powerpoint presentation...‣rhinorrhea, cough, oral ulcers or vesicles, conjunctivitis, stomatitis,...
TRANSCRIPT
7/24/2018
1
MedScape Pediatrics
Viewpoints – Top Articles
from 2017 and 2018
William (Bill) Basco, MD, MS,
Editor, MedScape Pediatrics Viewpoints
Disclosures:
▸ Neither Dr. Basco nor family members own financial interest in
MedScape or parent companies
▸ Off-label uses of medications will be revealed if they are
reviewed (most of the trials are off-label)
▸ MUSC Dept of Pediatrics receives payment for Dr. Basco’s role
at MedScape
What is MedScape Viewpoints?
▸ Year 2002 – Bill Basco became editor of MedScape Pediatric
Journal Scan
▸ Year 2007 – evolved to MedScape Viewpoints
▸ Monthly summaries of articles of interest
▸ Circulation: 2,000-80,000 page views per Viewpoint
Outline:
▸ I. Review Widely-accessed Articles in MedScape Pediatric
Viewpoints in either 2017 or 2018.
▸ II. Specific topics will include
‣ Otitis media – duration of antibiotic treatment
‣ Testing for pharyngitis
‣ Prevention of migraine
First, the 2017
highlights…
2017 - # 11
Pediatrics 2017 May;139(5)
7/24/2018
2
Pharyngitis Testing - Introduction
▸ Difficult to differentiate between viral and bacterial pharyngitis caused by group A Streptococcus (GAS)
▸ Significant overlap in the symptoms and physical findings
▸ Current guidelines recommend avoiding rapid antigen testing followed by throat culture (for all rapid-negative) if a patient presents with overt viral features. (Clin Infect Dis 2014 and 2012)
‣ Rhinorrhea, cough, oral ulcers or vesicles, conjunctivitis, stomatitis, and hoarseness
▸ Rationale: up to 1 in 5 children carry GAS, so testing all children with viral illnesses will identify some cases of pharyngitis with a positive culture for GAS that actually represent pharyngeal colonization.
Pharyngitis Testing – Method
▸ Study objectives:‣ Primary: to determine the prevalence of overt viral features in children
with sore throat for whom laboratory testing for GAS pharyngitis was performed (reflects the extent to which IDSA recommendations for testing are followed in practice).
‣ Secondary: to compare the prevalence of GAS in patients with and without viral features.
▸ Setting: Single Emergency Dept
▸ Years: 2013-2015
▸ Subjects: children aged 3-21 years presenting with sore throat
▸ Approach: ‣ GAS rapid antigen test first, with negatives cultured
‣ Attending clinicians documented specific symptoms and physical findings
Pharyngitis Testing - Results
▸ 320 total visits
‣ 3-7 years old 45% visits
‣ 8-12 years old 24% visits
‣ 13-17 years old 19% visits
‣ 18-21 years old 13% visits
▸ 60% were female
▸ 34% GAS positive; 28% rapid+; 6% were rapid negative, culture+
▸ About one third (35%) of the children were febrile upon admission.
▸ Overt viral features were common (63% overall),
‣ 49% having cough, 40% rhinorrhea, 4% oral ulcers or vesicles, and 2% conjunctival injection.
▸ Only 37% of the children presented with no viral features, whereas 30% had two or more features.
Pharyngitis Testing - Results
▸ GAS was confirmed in 34% of the overall sample.
▸ Statistically significant trend toward decreased GAS prevalence
as the number of viral features increased.
▸ For example
‣ without viral features = 42% had GAS pharyngitis
‣ with viral features = 29% had GAS pharyngitis
▸ Take home: viral features were present in large proportions of
both GAS-positive and GAS-negative children.
‣ Cough present in 51% of the GAS-negative and 43% of GAS+
children.
‣ Rhinorrhea present in 44% of the GAS-negative and 30% of GAS+
children.
Pharyngitis Testing - Conclusions
▸ Author conclusions:
‣ Distinguishing GAS pharyngitis from viral pharyngitis is challenging
‣ We should continue to apply criteria to reduce testing overall, and
number of viral features can help
‣ Maybe stop doing rapid testing at triage, before provider
assessment and exam?
