The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

Rheumatoid arthritis does not get transmitted through blood transfusions, according to findings from a large retrospective study of blood transfusions in Denmark and Sweden.

Two separate analyses showed that the risk of developing RA among transfusion recipients was not correlated to the presence of RA in the blood donor.
There had been concern about risks of transfusion because of RA’s long preclinical phase, in which RA pathogenesis factors circulate in the periphery and could potentially be transmitted in a transfusion. Mouse models had suggested that anti–citrullinated peptide/protein antibodies could spark or worsen arthritis, and RA fibroblast-like synoviocyte cell precursors could spread RA between joints.

Two previous studies, based on self-reported history of blood transfusion, reached the opposite conclusion regarding the risk of RA transmission.
The latest findings, published online in Annals of the Rheumatic Diseases, involved an analysis of data from the Danish–Swedish population-based research donations and transfusions database (SCANDAT2). In one model, they looked at 938,942 blood donors, 2,412 of whom were diagnosed with RA during the follow-up period. The researchers then analyzed data from 13,369 subjects who had been exposed to blood from donors who went on to develop RA, and compared them to 139,470 recipients who received blood from donors who did not develop RA. There was no statistically significant correlation between risk of RA among recipients by RA status of the donors, RA serotype in the donors, donor age at RA diagnosis, or elapsed time between donation and RA diagnosis.

In a second analysis, the researchers looked for RA clusters among recipients who might have received blood from a donor with RA. They found no association between RA risk for a given recipient based on whether other recipients from the same donor had gone on to develop RA.
“In light of the study’s strengths, including low likelihood of confounding and large study size ensuring meaningful statistical power, we believe the possibility of RA transmission is unlikely to be clinically relevant,” the authors wrote.

The study was funded by the Danish Rheumatism Association, the Odense University Hospital PhD Fund and Fund for clinical research, the Nordic Cancer Union, the Swedish Foundation for Strategic Research, the Swedish Research Council, and ALF funds. One author reported receiving grants from AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Samsung, and UCB.

SOURCE: Just SA et al. Ann Rheum Dis. 2018 Mar 1. doi: 10.1136/annrheumdis-2017-212844

Rheumatoid arthritis does not get transmitted through blood transfusions, according to findings from a large retrospective study of blood transfusions in Denmark and Sweden.

Two separate analyses showed that the risk of developing RA among transfusion recipients was not correlated to the presence of RA in the blood donor.
There had been concern about risks of transfusion because of RA’s long preclinical phase, in which RA pathogenesis factors circulate in the periphery and could potentially be transmitted in a transfusion. Mouse models had suggested that anti–citrullinated peptide/protein antibodies could spark or worsen arthritis, and RA fibroblast-like synoviocyte cell precursors could spread RA between joints.

Two previous studies, based on self-reported history of blood transfusion, reached the opposite conclusion regarding the risk of RA transmission.
The latest findings, published online in Annals of the Rheumatic Diseases, involved an analysis of data from the Danish–Swedish population-based research donations and transfusions database (SCANDAT2). In one model, they looked at 938,942 blood donors, 2,412 of whom were diagnosed with RA during the follow-up period. The researchers then analyzed data from 13,369 subjects who had been exposed to blood from donors who went on to develop RA, and compared them to 139,470 recipients who received blood from donors who did not develop RA. There was no statistically significant correlation between risk of RA among recipients by RA status of the donors, RA serotype in the donors, donor age at RA diagnosis, or elapsed time between donation and RA diagnosis.

In a second analysis, the researchers looked for RA clusters among recipients who might have received blood from a donor with RA. They found no association between RA risk for a given recipient based on whether other recipients from the same donor had gone on to develop RA.
“In light of the study’s strengths, including low likelihood of confounding and large study size ensuring meaningful statistical power, we believe the possibility of RA transmission is unlikely to be clinically relevant,” the authors wrote.

The study was funded by the Danish Rheumatism Association, the Odense University Hospital PhD Fund and Fund for clinical research, the Nordic Cancer Union, the Swedish Foundation for Strategic Research, the Swedish Research Council, and ALF funds. One author reported receiving grants from AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Samsung, and UCB.

SOURCE: Just SA et al. Ann Rheum Dis. 2018 Mar 1. doi: 10.1136/annrheumdis-2017-212844

Rheumatoid arthritis does not get transmitted through blood transfusions, according to findings from a large retrospective study of blood transfusions in Denmark and Sweden.

Two separate analyses showed that the risk of developing RA among transfusion recipients was not correlated to the presence of RA in the blood donor.
There had been concern about risks of transfusion because of RA’s long preclinical phase, in which RA pathogenesis factors circulate in the periphery and could potentially be transmitted in a transfusion. Mouse models had suggested that anti–citrullinated peptide/protein antibodies could spark or worsen arthritis, and RA fibroblast-like synoviocyte cell precursors could spread RA between joints.

Two previous studies, based on self-reported history of blood transfusion, reached the opposite conclusion regarding the risk of RA transmission.
The latest findings, published online in Annals of the Rheumatic Diseases, involved an analysis of data from the Danish–Swedish population-based research donations and transfusions database (SCANDAT2). In one model, they looked at 938,942 blood donors, 2,412 of whom were diagnosed with RA during the follow-up period. The researchers then analyzed data from 13,369 subjects who had been exposed to blood from donors who went on to develop RA, and compared them to 139,470 recipients who received blood from donors who did not develop RA. There was no statistically significant correlation between risk of RA among recipients by RA status of the donors, RA serotype in the donors, donor age at RA diagnosis, or elapsed time between donation and RA diagnosis.

In a second analysis, the researchers looked for RA clusters among recipients who might have received blood from a donor with RA. They found no association between RA risk for a given recipient based on whether other recipients from the same donor had gone on to develop RA.
“In light of the study’s strengths, including low likelihood of confounding and large study size ensuring meaningful statistical power, we believe the possibility of RA transmission is unlikely to be clinically relevant,” the authors wrote.

The study was funded by the Danish Rheumatism Association, the Odense University Hospital PhD Fund and Fund for clinical research, the Nordic Cancer Union, the Swedish Foundation for Strategic Research, the Swedish Research Council, and ALF funds. One author reported receiving grants from AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Samsung, and UCB.

SOURCE: Just SA et al. Ann Rheum Dis. 2018 Mar 1. doi: 10.1136/annrheumdis-2017-212844

Patients treated with opioids for moderate to severe chronic back pain or knee or hip osteoarthritis pain saw no significant improvement when results were compared with treatment using acetaminophen or nonsteroidal anti-inflammatory drugs in the randomized SPACE study.

These findings may help restructure how physicians treat patients with chronic pain in order to decrease the risk of opioid addiction in a population that is particularly susceptible.

©Rocky89/Thinkstock

In the 12-month SPACE (Strategies for Prescribing Analgesics Comparative Effectiveness) trial published March 6 in JAMA, the investigators reported randomizing a total of 240 patients to treatment with immediate-release opioids (morphine, oxycodone, or hydrocodone/acetaminophen) or acetaminophen or nonsteroidal anti-inflammatory drugs. The patients came from the Minneapolis VA system between June 2013 and December 2015. Patients in the opioid group were on average 57 years old, while those in the nonopioid group had an average age of 60 years. Men comprised 87% of all patients, and both groups were predominantly white (86%-88%) with chronic back pain (65%). The investigators excluded patients with physiological opioid dependence from ongoing opioid use.

Patients taking opioids saw no significant improvement in the primary outcome of pain-related function on the seven-item Brief Pain Inventory (BPI) interference scale over those taking nonopioids at the end of the 12-month period (P = .58), according to Dr. Krebs and her fellow investigators.

The main secondary outcome of pain intensity using the four-item BPI severity scale improved significantly more among the nonopioid group, which reported an average score of 3.5, compared with 4.0 in the opioid group (P = .03). However, the small difference of 0.5 is less than the minimal clinically important difference of 1.0, according to the investigators.

Anxiety control was the only secondary outcome measure that was significantly better among patients in the opioid group, which was unsurprising to the investigators. “This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” they wrote.

The investigators were uncertain about the significance of this small difference because overall anxiety levels were low, with 9% of patients reporting moderate severity anxiety symptoms at baseline.

Patients in the opioid group took a mean of 1.7 analgesics during the study period, compared with 3.8 in the nonopioid group. In the nonopioid group, the mean number of months that nonopioid analgesics were prescribed ranged from 2.6 for acetaminophen to 5.9 with oral NSAIDs. In this group, tramadol was prescribed to no more than 11% of patients during any particular month and was dispensed for a mean of 0.4 months overall.

Patients in the opioid group took opioids for a mean of 8.1 months, with all other analgesics taken for a mean of 0.4 months or less. The authors noted that in “each 90-day follow-up period, fewer than 15% of patients in the opioid group had a mean dispensed dosage of 50 morphine-equivalent mg/day or more.” Patients could be titrated up to a maximum daily dosage of 100 morphine-equivalent mg/day.

Patients prescribed opioids were significantly more likely to report medication-related symptoms, and while misuse was not significantly higher in the opioid group, the investigators said that “Overall, opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms.”

Further studies will need to include a more diverse population, they noted.

The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.

[email protected]

SOURCE: Krebs EE et al. JAMA. 2018 Mar 6;319(9):872-82

Patients treated with opioids for moderate to severe chronic back pain or knee or hip osteoarthritis pain saw no significant improvement when results were compared with treatment using acetaminophen or nonsteroidal anti-inflammatory drugs in the randomized SPACE study.

These findings may help restructure how physicians treat patients with chronic pain in order to decrease the risk of opioid addiction in a population that is particularly susceptible.

©Rocky89/Thinkstock

In the 12-month SPACE (Strategies for Prescribing Analgesics Comparative Effectiveness) trial published March 6 in JAMA, the investigators reported randomizing a total of 240 patients to treatment with immediate-release opioids (morphine, oxycodone, or hydrocodone/acetaminophen) or acetaminophen or nonsteroidal anti-inflammatory drugs. The patients came from the Minneapolis VA system between June 2013 and December 2015. Patients in the opioid group were on average 57 years old, while those in the nonopioid group had an average age of 60 years. Men comprised 87% of all patients, and both groups were predominantly white (86%-88%) with chronic back pain (65%). The investigators excluded patients with physiological opioid dependence from ongoing opioid use.

