-
American Journal of Rhinology & Allergy 2015Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and asthma are strongly associated, and patients suffering from both diseases are often difficult to treat.... (Review)
Review
BACKGROUND
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and asthma are strongly associated, and patients suffering from both diseases are often difficult to treat. However, no guidelines about the management of patients with CRS and coexisting asthma exist.
OBJECTIVE
The purpose of this systematic review was to evaluate the management of CRSwNP and coexisting asthma.
METHODS
We systematically searched electronic databases and included clinical trials in which the clinical outcomes after medical or surgical treatment of patients with CRSwNP and asthma were assessed. The strength of the evidence for each outcome was graded on the basis of study quality and consistency in findings.
RESULTS
We included seven trials in which the effect of montelukast, omalizumab, erythromycin, and functional endoscopic sinus surgery (FESS) were studied in 317 adults with CRSwNP and asthma. All the interventions improved the majority of subjective and objective nasal outcomes significantly. However, few studies found significant effects on pulmonary function tests. The strength of the evidence was low overall.
CONCLUSION
Both FESS and medical interventions with systemic anti-inflammatory drugs improved nasal outcomes, although their efficacy in relation to the lower airways remains unclear. A low number of studies met inclusion criteria for this systematic review, which emphasizes the need for high-quality trials to explore the treatment of patients with CRSwNP and coexisting asthma.
Topics: Acetates; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Endoscopy; Humans; Leukotriene Antagonists; Nasal Polyps; Omalizumab; Quality of Life; Quinolines; Rhinitis; Sinusitis; Sulfides
PubMed: 25975250
DOI: 10.2500/ajra.2015.29.4178 -
The West Indian Medical Journal May 2015To systematically assess the efficacy and safety of montelukast for postinfectious cough (PIC) and to propose a recommendation via a systematic review of all available...
OBJECTIVES
To systematically assess the efficacy and safety of montelukast for postinfectious cough (PIC) and to propose a recommendation via a systematic review of all available randomized controlled trials (RCTs).
METHODS
Electronic databases and relevant journals were searched for RCTs from inception to July 2014. In addition, some unpublished literature was also searched. All studies included in the systematic review met the same inclusion criteria. Methodological quality and evidence quality were examined according to Cochrane handbook. The data were extracted and trial quality was assessed independently by two reviewers.
RESULTS
Fourteen RCTs involving 1372 patients were included in our review. The methodological quality of the included trials was poor because one or more biases were observed in these studies. The quality of evidence was low to moderate levels. All trials reported better effect favouring montelukast treatment. Findings suggested that compared with other Western medication and Chinese medicine, montelukast showed significant effects in shortening cough relief time, increasing the clinic obvious effective rate, decreasing coughing frequency and severity, and improving quality of life. Adverse events were mentioned in six studies, but no serious adverse effects were reported in any of them.
CONCLUSIONS
Montelukast demonstrated potential positive efficacy and safety for PIC; however, we could not come to a firm conclusion on the efficacy and safety of montelukast for PIC. More high quality randomized controlled trials are required to confirm the efficacy and safety of montelukast for PIC.
PubMed: 28358440
DOI: 10.7727/wimj.2014.219 -
The Cochrane Database of Systematic... Mar 2015Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV). Management of bronchiolitis varies between clinicians, reflecting the lack of evidence for a specific treatment approach. The leukotriene pathway has been reported to be involved in the pathogenesis of bronchiolitis. Leukotriene inhibitors such as montelukast have been used in infants and young children with bronchiolitis. However, the results from limited randomised controlled trials (RCTs) are controversial and necessitate a thorough evaluation of their efficacy for bronchiolitis in infants and young children.
OBJECTIVES
To assess the efficacy and safety of leukotriene inhibitors for bronchiolitis in infants and young children.
SEARCH METHODS
We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to April week 4, 2014), EMBASE (1974 to May 2014), CINAHL (1981 to May 2014), LILACS (1982 to May 2014), Web of Science (1985 to May 2014), WHO ICTRP and ClinicalTrials.gov (6 May 2014).
SELECTION CRITERIA
RCTs comparing leukotriene inhibitors versus placebo or another intervention in infants and young children under two years of age diagnosed with bronchiolitis. Our primary outcomes were length of hospital stay and all-cause mortality. Secondary outcomes included clinical severity score, percentage of symptom-free days, percentage of children requiring ventilation, oxygen saturation, recurrent wheezing, respiratory rate and clinical adverse effects.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Collaboration methodological practices. Two authors independently assessed trial eligibility and extracted data, such as general information, participant characteristics, interventions and outcomes. We assessed risk of bias and graded the quality of the evidence. We used Review Manager software to pool results and chose random-effects models for meta-analysis.
