well on guselkumab,” Dr. Blauvelt said in response to an audience question.
A phase II study of guselkumab in treating moderate to severe psoriatic arthritis is ongoing.
VOYAGE 1 was funded by Janssen, which is developing guselkumab. Dr. Blauvelt reported receiving research grants from and serving as a scientific consultant to Janssen and numerous other pharmaceutical companies.
VIENNA – The investigational interleukin-23 inhibitor guselkumab decisively outperformed adalimumab in a head-to-head comparison for treatment of moderate or severe plaque psoriasis in the pivotal VOYAGE 1 study, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
VOYAGE 1 was a 48-week, multicenter, international phase III trial in which 837 patients were randomized 2:2:1 to guselkumab, adalimumab (Humira), or placebo, with the placebo group switched to guselkumab at 16 weeks. Roughly three-quarters of patients had moderate psoriasis, the rest had severe disease. One in five had previously been treated with biologic agents; the only biologic disallowed was adalimumab.
The primary endpoints required by regulatory agencies involved efficacy comparisons between guselkumab and placebo at 16 weeks. Those results were a foregone conclusion. Far more arresting were the prespecified secondary endpoints comparing guselkumab to adalimumab at 24 and 48 weeks.
“These are very exciting results. We’re seeing efficacy in this trial that has not ever been seen before in a phase III study,” said Dr. Blauvelt, president of the Oregon Medical Research Center in Portland.
Take, for example, an efficacy yardstick dermatologists are quite familiar with: the PASI 75 response, defined as at least a 75% improvement from baseline in the Psoriasis Area Severity Index score, which averaged 22 at baseline in this trial. The PASI 75 rate in guselkumab-treated patients was 91.2% at 16 weeks, remained at 91.2% at 24 weeks, and was 87.8% at week 48.
“To my knowledge this is the highest PASI 75 response rate that’s been seen in a phase III study of any biologic in psoriasis,” the dermatologist said.
The PASI 75 rates with adalimumab, a tumor necrosis factor–alpha blocker widely prescribed for psoriasis, were markedly lower, although just a few years ago they would have been considered stratospheric: 73.1% at 16 weeks, 72.2% at 24 weeks, and 62.6% at 48 weeks.
The same pattern held for PASI 90, PASI 100, Investigator’s Global Assessment (IGA), and quality-of-life measures.
“There is a clear early separation of guselkumab from adalimumab, sustained over time, curves staying flat, responses not dropping off,” Dr. Blauvelt said in summary.
Guselkumab was dosed at 100 mg subcutaneously at weeks 0 and 4, then every 8 weeks thereafter. Adalimumab was dosed subcutaneously at 80 mg at week 0, 40 mg at week 1, and then 40 mg every other week.
The two coprimary outcomes at week 16 in VOYAGE 1 were the guselkumab and placebo groups’ rates of clear or almost clear skin as defined by an IGA score of 0 or 1, and their PASI 90 response rates. An IGA of 0 or 1 was achieved by 85.1% of the guselkumab group compared with 6.9% on placebo. The week-16 PASI 90 rates – a “high bar” Dr. Blauvelt noted – were 73.3% and 2.9%, respectively.
“Clearly we’re now in an era where PASI 90 is the new PASI 75,” said session cochair Lajos Kemény, MD, professor and chairman of the department of dermatology and allergology at the University of Szeged, Hungary.
Guselkumab is a human monoclonal antibody directed at the p-19 subunit of interleukin-23, thereby preventing the inflammatory cytokine from binding to its receptor. In contrast, ustekinumab (Stelara) blocks both IL-23 and IL-12. Given that ustekinumab has established an excellent long-term safety record in PSOLAR, the Psoriasis Longitudinal Assessment and Registry, it stands to reason that guselkumab should have a favorable safety profile, too, since it targets only one of the two cytokines (J Drugs Dermatol. 2015 Jul;14[7]:706-14). And this indeed proved to be the case through 48 weeks in VOYAGE 1, according to Dr. Blauvelt.
Infections treated with antibiotics occurred in 6.1% of the guselkumab group, 7.2% of patients on adalimumab, and 7.5% on placebo. Mild to moderate injection site reactions occurred in 2.4% of patients on guselkumab and 7.5% on adalimumab. One patient on each of the biologics experienced an acute MI. Two malignancies occurred, both in the guselkumab group. One was prostate cancer, the other was a case of male breast cancer in a patient with a breast mass present at enrollment.
Results of two additional pivotal phase III trials, VOYAGE 2 and NAVIGATE, will be presented at future meetings. NAVIGATE is looking specifically at guselkumab’s performance in psoriasis patients with an inadequate response to ustekinumab.
“Those results look promising. It appears that patients who didn’t clear adequately on ustekinumab do well on guselkumab,” Dr. Blauvelt said in response to an audience question.
A phase II study of guselkumab in treating moderate to severe psoriatic arthritis is ongoing.
VOYAGE 1 was funded by Janssen, which is developing guselkumab. Dr. Blauvelt reported receiving research grants from and serving as a scientific consultant to Janssen and numerous other pharmaceutical companies.