Patients taking opioids saw no significant improvement in the primary outcome of pain-related function on the seven-item Brief Pain Inventory (BPI) interference scale over those taking nonopioids at the end of the 12-month period (P = .58), according to Dr. Krebs and her fellow investigators.

The main secondary outcome of pain intensity using the four-item BPI severity scale improved significantly more among the nonopioid group, which reported an average score of 3.5, compared with 4.0 in the opioid group (P = .03). However, the small difference of 0.5 is less than the minimal clinically important difference of 1.0, according to the investigators.

Anxiety control was the only secondary outcome measure that was significantly better among patients in the opioid group, which was unsurprising to the investigators. “This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” they wrote.

The investigators were uncertain about the significance of this small difference because overall anxiety levels were low, with 9% of patients reporting moderate severity anxiety symptoms at baseline.

Patients in the opioid group took a mean of 1.7 analgesics during the study period, compared with 3.8 in the nonopioid group. In the nonopioid group, the mean number of months that nonopioid analgesics were prescribed ranged from 2.6 for acetaminophen to 5.9 with oral NSAIDs. In this group, tramadol was prescribed to no more than 11% of patients during any particular month and was dispensed for a mean of 0.4 months overall.

Patients in the opioid group took opioids for a mean of 8.1 months, with all other analgesics taken for a mean of 0.4 months or less. The authors noted that in “each 90-day follow-up period, fewer than 15% of patients in the opioid group had a mean dispensed dosage of 50 morphine-equivalent mg/day or more.” Patients could be titrated up to a maximum daily dosage of 100 morphine-equivalent mg/day.

Patients prescribed opioids were significantly more likely to report medication-related symptoms, and while misuse was not significantly higher in the opioid group, the investigators said that “Overall, opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms.”

Further studies will need to include a more diverse population, they noted.

The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.

[email protected]

SOURCE: Krebs EE et al. JAMA. 2018 Mar 6;319(9):872-82

Patients treated with opioids for moderate to severe chronic back pain or knee or hip osteoarthritis pain saw no significant improvement when results were compared with treatment using acetaminophen or nonsteroidal anti-inflammatory drugs in the randomized SPACE study.

These findings may help restructure how physicians treat patients with chronic pain in order to decrease the risk of opioid addiction in a population that is particularly susceptible.

©Rocky89/Thinkstock

In the 12-month SPACE (Strategies for Prescribing Analgesics Comparative Effectiveness) trial published March 6 in JAMA, the investigators reported randomizing a total of 240 patients to treatment with immediate-release opioids (morphine, oxycodone, or hydrocodone/acetaminophen) or acetaminophen or nonsteroidal anti-inflammatory drugs. The patients came from the Minneapolis VA system between June 2013 and December 2015. Patients in the opioid group were on average 57 years old, while those in the nonopioid group had an average age of 60 years. Men comprised 87% of all patients, and both groups were predominantly white (86%-88%) with chronic back pain (65%). The investigators excluded patients with physiological opioid dependence from ongoing opioid use.

Patients taking opioids saw no significant improvement in the primary outcome of pain-related function on the seven-item Brief Pain Inventory (BPI) interference scale over those taking nonopioids at the end of the 12-month period (P = .58), according to Dr. Krebs and her fellow investigators.

The main secondary outcome of pain intensity using the four-item BPI severity scale improved significantly more among the nonopioid group, which reported an average score of 3.5, compared with 4.0 in the opioid group (P = .03). However, the small difference of 0.5 is less than the minimal clinically important difference of 1.0, according to the investigators.

Anxiety control was the only secondary outcome measure that was significantly better among patients in the opioid group, which was unsurprising to the investigators. “This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” they wrote.

The investigators were uncertain about the significance of this small difference because overall anxiety levels were low, with 9% of patients reporting moderate severity anxiety symptoms at baseline.

Patients in the opioid group took a mean of 1.7 analgesics during the study period, compared with 3.8 in the nonopioid group. In the nonopioid group, the mean number of months that nonopioid analgesics were prescribed ranged from 2.6 for acetaminophen to 5.9 with oral NSAIDs. In this group, tramadol was prescribed to no more than 11% of patients during any particular month and was dispensed for a mean of 0.4 months overall.

Patients in the opioid group took opioids for a mean of 8.1 months, with all other analgesics taken for a mean of 0.4 months or less. The authors noted that in “each 90-day follow-up period, fewer than 15% of patients in the opioid group had a mean dispensed dosage of 50 morphine-equivalent mg/day or more.” Patients could be titrated up to a maximum daily dosage of 100 morphine-equivalent mg/day.

Patients prescribed opioids were significantly more likely to report medication-related symptoms, and while misuse was not significantly higher in the opioid group, the investigators said that “Overall, opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms.”

Further studies will need to include a more diverse population, they noted.

The study was funded by an award from the U.S. Department of Veterans Affairs Health Services Research and Development Service. The investigators reported no relevant disclosures.

[email protected]

SOURCE: Krebs EE et al. JAMA. 2018 Mar 6;319(9):872-82

The Food and Drug Administration Feb. 6 approved ibalizumab-uiyk (Trogarzo) to treat multidrug-resistant HIV (MDR HIV) in adults, the agency announced.

“While most patients living with HIV can be successfully treated using a combination of two or more antiretroviral drugs, a small percentage of patients who have taken many HIV drugs in the past have multidrug-resistant HIV, limiting their treatment options and putting them at a high risk of HIV-related complications and progression to death,” Jeff Murray, MD, deputy director of the FDA Division of Antiviral Products, said in a statement. “Trogarzo is the first drug in a new class of antiretroviral medications that can provide significant benefit to patients who have run out of HIV treatment options. New treatment options may be able to improve their outcomes.”

Ibalizumab-uiyk, an HIV-1 inhibitor, was approved based on the results of a phase 3, single-arm study of 40 patients with MDR-HIV-1 who had high virus levels in their blood despite antiretroviral treatment. To be included in the study, all patients had to have received highly active antiretroviral therapy for at least 6 months prior. Over 24 weeks, patients were monitored to compare previous, infective treatments with ibalizumab-uiyk in conjunction with an optimized background regimen of antiretroviral drugs.

The majority of patients showed a significant decrease in their HIV-RNA levels 1 week after ibalizumab-uiyk was added to their previous drug regimens. After 24 weeks of treatment with ibalizumab-uiyk, in conjunction with other antiretroviral drugs, 43% of patients achieved HIV RNA suppression.

Ibalizumab-uiyk was granted Fast Track, Priority Review, and Breakthrough Therapy designations from the FDA. In addition, it was granted Orphan Drug designation, a program that encourages the development of drugs to treat rare diseases.

Ibalizumab-uiyk is administered once every 14 days in conjunction with other retroviral medications.

The most common adverse reactions to ibalizumab-uiyk were diarrhea, dizziness, nausea, and rash. Less common, and more severe, reactions were changes in the immune system.
Ibalizumab-uiyk will be marketed by Taimed Biologics USA.

[email protected]

The Food and Drug Administration Feb. 6 approved ibalizumab-uiyk (Trogarzo) to treat multidrug-resistant HIV (MDR HIV) in adults, the agency announced.

“While most patients living with HIV can be successfully treated using a combination of two or more antiretroviral drugs, a small percentage of patients who have taken many HIV drugs in the past have multidrug-resistant HIV, limiting their treatment options and putting them at a high risk of HIV-related complications and progression to death,” Jeff Murray, MD, deputy director of the FDA Division of Antiviral Products, said in a statement. “Trogarzo is the first drug in a new class of antiretroviral medications that can provide significant benefit to patients who have run out of HIV treatment options. New treatment options may be able to improve their outcomes.”

Ibalizumab-uiyk, an HIV-1 inhibitor, was approved based on the results of a phase 3, single-arm study of 40 patients with MDR-HIV-1 who had high virus levels in their blood despite antiretroviral treatment. To be included in the study, all patients had to have received highly active antiretroviral therapy for at least 6 months prior. Over 24 weeks, patients were monitored to compare previous, infective treatments with ibalizumab-uiyk in conjunction with an optimized background regimen of antiretroviral drugs.

The majority of patients showed a significant decrease in their HIV-RNA levels 1 week after ibalizumab-uiyk was added to their previous drug regimens. After 24 weeks of treatment with ibalizumab-uiyk, in conjunction with other antiretroviral drugs, 43% of patients achieved HIV RNA suppression.

Ibalizumab-uiyk was granted Fast Track, Priority Review, and Breakthrough Therapy designations from the FDA. In addition, it was granted Orphan Drug designation, a program that encourages the development of drugs to treat rare diseases.

Ibalizumab-uiyk is administered once every 14 days in conjunction with other retroviral medications.

The most common adverse reactions to ibalizumab-uiyk were diarrhea, dizziness, nausea, and rash. Less common, and more severe, reactions were changes in the immune system.
Ibalizumab-uiyk will be marketed by Taimed Biologics USA.

[email protected]

The Food and Drug Administration Feb. 6 approved ibalizumab-uiyk (Trogarzo) to treat multidrug-resistant HIV (MDR HIV) in adults, the agency announced.

“While most patients living with HIV can be successfully treated using a combination of two or more antiretroviral drugs, a small percentage of patients who have taken many HIV drugs in the past have multidrug-resistant HIV, limiting their treatment options and putting them at a high risk of HIV-related complications and progression to death,” Jeff Murray, MD, deputy director of the FDA Division of Antiviral Products, said in a statement. “Trogarzo is the first drug in a new class of antiretroviral medications that can provide significant benefit to patients who have run out of HIV treatment options. New treatment options may be able to improve their outcomes.”

Ibalizumab-uiyk, an HIV-1 inhibitor, was approved based on the results of a phase 3, single-arm study of 40 patients with MDR-HIV-1 who had high virus levels in their blood despite antiretroviral treatment. To be included in the study, all patients had to have received highly active antiretroviral therapy for at least 6 months prior. Over 24 weeks, patients were monitored to compare previous, infective treatments with ibalizumab-uiyk in conjunction with an optimized background regimen of antiretroviral drugs.

The majority of patients showed a significant decrease in their HIV-RNA levels 1 week after ibalizumab-uiyk was added to their previous drug regimens. After 24 weeks of treatment with ibalizumab-uiyk, in conjunction with other antiretroviral drugs, 43% of patients achieved HIV RNA suppression.

Ibalizumab-uiyk was granted Fast Track, Priority Review, and Breakthrough Therapy designations from the FDA. In addition, it was granted Orphan Drug designation, a program that encourages the development of drugs to treat rare diseases.

Ibalizumab-uiyk is administered once every 14 days in conjunction with other retroviral medications.

The most common adverse reactions to ibalizumab-uiyk were diarrhea, dizziness, nausea, and rash. Less common, and more severe, reactions were changes in the immune system.
Ibalizumab-uiyk will be marketed by Taimed Biologics USA.

[email protected]

Outpatient influenza-like illness activity continues to drop, but pediatric deaths for 2017-2018 are already higher than either of the last two entire seasons, according to the Centers for Disease and Prevention.

An additional 17 influenza-like illness-related (ILI) pediatric deaths were reported during the week ending Feb. 24, eight of which occurred in previous weeks. That brings the total to 114 for the 2017-2018 flu season so far, compared with 110 for the entire 2016-2017 season and 93 for the 2015-2016 season, the CDC reported Mar. 2.

The proportion of outpatient visits for ILI took another big drop, falling to 5.0% for the week, which was down from 6.4% the previous week and the seasonal high of 7.4% the 2 weeks before that (Feb. 10 and Feb. 3), CDC data show.

Flu-related hospitalizations, however, continued to rise to new highs, as the cumulative rate hit 81.7 per 100,000 population. In 2014-2015, the season with the highest number of hospitalizations since the CDC started keeping track, the cumulative rate for the corresponding week was 55.9 per 100,000, according to the CDC’s Fluview website.

The map of state-reported ILI activity shows that 25 states are at level 10 on the CDC’s 1-10 scale, which is down from 33 the week before. Eight other states and the District of Columbia were in the “high” range with activity at levels 8 and 9 for the week ending Feb. 24, the CDC said.

[email protected]

Outpatient influenza-like illness activity continues to drop, but pediatric deaths for 2017-2018 are already higher than either of the last two entire seasons, according to the Centers for Disease and Prevention.

An additional 17 influenza-like illness-related (ILI) pediatric deaths were reported during the week ending Feb. 24, eight of which occurred in previous weeks. That brings the total to 114 for the 2017-2018 flu season so far, compared with 110 for the entire 2016-2017 season and 93 for the 2015-2016 season, the CDC reported Mar. 2.

The proportion of outpatient visits for ILI took another big drop, falling to 5.0% for the week, which was down from 6.4% the previous week and the seasonal high of 7.4% the 2 weeks before that (Feb. 10 and Feb. 3), CDC data show.

Flu-related hospitalizations, however, continued to rise to new highs, as the cumulative rate hit 81.7 per 100,000 population. In 2014-2015, the season with the highest number of hospitalizations since the CDC started keeping track, the cumulative rate for the corresponding week was 55.9 per 100,000, according to the CDC’s Fluview website.

The map of state-reported ILI activity shows that 25 states are at level 10 on the CDC’s 1-10 scale, which is down from 33 the week before. Eight other states and the District of Columbia were in the “high” range with activity at levels 8 and 9 for the week ending Feb. 24, the CDC said.

[email protected]

Outpatient influenza-like illness activity continues to drop, but pediatric deaths for 2017-2018 are already higher than either of the last two entire seasons, according to the Centers for Disease and Prevention.

An additional 17 influenza-like illness-related (ILI) pediatric deaths were reported during the week ending Feb. 24, eight of which occurred in previous weeks. That brings the total to 114 for the 2017-2018 flu season so far, compared with 110 for the entire 2016-2017 season and 93 for the 2015-2016 season, the CDC reported Mar. 2.

The proportion of outpatient visits for ILI took another big drop, falling to 5.0% for the week, which was down from 6.4% the previous week and the seasonal high of 7.4% the 2 weeks before that (Feb. 10 and Feb. 3), CDC data show.

Flu-related hospitalizations, however, continued to rise to new highs, as the cumulative rate hit 81.7 per 100,000 population. In 2014-2015, the season with the highest number of hospitalizations since the CDC started keeping track, the cumulative rate for the corresponding week was 55.9 per 100,000, according to the CDC’s Fluview website.

The map of state-reported ILI activity shows that 25 states are at level 10 on the CDC’s 1-10 scale, which is down from 33 the week before. Eight other states and the District of Columbia were in the “high” range with activity at levels 8 and 9 for the week ending Feb. 24, the CDC said.

[email protected]

Opioid-related deaths in emergency departments increased by approximately 30% across all regions of the United States between 2016 and 2017, according to the Centers for Disease Control and Prevention.

Analysis of 91 million ED visits from the CDC’s National Syndromic Surveillance Program and Enhanced State Opioid Overdose Surveillance database found significant increases in opioid overdose deaths in 16 states, reaching as high as 109% in Wisconsin and 106% in Delaware, CDC officials said during a press briefing.

“We are currently seeing the highest drug overdose death rate ever recorded in the United States, driven by prescription opioids and by illicit opioids such as heroin and illicitly manufactured fentanyl,” said Anne Schuchat, MD, acting CDC director. “In 2016, there were more than 63,000 drug overdose deaths, and more than 42,000 of those deaths involved an opioid.”

Of the 91 million visits, a total of 261,755 were suspected of opioid overdoses across both databases.

The greatest increase was seen in the Midwest region (69.7%), followed by the West (40.3%), Northeast (21.3%), Southwest (20.2%), and Southeast (14%).

Death rates rose across all demographics, regardless of sex or age.

While Delaware recorded some of the highest increases in deaths, Massachusetts, New Hampshire, and Rhode Island decreased, although not within statistical significance.

“These decreases may possibly be related to implementation of interventions, including expansion of access to medication-assisted treatment,” said Dr. Schuchat. “The decrease in Kentucky during this period of time may reflect some fluctuations in drug supply.”​

To combat the rise in deaths, the CDC is encouraging an increase in naloxone distribution and training for first responders and community members.

The agency also recommends that local health departments begin using ED data to alert local communities when opioid-related deaths rise.

“This is a very difficult and fast-moving epidemic, and there are no easy solutions,” Dr. Schuchat said. [These data send] “a wake-up call about the need to improve what happens when patients leave the emergency department; all of us working together, government, public health, the medical community, law enforcement, and community members themselves can help fight this epidemic and save lives.”

[email protected]

SOURCE: Vivolo-Kantor AM et al. MMWR Morb Mortal Wkly Rep. 6 Mar 2018. doi: 10.15585/mmwr.mm6709e1.

Opioid-related deaths in emergency departments increased by approximately 30% across all regions of the United States between 2016 and 2017, according to the Centers for Disease Control and Prevention.

Analysis of 91 million ED visits from the CDC’s National Syndromic Surveillance Program and Enhanced State Opioid Overdose Surveillance database found significant increases in opioid overdose deaths in 16 states, reaching as high as 109% in Wisconsin and 106% in Delaware, CDC officials said during a press briefing.

“We are currently seeing the highest drug overdose death rate ever recorded in the United States, driven by prescription opioids and by illicit opioids such as heroin and illicitly manufactured fentanyl,” said Anne Schuchat, MD, acting CDC director. “In 2016, there were more than 63,000 drug overdose deaths, and more than 42,000 of those deaths involved an opioid.”

Of the 91 million visits, a total of 261,755 were suspected of opioid overdoses across both databases.

The greatest increase was seen in the Midwest region (69.7%), followed by the West (40.3%), Northeast (21.3%), Southwest (20.2%), and Southeast (14%).

Death rates rose across all demographics, regardless of sex or age.

While Delaware recorded some of the highest increases in deaths, Massachusetts, New Hampshire, and Rhode Island decreased, although not within statistical significance.

“These decreases may possibly be related to implementation of interventions, including expansion of access to medication-assisted treatment,” said Dr. Schuchat. “The decrease in Kentucky during this period of time may reflect some fluctuations in drug supply.”​

To combat the rise in deaths, the CDC is encouraging an increase in naloxone distribution and training for first responders and community members.

The agency also recommends that local health departments begin using ED data to alert local communities when opioid-related deaths rise.

“This is a very difficult and fast-moving epidemic, and there are no easy solutions,” Dr. Schuchat said. [These data send] “a wake-up call about the need to improve what happens when patients leave the emergency department; all of us working together, government, public health, the medical community, law enforcement, and community members themselves can help fight this epidemic and save lives.”

[email protected]

SOURCE: Vivolo-Kantor AM et al. MMWR Morb Mortal Wkly Rep. 6 Mar 2018. doi: 10.15585/mmwr.mm6709e1.

Opioid-related deaths in emergency departments increased by approximately 30% across all regions of the United States between 2016 and 2017, according to the Centers for Disease Control and Prevention.

Analysis of 91 million ED visits from the CDC’s National Syndromic Surveillance Program and Enhanced State Opioid Overdose Surveillance database found significant increases in opioid overdose deaths in 16 states, reaching as high as 109% in Wisconsin and 106% in Delaware, CDC officials said during a press briefing.

“We are currently seeing the highest drug overdose death rate ever recorded in the United States, driven by prescription opioids and by illicit opioids such as heroin and illicitly manufactured fentanyl,” said Anne Schuchat, MD, acting CDC director. “In 2016, there were more than 63,000 drug overdose deaths, and more than 42,000 of those deaths involved an opioid.”

Of the 91 million visits, a total of 261,755 were suspected of opioid overdoses across both databases.

The greatest increase was seen in the Midwest region (69.7%), followed by the West (40.3%), Northeast (21.3%), Southwest (20.2%), and Southeast (14%).

Death rates rose across all demographics, regardless of sex or age.

While Delaware recorded some of the highest increases in deaths, Massachusetts, New Hampshire, and Rhode Island decreased, although not within statistical significance.

“These decreases may possibly be related to implementation of interventions, including expansion of access to medication-assisted treatment,” said Dr. Schuchat. “The decrease in Kentucky during this period of time may reflect some fluctuations in drug supply.”​

To combat the rise in deaths, the CDC is encouraging an increase in naloxone distribution and training for first responders and community members.

The agency also recommends that local health departments begin using ED data to alert local communities when opioid-related deaths rise.

“This is a very difficult and fast-moving epidemic, and there are no easy solutions,” Dr. Schuchat said. [These data send] “a wake-up call about the need to improve what happens when patients leave the emergency department; all of us working together, government, public health, the medical community, law enforcement, and community members themselves can help fight this epidemic and save lives.”