MAIN RESULTS
We included five studies with a total of 1296 participants under two years of age hospitalised with bronchiolitis. Two studies with low risk of bias compared 4 mg montelukast (a leukotriene inhibitor) daily use from admission until discharge with a matching placebo. Both selected length of hospital stay as a primary outcome and clinical severity score as a secondary outcome. However, the effects of leukotriene inhibitors on length of hospital stay and clinical severity score were uncertain due to considerable heterogeneity between the study results and wide confidence intervals around the estimated effects (hospital stay: mean difference (MD) -0.95 days, 95% confidence interval (CI) -3.08 to 1.19, P value = 0.38, low quality evidence; clinical severity score on day two: MD -0.57, 95% CI -2.37 to 1.23, P value = 0.53, low quality evidence; clinical severity score on day three: MD 0.17, 95% CI -1.93 to 2.28, P value = 0.87, low quality evidence). The other three studies compared montelukast for several weeks for preventing post-bronchiolitis symptoms with placebo. We assessed one study as low risk of bias, whereas we assessed the other two studies as having a high risk of attrition bias. Due to the significant clinical heterogeneity in severity of disease, duration of treatment, outcome measurements and timing of assessment, we did not pool the results. Individual analyses of these studies did not show significant differences between the leukotriene inhibitors group and the control group in symptom-free days and incidence of recurrent wheezing. One study of 952 children reported two deaths in the leukotriene inhibitors group: neither was determined to be drug-related. No data were available on the percentage of children requiring ventilation, oxygen saturation and respiratory rate. Finally, three studies reported adverse events including diarrhoea, wheezing shortly after administration and rash. No differences were reported between the study groups.
AUTHORS' CONCLUSIONS
The current evidence does not allow definitive conclusions to be made about the effects of leukotriene inhibitors on length of hospital stay and clinical severity score in infants and young children with bronchiolitis. The quality of the evidence was low due to inconsistency (unexplained high levels of statistical heterogeneity) and imprecision arising from small sample sizes and wide confidence intervals, which did not rule out a null effect or harm. Data on symptom-free days and incidence of recurrent wheezing were from single studies only. Further large studies are required. We identified one registered ongoing study, which may make a contribution in the updates of this review.
Topics: Acetates; Bronchiolitis; Cyclopropanes; Humans; Infant; Length of Stay; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides
PubMed: 25773054
DOI: 10.1002/14651858.CD010636.pub2 -
International Journal of Dermatology Sep 2015Patients with chronic spontaneous urticaria (CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published... (Review)
Review
BACKGROUND
Patients with chronic spontaneous urticaria (CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published clinical evidence for patients who remain symptomatic despite treatment.
OBJECTIVE
To evaluate, via a systematic literature review, clinical evidence of management strategies for patients with CSU who remain symptomatic despite approved use of nonsedating H1 antihistamines.
METHODS
Using a prespecified protocol, we searched MEDLINE, Embase, the Cochrane Library (1 January 1960-20 December 2011), and published conference abstracts (2010-2012). Rigorous criteria identified trials in patients with CSU who had a history of inadequate response to previous treatment or had used combination treatments. Trials evaluating treatment-naïve patients or first-line therapies were excluded.
RESULTS
Qualitative data synthesized from 26 randomized, controlled trials, four prospective studies, and one retrospective study showed cyclosporine, desloratadine plus dapsone or dipyridamole, montelukast, and omalizumab reduced urticaria activity scores, weals, and pruritus, versus placebo. Optimal treatment doses and durations were unclear due to varying trial durations, outcome measurement scales, and assessment timings. No safety concerns were reported.
CONCLUSIONS
This review confirms that available evidence to guide treatment choice for patients with CSU with inadequate response to H1 antihistamines varies in quality. Further research is warranted due to low-quality trials with methodological and reporting limitations.
Topics: Cholinergic Antagonists; Chronic Disease; Drug Therapy, Combination; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Failure; Urticaria
PubMed: 25515967
DOI: 10.1111/ijd.12727 -
The Cochrane Database of Systematic... Sep 2014Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).
OBJECTIVES
To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.
SEARCH METHODS
We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE 2014, Issue 2), accessed from The Cochrane Library, MEDLINE (1950 to 30 January 2014), EMBASE (1980 to 30 January 2014), AMED (1985 to 30 January 2014), CINAHL (1980 to 30 January 2014) and LILACS (30 January 2014). We searched Current Controlled Trials to identify trials in progress.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.
DATA COLLECTION AND ANALYSIS
Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated searches in 2012 and 2014. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.
