Combination of Inhaled Corticosteroids and Long-Acting Beta Agonists Improves Lung Function in Children Born Prematurely
Combination therapy with an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) significantly improved lung spirometry results in children with significant lung function deficits compared with either steroids alone or placebo. These are results of a study conducted in Wales, at the Children’s Hospital for Wales in Cardiff, which tested the combination in school-aged children who had been born prematurely (before 34 weeks’ gestation). These children are known to be at increased risk of decreases in future lung function, especially when they are diagnosed with bronchopulmonary dysplasia (BPD) in infancy.
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The randomized controlled trial enrolled 53 children ages 7 to 14, who were born at <34 weeks’ gestation, with low lung function (pretreatment %FEV1 [percent forced expiratory volume in 1 second] ≤85%) and examined whether 12 weeks of treatment would improve incentive spirometry results and exercise capacity. Approximately 40% of participants in the study had BPD; other signs of respiratory morbidity were similar in all groups. They were randomized to the ICS fluticasone 50 mcg plus placebo (n = 20), fluticasone 50 mcg plus the LABA salmeterol 25 mcg (n = 19), and placebo (n = 14), all given as 2 puffs per day for 12 weeks.
Both ICS and ICS/LABA combination treatment produced improvements in %FEV1, both significantly greater than placebo. The increase in %FEV1 with ICS was 7.7% higher than placebo; with the ICS/LABA combination, the increase was twice as great: 14.1% higher than placebo. The %FEV1 increased from 75.1% to 81.1% (mean difference, 6.0%) in the ICS group and from 77.9% to 86.2% (mean difference, 8.3%) in the ICS/LABA group. Active treatment decreased the fractional exhaled nitric oxide (FENO) and increased postexercise bronchodilator response but didn’t improve exercise capacity. The FENO dropped from 29.8 ppb (parts per billion) to 15.7 ppb in the ICS group and from 25.2 ppb to 15.9 ppb in the ICS/LABA group. FENO didn’t decrease after placebo.
The combination ICS/LABA may produce its greater effects by targeting both the structural changes in the respiratory system of children born preterm and inflammatory processes, as suggested by the improvement in FENO. The lack of improvement in exercise capacity in this trial may have resulted from the test not being sensitive enough to note small differences, especially in a population that might have been habitually inactive. (Goulden, N., et al. (2022). Inhaled corticosteroids alone and in combination with long-acting β2 receptor agonists to treat reduced lung function in preterm-born children: A randomized clinical trial. JAMA Pediatr,176(2), 133–141. Retrieved March 2022 from https://jamanetwork.com/journals/jamapediatrics/fullarticle/2786783)
Released: March 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Third Dose Boosts COVID-19 Vaccine Efficacy in Patients with CLL
In an Israeli study, in patients with CLL (chronic lymphocytic leukemia) who had failed to achieve an antibody response to two doses of an mRNA vaccine against SARS-CoV2, close to a quarter of the patients in the study became seropositive after a third dose.
Patients were enrolled from July 2020 to August 2021; eligible patients had a diagnosis of CLL or small lymphocytic lymphoma (SLL), were age 18 or older, had no know history of SARS-CoV2 infection, and had failed to respond to a second dose of a vaccine against SARS-CoV2. The 172 patients were classified into three groups: the treatment-naive (n = 40, 23.3%), those who were on active treatment for CLL/SLL (n = 100, 58.1%), and those not currently receiving treatment who had been treated previously (n = 32, 18.6%). Among those who had received treatment in the past, 24 (75%) were in remission, 18 of them in complete remission, and 8 (25%) were experiencing relapse. Patients on active treatment included 59 who were receiving a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib) and 39 receiving venetoclax either with or without an anti-CD20 antibody (rituximab or obinutuzumab).
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Serologic response after the third vaccine dose correlated with the degree of immunosuppression accompanying CLL in each patient. Antibody response was seen in 41/172 patients (23.8%), with a median antibody level of 2 AU/mL. Treatment-naïve patients and those who were no longer receiving treatment for their illness had higher response rates and higher antibody levels: 16/40 (40%) of treatment-naive patients had antibody response, with median antibody level of 8 AU/mL, and 13/32 of patients no longer on treatment, with median antibody level of 6 AU/mL. In actively treated patients, response rates were lower (n = 12/100, 12%), with a median antibody level of 0 AU/mL.