[email protected]

SOURCE: Vivolo-Kantor AM et al. MMWR Morb Mortal Wkly Rep. 6 Mar 2018. doi: 10.15585/mmwr.mm6709e1.

There was no significant difference in vaccine antigen exposure through the first 23 months of life between children with non–vaccine-targeted infections and controls between 24 and 47 months of age, according to results published March 6 in JAMA.

This was determined in a nested, matched case-control study of 193 infection cases and 751 controls, in whom estimated mean cumulative vaccine antigen exposure was 240.6 for cases of non–vaccine-targeted infections, and 242.9 for controls, reported Jason M. Glanz, PhD, of Kaiser Permanente Colorado, Denver, and his coauthors. The between-group difference was –2.3 (P = .55), a nonsignificant difference.

Using data from the Centers for Disease Control and Prevention-funded Vaccine Safety Datalink (VSD), the investigators identified children born between Jan. 1, 2003, and Sep. 31, 2013. Exclusion criteria were not having at least two well-child visits before the first birthday, medical contraindications to vaccination, or receiving vaccines not recommended by the Advisory Committee on Immunization Practices. Eligible children were followed through age 47 months or until disenrollment from their health care organization, the authors said.

ICD-9 and ICD-10 codes were used to identify non–vaccine-targeted infections, including upper and lower respiratory infections, gastrointestinal infections, and other viral and bacterial infections from ages 24to 47 months. A medical record review was performed to confirm case status. Cases were included only if it was confirmed that the infection occurred, that it was an incident outcome, that the outcome was the primary reason for the medical visit, that the outcome occurred in the inpatient or emergency department setting, and that there was no evidence that the child was diagnosed as having a vaccine preventable disease (VPD) on the same day as the infection. Controls did not have a VPD or record of a non–vaccine-targeted infection prior to the index date, Dr. Glanz and his colleagues said.

Antigen exposure was measured as the number of immunogenic proteins and polysaccharides in each vaccine, and was estimated from birth through age 23 months in both groups. Cumulative antigen exposure was estimated by adding the number of antigens in each non–vaccine-targeted infection and controls.

Estimated mean cumulative vaccine antigen exposure was 240.6 for cases of non–vaccine-targeted infections, and 242.9 for controls, the authors reported. The matched odds ratio (mOR) for estimated cumulative antigen exposure through age 23 months was not significant in children with infections, compared with controls (mOR = 0.94; 95% confidence interval, 0.84-1.07). The estimated maximum single-day antigen exposure was not significantly associated with non–vaccine-targeted infection (mOR = 1.07; 95% CI, 0.81-1.41).

The findings of this study “did not reveal any beneficial or detrimental associations with estimated cumulative vaccine antigen exposure in young children with non–vaccine-targeted infections in ED and inpatient settings,” wrote Dr. Glanz and coauthors. In addition, the study “did not find evidence that multiple vaccine exposure was associated with the risk for non-targeted infectious diseases.”

The CDC funded the study. The authors reported receiving contracts, grants, and other funding from the CDC.

SOURCE: Glanz JM et al. JAMA. 2018;319(9):906-13.

There was no significant difference in vaccine antigen exposure through the first 23 months of life between children with non–vaccine-targeted infections and controls between 24 and 47 months of age, according to results published March 6 in JAMA.

This was determined in a nested, matched case-control study of 193 infection cases and 751 controls, in whom estimated mean cumulative vaccine antigen exposure was 240.6 for cases of non–vaccine-targeted infections, and 242.9 for controls, reported Jason M. Glanz, PhD, of Kaiser Permanente Colorado, Denver, and his coauthors. The between-group difference was –2.3 (P = .55), a nonsignificant difference.

Using data from the Centers for Disease Control and Prevention-funded Vaccine Safety Datalink (VSD), the investigators identified children born between Jan. 1, 2003, and Sep. 31, 2013. Exclusion criteria were not having at least two well-child visits before the first birthday, medical contraindications to vaccination, or receiving vaccines not recommended by the Advisory Committee on Immunization Practices. Eligible children were followed through age 47 months or until disenrollment from their health care organization, the authors said.

ICD-9 and ICD-10 codes were used to identify non–vaccine-targeted infections, including upper and lower respiratory infections, gastrointestinal infections, and other viral and bacterial infections from ages 24to 47 months. A medical record review was performed to confirm case status. Cases were included only if it was confirmed that the infection occurred, that it was an incident outcome, that the outcome was the primary reason for the medical visit, that the outcome occurred in the inpatient or emergency department setting, and that there was no evidence that the child was diagnosed as having a vaccine preventable disease (VPD) on the same day as the infection. Controls did not have a VPD or record of a non–vaccine-targeted infection prior to the index date, Dr. Glanz and his colleagues said.

Antigen exposure was measured as the number of immunogenic proteins and polysaccharides in each vaccine, and was estimated from birth through age 23 months in both groups. Cumulative antigen exposure was estimated by adding the number of antigens in each non–vaccine-targeted infection and controls.

Estimated mean cumulative vaccine antigen exposure was 240.6 for cases of non–vaccine-targeted infections, and 242.9 for controls, the authors reported. The matched odds ratio (mOR) for estimated cumulative antigen exposure through age 23 months was not significant in children with infections, compared with controls (mOR = 0.94; 95% confidence interval, 0.84-1.07). The estimated maximum single-day antigen exposure was not significantly associated with non–vaccine-targeted infection (mOR = 1.07; 95% CI, 0.81-1.41).

The findings of this study “did not reveal any beneficial or detrimental associations with estimated cumulative vaccine antigen exposure in young children with non–vaccine-targeted infections in ED and inpatient settings,” wrote Dr. Glanz and coauthors. In addition, the study “did not find evidence that multiple vaccine exposure was associated with the risk for non-targeted infectious diseases.”

The CDC funded the study. The authors reported receiving contracts, grants, and other funding from the CDC.

SOURCE: Glanz JM et al. JAMA. 2018;319(9):906-13.

There was no significant difference in vaccine antigen exposure through the first 23 months of life between children with non–vaccine-targeted infections and controls between 24 and 47 months of age, according to results published March 6 in JAMA.

This was determined in a nested, matched case-control study of 193 infection cases and 751 controls, in whom estimated mean cumulative vaccine antigen exposure was 240.6 for cases of non–vaccine-targeted infections, and 242.9 for controls, reported Jason M. Glanz, PhD, of Kaiser Permanente Colorado, Denver, and his coauthors. The between-group difference was –2.3 (P = .55), a nonsignificant difference.

Using data from the Centers for Disease Control and Prevention-funded Vaccine Safety Datalink (VSD), the investigators identified children born between Jan. 1, 2003, and Sep. 31, 2013. Exclusion criteria were not having at least two well-child visits before the first birthday, medical contraindications to vaccination, or receiving vaccines not recommended by the Advisory Committee on Immunization Practices. Eligible children were followed through age 47 months or until disenrollment from their health care organization, the authors said.

ICD-9 and ICD-10 codes were used to identify non–vaccine-targeted infections, including upper and lower respiratory infections, gastrointestinal infections, and other viral and bacterial infections from ages 24to 47 months. A medical record review was performed to confirm case status. Cases were included only if it was confirmed that the infection occurred, that it was an incident outcome, that the outcome was the primary reason for the medical visit, that the outcome occurred in the inpatient or emergency department setting, and that there was no evidence that the child was diagnosed as having a vaccine preventable disease (VPD) on the same day as the infection. Controls did not have a VPD or record of a non–vaccine-targeted infection prior to the index date, Dr. Glanz and his colleagues said.

Antigen exposure was measured as the number of immunogenic proteins and polysaccharides in each vaccine, and was estimated from birth through age 23 months in both groups. Cumulative antigen exposure was estimated by adding the number of antigens in each non–vaccine-targeted infection and controls.

Estimated mean cumulative vaccine antigen exposure was 240.6 for cases of non–vaccine-targeted infections, and 242.9 for controls, the authors reported. The matched odds ratio (mOR) for estimated cumulative antigen exposure through age 23 months was not significant in children with infections, compared with controls (mOR = 0.94; 95% confidence interval, 0.84-1.07). The estimated maximum single-day antigen exposure was not significantly associated with non–vaccine-targeted infection (mOR = 1.07; 95% CI, 0.81-1.41).

The findings of this study “did not reveal any beneficial or detrimental associations with estimated cumulative vaccine antigen exposure in young children with non–vaccine-targeted infections in ED and inpatient settings,” wrote Dr. Glanz and coauthors. In addition, the study “did not find evidence that multiple vaccine exposure was associated with the risk for non-targeted infectious diseases.”

The CDC funded the study. The authors reported receiving contracts, grants, and other funding from the CDC.

SOURCE: Glanz JM et al. JAMA. 2018;319(9):906-13.

The Food and Drug Administration has authorized the first direct-to-consumer (DTC) test to report on three specific BRCA1/BRCA2 breast cancer gene mutations. 

Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants) does not identify the most common BRCA1/2 mutations but rather the three most common in people of Ashkenazi (Eastern European) Jewish descent, the FDA said in a press statement. 

The three mutations identified by the test are present in about 2% of Ashkenazi Jewish women, but rarely in other ethnic populations. Any individual who takes the test may have other mutations in BRCA1 or BRCA2 genes, or other cancer-related gene mutations that are not detected by this test. 

“This test provides information to certain individuals who may be at increased breast, ovarian, or prostate cancer risk and who might not otherwise get genetic screening and is a step forward in the availability of DTC genetic tests. But it has a lot of caveats,” Donald St. Pierre, acting director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in the press statement. “While the detection of a BRCA mutation on this test does indicate an increased risk, only a small percentage of Americans carry one of these three mutations and most BRCA mutations that increase an individual’s risk are not detected by this test. The test should not be used as a substitute for seeing your doctor for cancer screenings or counseling on genetic and lifestyle factors that can increase or decrease cancer risk.”

The authorization was based on data provided by the company to indicate the test correctly identifies the three genetic variants in saliva samples and is reproducible. In addition, the company submitted data to demonstrate that the instructions are comprehensible and easy to follow. 

The FDA cautions that consumers and health care professionals “should not use the test results to determine any treatments, including antihormone therapies and prophylactic removal of the breasts or ovaries.” Decisions should be made only after confirmatory testing and genetic counseling, they said. 

The Food and Drug Administration has authorized the first direct-to-consumer (DTC) test to report on three specific BRCA1/BRCA2 breast cancer gene mutations. 

Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants) does not identify the most common BRCA1/2 mutations but rather the three most common in people of Ashkenazi (Eastern European) Jewish descent, the FDA said in a press statement. 

The three mutations identified by the test are present in about 2% of Ashkenazi Jewish women, but rarely in other ethnic populations. Any individual who takes the test may have other mutations in BRCA1 or BRCA2 genes, or other cancer-related gene mutations that are not detected by this test. 

“This test provides information to certain individuals who may be at increased breast, ovarian, or prostate cancer risk and who might not otherwise get genetic screening and is a step forward in the availability of DTC genetic tests. But it has a lot of caveats,” Donald St. Pierre, acting director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in the press statement. “While the detection of a BRCA mutation on this test does indicate an increased risk, only a small percentage of Americans carry one of these three mutations and most BRCA mutations that increase an individual’s risk are not detected by this test. The test should not be used as a substitute for seeing your doctor for cancer screenings or counseling on genetic and lifestyle factors that can increase or decrease cancer risk.”

The authorization was based on data provided by the company to indicate the test correctly identifies the three genetic variants in saliva samples and is reproducible. In addition, the company submitted data to demonstrate that the instructions are comprehensible and easy to follow. 

The FDA cautions that consumers and health care professionals “should not use the test results to determine any treatments, including antihormone therapies and prophylactic removal of the breasts or ovaries.” Decisions should be made only after confirmatory testing and genetic counseling, they said. 

The Food and Drug Administration has authorized the first direct-to-consumer (DTC) test to report on three specific BRCA1/BRCA2 breast cancer gene mutations. 

Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants) does not identify the most common BRCA1/2 mutations but rather the three most common in people of Ashkenazi (Eastern European) Jewish descent, the FDA said in a press statement. 

The three mutations identified by the test are present in about 2% of Ashkenazi Jewish women, but rarely in other ethnic populations. Any individual who takes the test may have other mutations in BRCA1 or BRCA2 genes, or other cancer-related gene mutations that are not detected by this test. 

“This test provides information to certain individuals who may be at increased breast, ovarian, or prostate cancer risk and who might not otherwise get genetic screening and is a step forward in the availability of DTC genetic tests. But it has a lot of caveats,” Donald St. Pierre, acting director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in the press statement. “While the detection of a BRCA mutation on this test does indicate an increased risk, only a small percentage of Americans carry one of these three mutations and most BRCA mutations that increase an individual’s risk are not detected by this test. The test should not be used as a substitute for seeing your doctor for cancer screenings or counseling on genetic and lifestyle factors that can increase or decrease cancer risk.”

The authorization was based on data provided by the company to indicate the test correctly identifies the three genetic variants in saliva samples and is reproducible. In addition, the company submitted data to demonstrate that the instructions are comprehensible and easy to follow. 

The FDA cautions that consumers and health care professionals “should not use the test results to determine any treatments, including antihormone therapies and prophylactic removal of the breasts or ovaries.” Decisions should be made only after confirmatory testing and genetic counseling, they said. 

What causes psoriasis in children?

Psoriasis is a chronic immune-mediated inflammatory skin disease with a genetic predisposition (Eichenfield et al). Similar to many inflammatory skin diseases, school-aged children have a greater predisposition before or in early adolescence. As with adult disease, pediatric psoriasis has a complex pathogenesis largely related to aberrant immune response to triggers such as infections (eg, streptococcal pharyngitis, perianal streptococcal dermatitis, upper respiratory viral infections), trauma (ie, Koebner phenomenon), stress, and obesity.

What are the emerging data and recommendations on screening for comorbidities in children with psoriasis?

Similar to psoriasis in adults, obesity and the metabolic syndrome are a true association with pediatric psoriasis that has been discussed in the literature (Eichenfield et al). Although many children with psoriasis have obesity as a potential comorbidity, the risk of cardiovascular comorbidities independent of obesity is high in pediatric psoriasis including elevated lipids, hypertension, polycystic ovaries, nonalcoholic liver disease, and elevated liver enzymes (Tollefson et al). Children with psoriasis have greater central obesity and adiposity, often accompanied by a family history of obesity. Interventions in this direction may be needed for long-term disease control and general health (Mercy and Paller). One target population is hospitalized children with psoriasis, particularly black and Hispanic children aged 0 to 9 years. This population has been identified to have a greater risk for obesity, diabetes mellitus, hypertension, arrhythmia, and valvular heart disease (Kwa et al). Therefore, it can be said that dermatologists can help to improve the overall health and lifestyle long-term in children with psoriasis.

Early-onset disease also is associated with greater risk for lifetime quality-of-life impairments including poor lifetime dermatology life quality index scores, depression and psoriasis-induced depression, social discrimination, sleep problems, and recreational drug usage (Kim et al).

How does psoriasis in children differ from adults?

Children have a variety of features that differ from adult disease. First, they are more likely to have an infectious trigger and therefore may have an identifiable treatable source. Second, they are more likely to have a family history of disease, with one-third having a relative with psoriasis, therefore, identifying the child at risk for long-standing disease. Third, children have far more visible head and neck disease, especially facial involvement including eyelids (Raychaudhuri and Gross), which increases the risk of bullying, social stigma, and negative effects on self-image. Of course, site is affected by age, and in infancy diaper dermatitis and inverse disease with maceration and overlying candidal diaper dermatitis can occur. Although children have less joint disease, it can be dramatic and crippling to the developing child.

What treatments are available for children?

In childhood, identification of precipitating infections such as streptococcal infection is ideal with appropriate intervention thereafter. Topical therapies are appropriate for limited disease with minimal disability; however, phototherapy and systemic agents can be used in pediatric psoriasis in extensive cases. Topical therapies can include corticosteroids, calcineurin inhibitors often used in sensitive skin such as the face and intertriginous areas, and calcipotriene (Eichenfield et al). Additional agents such as tar and salicylic acid can be used, with limitations on the latter due to risk for absorption in smaller children. Systemic interventions often are introduced after years of disease. A recent study identified practitioners with special interest in pediatric psoriasis and determined that systemic interventions were on average introduced 3 years after psoriasis was diagnosed and most commonly included methotrexate followed by etanercept, the latter having fewer gastrointestinal tract side effects. The panel found that usage of folic acid 6 days weekly minimized gastrointestinal tract side effects with methotrexate. Acitretin and cyclosporine were alternatives (Bronckers et al; Psoriasis Investigator Group [PsIG] of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis [EWGPP]).

Recently, dermatologists have become aware of the dramatic benefits of immune response modifiers and some biologics on pediatric psoriasis. In the setting of joint and skin involvement, I allow the rheumatologist to make the choice of agents for the child's best outcome. However, for pediatric and adolescent psoriasis, we now have 2 US Food and Drug Administration-approved agents and more rapid and thorough testing of adult-approved agents in children, with a hope of greater ability to modify disease course at a younger age, both now and in the future.

Which biologics are approved for the pediatric patient population?

Currently, in the United States 2 biologics have been approved: (1) etanercept, a fusion protein of tumor necrosis factor receptor extracellular domain linked to the Fc portion of human IgG, for moderate to severe plaque psoriasis in patients 4 years and older, and (2) ustekinumab, a human IgG1κ monoclonal antibody against the shared p40 subunit of the IL-12 and IL-23 cytokines, for moderate to severe plaque psoriasis in patients 12 years and older based on the encouraging data of the CADMUS trial (Kellen et al; Landells et al). In Europe, adalimumab has been approved as a first-line therapy in pediatric psoriasis (age ≥4 years), and etanercept (age ≥6 years) and ustekinumab (age ≥12 years) have been approved as second-line agents, all with grade A evidence, according to a recent Italian panel (Fortina et al). (A thorough review of the guidelines on screening, administration, and vaccination is available from Eichenfield et al.)

What treatments are in the pipeline?

In the United States we have clinical trials ongoing of adult-approved topical and immune response-modifying agents such as apremilast. These agents, as they become available and the data are gathered, will be added to what I refer to as our "pharmamentarium" of agents we can use to combat a difficult and disabling illness. 

What gaps are there in the pediatric psoriasis research?

Currently, there is poor awareness that there is research for pediatric psoriasis, and there is a need for pediatric groups and the National Psoriasis Foundation to allow children, adolescents, and their families to know that clinical trials are available looking into newer, more targeted, and less immunosuppressive agents. There is new hope on the horizon!

Suggested Readings

Bronckers IMGJ, Seyger MMB, West DP, et al; Psoriasis Investigator Group (PsIG) of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis (EWGPP). Safety of systemic agents for the treatment of pediatric psoriasis. JAMA Dermatol. 2017;153:1147-1157.

Eichenfield LF, Paller AS, Tom WL, et al. Pediatric psoriasis: evolving perspectives [published online January 4, 2018]. Pediatr Dermatol. doi:10.1111/pde.13382.

Fortina AB, Bardazzi F, Berti S, et al. Treatment of severe psoriasis in children: recommendations of an Italian expert group [published online August 23, 2017]. Eur J Pediatr. 2017;176:1339-1354.

Kellen R, Silverberg NB, Lebwohl M. Efficacy and safety of ustekinumab in adolescents. Pediatric Health Med Ther. 2016;7:109-120.

Kim GE, Seidler E, Kimball AB. Effect of age at diagnosis on chronic quality of life and long-term outcomes of individuals with psoriasis [published online December 29, 2014]. Pediatr Dermatol. 2015;32:656-662.

Kwa L, Kwa MC, Silverberg JI. Cardiovascular comorbidities of pediatric psoriasis among hospitalized children in the United States. J Am Acad Dermatol. 2017;77:1023-1029.

Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study [published online August 7, 2015]. J Am Acad Dermatol. 2015;73:594-603.

Mercy KM, Paller AS. The relationship between obesity and psoriasis in the pediatric population: implications and future directions. Cutis. 2013;92:107-109.

Raychaudhuri SP, Gross J. A comparative study of pediatric onset psoriasis with adult onset psoriasis. Pediatr Dermatol. 2000;17:174-178.

Tollefson MM, Van Houten HK, Asante D, et al. Association of psoriasis with comorbidity development in children with psoriasis [published online January 10, 2018]. JAMA Dermatol. doi:10.1001/jamadermatol.2017.5417. 

What causes psoriasis in children?

