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Current Medical Research and Opinion Nov 2013Allergic rhinitis is a complex inflammatory disease whose pathophysiology involves local and systemic mechanisms. Rupatadine, a molecule with intense antihistaminic... (Review)
Review
BACKGROUND
Allergic rhinitis is a complex inflammatory disease whose pathophysiology involves local and systemic mechanisms. Rupatadine, a molecule with intense antihistaminic activity and with antagonist PAF effects through its interaction with specific receptors, is indicated for the treatment of intermittent or persistent allergic rhinitis and urticaria.
SCOPE
This systematic review was aimed at identifying in the most important databases, up to January 2013, the double-blind placebo-controlled randomized trials administering rupatadine in allergic rhinitis. No restriction was introduced for treatment duration and dose, study design, population age, allergen exposition and disease classification. The methodological quality of included studies and risk of bias were systematically assessed. Meta-analysis was performed when possible to summarize information.
FINDINGS
Seventeen of 413 initially identified records were fully assessed for eligibility. Ten trials involving 2573 patients overall met the inclusion criteria and entered the analysis. Their internal validity was satisfactory. Data synthesis showed that rupatadine is superior to placebo in relieving the overall allergy symptoms on reflective (SMD: -0.37, 95% CI -0.46 to -0.27; p < 0.00001) and instantaneous (SMD: -0.41, 95% CI -0.71 to -0.11; p = 0.007) assessment, the nasal symptoms considered together (reflective SMD: -0.36, 95% CI -0.48 to -0.25; p < 0.00001; instantaneous SMD: -0.39, 95% CI -0.61 to -0.17; p = 0.0004) or individually and ocular symptoms. Inter-study heterogeneity was low for the main outcomes and the risk of publication bias was judged as unlikely. A number of secondary endpoints were favorably affected by rupatadine. No difference was observed in the incidence of total adverse reactions between rupatadine and placebo (OR 1.23, 95% CI 0.95 to 1.59; p = 0.12).
CONCLUSION
Randomized double-blind controlled trials show a favorable risk-benefit ratio in rupatadine for the treatment of allergic rhino-conjunctivitis. This evidence is strengthened when data are pooled in the form of meta-analysis, where accurate and robust effect estimations are derived from a large population.
Topics: Conjunctivitis, Allergic; Cyproheptadine; Histamine Antagonists; Humans; Platelet Activating Factor; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria
PubMed: 23826741
DOI: 10.1185/03007995.2013.822855 -
Ophthalmology Nov 2013To assess the efficacy and safety of topical cyclosporine versus placebo in the treatment of allergic conjunctivitis. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the efficacy and safety of topical cyclosporine versus placebo in the treatment of allergic conjunctivitis.
DESIGN
Systematic review and meta-analysis.
PARTICIPANTS
Seven qualified studies incorporating 306 eyes of 153 patients were analyzed.
METHODS
Searches of randomized controlled trials were conducted in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform.
MAIN OUTCOME MEASURES
We assessed the methodologic quality of individual included trials and performed meta-analyses using the random effects model if P<0.1 in the test for heterogeneity, or otherwise used the fixed effects model. We assessed scores of composite signs and symptoms, reduction in steroid eye drop use in steroid-dependent patients, and safety outcomes (i.e., stinging or burning sensation).
RESULTS
At 2 weeks of follow-up or longer, evidence suggests a statistically significant improvement in the composite signs (standardized mean difference [SMD], -1.21; 95% confidence interval [CI], -1.80 to -0.62; I(2) = 71%) and symptoms (SMD, -0.84; 95% CI, -1.51 to -0.16; I(2) = 80%) after topical cyclosporine treatment for allergic conjunctivitis regardless of the dosage of treatment. There was a significant reduction (mean difference, -61.16; 95% CI, -101.61 to -20.72; I(2) = 58%) in the use of steroid eye drops in patients with steroid-dependent allergic conjunctivitis. Stinging or burning sensation (odds ratio, 2.56; 95% CI, 0.19-35.06; I(2) = 73%) was common in both the cyclosporine and placebo groups.
CONCLUSIONS
This systematic review and meta-analysis suggests topical cyclosporine could be an effective and safe treatment method for allergic conjunctivitis. Further randomized controlled trials with larger sample sizes and standardized outcome measurements, follow-up periods, and cyclosporine concentrations are warranted to determine the short- and long-term efficacy and safety and the minimal effective dosage of topical cyclosporine for allergic conjunctivitis.