MAIN RESULTS
We included 12 trials of varying sample sizes (N = 9 to 135), mainly from high-income countries, including a total of 578 participants. Ten trials recruited children (N = 448 participants). Two trials recruited adolescents and adults (N = 130 participants). We considered only three trials to be of high methodological quality (one trial each of diphenhydramine, pertussis immunoglobulin and montelukast). Included studies did not show a statistically significant benefit for any of the interventions. Only six trials, including a total of 196 participants, reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) -4.7 to 8.5 (N = 49 participants from one trial). One trial on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02, N = 47 participants) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4, N = 46 participants). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4, N = 11 participants from one trial) and salbutamol showed no change in coughing paroxysms per day (MD -0.2; 95% CI -4.1 to 3.7, N = 42 participants from two trials). Only one trial comparing pertussis immunoglobulin versus placebo (N = 47 participants) reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site).
AUTHORS' CONCLUSIONS
There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough. More high-quality trials are needed to assess the effectiveness of potential antitussive treatments in patients with whooping cough.
Topics: Acetates; Adolescent; Adult; Albuterol; Anti-Inflammatory Agents; Bordetella pertussis; Child; Cough; Cyclopropanes; Dexamethasone; Diphenhydramine; Histamine H1 Antagonists; Humans; Immunoglobulins; Length of Stay; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Whooping Cough
PubMed: 25243777
DOI: 10.1002/14651858.CD003257.pub5 -
Allergy and Asthma Proceedings 2014It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma... (Meta-Analysis)
Meta-Analysis Review
It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma exacerbations is not systematically assessed. This study was designed to systematically explore the evidence for montelukast, as first-line or add-on therapy, in preventing and treating asthma exacerbations in adult patients with asthma. Randomized controlled trials were searched in PubMed, CENTRAL, Web of Science, Embase, and OVID up to March 2013, where montelukast prevented or treated asthma exacerbations in adults. Primary outcomes were the number of patients experiencing exacerbations in chronic asthma and hospitalizations in acute asthma. Odds ratio (OR) with 95% confidence intervals (CI), risk difference, and number needed to treat (NNT) were calculated and pooled. Adverse events were also assessed in chronic asthma. Twenty trials for chronic asthma and six for acute asthma were identified. In comparison with placebo, adults with chronic asthma receiving montelukast had significantly reduced number of exacerbations (OR = 0.60 and 95% CI, 0.49, 0.74; NNT = 17 and 95% CI, 12, 29). However, montelukast was inferior to inhaled corticosteroids (ICSs) (OR = 1.63; 95% CI, 1.29, 2.0) and ICS plus long-acting beta2-agonist (LABA; OR = 3.94; 95% CI, 1.64, 9.48) as the first-line therapies and LABA (OR = 1.22; 95% CI, 1.05, 1.42) as the add-on therapies in reducing asthma exacerbations. In acute asthma, montelukast could statistically improve peak expiratory flow percent predicted (p = 0.008) and reduce systemic corticosteroid intake (p = 0.005). Montelukast had low risk in hoarseness and insomnia. Our meta-analysis suggests that montelukast significantly reduces mild, moderate, and part of severe exacerbations in chronic mild to moderate asthma, but it has inferior efficacy to ICS or ICS plus LABA.
Topics: Acetates; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Cyclopropanes; Disease Progression; Humans; Leukotriene Antagonists; Quinolines; Sulfides; Treatment Outcome
PubMed: 24992547
DOI: 10.2500/aap.2014.35.3745 -
Allergy, Asthma, and Clinical... 2014A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are... (Review)
Review
A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.
PubMed: 24817895
DOI: 10.1186/1710-1492-10-24 -
International Journal of Clinical... Apr 2014Respiratory medications are frequently prescribed for use in children. Several studies have reported information on the safety of asthma medications in clinical studies... (Review)
Review
BACKGROUND
Respiratory medications are frequently prescribed for use in children. Several studies have reported information on the safety of asthma medications in clinical studies in adults, but information about safety in children is scarce.
OBJECTIVE
To review published clinical trials on the occurrence and characteristics of adverse drug reactions (ADRs) in children, reported for asthma medications licensed for paediatric use.
METHODS
We systematically reviewed the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed, Embase, Cochrane Library, PsycINFO, IPA, and CINAHLs databases were searched from origin until July 2013 for studies reporting ADRs for beta2-receptor agonists, inhaled corticosteroids, leukotriene receptor antagonists and combination products in children from birth to age 17. Information on ADR reporting rates, age and gender, type and seriousness of ADRs, design, setting, observation period, type of assessors, and funding sources was extracted from the articles.
RESULTS
Literature searches resulted in 162 potential relevant articles. However only 12 of these studies were included in this review as they reported information about ADR rates from use of salmeterol, formoterol, fluticasone, montelukast, zafirlukast and budesonide/formoterol in children. The total population was approximately 3,000 children; the majority was 6- to 11-year-olds and two thirds of these were boys. The observation period varied from 1 to 22 months. The most frequently reported ADRs were exacerbation of asthma, respiratory tract infection, cough, fever and headache. Only few ADRs were rated as being serious, however a number of children dropped out of the clinical trials due to serious ADRs, and, therefore, the real number of serious ADRs is probably higher.
