[Summary text]
Skal allergen-specifik immunterapi bruges til behandling af allergisk rhinoconjunctivitis udløst af pollen hos patienter, der ikke er symptomfrie på antihistamin og nasalsteriod?
Symptomscore (kritisk)
Medicinscore (kritisk)
Anafylaksi (kritisk)
Livskvalitet (vigtig)
Fraværsdage (vigtig)
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Placebo
Included criteria: Subjects included in the study were 5 to 17 years of age with a clinicalhistory of physician-diagnosed grass pollen–induced ARC with or withoutasthma. Key inclusion criteria for the observation and treatment periods wereaimed at recruiting subjects with moderate-to-severe ARC and were asfollows: treatment for ARC during the previous GPS; a positive skin prick testresponse to P pratense (standardized timothy grass extract, 100,000 bioequivalentallergen units/mL, 5-mL vial, administered by means of a DuoTip [LincolnDiagnostics, Decatur, Ill] to the inner forearm), with the average of thehorizontal and vertical wheal diameters 5 mm or larger than that elicited bythe saline control (positive control was Histatrol Histamine Positive Control1.0 mg/mL, 5-mL vial [ALK-Abello, Hørsholm, Denmark]), a positive specificIgE level against P pratense of 0.7 kU/L or greater (measured by meansof ImmunoCAP; Phadia AB, Portage, Mich), and an FEV1 of 70% or greater ofpredicted value at screening.
Excluded criteria: Key exclusion criteria were as follows: clinicalhistory of symptomatic seasonal or perennial ARC, asthma, or both requiringmedication because of an allergen other than grass during or potentially overlappingthe GPS; immunosuppressive treatment in the 3 months before screening;clinical history of persistent severe asthma, chronic urticaria/angioedema,or chronic rhinosinusitis; or current severe atopic dermatitis. For subjects whoparticipated in the observational period, those who did not experience a rhinoconjunctivitissymptom score increase of 4 points or more for at least 2 dayscompared with the preseason score or did not use ARC symptomatic medicationfor at least 2 days during the observational period were also excluded.
Intervention Characteristics
Intervention
Placebo
Continuous:
Adverse Events:
Sponsorship source:
Country: USA
Setting:
Comments:
Authors name: Blaiss M
Institution: dept. pediatrics and medicine
Email:
Address:
Identification:
Participants:
Study design:
Baseline characteristics:
Lone Winther analysis set include treated patients: 149 intervention and 158 placebo.Grass: 175 started treatment and 142 completed treatment: 33 excluded but of these 7 were included in analysisPlacebo: 169 started treatment and 140 completed: 29 excluded but of these 18 were included in analysis
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Lone Winther Other studies have used peak seasons as well. This study included.
Dichotomous outcomes:
Adverse outcomes:
Lone Winther 70% vs 25% experienced treatment related AE, in SLIT and placebo, respectively
Estimates and risk of bias assessments are from Radulovic et al (year)
Estimates and risk of bias assessments are from Radulovic et al (year)
Estimates and risk of bias assessments are from Radulovic et al (year)
Fra opdaterende søgning.
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Placebo
Included criteria: A clinical history of grass pollen–induced SAR that was inadequately controlled in previous years despite using antihistamines, topical steroids, and/or cromoglycate eye drops. Grass pollen allergy was confirmed by means of skin and blood tests (wheal diameter of 3 mm with Soluprick SQ 10 HEP Phleum pretense, ALK-Abello´, Hørsholm, Denmark; grass pollen–specific IgE class 2, Pharmacia CAP, Uppsala, Sweden)
Excluded criteria: Patients with additional sensitizations were allowed to participate unless they had significant rhinoconjunctivitis, sinusitis, and/or asthma outside the grass pollen season or daily contact with animals causing symptoms. Patients who had received SIT within the past 5 years were also excluded.
Intervention Characteristics
Intervention
Placebo
Continuous:
Dichotomous:
Sponsorship source:
Country: England
Setting:
Comments:
Authors name: Frew A. J.
Institution: allergy and inflammation research subdivision, school of medicine, university of southampton
Email:
Address:
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Dichotomous outcomes:
Adverse outcomes:
SE/SDs from Nelson et al 2011 and Durham et al 2006 imputed and used in analyses.