Topics: Administration, Topical; Conjunctivitis, Allergic; Cyclosporine; Databases, Factual; Humans; Immunosuppressive Agents; Ophthalmic Solutions; Treatment Outcome
PubMed: 23743438
DOI: 10.1016/j.ophtha.2013.03.044 -
Pediatrics Jun 2013Subcutaneous immunotherapy (SCIT) is approved in the United States for the treatment of pediatric asthma and rhinitis; sublingual immunotherapy (SLIT) does not have... (Review)
Review
BACKGROUND AND OBJECTIVE
Subcutaneous immunotherapy (SCIT) is approved in the United States for the treatment of pediatric asthma and rhinitis; sublingual immunotherapy (SLIT) does not have regulatory approval but is used in clinical practice. The objective of this study was to systematically review the evidence regarding the efficacy and safety of SCIT and SLIT for the treatment of pediatric asthma and allergic rhinoconjunctivitis.
METHODS
Two independent reviewers selected articles for inclusion, extracted data, and graded the strength of evidence for each clinical outcome. All studies were randomized controlled trials of children with allergic asthma or rhinoconjunctivitis treated with SCIT or an aqueous formulation of SLIT. Data sources were Medline, Embase, LILACS, CENTRAL, and the Cochrane Central Register of Controlled Trials through May 2012.
RESULTS
In 13 trials, 920 children received SCIT or usual care; in 18 studies, 1583 children received SLIT or usual care. Three studies compared SCIT with SLIT head-to-head in 135 children. The strength of evidence is moderate that SCIT improves asthma and rhinitis symptoms and low that SCIT improves conjunctivitis symptoms and asthma medication scores. Strength of evidence is high that SLIT improves asthma symptoms and moderate that SLIT improves rhinitis and conjunctivitis symptoms and decreases medication usage. The evidence is low to support SCIT over SLIT for improving asthma or rhinitis symptoms or medication usage. Local reactions were frequent with SCIT and SLIT. There was 1 report of anaphylaxis with SCIT.
CONCLUSIONS
Evidence supports the efficacy of both SCIT and SLIT for the treatment of asthma and rhinitis in children.
Topics: Administration, Sublingual; Adolescent; Asthma; Child; Child, Preschool; Conjunctivitis, Allergic; Desensitization, Immunologic; Humans; Rhinitis, Allergic, Seasonal; Treatment Outcome
PubMed: 23650298
DOI: 10.1542/peds.2013-0343 -
JAMA Mar 2013Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be... (Review)
Review
IMPORTANCE
Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization.
OBJECTIVE
To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma.
EVIDENCE ACQUISITION
The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence.
RESULTS
Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n = 1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than 40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported.
CONCLUSIONS AND RELEVANCE
The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review.
Topics: Administration, Sublingual; Allergens; Asthma; Conjunctivitis, Allergic; Desensitization, Immunologic; Humans; Off-Label Use; Randomized Controlled Trials as Topic; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Treatment Outcome
PubMed: 23532243
DOI: 10.1001/jama.2013.2049 -
The Cochrane Database of Systematic... Sep 2012Some breastfed infants with atopic eczema benefit from elimination of cow milk, egg, or other antigens from their mother's diet. Maternal dietary antigens are also known... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some breastfed infants with atopic eczema benefit from elimination of cow milk, egg, or other antigens from their mother's diet. Maternal dietary antigens are also known to cross the placenta.
OBJECTIVES
To assess the effects of prescribing an antigen avoidance diet during pregnancy or lactation, or both, on maternal and infant nutrition and on the prevention or treatment of atopic disease in the child.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 July 2012).
SELECTION CRITERIA
All randomized or quasi-randomized comparisons of maternal dietary antigen avoidance prescribed to pregnant or lactating women. We excluded trials of multimodal interventions that included manipulation of the infant's diet other than breast milk or of non-dietary aspects of the infant's environment.
DATA COLLECTION AND ANALYSIS
We extracted data from published reports, supplemented by additional information received from the trialists we contacted.