‣ More data are needed
▸ Viewpoint:
‣ This is tough!
‣ 1 viral feature – 29% have GAS, and that’s near the carriage rate
‣ Maybe really reduce testing for those with > 2 viral symptoms
2017 - # 8
N Engl J Med. 2017 Jan 12;376(2):115-124
7/24/2018
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Migraine Prevention - Introduction
▸ Childhood and Adolescent Migraine Prevention (CHAMP) trial
‣ (NEJM 2017; 376: 115-24)
▸ Two active drugs tested
‣ amitriptyline vs topiramate
▸ Drugs chosen by consensus views that they were the ones
most commonly used to prevent migraine in kids.
▸ Hypothesis:
‣ 1. both active treatments would perform better than placebo, and
‣ 2. one of the active treatments would prove superior to the other
Migraine Prevention - Method
▸ Subjects: children (aged 8-17 years) with migraine, with at least
“mild” disability on a standard scale
▸ Setting: 31 US sites.
▸ Treatment:
‣ randomly assigned in a 2:2:1 ratio to receive the two active
treatments and the placebo regimen, respectively.
▸ Amitriptyline was dosed at 1 mg/kg daily, divided BID
▸ Topiramate was dosed at 2 mg/kg daily, divided BID
▸ Placebo BID
▸ Once the children experienced appropriate dose escalation,
they were maintained on a 16-week treatment phase at highest
tolerated dose.
Migraine Prevention - Method
▸ Primary outcome: 28-day headache diary after at least 24
weeks of treatment, compared with headache days at
baseline.
▸ Treatment success = 50% or greater decrease in the
number of headache days between the baseline and final
assessment.
▸ Secondary outcomes: changes in headache-related
disability
▸ Original trial planned to enroll 675 patients, but it was
discontinued at the first planned interim analysis
Migraine Prevention - Results
▸ Average age of enrollees was 14.2 years
▸ 68% were female.
▸ Race/ethnicity
‣ mostly white (70%), but with a notable proportion of black enrollees
(19%)
‣ 88% were of non-Hispanic ethnicity.
▸ The average number of headache days during the baseline
period was 11.4.
Migraine Prevention – Results
Outcome Amytriptyline
(N=132)
Topiramate
(N=130)
Placebo
(N=66)
Primary
(50%
reduction)
52% 55% 61%
Secondary
(HA days/mo)
Base: 11.3
Final: 4.6
Base: 11.3
Final: 4.6
Base: 11.1
Final: 5.2
Withdrew
because of
Side Effects
5% 6% 2%
Migraine Prevention – Conclusions
▸ Author Conclusions:‣ no significant differences in response among the two treatment groups
compared with placebo during 24 weeks of active treatment.
▸ Viewpoint‣ Severe disappointment! Sobering that the two drugs suggested by
experts and previous trials to offer the best opportunity for prevention of migraine had so little effect.
▸ Positive side:‣ notable placebo effect, or
‣ regression to the mean over time, or
‣ true improvement over time offer some hope for patients and providers.
‣ In an accompanying editorial, Jacksoncommented that the marked placebo response rate in this study is commonly seen in headache trials, and suggests that we should focus on non-pharm approaches
7/24/2018
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2017 - # 5
Pediatrics. 2017
Aug;140(2)
Penicillin Allergy - Introduction
▸ Many patients with reported penicillin allergy are not truly
penicillin allergic.
‣ J Allergy Clin Immunol Pract. 2017;5:686-693.
‣ Acad Pediatr. 2017;17:251-255
▸ Testing for penicillin allergy is a lengthy and complicated
sequence.
‣ percutaneous skin testing,
‣ followed by subcutaneous injections,
‣ followed by an oral challenge.
▸ So, many are assumed but not proven allergic
Penicillin Allergy - Method
▸ Subjects: children aged 3.5-18 years who presented to a single emergency department and whose parents reported that the child had a penicillin allergy.
▸ Instrument: 17-item questionnaire, obtaining details on the purported allergic reaction, including signs and symptoms experienced by the child and any family history of atopic illness.
▸ Applied an algorhithm to identify a cohort of "low-risk" children who likely did not have true penicillin allergy and could therefore be tested for penicillin allergy.