Among patients who had previously received treatment, serologic response rates of those in complete remission was 38.9%, in partial remission was 50%, and those experiencing relapse was 37.5%. Among those on active treatment, those receiving BTK inhibitors had a response rate of 15.3% and those receiving venetoclax with or without anti-CD20 antibodies had a response rate of 7.7%. Only 1 of 28 patients (3.6%) treated with anti-CD20 antibodies within 12 months of the third dose responded, compared to 15/63 (22.7%) of those treated with anti-CD20 antibodies at least 12 months before. Each month that elapsed from the end of anti-CD20 antibody treatment increased odds for serologic response to the vaccine by 1.03 times.
The study authors suggested that an additional booster be considered for all patients with CLL who had been vaccinated with mRNA vaccines. Since results were lowest in those on active therapy, they suggest that it may be appropriate to delay the start of treatment to allow for vaccination before treatment produces immunosuppression. (Herishanu, Y., et al. (2022). Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood, 139(5): 678–685. Retrieved March 2022 from https://ashpublications.org/blood/article/139/5/678/482889/Efficacy-of-a-third-BNT162b2-mRNA-COVID-19-vaccine?searchresult=1)
Released: March 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Statin Intolerance May Be Overestimated
Findings of a recent meta-analysis indicate that intolerance to statin therapy is much less common than previous data suggested, showing that fewer than 1 in 10 patients are unable to tolerate the cholesterol-lowering treatment. Nonadherence to statin therapy due to the fear of statin intolerance results in suboptimal treatment for dyslipidemia and a high risk of cardiovascular events.
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The meta-analysis of 176 studies (involving more than 4 million patients) published in the European Heart Journal found that 9.1% of patients had statin intolerance. The analysis included 112 randomized clinical trials and 64 cohort studies of statin-treated patients followed for a mean of 19 months. It estimated the overall prevalence of statin intolerance and also aimed to determine prevalence according to differing international diagnostic criteria and in different disease settings. In addition, the researchers identified possible risk factors for statin intolerance.
In published studies, the mean prevalence of statin intolerance in randomized clinical trials was 4.9%, and in cohort studies was 17%. The higher prevalence in cohort studies, which is as high as 30%, is most likely an overestimate and could be attributable to “nocebo” effects. On the other hand, it’s possible that exclusion criteria in randomized controlled trials may result in underestimates, as older patients and those with comorbidities associated with statin intolerance are excluded. When examining prevalence of intolerance based on varied diagnostic criteria, it was 7% in studies that used the National Lipid Association (NLA) criteria, which defines intolerance as an adverse effect that limits quality of life and leads to a decision to decrease or stop the statin. Prevalence under International Lipid Expert Panel criteria, which were similar to those of NLA, was 6.7%. Under the stricter definition provided by the European Atherosclerosis Society, which focused specifically on statin-associated muscle symptoms (SAMS) and CK elevations, prevalence was 5.9%.
Increased risk of statin intolerance was associated with demographic characteristics and with clinical indices. Women had a 47% higher relative risk (RR) of statin intolerance compared to men, and the RR was 31.2% higher in those over age 65 than in younger patients. Positive associations were also seen in patients with obesity (RR, 30.6%), diabetes (RR, 26.6%), and hypothyroidism (RR, 37.6%). The positive associations in Black and Asian patients and in those with chronic liver and kidney disease were smaller, but still clinically significant.
Nonadherence with statin therapy is most commonly ascribed to muscle pain, but it’s important for clinicians to determine whether that muscle pain is actually related to statin use. The criteria necessary for a diagnosis of SAMS are that the symptoms (pain, weakness, or cramps, often with CK changes or severe myopathy) must appear within 12 weeks after treatment initiation or dose increase. Clinicians should explore whether muscle pain at later stages results from interactions with a new medication or as a result of a comorbid condition that’s not controlled. (O’Riordan, M. (2022). Statin intolerance overestimated – Only ‘small number’ get side effects: Meta-analysis. TCTmd.com. Retrieved March 2022 from https://www.tctmd.com/news/statin-intolerance-overestimated-only-small-number-get-side-effects-meta-analysis
Bytyҫi, I., et al. (2022). Prevalence of statin intolerance: A meta-analysis. Eur Heart J, 1–16. Retrieved March 2022 from https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac015/6529098?login=false)
Released: March 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer