Subcutaneous vs Sublingual Immunotherapy in Rhinitis
Subcutaneous vs Sublingual Immunotherapy in Rhinitis
The secondary outcomes that have been used in allergic rhinitis clinical trials include the following.
A valuable secondary outcome is the reporting of individual symptoms (nasal and ocular), as changes here allow assessment of the effect of the immunotherapy on each target organ affected by the allergy.
The assessment of health-related quality of life is a beneficial secondary outcome parameter to reflect the patients' apparent effect of the immunotherapy. Unlike symptom or medication scores, rhinoconjunctivitis-specific quality of life questionnaires have been validated for adults and children.
The visual analogue scale (VAS) is regarded as a valuable and sensitive tool to monitor the severity of symptoms and to detect changes from baseline to posttreatment conditions. A significant disadvantage addresses the lack of extreme values of the VAS, as patients tend to rate their symptom severity avoiding the extremes.
The evaluation of symptom-free or well days, described as 'days without intake of rescue medication and a symptom score below a predefined and clinically justified threshold' is recommended by EMA as a secondary endpoint. A similar approach might be to assess worst days, namely 'days with severe symptoms' instead, to support the primary efficacy outcome parameter.
In pollen allergy trials, pollen counts applying equivalent biometric techniques and reflecting the patients' distribution have to be evaluated. Studies found out that pollen counts are only weakly correlated with symptoms and an exact definition of the relevant pollen exposure including threshold values is still lacking. Moreover, recent studies have demonstrated that the expression of major allergens may highly vary between pollen in different areas and at different time-points.
Functional measures (objective measures such as conjunctival, bronchial or nasal provocation tests, acoustic rhinometry, spirometry and peak expiratory flow rate) and in vitro parameters such as allergen-specific immunoglobulin E (IgE) and specific immunoglobulin G (IgG) levels are universally accepted as useful support of the primary clinical outcome. However, these surrogate markers or laboratory parameters can only provide additional information and not replace the primary endpoint for efficacy.
The thorough reporting of safety is of major importance in clinical trials. As recommendations propose, all adverse events have to be classified according to their severity and to their relationship to the treatment. Moreover, adverse events should be documented as local or systemic side effects applying the most recently approved international classifications. Despite these recommendations, there is still a great heterogeneity in classification and reporting of adverse events in SLIT and SCIT trials, making comparability difficult.
Secondary Outcomes
The secondary outcomes that have been used in allergic rhinitis clinical trials include the following.
Individual Symptoms
A valuable secondary outcome is the reporting of individual symptoms (nasal and ocular), as changes here allow assessment of the effect of the immunotherapy on each target organ affected by the allergy.
Quality of Life
The assessment of health-related quality of life is a beneficial secondary outcome parameter to reflect the patients' apparent effect of the immunotherapy. Unlike symptom or medication scores, rhinoconjunctivitis-specific quality of life questionnaires have been validated for adults and children.
Visual Analogue Scale
The visual analogue scale (VAS) is regarded as a valuable and sensitive tool to monitor the severity of symptoms and to detect changes from baseline to posttreatment conditions. A significant disadvantage addresses the lack of extreme values of the VAS, as patients tend to rate their symptom severity avoiding the extremes.
Well Days
The evaluation of symptom-free or well days, described as 'days without intake of rescue medication and a symptom score below a predefined and clinically justified threshold' is recommended by EMA as a secondary endpoint. A similar approach might be to assess worst days, namely 'days with severe symptoms' instead, to support the primary efficacy outcome parameter.
Pollen Counts
In pollen allergy trials, pollen counts applying equivalent biometric techniques and reflecting the patients' distribution have to be evaluated. Studies found out that pollen counts are only weakly correlated with symptoms and an exact definition of the relevant pollen exposure including threshold values is still lacking. Moreover, recent studies have demonstrated that the expression of major allergens may highly vary between pollen in different areas and at different time-points.
Surrogate Markers
Functional measures (objective measures such as conjunctival, bronchial or nasal provocation tests, acoustic rhinometry, spirometry and peak expiratory flow rate) and in vitro parameters such as allergen-specific immunoglobulin E (IgE) and specific immunoglobulin G (IgG) levels are universally accepted as useful support of the primary clinical outcome. However, these surrogate markers or laboratory parameters can only provide additional information and not replace the primary endpoint for efficacy.
Safety
The thorough reporting of safety is of major importance in clinical trials. As recommendations propose, all adverse events have to be classified according to their severity and to their relationship to the treatment. Moreover, adverse events should be documented as local or systemic side effects applying the most recently approved international classifications. Despite these recommendations, there is still a great heterogeneity in classification and reporting of adverse events in SLIT and SCIT trials, making comparability difficult.
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