MAIN RESULTS
The evidence from five trials, involving 952 participants, does not suggest a protective effect of maternal dietary antigen avoidance during pregnancy on the incidence of atopic eczema during the first 18 months of life. Data on allergic rhinitis or conjunctivitis, or both, and urticaria are limited to a single trial each and are insufficient to draw meaningful inferences. Longer-term atopic outcomes have not been reported. The restricted diet during pregnancy was associated with a slightly but statistically significantly lower mean gestational weight gain, a non-significantly higher risk of preterm birth, and a non-significant reduction in mean birthweight.The evidence from two trials, involving 523 participants, did not observe a significant protective effect of maternal antigen avoidance during lactation on the incidence of atopic eczema during the first 18 months or on positive skin-prick tests to cow milk, egg, or peanut antigen at one, two, or seven years.One crossover trial involving 17 lactating mothers of infants with established atopic eczema found that maternal dietary antigen avoidance was associated with a non-significant reduction in eczema severity.
AUTHORS' CONCLUSIONS
Prescription of an antigen avoidance diet to a high-risk woman during pregnancy is unlikely to reduce substantially her child's risk of atopic diseases, and such a diet may adversely affect maternal or fetal nutrition, or both. Prescription of an antigen avoidance diet to a high-risk woman during lactation may reduce her child's risk of developing atopic eczema, but better trials are needed.Dietary antigen avoidance by lactating mothers of infants with atopic eczema may reduce the severity of the eczema, but larger trials are needed.
Topics: Allergens; Dermatitis, Atopic; Diet, Protein-Restricted; Dietary Proteins; Female; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Infant; Infant, Newborn; Lactation; Pregnancy; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 22972039
DOI: 10.1002/14651858.CD000133.pub3 -
The Journal of Family Practice Jul 2012Intranasal steroids provide better relief for adult sufferers, according to nonstandardized, nonclinically validated scales. Steroids reduce subjective total nasal... (Comparative Study)
Comparative Study Review
Intranasal steroids provide better relief for adult sufferers, according to nonstandardized, nonclinically validated scales. Steroids reduce subjective total nasal symptom scores (TNSS)--representing sneezing, itching, congestion, and rhinorrhea--by about 25% more than placebo, whereas oral antihistamines decrease TNSS by 5% to 10% (strength of recommendation [SOR]: B, systematic review of randomized controlled trials [RCTs], most without clinically validated or standardized outcome measures). Intranasal steroids improve subjective eye symptom scores as well as (or better than) oral antihistamines in adults who also have allergic conjunctivitis (SOR: A, systematic review, RCTs).
Topics: Administration, Intranasal; Administration, Oral; Histamine Antagonists; Humans; Practice Guidelines as Topic; Rhinitis, Allergic, Seasonal; Steroids; Treatment Outcome
PubMed: 22754886
DOI: No ID Found -
Clinical and Experimental Allergy :... Sep 2011Allergic conjunctivitis (AC) is a common manifestation and represents an important co-morbidity of allergic rhinitis (AR). Sublingual immunotherapy (SLIT) is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Allergic conjunctivitis (AC) is a common manifestation and represents an important co-morbidity of allergic rhinitis (AR). Sublingual immunotherapy (SLIT) is an effective and safe treatment for nasal symptoms of AR; its effectiveness is however less well established for ocular symptoms.
OBJECTIVES
To evaluate the effectiveness of SLIT in reducing ocular symptoms, the need for ocular treatments and the threshold exposure for conjunctival immediate allergen sensitivity (CIAS).
METHODS
We searched eight databases up to January 2010. We included only randomized controlled trials (RCT), double-blind and placebo-controlled evaluating the efficacy of SLIT in patients with symptoms of allergic rhinoconjunctivitis (ARC) or AC. Primary outcome measures were total ocular symptom scores, individual ocular symptoms scores (itchy eyes, eye redness, watery eyes, swelling eyes), eye drops use and CIAS. Meta-analysis was undertaken using RevMan 5 software.