▸ Low-risk reactions for penicillin allergy‣ Mild skin (with or without itching),
‣ Gastrointestinal symptoms (such as vomiting or diarrhea), and
‣ Some upper respiratory symptoms (such as runny nose or cough).
‣ ***A child with only a family history of allergy was considered low-risk.
▸ High risk reactions for penicillin allergy were eliminated: ‣ Respiratory or cardiovascular symptoms, anaphylaxis
‣ Blood pressure changes, and
‣ Severe skin reactions – bullous
Penicillin Allergy – Method
▸ Low-risk children contacted after the emergency department visit to determine whether they would like to return for penicillin testing.
▸ If agreed, testing went through the standard three-step testing sequence.
‣ Percutaneous, intradermal, then oral challenge
‣ Skin testing considered positive for wheal ≥3 mm in diameter.
‣ A child with a positive skin test could proceed to a graduated oral challenge if no systemic symptoms were present.
▸ Most of the families of the low-risk children were interested in testing, and ultimately 100 children completed the full testing sequence.
▸ Questionnaires were completed for 597 children.
▸ Most study children (72.6%) were classified as low-risk by the screening instrument, with 27.3% having at least one high-risk symptom.
Penicillin Allergy - Results
▸ N= 100 subjects, Median age = 9 years
▸ 60% were white, and 20% were African-American.
▸ 92% of diagnoses of penicillin allergy were made by a PCP
▸ 14% of the reported reactions were actually witnessed by a medical provider.
‣ Rash (97%) Itching (63%) were the most commonly reported allergy symptoms; 17% of the 100 children tested had reported hives, 7% had diarrhea, 2% had nausea, and 2% had vomiting. Other symptoms were all present in ≤1% of the children.
▸ Of 100 children tested for allergy
‣ 3 (3%) had a positive skin prick test.
‣ All (100%; 95% confidence interval, 96.4%-100%) were able to complete the oral challenge.
Penicillin Allergy - Conclusions
▸ Authors: Children who were classified as low-risk for true penicillin allergy based on the screening instrument had subsequent negative penicillin allergy test results.
▸ Viewpoint:
‣ This could be viewed as a pilot study.
‣ Approach and a tool to may be helpful to determine which children can safely be prescribed penicillin drugs.
‣ The investigators acknowledged that this is "not quite ready for primetime," and it is perhaps for that reason that they did not publish the survey tool as an appendix to the manuscript.
‣ What can you do: Consider avoiding label if symptoms are mild and you did not see it. Detailed documentation and assessment of any potential allergic reaction in an effort to avoid misclassifying children as allergic in the first place.
7/24/2018
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2017 - # 4
N Engl J Med. 2016;375:2446-2456.
AOM Treatment Length - Introduction
▸ Not treating acute otitis media (AOM) in children aged <3 years
with antibiotics produces worse outcomes than treating
▸ Not known whether shorter durations of treatment are
appropriate in these younger children as a way of reducing
antibiotic use.
▸ Research Question:
‣ Is a 5-day course of antibiotic treatment non-
inferior to a 10-day treatment course?
AOM Treatment Length - Method
▸ Type: Randomized, double-blind, non-inferiority trial
▸ Subjects: 6-23 months old (N=520)
▸ Setting: Practices in Pittsburg area and Kentucky, 2012-2015
▸ Eligible:
‣ At least 2 doses of pneumococcal conjugate vaccine
‣ Appropriate exam findings and symptom scale findings
▸ Treatment: 1:1 randomization to:
‣ 10 days amox-clavulanate (dosed at 90 mg/kg/d of amox)
‣ OR, 5 days amox-clavulanate, then 5 days of similar placebo
▸ Outcome: % Clinical Failure:
‣ Worse symptoms
‣ Worse exam findings
‣ Incomplete resolution of symptoms by end of treatment
AOM Treatment Length - Results
▸ 51% of the enrolled children were <1 year old
▸ 58% had exposure to three or more other children
▸ 55% of all of the children had what was considered a severe illness based on fever and pain
▸ 49% of the children had bilateral otitis
▸ The study was discontinued early because an interim analysis showed that the shorter course was not performing in a non-inferior manner, with too many failures among the children treated for only 5 days.