Psoriasis is a chronic immune-mediated inflammatory skin disease with a genetic predisposition (Eichenfield et al). Similar to many inflammatory skin diseases, school-aged children have a greater predisposition before or in early adolescence. As with adult disease, pediatric psoriasis has a complex pathogenesis largely related to aberrant immune response to triggers such as infections (eg, streptococcal pharyngitis, perianal streptococcal dermatitis, upper respiratory viral infections), trauma (ie, Koebner phenomenon), stress, and obesity.

What are the emerging data and recommendations on screening for comorbidities in children with psoriasis?

Similar to psoriasis in adults, obesity and the metabolic syndrome are a true association with pediatric psoriasis that has been discussed in the literature (Eichenfield et al). Although many children with psoriasis have obesity as a potential comorbidity, the risk of cardiovascular comorbidities independent of obesity is high in pediatric psoriasis including elevated lipids, hypertension, polycystic ovaries, nonalcoholic liver disease, and elevated liver enzymes (Tollefson et al). Children with psoriasis have greater central obesity and adiposity, often accompanied by a family history of obesity. Interventions in this direction may be needed for long-term disease control and general health (Mercy and Paller). One target population is hospitalized children with psoriasis, particularly black and Hispanic children aged 0 to 9 years. This population has been identified to have a greater risk for obesity, diabetes mellitus, hypertension, arrhythmia, and valvular heart disease (Kwa et al). Therefore, it can be said that dermatologists can help to improve the overall health and lifestyle long-term in children with psoriasis.

Early-onset disease also is associated with greater risk for lifetime quality-of-life impairments including poor lifetime dermatology life quality index scores, depression and psoriasis-induced depression, social discrimination, sleep problems, and recreational drug usage (Kim et al).

How does psoriasis in children differ from adults?

Children have a variety of features that differ from adult disease. First, they are more likely to have an infectious trigger and therefore may have an identifiable treatable source. Second, they are more likely to have a family history of disease, with one-third having a relative with psoriasis, therefore, identifying the child at risk for long-standing disease. Third, children have far more visible head and neck disease, especially facial involvement including eyelids (Raychaudhuri and Gross), which increases the risk of bullying, social stigma, and negative effects on self-image. Of course, site is affected by age, and in infancy diaper dermatitis and inverse disease with maceration and overlying candidal diaper dermatitis can occur. Although children have less joint disease, it can be dramatic and crippling to the developing child.

What treatments are available for children?

In childhood, identification of precipitating infections such as streptococcal infection is ideal with appropriate intervention thereafter. Topical therapies are appropriate for limited disease with minimal disability; however, phototherapy and systemic agents can be used in pediatric psoriasis in extensive cases. Topical therapies can include corticosteroids, calcineurin inhibitors often used in sensitive skin such as the face and intertriginous areas, and calcipotriene (Eichenfield et al). Additional agents such as tar and salicylic acid can be used, with limitations on the latter due to risk for absorption in smaller children. Systemic interventions often are introduced after years of disease. A recent study identified practitioners with special interest in pediatric psoriasis and determined that systemic interventions were on average introduced 3 years after psoriasis was diagnosed and most commonly included methotrexate followed by etanercept, the latter having fewer gastrointestinal tract side effects. The panel found that usage of folic acid 6 days weekly minimized gastrointestinal tract side effects with methotrexate. Acitretin and cyclosporine were alternatives (Bronckers et al; Psoriasis Investigator Group [PsIG] of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis [EWGPP]).

Recently, dermatologists have become aware of the dramatic benefits of immune response modifiers and some biologics on pediatric psoriasis. In the setting of joint and skin involvement, I allow the rheumatologist to make the choice of agents for the child's best outcome. However, for pediatric and adolescent psoriasis, we now have 2 US Food and Drug Administration-approved agents and more rapid and thorough testing of adult-approved agents in children, with a hope of greater ability to modify disease course at a younger age, both now and in the future.

Which biologics are approved for the pediatric patient population?

Currently, in the United States 2 biologics have been approved: (1) etanercept, a fusion protein of tumor necrosis factor receptor extracellular domain linked to the Fc portion of human IgG, for moderate to severe plaque psoriasis in patients 4 years and older, and (2) ustekinumab, a human IgG1κ monoclonal antibody against the shared p40 subunit of the IL-12 and IL-23 cytokines, for moderate to severe plaque psoriasis in patients 12 years and older based on the encouraging data of the CADMUS trial (Kellen et al; Landells et al). In Europe, adalimumab has been approved as a first-line therapy in pediatric psoriasis (age ≥4 years), and etanercept (age ≥6 years) and ustekinumab (age ≥12 years) have been approved as second-line agents, all with grade A evidence, according to a recent Italian panel (Fortina et al). (A thorough review of the guidelines on screening, administration, and vaccination is available from Eichenfield et al.)

What treatments are in the pipeline?

In the United States we have clinical trials ongoing of adult-approved topical and immune response-modifying agents such as apremilast. These agents, as they become available and the data are gathered, will be added to what I refer to as our "pharmamentarium" of agents we can use to combat a difficult and disabling illness. 

What gaps are there in the pediatric psoriasis research?

Currently, there is poor awareness that there is research for pediatric psoriasis, and there is a need for pediatric groups and the National Psoriasis Foundation to allow children, adolescents, and their families to know that clinical trials are available looking into newer, more targeted, and less immunosuppressive agents. There is new hope on the horizon!

Suggested Readings

Bronckers IMGJ, Seyger MMB, West DP, et al; Psoriasis Investigator Group (PsIG) of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis (EWGPP). Safety of systemic agents for the treatment of pediatric psoriasis. JAMA Dermatol. 2017;153:1147-1157.

Eichenfield LF, Paller AS, Tom WL, et al. Pediatric psoriasis: evolving perspectives [published online January 4, 2018]. Pediatr Dermatol. doi:10.1111/pde.13382.

Fortina AB, Bardazzi F, Berti S, et al. Treatment of severe psoriasis in children: recommendations of an Italian expert group [published online August 23, 2017]. Eur J Pediatr. 2017;176:1339-1354.

Kellen R, Silverberg NB, Lebwohl M. Efficacy and safety of ustekinumab in adolescents. Pediatric Health Med Ther. 2016;7:109-120.

Kim GE, Seidler E, Kimball AB. Effect of age at diagnosis on chronic quality of life and long-term outcomes of individuals with psoriasis [published online December 29, 2014]. Pediatr Dermatol. 2015;32:656-662.

Kwa L, Kwa MC, Silverberg JI. Cardiovascular comorbidities of pediatric psoriasis among hospitalized children in the United States. J Am Acad Dermatol. 2017;77:1023-1029.

Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study [published online August 7, 2015]. J Am Acad Dermatol. 2015;73:594-603.

Mercy KM, Paller AS. The relationship between obesity and psoriasis in the pediatric population: implications and future directions. Cutis. 2013;92:107-109.

Raychaudhuri SP, Gross J. A comparative study of pediatric onset psoriasis with adult onset psoriasis. Pediatr Dermatol. 2000;17:174-178.

Tollefson MM, Van Houten HK, Asante D, et al. Association of psoriasis with comorbidity development in children with psoriasis [published online January 10, 2018]. JAMA Dermatol. doi:10.1001/jamadermatol.2017.5417. 

What causes psoriasis in children?

Psoriasis is a chronic immune-mediated inflammatory skin disease with a genetic predisposition (Eichenfield et al). Similar to many inflammatory skin diseases, school-aged children have a greater predisposition before or in early adolescence. As with adult disease, pediatric psoriasis has a complex pathogenesis largely related to aberrant immune response to triggers such as infections (eg, streptococcal pharyngitis, perianal streptococcal dermatitis, upper respiratory viral infections), trauma (ie, Koebner phenomenon), stress, and obesity.

What are the emerging data and recommendations on screening for comorbidities in children with psoriasis?

Similar to psoriasis in adults, obesity and the metabolic syndrome are a true association with pediatric psoriasis that has been discussed in the literature (Eichenfield et al). Although many children with psoriasis have obesity as a potential comorbidity, the risk of cardiovascular comorbidities independent of obesity is high in pediatric psoriasis including elevated lipids, hypertension, polycystic ovaries, nonalcoholic liver disease, and elevated liver enzymes (Tollefson et al). Children with psoriasis have greater central obesity and adiposity, often accompanied by a family history of obesity. Interventions in this direction may be needed for long-term disease control and general health (Mercy and Paller). One target population is hospitalized children with psoriasis, particularly black and Hispanic children aged 0 to 9 years. This population has been identified to have a greater risk for obesity, diabetes mellitus, hypertension, arrhythmia, and valvular heart disease (Kwa et al). Therefore, it can be said that dermatologists can help to improve the overall health and lifestyle long-term in children with psoriasis.

Early-onset disease also is associated with greater risk for lifetime quality-of-life impairments including poor lifetime dermatology life quality index scores, depression and psoriasis-induced depression, social discrimination, sleep problems, and recreational drug usage (Kim et al).

How does psoriasis in children differ from adults?

Children have a variety of features that differ from adult disease. First, they are more likely to have an infectious trigger and therefore may have an identifiable treatable source. Second, they are more likely to have a family history of disease, with one-third having a relative with psoriasis, therefore, identifying the child at risk for long-standing disease. Third, children have far more visible head and neck disease, especially facial involvement including eyelids (Raychaudhuri and Gross), which increases the risk of bullying, social stigma, and negative effects on self-image. Of course, site is affected by age, and in infancy diaper dermatitis and inverse disease with maceration and overlying candidal diaper dermatitis can occur. Although children have less joint disease, it can be dramatic and crippling to the developing child.

What treatments are available for children?

In childhood, identification of precipitating infections such as streptococcal infection is ideal with appropriate intervention thereafter. Topical therapies are appropriate for limited disease with minimal disability; however, phototherapy and systemic agents can be used in pediatric psoriasis in extensive cases. Topical therapies can include corticosteroids, calcineurin inhibitors often used in sensitive skin such as the face and intertriginous areas, and calcipotriene (Eichenfield et al). Additional agents such as tar and salicylic acid can be used, with limitations on the latter due to risk for absorption in smaller children. Systemic interventions often are introduced after years of disease. A recent study identified practitioners with special interest in pediatric psoriasis and determined that systemic interventions were on average introduced 3 years after psoriasis was diagnosed and most commonly included methotrexate followed by etanercept, the latter having fewer gastrointestinal tract side effects. The panel found that usage of folic acid 6 days weekly minimized gastrointestinal tract side effects with methotrexate. Acitretin and cyclosporine were alternatives (Bronckers et al; Psoriasis Investigator Group [PsIG] of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis [EWGPP]).