RESULTS
From 811 abstracts that were screened, 109 studies were reviewed in their full text version. Forty two trials including 3958 participants (n=2011 SLIT and n=1947 placebo) had data suitable for inclusion in the meta-analysis. SLIT induced a significant reduction on both total ocular symptom scores (SMD: -0.41; 95%CI: -0.53 to -0.28; I(2) : 59%) and individual ocular symptoms scores [red (-0.33; -0.45 to -0.22), itchy (-0.31; -0.42 to -0.20) and watery eyes (-0.23; -0.34 to -0.11)] compared with placebo. Participants in the SLIT group showed an increase in the threshold dose for the CIAS (SMD: 0.35; 0.00-0.69). No significant reduction was observed on eye drops use (SMD: -0.10; -0.22 to 0.03).
CONCLUSIONS AND CLINICAL RELEVANCE
SLIT is effective in reducing total and individual ocular symptom scores in subjects with ARC or conjunctivitis. No significant reduction was observed in ocular eye drops use.
Topics: Administration, Sublingual; Allergens; Conjunctivitis, Allergic; Desensitization, Immunologic; Humans; Publication Bias; Sensitivity and Specificity; Treatment Outcome
PubMed: 21848759
DOI: 10.1111/j.1365-2222.2011.03835.x -
The Cochrane Database of Systematic... Jul 2011Allergic ocular symptoms, although frequently trivialised, are common and represent an important comorbidity of allergic rhinitis. Sublingual Immunotherapy (SLIT) is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Allergic ocular symptoms, although frequently trivialised, are common and represent an important comorbidity of allergic rhinitis. Sublingual Immunotherapy (SLIT) is an effective and well-tolerated treatment for allergic rhinitis, but its effects on symptoms of ocular allergy have not been well established.
OBJECTIVES
To evaluate the efficacy of SLIT compared with placebo for reductions in ocular symptoms, topical ocular medication requirements and conjunctival immediate allergen sensitivity.
SEARCH STRATEGY
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 1), MEDLINE (January 1950 to January 2011), EMBASE (January 1980 to January 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2011), Web of Science (January 1970 to January 2011), Biosis Previews, (January 1979 to January 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (January 2011), ClinicalTrials.gov (www.clinicaltrials.gov) (January 2011), the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.actr.org.au) (July 2010), SCOPUS (November 2008) and the UK Clinical Trials Gateway (January 2010). There were no language or date restrictions in the search for trials. All electronic databases except for SCOPUS, the UK Clinical Trials Gateway and ANZCTR were last searched on 19 January 2011.
SELECTION CRITERIA
Randomised controlled trials (RCTs), double-masked and placebo controlled, which evaluated the efficacy of SLIT in patients with symptoms of allergic rhinoconjunctivitis (ARC) or allergic conjunctivitis (AC).
DATA COLLECTION AND ANALYSIS
The primary outcome was the total ocular symptom scores. Secondary endpoints included individual ocular symptom scores (such as itchy eyes, red eyes, watery eyes, swollen eyes), ocular medication scores (eye drops) and conjunctival immediate allergen sensitivity (CIAS). Data were analysed and reported as standardised mean differences (SMDs) using Review Manager software.
MAIN RESULTS
Forty-two trials (n = 3958 total participants; n= 2011 SLIT and n = 1947 placebo) had available data to evaluate the efficacy of SLIT on AC and were included in the meta-analyses. Heterogeneity among studies (I(2) statistic) was around 50% or below for all endpoints. Sublingual immunotherapy induced a significant reduction in both total ocular symptom scores (SMD -0.41; 95% confidence interval (CI) -0.53 to -0.28; P < 0.00001; I(2) = 59%) and individual ocular symptom scores for red eyes (SMD -0.33; 95% CI -0.45 to -0.22; P < 0.00001; I(2) = 27%), itchy eyes (SMD -0.31; 95% CI -0.42 to -0.20; P < 0.00001; I(2) = 46%) and watery eyes (SMD -0.23; 95% CI -0.34 to -0.11; P < 0.0001; I(2) = 42%) compared to placebo. Those participants having active treatment showed an increase in the threshold dose for the conjunctival allergen provocation test (SMD 0.35; 95% CI 0.00 to 0.69; P = 0.05; I(2) = 43%). No significant reduction was observed in ocular eye drops use (SMD -0.10; 95% CI -0.22 to 0.03; P = 0.13; I(2) = 34%).