▸ Clinical failure was twice as common in short-duration tx group
‣ 34% in the 5-day treatment group
‣ 16% in the10-day treatment group, correlating to a number-needed-to-treat of six to prevent one clinical failure.
OM Treatment Length - Conclusions
▸ Authors: Among children 6-23 months old, shorter duration
treatment of AOM had less favorable outcomes
▸ Viewpoint:
‣ Win some, lose some
‣ Can still be active in antimicrobial stewardship by being careful about
making diagnoses, but don’t skimp on antibiotic duration
‣ Remember that these are younger children – might still be
reasonable to consider shorter duration with older children, but
“older” is not well defined On to 2018 highlights…
7/24/2018
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#8 – 2018
(Reportedly – Mike Bowman)
N Engl J Med. 2018
Mar 8;378(10):891-901
Increasing ICS for Asthma - Introduction
▸ Inhaled corticosteroids are the mainstay controller for
persistent asthma
▸ Exacerbations still happen
▸ Research Question:
‣ Can increasing the dose of ICS when asthma symptoms
first begin to worsen can help to prevent asthma
exacerbations? (and therefore avoid systemic steroids..)
Increasing ICS for Asthma - Method
▸ Study type: Randomized, double-blind, parallel-group trial (17 sites in
the United States).
▸ Subjects:
‣ 5-11 years old
‣ Mild or moderate persistent asthma
‣ Had experienced at least one asthma exacerbation for which they
received systemic glucocorticoids in the year before enrollment.
‣ Exhibited reasonable control of their asthma before enrollment on
the basis of standardized measures.
▸ During 4-week run-in period, study children were:
‣ switched to the same low-dose inhaled corticosteroid
‣ trained in the use of a daily electronic diary for symptom
documentation
‣ completed an asthma control test.
Increasing ICS for Asthma - Method
▸ TREATMENT GROUPS - For the rest of study, (48 weeks), the children were
randomized in 1:1 ration to either
▸ continue the routine dose (88 µg daily) or …
▸ change to a high dose (440 µg daily) of fluticasone for 7 days each time
they experienced asthma symptoms that moved them into the "yellow
zone" of their treatment plan. (Quintupling the dose)
▸ Main outcome = frequency of severe asthma exacerbations that required
systemic glucocorticoids.
▸ Secondary outcomes
▸ time to first asthma exacerbation
▸ unscheduled emergency department or urgent care visits
▸ hospitalizations
▸ total glucocorticoid exposure
▸ growth
Increasing ICS for Asthma - Results
▸ Each study group had 127 children.
‣ 94 completers in the high-dose group and 98 children in the low-
dose group
‣ 64.2% were boys
‣ 38.2% of the children were exposed to tobacco smoke
‣ Adherence among children was assessed to be 98%
‣ Diary completion was about 73% for both groups
‣ Mean age of children at enrollment = 8 years
▸ Subjects averaged 2.4 episodes of “Yellow Zone” symptoms
▸ Primary Outcome: No difference in annual exacerbations that
required systemic steroids
▸ No differences in
‣ Yellow Zone episodes
‣ Prednisone use
‣ “Treatment failure”
‣ (2 exacerbations/6mo)
‣ ED visits
▸ All 4 hospitalizations were
in “high dose” group
Increasing ICS for
Asthma - Results
7/24/2018
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Increasing ICS for Asthma - Results
▸ Additional Secondary outcomes…
▸ Asthma symptom control over entire period
‣ 96% in low-dose group
‣ 95% in the high-dose group
▸ Decreased growth velocity in “high dose” group compared to
‘low dose” (by 0.23 cm/Year), or 4% lower than “low dose”
subjects
Increasing ICS for Asthma - Conclusions
▸ Authors: among children aged 5-11 years whose asthma was treated with daily ICS, increasing the dose of inhaled glucocorticoids at the first loss of asthma control did not reduce severe exacerbations
▸ Viewpoint:
▸ Disappointing!
▸ Some good news - >80% of the yellow-zone episodes DID NOT progress to requiring systemic steroids. So, may be hard to show difference.