CONCLUSIONS
Few clinical trials reporting ADRs from use of asthma medications in children were identified in the literature. These studies reported only a few types of ADRs, the majority being non-serious.
Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Infant; Male; Publication Bias
PubMed: 24562976
DOI: 10.1007/s11096-014-9924-y -
The Cochrane Database of Systematic... Jan 2014Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists (LABA) and anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.
OBJECTIVES
To compare the safety and efficacy of adding LABA versus LTRA to the treatment regimen for children and adults with asthma who remain symptomatic in spite of regular treatment with ICS. We specifically wished to examine the relative impact of the two agents on asthma exacerbations, lung function, symptoms, quality of life, adverse health events and withdrawals.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register until December 2012. We consulted reference lists of all included studies and contacted pharmaceutical manufacturers to ask about other published or unpublished studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS along with a fixed dose of a LABA or an LTRA for a minimum of four weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design when necessary.
MAIN RESULTS
We included 18 RCTs (7208 participants), of which 16 recruited adults and adolescents (6872) and two recruited children six to 17 years of age (336) with asthma and significant reversibility to bronchodilator at baseline. Fourteen (79%) trials were of high methodological quality.The risk of exacerbations requiring systemic corticosteroids (primary outcome of the review) was significantly lower with the combination of LABA + ICS compared with LTRA + ICS-from 13% to 11% (eight studies, 5923 adults and 334 children; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 0.99; high-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) with LABA compared with LTRA to prevent one additional exacerbation over four to 102 weeks was 62 (95% CI 34 to 794). The choice of LTRA, the dose of ICS and the participants' age group did not significantly influence the magnitude of effect. Although results were inconclusive, the effect appeared stronger in trials that used a single device rather than two devices to administer ICS and LABA and in trials of less than 12 weeks' duration.The addition of LABA to ICS was associated with a statistically greater improvement from baseline in lung function, as well as in symptoms, rescue medication use and quality of life, although the latter effects were modest. LTRA was superior in the prevention of exercise-induced bronchospasm. More participants were satisfied with the combination of LABA + ICS than LTRA + ICS (three studies, 1625 adults; RR 1.12, 95% CI 1.04 to 1.20; moderate-quality evidence). The overall risk of withdrawal was significantly lower with LABA + ICS than with LTRA + ICS (13 studies, 6652 adults and 308 children; RR 0.84, 95% CI 0.74 to 0.96; moderate-quality evidence). Although the risk of overall adverse events was equivalent between the two groups, the risk of serious adverse events (SAE) approached statistical significance in disfavour of LABA compared with LTRA (nine studies, 5658 adults and 630 children; RR 1.33, 95% CI 0.99 to 1.79; P value 0.06; moderate-quality evidence), with no apparent impact of participants' age group.The following adverse events were reported, but no significant differences were demonstrated between groups: headache (11 studies, N = 6538); cardiovascular events (five studies, N = 5163), osteopenia and osteoporosis (two studies, N = 2963), adverse events (10 studies, N = 5977 adults and 300 children). A significant difference in the risk of oral moniliasis was noted, but this represents a low occurrence rate.
AUTHORS' CONCLUSIONS
In adults with asthma that is inadequately controlled by predominantly low-dose ICS with significant bronchodilator reversibility, the addition of LABA to ICS is modestly superior to the addition of LTRA in reducing oral corticosteroid-treated exacerbations, with an absolute reduction of two percentage points. Differences favouring LABA over LTRA as adjunct therapy were observed in lung function and, to a lesser extend, in rescue medication use, symptoms and quality of life. The lower overall withdrawal rate and the higher proportion of participants satisfied with their therapy indirectly favour the combination of LABA + ICS over LTRA + ICS. Evidence showed a slightly increased risk of SAE with LABA compared with LTRA, with an absolute increase of one percentage point. Our findings modestly support the use of a single inhaler for the delivery of both LABA and low- or medium-dose ICS. Because of the paucity of paediatric trials, we are unable to draw firm conclusions about the best adjunct therapy in children.
Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Child; Chronic Disease; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Randomized Controlled Trials as Topic; Young Adult
PubMed: 24459050
DOI: 10.1002/14651858.CD003137.pub5 -
The Journal of Allergy and Clinical... Feb 2014Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control. (Review)
Review
BACKGROUND
Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control.
OBJECTIVE
We sought to systematically evaluate the efficacy and safety of systemic treatments for moderate-to-severe AD.
METHODS
A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events.
RESULTS
Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures.
CONCLUSION
Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required.
Topics: Azathioprine; Cyclosporine; Dermatitis, Atopic; Glucocorticoids; Humans; Immunosuppressive Agents; Interferon-gamma; Methotrexate; Mycophenolic Acid
PubMed: 24269258
DOI: 10.1016/j.jaci.2013.07.049