Fra opdaterende søgning
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Placebo
Included criteria: Subjects included in the study (both the observational and treatment years, unless otherwise noted) were 18 to 65 years of age with a physician-diagnosed history of grass pollen–induced ARC with or without asthma and had received treatment for their ARC during the previous GPS. At screening, subjects were required to meet the following criteria: a positive skin prick test response to P pratense defined as a wheal diameter of 5 mm or larger than that elicited by the saline control (standardized timothy grass extract 100,000 BAU/mL, 5 mL [ALK-Abell o, Hørsholm, Denmark] administered to the inner forearm with a DuoTip [Lincoln Diagnostics, Decatur, Ill]; positive control, HistatrolHistamine Positive Control 1.0 mg/mL, 5-mL [ALK-Abello, Hørsholm, Denmark]), a positive P pratense–specific IgE level (_ 0.7 kU/L; measured by using the ImmunoCAP assay, Phadia AB, Portage, Mich), and an FEV 1 of 70% or greater of predicted value. For those subjects who participated in theobservational period, an increase in rhinoconjunctivitis symptom score of 4 or greater (maximum possible score, 18) above the preseasonal average score for at least 2 days or symptomatic medication use for at least 2 days during the ob-servational period was also required to continue into the treatment period of the trial.
Excluded criteria: Reasons for exclusion from the trial included a history of symptomatic seasonal or perennial ARC, asthma, or both to an allergen other than the northern grasses that required medication during or potentially overlapping the GPS,immunotherapy within the previous 5 years, a history of severe asthma, chronic urticaria/angioedema, chronic sinusitis, or current severe atopic dermatitis.
Intervention Characteristics
Intervention
Placebo
Continuous:
Adverse Events:
Sponsorship source:
Country: USA
Setting:
Comments:
Authors name: Nelson
Institution: Department of medicine, division of allergy and immunology, national jewish health, denver
Email:
Address:
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Dichotomous outcomes:
Adverse outcomes:
Fra opdaterende søgning.
Fra Dretzkes et al (year)
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Placebo
Included criteria: Criteria were as follows: (1) a history of severe hayfever uncontrolled by conventional antiallergic drugs, and (2) positiveskin prick test result (wheal > 5 mm) to grass pollen.
Excluded criteria: Patientswere excluded if they had a history of multiple allergies or hadreceived immunotherapy in the preceding 5 years. Patients with seasonalchest symptoms were actively sought for inclusion providedtheir baseline methacholine PC20 (concentration of inhaled methacholinethat caused a 20% decrease in FEV1) was greater than 2mg/mL (normal range > 16 mg/mL).
Intervention Characteristics
Intervention
Placebo
Continuous:
Adverse Events:
Sponsorship source:
Country: England
Setting:
Comments:
Authors name: Walker
Institution: Upper respiratory medicine, imperial college school of medicine at the national heart and lung institute, london
Email:
Address:
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Dichotomous outcomes:
Adverse outcomes:
Wrong intervention
Wrong patient population
Wrong patient population
Wrong patient population
Wrong intervention
Wrong intervention
Wrong patient population
modificeret allergen
Wrong intervention
Wrong patient population
Wrong intervention
modificeret allergen
Wrong patient population
not SQ
Wrong intervention
product not in DK
Wrong intervention
Study included in other article
Wrong intervention
Wrong patient population
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
not SQ
Wrong intervention
Wrong intervention
modificeret allergen
Wrong intervention
Wrong intervention
Wrong patient population
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong patient population
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
not SQ
Wrong intervention
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Quote: "Randomization was conducted by an external randomization group using an interactive voice-response system according to a computer-generated sched- ule in appropriately sized blocks and was stratified by study site and the sub- ject’s asthma status."
Quote: "ALK-Abello ´ generated the randomization sequence, which was retained until all assessments and recordings were completed."
Comment: Is alka-abello the right ones to generate the sequence?