▸ Reminder: findings do not apply to those NOT on controller
▸ In the same NEJM issue, an adult and adolescent pragmatic (open-label) trial demonstrated that the severity of asthma exacerbations was reduced with quadrupling the inhaled steroid dose. However, the open-label, non-masked nature of that trial limits its ability to provide a definitive answer.
2018 - # 4
Lancet Public
Health.
2018;3:e64-e71
Parents providing alcohol - Introduction
▸ Approaches to alcohol consumption by adolescents vary
among developed countries.
▸ Available data are unclear on whether parental provision of
alcohol in social settings is a risk factor for alcohol misuse or
alcohol disorders in adolescents as they age.
▸ This prospective study in Australia recruited 1927 eligible
families/teens in 2010 and 2011
▸ Mean age 12.9 years when enrolled
▸ Alcohol use and exposure was assessed annually for about 5
years
Parents providing alcohol - Method
▸ Exposure groups:
‣ parental supply of alcohol
‣ nonparental supply of alcohol
‣ combination of these exposures
‣ compared to non-exposed
▸ Outcomes – 5 measures of alcohol use/misuse
‣ Binge drinking (> 4 drinks/setting)
‣ Alcohol-related harms
‣ Symptoms of alcohol abuse
‣ Alcohol dependence
‣ Alcohol use disorder
▸
Parents providing alcohol - Results
▸ By age 17 years
‣ 57% had been provided alcohol by parents
‣ 60% had experienced at least one alcohol-related harm
‣ 55% exhibited binge drinking
‣ 7% exhibited alcohol abuse symptoms
‣ 12% alcohol dependence syndrome
‣ 22% alcohol use disorder syndrome
7/24/2018
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Parents providing alcohol - Parents providing alcohol - Conclusions
▸ Authors:
‣ Providing alcohol to teenagers is associated with harm, whether from
parents or non-parents
‣ There is no evidence that parental provision is “protective”
▸ Viewpoint:
‣ Nonrandomized, single country, so not sure how applicable to US
‣ Did not control for other sociodemographic variables known to be
linked with alcohol consumption
‣ Longitudinal nature of the study adds power to findings
‣ Be sceptical the notion that providing minor children with alcohol will
protect them from adverse alcohol-related outcomes
2018 - #1
J Pediatr. 2017
Dec;191:190-196
Dex vs Prednisone - Introduction
▸ Systemic steroids are recommended for pediatric asthma
exacerbations.
‣ Global Initiative for Asthma (GINA). 2017 GINA report, global
strategy for asthma management and prevention.
‣ Traditional approach - 5-days of oral prednisone or prednisolone.
▸ Why dexamethasone:
‣ Better acceptability to patients (Pediatrics. 2014;133:493-499)
‣ Has longer half-life (36-72 h); therefore, maybe just 2 doses?
▸ Unanswered questions:
‣ How many dexamethasone doses are needed?
‣ What should the dose be?
Dex vs Prednisone - Method
▸ Research Question: Are 2 doses of dexamethasone as
effective as 5 days of prednisolone/prednisone for
exacerbation?
▸ Study type: Randomized, open-label, noninferiority trial.