Recently, dermatologists have become aware of the dramatic benefits of immune response modifiers and some biologics on pediatric psoriasis. In the setting of joint and skin involvement, I allow the rheumatologist to make the choice of agents for the child's best outcome. However, for pediatric and adolescent psoriasis, we now have 2 US Food and Drug Administration-approved agents and more rapid and thorough testing of adult-approved agents in children, with a hope of greater ability to modify disease course at a younger age, both now and in the future.

Which biologics are approved for the pediatric patient population?

Currently, in the United States 2 biologics have been approved: (1) etanercept, a fusion protein of tumor necrosis factor receptor extracellular domain linked to the Fc portion of human IgG, for moderate to severe plaque psoriasis in patients 4 years and older, and (2) ustekinumab, a human IgG1κ monoclonal antibody against the shared p40 subunit of the IL-12 and IL-23 cytokines, for moderate to severe plaque psoriasis in patients 12 years and older based on the encouraging data of the CADMUS trial (Kellen et al; Landells et al). In Europe, adalimumab has been approved as a first-line therapy in pediatric psoriasis (age ≥4 years), and etanercept (age ≥6 years) and ustekinumab (age ≥12 years) have been approved as second-line agents, all with grade A evidence, according to a recent Italian panel (Fortina et al). (A thorough review of the guidelines on screening, administration, and vaccination is available from Eichenfield et al.)

What treatments are in the pipeline?

In the United States we have clinical trials ongoing of adult-approved topical and immune response-modifying agents such as apremilast. These agents, as they become available and the data are gathered, will be added to what I refer to as our "pharmamentarium" of agents we can use to combat a difficult and disabling illness. 

What gaps are there in the pediatric psoriasis research?

Currently, there is poor awareness that there is research for pediatric psoriasis, and there is a need for pediatric groups and the National Psoriasis Foundation to allow children, adolescents, and their families to know that clinical trials are available looking into newer, more targeted, and less immunosuppressive agents. There is new hope on the horizon!

Suggested Readings

Bronckers IMGJ, Seyger MMB, West DP, et al; Psoriasis Investigator Group (PsIG) of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis (EWGPP). Safety of systemic agents for the treatment of pediatric psoriasis. JAMA Dermatol. 2017;153:1147-1157.

Eichenfield LF, Paller AS, Tom WL, et al. Pediatric psoriasis: evolving perspectives [published online January 4, 2018]. Pediatr Dermatol. doi:10.1111/pde.13382.

Fortina AB, Bardazzi F, Berti S, et al. Treatment of severe psoriasis in children: recommendations of an Italian expert group [published online August 23, 2017]. Eur J Pediatr. 2017;176:1339-1354.

Kellen R, Silverberg NB, Lebwohl M. Efficacy and safety of ustekinumab in adolescents. Pediatric Health Med Ther. 2016;7:109-120.

Kim GE, Seidler E, Kimball AB. Effect of age at diagnosis on chronic quality of life and long-term outcomes of individuals with psoriasis [published online December 29, 2014]. Pediatr Dermatol. 2015;32:656-662.

Kwa L, Kwa MC, Silverberg JI. Cardiovascular comorbidities of pediatric psoriasis among hospitalized children in the United States. J Am Acad Dermatol. 2017;77:1023-1029.

Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study [published online August 7, 2015]. J Am Acad Dermatol. 2015;73:594-603.

Mercy KM, Paller AS. The relationship between obesity and psoriasis in the pediatric population: implications and future directions. Cutis. 2013;92:107-109.

Raychaudhuri SP, Gross J. A comparative study of pediatric onset psoriasis with adult onset psoriasis. Pediatr Dermatol. 2000;17:174-178.

Tollefson MM, Van Houten HK, Asante D, et al. Association of psoriasis with comorbidity development in children with psoriasis [published online January 10, 2018]. JAMA Dermatol. doi:10.1001/jamadermatol.2017.5417. 

What do patients need to know initially about psoriasis treatment?

It is important to set expectations with the patient based on the treatment selected, not only for patient satisfaction but to forge an enduring bond with the patient so he/she will trust you to guide the treatment plan if the first therapy does not work as well as anticipated. Because psoriasis is a longitudinal disease process, the patient-physician relationship should be, too. Certainly, these principles generally apply among all patient groups and demographics; however, one may take into account a few special circumstances when dealing with psoriasis. In a pediatric patient, I may try to see if topical therapy including calcipotriene can adequately treat the skin disease before pursuing systemic treatment. The rationale is 2-fold: (1) this patient would be committed to an extended period on immunomodulatory therapy if he/she truly requires it, and (2) some of the forms of psoriasis in children, such as guttate psoriasis, may be self-limited, so it is reasonable to see if it will persist before forging ahead with a long-term systemic medication. In patients with a recent history of cancer, I would likely choose an oral medication such as apremilast before a biologic; even though there are no real data to suggest biologics are associated with higher rates of solid-organ malignancy, most practitioners would err on the side of being more conservative. For patients with human immunodeficiency virus, the tendency is to use the agents with more data (eg, tumor necrosis factor α inhibitors) due to safety concerns with an immunomodulatory medication.

What are your go-to treatments?

I tend to be as aggressive as the patient wants to be with therapy. I regularly see patients in whom multiple systemic treatments have failed and a more creative regimen is needed, such as combining a biologic medication with an oral antipsoriatic treatment (eg, apremilast, acitretin). However, I do have patients with moderate to severe psoriasis who have not seen a dermatologist before. I do not find it necessary to have topical treatments fail before starting a biologic; after all, the sequelae of long-term topical steroid use are notable.

With the newer biologics on the market, such as the IL-17 and IL-23 inhibitors, the sky's the limit for psoriasis area and severity index clearance, but the true benefit is that these medications are much more targeted toward the pathogenesis of psoriasis. Unfortunately, we have to be mindful of insurance and formulary restrictions, but when faced with choosing a broad-acting immunomodulatory agent or a more specific/targeted immunomodulatory agent for an inflammatory disease, most dermatologists would choose the more targeted medication. The data support that the newer agents have better psoriasis area and severity index responses and a much greater proportion of clearance, but there is something to be said about biologics such as etanercept, adalimumab, and ustekinumab, which have been on the market for much longer and have shown durable response with a longer track record of safety and efficacy. Recent head-to-head comparisons can help guide treatment. For instance, patients who achieved suboptimal clearance on ustekinumab can safely and reasonably be switched to guselkumab based on the findings of the NAVIGATE study, which looked at this exact situation. More of these studies looking at specific prior treatment failures and improvement upon switching to a newer agent are needed to underscore the efficacy of these drugs and also to help argue for their placement on insurance formularies.

For a new patient with psoriasis, I will screen for psoriatic arthritis, look at involvement (eg, body surface area, individual plaque severity/thickness, locations such as scalp and extremities), and assess patient attitudes toward different treatments. Two patients with the exact same clinical appearance might have completely different strategies, one wanting to be as aggressive as possible to get rid of the psoriasis and the other not believing in systemic treatments and wanting to be as "natural" as possible.

For patients with only cutaneous involvement, the dosing frequency and efficacy of the newer IL-17 and IL-23 classes of medications are hard to beat. If a patient has notable psoriatic arthritis, I still tend to reach for a tumor necrosis factor α inhibitor first. For patients with limited involvement, especially those with scalp and/or palmoplantar psoriasis, I have found that apremilast works quite well. Apremilast, in general, would be a good first-step medication for patients wary of systemic therapy, and with its relatively benign side-effect profile, it has almost completely supplanted methotrexate in my practice. We also have a few newer topical medicines such as a calcipotriene 0.005%-betamethasone dipropionate 0.064% foam and a betamethasone dipropionate spray 0.05% that have proven useful, with more products in the pipeline.

How do you keep patients compliant with treatment?

Setting expectations is most important, and letting patients know what to expect from their first visit really helps to keep them satisfied with the plan and progress. Giving the patient a say in guiding the treatment and perhaps coming up with a rough treatment plan with a defined timeline also helps, such as starting with a topical regimen but moving on to an oral medicine if the topical does not work within 2 to 3 months, and then a biologic if oral therapy does not work well within 3 to 6 months. It is important not to push the patient to pursue a more aggressive therapy unless he/she wants to, otherwise the patient might not be compliant or may stop altogether.

What do you do if they refuse treatment?

If the patient is in your office, clearly he/she does want some help. Try to figure out what is at the root of the treatment refusal. Is the patient refusing topical steroids because he/she is afraid of them? Is the patient unable to stomach having to inject himself/herself? Finding the basis of their reticence may take more time, but we usually can find a mutually agreeable plan of action. Even if the first step is to watch and wait, you want the patient leaving your office knowing that if things do not progress as expected or get worse, they can have faith in you to come back and get more help.

What resources do you recommend to patients for more information?

The National Psoriasis Foundation is a great resource for patients. They have numerous outreach programs and a wealth of patient information. Also, the American Academy of Dermatology is a good resource, not just for patients but for providers; for example, the academy offers appeals letters that can be sent to insurance companies to try to advocate for a specific medication for patients.

Suggested Readings

Help patients appeal denial of psoriasis drugs. American Academy of Dermatology website. https://www.aad.org/members/publications/member-to-member/2017/jan-27-2017/help-patients-appeal-denial-of-psoriasis-drugs. Accessed February 9, 2018.

Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial [published online October 10, 2017]. Br J Dermatol. 2018;178:114-123.

What do patients need to know initially about psoriasis treatment?

It is important to set expectations with the patient based on the treatment selected, not only for patient satisfaction but to forge an enduring bond with the patient so he/she will trust you to guide the treatment plan if the first therapy does not work as well as anticipated. Because psoriasis is a longitudinal disease process, the patient-physician relationship should be, too. Certainly, these principles generally apply among all patient groups and demographics; however, one may take into account a few special circumstances when dealing with psoriasis. In a pediatric patient, I may try to see if topical therapy including calcipotriene can adequately treat the skin disease before pursuing systemic treatment. The rationale is 2-fold: (1) this patient would be committed to an extended period on immunomodulatory therapy if he/she truly requires it, and (2) some of the forms of psoriasis in children, such as guttate psoriasis, may be self-limited, so it is reasonable to see if it will persist before forging ahead with a long-term systemic medication. In patients with a recent history of cancer, I would likely choose an oral medication such as apremilast before a biologic; even though there are no real data to suggest biologics are associated with higher rates of solid-organ malignancy, most practitioners would err on the side of being more conservative. For patients with human immunodeficiency virus, the tendency is to use the agents with more data (eg, tumor necrosis factor α inhibitors) due to safety concerns with an immunomodulatory medication.