A total of 1,501 subjects who continued to qualify for the study were randomized in a 1:1 ratio according to a computer-generated randomization schedule;
computer generated (SASS)
Quote: "Subjects were randomized by using a computer-generated random- ization schedule in blocks of appropriate size."
statification was performed by center and randomasation was perfomed in block of 5 by the study sponser using the SAS version 8e
Comment: computer generated random numbers
Quote: "Randomization was performed independently by the supplier of the grass pollen vaccine. The treatment schedule and assessments were performed double-blind,"
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Unclear
Unclear
Quote: "Investigators allocated subjects the next randomization number from the randomized sequence."
Comment: is this rodden?
randomization was conducted by an external randomization group using an interactive voice response system and was stratified by asthmatic status and age category
Quote: "Randomization was conducted by an external randomization group using an interactive voice-response sys- tem and was stratified by study site and the asthmatic status of the subject."
randomazation code kept strigtly confidential
Comment: It is unclear if the sequence was concealed
Quote: "The treatment schedule and assessments were performed double-blind, with treatment allocations kept in sealed envelopes by the principal investigator."
Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Quote: "Subjects and investigators were blinded to treatment by using a matching placebo in identical packaging to the grass AIT treatment. Blinding was maintained until the data were locked."
Quote: "Study medication was provided as a suspension in vials. Placebo and active medications were identical, except for grass pollen extract."
The sponsor, subject, and investigational staff (investigator and evaluators) were blinded to treatment. Placebo was indistinguishable from the active tablet in appearance, smell, and taste but contained no pollen extract. Subjects were treated once daily with placebo or MK-7243 for at least 12 weeks before and during the entire 2012 grass pollen season (GPS; eFig 1).
Quote: "Double blinding (subject and investigator) was established by use of a match- ing placebo tablet. Blinding was maintained until the database was locked."
investigators and patients were blinded through out the trial
Comment: Immune therapists was not blinded. The outcome rapporter of adverse event was not blinded. it is unclear of the patients were blinded despite of a dubbel dummy technique.
Quote: "P5. Place- bo injections of identical appearance contained 0.01 mg/mL hista- mine acid phosphate (in PBS) in allergen diluent."
Detection bias due to knowledge of the allocated interventions by outcome assessors
Comment: Blinding was maintained until the data were locked.
Unclear
Unclear
Unclear
Quote: "Staff administering medication and assessing outcomes were blinded to the treatment."
The sponsor, subject, and investigational staff (investigator and evaluators) were blinded to treatment. Placebo was indistinguishable from the active tablet in appearance, smell, and taste but contained no pollen extract. Subjects were treated once daily with placebo or MK-7243 for at least 12 weeks before and during the entire 2012 grass pollen season (GPS; eFig 1).
unclear
unclear
not reported
Comment: the coordinater (blinded) was in charge of testing.
Comment: Not described
Attrition bias due to amount, nature or handling of incomplete outcome data
Comment: Data analysis set included some of the excluded patients.No imputation of missing data. No mention of percentage of daily data completed.
Comment: They do not use an imputation method for the efficacy results. For the adverse events they dol.
This was a multicenter, double-blinded, randomized, placebo- controlled, parallel-group study (P08067; clinicaltrials.gov; regis- tration NCT01385371) conducted in the United States and Canada.
ITT analysis used
low risk
Comment: ITT was not used
Quote: "All analyses were performed on an intention-to-treat basis."
Comment: ITT was used
Reporting bias due to selective outcome reporting
Unclear
Comment: Protocol not located. It seems like they have presented all relevant outcomes and adverse events.
This was a multicenter, double-blinded, randomized, placebo- controlled, parallel-group study (P08067; clinicaltrials.gov; regis- tration NCT01385371) conducted in the United States and Canada.
unclear
protocol found and likely they have reported what they planned
Comment: Protocol not located
Comment: Protocol not located
Bias due to problems not covered elsewhere in the table
unclear
It is unclear whether funding from pharmaceutical company influenced the study
high pre season scores. No symptom score flucturation with grass pollen. Mite sensitization high.
Quote: "Supported by Merck & Co."
Comment: It is unclear wether this finansial suppor affects the results.
pharmacutical sponsored throughout all of the study
Comment: funded by ALK Abello