▸ Subjects: 12 mo – 14 years, single ED, 2014-2015
▸ Inclusion: at least 2 episodes of exacerbation that responded to
beta-agonists; had asthma sx at enrollment
▸ Exclusion: Severe exacerbation, ICU, required Mg
▸ Treatment arms:
‣ Dexamethasone – 0.6 mg/kg (12 mg max) at enrollment and day 2
‣ Prednisone 1.5 mg/kg at enrollment (60 mg max), then 1 mg/kg/day
on days 2-5
Dex vs Prednisone - Method
▸ N = 590 children randomized
▸ > 95% completed study
▸ Outcomes:
‣ Phone follow up calls at 7 days and 15 days post ED visit
‣ Primary outcome: Percentage still experiencing asthma sx at day 7
‣ Secondary: Quality-of-life, ED returns, admissions, sx scores
‣ Note: non-inferiority was determined by < 6% difference in sx scores
7/24/2018
9
Dex vs Prednisone - Results
VariablesDexamethasone
group (n = 281)
Prednisone group
(n = 276)P
Persistence of symptoms by
PACT at day 7159 (56.6%) 161 (58.3%) ns
95% CI (50.6%-
62.6%)
95% CI (52.3%-
64.2%)
Persistent symptoms
While sitting quietly 16 (5.7%) 24 (8.7%) ns
With light activity 41 (14.6%) 44 (15.9%) ns
With sports 75 (26.7%) 91 (33%) ns
While asleep at night 127 (45.2%) 123 (44.6%) ns
In the morning 30 (10.7%) 34 (12.3%) ns
Need of bronchodilator 242 (86.1%) 252 (91.3%) ns
ARQoL at day 7* 80.0 (16.8) 77.7 (18.5) ns
Primary outcome in all patients included in the study
Dex vs Prednisone - Results
VariablesDexamethasone group
(n = 281)Prednisone group (n = 276) P
Observation admission 57 (20.3%) 53 (19.2%) ns
ED LOS, h* 4.9 (5.4) 4.8 (5.7) ns
Hospital admission 10 (3.6%) 7 (2.5%) ns
Unscheduled return to ED 13 (4.6%) 9 (3.3%) ns
Hospital readmission 1 (0.4%) 2 (0.7%) ns
Visits to primary care 212 (75.4%) 196 (71%) ns
Parental satisfaction 210 (93.8%) 179 (94.7%) ns
Vomiting 6 (2.1%) 12 (4.4%) ns
Adherence to treatment 279 (99.3%) 265 (96%) <.05
Further systemic steroids
administered22 (7.8%) 16 (6.2%) ns
Secondary outcomes in all patients included in the study
Dex vs Prednisone - Conclusions
▸ Authors:
‣ 2 doses of dexamethasone were non-inferior
‣ Applies to mild- and moderate-severity exacerbations
▸ Viewpoint:
‣ Great to see randomized data
‣ Appears to be an attractive option for providers and families
‣ 2-dose vs 10-dose comparison almost unfair, but > 96% both groups
‣ DOES NOT support a single-dose regimen – not tested in this study,
but (anecdotally) seems to be commonly done
2018 – Editors Choice
If only this were real…
N Engl J Med 2018;
378:1865-1876
As needed inhaled steroid+LABA - Introduction
▸ Short-acting beta-agonist (SABA) – terbutaline for this study
▸ Long-acting beta-agonist (LABA) – formoterol for this study
▸ Inhaled corticosteroids (ICS) – budesonide for this study
▸ Not really news, but for review:
‣ ICS is the mainstay controller for persistent asthma
‣ ICS adherence is a challenge
‣ For children, ICS exposure poses growth concerns
▸ Research Question:
▸ Can ICS+LABA PRN perform as well as ICS maintenance or SABA PRN
As needed inhaled steroid+LABA – Method
▸ Subjects: 12 or older, enrolled 2014-2016 (ended 2017)
▸ N = about 1280 per group (3 groups)
▸ Trial: Randomized, double-blind
▸ Inclusion:‣ Documented asthma that required controller (“persistent” asthma)
‣ No recent systemic steroids
‣ Non-severe asthma
▸ Regimens:‣ 1. SABA PRN: twice-daily placebo plus terbutaline (0.5 mg, used on an as-
needed basis; terbutaline group)
‣ 2. ICS+LABA PRN: twice-daily placebo plus budesonide–formoterol (200 μg of budesonide and 6 μg of formoterol, used on an as-needed basis
‣ 3. ICS MAINT: twice-daily budesonide (200 μg) plus terbutaline (0.5 mg, used on an as-needed basis; budesonide maintenance group).
7/24/2018
10
As needed inhaled steroid+LABA – Trial Design As needed inhaled steroid+LABA – Method:
▸ Primary outcome:
‣ Hypothesis: ICS+LABA (both PRN) was superior to SABA PRN based on “weeks with well-controlled asthma”
‣ Well-controlled was a combination of
‣ Diary symptom scores
‣ Nocturnal awakenings
‣ Peak Flow measurements
▸ Secondary outcomes:
‣ Hypothesis: ICS+LABA (PRN) was “non-inferior” to ICS (Maintenance) for
‣ Weeks of good control
‣ Time to first severe exacerbation
‣ Quality of Life
‣ Steroid dose (cumulative) exposure
As needed inhaled steroid+LABA - Results
▸ Severe exacerbation – occurred in 19.7% of subjects
▸ Adherence to the BID treatment was about 79% (all subjects) and did not differ among groups
▸ Primary Outcome
‣ ICS+LABA (Budesonide–formoterol) PRN was superior to SABA PRN (terbutaline) for mean percentage of weeks with well-controlled asthma per patient (34.4% vs. 31.1% of weeks; odds ratio, 1.14; 95% confidence interval [CI], 1.00 to 1.30; P=0.046)
▸ Secondary Outcome
‣ ICS+LABA (Budesonide–formoterol) PRN was inferior to ICS MAINTENANCE (budesonide) for mean percentage of weeks with well-controlled asthma per patient (34.4% vs. 44.4%; odds ratio, 0.64; 95% CI, 0.57 to 0.73)
As needed inhaled steroid+LABA - Results
N Engl J Med 2018; 378:1865-1876
As needed inhaled steroid+LABA - Results
▸ Other Secondary outcomes
‣ ICS+LABA (Budesonide–formoterol) PRN was superior to SABA PRN (terbutaline) for
‣ Rate of severe exacerbations
‣ Prolonging time to first severe exacerbation
‣ ICS+LABA (Budesonide–formoterol) PRN was equal to ICS MAINTENANCE (budesonide) for
‣ Rate of severe exacerbations
‣ Prolonging time to first severe exacerbation
‣ ICS+LABA PRN delivered 1/5 of steroid cumulative exposure (dose) compared to ICS MAINTENANCE
Similar Trial
7/24/2018
11
ICS+LABA PRN vs ICS MAINTENANCE
▸ Same sites and investigators
▸ Same study structure – 52 week total
▸ Same outcomes
▸ Findings:
‣ Budesonide–formoterol used as needed was noninferior to
budesonide maintenance therapy for severe exacerbations; the
annualized rate of severe exacerbations was 0.11 (95% confidence
interval [CI], 0.10 to 0.13) and 0.12 (95% CI, 0.10 to 0.14),
respectively (rate ratio, 0.97; upper one-sided 95% confidence limit,
1.16).
‣ Similar time to first exacerbation
‣ Quality of life and symptom scores BETTER with ICS MAINT
As needed inhaled steroid+LABA - Conclusions
▸ Authors:
‣ In patients with mild asthma, as-needed budesonide–formoterol
provided superior asthma-symptom control to as-needed terbutaline,
for weeks with well-controlled asthma, but was inferior to budesonide
maintenance therapy.
▸ Viewpoint:
‣ This should be considered “preliminary” data for children, and maybe
even adolescents
‣ Unable to separate out results for 12-18 years old
‣ Even if holds for children, must balance
‣ Inhaled steroid exposure and cost, vs
‣ Weekly symptoms
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References:
▸ Pharyngitis Testing Study - Pediatrics 2017 May;139(5)
▸ IDSA GAS guidelines -
https://academic.oup.com/cid/article/55/10/e86/321183
▸ CHAMP Trial (Migraine Prevention) - NEJM 2017; 376: 115-24
▸ CHAMP TRIAL editorial - Engl J Med 376:2, 169-170
▸ Penicillin Allergy study - Pediatrics. 2017 Aug;140(2)
▸ AOM Duration Trial - N Engl J Med. 2016;375:2446-2456.
References:
▸ Quintupling Inhaled Steroids - N Engl J Med. 2018 Mar
8;378(10):891-901
▸ Parental Supply of Alcohol - Lancet Public Health. 2018;3:e64-e71
▸ Dex vs Prednisone for acute asthma exacerbations - J Pediatr. 2017
Dec;191:190-196
▸ 2018 Global Strategy for Asthma Management and Prevention -
https://ginasthma.org/2018-gina-report-global-strategy-for-asthma-
management-and-prevention/
▸ Inhaled budesonide-formoterol as needed for mild asthma - N Engl J
Med 2018; 378:1865-1876
▸ Inhaled budesonide-fomotorol vs maintenance budesonide - N Engl J
Med 2018; 378:1877-1887