What are your go-to treatments?

I tend to be as aggressive as the patient wants to be with therapy. I regularly see patients in whom multiple systemic treatments have failed and a more creative regimen is needed, such as combining a biologic medication with an oral antipsoriatic treatment (eg, apremilast, acitretin). However, I do have patients with moderate to severe psoriasis who have not seen a dermatologist before. I do not find it necessary to have topical treatments fail before starting a biologic; after all, the sequelae of long-term topical steroid use are notable.

With the newer biologics on the market, such as the IL-17 and IL-23 inhibitors, the sky's the limit for psoriasis area and severity index clearance, but the true benefit is that these medications are much more targeted toward the pathogenesis of psoriasis. Unfortunately, we have to be mindful of insurance and formulary restrictions, but when faced with choosing a broad-acting immunomodulatory agent or a more specific/targeted immunomodulatory agent for an inflammatory disease, most dermatologists would choose the more targeted medication. The data support that the newer agents have better psoriasis area and severity index responses and a much greater proportion of clearance, but there is something to be said about biologics such as etanercept, adalimumab, and ustekinumab, which have been on the market for much longer and have shown durable response with a longer track record of safety and efficacy. Recent head-to-head comparisons can help guide treatment. For instance, patients who achieved suboptimal clearance on ustekinumab can safely and reasonably be switched to guselkumab based on the findings of the NAVIGATE study, which looked at this exact situation. More of these studies looking at specific prior treatment failures and improvement upon switching to a newer agent are needed to underscore the efficacy of these drugs and also to help argue for their placement on insurance formularies.

For a new patient with psoriasis, I will screen for psoriatic arthritis, look at involvement (eg, body surface area, individual plaque severity/thickness, locations such as scalp and extremities), and assess patient attitudes toward different treatments. Two patients with the exact same clinical appearance might have completely different strategies, one wanting to be as aggressive as possible to get rid of the psoriasis and the other not believing in systemic treatments and wanting to be as "natural" as possible.

For patients with only cutaneous involvement, the dosing frequency and efficacy of the newer IL-17 and IL-23 classes of medications are hard to beat. If a patient has notable psoriatic arthritis, I still tend to reach for a tumor necrosis factor α inhibitor first. For patients with limited involvement, especially those with scalp and/or palmoplantar psoriasis, I have found that apremilast works quite well. Apremilast, in general, would be a good first-step medication for patients wary of systemic therapy, and with its relatively benign side-effect profile, it has almost completely supplanted methotrexate in my practice. We also have a few newer topical medicines such as a calcipotriene 0.005%-betamethasone dipropionate 0.064% foam and a betamethasone dipropionate spray 0.05% that have proven useful, with more products in the pipeline.

How do you keep patients compliant with treatment?

Setting expectations is most important, and letting patients know what to expect from their first visit really helps to keep them satisfied with the plan and progress. Giving the patient a say in guiding the treatment and perhaps coming up with a rough treatment plan with a defined timeline also helps, such as starting with a topical regimen but moving on to an oral medicine if the topical does not work within 2 to 3 months, and then a biologic if oral therapy does not work well within 3 to 6 months. It is important not to push the patient to pursue a more aggressive therapy unless he/she wants to, otherwise the patient might not be compliant or may stop altogether.

What do you do if they refuse treatment?

If the patient is in your office, clearly he/she does want some help. Try to figure out what is at the root of the treatment refusal. Is the patient refusing topical steroids because he/she is afraid of them? Is the patient unable to stomach having to inject himself/herself? Finding the basis of their reticence may take more time, but we usually can find a mutually agreeable plan of action. Even if the first step is to watch and wait, you want the patient leaving your office knowing that if things do not progress as expected or get worse, they can have faith in you to come back and get more help.

What resources do you recommend to patients for more information?

The National Psoriasis Foundation is a great resource for patients. They have numerous outreach programs and a wealth of patient information. Also, the American Academy of Dermatology is a good resource, not just for patients but for providers; for example, the academy offers appeals letters that can be sent to insurance companies to try to advocate for a specific medication for patients.

Suggested Readings

Help patients appeal denial of psoriasis drugs. American Academy of Dermatology website. https://www.aad.org/members/publications/member-to-member/2017/jan-27-2017/help-patients-appeal-denial-of-psoriasis-drugs. Accessed February 9, 2018.

Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial [published online October 10, 2017]. Br J Dermatol. 2018;178:114-123.

What do patients need to know initially about psoriasis treatment?

It is important to set expectations with the patient based on the treatment selected, not only for patient satisfaction but to forge an enduring bond with the patient so he/she will trust you to guide the treatment plan if the first therapy does not work as well as anticipated. Because psoriasis is a longitudinal disease process, the patient-physician relationship should be, too. Certainly, these principles generally apply among all patient groups and demographics; however, one may take into account a few special circumstances when dealing with psoriasis. In a pediatric patient, I may try to see if topical therapy including calcipotriene can adequately treat the skin disease before pursuing systemic treatment. The rationale is 2-fold: (1) this patient would be committed to an extended period on immunomodulatory therapy if he/she truly requires it, and (2) some of the forms of psoriasis in children, such as guttate psoriasis, may be self-limited, so it is reasonable to see if it will persist before forging ahead with a long-term systemic medication. In patients with a recent history of cancer, I would likely choose an oral medication such as apremilast before a biologic; even though there are no real data to suggest biologics are associated with higher rates of solid-organ malignancy, most practitioners would err on the side of being more conservative. For patients with human immunodeficiency virus, the tendency is to use the agents with more data (eg, tumor necrosis factor α inhibitors) due to safety concerns with an immunomodulatory medication.

What are your go-to treatments?

I tend to be as aggressive as the patient wants to be with therapy. I regularly see patients in whom multiple systemic treatments have failed and a more creative regimen is needed, such as combining a biologic medication with an oral antipsoriatic treatment (eg, apremilast, acitretin). However, I do have patients with moderate to severe psoriasis who have not seen a dermatologist before. I do not find it necessary to have topical treatments fail before starting a biologic; after all, the sequelae of long-term topical steroid use are notable.

With the newer biologics on the market, such as the IL-17 and IL-23 inhibitors, the sky's the limit for psoriasis area and severity index clearance, but the true benefit is that these medications are much more targeted toward the pathogenesis of psoriasis. Unfortunately, we have to be mindful of insurance and formulary restrictions, but when faced with choosing a broad-acting immunomodulatory agent or a more specific/targeted immunomodulatory agent for an inflammatory disease, most dermatologists would choose the more targeted medication. The data support that the newer agents have better psoriasis area and severity index responses and a much greater proportion of clearance, but there is something to be said about biologics such as etanercept, adalimumab, and ustekinumab, which have been on the market for much longer and have shown durable response with a longer track record of safety and efficacy. Recent head-to-head comparisons can help guide treatment. For instance, patients who achieved suboptimal clearance on ustekinumab can safely and reasonably be switched to guselkumab based on the findings of the NAVIGATE study, which looked at this exact situation. More of these studies looking at specific prior treatment failures and improvement upon switching to a newer agent are needed to underscore the efficacy of these drugs and also to help argue for their placement on insurance formularies.

For a new patient with psoriasis, I will screen for psoriatic arthritis, look at involvement (eg, body surface area, individual plaque severity/thickness, locations such as scalp and extremities), and assess patient attitudes toward different treatments. Two patients with the exact same clinical appearance might have completely different strategies, one wanting to be as aggressive as possible to get rid of the psoriasis and the other not believing in systemic treatments and wanting to be as "natural" as possible.

For patients with only cutaneous involvement, the dosing frequency and efficacy of the newer IL-17 and IL-23 classes of medications are hard to beat. If a patient has notable psoriatic arthritis, I still tend to reach for a tumor necrosis factor α inhibitor first. For patients with limited involvement, especially those with scalp and/or palmoplantar psoriasis, I have found that apremilast works quite well. Apremilast, in general, would be a good first-step medication for patients wary of systemic therapy, and with its relatively benign side-effect profile, it has almost completely supplanted methotrexate in my practice. We also have a few newer topical medicines such as a calcipotriene 0.005%-betamethasone dipropionate 0.064% foam and a betamethasone dipropionate spray 0.05% that have proven useful, with more products in the pipeline.

How do you keep patients compliant with treatment?

Setting expectations is most important, and letting patients know what to expect from their first visit really helps to keep them satisfied with the plan and progress. Giving the patient a say in guiding the treatment and perhaps coming up with a rough treatment plan with a defined timeline also helps, such as starting with a topical regimen but moving on to an oral medicine if the topical does not work within 2 to 3 months, and then a biologic if oral therapy does not work well within 3 to 6 months. It is important not to push the patient to pursue a more aggressive therapy unless he/she wants to, otherwise the patient might not be compliant or may stop altogether.

What do you do if they refuse treatment?

If the patient is in your office, clearly he/she does want some help. Try to figure out what is at the root of the treatment refusal. Is the patient refusing topical steroids because he/she is afraid of them? Is the patient unable to stomach having to inject himself/herself? Finding the basis of their reticence may take more time, but we usually can find a mutually agreeable plan of action. Even if the first step is to watch and wait, you want the patient leaving your office knowing that if things do not progress as expected or get worse, they can have faith in you to come back and get more help.

What resources do you recommend to patients for more information?

The National Psoriasis Foundation is a great resource for patients. They have numerous outreach programs and a wealth of patient information. Also, the American Academy of Dermatology is a good resource, not just for patients but for providers; for example, the academy offers appeals letters that can be sent to insurance companies to try to advocate for a specific medication for patients.

Suggested Readings

Help patients appeal denial of psoriasis drugs. American Academy of Dermatology website. https://www.aad.org/members/publications/member-to-member/2017/jan-27-2017/help-patients-appeal-denial-of-psoriasis-drugs. Accessed February 9, 2018.

Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial [published online October 10, 2017]. Br J Dermatol. 2018;178:114-123.