AUTHORS' CONCLUSIONS
Overall, SLIT is moderately effective in reducing total and individual ocular symptom scores in participants with ARC and AC. There were however some concerns about the overall quality of the evidence-base, this relating to inadequate descriptions of allocation concealment in some studies, statistical heterogeneity and the possibility of publication bias. There is a need for further large rigorously designed studies that study long-term effectiveness after discontinuation of treatment and establish the cost-effectiveness of SLIT.
Topics: Administration, Sublingual; Allergens; Conjunctivitis, Allergic; Humans; Immunotherapy; Plant Extracts; Pollen; Randomized Controlled Trials as Topic; Rhinitis
PubMed: 21735416
DOI: 10.1002/14651858.CD007685.pub2 -
Allergy and Asthma Proceedings 2011Current treatment options for allergic rhinoconjunctivitis include topical antihistamines, vasoconstrictors, mast cell stabilizers, intranasal corticosteroids (INCS),... (Review)
Review
Current treatment options for allergic rhinoconjunctivitis include topical antihistamines, vasoconstrictors, mast cell stabilizers, intranasal corticosteroids (INCS), and nonsteroidal anti-inflammatory drugs that are generally used as a supplement to oral or intranasal therapies, necessitating the use of multiple treatments for the different symptoms of allergic rhinitis (AR). To assess the efficacy of INCS for ocular symptoms (OS) of AR. A search was performed of clinical trials (n = 32) from 1973 to 2009 of English articles (Medline, Embase, and PubMed) using "intranasal corticosteroid," "allergic rhinitis," "ocular symptoms," "allergic conjunctivitis," and "rhinoconjunctivitis" as key words. Quality assessment for the 32 eligible studies was performed using the Jadad score. Statistical analysis for continuous data was done by weighted mean difference or standardized mean difference. Thirty-two trials were included and separated into three different groups. The overall weighted mean was obtained from the Jadad score and came out to 9.29 (95% CI, 8.7-9.88). For meta-analysis for total OS scores and individual symptoms (10 parallel studies) the weighted mean was 10.17 (95% CI, 9.34-11). In the parallel studies, meta-analysis of individual symptoms (nine studies) gave a weighted mean of 10.09 (95% CI, 9.55-10.63). For eye symptoms but no individual symptoms (13 studies), the weighted mean was 8.56 (95% CI, 7.66-9.46). To date, clinical studies conducted statistically showed the efficacy of INCS on the OS of AR as evidenced by the meta-analysis results for the studies reporting total OSs.
Topics: Administration, Intranasal; Adrenal Cortex Hormones; Anti-Allergic Agents; Conjunctivitis, Allergic; Humans; Rhinitis, Allergic, Perennial; Treatment Outcome
PubMed: 21262095
DOI: 10.2500/aap.2011.32.3420 -
Allergy Jul 2011Ocular allergy represents one of the most common conditions encountered by allergists and ophthalmologists. However, there is wide variability of study designs in... (Review)
Review
BACKGROUND
Ocular allergy represents one of the most common conditions encountered by allergists and ophthalmologists. However, there is wide variability of study designs in clinical trials of allergic conjunctivitis, which results in conflicting evidence on their optimal management. We conducted a systematic review of clinical trials to critically evaluate their quality and to highlight biases to be avoided in future clinical research in ocular allergy.
METHODS
Clinical trials in allergic conjunctivitis performed since 1965 were retrieved, and data on patients, interventions, comparison of interventions, and outcomes were extracted. Four authors independently assessed articles for inclusion in the systematic review and assessed trials' quality using the Jadad scale.
RESULTS
Three hundred and sixty-two trials were included in the study. Only a minority of trials fulfilled all the criteria of proper clinical trial design. In most of the studies, there was a very limited use of objective (quantifiable) parameters for both patients' selection and evaluation of drug efficacy and safety. Several outcomes of primary importance, such as disease relapses and recurrence rate, were omitted in clinical trials of allergic conjunctivitis.
CONCLUSIONS
Evidence coming out of clinical trials in ocular allergy is limited, and this affects the strength of recommendations to health care providers and policy makers for optimal management. Standardized diagnostic criteria for patient selection and quantifiable primary outcomes are recommended to improve the design of future clinical trials in allergic conjunctivitis.
Topics: Anti-Allergic Agents; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine Antagonists; Humans; Research Design; Treatment Outcome
PubMed: 21261658
DOI: 10.1111/j.1398-9995.2010.02536.x