VIENNA – The investigational interleukin-23 inhibitor guselkumab decisively outperformed adalimumab in a head-to-head comparison for treatment of moderate or severe plaque psoriasis in the pivotal VOYAGE 1 study, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
VOYAGE 1 was a 48-week, multicenter, international phase III trial in which 837 patients were randomized 2:2:1 to guselkumab, adalimumab (Humira), or placebo, with the placebo group switched to guselkumab at 16 weeks. Roughly three-quarters of patients had moderate psoriasis, the rest had severe disease. One in five had previously been treated with biologic agents; the only biologic disallowed was adalimumab.
The primary endpoints required by regulatory agencies involved efficacy comparisons between guselkumab and placebo at 16 weeks. Those results were a foregone conclusion. Far more arresting were the prespecified secondary endpoints comparing guselkumab to adalimumab at 24 and 48 weeks.
“These are very exciting results. We’re seeing efficacy in this trial that has not ever been seen before in a phase III study,” said Dr. Blauvelt, president of the Oregon Medical Research Center in Portland.
Take, for example, an efficacy yardstick dermatologists are quite familiar with: the PASI 75 response, defined as at least a 75% improvement from baseline in the Psoriasis Area Severity Index score, which averaged 22 at baseline in this trial. The PASI 75 rate in guselkumab-treated patients was 91.2% at 16 weeks, remained at 91.2% at 24 weeks, and was 87.8% at week 48.
“To my knowledge this is the highest PASI 75 response rate that’s been seen in a phase III study of any biologic in psoriasis,” the dermatologist said.
The PASI 75 rates with adalimumab, a tumor necrosis factor–alpha blocker widely prescribed for psoriasis, were markedly lower, although just a few years ago they would have been considered stratospheric: 73.1% at 16 weeks, 72.2% at 24 weeks, and 62.6% at 48 weeks.
The same pattern held for PASI 90, PASI 100, Investigator’s Global Assessment (IGA), and quality-of-life measures.
“There is a clear early separation of guselkumab from adalimumab, sustained over time, curves staying flat, responses not dropping off,” Dr. Blauvelt said in summary.
Guselkumab was dosed at 100 mg subcutaneously at weeks 0 and 4, then every 8 weeks thereafter. Adalimumab was dosed subcutaneously at 80 mg at week 0, 40 mg at week 1, and then 40 mg every other week.
The two coprimary outcomes at week 16 in VOYAGE 1 were the guselkumab and placebo groups’ rates of clear or almost clear skin as defined by an IGA score of 0 or 1, and their PASI 90 response rates. An IGA of 0 or 1 was achieved by 85.1% of the guselkumab group compared with 6.9% on placebo. The week-16 PASI 90 rates – a “high bar” Dr. Blauvelt noted – were 73.3% and 2.9%, respectively.
“Clearly we’re now in an era where PASI 90 is the new PASI 75,” said session cochair Lajos Kemény, MD, professor and chairman of the department of dermatology and allergology at the University of Szeged, Hungary.
Guselkumab is a human monoclonal antibody directed at the p-19 subunit of interleukin-23, thereby preventing the inflammatory cytokine from binding to its receptor. In contrast, ustekinumab (Stelara) blocks both IL-23 and IL-12. Given that ustekinumab has established an excellent long-term safety record in PSOLAR, the Psoriasis Longitudinal Assessment and Registry, it stands to reason that guselkumab should have a favorable safety profile, too, since it targets only one of the two cytokines (J Drugs Dermatol. 2015 Jul;14[7]:706-14). And this indeed proved to be the case through 48 weeks in VOYAGE 1, according to Dr. Blauvelt.
Infections treated with antibiotics occurred in 6.1% of the guselkumab group, 7.2% of patients on adalimumab, and 7.5% on placebo. Mild to moderate injection site reactions occurred in 2.4% of patients on guselkumab and 7.5% on adalimumab. One patient on each of the biologics experienced an acute MI. Two malignancies occurred, both in the guselkumab group. One was prostate cancer, the other was a case of male breast cancer in a patient with a breast mass present at enrollment.
Results of two additional pivotal phase III trials, VOYAGE 2 and NAVIGATE, will be presented at future meetings. NAVIGATE is looking specifically at guselkumab’s performance in psoriasis patients with an inadequate response to ustekinumab.
“Those results look promising. It appears that patients who didn’t clear adequately on ustekinumab do well on guselkumab,” Dr. Blauvelt said in response to an audience question.
A phase II study of guselkumab in treating moderate to severe psoriatic arthritis is ongoing.
VOYAGE 1 was funded by Janssen, which is developing guselkumab. Dr. Blauvelt reported receiving research grants from and serving as a scientific consultant to Janssen and numerous other pharmaceutical companies.
Key clinical point:
Major finding: The PASI 90 response rate at 24 weeks was 80% in psoriasis patients on guselkumab compared with 53% in those on adalimumab.
Data source: A randomized, multinational, 48-week, pivotal phase III clinical trial involving 837 psoriasis patients assigned to guselkumab, adalimumab, or placebo.
Disclosures: The VOYAGE 1 trial was funded by Janssen, which is developing guselkumab. The study presenter reported receiving research grants from and serving as a scientific consultant to Janssen and numerous other pharmaceutical companies.